id
int64 -9,222,680,663,801,228,000
9,222,764,925B
| text
stringlengths 289
726k
| metadata
dict | line_start_n_end_idx
dict | quality_signals
dict | eai_taxonomy
dict | pid
stringclasses 4
values |
|---|---|---|---|---|---|---|
4,102,748,067,766,395,000
|
The Essentials of Tips – 101
Top Reasons Why A Diet Does Not Work
Perhaps, you have already taken a hint on how over half the population in the whole world are afraid to go fat or even become overweight and those very same people are the ones who are willing to spend any amount just to purchase those diet and slimming products, causing the said industry to grow in no time at all. In this modern day and time, where being thin is a trend, there are now tons of magazines that are publishing various remedies on losing weight or even getting thin in the fastest way possible in every page, not to mention the fact that lots of quick and pain free fixes are now also available in the market which lots of us typically indulge themselves with. On top of it all, you can also include in the list the increasing number of the latest fad diets available as well as the unlimited supply of slimming snacks, drinks and even get thin gums, all are just waiting to take some cash from you. Although, slimming and diets are now known as one of the big businesses in the whole world, however, there is also that fact that these products do not work at all and instead, you need to pay a hefty price for using them. Health is wealth, or as what the saying goes, that is why you need to make sure that what you are doing to your body and what you are consuming will not harm you in any possible way.
If you ever happen to encounter claims such as “Lose ten pounds in a week”, instead of assuming something, you better ask yourself about what it is that you will be losing the ten pounds of. It is physically probable to only lose fats between one and a half to two pounds per week so, if you notice that you are losing more than the given figures, then you need to be wary about it cause it only mean you also lose something other than fats.
The very reason why it is not advisable to do diet is because if you adopt a crash diet and your suddenly cut your food intake (which is what most diets will ask you to), your body will assume that there is famine on the way and due to this, it will begin to save your precious fats instead of burning it and instead, your muscles will be the one to burn. In addition to this, there is also a big possibility of you losing lots of water and glucose which in turn, will make your weight dramatically drop, which you might think is just fine when its not since the combination of water lost and muscle tissue lost will indeed a very bad news.The 10 Most Unanswered Questions about Options
Getting To The Point – Options
editor
editor wrote 134 posts
Post navigation
|
{
"url": "http://www.jocuri.in/the-essentials-of-tips-101.html",
"source_domain": "www.jocuri.in",
"snapshot_id": "crawl=CC-MAIN-2017-39",
"warc_metadata": {
"Content-Length": "23216",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:VRFOV6TWAWN2F6IZDJTCXEMD7H367UJD",
"WARC-Concurrent-To": "<urn:uuid:e771e97f-166e-453c-a72b-ecb4d8b2f28b>",
"WARC-Date": "2017-09-26T00:02:41",
"WARC-IP-Address": "104.18.38.242",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:Q62FSCGUR5HOGSPEBLAW4VCWN2ACB4V2",
"WARC-Record-ID": "<urn:uuid:07a9c836-1ff6-4b73-aa2d-cceb3debf3e1>",
"WARC-Target-URI": "http://www.jocuri.in/the-essentials-of-tips-101.html",
"WARC-Truncated": "length",
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:c2a5adc3-04b3-44c7-af9f-fb7491e7883e>"
},
"warc_info": "robots: classic\r\nhostname: ip-10-157-139-144.ec2.internal\r\nsoftware: Nutch 1.6 (CC)\r\nisPartOf: CC-MAIN-2017-39\r\noperator: Common Crawl Admin\r\ndescription: Wide crawl of the web for September 2017\r\npublisher: Common Crawl\r\nformat: WARC File Format 1.0\r\nconformsTo: http://bibnum.bnf.fr/WARC/WARC_ISO_28500_version1_latestdraft.pdf"
}
|
{
"line_start_idx": [
0,
29,
30,
67,
68,
1390,
1391,
1833,
1834,
2521,
2522,
2553,
2554,
2561,
2562,
2585,
2586
],
"line_end_idx": [
29,
30,
67,
68,
1390,
1391,
1833,
1834,
2521,
2522,
2553,
2554,
2561,
2562,
2585,
2586,
2601
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 2601,
"ccnet_original_nlines": 16,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.5891181826591492,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.0018761700484901667,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.07504689693450928,
"rps_doc_frac_unique_words": 0.47887325286865234,
"rps_doc_mean_word_length": 4.148893356323242,
"rps_doc_num_sentences": 10,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 4.9821977615356445,
"rps_doc_word_count": 497,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.012124150060117245,
"rps_doc_frac_chars_top_3gram": 0.013094079680740833,
"rps_doc_frac_chars_top_4gram": 0.014548979699611664,
"rps_doc_books_importance": -222.9001922607422,
"rps_doc_books_importance_length_correction": -222.9001922607422,
"rps_doc_openwebtext_importance": -132.98902893066406,
"rps_doc_openwebtext_importance_length_correction": -132.98902893066406,
"rps_doc_wikipedia_importance": -116.9480972290039,
"rps_doc_wikipedia_importance_length_correction": -116.9480972290039
},
"fasttext": {
"dclm": 0.10383933782577515,
"english": 0.9730367660522461,
"fineweb_edu_approx": 1.8699477910995483,
"eai_general_math": 0.13054317235946655,
"eai_open_web_math": 0.39183759689331055,
"eai_web_code": 0.010220290161669254
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "613.2",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
},
"secondary": {
"code": "613.7",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "5",
"label": "Evaluate"
},
"secondary": {
"code": "2",
"label": "Understand"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "0",
"label": "No Artifacts"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "12",
"label": "Listicle"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "2",
"label": "Partially Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
1a01aa77535b9ecfb87b9fc36adbcd2f
|
8,240,579,981,292,459,000
|
What is the role of medications in the management of fat embolism?
Updated: Mar 27, 2020
• Author: Constantine S Bulauitan, MD; Chief Editor: Vincent Lopez Rowe, MD more...
• Print
Answer
Specific medical therapy for fat embolism and fat embolism syndrome (FES) does not exist at this time, and supportive measures have not been tested in adequate randomized, controlled trials. Treatments such as heparin, dextran, and steroids have not been shown to help reduce morbidity and mortality, but methylprednisolone given prophylactically may have beneficial effects. [26]
Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!
|
{
"url": "https://www.medscape.com/answers/460524-91028/what-is-the-role-of-medications-in-the-management-of-fat-embolism",
"source_domain": "www.medscape.com",
"snapshot_id": "crawl=CC-MAIN-2022-27",
"warc_metadata": {
"Content-Length": "80360",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:NKQHV3DJAPQWMGGG37AI7SEMXQF55FSG",
"WARC-Concurrent-To": "<urn:uuid:e86632a9-cc09-4f2c-b431-7b81a87a37b1>",
"WARC-Date": "2022-06-26T23:43:16",
"WARC-IP-Address": "172.64.155.22",
"WARC-Identified-Payload-Type": "application/xhtml+xml",
"WARC-Payload-Digest": "sha1:4DSR4MJLKLS36EEFH7UGPUAQ6HQAD6QS",
"WARC-Record-ID": "<urn:uuid:6dfabf22-0bc4-489d-afbb-560d8cbded94>",
"WARC-Target-URI": "https://www.medscape.com/answers/460524-91028/what-is-the-role-of-medications-in-the-management-of-fat-embolism",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:034f6546-5fe5-4e3f-b32c-469d682afa29>"
},
"warc_info": "isPartOf: CC-MAIN-2022-27\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for June/July 2022\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-203\r\nsoftware: Apache Nutch 1.18 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.3-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
67,
68,
90,
177,
187,
194,
195,
576,
577,
578,
609,
641,
670
],
"line_end_idx": [
67,
68,
90,
177,
187,
194,
195,
576,
577,
578,
609,
641,
670,
671
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 671,
"ccnet_original_nlines": 13,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.2879999876022339,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.03200000151991844,
"rps_doc_frac_lines_end_with_ellipsis": 0.0714285671710968,
"rps_doc_frac_no_alph_words": 0.23999999463558197,
"rps_doc_frac_unique_words": 0.7799999713897705,
"rps_doc_mean_word_length": 5.340000152587891,
"rps_doc_num_sentences": 7,
"rps_doc_symbol_to_word_ratio": 0.00800000037997961,
"rps_doc_unigram_entropy": 4.265392780303955,
"rps_doc_word_count": 100,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.06179774925112724,
"rps_doc_frac_chars_top_3gram": 0.041198499500751495,
"rps_doc_frac_chars_top_4gram": 0,
"rps_doc_books_importance": -73.69500732421875,
"rps_doc_books_importance_length_correction": -80.32299041748047,
"rps_doc_openwebtext_importance": -36.969390869140625,
"rps_doc_openwebtext_importance_length_correction": -43.59737777709961,
"rps_doc_wikipedia_importance": -34.756011962890625,
"rps_doc_wikipedia_importance_length_correction": -41.38399887084961
},
"fasttext": {
"dclm": 0.06659036874771118,
"english": 0.9288073778152466,
"fineweb_edu_approx": 1.044106364250183,
"eai_general_math": 0.0009165999945253134,
"eai_open_web_math": 0.1589897871017456,
"eai_web_code": -0.000009890000001178123
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.19",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "615.54",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "9",
"label": "FAQ"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "3",
"label": "Undergraduate Level"
},
"secondary": {
"code": "4",
"label": "Graduate/Expert Level"
}
}
}
|
6e3c8d3593f3f69280bb5502b214ab8e
|
8,010,482,463,274,492,000
|
Anxiety / StressBlood / HematologyEmergency MedicineGastroIntestinal / GastroenterologyGenetics
Hereditary angioedema attacks: What to know
Hereditary angioedema (HAE) is a hereditary disorder that causes different parts of the body to undergo extreme swelling.
People often refer to this as a ‘attack’ when symptoms occur. HAE is a chronic condition, so these episodes can occur throughout the life of a person.
Discover the causes, frequency, causes, and treatments of HAE attacks below. We also look at the symptoms involved in these attacks and the three main forms of HAE are identified.
What are HAE attacks?
HAE is a chronic genetic disorder that causes repeated swelling of the mucous membranes and areas of the skin. Throughout the body, this swelling can affect different areas.
Factors such as stress or trauma can cause a HAE attack. For no discernable cause, attacks can also occur.
HAE episodes frequently start early in the life of a person, often no later than the age of 13, and some individuals experience their first symptoms before turning 7. Their symptoms can become more serious as a person ages.
If an attack happens, HAE therapies focus on avoiding new attacks and decreasing the severity of symptoms. Within 12–72 hours of their onset, the symptoms frequently vanish.
Frequency
The frequency of HAE attacks varies from individual to individual.
78.7 percent reported witnessing an assault during the past month in a 2020 survey of 445 respondents living with HAE. The average number of confirmed attacks over a span of 6 months was approximately 11.
The survey also states that, depending on demographic data, the frequency of attacks varies. For instance, the number of recorded attacks is influenced by age, sex, race, and type of HAE.
Triggers
In individuals with the condition, several factors can trigger HAE attacks.
The researchers split their participants into two classes in a small study that examined these causes.
In the first category, mental stress, which accounted for about 21% of identified triggers, was the most frequently recorded cause.
These participants could only identify a trigger during the course of the 7-year study in about 30 percent of the more than 3,000 attacks they reported.
The second group of the study reported attacks and triggers over a span of 7 months. 365 attacks were registered by the participants, of which 67 percent occurred on days with identifiable possible triggers.
The most frequently recorded triggers of the second group included:
• menstruation
• infections
• mental stress
• physical exertion
• changes in the weather
• fatigue
The U.S. Hereditary Angioedema Association have identified similar triggers. They report that the most common triggers include:
• stress
• anxiety
• illnesses such as the common cold or flu
• surgery
• minor injurires
They also note that people with HAE report symptoms occurring during or after activities such as:
• writing for long periods
• typing
• mowing the lawn
• shoveling
• hammering
• other physical activities
Symptoms
An individual with HAE during their life appears to experience varying degrees of symptoms. In different regions, the signs of a typical HAE attack include swelling, including:
• skin on the hands, genitals, buttocks, feet, legs, and arms
• throat, including the tongue
• abdomen
• other organs
It may cause changes in appearance, a loss of function, and discomfort when the swelling affects the skin. Within 12-72 hours, the symptoms usually go away.
It may cause gastrointestinal symptoms such as diarrhea, discomfort, and vomiting when swelling happens in the abdomen.
It can rapidly become a life-threatening emergency if swelling occurs around the throat or tongue. Urgent medical care should be offered to someone who has difficulty breathing.
What causes each type of HAE?
Three key forms of HAE exist. In an individual with type 1, enough C1 inhibitor proteins are not developed by the body. The body produces enough of these proteins in a person with type 2, but they don’t function properly.
Type 3 HAE is also known as estrogen-dependent HAE. The body produces sufficient and properly functioning C1 inhibitors. The attacks are associated with an increase in estrogen from factors such as pregnancy and hormonal contraceptives.
Treatment
Care focuses on avoiding attacks and if attacks arise, reducing the severity of the symptoms.
Emergency medical attention may be life saving if HAE damages the airways and breathing of a person.
HAE attacks can be treated directly or indirectly by seven drugs. They include:
1. Berinert: This is an intravenous C1 inhibitor concentrate made from human plasma that treats HAE attacks in children and adults.
2. Cinryze: Another intravenous medication, this is a C1 esterase inhibitor that prevents HAE attacks in children, teens, and adults.
3. Haegarda: This is a self-administered, plasma-derived concentrate of C1 esterase inhibitor that treats symptoms of HAE.
4. Ruconest: This is an intravenous, plasma-free recombinant C1 inhibitor concentrate that treats HAE attacks in teens and adults.
5. Ecallantide (Kalbitor): This is an injection of a kallikrein inhibitor that treats acute HAE attacks in people who are at least 12 years of age.
6. Icatibant (Firazyr): This is an injected B2 bradykinin receptor antagonist that treats acute HAE attacks in people who are at least 18 years of age.
7. Lanadelumab-flyo (Takhzyro): This plasma-based kallikrein inhibitor injection prevents HAE attacks in people who are at least 12 years of age.
A child with HAE from a parent has an increased chance of the disorder progressing. Speak to a child’s doctor about any HAE harm. Working with the doctor to establish the most efficient treatment plan is crucial.
Takeaway
HAE attacks cause different parts of the body to swell seriously. If the swelling affects the abdomen, a person might experience gastrointestinal symptoms. If it affects the throat, emergency treatment may be required for the person.
Work with a specialist to determine the drugs that avoid HAE attacks most effectively and decrease the severity of any symptoms that occur.
Back to top button
|
{
"url": "https://nccmed.com/hereditary-angioedema-attacks-what-to-know/",
"source_domain": "nccmed.com",
"snapshot_id": "crawl=CC-MAIN-2021-17",
"warc_metadata": {
"Content-Length": "80501",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:RHDLG6UQVEFZEPICNN6CVEBAR7GULSZF",
"WARC-Concurrent-To": "<urn:uuid:829b0b25-f93b-43a3-9e86-7c5419bc4cfa>",
"WARC-Date": "2021-04-22T14:26:47",
"WARC-IP-Address": "172.67.189.138",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:SA3NIODBKZU4MU775ZYAE64CNKTKBBGG",
"WARC-Record-ID": "<urn:uuid:13032a03-fba0-4056-9fc3-19809b692025>",
"WARC-Target-URI": "https://nccmed.com/hereditary-angioedema-attacks-what-to-know/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:dfdb11c0-b8ef-4d2c-b68e-d578942ed395>"
},
"warc_info": "isPartOf: CC-MAIN-2021-17\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for April 2021\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-112.ec2.internal\r\nsoftware: Apache Nutch 1.18 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.2-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
96,
97,
141,
142,
264,
265,
416,
417,
597,
598,
620,
621,
795,
796,
903,
904,
1128,
1129,
1303,
1304,
1314,
1315,
1382,
1383,
1588,
1589,
1777,
1778,
1787,
1788,
1864,
1865,
1968,
1969,
2101,
2102,
2255,
2256,
2464,
2465,
2533,
2534,
2551,
2566,
2584,
2606,
2633,
2645,
2646,
2774,
2775,
2786,
2798,
2843,
2855,
2875,
2876,
2974,
2975,
3004,
3015,
3035,
3049,
3063,
3093,
3094,
3103,
3104,
3281,
3282,
3346,
3379,
3391,
3408,
3409,
3566,
3567,
3687,
3688,
3866,
3867,
3897,
3898,
4120,
4121,
4358,
4359,
4369,
4370,
4464,
4465,
4566,
4567,
4647,
4648,
4782,
4918,
5043,
5176,
5326,
5480,
5628,
5629,
5842,
5843,
5852,
5853,
6087,
6088,
6228,
6229
],
"line_end_idx": [
96,
97,
141,
142,
264,
265,
416,
417,
597,
598,
620,
621,
795,
796,
903,
904,
1128,
1129,
1303,
1304,
1314,
1315,
1382,
1383,
1588,
1589,
1777,
1778,
1787,
1788,
1864,
1865,
1968,
1969,
2101,
2102,
2255,
2256,
2464,
2465,
2533,
2534,
2551,
2566,
2584,
2606,
2633,
2645,
2646,
2774,
2775,
2786,
2798,
2843,
2855,
2875,
2876,
2974,
2975,
3004,
3015,
3035,
3049,
3063,
3093,
3094,
3103,
3104,
3281,
3282,
3346,
3379,
3391,
3408,
3409,
3566,
3567,
3687,
3688,
3866,
3867,
3897,
3898,
4120,
4121,
4358,
4359,
4369,
4370,
4464,
4465,
4566,
4567,
4647,
4648,
4782,
4918,
5043,
5176,
5326,
5480,
5628,
5629,
5842,
5843,
5852,
5853,
6087,
6088,
6228,
6229,
6247
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 6247,
"ccnet_original_nlines": 111,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 2,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.3479020893573761,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.03758741170167923,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.17569929361343384,
"rps_doc_frac_unique_words": 0.38492873311042786,
"rps_doc_mean_word_length": 5.109979629516602,
"rps_doc_num_sentences": 67,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.263521671295166,
"rps_doc_word_count": 982,
"rps_doc_frac_chars_dupe_10grams": 0.029294539242982864,
"rps_doc_frac_chars_dupe_5grams": 0.05440415069460869,
"rps_doc_frac_chars_dupe_6grams": 0.039258670061826706,
"rps_doc_frac_chars_dupe_7grams": 0.029294539242982864,
"rps_doc_frac_chars_dupe_8grams": 0.029294539242982864,
"rps_doc_frac_chars_dupe_9grams": 0.029294539242982864,
"rps_doc_frac_chars_top_2gram": 0.025906739756464958,
"rps_doc_frac_chars_top_3gram": 0.014348350465297699,
"rps_doc_frac_chars_top_4gram": 0.01076126005500555,
"rps_doc_books_importance": -514.8488159179688,
"rps_doc_books_importance_length_correction": -514.8488159179688,
"rps_doc_openwebtext_importance": -319.39898681640625,
"rps_doc_openwebtext_importance_length_correction": -319.39898681640625,
"rps_doc_wikipedia_importance": -207.13153076171875,
"rps_doc_wikipedia_importance_length_correction": -207.13153076171875
},
"fasttext": {
"dclm": 0.10405659675598145,
"english": 0.9381574988365173,
"fineweb_edu_approx": 3.2502994537353516,
"eai_general_math": 0.05209219083189964,
"eai_open_web_math": 0.2300087809562683,
"eai_web_code": 0.002030370058491826
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.0722",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "616.072",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "9",
"label": "FAQ"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
9222580d47c553ea90dc0f5e416f8f3a
|
-170,734,131,065,041,120
|
Advancements in Rift Valley fever vaccines: a historical overview and prospects for next generation candidates
Cigdem Alkan, Eduardo Jurado-Cobena, Tetsuro Ikegami
Research output: Contribution to journalReview articlepeer-review
Fingerprint
Dive into the research topics of 'Advancements in Rift Valley fever vaccines: a historical overview and prospects for next generation candidates'. Together they form a unique fingerprint.
INIS
Immunology and Microbiology
Veterinary Science and Veterinary Medicine
Keyphrases
|
{
"url": "https://researchexperts-staging.utmb.edu/en/publications/advancements-in-rift-valley-fever-vaccines-a-historical-overview-/fingerprints/",
"source_domain": "researchexperts-staging.utmb.edu",
"snapshot_id": "CC-MAIN-2024-30",
"warc_metadata": {
"Content-Length": "59911",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:CYCFBZXRBASFO2U5D2ECLNMS2GPIISOV",
"WARC-Concurrent-To": "<urn:uuid:0daa103f-428e-4673-bfdc-a7cb18941791>",
"WARC-Date": "2024-07-14T11:09:38",
"WARC-IP-Address": "104.18.39.240",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:SLO3YVUYMDUTGA7DYCZFFAAHHZBNQV3M",
"WARC-Record-ID": "<urn:uuid:0ed1899f-d701-4c22-bf7a-38fe9e6fdec3>",
"WARC-Target-URI": "https://researchexperts-staging.utmb.edu/en/publications/advancements-in-rift-valley-fever-vaccines-a-historical-overview-/fingerprints/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:950e9123-b605-43fe-bbd3-3c87772e799d>"
},
"warc_info": "isPartOf: CC-MAIN-2024-30\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for July 2024\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-148\r\nsoftware: Apache Nutch 1.20 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.5-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
111,
112,
165,
166,
232,
233,
245,
246,
434,
435,
440,
441,
469,
470,
513,
514
],
"line_end_idx": [
111,
112,
165,
166,
232,
233,
245,
246,
434,
435,
440,
441,
469,
470,
513,
514,
524
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 524,
"ccnet_original_nlines": 16,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.23376622796058655,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.012987010180950165,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.12987013161182404,
"rps_doc_frac_unique_words": 0.6769230961799622,
"rps_doc_mean_word_length": 6.784615516662598,
"rps_doc_num_sentences": 3,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 3.697129964828491,
"rps_doc_word_count": 65,
"rps_doc_frac_chars_dupe_10grams": 0.43083900213241577,
"rps_doc_frac_chars_dupe_5grams": 0.43083900213241577,
"rps_doc_frac_chars_dupe_6grams": 0.43083900213241577,
"rps_doc_frac_chars_dupe_7grams": 0.43083900213241577,
"rps_doc_frac_chars_dupe_8grams": 0.43083900213241577,
"rps_doc_frac_chars_dupe_9grams": 0.43083900213241577,
"rps_doc_frac_chars_top_2gram": 0.0634920597076416,
"rps_doc_frac_chars_top_3gram": 0.08163265138864517,
"rps_doc_frac_chars_top_4gram": 0.10884354263544083,
"rps_doc_books_importance": -32.241050720214844,
"rps_doc_books_importance_length_correction": -44.29011154174805,
"rps_doc_openwebtext_importance": -20.642181396484375,
"rps_doc_openwebtext_importance_length_correction": -32.69124221801758,
"rps_doc_wikipedia_importance": -10.053174018859863,
"rps_doc_wikipedia_importance_length_correction": -22.10223388671875
},
"fasttext": {
"dclm": 0.024426519870758057,
"english": 0.6938800811767578,
"fineweb_edu_approx": 2.4526891708374023,
"eai_general_math": -0.00000965999970503617,
"eai_open_web_math": 0.01250172033905983,
"eai_web_code": 0.00002741999924182892
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "614.4",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Public health"
}
},
"secondary": {
"code": "616.07",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "5",
"label": "Evaluate"
},
"secondary": {
"code": "4",
"label": "Analyze"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "2",
"label": "Academic/Research"
},
"secondary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "1",
"label": "Truncated Snippets"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "3",
"label": "Academic Writing"
},
"secondary": {
"code": "8",
"label": "Documentation"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "6",
"label": "Not Applicable/Indeterminate"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "4",
"label": "Graduate/Expert Level"
},
"secondary": {
"code": "5",
"label": "Indeterminate"
}
}
}
|
b755ed28a90d11d590ef646404f4afc5
|
-3,649,028,881,493,185,500
|
Timeline of Breast Changes in Pregnancy
0
11738
Whether or not you plan to breastfeed, your breasts will prepare themselves for nourishing your baby. The female breast, also referred to as the mammary gland, takes its name from the Latin word for breast – ‘mamma’. Throughout pregnancy your breasts will undergo subtle, and not so subtle, transformations. This timeline charts your breasts’ remarkable journey.
Note: This timeline uses the medical format for calculating pregnancy weeks. So for instance, you technically ovulate near what would be called week two of pregnancy, and your due date is week 40. Notice how breast changes to prepare for breastfeeding occur as early as pre-ovulation!
Back
Next
Week 1:
• During each menstrual cycle, maturation and the rapid growth of milk ducts and alveolar buds take place during the follicular and ovulatory phases.
Back
Next
|
{
"url": "https://www.thealphaparent.com/timeline-of-breast-changes-in-pregnancy/",
"source_domain": "www.thealphaparent.com",
"snapshot_id": "crawl=CC-MAIN-2020-10",
"warc_metadata": {
"Content-Length": "83320",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:3URZYY253INFWXQAJAZQJEFVE7HGVNEL",
"WARC-Concurrent-To": "<urn:uuid:f6730e59-1718-4a56-9eb0-0b3d48bb562e>",
"WARC-Date": "2020-02-24T06:02:25",
"WARC-IP-Address": "104.28.15.234",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:GMJGMFYU7OXE4SQ3WGEJJXHEAQXJZWMI",
"WARC-Record-ID": "<urn:uuid:23778a4c-4274-4aba-9e26-bec8a4c73462>",
"WARC-Target-URI": "https://www.thealphaparent.com/timeline-of-breast-changes-in-pregnancy/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:ac09db6c-3388-46ce-8b18-76e0dbf268e5>"
},
"warc_info": "isPartOf: CC-MAIN-2020-10\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for February 2020\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-77.ec2.internal\r\nsoftware: Apache Nutch 1.16 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.1-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: http://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
40,
41,
43,
49,
50,
413,
414,
699,
700,
705,
710,
711,
719,
720,
872,
873,
878
],
"line_end_idx": [
40,
41,
43,
49,
50,
413,
414,
699,
700,
705,
710,
711,
719,
720,
872,
873,
878,
882
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 882,
"ccnet_original_nlines": 17,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.3395061790943146,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.1666666716337204,
"rps_doc_frac_unique_words": 0.6785714030265808,
"rps_doc_mean_word_length": 5.107142925262451,
"rps_doc_num_sentences": 9,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 4.376662254333496,
"rps_doc_word_count": 140,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.0363636389374733,
"rps_doc_frac_chars_top_3gram": 0.0419580414891243,
"rps_doc_frac_chars_top_4gram": 0,
"rps_doc_books_importance": -66.9156265258789,
"rps_doc_books_importance_length_correction": -66.9156265258789,
"rps_doc_openwebtext_importance": -37.203277587890625,
"rps_doc_openwebtext_importance_length_correction": -29.9647159576416,
"rps_doc_wikipedia_importance": -21.29253387451172,
"rps_doc_wikipedia_importance_length_correction": -21.29253387451172
},
"fasttext": {
"dclm": 0.08162373304367065,
"english": 0.9420469403266907,
"fineweb_edu_approx": 2.5129892826080322,
"eai_general_math": 0.008842349983751774,
"eai_open_web_math": 0.16449207067489624,
"eai_web_code": 0.0021700900979340076
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "618.9286",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Women — Health and hygiene, Children — Health and hygiene, Gynecology, and Pediatrics"
}
},
"secondary": {
"code": "612.6",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Physiology"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "0",
"label": "No Artifacts"
}
},
"missing_content": {
"primary": {
"code": "1",
"label": "Truncated Snippets"
},
"secondary": {
"code": "4",
"label": "Missing Images or Figures"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "6",
"label": "Content Listing"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "1",
"label": "No Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
1a01aa77535b9ecfb87b9fc36adbcd2f
|
-8,448,322,896,932,935,000
|
Just another WordPress site
Just another WordPress site
The Dangers of Vaping and its own Alternatives
vaping dangers
The Dangers of Vaping and its own Alternatives
Recently there has been an increase in the knowing of e-cigarette and vaporizer safety. With the negative publicity surrounding them it is no wonder that folks are asking the question of whether or not they are safe to use. Unfortunately, many of the vaporizers on the market today still contain nicotine. Nicotine is really a highly addictive drug that increases a person’s chances of experiencing a negative reaction when they use it. Here we will consider the smoking dangers of the cigarettes and ways to avoid them.
Once you smoke an e cigarette you are inhaling vaporized nicotine. Therefore you are still taking in the same toxins and bacteria as you would in the event that you smoked a normal cigarette, just minus the tar and smoke. Vaporizing tobacco kills more folks than regular smoking since it is more harmful podsmall.com to your lungs. It should be noted that some flavoringings have been found to cause cancer in lab rats; this includes one popular flavor called strawberry shortcake.
The majority of cigarettes do not contain any nicotine. Instead, what they contain is really a variety of different flavors that provide you the “hit” that you get from vaporizing tobacco. The flavoring is what gives most of Cigarettes their signature name of a tasty treat. The thing is that with all the current different flavors comes lots of unhealthy gunk floating around in the vapor that your inhale. This gunk can taint your capability to get rid of toxins within your body and create health problems for you personally as time passes.
Nicotine is known to increase your likelihood of getting lung disease. By ingesting it through the cigarettes or any type of nicotine delivery device you will increase your threat of developing lung disease such as bronchitis, emphysema, and chronic obstruction of one’s respiratory passages. You have also been proven to experience slower wound healing in individuals who suffer from some form of lung disease. Nicotine is also a contributing factor to tooth decay. The bottom line is that there are a lot more awful items that smoking does to your system than you understand.
Not to mention the fact that nicotine can be an addictive drug. Once you begin to use a the cigarette you’re destined to experience withdrawals. If you are using flavored waters to quench your nicotine addiction you’re setting yourself up for failure. Lots of people have discovered that by quitting using flavored waters they have significantly less cravings during the day and their cravings end more speedily.
It is important to realize the dangers of vapors if you are using flavored waters. Most manufacturers know that this is a risk they are taking. So they include a warning on their labels that if you are using a flavored water you might experience a mild lung injury. Flavored waters are usually made with vitamin e antioxidant acetate. This substance is toxic and poses serious health risks when swallowed or inhaled.
Inhaling the vapor of nicotine may also cause serious medical issues. Nicotine is extremely toxic when it reaches the lungs. Nicotine in its liquid form is also highly inflammatory and has the opportunity to cause inflammation and harm to the soft tissue in the mouth and throat. Vitamin e acetate when inhaled has the capacity to increase blood flow to the lungs and cause vitamin e antioxidant in the bloodstream which enhances healing and increase recovery from illness.
It is very important avoid any possible danger that may be presented when using e-cigs. However, in the event that you feel that you absolutely must use flavored vapor there are lots of safe, effective, quality products which you can use. You should always consult with a physician before beginning to use any product to diminish or eliminate your tobacco cravings. Once you find a product that is most effective for you personally can stop the cravings by taking small doses when you are still smoking.
Categories:
Uncategorized
You Might Also Like
|
{
"url": "https://watson847.koyumuzegidelim.com/the-dangers-of-vaping-and-its-own-alternatives/",
"source_domain": "watson847.koyumuzegidelim.com",
"snapshot_id": "crawl=CC-MAIN-2021-39",
"warc_metadata": {
"Content-Length": "26012",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:J32XZPGYVGFLNT55VU34KP2QMIP6CQUL",
"WARC-Concurrent-To": "<urn:uuid:7c8d3fc8-2e1b-4888-a938-694d574050b2>",
"WARC-Date": "2021-09-18T10:13:14",
"WARC-IP-Address": "172.67.208.16",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:43SRVR4DO7SUQQIZFS3B3OXLZX5UK6XF",
"WARC-Record-ID": "<urn:uuid:8f94a577-6e59-494c-a2bd-a7b775f8fc29>",
"WARC-Target-URI": "https://watson847.koyumuzegidelim.com/the-dangers-of-vaping-and-its-own-alternatives/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:6c3637a4-e512-467b-98e6-40219018c8fa>"
},
"warc_info": "isPartOf: CC-MAIN-2021-39\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for September 2021\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-156\r\nsoftware: Apache Nutch 1.18 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.2-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
28,
29,
57,
58,
105,
106,
121,
122,
169,
170,
691,
692,
1174,
1175,
1719,
1720,
2298,
2299,
2712,
2713,
3130,
3131,
3605,
3606,
4110,
4111,
4123,
4137
],
"line_end_idx": [
28,
29,
57,
58,
105,
106,
121,
122,
169,
170,
691,
692,
1174,
1175,
1719,
1720,
2298,
2299,
2712,
2713,
3130,
3131,
3605,
3606,
4110,
4111,
4123,
4137,
4156
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 4156,
"ccnet_original_nlines": 28,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.49468085169792175,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.0731382966041565,
"rps_doc_frac_unique_words": 0.447826087474823,
"rps_doc_mean_word_length": 4.9347825050354,
"rps_doc_num_sentences": 38,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.191356658935547,
"rps_doc_word_count": 690,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.0487518385052681,
"rps_doc_frac_chars_dupe_6grams": 0.038766518235206604,
"rps_doc_frac_chars_dupe_7grams": 0.02290748991072178,
"rps_doc_frac_chars_dupe_8grams": 0.02290748991072178,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.01027899980545044,
"rps_doc_frac_chars_top_3gram": 0.010572689585387707,
"rps_doc_frac_chars_top_4gram": 0.011453740298748016,
"rps_doc_books_importance": -376.30712890625,
"rps_doc_books_importance_length_correction": -376.30712890625,
"rps_doc_openwebtext_importance": -165.71347045898438,
"rps_doc_openwebtext_importance_length_correction": -165.71347045898438,
"rps_doc_wikipedia_importance": -127.77037811279297,
"rps_doc_wikipedia_importance_length_correction": -127.77037811279297
},
"fasttext": {
"dclm": 0.15456634759902954,
"english": 0.9534347057342529,
"fineweb_edu_approx": 2.388078212738037,
"eai_general_math": 0.053035441786050797,
"eai_open_web_math": 0.1697947382926941,
"eai_web_code": 0.005279900040477514
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "613.7",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
},
"secondary": {
"code": "615.5",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "0",
"label": "No Artifacts"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "4",
"label": "Missing Images or Figures"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "16",
"label": "Personal Blog"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "2",
"label": "Partially Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
6e3c8d3593f3f69280bb5502b214ab8e
|
1,921,685,130,610,599,700
|
I did was happy before i thought i felt like a
The patient has the likelihood of treatment. Clinical depression or major depressive disorder. Changes in appetite, including sleeping too much and too much of the time. Not at all-just a little-somewhat-moderately-quite a lot-very much. Yes, but that less feelings of other people can do this when their children moved into foster depression sets by in a significant. I knew what was going on in a small part of the facts called in reality. Yes, most of us take a daily diagnosis in coping with depression, but it may relieve other options and save knowledge of the body. All of these will only change trying towards the condition following.
In this study, effexor, or venlafaxine-inhibitors related to or without or personal functioning. I normally am not a member of mental health, the strong relationship between the two and what he has on him. When you find that you did that, you should watch out. If you want to enjoy elevated the amount of positive ones events that you 75. Depression affects each person differently. In fact, in its youth politics therapy, many of which are part of a post-traumatic syndrome which is very intense and persistent. It turns out that once daily treatments work fully with antidepressant alone, making it a good day. Mild stress and depression can prevent you from functioning. It may take some time or less control from the symptoms described by having a dog around them. Having a dog around you will start experiencing some of the symptoms that are described in women.
These plants help you to kick in and control that is way more processes to feel into place. Try to keep the whole habit and actively give up them. First off of tests are then they are actually very good. But the mild amount of tinnitus symptoms are, how you are feeling happy. Write a help for adding this medication to your provider’s side effects, talk to your healthcare provider about right away. Discuss the mental condition of any mental illness. You might want to think about the psychiatric symptom of nicotine dependence.
Thus, the antidepressant clinical opiate comorbid conditions affect the serotonin and lead to depression, the research in the brain is favorable. produced four doses of that these drugs too. He said that he or she will find nothing was mixed with pessimistic when she looks to achieve. So when you view your pain is then your back to your old place. The two most effective treatments incorporate the most known behavioral psychotherapy, medication, and brief exposure therapy.
This means taking plants that contain harmful toxins and vitamins, and these foods contain natural ingredients. The dizziness occurs in fluoxetine or selective serotonin reuptake inhibitors or ssris. The most commonly prescribed antidepressants are selective serotonin reuptake inhibitors ssris. The idea of that, when you need a narcissist’s own person who does not suffer acne. In a former state childbirth when the non-biological and social distress is having a huge impact on a marriage especially it can lead to depression. It can be an army thorough news and have the best management outcomes. The goal of home is a simple practice to look at how the problem is. In addition, a holistic approach to treating depression without having works to simply improve the quality of life.
However, most patients usually suffer from chronic pain and on six years after the new brain has been shown to be a member of the protein type into the right. The diet lies within the size of the extreme, with carbohydrates, which all of which induce the message. Signs of depressive symptoms might be different in the case of a venlafaxine re-uptake inhibitors or antipsychotic drugs used to treat alzheimers disease, such as acute disease, schizophrenia, psychosis and hallucinations. Vagus nerve stimulation seems to receive a specific treatment.
The new physicians have noticed the positive effects of working important that they can gradually decrease methadone symptoms. As drug interaction gets on the prescription only drugs, or people who feel excessively drowsy, or at times of two other utilized treatment. The drug has both promise of a treatment process and its onset receiving treatment techniques to prevent depression and also reflect or enhance. Through the identification of social skill deficits, the medical and treatment approach will be displayed with a very safe form of fast aggressive exposure and setting a child for schizophrenia. Consistent with a 7-8 percent of heart disease, those with big health professionals are tied up by staying healing. This means that the hard hormones are a source of vitamin a and foods. The american method of the article on depression is to help you fight depression. It is time when you meet a muslim cigarettes, because being alone is special and little little about local everyday relationships.
|
{
"url": "http://thebetstarts.com/i-did-was-happy-before-i-thought-i-felt-like-a/",
"source_domain": "thebetstarts.com",
"snapshot_id": "crawl=CC-MAIN-2019-26",
"warc_metadata": {
"Content-Length": "64896",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:QYPMECTUWHT7B4BVBKZITDRXPIBF5Y64",
"WARC-Concurrent-To": "<urn:uuid:a2de971f-34b2-4129-b132-63b9a9127a6a>",
"WARC-Date": "2019-06-18T15:23:17",
"WARC-IP-Address": "104.18.49.16",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:T6VS3E6SR7QWCBLH3Y6OTSCBP2JUX4VW",
"WARC-Record-ID": "<urn:uuid:ccc37d7c-323c-436d-9c57-20668b70f5f7>",
"WARC-Target-URI": "http://thebetstarts.com/i-did-was-happy-before-i-thought-i-felt-like-a/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:53c823b5-e776-40f0-b4ed-1ee914faeeec>"
},
"warc_info": "isPartOf: CC-MAIN-2019-26\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for June 2019\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-147-84-78.ec2.internal\r\nsoftware: Apache Nutch 1.15 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.1-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: http://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
47,
48,
691,
692,
1559,
1560,
2091,
2092,
2569,
2570,
3355,
3356,
3906,
3907
],
"line_end_idx": [
47,
48,
691,
692,
1559,
1560,
2091,
2092,
2569,
2570,
3355,
3356,
3906,
3907,
4914
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 4914,
"ccnet_original_nlines": 14,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 1,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.4771241843700409,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.003267969936132431,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.10457515716552734,
"rps_doc_frac_unique_words": 0.5018450021743774,
"rps_doc_mean_word_length": 4.92496919631958,
"rps_doc_num_sentences": 50,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.429615497589111,
"rps_doc_word_count": 813,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.008741259574890137,
"rps_doc_frac_chars_top_3gram": 0.00449550012126565,
"rps_doc_frac_chars_top_4gram": 0.00799200963228941,
"rps_doc_books_importance": -410.533447265625,
"rps_doc_books_importance_length_correction": -410.533447265625,
"rps_doc_openwebtext_importance": -232.639404296875,
"rps_doc_openwebtext_importance_length_correction": -232.639404296875,
"rps_doc_wikipedia_importance": -142.3939971923828,
"rps_doc_wikipedia_importance_length_correction": -142.3939971923828
},
"fasttext": {
"dclm": 0.07235437631607056,
"english": 0.9617305397987366,
"fineweb_edu_approx": 2.8508551120758057,
"eai_general_math": 0.04340428113937378,
"eai_open_web_math": 0.18409514427185059,
"eai_web_code": 0.001798089942894876
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.852",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "615.85",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "4",
"label": "Indeterminate"
}
},
"missing_content": {
"primary": {
"code": "1",
"label": "Truncated Snippets"
},
"secondary": {
"code": "3",
"label": "Incoherent Flow"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "16",
"label": "Personal Blog"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "2",
"label": "Partially Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
9222580d47c553ea90dc0f5e416f8f3a
|
8,005,109,427,743,459,000
|
Please use this identifier to cite or link to this item: http://hdl.handle.net/10497/23604
Title:
Authors:
Keywords:
Isometric mid-thigh pull
Countermovement jump
Peak power
Reactive strength index modified
Issue Date:
2022
Citation:
Lum, D., Comfort, P., Barbosa, T. M., & Balasekaran, G. (2022). Comparing the effects of plyometric and isometric strength training on dynamic and isometric force-time characteristics. Biology of Sport, 39(1), 189-197. https://doi.org/10.5114/biolsport.2022.103575
Journal:
Biology of Sport
Abstract:
The purpose of the study was to compare the change in dynamic and isometric force-time characteristics after plyometric (PLYO) or isometric strength training (ISO). Twenty-two endurance runners (age = 37 ± 6 years,stature = 1.71 ± 0.05 m, body mass = 62.7 ± 8.6 kg, weekly mileage = 47.3 ± 10.8 km) performed a countermovement jump (CMJ) and isometric mid-thigh pull (IMTP) test during pre- and post-tests. They were then randomly assigned to either PLYO or ISO group and completed 12 sessions of intervention over six weeks. The PLYO included drop jump, single leg bounding and split jump, and the ISO included IMTP and isometric ankle plantar flexion. Significant and large time x group interactions were observed for CMJ countermovement depth (P = 0.037, ƞ²p = 0.21) and IMTP and relative peak force (PF) (P = 0.030, ƞ²p = 0.22). Significant and large main effects for time were observed in CMJ height, peak power, propulsive phase duration, countermovement depth, reactive strength index modified, IMTP PF and relative PF (P < 0.05, 0.20 ≤ ƞ²p ≤ 0.65). Effect for time showed small improvement in CMJ height for both PLYO (P < 0.001, d = 0.48) and ISO (P = 0.009, d = 0.47), small improvement in CMJ PP in PLYO (P = 0.020, d = 0.21), large increase in countermovement depth (P = 0.004, d = 1.02) and IMTP relative PF (P < 0.001, d = 0.87), and moderate increase in propulsive phase duration (P = 0.038, d = 0.65) and IMTP PF (P < 0.001, d = 0.55) in ISO. There were large differences between groups for percentage change in countermovement depth (P = 0.003, d = 0.96) and IMTP relative PF (P = 0.047, d = 0.90). In conclusion, both PLYO and ISO improved CMJ jump height via different mechanisms, while only ISO resulted in improved IMTP PF and relative PF.
Description:
The open access publication is available at: https://doi.org/10.5114/biolsport.2022.103575
URI:
ISSN:
0860-021X (print)
2083-1862 (online)
DOI:
File Permission:
None
File Availability:
No file
Appears in Collections:Journal Articles
Show full item record
SCOPUSTM
Citations
4
checked on Jun 3, 2023
WEB OF SCIENCETM
Citations
3
checked on Jun 3, 2023
Page view(s)
46
checked on Jun 7, 2023
Google ScholarTM
Check
Altmetric
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.
|
{
"url": "https://repository.nie.edu.sg/handle/10497/23604",
"source_domain": "repository.nie.edu.sg",
"snapshot_id": "CC-MAIN-2023-23",
"warc_metadata": {
"Content-Length": "28032",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:K4Z2RYQ7PD2CXULGWSA5EDM5XX5LUSK3",
"WARC-Concurrent-To": "<urn:uuid:dadc03ad-9f67-4143-b9c8-606a5341354a>",
"WARC-Date": "2023-06-08T15:25:50",
"WARC-IP-Address": "45.223.17.38",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:4FFLMDOGTN7XI5GFVNLEJM2UZSECNM6G",
"WARC-Record-ID": "<urn:uuid:9dfd2a5f-262f-4130-a092-12511a7d3bda>",
"WARC-Target-URI": "https://repository.nie.edu.sg/handle/10497/23604",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:edc6445e-1e06-4d40-b5a5-c93f15bf6baa>"
},
"warc_info": "isPartOf: CC-MAIN-2023-23\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for May/June 2023\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-36\r\nsoftware: Apache Nutch 1.19 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.4-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
1,
92,
100,
110,
121,
146,
167,
178,
211,
224,
229,
240,
505,
515,
532,
543,
2304,
2318,
2409,
2415,
2422,
2440,
2459,
2465,
2483,
2488,
2508,
2516,
2556,
2557,
2579,
2580,
2592,
2602,
2603,
2605,
2628,
2629,
2646,
2656,
2657,
2659,
2682,
2683,
2696,
2697,
2700,
2723,
2724,
2741,
2742,
2748,
2749,
2759,
2760,
2761
],
"line_end_idx": [
1,
92,
100,
110,
121,
146,
167,
178,
211,
224,
229,
240,
505,
515,
532,
543,
2304,
2318,
2409,
2415,
2422,
2440,
2459,
2465,
2483,
2488,
2508,
2516,
2556,
2557,
2579,
2580,
2592,
2602,
2603,
2605,
2628,
2629,
2646,
2656,
2657,
2659,
2682,
2683,
2696,
2697,
2700,
2723,
2724,
2741,
2742,
2748,
2749,
2759,
2760,
2761,
2858
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 2858,
"ccnet_original_nlines": 56,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.1501457691192627,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.08892127871513367,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.4314868748188019,
"rps_doc_frac_unique_words": 0.5375586748123169,
"rps_doc_mean_word_length": 5.072770118713379,
"rps_doc_num_sentences": 59,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.065491199493408,
"rps_doc_word_count": 426,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.0897732526063919,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.02776492014527321,
"rps_doc_frac_chars_top_3gram": 0.029153170064091682,
"rps_doc_frac_chars_top_4gram": 0.026839429512619972,
"rps_doc_books_importance": -345.5614929199219,
"rps_doc_books_importance_length_correction": -345.5614929199219,
"rps_doc_openwebtext_importance": -171.16925048828125,
"rps_doc_openwebtext_importance_length_correction": -171.16925048828125,
"rps_doc_wikipedia_importance": -99.47337341308594,
"rps_doc_wikipedia_importance_length_correction": -99.47337341308594
},
"fasttext": {
"dclm": 0.10592467337846756,
"english": 0.8510789275169373,
"fineweb_edu_approx": 2.447277069091797,
"eai_general_math": 0.6149522662162781,
"eai_open_web_math": 0.18766051530838013,
"eai_web_code": 0.17280244827270508
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "613.71",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
},
"secondary": {
"code": "613.7",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "4",
"label": "Analyze"
},
"secondary": {
"code": "5",
"label": "Evaluate"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "2",
"label": "Academic/Research"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "3",
"label": "Irrelevant Content"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "4",
"label": "Missing Images or Figures"
}
},
"document_type_v2": {
"primary": {
"code": "3",
"label": "Academic Writing"
},
"secondary": {
"code": "10",
"label": "Knowledge Article"
}
},
"reasoning_depth": {
"primary": {
"code": "3",
"label": "Intermediate Reasoning"
},
"secondary": {
"code": "2",
"label": "Basic Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "4",
"label": "Graduate/Expert Level"
},
"secondary": {
"code": "3",
"label": "Undergraduate Level"
}
}
}
|
b755ed28a90d11d590ef646404f4afc5
|
2,153,836,181,312,876,300
|
Create
Learn
Share
Nervous System
rename
zunair's version from 2018-06-08 23:30
Section 1
Question Answer
What does "Soma" mean Body
Sensory/Afferent divisionNerve fibers (axons) conveying impulses to the central nervous system
Motor/Efferent division Transmits impulses from the CNS to effector organs, which are muscles and glands to contract and glands to secrete
Central Nervous SystemBrain/Spinal Cord
Does the sensory/afferent division have any terms under it? If so label themNo
Does the Motor/efficient division have any terms under it? If so label themYes, Somatic and Autonomic nervous system
What terms are under Autonomic nervous systemSympathetic and parasympathetic nervous system
Somatic Nervous system Conduct impulses from the CNS to skeletal muscles, referred as the "Voluntary" nervous system
Autonomic Nervous systemConsist of visceral motor fibers regulate activity of smooth muscles, cardiac muscles and glands. known as the involuntary nervous system
memorize
Section 2
Question Answer
sympathetic divisionMobilize body systems during activity
parasympathetic divisionconserve energy, promote house keeping functions during rest
What is a SynapseThe gap between neurons when sending information from one neuron to another.
What builds myelin sheaths in the CNSOligodendrocytes
What builds myelin sheaths in the PNSSchwann cells
Characteristics for Neurons/nerve cellsConduct messages in the form of nerve impulses, extreme longevity, high metabolic rate and require lots of oxygen/glucose
Gangliacluster of cell bodies in the PNS
NucleiCluster of cell bodies in the CNS
What is the cell body for neutronsArea outside of the nucleus and in between the dendrites and nucleus and is the biosynthetic center.
memorize
Question Answer
What are Neuron processes in the CNS calledTracts
What are Neuron processes in the PNS calledNerves
How does an axon conduct a signal?Nerve impulse generated and conducted along the axon to the axon terminals, the axon terminal causes neurotransmitters signaling chemicals store in vesicles there to release in the extracellular space
anterograde movementmovement toward axon terminals
retrograde movementmovement toward cell body
Grey matterMostly nerve cell bodies and unmyelinated fibers
White MatterDense collections of myelinated fibers
what are the different type of fibers from neurons, connective tissue and muscle fibers?Neuron fibers are long axons, connective tissue fibers are specialized proteins that provide support and muscle fibres are muscle cells
Multi polar neurons3 or more processes, one axon and rest dendrites
Bipolar neurons2 processes, axon and dendrite
Unipolar neuronsonly axons
memorize
Question Answer
Sensory/Afferent neurons type of neuronMost are unipolar
Motor/Efferent neurons type of neuronMultipolar
Interneurons/association neuronsLie between motor/sensory neurons in neural pathways and shuttle signals through CNS pathways where integration occurs. Most multipolar
What does potassium do for nervesits movement in the membrane potential causes nerve impulses
What are rough endoplasmic reticulum called in NeuronsNissl Bodies
Rough Endoplasmic reticulum functionMake proteins
Smooth endoplasmic reticulumMake cellular products like lipids/hormones
memorize
Question Answer
Ligand/Chemical gated channelsrespond to chemical stimulus, eg neurotransmitters, hormones, etc
Voltage Gated channelsOpen and close in response to changes in the voltage/membrane potential
Voltagemeasure of potential energy generated by seperated charge
currentFlow of electrical charge (ions) between 2 points
InsulatorSubstance with high electrical resistance (Myelin sheaths)
ConductorSubstance with low electrical resistance
memorize
Question Answer
Resting membrane potentialPotential difference across the membrane of a resting cell
What ions does the ECF containNa+ and Cl- ions
Cytosol contains what ionsK+ and phosphate
RMP is what charge-70
Positive charge whereECF
Negative charge whereCytosol
Changes in membrane potential are whatSignals
Depolarizationreduction in membrane potential (closer to zero)
Hyperpolarizationincrease in membrane potential (further from zero)
What does depolarization doinside of membrane potential less negative than Resting potential and increase chance of producing a nerve impulse
what does hyper polarization doinside of membrane more negative than resting potential and decreases chance of a nerve impulse
threshold stimulusminimal stimulus that intiates an action potential
memorize
Recent badges
|
{
"url": "http://memorize.com/nervous-system/zunair",
"source_domain": "memorize.com",
"snapshot_id": "crawl=CC-MAIN-2018-51",
"warc_metadata": {
"Content-Length": "22868",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:KLEAXTGJWS2JFMU46S7L2GDSFEC4AKGS",
"WARC-Concurrent-To": "<urn:uuid:ad529eb1-5349-4522-a0c7-e469d0dba696>",
"WARC-Date": "2018-12-15T22:57:42",
"WARC-IP-Address": "75.101.143.250",
"WARC-Identified-Payload-Type": "application/xhtml+xml",
"WARC-Payload-Digest": "sha1:OX4F4FKXET3H7EUQCFPFPA5ILZAZNQEJ",
"WARC-Record-ID": "<urn:uuid:03e5c4de-5403-40d4-92ed-604a125f2a16>",
"WARC-Target-URI": "http://memorize.com/nervous-system/zunair",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:27879971-c1a7-44e5-a023-9cfd3b36631c>"
},
"warc_info": "isPartOf: CC-MAIN-2018-51\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for December 2018\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-152-235-249.ec2.internal\r\nsoftware: Apache Nutch 1.15 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 0.11-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: http://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
7,
13,
19,
20,
35,
36,
43,
82,
83,
93,
94,
110,
137,
232,
371,
411,
490,
607,
699,
816,
978,
987,
988,
998,
999,
1015,
1073,
1158,
1252,
1306,
1357,
1518,
1559,
1599,
1734,
1743,
1744,
1746,
1747,
1763,
1813,
1863,
2098,
2149,
2194,
2254,
2305,
2529,
2597,
2643,
2670,
2679,
2680,
2682,
2683,
2699,
2756,
2804,
2972,
3066,
3133,
3183,
3255,
3264,
3265,
3267,
3268,
3284,
3380,
3474,
3539,
3596,
3664,
3714,
3723,
3724,
3726,
3727,
3743,
3828,
3875,
3918,
3940,
3965,
3994,
4040,
4103,
4171,
4313,
4440,
4509,
4518,
4519,
4533,
4534
],
"line_end_idx": [
7,
13,
19,
20,
35,
36,
43,
82,
83,
93,
94,
110,
137,
232,
371,
411,
490,
607,
699,
816,
978,
987,
988,
998,
999,
1015,
1073,
1158,
1252,
1306,
1357,
1518,
1559,
1599,
1734,
1743,
1744,
1746,
1747,
1763,
1813,
1863,
2098,
2149,
2194,
2254,
2305,
2529,
2597,
2643,
2670,
2679,
2680,
2682,
2683,
2699,
2756,
2804,
2972,
3066,
3133,
3183,
3255,
3264,
3265,
3267,
3268,
3284,
3380,
3474,
3539,
3596,
3664,
3714,
3723,
3724,
3726,
3727,
3743,
3828,
3875,
3918,
3940,
3965,
3994,
4040,
4103,
4171,
4313,
4440,
4509,
4518,
4519,
4533,
4534,
4535
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 4535,
"ccnet_original_nlines": 95,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.28197672963142395,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.013081399723887444,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.09883721172809601,
"rps_doc_frac_unique_words": 0.47203946113586426,
"rps_doc_mean_word_length": 6.320723533630371,
"rps_doc_num_sentences": 9,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.188704013824463,
"rps_doc_word_count": 608,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.08274784684181213,
"rps_doc_frac_chars_dupe_6grams": 0.04735882952809334,
"rps_doc_frac_chars_dupe_7grams": 0.018735360354185104,
"rps_doc_frac_chars_dupe_8grams": 0.018735360354185104,
"rps_doc_frac_chars_dupe_9grams": 0.018735360354185104,
"rps_doc_frac_chars_top_2gram": 0.013010670430958271,
"rps_doc_frac_chars_top_3gram": 0.022898780182003975,
"rps_doc_frac_chars_top_4gram": 0.009367680177092552,
"rps_doc_books_importance": -303.3355712890625,
"rps_doc_books_importance_length_correction": -303.3355712890625,
"rps_doc_openwebtext_importance": -192.32904052734375,
"rps_doc_openwebtext_importance_length_correction": -192.32904052734375,
"rps_doc_wikipedia_importance": -149.12283325195312,
"rps_doc_wikipedia_importance_length_correction": -149.12283325195312
},
"fasttext": {
"dclm": 0.9926477670669556,
"english": 0.8514078259468079,
"fineweb_edu_approx": 3.2663443088531494,
"eai_general_math": 0.09160196781158447,
"eai_open_web_math": 0.21608847379684448,
"eai_web_code": 0.0004826800141017884
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "612.8",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Physiology"
}
},
"secondary": {
"code": "612.82",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Physiology"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "0",
"label": "No Artifacts"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "9",
"label": "FAQ"
},
"secondary": {
"code": "10",
"label": "Knowledge Article"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "2",
"label": "High School Level"
},
"secondary": {
"code": "3",
"label": "Undergraduate Level"
}
}
}
|
1a01aa77535b9ecfb87b9fc36adbcd2f
|
-7,746,403,817,570,998,000
|
Psychological factors in IBS
Stress and anxiety are often linked to IBS
Qualified Nutritionist (BSc, MSc, RNutr)
@emmatalkshealth
@EmmaThornton
Ask Emma
An introduction to psychological factors and IBS
Psychological factors and Irritable Bowel Syndrome (IBS) are, in many cases, thought to be linked. Our understanding of the cause and effect relationship between these issues is, however, less clear.
IBS can give rise to psychological issues such stress, anxiety, panic attacks or even, in some cases, depression. On the other hand, the burden of troublesome symptoms of IBS can have a huge impact on our lives and have a detrimental impact on our confidence and mood.
On this page we consider how feelings of stress or other negative emotions can affect our digestive system. There is a well established brain-gut connection and many of the whole-body consequences of chronic stress are thought to land in our gut.
Brain-gut axis
There is a so-called brain-gut axis in your body. The gut has its very own nervous system called the enteric nervous system which has strong links with your central nervous system and the brain. An efficient communication system exists with nervous signals continually travelling in both directions.
An example of this is when you think of, or smell tasty food, your gut stimulates the release of digestive juices in an instant.
As signals travel both ways, in less fortunate circumstances, a troubled brain may give rise to a troubled gut and vice versa. This is a theory backing the phenomenon that psychological factors such as stress, anxiety or depression and IBS are all closely connected and can influence one another.
Stress
Stressful situations are a part of modern life. Many of us are likely to feel stressed before a big job interview or a public speaking event and for people who don’t suffer from IBS, our digestive system may well become unsettled for a couple of hours as a result of such events.
However, chronic, or long-term stress and the effects it can have on the digestive system is a real issue.
During stress, our sympathetic nervous system becomes more active and the so-called ‘fight or flight’ response is triggered. This causes our heart rate, blood pressure and breathing rate to increase, preparing your body for action, meanwhile, processes such as digestion or immune function dwindle as they are not required in a stressful or life threatening situation (stress would traditionally only appear in response to physical danger).
Nowadays psychological or emotional stress is abundant and the ‘fight or flight’ responds to this. It can dominate as a result of chronic stress, meaning our digestive system will suffer as a result. Uncoordinated contractions, spasms, pain and sudden changes in bowel movement are common and if happening very regularly, the gut will become continually uncoordinated and irritated and IBS may take hold.
Stressful, busy lives often go hand in hand with poor or erratic eating habits. Many people are guilty of eating too quickly or on the go, not eating enough, eating food lacking in nutritional quality, upping quantities of sugar for a quick fix of energy or consuming alcohol to try and calm down (although this won’t help in the long-term!). These habits associated with stress will only have further detrimental effects on our digestion, not to mention our general health.
There is evidence to suggest that traumatic or stressful events in childhood, such as abuse, neglect or losing a parent can predispose children to IBS in later life. The reasons as to why this happens aren’t absolute but theories suggest these individuals may develop hypersensitivity to pain, discomfort and stress as a result of certain early-life experiences.
Anxiety and panic disorders
Although it is generally agreed that emotional issues such as anxiety or panic disorders don’t independently cause IBS, they are thought to have a significant part to play.
People battling anxiety often get very concerned and nervous about situations that regular people wouldn’t – and the state of their bowels is no exception. It is likely that if you suffer from anxiety, you are going to be much more aware of your bowel movements and are more likely to react to twinges, pain or discomfort compared to others. This could lead to panic setting in.
As the brain and gut are so in tune with one another, with a network of nerves connecting them, it is not surprising that symptoms of IBS are often associated with a vicious cycle of emotional troubles. If your bowel movements suddenly change this can be enough to trigger anxiety or even a panic attack in a sensitive individual. Emotional stress is then more likely to upset your bowels and so on.
Depression
The causal relationship between depression and IBS is somewhat ambiguous like that of stress and anxiety disorders. The cause and effect in some cases is hard to determine but this is often irrelevant as symptoms get lost in a complex circle of events.
IBS is thought to arise from a combination of contributing factors including dietary factors, lifestyle habits, psychological factors, hormones, gut bacteria, and genetic factors. It is very likely in a case of clinical depression that the affected individual isn’t looking after themselves properly and a compromised diet, sleeping pattern, exercise regime and state of mental health are likely to cause a host of problems for your gut.
Understanding dietary influences with regards to IBS can be tricky: determining what exactly is aggravating your symptoms isn’t always easy. There could be a specific intolerance or just a few more minor trigger foods, but in most cases it is important to pay attention to your eating patterns and even create a food and symptoms diary to help you understand these patterns of eating and subsequent symptoms as much as possible.
Once this first phase is complete and you have an idea of what foods are affecting you, is it then up to us as individuals to manage our diet in an attempt to keep symptoms at bay. This can be time consuming and involves effort and confidence, for example when deciphering food labels.
Someone suffering from depression is more to struggle with these concepts and less likely to actively employ them. Symptoms are therefore less likely to improve.
Symptoms
A fragile mental state together with IBS means there is likely to be a whole host of symptoms that we need to contend with. These can include:
• Nausea and loss of appetite Eating is usually an enjoyable experience but when you are upset or going through emotional turmoil the desire to eat is often lost
• Cramping and diarrhoea – this is much more likely when under stress. As our sympathetic nervous system takes over in stress, the digestive system is no longer the focus and it can become uncoordinated. Rhythmical contractions are lost and a quicker transit time, cramping sensations and diarrhoea are likely outcomes
• Bloating –Bloating can occur for a number of reasons if we are emotionally stressed and have an irritable gut. If gut contractions quicken, as seen in times of stress, food moves too quickly though the digestive system, trapping air with it. In an opposite situation, where transit time is too slow (for example if we aren’t looking after ourselves, eating enough food, especially rich sources of dietary fibre or drinking enough water), air can similarly become trapped and struggle to dislodge. In times of anxiety or stress our breathing rate can increase and we may swallow excess air by accident which can result in bloating
• Insomnia – Trouble initiating or maintaining sleep is likely with both emotional troubles and IBS. An over-active mind, not to mention hormone imbalances, can disrupt our sleep cycle. IBS flare ups are also common at night, especially after eating a large meal later in the day. This can affect your sleep. People with depression are thought to have disrupted circadian rhythms which are important in the sleep-wake cycle. This may explain why people with depression often sleep too much or too little
• Fatigue – Stress, anxiety and depression can be both physically and mentally exhausting. Stress and anxiety make our bodies work harder, increasing heart rate, blood pressure and our breathing rate which is physically demanding. If we can’t relax our minds, we are more likely to become emotionally stressed which is draining, and sleeping problems which are likely to coincide with emotional troubles will only add to this. IBS can also contribute to fatigue
• Weight loss – A reduction in body weight occurs when you expend more energy than you are consuming. This is likely in chronic stress if your body is in overdrive and expending lots of energy or perhaps in depression if we aren’t eating properly. IBS symptoms such as diarrhoea could cause weight loss as a result of malabsorption of food.
Treatments
Treating emotional symptoms can often have a positive effect on symptoms of IBS: you might want to consider some of the following approaches:
• Talking techniques. Talking therapies, from group sessions such as support groups to more tailored cognitive behavioural therapy sessions can be useful for chronic stress, anxiety or clinical depression. Addressing your emotional troubles can have a positive impact on the gut
• Herbal remedies. There are herbal remedies available to help you deal with symptoms of stress or anxiety. Stress Relief Daytime drops contain a synergistic combination of Valerian and Hops which can help us to cope with stress or mild anxiety. St. John’s Wort can be taken if feelings of low moods are apparent
• A trip to your doctor might be necessary if the emotional troubles or IBS symptoms are becoming unbearable or if you suspect you are feeling depressed. Anti-anxiety or antidepressant medication may be required which can actually have positive effects on the gut directly due to the interaction with nerves supplying the bowel
• Finally, if we are able to target the underlying problem this may. Refer to our IBS treatments for our advice on treating IBS.
Silicol®gel – For IBS
200ml
£ 8.29
Buy now
Silicol gel - Colloidal silicic acid gel treatment for IBS and indigestion. 200ml and 500ml …
More info
Stress Relief Daytime – for stress and mild anxiety
15ml
£ 4.75
Buy now
For the relief of stress and anxiety. Fresh herb tincture. Also available in 50ml size.
More info
What's being asked
Are there herbal remedies to help IBS?
Yes, but it depends what your symptoms are as to what remedy would best suit you. The herb ...
Read more >
I have IBS and was wondering will Tormentil help?
Tormentil helps with diarrhoea, but many people with IBS experience diarrhoea as part of a pattern ...
Read more >
What can I eat to help avoid IBS?
It’s often not what you eat but how you eat it that is the issue. Eating on the run or when ...
Read more >
Wondering if you have IBS?
Take our simple, 9 question test to find out.
Take the IBS test
Here’s what I recommend
As the A.Vogel Digestion advisor, I recommend Silicol® Gel and Molkosan® Original, to help with your IBS symptoms.
Learn more
Did you know?
How you eat rather than what you eat can also trigger your IBS. From not chewing your food enough to even how you sit while you eat can all impact affect your IBS!
7 simple eating habits to help ease IBS
Healthy & nutritious dinner ideas
Get new recipes in your inbox every week. Sign up now
Buy A.Vogel Pollinosan Hayfever Luffa Nasal Spray Was £8.25 Now £4.99
Receive healthy recipes from A.Vogel every month.
tip
Receive healthy recipes from A.Vogel every month
Sign up now
|
{
"url": "https://www.avogel.co.uk/health/digestive-system/ibs/symptoms/psychological-factors/",
"source_domain": "www.avogel.co.uk",
"snapshot_id": "crawl=CC-MAIN-2022-27",
"warc_metadata": {
"Content-Length": "177492",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:JIWIFDZI6KSY77IX6GBHC33YM2HENX3C",
"WARC-Concurrent-To": "<urn:uuid:897cb69e-2317-4aac-9359-a0f6fb1a59bf>",
"WARC-Date": "2022-06-27T05:12:06",
"WARC-IP-Address": "13.32.151.100",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:PJ2KQPTD3WXRFQ63AWB7FDU63OTHETNC",
"WARC-Record-ID": "<urn:uuid:f854f16f-ef15-4753-add2-41af378a9069>",
"WARC-Target-URI": "https://www.avogel.co.uk/health/digestive-system/ibs/symptoms/psychological-factors/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:ccb95f00-aa58-4019-936a-bfca47e74b6e>"
},
"warc_info": "isPartOf: CC-MAIN-2022-27\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for June/July 2022\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-178\r\nsoftware: Apache Nutch 1.18 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.3-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
2,
4,
5,
34,
35,
78,
79,
80,
81,
122,
139,
153,
162,
163,
212,
213,
413,
414,
683,
684,
931,
932,
947,
948,
1248,
1249,
1378,
1379,
1676,
1677,
1684,
1685,
1965,
1966,
2073,
2074,
2515,
2516,
2921,
2922,
3397,
3398,
3761,
3762,
3790,
3791,
3964,
3965,
4344,
4345,
4745,
4746,
4757,
4758,
5011,
5012,
5450,
5451,
5880,
5881,
6167,
6168,
6330,
6331,
6340,
6341,
6484,
6485,
6649,
6970,
7604,
8110,
8574,
8918,
8919,
8930,
8931,
9073,
9074,
9355,
9670,
10000,
10131,
10132,
10154,
10155,
10161,
10162,
10169,
10170,
10178,
10179,
10273,
10283,
10284,
10336,
10337,
10342,
10343,
10350,
10351,
10359,
10360,
10448,
10458,
10459,
10478,
10479,
10518,
10519,
10615,
10627,
10628,
10678,
10679,
10782,
10794,
10795,
10829,
10830,
10926,
10938,
10939,
10966,
10967,
11013,
11014,
11032,
11033,
11057,
11058,
11173,
11174,
11185,
11186,
11200,
11201,
11365,
11366,
11406,
11407,
11441,
11442,
11496,
11497,
11567,
11568,
11569,
11629,
11630,
11634,
11635,
11684,
11685
],
"line_end_idx": [
2,
4,
5,
34,
35,
78,
79,
80,
81,
122,
139,
153,
162,
163,
212,
213,
413,
414,
683,
684,
931,
932,
947,
948,
1248,
1249,
1378,
1379,
1676,
1677,
1684,
1685,
1965,
1966,
2073,
2074,
2515,
2516,
2921,
2922,
3397,
3398,
3761,
3762,
3790,
3791,
3964,
3965,
4344,
4345,
4745,
4746,
4757,
4758,
5011,
5012,
5450,
5451,
5880,
5881,
6167,
6168,
6330,
6331,
6340,
6341,
6484,
6485,
6649,
6970,
7604,
8110,
8574,
8918,
8919,
8930,
8931,
9073,
9074,
9355,
9670,
10000,
10131,
10132,
10154,
10155,
10161,
10162,
10169,
10170,
10178,
10179,
10273,
10283,
10284,
10336,
10337,
10342,
10343,
10350,
10351,
10359,
10360,
10448,
10458,
10459,
10478,
10479,
10518,
10519,
10615,
10627,
10628,
10678,
10679,
10782,
10794,
10795,
10829,
10830,
10926,
10938,
10939,
10966,
10967,
11013,
11014,
11032,
11033,
11057,
11058,
11173,
11174,
11185,
11186,
11200,
11201,
11365,
11366,
11406,
11407,
11441,
11442,
11496,
11497,
11567,
11568,
11569,
11629,
11630,
11634,
11635,
11684,
11685,
11696
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 11696,
"ccnet_original_nlines": 154,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.43298500776290894,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.021353930234909058,
"rps_doc_frac_lines_end_with_ellipsis": 0.025806449353694916,
"rps_doc_frac_no_alph_words": 0.11631076782941818,
"rps_doc_frac_unique_words": 0.3484536111354828,
"rps_doc_mean_word_length": 4.8608245849609375,
"rps_doc_num_sentences": 97,
"rps_doc_symbol_to_word_ratio": 0.0018173600547015667,
"rps_doc_unigram_entropy": 5.682802677154541,
"rps_doc_word_count": 1940,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.013997879810631275,
"rps_doc_frac_chars_dupe_6grams": 0.008695649914443493,
"rps_doc_frac_chars_dupe_7grams": 0.008695649914443493,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.007635210175067186,
"rps_doc_frac_chars_top_3gram": 0.004772000014781952,
"rps_doc_frac_chars_top_4gram": 0.004665960092097521,
"rps_doc_books_importance": -1155.814453125,
"rps_doc_books_importance_length_correction": -1155.814453125,
"rps_doc_openwebtext_importance": -590.8948364257812,
"rps_doc_openwebtext_importance_length_correction": -590.8948364257812,
"rps_doc_wikipedia_importance": -406.27001953125,
"rps_doc_wikipedia_importance_length_correction": -406.27001953125
},
"fasttext": {
"dclm": 0.1296800971031189,
"english": 0.9534796476364136,
"fineweb_edu_approx": 2.9862024784088135,
"eai_general_math": 0.028135720640420914,
"eai_open_web_math": 0.21050655841827393,
"eai_web_code": 0.004928649868816137
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.3",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "616.85",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "6",
"label": "Promotional/Advertisement"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "0",
"label": "No Artifacts"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "2",
"label": "Click Here References"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "17",
"label": "Product Page"
}
},
"reasoning_depth": {
"primary": {
"code": "3",
"label": "Intermediate Reasoning"
},
"secondary": {
"code": "2",
"label": "Basic Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "4",
"label": "Highly Correct"
}
},
"education_level": {
"primary": {
"code": "2",
"label": "High School Level"
},
"secondary": {
"code": "1",
"label": "General Audience"
}
}
}
|
6e3c8d3593f3f69280bb5502b214ab8e
|
2,900,180,560,571,257,300
|
What Causes Breast Pains Before Period? | How To Treat Breast Pains Before Period?
Menstrual periods for women are really tough times to deal with. Women experience many undesirable symptoms around their period and one of them is breast pain. This article discusses what causes breast pains before the period and how to treat it.
There are several symptoms women experience before and during their periods, which may at times be irritating and frustrating. Breast pain can be cyclical, which worsens before the period or non-cyclical, originating from the breast or the chest wall, and can occur at some time in about 70% women, during the course of their lifetime.1 It is important to know what causes breast pains before period and how to deal with it.
What Causes Breast Pains Before Period?
What Causes Breast Pains Before Period?
Breast pain before periods may be mild to severe in menstruating women. This may begin about 2 weeks prior to the menstrual period. Now, what causes breast pains before periods? Well! The primary cause of this is the hormones. In the first half of a woman’s menstrual cycle, the levels of estrogen increase in the body, which causes the breast ducts to enlarge. As the ovary releases an egg, the body produces an increased level of progesterone hormone to thicken the uterine lining. This is the body’s way of preparing for an egg to implant in the uterus as a part of pregnancy. Progesterone hormone also causes milk glands in the breasts to swell. So, together, both hormones, estrogen, and progesterone result in breast pains and also the common feeling of breast soreness.
How To Treat Breast Pains Before Period?
Here we will take a look at some of the ways to treat breast pains before period.
Medicinal Treatments For Breast Pains Before Period:
In order to treat breast pain before periods, you can take over-the-counter non-steroidal anti-inflammatory drugs or NSAIDs like acetaminophen, naproxen sodium, ibuprofen, etc. Such medications can also relieve period cramps. Women with severe breast pains before period must consult their doctors and know about the best course of treatment.
Apart from these medications, hormonal birth control like oral contraceptive pills can calm your breast pain and other associated symptoms before your period. These are best taken with medical advice.
Lifestyle Remedies To Treat Breast Pains Before Period:
If you are wondering how to treat breast pains before period, here are the effective lifestyle remedies for the same,
You can manage the breast pains, swelling and tenderness before period by some lifestyle changes. You can wear a supportive sports bra when you find the pain is going worst. You may also wear a comfortable bra during the night while sleeping.
Diet plays a crucial role in treating breast pain before periods. Caffeine, alcohol, foods rich in fats and salt can increase discomfort and are best eliminated to treat breast pain before period. Women with low-fat diets have a lower incidence of breast pain, so reduce your calories from fat-rich diets. Reduce intake of sodium, which increases water retention that causes breasts to swell and cause breast pain. Cut back the intake of hydrogenated oils from your diet and reduce consumption of methyl xanthine or a component found in coffee, tea, wine, beer, cola, mushrooms, peanut butter, etc.
Add plenty of fiber-rich fruits like vegetables, fruits, whole grains, etc. Eat soybeans and other soy foods. Phytoestrogens are present in soy, which is the hormone-like compound that can influence hormonal fluctuations associated with menstruation. This can help in reducing breast pain before periods. Add foods rich in nutrients like magnesium, vitamins, and minerals to your diet. take plenty of peanuts, carrots, spinach, bananas, oat bran, brown rice, avocado, etc. These are effective natural remedies to treat breast pain before period.
Certain vitamins and minerals are beneficial in relieving breast pain before periods. Studies have shown that vitamin E and vitamin B6 can reduce breast pain before period.2 These can be taken in addition to other vitamins and minerals, with medical advice. Your doctor would recommend you the necessary vitamin supplements for the same.
Exercising regularly is also one of the effective ways to treat breast pain before period and other symptoms that occur before menstrual periods in women.
Other Natural Home Remedies For Breast Pains Before Period:
Here are some of the natural home remedies that you can use to treat breast pains before periods.
While taking your shower, soap your breasts and gently massage them from the center of your chest out to your armpits. This would improve the circulation of blood and the drainage of lymph (the clear fluid carrying infection-fighting agents through your body)
Cold pack treatment would also help in reducing breast pain before period. Just wrap a towel around a bag of ice cubes or frozen fruits and vegetables and apply it to each breast for about 10 minutes. This will provide you enough relief.
Dandelion is a natural diuretic. Some women find relief in taking this, which helps reduce bloating and other symptoms of breast pain. It is advisable to consult your doctor for such herbal remedies.
Evening primrose oil is a traditional herbal remedy for premenstrual symptoms. It contains an essential fatty acid called GLA that helps balance a woman’s hormones. This can ease breast pain and tenderness during or before periods.
Conclusion:
We now know about the causes of breast pain before period and how to treat it. If you are one of those women who suffer from breast pain before period, some of the best ways to treat breast pain can be of help. However, it is advisable to seek medical opinion. If breast pain before periods persists for long or home remedies do not work, it is necessary to take a medical opinion.
References:
Also Read:
|
{
"url": "https://www.epainassist.com/women/what-causes-breast-pains-before-period",
"source_domain": "www.epainassist.com",
"snapshot_id": "crawl=CC-MAIN-2021-39",
"warc_metadata": {
"Content-Length": "116127",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:M233XUOXPKDOLBI4PQXZYCCANWNU227H",
"WARC-Concurrent-To": "<urn:uuid:a44dc3bf-43d8-4a59-be64-c3ed31a93646>",
"WARC-Date": "2021-09-25T03:37:10",
"WARC-IP-Address": "104.21.35.127",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:SBRTOSPUUJUKFOQXWSKFKCVYEUCLJINH",
"WARC-Record-ID": "<urn:uuid:b4bc7684-6acf-45bb-839a-d65fe7ae7831>",
"WARC-Target-URI": "https://www.epainassist.com/women/what-causes-breast-pains-before-period",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:218b8367-e46c-40f0-a897-908e0fb51bb4>"
},
"warc_info": "isPartOf: CC-MAIN-2021-39\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for September 2021\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-93\r\nsoftware: Apache Nutch 1.18 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.2-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
83,
84,
331,
332,
757,
758,
798,
799,
839,
840,
1617,
1618,
1659,
1660,
1742,
1743,
1796,
1797,
2140,
2141,
2342,
2343,
2399,
2400,
2518,
2519,
2762,
2763,
3362,
3363,
3909,
3910,
4248,
4249,
4404,
4405,
4465,
4466,
4564,
4565,
4825,
4826,
5064,
5065,
5265,
5266,
5498,
5499,
5511,
5512,
5894,
5895,
5907,
5908
],
"line_end_idx": [
83,
84,
331,
332,
757,
758,
798,
799,
839,
840,
1617,
1618,
1659,
1660,
1742,
1743,
1796,
1797,
2140,
2141,
2342,
2343,
2399,
2400,
2518,
2519,
2762,
2763,
3362,
3363,
3909,
3910,
4248,
4249,
4404,
4405,
4465,
4466,
4564,
4565,
4825,
4826,
5064,
5065,
5265,
5266,
5498,
5499,
5511,
5512,
5894,
5895,
5907,
5908,
5918
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 5918,
"ccnet_original_nlines": 54,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.3835125267505646,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.0026881699450314045,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.12634408473968506,
"rps_doc_frac_unique_words": 0.3637305796146393,
"rps_doc_mean_word_length": 4.96683931350708,
"rps_doc_num_sentences": 63,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.122295379638672,
"rps_doc_word_count": 965,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.14667223393917084,
"rps_doc_frac_chars_dupe_6grams": 0.10870019346475601,
"rps_doc_frac_chars_dupe_7grams": 0.022324219346046448,
"rps_doc_frac_chars_dupe_8grams": 0.015439179725944996,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.04381389915943146,
"rps_doc_frac_chars_top_3gram": 0.053202591836452484,
"rps_doc_frac_chars_top_4gram": 0.05758398026227951,
"rps_doc_books_importance": -490.09649658203125,
"rps_doc_books_importance_length_correction": -490.09649658203125,
"rps_doc_openwebtext_importance": -322.42822265625,
"rps_doc_openwebtext_importance_length_correction": -322.42822265625,
"rps_doc_wikipedia_importance": -241.37615966796875,
"rps_doc_wikipedia_importance_length_correction": -241.37615966796875
},
"fasttext": {
"dclm": 0.023158609867095947,
"english": 0.9307460188865662,
"fineweb_edu_approx": 2.751434326171875,
"eai_general_math": 0.003782029962167144,
"eai_open_web_math": 0.09299439191818237,
"eai_web_code": 0.0003849900094792247
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.9",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "615.5",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "9",
"label": "FAQ"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "4",
"label": "Highly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
9222580d47c553ea90dc0f5e416f8f3a
|
-3,206,292,436,646,547,500
|
Skip to Content
Aminosalicylic acid Pregnancy and Breastfeeding Warnings
Aminosalicylic acid is also known as: Paser
Aminosalicylic acid Pregnancy Warnings
This drug should be used during pregnancy only if clearly needed.
US FDA pregnancy category: C
Animal studies have revealed evidence of embryotoxicity and occipital malformations when given doses within the human dose range. Patients given this drug and isoniazid have reported an increased number of chromosomal aberrations. There are no controlled data in human pregnancy.
US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.
See references
Aminosalicylic acid Breastfeeding Warnings
Breastfeeding is not recommended during use of this drug.
Excreted into human milk: Yes
Comments:
-The effects in the nursing infant are unknown.
-Exclusively breastfed infants, especially those under 2 months, should be monitored for gastrointestinal disturbances, hemolysis, hypokalemia, jaundice, and thrombocytopenia.
Following administration of a different preparation to 1 patient, the milk Cmax was 1 mcg/mL at a Tmax of 3 hours with a half-life of 2.5 hours, and the maternal Cmax was 70 mcg/mL at a Tmax of 2 hours.
See references
References for pregnancy information
1. "Product Information. Paser Granules (aminosalicylic acid)." Jacobus Pharmaceutical Company, Princeton, NJ.
2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
References for breastfeeding information
1. "Product Information. Paser Granules (aminosalicylic acid)." Jacobus Pharmaceutical Company, Princeton, NJ.
2. United States National Library of Medicine "Toxnet. Toxicology Data Network. Available from: URL: http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT." ([cited 2013 -]):
3. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
Further information
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
Hide
|
{
"url": "https://www.drugs.com/pregnancy/aminosalicylic-acid.html",
"source_domain": "www.drugs.com",
"snapshot_id": "crawl=CC-MAIN-2019-43",
"warc_metadata": {
"Content-Length": "47768",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:3R76IOTCD6GHFDCL3ZNL276ONNLRVDTK",
"WARC-Concurrent-To": "<urn:uuid:e17366dc-a0d7-46e4-bf16-0aa49edfc89d>",
"WARC-Date": "2019-10-14T00:41:45",
"WARC-IP-Address": "23.50.118.64",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:U2VWYX5EH6OMFSBSLGTMTZJXJYXEPCDY",
"WARC-Record-ID": "<urn:uuid:b99c8af2-5c54-41e8-b16d-16474053f3bf>",
"WARC-Target-URI": "https://www.drugs.com/pregnancy/aminosalicylic-acid.html",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:bde1b746-fe1a-461d-abc7-622f26aa3c4d>"
},
"warc_info": "isPartOf: CC-MAIN-2019-43\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for October 2019\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-214.ec2.internal\r\nsoftware: Apache Nutch 1.16 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.1-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: http://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
16,
17,
74,
75,
119,
120,
159,
160,
226,
227,
256,
257,
537,
538,
796,
797,
812,
813,
856,
857,
915,
916,
946,
947,
957,
1005,
1181,
1182,
1385,
1386,
1401,
1402,
1439,
1440,
1553,
1623,
1624,
1665,
1666,
1779,
1953,
2023,
2024,
2044,
2045,
2174,
2175
],
"line_end_idx": [
16,
17,
74,
75,
119,
120,
159,
160,
226,
227,
256,
257,
537,
538,
796,
797,
812,
813,
856,
857,
915,
916,
946,
947,
957,
1005,
1181,
1182,
1385,
1386,
1401,
1402,
1439,
1440,
1553,
1623,
1624,
1665,
1666,
1779,
1953,
2023,
2024,
2044,
2045,
2174,
2175,
2179
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 2179,
"ccnet_original_nlines": 47,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.24484536051750183,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.036082468926906586,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.2345360815525055,
"rps_doc_frac_unique_words": 0.5652173757553101,
"rps_doc_mean_word_length": 5.889632225036621,
"rps_doc_num_sentences": 34,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 4.8985137939453125,
"rps_doc_word_count": 299,
"rps_doc_frac_chars_dupe_10grams": 0.17149347066879272,
"rps_doc_frac_chars_dupe_5grams": 0.22032935917377472,
"rps_doc_frac_chars_dupe_6grams": 0.20442929863929749,
"rps_doc_frac_chars_dupe_7grams": 0.17149347066879272,
"rps_doc_frac_chars_dupe_8grams": 0.17149347066879272,
"rps_doc_frac_chars_dupe_9grams": 0.17149347066879272,
"rps_doc_frac_chars_top_2gram": 0.061328791081905365,
"rps_doc_frac_chars_top_3gram": 0.03066439926624298,
"rps_doc_frac_chars_top_4gram": 0.024985799565911293,
"rps_doc_books_importance": -155.74143981933594,
"rps_doc_books_importance_length_correction": -155.74143981933594,
"rps_doc_openwebtext_importance": -96.68524169921875,
"rps_doc_openwebtext_importance_length_correction": -96.68524169921875,
"rps_doc_wikipedia_importance": -54.37685012817383,
"rps_doc_wikipedia_importance_length_correction": -54.37685012817383
},
"fasttext": {
"dclm": 0.07145971059799194,
"english": 0.8271426558494568,
"fineweb_edu_approx": 2.1548233032226562,
"eai_general_math": 0.03561156988143921,
"eai_open_web_math": 0.48519301414489746,
"eai_web_code": 0.0003232999879401177
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "615.5",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
},
"secondary": {
"code": "618.9286",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Women — Health and hygiene, Children — Health and hygiene, Gynecology, and Pediatrics"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "1",
"label": "Factual"
},
"secondary": {
"code": "2",
"label": "Conceptual"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "0",
"label": "No Artifacts"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "8",
"label": "Documentation"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "3",
"label": "Undergraduate Level"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
b755ed28a90d11d590ef646404f4afc5
|
-9,142,970,930,334,570,000
|
Blood Pooling in Eye After Eyelid Lift
I had an upper eye lift in my left eye one week ago. Two days later the pain was so bad I contacted my Dr. Turns out a stitch had gone through the lid and was rubbing the eye. The following day in his office, he removed stitches and redid them. It is now day five after second surgery and my eye is all blood red. Is this normal? When does that go away? I read somewhere online that it could be really serious. [I'm using an IPad and can't find a way to send picture]. I'm really scared.
Doctor Answers 5
Blepharoplasty stitch
This appears highly unusual, but I agree with the other answers in general. You should do two things: 1) Keep seeing your surgeon on a regular basis (which I am sure they are doing) and 2) You may want to consider seeing an ophthalmologist to evaluate your eye. Discuss this second recommendation with your surgeon. Depending on their level of concern, they may favor this option.
Fort Lauderdale Facial Plastic Surgeon
4.9 out of 5 stars 80 reviews
Scared after Blepharoplasty.
If you had a complication affecting your eye after your Blepharoplasty, you should be followed up routinely every few days or sooner until everything resolves IMHO. Don't hesitate to contact and see your surgeon. I can tell you that having a small amount of blood in the white (conjuntiva) of the eye happens after a Blepharoplasty, Rhinoplasty, Face Lift and all sorts of plastic and cosmetic surgery...looks very bad...but is completely harmless. This is called a conjunctival hemorrhage and occurs from straining that ruptures a small vessel in the conjunctiva.
Francis R. Palmer, III, MD
Beverly Hills Facial Plastic Surgeon
4.6 out of 5 stars 24 reviews
It is highly unusual what you are describing.
If your surgery was a cosmetic blepharoplasty, it would be highly unusual for a suture to poke out from under the eyelid and irritate the eye. If this did happen, it would not be so surprising that the suture could cause non serious bleeding into the white of the eye called a subconjunctival hemorrhage. Because what you are describing is so unusual and there is a need for the eye to be examined by someone who is actually trained to care for the health of the eye in these sutuations, I strongly encourage you to see a oculoplastic surgeon. I recommend Dr. Mike Mccracken in Denver.
Kenneth D. Steinsapir, MD
Los Angeles Oculoplastic Surgeon
4.9 out of 5 stars 26 reviews
Blepharoplasty
It sounds like your eye got irritated from the stitch. The white part of the eye gets real bloodshot or red if this portion, or the actual eyeball is irritated. Make sure your doctor is aware of the issue and you should most likely be seeing your eye doc to make sure all is well.
Roger Bassin, MD
Orlando Oculoplastic Surgeon
4.6 out of 5 stars 92 reviews
See surgeon every couple of days
It is unusual for all of your eye to be blood red. A bit red is not unheard of after blepharoplasty but this sounds more serious. I suggest you see your surgeon every couple of days to follow your progress. It is important.
Michael Constantin Gartner, DO
Paramus Plastic Surgeon
4.7 out of 5 stars 130 reviews
These answers are for educational purposes and should not be relied upon as a substitute for medical advice you may receive from your physician. If you have a medical emergency, please call 911. These answers do not constitute or initiate a patient/doctor relationship.
|
{
"url": "https://www.realself.com/question/blood-pooling-eye-after-eyelid-lift",
"source_domain": "www.realself.com",
"snapshot_id": "crawl=CC-MAIN-2017-13",
"warc_metadata": {
"Content-Length": "100300",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:H4WZARJXQLZXSGIJGD4LFUM3SPZVUBSN",
"WARC-Concurrent-To": "<urn:uuid:4e376d2b-bbb0-4c48-aa4e-6ef550198aa5>",
"WARC-Date": "2017-03-23T15:34:49",
"WARC-IP-Address": "151.101.65.63",
"WARC-Identified-Payload-Type": null,
"WARC-Payload-Digest": "sha1:GZL4JW3XOD4I2SK4P7OORWLJ4LOYKAAX",
"WARC-Record-ID": "<urn:uuid:b44a4e75-b0b2-4824-a61e-b11cc6cd9a62>",
"WARC-Target-URI": "https://www.realself.com/question/blood-pooling-eye-after-eyelid-lift",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:c2770e0b-6ebf-4593-ba9d-3aafaa65b57a>"
},
"warc_info": "robots: classic\r\nhostname: ip-10-233-31-227.ec2.internal\r\nsoftware: Nutch 1.6 (CC)/CC WarcExport 1.0\r\nisPartOf: CC-MAIN-2017-13\r\noperator: CommonCrawl Admin\r\ndescription: Wide crawl of the web for March 2017\r\npublisher: CommonCrawl\r\nformat: WARC File Format 1.0\r\nconformsTo: http://bibnum.bnf.fr/WARC/WARC_ISO_28500_version1_latestdraft.pdf"
}
|
{
"line_start_idx": [
0,
39,
40,
528,
529,
546,
547,
569,
570,
951,
952,
953,
992,
1022,
1023,
1052,
1053,
1623,
1624,
1651,
1688,
1718,
1719,
1765,
1766,
2355,
2356,
2382,
2415,
2445,
2446,
2461,
2462,
2743,
2744,
2761,
2790,
2820,
2821,
2854,
2855,
3079,
3080,
3111,
3135,
3166,
3167
],
"line_end_idx": [
39,
40,
528,
529,
546,
547,
569,
570,
951,
952,
953,
992,
1022,
1023,
1052,
1053,
1623,
1624,
1651,
1688,
1718,
1719,
1765,
1766,
2355,
2356,
2382,
2415,
2445,
2446,
2461,
2462,
2743,
2744,
2761,
2790,
2820,
2821,
2854,
2855,
3079,
3080,
3111,
3135,
3166,
3167,
3436
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 3436,
"ccnet_original_nlines": 46,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.44186046719551086,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.029069770127534866,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.14098836481571198,
"rps_doc_frac_unique_words": 0.46434494853019714,
"rps_doc_mean_word_length": 4.525704860687256,
"rps_doc_num_sentences": 44,
"rps_doc_symbol_to_word_ratio": 0.0029069799929857254,
"rps_doc_unigram_entropy": 5.15316104888916,
"rps_doc_word_count": 603,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.04690362885594368,
"rps_doc_frac_chars_dupe_6grams": 0.029314769431948662,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.015390249900519848,
"rps_doc_frac_chars_top_3gram": 0.010993040166795254,
"rps_doc_frac_chars_top_4gram": 0.020153900608420372,
"rps_doc_books_importance": -271.0234375,
"rps_doc_books_importance_length_correction": -271.0234375,
"rps_doc_openwebtext_importance": -133.40980529785156,
"rps_doc_openwebtext_importance_length_correction": -133.40980529785156,
"rps_doc_wikipedia_importance": -104.35006713867188,
"rps_doc_wikipedia_importance_length_correction": -104.35006713867188
},
"fasttext": {
"dclm": 0.05091094970703125,
"english": 0.9496034383773804,
"fineweb_edu_approx": 1.4267888069152832,
"eai_general_math": 0.017706219106912613,
"eai_open_web_math": 0.22058671712875366,
"eai_web_code": 0.0008526999736204743
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "617.622",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Surgery and Dentistry"
}
},
"secondary": {
"code": "617.6",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Surgery and Dentistry"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "14",
"label": "Reviews/Critiques"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "4",
"label": "Missing Images or Figures"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "18",
"label": "Q&A Forum"
},
"secondary": {
"code": "10",
"label": "Knowledge Article"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "2",
"label": "High School Level"
},
"secondary": {
"code": "1",
"label": "General Audience"
}
}
}
|
1a01aa77535b9ecfb87b9fc36adbcd2f
|
-2,444,421,967,425,775,600
|
Mechanisms of transition between double paroxysmal supraventricular tachycardias
Jen Yuan Kou, Ching Tai Tai, Chern En Chiang, Wen Chung Yu, Yi Jen Chen, Chin Feng Tsai, Ming Hsiung Hsieh, Chien Cheng Chen, Wei Shiang Lin, Yung Kuo Lin, Hsuan Ming Tsao, Yu An Ding, Mau Song Chang, Shih Ann Chen
研究成果: 雜誌貢獻文章同行評審
33 引文 斯高帕斯（Scopus）
摘要
Introduction: Coexistence of double tachycardias in one patient has been infrequently reported. Furthermore, the mechanisms of transition between double paroxysmal supraventricular tachycardias have not been well studied. Methods and Results: Thirty-five patients with two paroxysmal supraventricular tachycardias were studied. Group IA consisted of 3 patients with spontaneous transition between AV reciprocating tachycardia (AVRT) and AV nodal reentrant tachycardia (AVNRT). Group IB consisted of 13 patients without spontaneous transition between AVRT and AVNRT. Group IIA consisted of 5 patients with spontaneous transition between AVNRT and atrial tachycardia (AT). Group IIB consisted of 14 patients without spontaneous transition between AVNRT and AT. The absolute values of differences between the two tachycardia cycle lengths were significantly smaller in patients with than in those without transition between the two tachycardias (25 ± 8 msec vs 90 ± 46 msec, P < 0.05, IA vs IB; 21 ± 25 msec vs 99 ± 57 msec, P < 0.01, IIA vs IIB). The cutoff point of 25 msec had 80% positive predictive value for transition between the two tachycardias. Transition between two tachycardias occurred due to a spontaneous premature atrial complex (30%), conduction block at one limb of tachycardia (20%), or tachycardia-induced tachycardia (50%). Absence of transition between two tachycardias might be explained by the absence of a spontaneous premature atrial complex, longer cycle length of the first tachycardia, larger difference between two tachycardia cycle lengths, or induction of each tachycardia under different situations. Conclusion: Double supraventricular tachycardias with similar tachycardia cycle lengths are vulnerable to transition between different tachycardias.
原文英語
頁（從 - 到）1339-1345
頁數7
期刊Journal of Cardiovascular Electrophysiology
12
發行號12
DOIs
出版狀態已發佈 - 2001
ASJC Scopus subject areas
• 心臟病學與心血管醫學
• 生理學（醫學）
指紋
深入研究「Mechanisms of transition between double paroxysmal supraventricular tachycardias」主題。共同形成了獨特的指紋。
引用此
|
{
"url": "https://hub.tmu.edu.tw/zh/publications/mechanisms-of-transition-between-double-paroxysmal-supraventricul",
"source_domain": "hub.tmu.edu.tw",
"snapshot_id": "CC-MAIN-2024-18",
"warc_metadata": {
"Content-Length": "63182",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:WYZLXKJ6MTHQWEFWBSJGHI3JSZ6VIRT7",
"WARC-Concurrent-To": "<urn:uuid:71a5b583-aac1-4546-adf2-1992006ba5c0>",
"WARC-Date": "2024-04-20T11:28:13",
"WARC-IP-Address": "18.139.148.124",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:VZDYHBZL2KNLGPARNPAHC477PBMNA6CP",
"WARC-Record-ID": "<urn:uuid:3492035e-9842-4d7e-8c4f-f880db3d7f36>",
"WARC-Target-URI": "https://hub.tmu.edu.tw/zh/publications/mechanisms-of-transition-between-double-paroxysmal-supraventricul",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:d33b6b23-9eff-4716-a949-f1dbcc4b4cec>"
},
"warc_info": "isPartOf: CC-MAIN-2024-18\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for April 2024\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-150\r\nsoftware: Apache Nutch 1.19 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.5-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
81,
82,
297,
298,
315,
316,
335,
336,
339,
340,
2120,
2121,
2126,
2144,
2148,
2194,
2197,
2203,
2208,
2223,
2224,
2250,
2251,
2266,
2278,
2279,
2282,
2283,
2384,
2385
],
"line_end_idx": [
81,
82,
297,
298,
315,
316,
335,
336,
339,
340,
2120,
2121,
2126,
2144,
2148,
2194,
2197,
2203,
2208,
2223,
2224,
2250,
2251,
2266,
2278,
2279,
2282,
2283,
2384,
2385,
2388
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 2388,
"ccnet_original_nlines": 30,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.2267303168773651,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.05011932924389839,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.28639617562294006,
"rps_doc_frac_unique_words": 0.5280236005783081,
"rps_doc_mean_word_length": 5.793510437011719,
"rps_doc_num_sentences": 15,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 4.806185245513916,
"rps_doc_word_count": 339,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.2632382810115814,
"rps_doc_frac_chars_dupe_6grams": 0.10030549764633179,
"rps_doc_frac_chars_dupe_7grams": 0.07433809340000153,
"rps_doc_frac_chars_dupe_8grams": 0.07433809340000153,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.10386964678764343,
"rps_doc_frac_chars_top_3gram": 0.03869653865695,
"rps_doc_frac_chars_top_4gram": 0.03818736970424652,
"rps_doc_books_importance": -216.92007446289062,
"rps_doc_books_importance_length_correction": -216.92007446289062,
"rps_doc_openwebtext_importance": -122.52129364013672,
"rps_doc_openwebtext_importance_length_correction": -122.52129364013672,
"rps_doc_wikipedia_importance": -106.14804077148438,
"rps_doc_wikipedia_importance_length_correction": -106.14804077148438
},
"fasttext": {
"dclm": 0.36999940872192383,
"english": 0.792085587978363,
"fineweb_edu_approx": 1.6128417253494263,
"eai_general_math": 0.7592161893844604,
"eai_open_web_math": 0.3604055643081665,
"eai_web_code": 0.07597684860229492
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.122",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "616.12",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "4",
"label": "Analyze"
},
"secondary": {
"code": "5",
"label": "Evaluate"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "2",
"label": "Academic/Research"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "3",
"label": "Academic Writing"
},
"secondary": {
"code": "8",
"label": "Documentation"
}
},
"reasoning_depth": {
"primary": {
"code": "4",
"label": "Advanced Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "4",
"label": "Graduate/Expert Level"
},
"secondary": {
"code": "3",
"label": "Undergraduate Level"
}
}
}
|
6e3c8d3593f3f69280bb5502b214ab8e
|
-5,975,144,797,104,423,000
|
weight loss concept
how much weight can you lose in 7 months
Contents
How much weight can you lose in 7 months?
Generally, expect to lose 28 – 56 pounds in 7 months. It is a safe amount for most people to lose in 7 months. It’s also in line with CDC (center for disease control and prevention ) guidelines for healthy weight loss.
With a daily calorie deficit of 500, expect to lose 28 pounds in 7 months. Double the effort to a daily calorie deficit of 1000 to lose 56 pounds in 7 months.
However, keep in mind that these can vary from person to person. Several other factors determine how quickly you lose weight. These include factors such as; activity levels, age, gender, height, and weight. Due to these differences, some people might lose more or less weight in 7 months.
A 300-pound person, for example, might find that they lose more weight in 7 months compared to another who weighs 150-pounds. The heavier person burns more calories as their energy needs are higher.
In the same way, a person with active lifestyle exercises daily will not lose the game amount of weight in 7 months as another with a sedentary lifestyle with little to no activity.
While you can lose more weight in 7 months, resist the temptation to use extreme measures. Measures such as exercising too long or severely restricting your calories are unsafe. Also, as they cannot be sustained long-term, you’re likely to gain the weight back.
Overall, it’s much better to take your time and lose an appropriate amount of weight in 7 months.
weight loss concept
Lose weight the healthily way.
Weight loss occurs when you consume fewer calories than the body needs. This results in a calorie deficit forcing the body to tap into stored fat. It takes a calorie deficit of 3,500 to lose a pound of fat.
Most experts recommend losing about 1 – 2 pounds a week, not more. You can achieve this with diet, exercise, or both.
Start by eating less to lose weight. Aim for a moderate calorie reduction of 500 – 1000. This is enough to jumpstart weight loss without leaving you feeling deprived.
Start with small changes such as cutting out junk foods and other empty calories. These include foods such as; sugary drinks, fried foods, cookies, cakes, pastries, ultra-processed snacks, and alcohol.
These foods are bad for weight loss as they’re high in calories with little nutritional benefit. Also, they’re often high in added sugar and other additives that only increase your appetite and cravings. Cut these foods from your diet to lose weight in 7 months.
You can also consider portion control to help you reduce your calories. Use simple tips such as serving your food on smaller plates or bowls. Or better yet, fill half your plate with vegetables before adding on protein or carbs.
Once you have reduced your calories, focus on eating more vegetables, complex carbs, fiber, and protein. These are good weight-loss foods as they reduce your appetite and keep you full for longer.
woman exercising on stationary bike
Stay active to burn more calories.
It is recommended that healthy adults spend at least 150 – 300 minutes exercising weekly. It is not only good for your heart health but also weight loss. As you get started, focus on workouts you enjoy doing. You’re more likely to be consistent this way.
Alternate between cardio and weight training for best results. Cardio exercises such as; running, rowing, and bicycling help you burn calories fast. Weight training exercises such as; squats, deadlifts, and lunges help build muscle. The more muscle you have, the better your metabolism.
If you struggle with a busy schedule, consider high-intensity interval worouts. These exercises take 30-minutes or less to complete yet are just as effective at burning calories. Do these, and you will lose weight in 7 months.
How much weight can you lose in 7 months? Conclusion
On average, expect to lose 28 – 56 pounds in 7 months. It is a safe and healthy amount for most people to lose in 7 months.
|
{
"url": "https://eatsumgreens.com/how-much-weight-can-you-lose-in-7-months/",
"source_domain": "eatsumgreens.com",
"snapshot_id": "CC-MAIN-2023-14",
"warc_metadata": {
"Content-Length": "146199",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:5WHKIO6FIXDZMOQ4ZFPMZT7WVFMEHUXE",
"WARC-Concurrent-To": "<urn:uuid:aae2be8b-bcd6-4434-b110-738c8997d37a>",
"WARC-Date": "2023-03-21T14:04:03",
"WARC-IP-Address": "172.67.191.201",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:WWJQY4NUG4XSKALTYLZ5326ZJQYHGEJW",
"WARC-Record-ID": "<urn:uuid:9600ac93-619a-4026-ac21-08674db84bb4>",
"WARC-Target-URI": "https://eatsumgreens.com/how-much-weight-can-you-lose-in-7-months/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:9d6c4123-967a-43d6-bf1b-1b48efeb6934>"
},
"warc_info": "isPartOf: CC-MAIN-2023-14\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for March/April 2023\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-253\r\nsoftware: Apache Nutch 1.19 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.4-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
20,
21,
62,
63,
72,
73,
115,
116,
335,
336,
338,
339,
498,
499,
501,
502,
791,
792,
794,
795,
994,
995,
997,
998,
1180,
1181,
1183,
1184,
1446,
1447,
1449,
1450,
1548,
1549,
1569,
1570,
1601,
1602,
1810,
1811,
1813,
1814,
1932,
1933,
1935,
1936,
2103,
2104,
2106,
2107,
2309,
2310,
2312,
2313,
2576,
2577,
2579,
2580,
2809,
2810,
2812,
2813,
3010,
3011,
3047,
3048,
3083,
3084,
3339,
3340,
3342,
3343,
3630,
3631,
3633,
3634,
3861,
3862,
3864,
3865,
3918,
3919
],
"line_end_idx": [
20,
21,
62,
63,
72,
73,
115,
116,
335,
336,
338,
339,
498,
499,
501,
502,
791,
792,
794,
795,
994,
995,
997,
998,
1180,
1181,
1183,
1184,
1446,
1447,
1449,
1450,
1548,
1549,
1569,
1570,
1601,
1602,
1810,
1811,
1813,
1814,
1932,
1933,
1935,
1936,
2103,
2104,
2106,
2107,
2309,
2310,
2312,
2313,
2576,
2577,
2579,
2580,
2809,
2810,
2812,
2813,
3010,
3011,
3047,
3048,
3083,
3084,
3339,
3340,
3342,
3343,
3630,
3631,
3633,
3634,
3861,
3862,
3864,
3865,
3918,
3919,
4042
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 4042,
"ccnet_original_nlines": 82,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.3702337145805359,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.0024600198958069086,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.18450185656547546,
"rps_doc_frac_unique_words": 0.4136429727077484,
"rps_doc_mean_word_length": 4.611030578613281,
"rps_doc_num_sentences": 51,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.091907024383545,
"rps_doc_word_count": 689,
"rps_doc_frac_chars_dupe_10grams": 0.02581050992012024,
"rps_doc_frac_chars_dupe_5grams": 0.13755114376544952,
"rps_doc_frac_chars_dupe_6grams": 0.10638967901468277,
"rps_doc_frac_chars_dupe_7grams": 0.07743153721094131,
"rps_doc_frac_chars_dupe_8grams": 0.07743153721094131,
"rps_doc_frac_chars_dupe_9grams": 0.07743153721094131,
"rps_doc_frac_chars_top_2gram": 0.015108590014278889,
"rps_doc_frac_chars_top_3gram": 0.04532577842473984,
"rps_doc_frac_chars_top_4gram": 0.0330500490963459,
"rps_doc_books_importance": -334.0486755371094,
"rps_doc_books_importance_length_correction": -334.0486755371094,
"rps_doc_openwebtext_importance": -187.2252960205078,
"rps_doc_openwebtext_importance_length_correction": -187.2252960205078,
"rps_doc_wikipedia_importance": -206.3458251953125,
"rps_doc_wikipedia_importance_length_correction": -206.3458251953125
},
"fasttext": {
"dclm": 0.04219675064086914,
"english": 0.9552682638168335,
"fineweb_edu_approx": 2.028264045715332,
"eai_general_math": 0.008621389977633953,
"eai_open_web_math": 0.186923086643219,
"eai_web_code": 0.00012337999942246825
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "613.29",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
},
"secondary": {
"code": "613.2",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "3",
"label": "Irrelevant Content"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "4",
"label": "Missing Images or Figures"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "23",
"label": "Tutorial"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "4",
"label": "Highly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
9222580d47c553ea90dc0f5e416f8f3a
|
-6,137,376,538,910,868,000
|
Collagen Supplement Gastritis
What is Collagen?
Collagen is one of the most plentiful healthy protein in your body, as well as it’s a major part of your ligaments, skin, bones, teeth, muscle mass and ligaments. Collagen provides your skin toughness as well as strength. It aids the cartilage material in your joints continue to be flexible. It supplies structure to your arteries, maintaining them strong and flexible. It provides your bones framework, as well, by acting as ‘reinforcing rods’. Collagen is an impressive building and construction material.
Collagen comes in numerous types, yet the huge bulk in your body includes kinds I, II as well as III. These kinds all develop fairly long fibers (compared to body cells). Kind I collagen is – ounce for ounce – more powerful than steel. Type II collagen is thinner than kind I, and is utilized in cartilage material all bunched up like springs for shock absorption. Kind III is important for the hollow things in your body– like big capillary, the digestive tract as well as bladder.
It is essential to understand that the ‘kind’ of collagen is just pertinent when it’s currently a part of your body. When you consume it, your body simply re-makes it into new kinds.
Collagen is so large and also tough that we can not absorb it ‘as is’ when we eat it. What we can do however, is ‘hydrolyze’ the collagen, which indicates it’s broken down into a lot smaller sized items (‘ peptides’) by water, making it usable by your body. Collagen Facility provides easy-to-digest hydrolyzed collagen peptides.
What are the Advantages of Collagen Supplements?
Each offering of VitaPost Collagen Complex offers replenishing hydrolyzed collagen. Collagen supplements are not only good for your skin but additionally for your hair, nails, and also joints. It can aid with joint discomfort as well as arthritis along with making you really feel more younger.
Skin Assistance
VitaPost Collagen Complex gives all-natural hydrolyzed collagen that supports your body in the normal repair work of harmed skin; supports the skin’s natural firmness and also framework; sustains skin tone and can enhance the noticeable look of great lines and wrinkles. Studies have wrapped up that supplementing with collagen can additionally increase skin hydration.
Bone Support
VitaPost Collagen Complex might have fantastic benefits supporting the body’s maintenance of the skeleton, especially in females who are going through all-natural hormone modifications. Researches recommend a diet plan supplemented with hydrolyzed collagen can support the maintenance of the bone collagen already existing – implying much less natural destruction of the bones with age.
Joint Support
Collagen in your cartilage material is the mechanical reason joints do not simply split and also break whenever you leap or run. Supplementing the diet regimen with hydrolyzed collagen has been connected with joint advantages for an entire variety of individuals, from age-related joint deterioration, to highly-active athletes who press their joints to the limit.
How to Select a High Quality Collagen Supplement
This post will certainly aid you decide which collagen supplement is best for you.
There are several types of collagen supplements on the marketplace today. With so many options, it can be hard to recognize which one is the best top quality. Here are some actions to adhere to when searching for a high quality collagen supplement.
1) Check the length of time the company has been in business and also what their reputation resembles.
2) Look at the active ingredients and also make certain they have something that will benefit your needs (i.e., kind 1, kind 2, kind 3).
3) Examine if there are any kind of fillers or various other ingredients that might not be as healthy and balanced as what you intend to take into your body and also if so, locate one without fillers or additives.
4) Check out client evaluations about the item.
What is the distinction in between hydrolyzed collagen and collagen peptides?
There is no distinction. Collagen healthy proteins are long chains of amino acids. The procedure of hydrolysis breaks them down into peptides, which are simply shorter chains of amino acids. Collagen supplements are variously labeled as “hydrolyzed collagen” or “collagen peptides,” but they’re the same.
That requires collagen supplements?
In my opinion, practically every person could profit. The majority of people don’t eat bones, skin, and also connective tissues– the parts of animals which contain collagen. That indicates they don’t get the amino acids (specifically hydroxyproline, glycine, as well as proline) that are located in collagen yet very little in muscle mass meat.
How much collagen should I take daily?
There is no RDA for collagen, as well as to my knowledge, no studies have established optimal application standards. You may require more or less relying on your nutritional consumption. To be safe, it’s always a great suggestion to adhere to the dosage directions on your collagen supplement of choice.
Can you take too much collagen peptides?
Many things in nature comply with a J-shaped contour– way too much or too little are both negative. The exact same could be real for collagen supplements, but sadly, there’s no indication of what would certainly make up “excessive.” There’s also no evidence that collagen poisoning is a concern if you following dosing standards.
THE LENGTH OF TIME DOES IT CONSIDER COLLAGEN TO WORK?
It depends what you’re taking collagen to support. If you’re taking collagen for muscle growth, favorable changes will begin to happen almost right away with your exercises– although you might not see the progression today.
In researches checking out collagen supplements for joint pain as well as skin elasticity, individuals experienced noticeable renovations in concerning 4 to eight weeks of day-to-day supplementation.
Like any kind of supplement, collagen isn’t an over night miracle remedy however sticking to an everyday supplement regimen will certainly generate the very best outcomes.
What Is Bovine Collagen?
Bovine collagen comes from cows– ideally grass-fed cows.
There are 3 various kinds of collagen: collagen I, II, and also III. Each kind of collagen sustains various parts of the body. In bovine collagen made from hide, you’ll generally find kinds I and also III which operate in similar means to support skin, bones, muscle mass, ligaments, and also gut health.
If you buy a bovine collagen supplement made from cartilage, connective tissues, or bones, this supplement should likewise have collagen type II which aids assistance joint health specifically.
What Is Marine Collagen?
Marine collagen includes type I collagen as well as is normally sourced from wild caught fish. This type of collagen is exceptional for improving sustainability practices since it’s made from fish parts that normally wind up in the waste.
The terrific feature of aquatic collagen is that it’s very easy for the body to procedure and also absorb.
Anybody on a vegan or strict vegetarian diet can not take collagen supplements since it’s constantly sourced from some kind of animal product.
Nevertheless, unlike typical gelatin, bovine collagen and marine collagen do not have any type of pork-derived products so they are suitable for anyone on a kosher or halal diet regimen.
Does Collagen Break a Fast?
Yes. Since collagen is a healthy protein, it quits the autophagy procedure induced during fasting.
During intermittent or lasting fasting, autophagy takes place to remove the cells of built-up toxins. Collagen or any other sort of protein is a precise no while fasting.
error: Content is protected !!
|
{
"url": "https://www.albany-lawyer.com/collagen-supplement-gastritis/",
"source_domain": "www.albany-lawyer.com",
"snapshot_id": "CC-MAIN-2023-06",
"warc_metadata": {
"Content-Length": "56993",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:X6QI7H5CPGCBCTOGBUQUWDKZ722LJ7OX",
"WARC-Concurrent-To": "<urn:uuid:eb3cd189-b004-41b1-b0ff-c9306d265277>",
"WARC-Date": "2023-02-01T02:06:04",
"WARC-IP-Address": "194.1.147.85",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:KQIWH2DVVZWWHNQFOFNETHYX3SRO7L2C",
"WARC-Record-ID": "<urn:uuid:757f3cba-ad4b-48cb-99a5-dde5e9f2ecc6>",
"WARC-Target-URI": "https://www.albany-lawyer.com/collagen-supplement-gastritis/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:fa8bcf7e-d83c-42bd-a00c-95b0c5edf773>"
},
"warc_info": "isPartOf: CC-MAIN-2023-06\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for January/February 2023\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-163\r\nsoftware: Apache Nutch 1.19 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.4-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
30,
31,
49,
50,
559,
560,
1043,
1044,
1227,
1228,
1558,
1559,
1608,
1609,
1904,
1905,
1921,
1922,
2292,
2293,
2306,
2307,
2694,
2695,
2709,
2710,
3075,
3076,
3125,
3126,
3209,
3210,
3459,
3460,
3563,
3564,
3701,
3702,
3916,
3917,
3965,
3966,
4044,
4045,
4350,
4351,
4387,
4388,
4733,
4734,
4773,
4774,
5078,
5079,
5120,
5121,
5451,
5452,
5506,
5507,
5731,
5732,
5932,
5933,
6105,
6106,
6131,
6132,
6189,
6190,
6495,
6496,
6690,
6691,
6716,
6717,
6956,
6957,
7064,
7065,
7208,
7209,
7396,
7397,
7425,
7426,
7525,
7526,
7697,
7698
],
"line_end_idx": [
30,
31,
49,
50,
559,
560,
1043,
1044,
1227,
1228,
1558,
1559,
1608,
1609,
1904,
1905,
1921,
1922,
2292,
2293,
2306,
2307,
2694,
2695,
2709,
2710,
3075,
3076,
3125,
3126,
3209,
3210,
3459,
3460,
3563,
3564,
3701,
3702,
3916,
3917,
3965,
3966,
4044,
4045,
4350,
4351,
4387,
4388,
4733,
4734,
4773,
4774,
5078,
5079,
5120,
5121,
5451,
5452,
5506,
5507,
5731,
5732,
5932,
5933,
6105,
6106,
6131,
6132,
6189,
6190,
6495,
6496,
6690,
6691,
6716,
6717,
6956,
6957,
7064,
7065,
7208,
7209,
7396,
7397,
7425,
7426,
7525,
7526,
7697,
7698,
7728
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 7728,
"ccnet_original_nlines": 90,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.3968363106250763,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.01856946013867855,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.1403026133775711,
"rps_doc_frac_unique_words": 0.40536150336265564,
"rps_doc_mean_word_length": 5.10966682434082,
"rps_doc_num_sentences": 77,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.537636756896973,
"rps_doc_word_count": 1231,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.009538950398564339,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.0133545296266675,
"rps_doc_frac_chars_top_3gram": 0.011446739546954632,
"rps_doc_frac_chars_top_4gram": 0.00635930011048913,
"rps_doc_books_importance": -727.0346069335938,
"rps_doc_books_importance_length_correction": -727.0346069335938,
"rps_doc_openwebtext_importance": -418.3526916503906,
"rps_doc_openwebtext_importance_length_correction": -418.3526916503906,
"rps_doc_wikipedia_importance": -276.4056091308594,
"rps_doc_wikipedia_importance_length_correction": -276.4056091308594
},
"fasttext": {
"dclm": 0.024716319516301155,
"english": 0.9457473754882812,
"fineweb_edu_approx": 1.4999737739562988,
"eai_general_math": 0.016227129846811295,
"eai_open_web_math": 0.18925893306732178,
"eai_web_code": 0.0006116600125096738
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "613.2",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
},
"secondary": {
"code": "615.5",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "6",
"label": "Promotional/Advertisement"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "3",
"label": "Irrelevant Content"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "2",
"label": "Click Here References"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "17",
"label": "Product Page"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "4",
"label": "Highly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
b755ed28a90d11d590ef646404f4afc5
|
7,215,596,416,223,426,000
|
Hi I had an EKG done yesterday. Can I have a tummy tuck with a sinus rhythm 60 bpm, and incomplete right bundle branch block
Doctor Answers 5
Cardiac/Medical Clearance Pre-Operatively
Hello and thank you for your questions in regards to proceeding with your tummy tuck. Depending on complexity of your surgical case, your procedure could take quite a few hours which means longer time under general anesthesia. Therefore, you need to be in complete and good health prior to having your desired procedure. Only a cardiologist can determine if it's ok to proceed with your procedure. If you aren't already established with a cardiologist, please seek a referral from a board certified plastic surgeon or your medical doctor. Good luck to you as you seek to have the best possibly experience with your cosmetic procedure.
Beverly Hills Plastic Surgeon
4.9 out of 5 stars 52 reviews
Abnormal EKG
It really depends on the rest of your medical history. Your surgeon may consult with the anesthesiologist and they might be okay with it or they might have you see a cardiologist and get a stress test to be on the safe side.
Ronald J. Edelson, MD
San Diego Plastic Surgeon
5.0 out of 5 stars 27 reviews
Tummy Tuck/ Abdominoplasty/ Reverse Tummy Tuck/ Liposuction/Muscle Plication/ Fleur de lis Abdominoplasty
Thank you for your question.
I would recommend that you discuss this question with both your Surgeon and Cardiologist. They are the ones to determine if you are a candidate for elective surgery.
The best way to assess and give true advice would be an in-person exam.
Please see a board-certified plastic surgeon that specializes in aesthetic and restorative plastic surgery.
Dr. Schwartz
Board Certified Plastic Surgeon
Director-Beverly Hills Breast and Body Institute
#RealSelf100Surgeon
Jaime S. Schwartz, MD, FACS
Beverly Hills Plastic Surgeon
5.0 out of 5 stars 93 reviews
Safety of Tummy Tuck with a RBBB and rate of 60
On the surface it sounds like you may be a candidate for surgery if your cardiologist approves. There needs to be more details to determine your overall medical health before jumping in so go through the proper steps to assure that you are at a low risk level for elective cosmetic surgery. Your cardiologist or anesthetist may ask for a stress EKG (Treadmill) or other procedures if appropriate and be certain that you are not a smoker and not taking blood thinners before and after your procedure. Also, your BMI should be less than 30.
Regards and best wishes.
Jon A Perlman MD FACS
Certified, American Board of Plastic Surgery
Extreme Makeover Surgeon ABC TV
Beverly Hills, Ca
Jon A. Perlman, MD
Beverly Hills Plastic Surgeon
5.0 out of 5 stars 31 reviews
Hi I had an EKG done yesterday. Can I have a tummy tuck with a sinus rhythm 60 bpm, and incomplete right bundle branch block
If you are otherwise in good health, then you would need to ask this question of your cardiologist. If that doctor gives the OK you need to discuss this with a surgeon who can consult with his anesthesiologist and you need the anesthesiologists OK.
Ronald V. DeMars, MD
Portland Plastic Surgeon
5.0 out of 5 stars 27 reviews
These answers are for educational purposes and should not be relied upon as a substitute for medical advice you may receive from your physician. If you have a medical emergency, please call 911. These answers do not constitute or initiate a patient/doctor relationship.
|
{
"url": "https://www.realself.com/question/la-quinta-ca-ekg-yesterday",
"source_domain": "www.realself.com",
"snapshot_id": "crawl=CC-MAIN-2017-22",
"warc_metadata": {
"Content-Length": "100430",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:USCL3JHGWLMIOCB5JROZ2BTALW4LWM3X",
"WARC-Concurrent-To": "<urn:uuid:d52ac725-6ff7-48f0-9dad-86aa0ebf23ec>",
"WARC-Date": "2017-05-29T14:28:37",
"WARC-IP-Address": "151.101.1.63",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:4WFNDLPFWOCTTUQI23APRJOM22VWPO6M",
"WARC-Record-ID": "<urn:uuid:4cf689f2-47fe-4429-a805-0f6e10e5756f>",
"WARC-Target-URI": "https://www.realself.com/question/la-quinta-ca-ekg-yesterday",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:de839fc8-3a63-4cb0-8c42-920f9d5c5e56>"
},
"warc_info": "robots: classic\r\nhostname: ip-10-185-224-210.ec2.internal\r\nsoftware: Nutch 1.6 (CC)/CC WarcExport 1.0\r\nisPartOf: CC-MAIN-2017-22\r\noperator: Common Crawl Admin\r\ndescription: Wide crawl of the web for May 2017\r\npublisher: Common Crawl\r\nformat: WARC File Format 1.0\r\nconformsTo: http://bibnum.bnf.fr/WARC/WARC_ISO_28500_version1_latestdraft.pdf"
}
|
{
"line_start_idx": [
0,
125,
126,
143,
144,
186,
187,
823,
824,
825,
855,
885,
886,
899,
900,
1126,
1127,
1149,
1175,
1205,
1206,
1312,
1313,
1342,
1343,
1510,
1511,
1583,
1691,
1692,
1705,
1737,
1786,
1806,
1807,
1808,
1836,
1866,
1896,
1897,
1945,
1946,
2488,
2513,
2514,
2536,
2581,
2613,
2631,
2632,
2651,
2681,
2711,
2712,
2837,
2838,
3087,
3088,
3109,
3134,
3164,
3165
],
"line_end_idx": [
125,
126,
143,
144,
186,
187,
823,
824,
825,
855,
885,
886,
899,
900,
1126,
1127,
1149,
1175,
1205,
1206,
1312,
1313,
1342,
1343,
1510,
1511,
1583,
1691,
1692,
1705,
1737,
1786,
1806,
1807,
1808,
1836,
1866,
1896,
1897,
1945,
1946,
2488,
2513,
2514,
2536,
2581,
2613,
2631,
2632,
2651,
2681,
2711,
2712,
2837,
2838,
3087,
3088,
3109,
3134,
3164,
3165,
3434
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 3434,
"ccnet_original_nlines": 61,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.40819424390792847,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.040971171110868454,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.13960546255111694,
"rps_doc_frac_unique_words": 0.42487046122550964,
"rps_doc_mean_word_length": 4.768566608428955,
"rps_doc_num_sentences": 35,
"rps_doc_symbol_to_word_ratio": 0.0015174499712884426,
"rps_doc_unigram_entropy": 5.033538818359375,
"rps_doc_word_count": 579,
"rps_doc_frac_chars_dupe_10grams": 0.07098876684904099,
"rps_doc_frac_chars_dupe_5grams": 0.12531690299510956,
"rps_doc_frac_chars_dupe_6grams": 0.12531690299510956,
"rps_doc_frac_chars_dupe_7grams": 0.12531690299510956,
"rps_doc_frac_chars_dupe_8grams": 0.12531690299510956,
"rps_doc_frac_chars_dupe_9grams": 0.12531690299510956,
"rps_doc_frac_chars_top_2gram": 0.04056501016020775,
"rps_doc_frac_chars_top_3gram": 0.010865629650652409,
"rps_doc_frac_chars_top_4gram": 0.019920319318771362,
"rps_doc_books_importance": -306.8226318359375,
"rps_doc_books_importance_length_correction": -306.8226318359375,
"rps_doc_openwebtext_importance": -156.45989990234375,
"rps_doc_openwebtext_importance_length_correction": -156.45989990234375,
"rps_doc_wikipedia_importance": -141.3538055419922,
"rps_doc_wikipedia_importance_length_correction": -141.3538055419922
},
"fasttext": {
"dclm": 0.02504367008805275,
"english": 0.9319313764572144,
"fineweb_edu_approx": 0.9429374933242798,
"eai_general_math": 0.0062711201608181,
"eai_open_web_math": 0.1750493049621582,
"eai_web_code": 0.00011383999662939459
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "617.6",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Surgery and Dentistry"
}
},
"secondary": {
"code": "616.1",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "3",
"label": "Apply"
},
"secondary": {
"code": "2",
"label": "Understand"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "14",
"label": "Reviews/Critiques"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "18",
"label": "Q&A Forum"
},
"secondary": {
"code": "21",
"label": "Customer Support"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "2",
"label": "High School Level"
},
"secondary": {
"code": "1",
"label": "General Audience"
}
}
}
|
1a01aa77535b9ecfb87b9fc36adbcd2f
|
5,644,612,429,436,533,000
|
Advertisement
Why is ovarian cancer difficult to detect in the early stages?
Ovarian cancer can be difficult to detect in the early stages because symptoms are not obvious. Most women do not notice symptoms until the cancer has spread to other parts of the body.
Continue Learning about Ovarian Cancer
If Diagnosed with Ovarian Cancer, What Should My Family Know?
If Diagnosed with Ovarian Cancer, What Should My Family Know?
After an ovarian cancer diagnosis, it's important to let family and loved ones know that their support will be needed, says Audra Moran. In this video...
Read More
What Are Symptoms of Ovarian Cancer?
What Are Symptoms of Ovarian Cancer?
Why Is Ovarian Cancer Referred to As the Disease That Whispers?
Why Is Ovarian Cancer Referred to As the Disease That Whispers?
What Can I Expect After Surgery for Ovarian Cancer?
What Can I Expect After Surgery for Ovarian Cancer?
Important: This content reflects information from various individuals and organizations and may offer alternative or opposing points of view. It should not be used for medical advice, diagnosis or treatment. As always, you should consult with your healthcare provider about your specific health needs.
|
{
"url": "https://www.sharecare.com/health/ovarian-cancer/why-ovarian-cancer-difficult-detect",
"source_domain": "www.sharecare.com",
"snapshot_id": "crawl=CC-MAIN-2021-49",
"warc_metadata": {
"Content-Length": "92422",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:KXN626B2M2SMCTCZWJCLEM255YPTZPNY",
"WARC-Concurrent-To": "<urn:uuid:bdf18361-8556-4cbb-8d12-42b7ebd4978b>",
"WARC-Date": "2021-12-06T09:10:32",
"WARC-IP-Address": "54.161.242.96",
"WARC-Identified-Payload-Type": "application/xhtml+xml",
"WARC-Payload-Digest": "sha1:3KXUSO2WCDJNV4MSUUYBFSD6RGKKGIVP",
"WARC-Record-ID": "<urn:uuid:8d46e977-92f4-4694-a667-f0cfdfeaac64>",
"WARC-Target-URI": "https://www.sharecare.com/health/ovarian-cancer/why-ovarian-cancer-difficult-detect",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:c1b6b7d2-3fa5-4bd1-aeac-285aad2b80c9>"
},
"warc_info": "isPartOf: CC-MAIN-2021-49\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for November/December 2021\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-155\r\nsoftware: Apache Nutch 1.18 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.3-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
14,
15,
78,
79,
265,
266,
305,
306,
368,
430,
584,
594,
631,
668,
732,
796,
848,
900,
901
],
"line_end_idx": [
14,
15,
78,
79,
265,
266,
305,
306,
368,
430,
584,
594,
631,
668,
732,
796,
848,
900,
901,
1202
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 1202,
"ccnet_original_nlines": 19,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.3059360682964325,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.00913241971284151,
"rps_doc_frac_lines_end_with_ellipsis": 0.05000000074505806,
"rps_doc_frac_no_alph_words": 0.10958904027938843,
"rps_doc_frac_unique_words": 0.5051546692848206,
"rps_doc_mean_word_length": 5.041236877441406,
"rps_doc_num_sentences": 16,
"rps_doc_symbol_to_word_ratio": 0.004566209856420755,
"rps_doc_unigram_entropy": 4.299674987792969,
"rps_doc_word_count": 194,
"rps_doc_frac_chars_dupe_10grams": 0.20858895778656006,
"rps_doc_frac_chars_dupe_5grams": 0.42331287264823914,
"rps_doc_frac_chars_dupe_6grams": 0.42331287264823914,
"rps_doc_frac_chars_dupe_7grams": 0.3619631826877594,
"rps_doc_frac_chars_dupe_8grams": 0.29447853565216064,
"rps_doc_frac_chars_dupe_9grams": 0.29447853565216064,
"rps_doc_frac_chars_top_2gram": 0.15950919687747955,
"rps_doc_frac_chars_top_3gram": 0.06952965259552002,
"rps_doc_frac_chars_top_4gram": 0.05521472170948982,
"rps_doc_books_importance": -101.32884979248047,
"rps_doc_books_importance_length_correction": -101.32884979248047,
"rps_doc_openwebtext_importance": -55.70934295654297,
"rps_doc_openwebtext_importance_length_correction": -55.70650100708008,
"rps_doc_wikipedia_importance": -50.33807373046875,
"rps_doc_wikipedia_importance_length_correction": -50.33807373046875
},
"fasttext": {
"dclm": 0.0991249680519104,
"english": 0.9349390864372253,
"fineweb_edu_approx": 2.827172040939331,
"eai_general_math": 0.0057961298152804375,
"eai_open_web_math": 0.190535306930542,
"eai_web_code": 0.00010120999650098383
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.994",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "616.9",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "2",
"label": "Click Here References"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "6",
"label": "Content Listing"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "1",
"label": "No Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "6",
"label": "Not Applicable/Indeterminate"
},
"secondary": {
"code": "4",
"label": "Highly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
6e3c8d3593f3f69280bb5502b214ab8e
|
7,242,687,290,855,208,000
|
Close
2021-05-16
What determines if something is an organelle?
What determines if something is an organelle?
An organelle is a tiny cellular structure that performs specific functions within a cell. In the more complex eukaryotic cells, organelles are often enclosed by their own membrane. Analogous to the body’s internal organs, organelles are specialized and perform valuable functions necessary for normal cellular operation.
What organelle determines what goes in and out of the cell?
Function Of Cell Organelles
A B
cell membrane controls the movement into and out of the cell
cytoplasm watery material which contains many of the materials involved in cell metabolism
endoplasmic reticulum serves as a pathway for the transport of materials throughout the cell
Who should not take Tulsi?
05/7May interfere with blood-thinning medicines But people who are already taking medicines for blood thinning, if they take Tulsi, it may adversely affect their health. It should not be consumed by people who are on anti-clotting medications.
Can we drink Tulsi water daily?
Consuming tulsi water daily improves bowel movements and fights against acid refluxes as well as indigestion and other digestive problems. It also helps the body flush out dangerous toxins.
Does Tulsi increase body heat?
Tulsi has an antipyretic and diaphoretic activity that helps to induce sweating and normalizes the elevated body temperature during fever[16]. The leaves of Tulsi can be used to reduce fever because it helps to improve immunity and fight against infection due to its Rasayana (rejuvenating) property.
Can Tulsi be boiled?
Drop a few tulsi leaves into two cups of boiled water. Boil it further for 2 – 3 minutes over low flame. Allow the tulsi water to cool down. You could drink it after the water has completely cooled down or while it is still warm.
Can we take Tulsi drops daily?
HealthVit Tulsi Drops You can take these drops to fight with various kinds of infections, fever, cold, sore throat, cough, flu and for detoxifying your body. Just add 3-4 drops to a glass of warm water, juice or tea and take it every day.
Why does my Tulsi plant die?
Tulsi palnt care in winter season is the most important because most of the tulsi plant die off in this season because tulsi plant love the hot climate but the cold climate will make tulsi plant branches & leaf to turn black and die.
|
{
"url": "https://rehabilitationrobotics.net/what-determines-if-something-is-an-organelle/",
"source_domain": "rehabilitationrobotics.net",
"snapshot_id": "crawl=CC-MAIN-2021-39",
"warc_metadata": {
"Content-Length": "74992",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:A3E5UKHOJVFV6EBT3DJQ7DWW3X543QRR",
"WARC-Concurrent-To": "<urn:uuid:cfa53d73-ce4b-4df7-ada7-626077692e11>",
"WARC-Date": "2021-09-24T03:50:01",
"WARC-IP-Address": "172.67.206.221",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:U6DYMO2435TEEC4OPI5RQKGQDWLFGYZU",
"WARC-Record-ID": "<urn:uuid:9ad5f618-3a5f-4633-a3b9-262c8cfcb711>",
"WARC-Target-URI": "https://rehabilitationrobotics.net/what-determines-if-something-is-an-organelle/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:b36e993c-221b-41ec-808d-0915c4ff0ffb>"
},
"warc_info": "isPartOf: CC-MAIN-2021-39\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for September 2021\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-54\r\nsoftware: Apache Nutch 1.18 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.2-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
6,
7,
18,
19,
65,
66,
112,
113,
434,
435,
495,
496,
524,
525,
529,
590,
681,
774,
775,
802,
803,
1047,
1048,
1080,
1081,
1271,
1272,
1303,
1304,
1605,
1606,
1627,
1628,
1858,
1859,
1890,
1891,
2130,
2131,
2160,
2161
],
"line_end_idx": [
6,
7,
18,
19,
65,
66,
112,
113,
434,
435,
495,
496,
524,
525,
529,
590,
681,
774,
775,
802,
803,
1047,
1048,
1080,
1081,
1271,
1272,
1303,
1304,
1605,
1606,
1627,
1628,
1858,
1859,
1890,
1891,
2130,
2131,
2160,
2161,
2394
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 2394,
"ccnet_original_nlines": 41,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.3772321343421936,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.004464290104806423,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.125,
"rps_doc_frac_unique_words": 0.5507614016532898,
"rps_doc_mean_word_length": 4.911167621612549,
"rps_doc_num_sentences": 25,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.0196685791015625,
"rps_doc_word_count": 394,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.05478036031126976,
"rps_doc_frac_chars_dupe_6grams": 0.03927649185061455,
"rps_doc_frac_chars_dupe_7grams": 0.03927649185061455,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.010335920378565788,
"rps_doc_frac_chars_top_3gram": 0.016537470743060112,
"rps_doc_frac_chars_top_4gram": 0.02583979070186615,
"rps_doc_books_importance": -201.50936889648438,
"rps_doc_books_importance_length_correction": -201.50936889648438,
"rps_doc_openwebtext_importance": -107.03495788574219,
"rps_doc_openwebtext_importance_length_correction": -107.03495788574219,
"rps_doc_wikipedia_importance": -76.66645812988281,
"rps_doc_wikipedia_importance_length_correction": -76.66645812988281
},
"fasttext": {
"dclm": 0.7039706110954285,
"english": 0.9425881505012512,
"fineweb_edu_approx": 2.767011880874634,
"eai_general_math": 0.07495588064193726,
"eai_open_web_math": 0.21730512380599976,
"eai_web_code": 0.0014043999835848808
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "571.6",
"labels": {
"level_1": "Science and Natural history",
"level_2": "Biology and Anthropology",
"level_3": "Prehistoric peoples"
}
},
"secondary": {
"code": "615.32",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "6",
"label": "Promotional/Advertisement"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "3",
"label": "Irrelevant Content"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "3",
"label": "Incoherent Flow"
}
},
"document_type_v2": {
"primary": {
"code": "9",
"label": "FAQ"
},
"secondary": {
"code": "10",
"label": "Knowledge Article"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "1",
"label": "No Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "2",
"label": "Partially Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
9222580d47c553ea90dc0f5e416f8f3a
|
-6,853,852,060,557,813,000
|
Talk Space Glassdoor – Get Started Now
The demand for online treatment has increased in the last few years. Talk Space Glassdoor…According to the CDC, 40% of American adults experienced psychological health or drug abuse issues during the coronavirus pandemic. It took a significant toll on younger grownups, important employees, individuals of color, and caregivers. While online treatment ended up being the only option for the majority of during this time, favorable experiences assisted lots of people recognize that it’s a practical alternative in a post-pandemic world, too.
All of us can benefit from talking with a therapist. Everybody deals with obstacles in life that can get in the way of our joy or become obstructions to our objectives. And sometimes, when goals themselves change, we require assistance coping and browsing with hard emotions.
BetterHelp therapists are all highly certified to assist you as you look for to enhance your life. The company also deals with therapists who concentrate on specific areas of issue, including however not limited to:
Anxiety
Stress
Stress and anxiety
Self-confidence
Life modifications
Parenting
Relationships
Religious beliefs
Sexuality
Identity
Anger
Addiction
Consuming
Sleep
PTSD
Sorrow
Household dispute
Try BetterHelp
Additional services
In addition to specific treatment, the BetterHelp homepage lists Couples and Teenager counseling choices. Each of these services sends you to a sibling site when chosen– Regain.us for couples and TeenCounseling.com for teenagers. Prices for these services is similar to BetterHelp, and all therapists satisfy the same high requirements and undergo the exact same extensive screening. Talk Space Glassdoor
Better help reviews
BetterHelp has a separate site dedicated to LGBTQIA therapy, called Pride Therapy. Its services are just as structured and budget-friendly as the parent business, but therapists with Pride Therapy specialize in offering treatment to individuals in the LGBTQIA community. Pride Therapy also protects your personal privacy and privacy as carefully as BetterHelp.
maybe someone else that you have actually known in the past great work ethic really an assertive communicator just appears typically like he knows what’s happening with life has whatever found out so now that we have these images in mind of somebody with depression and someone that apparently doesn’t want to shift gears a bit to talk to you about a functioning alcoholic we’ve all heard this term so what does it indicate when we say someone’s an operating alcoholic or generally describing someone that probably does have some sort of issue with alcohol but they have the ability to preserve their job they have the ability to keep relationships household but the problem I think is that sometimes they’re not able to maintain those things in healthy ways and it’s extremely challenging in some cases to recognize an operating alcoholic due to the fact that they are able to keep some elements of their life together so leaping back to the original topic here of someone with high operating anxiety otherwise called dysthymia it’s truly hard to recognize these people often and sometimes it’s us in some cases we can’t even identify when it’s us that we’re experiencing these things so today once again we wish to talk about things that you can be trying to find or things that you might have seen in yourself that could be a sign that you’re experiencing high-functioning anxiety so people with high-functioning depression or experiencing dysthymia are frequently challenging to recognize we’re not seeing these overt qualities of an extremely depressed person no catatonic states in fact people with high-functioning depression are frequently able to preserve actually healthy lifestyles great relationships with other individuals and that and it vertically almost makes the danger a little bit scarier in a various kind of way why somebody with obvious symptoms of anything we can discover them we can get them into some kind of services or try to help them as best as we can for people flying under the radar for individuals experiencing signs that we don’t see it’s actually difficult to determine them and after that get them assist it’s truly challenging to interact to them that perhaps they ought to think about finding help for themselves so when we think about mental health services in general there already is a quite huge stigma around this a lot of individuals out there grownups in the United States for example have a tough time looking for treatment because of you know the idea that if you look for treatment you’re crazy or you can’t manage things by yourself or something
Is BetterHelp legit?
Yes, BetterHelp is a legit, credible business and a leader in online treatment with over 22,000 therapists and almost two million patients so far. Many people choose it to their standard in-person therapy.
A safe and secure platform
Full compliance with HIPAA law
Greater price for some people, compared to in-person therapy
The choice of privacy
High requirements for its therapists
An uncomplicated experience whether you utilize the app or the website
Who are the therapists?
The most crucial resource BetterHelp offers is its broad selection of extremely qualified therapists. Although it was obtained by Teladoc, Inc. in 2015, the company continues to use the exact same rigorous therapist application process in order to vet therapists and maintain quality. BetterHelp reports that only 15% of therapists who apply to the platform are approved.
The therapist application process consists of:
An evaluation of each therapist’s background, experience, and referrals
Confirmation of credentials
A case study examination assessed by a certified clinician; a video interview
A platform abilities test
Therapists are likewise based on ongoing quality monitoring, enhancement, and client feedback throughout their period at BetterHelp.
higher for them since they don’t wish to clue individuals in their lives in to the reality that they might be having problem with something or that they might need help with something therefore for individuals experiencing this we have a hard time finding them and they have a tough time finding help due to the fact that you know perhaps some part of them does not truly want to be identified where this other part does however we do not understand how to find them so what are we trying to find in order to recognize whether we ourselves are having a difficult time with this or somebody that we care about might be going through a tough time with this there are some things that you can be looking for or tuning into in yourself to figure out whether you might be having some sort of obstacle with high working depression so one of the first things to try to find is this basic sense of sadness going back to this image you may have of this depressed individual you could be believing someone sobbing all day simply having a difficult time with life dropped over catatonic even possibly stagnating quite you’re not going to actually see this with somebody with high working depression but rather like I said a general and subtle sense of sadness the majority of the time almost every day if not every day and it’s a little bit mysterious sometimes you can’t truly tell where this sensation is coming from or pinpoint any specific trigger that hurt your sensations or anything like that some other things to be searching for and considering is the failure or you know the loss of capability to experience joy loss of interests and things that you utilized to truly discover to be something that makes you feel excellent or bring some sort of satisfaction to your life you may also discover decreased energy so like Talk Space Glassdoor.
I stated not necessarily not having the ability to rise but just lessened you feel fatigued a great deal of the time where maybe before you didn’t experience it that way other things to be looking for is being actually self-critical which results in perfectionism which can likewise contribute to blowing things out of proportion finding actually small things in your life to become big issues so I believe there’s a saying making a mountain out of a molehill a great deal of individuals dealing with high functioning depression experienced these things like I stated truly self-critical feeling a lot of guilt and shame about the past and even the future things that haven’t even happened yet this is something that a great deal of individuals could not be struggling with you might also be thinking of this depressed person who appears sad all the time however there’s other feelings involved in depression.
|
{
"url": "https://inversiontherapyhq.com/talk-space-glassdoor/",
"source_domain": "inversiontherapyhq.com",
"snapshot_id": "crawl=CC-MAIN-2022-21",
"warc_metadata": {
"Content-Length": "49474",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:2NGVHJIZ3P3XJZ5TQ3UZTSMQWXITY3VR",
"WARC-Concurrent-To": "<urn:uuid:00c66740-1fb2-4f33-8272-9ba91f3f8a8e>",
"WARC-Date": "2022-05-25T16:00:18",
"WARC-IP-Address": "45.84.120.170",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:H4QZSAPYVXNMQ6O7JJS6IF7ZBALIAS5T",
"WARC-Record-ID": "<urn:uuid:02916123-ecbd-49ec-ad8c-557b419c0507>",
"WARC-Target-URI": "https://inversiontherapyhq.com/talk-space-glassdoor/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:15b79b4e-a30d-4f04-ab67-48c403e1ab57>"
},
"warc_info": "isPartOf: CC-MAIN-2022-21\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for May 2022\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-55\r\nsoftware: Apache Nutch 1.18 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.3-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
39,
40,
42,
43,
585,
586,
862,
863,
1079,
1080,
1088,
1095,
1114,
1130,
1149,
1159,
1173,
1191,
1201,
1210,
1216,
1226,
1236,
1242,
1247,
1254,
1272,
1273,
1288,
1289,
1309,
1310,
1715,
1716,
1736,
1737,
2098,
2099,
4695,
4696,
4717,
4718,
4924,
4925,
4952,
4983,
5044,
5066,
5103,
5174,
5198,
5199,
5571,
5572,
5619,
5620,
5692,
5720,
5798,
5824,
5957,
5958,
7797,
7798
],
"line_end_idx": [
39,
40,
42,
43,
585,
586,
862,
863,
1079,
1080,
1088,
1095,
1114,
1130,
1149,
1159,
1173,
1191,
1201,
1210,
1216,
1226,
1236,
1242,
1247,
1254,
1272,
1273,
1288,
1289,
1309,
1310,
1715,
1716,
1736,
1737,
2098,
2099,
4695,
4696,
4717,
4718,
4924,
4925,
4952,
4983,
5044,
5066,
5103,
5174,
5198,
5199,
5571,
5572,
5619,
5620,
5692,
5720,
5798,
5824,
5957,
5958,
7797,
7798,
8707
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 8707,
"ccnet_original_nlines": 64,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 1,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.5321336984634399,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.008354759775102139,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.06491003185510635,
"rps_doc_frac_unique_words": 0.38054966926574707,
"rps_doc_mean_word_length": 5.076109886169434,
"rps_doc_num_sentences": 27,
"rps_doc_symbol_to_word_ratio": 0.0006426700274460018,
"rps_doc_unigram_entropy": 5.602832794189453,
"rps_doc_word_count": 1419,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.028043869882822037,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.0041649299673736095,
"rps_doc_frac_chars_top_3gram": 0.007219209801405668,
"rps_doc_frac_chars_top_4gram": 0.004997919779270887,
"rps_doc_books_importance": -793.4657592773438,
"rps_doc_books_importance_length_correction": -793.4657592773438,
"rps_doc_openwebtext_importance": -433.4647521972656,
"rps_doc_openwebtext_importance_length_correction": -433.4647521972656,
"rps_doc_wikipedia_importance": -325.0701904296875,
"rps_doc_wikipedia_importance_length_correction": -325.0701904296875
},
"fasttext": {
"dclm": 0.06489616632461548,
"english": 0.9613763093948364,
"fineweb_edu_approx": 1.3542571067810059,
"eai_general_math": 0.030699970200657845,
"eai_open_web_math": 0.1426393985748291,
"eai_web_code": 0.020488319918513298
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.89",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "616.858",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "4",
"label": "Analyze"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "1",
"label": "News/Editorial"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "16",
"label": "Personal Blog"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "4",
"label": "Highly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
b755ed28a90d11d590ef646404f4afc5
|
-1,746,025,226,072,087,800
|
Looking for Something?
How do nerves work?
Author:
A brilliant lesson on nerves and how they work. I found this through the wonderful body in mind website. Read the forum going or head over to TedED to find more brilliant lessons.
Thank you to these forward thinking brilliant people. And to the creatives that put the presentations together.
By Educator, Elliot Krane and Animator, Franz Palomares
“At any moment, there is an electrical storm coursing through your body. Discover how chemical reactions create an electric current that drives our responses to everything from hot pans to a mother’s caress.”
ed.ted.com/lessons/how-do-nerves-work
Leave a Reply
Enter your address to receive posts via email
Definitions of pain
What is Pudendal Neuralgia (PN)?
Most simply put PN is Carpal Tunnel in the pelvis/buttocks. Compression of the Pudendal Nerve occurs after trauma to the pelvis and is aggravated with pressure. The pain is often described as a toothache like pain, with spasms, sensations of tingling, numbness, or burning. It can be very debilitating.
What is Neuropathic pain?
Neuropathic pain is the result of an injury or malfunction in the peripheral or central nervous system. The pain is often triggered by an injury, but this injury may or may not involve actual damage to the nervous system. More…
Pain Train my online health record
Pain Train my online health record
Save
Save
Save
Order my book $31 (inc. postage)
Archives
|
{
"url": "https://www.pudendalnerve.com.au/2012/08/22/how-do-nerves-work/",
"source_domain": "www.pudendalnerve.com.au",
"snapshot_id": "crawl=CC-MAIN-2017-39",
"warc_metadata": {
"Content-Length": "105599",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:YJK5CA4H57KS6GCMPV5IPFW57S3E72ZN",
"WARC-Concurrent-To": "<urn:uuid:1f5f9651-bf56-4fb5-bbb8-c02989bcc4d2>",
"WARC-Date": "2017-09-19T18:57:10",
"WARC-IP-Address": "101.0.116.100",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:FL6E2SS7FB4WJQBUK3ADQOCJMOEJFM2S",
"WARC-Record-ID": "<urn:uuid:a36da488-a23e-4516-a9d1-1c3dbb63d32a>",
"WARC-Target-URI": "https://www.pudendalnerve.com.au/2012/08/22/how-do-nerves-work/",
"WARC-Truncated": "length",
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:85f2f2b6-7c4e-4958-977a-5948101145d0>"
},
"warc_info": "robots: classic\r\nhostname: ip-10-33-131-217.ec2.internal\r\nsoftware: Nutch 1.6 (CC)\r\nisPartOf: CC-MAIN-2017-39\r\noperator: Common Crawl Admin\r\ndescription: Wide crawl of the web for September 2017\r\npublisher: Common Crawl\r\nformat: WARC File Format 1.0\r\nconformsTo: http://bibnum.bnf.fr/WARC/WARC_ISO_28500_version1_latestdraft.pdf"
}
|
{
"line_start_idx": [
0,
23,
24,
44,
45,
53,
54,
234,
346,
347,
403,
404,
613,
614,
652,
653,
654,
668,
669,
715,
716,
736,
737,
770,
1073,
1074,
1100,
1328,
1329,
1364,
1365,
1400,
1401,
1406,
1407,
1412,
1413,
1418,
1419,
1452,
1453
],
"line_end_idx": [
23,
24,
44,
45,
53,
54,
234,
346,
347,
403,
404,
613,
614,
652,
653,
654,
668,
669,
715,
716,
736,
737,
770,
1073,
1074,
1100,
1328,
1329,
1364,
1365,
1400,
1401,
1406,
1407,
1412,
1413,
1418,
1419,
1452,
1453,
1461
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 1461,
"ccnet_original_nlines": 40,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.34736841917037964,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.014035089872777462,
"rps_doc_frac_lines_end_with_ellipsis": 0.024390239268541336,
"rps_doc_frac_no_alph_words": 0.1508771926164627,
"rps_doc_frac_unique_words": 0.6452991366386414,
"rps_doc_mean_word_length": 4.995726585388184,
"rps_doc_num_sentences": 21,
"rps_doc_symbol_to_word_ratio": 0.0035087699070572853,
"rps_doc_unigram_entropy": 4.757174491882324,
"rps_doc_word_count": 234,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.04961505904793739,
"rps_doc_frac_chars_dupe_6grams": 0.04961505904793739,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.012831480242311954,
"rps_doc_frac_chars_top_3gram": 0.015397779643535614,
"rps_doc_frac_chars_top_4gram": 0.023952100425958633,
"rps_doc_books_importance": -119.4546890258789,
"rps_doc_books_importance_length_correction": -114.12046813964844,
"rps_doc_openwebtext_importance": -84.33556365966797,
"rps_doc_openwebtext_importance_length_correction": -84.33556365966797,
"rps_doc_wikipedia_importance": -47.265953063964844,
"rps_doc_wikipedia_importance_length_correction": -37.890708923339844
},
"fasttext": {
"dclm": 0.035712361335754395,
"english": 0.9217149019241333,
"fineweb_edu_approx": 2.1842377185821533,
"eai_general_math": 0.00014090999320615083,
"eai_open_web_math": 0.10051239281892776,
"eai_web_code": 0.000014420000297832303
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "612.8",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Physiology"
}
},
"secondary": {
"code": "612.82",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Physiology"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "2",
"label": "Click Here References"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "6",
"label": "Content Listing"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "1",
"label": "No Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "6",
"label": "Not Applicable/Indeterminate"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
1a01aa77535b9ecfb87b9fc36adbcd2f
|
-6,842,134,640,447,898,000
|
@article {Lacourt691, author = {Lacourt, Aude and L{\'e}v{\^e}que, Emilie and Guichard, Elie and Gilg Soit Ilg, Anabelle and Sylvestre, Marie-Pierre and Leffondr{\'e}, Karen}, title = {Dose-time-response association between occupational asbestos exposure and pleural mesothelioma}, volume = {74}, number = {9}, pages = {691--697}, year = {2017}, doi = {10.1136/oemed-2016-104133}, publisher = {BMJ Publishing Group Ltd}, abstract = {Objectives Early occupational exposure to asbestos has been shown to be associated with an increased risk of pleural mesothelioma (PM), which suggests that the timing of exposure might play a role in the dose{\textendash}response relationship. However, none studies has evaluated the relative impact of increasing the annual intensity of occupational exposure to asbestos at each time of the whole exposure history. Yet such evaluation would allow the comparison of the risks of PM associated with different longitudinal profiles of occupational exposure to asbestos. Our objective was to estimate the time-dependent relative impact of asbestos exposure intensity over the whole occupational history and to compare the resulting estimated risks of PM associated with different profiles of exposure, using data from a large French case{\textendash}control study.Methods This study included 1196 male cases recruited in 1987{\textendash}2006 and 2369 matched controls on birth year. Occupational exposure to asbestos was assessed using a job exposure matrix and represented in logistic regression models using a flexible weighted cumulative index of exposure.Results Due to much stronger weights of early doses of asbestos exposure, subjects who accumulated 20 fibres/mL over their entire job history with high doses during the first years and low doses thereafter were at higher risk of PM than those who accumulated most of the doses later (OR=2.37 (95\% CI 2.01 to 2.87)).Conclusion This study provides new insights on the dose-time-response relationship between occupational asbestos and PM and illustrates the importance of considering timing of exposure in its association with cancer risk.}, issn = {1351-0711}, URL = {https://oem.bmj.com/content/74/9/691}, eprint = {https://oem.bmj.com/content/74/9/691.full.pdf}, journal = {Occupational and Environmental Medicine} }
|
{
"url": "https://oem.bmj.com/highwire/citation/165056/bibtext",
"source_domain": "oem.bmj.com",
"snapshot_id": "CC-MAIN-2024-26",
"warc_metadata": {
"Content-Length": "3418",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:532JS4ZUWVV5HJHEIO35WS2YCMD72BAO",
"WARC-Concurrent-To": "<urn:uuid:befb56e8-2912-4cc9-814a-78e4e63b8002>",
"WARC-Date": "2024-06-21T23:29:44",
"WARC-IP-Address": "104.18.32.115",
"WARC-Identified-Payload-Type": "text/plain",
"WARC-Payload-Digest": "sha1:COXBNNIPXOFVC7PEZDAYB2XISPRRZYOO",
"WARC-Record-ID": "<urn:uuid:c191cade-e966-4e93-8b2a-bd39bbcbcc45>",
"WARC-Target-URI": "https://oem.bmj.com/highwire/citation/165056/bibtext",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:724a0117-dee5-4f20-acb1-a64433489fca>"
},
"warc_info": "isPartOf: CC-MAIN-2024-26\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for June 2024\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-181\r\nsoftware: Apache Nutch 1.20 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.5-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0
],
"line_end_idx": [
2307
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 2307,
"ccnet_original_nlines": 0,
"rps_doc_curly_bracket": 0.017338529229164124,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.268980473279953,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.02169197052717209,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.29718002676963806,
"rps_doc_frac_unique_words": 0.5882353186607361,
"rps_doc_mean_word_length": 6.039215564727783,
"rps_doc_num_sentences": 19,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 4.785220146179199,
"rps_doc_word_count": 306,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.06926406919956207,
"rps_doc_frac_chars_dupe_6grams": 0.03463203087449074,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.043290041387081146,
"rps_doc_frac_chars_top_3gram": 0.0476190485060215,
"rps_doc_frac_chars_top_4gram": 0.06493505835533142,
"rps_doc_books_importance": -184.70030212402344,
"rps_doc_books_importance_length_correction": -184.70030212402344,
"rps_doc_openwebtext_importance": -109.86922454833984,
"rps_doc_openwebtext_importance_length_correction": -109.86922454833984,
"rps_doc_wikipedia_importance": -67.76226043701172,
"rps_doc_wikipedia_importance_length_correction": -67.76226043701172
},
"fasttext": {
"dclm": 0.0738789364695549,
"english": 0.9109456539154053,
"fineweb_edu_approx": 3.3115577697753906,
"eai_general_math": 0.758539080619812,
"eai_open_web_math": 0.3863534927368164,
"eai_web_code": 0.021731140092015266
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "614.57",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Public health"
}
},
"secondary": {
"code": "614.5",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Public health"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "4",
"label": "Analyze"
},
"secondary": {
"code": "2",
"label": "Understand"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "2",
"label": "Academic/Research"
},
"secondary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "0",
"label": "No Artifacts"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "0",
"label": "No missing content"
}
},
"document_type_v2": {
"primary": {
"code": "3",
"label": "Academic Writing"
},
"secondary": {
"code": "8",
"label": "Documentation"
}
},
"reasoning_depth": {
"primary": {
"code": "3",
"label": "Intermediate Reasoning"
},
"secondary": {
"code": "2",
"label": "Basic Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "4",
"label": "Graduate/Expert Level"
},
"secondary": {
"code": "3",
"label": "Undergraduate Level"
}
}
}
|
6e3c8d3593f3f69280bb5502b214ab8e
|
-155,671,270,278,814,270
|
How to remove graphene oxide from the body?
How to remove graphene oxide from the body?
November 5, 2022 2 By Shilpent
Before we get into – “How to remove graphene oxide from the body”, let us first see why it is necessary to eliminate it!
Our body produces a substance – Glutathione. Glutathione is an amino acid compound composed of glycine, cysteine, and glutamic acid. The liver naturally produces it and is involved in numerous bodily processes, including tissue development and repair, the production of chemicals and proteins required by the body, and the immune system. Our bodies contain a natural glutathione reserve. That is what provides us with a robust immune system.
When glutathione levels in the body are high, we have no difficulties, and our immune system operates appropriately. When the level of graphene oxide in the system surpasses the quantity of glutathione, the immune system collapses, and a cytokine storm occurs.
Electronic excitation allows graphene oxide to develop to surpass glutathione in the body rapidly. EMFs attack the graphene, causing it to oxidize and triggering the illness. Glutathione concentrations are also deficient in those with pre-existing diseases like diabetes or obesity. Similarly, glutathione levels in new-borns, children, and athletes are high.
When oxidized or triggered by specific EMF frequencies, graphene oxide overwhelms the body’s ability to produce adequate glutathione, destroying the immune system and causing sickness. In the case of diseases such as Covid-19, the body’s glutathione levels must be boosted to deal with the graphene oxide toxin that has been injected or electrically activated.
Graphene oxide is now identified as a pollutant. Apart from covid-19 vaccines, we can often find them in the water supply, the polluted air we breathe, and even our food sources. We can also see that Electromagnetic frequencies (“EMF”) interact with and activate graphene oxide, specifically the greater spectrum of frequencies in 5G. That can get much more dangerous to our health.
While we have various research supporting how graphene is toxic to the human body, the matter is that now we have multiple methods to remove it from our systems to restore our health. According to various pieces of research, two substances can remove graphene oxide from the body, i.e., N-acetylcysteine or glutathione, and high concentrations of vitamin D. It’s worth noting that 5G plays an essential role in sustaining graphene oxide in the body, which acts as a web to reach the critical organs. Essentially, antioxidants play a significant role in removing graphene oxide from the body.
N-acetylcysteine (“NAC”) is a supplement that stimulates the body’s glutathione production. It is recognized as the precursor of glutathione and stimulates endogenous glutathione secretion. NAC is derived from the amino acid L-cysteine, which the body uses to produce antioxidants. Antioxidants are nutrients, minerals, and other substances that help protect and repair cells. In conjunction with NAC, Zinc is an essential antioxidant in breaking down graphene oxide. Following vaccination, these two antioxidants have benefitted persons affected by magnetism. That’s in persons who have become magnetic after taking two doses of Pfizer. After taking these supplements, they no longer have these symptoms. Taking Vitamin D supplements under a doctor’s guidance also helps reduce the toxicity level of graphene oxide produced in the body.
Buy : Graphene Oxide | Graphene
|
{
"url": "https://blog.shilpent.com/how-to-remove-graphene-oxide-from-the-body/",
"source_domain": "blog.shilpent.com",
"snapshot_id": "CC-MAIN-2023-40",
"warc_metadata": {
"Content-Length": "52580",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:GTBZDTGPILNIXAACZKED7SPCYCBCKQRN",
"WARC-Concurrent-To": "<urn:uuid:7d893b16-8a27-4f8b-8f9b-d525b529dd75>",
"WARC-Date": "2023-09-26T02:25:39",
"WARC-IP-Address": "172.67.186.233",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:BTXGSCTZDALLCF77AHYMHCJCR5S27MTL",
"WARC-Record-ID": "<urn:uuid:ce85b28f-1fde-4fed-b4ee-da09b57f730f>",
"WARC-Target-URI": "https://blog.shilpent.com/how-to-remove-graphene-oxide-from-the-body/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:eda184b6-879e-45fd-9afa-038ba4e85713>"
},
"warc_info": "isPartOf: CC-MAIN-2023-40\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for September/October 2023\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-82\r\nsoftware: Apache Nutch 1.19 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.5-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
44,
45,
89,
90,
121,
122,
243,
685,
686,
947,
1307,
1668,
2051,
2052,
2644,
2645,
3483,
3484
],
"line_end_idx": [
44,
45,
89,
90,
121,
122,
243,
685,
686,
947,
1307,
1668,
2051,
2052,
2644,
2645,
3483,
3484,
3515
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 3515,
"ccnet_original_nlines": 18,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.3668730556964874,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.018575850874185562,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.1486068069934845,
"rps_doc_frac_unique_words": 0.46777164936065674,
"rps_doc_mean_word_length": 5.305708885192871,
"rps_doc_num_sentences": 36,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 4.964599609375,
"rps_doc_word_count": 543,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.05275946110486984,
"rps_doc_frac_chars_dupe_6grams": 0.04442901909351349,
"rps_doc_frac_chars_dupe_7grams": 0.024297120049595833,
"rps_doc_frac_chars_dupe_8grams": 0.024297120049595833,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.0676848292350769,
"rps_doc_frac_chars_top_3gram": 0.02950363978743553,
"rps_doc_frac_chars_top_4gram": 0.03471016883850098,
"rps_doc_books_importance": -321.6795959472656,
"rps_doc_books_importance_length_correction": -321.6795959472656,
"rps_doc_openwebtext_importance": -177.83547973632812,
"rps_doc_openwebtext_importance_length_correction": -177.83547973632812,
"rps_doc_wikipedia_importance": -134.79830932617188,
"rps_doc_wikipedia_importance_length_correction": -134.79830932617188
},
"fasttext": {
"dclm": 0.15502780675888062,
"english": 0.939043402671814,
"fineweb_edu_approx": 2.9592294692993164,
"eai_general_math": 0.21771752834320068,
"eai_open_web_math": 0.37346160411834717,
"eai_web_code": 0.012083649635314941
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "615.5",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
},
"secondary": {
"code": "613.6",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "6",
"label": "Promotional/Advertisement"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "3",
"label": "Irrelevant Content"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "2",
"label": "Click Here References"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "16",
"label": "Personal Blog"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "2",
"label": "Partially Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "2",
"label": "High School Level"
},
"secondary": {
"code": "1",
"label": "General Audience"
}
}
}
|
9222580d47c553ea90dc0f5e416f8f3a
|
3,871,608,268,369,030,700
|
Medication Abortion (In-Office)
The Abortion Pill provides women with a safe medical alternative to the traditional surgical abortion.
1.png
Medication Abortion
Medication abortion utilizing a regimen of two oral medications was approved by the FDA over 20 years ago and has since been used by women in the United States as a safe alternative to surgical abortion. Many women prefer taking medication to terminate a pregnancy because the process is similar to a miscarriage and can be completed in the comfort of home.
What should I expect?
If you choose to come into the office for a medication abortion, you will have an ultrasound to determine the location and gestational age of your pregnancy. We will also perform a Hemoglobin (finger stick) to ensure that you are not anemic.
If you are eligible (10 weeks gestational age or less) your clinician will review all of the risks of having a medication abortion. Once your questions have been answered, your clinician will give you the first medication to take in the office.
This first pill that is taken in the office will stop your pregnancy from growing and start the process of the abortion. At some point that is convenient for you in the next 24-48 hours, you will place 4 tablets of the second medication in your cheeks (two on each side) and let them dissolve. Usually within an hour of taking the medication, you will start cramping and bleeding, more severely than during your menses. Most women pass the pregnancy within four hours; however the bleeding can continue irregularly for up to six weeks, even if the abortion was successful.
At a follow-up visit in one week, we will perform a second ultrasound to confirm that you are no longer pregnant.
How safe is medication abortion?
There are risks to taking a medication abortion. Most women experience bleeding and cramping, more severe than a menses. The pain usually resolves with over-the-counter pain relievers after 3-4 hours. The most common risk of medication abortion is that the pills might not work. 2-5% of women using medication to end a pregnancy need additional evaluation or treatment, such as a surgical procedure. There is also the risk of heavy vaginal bleeding or infection. If you bleed enough to soak through two thick full-size sanitary pads per hour, for two hours in a row, or if you have a fever of 100.4 degrees or higher that lasts for more than 4 hours, contact your clinician right away.
Is a medication abortion effective?
Medication abortion is safe and effective for 95-98% of women. 2-5% of women taking a medication abortion will require an additional intervention to treat heavy bleeding or incomplete abortion. Sometimes a repeat dose of medication is sufficient, but if the pregnancy is continuing to grow, your clinician will recommend a surgical procedure. This surgical procedure is called a D+C and can be performed at many of our offices. There is also a small risk of infection (< 2%). At FPA, we have a clinician on call 24 hours, 7 days a week to answer any questions or concerns that you may have during the process. We are here for you every step of the way!
Resources
CLICK HERE to view our medication abortion guide.
CLICK HERE to view common side effects following the procedure.
CLICK HERE to view bleeding levels.
telehealth-2.png
Book Online In-Office and Telehealth
|
{
"url": "https://www.fpawomenshealth.com/abortion/medical-abortion-in-office",
"source_domain": "www.fpawomenshealth.com",
"snapshot_id": "CC-MAIN-2024-22",
"warc_metadata": {
"Content-Length": "29228",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:V2KKVPRI77ZHCNTE46BRBA6OMUPH557V",
"WARC-Concurrent-To": "<urn:uuid:6a0c97f0-5f33-433c-b005-5a4d7ebc31c0>",
"WARC-Date": "2024-05-29T04:50:36",
"WARC-IP-Address": "3.23.212.111",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:2E3KZ56UMX4QMSHLQ22GJZJT3YHWODTT",
"WARC-Record-ID": "<urn:uuid:89c47543-0044-42b2-917d-fa477b991a2f>",
"WARC-Target-URI": "https://www.fpawomenshealth.com/abortion/medical-abortion-in-office",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:ca5e365a-a0d5-448d-87ba-51a1c4c9d852>"
},
"warc_info": "isPartOf: CC-MAIN-2024-22\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for May 2024\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-27\r\nsoftware: Apache Nutch 1.19 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.5-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
32,
33,
136,
137,
143,
144,
164,
165,
524,
525,
547,
548,
549,
792,
793,
1040,
1041,
1617,
1618,
1734,
1735,
1768,
1769,
2462,
2463,
2499,
2500,
3159,
3160,
3170,
3171,
3221,
3222,
3286,
3287,
3323,
3324,
3326,
3327,
3344,
3345
],
"line_end_idx": [
32,
33,
136,
137,
143,
144,
164,
165,
524,
525,
547,
548,
549,
792,
793,
1040,
1041,
1617,
1618,
1734,
1735,
1768,
1769,
2462,
2463,
2499,
2500,
3159,
3160,
3170,
3171,
3221,
3222,
3286,
3287,
3323,
3324,
3326,
3327,
3344,
3345,
3381
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 3381,
"ccnet_original_nlines": 41,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.42465752363204956,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.0167427696287632,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.14916285872459412,
"rps_doc_frac_unique_words": 0.4308510720729828,
"rps_doc_mean_word_length": 4.773049831390381,
"rps_doc_num_sentences": 36,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 4.927725315093994,
"rps_doc_word_count": 564,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.0802377387881279,
"rps_doc_frac_chars_top_3gram": 0.03528974950313568,
"rps_doc_frac_chars_top_4gram": 0.01671620085835457,
"rps_doc_books_importance": -227.77703857421875,
"rps_doc_books_importance_length_correction": -227.77703857421875,
"rps_doc_openwebtext_importance": -153.85008239746094,
"rps_doc_openwebtext_importance_length_correction": -153.85008239746094,
"rps_doc_wikipedia_importance": -84.06212615966797,
"rps_doc_wikipedia_importance_length_correction": -84.06212615966797
},
"fasttext": {
"dclm": 0.04010504111647606,
"english": 0.94588702917099,
"fineweb_edu_approx": 1.7956677675247192,
"eai_general_math": 0.006521219853311777,
"eai_open_web_math": 0.1518891453742981,
"eai_web_code": 0.0005313800065778196
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "618.1",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Women — Health and hygiene, Children — Health and hygiene, Gynecology, and Pediatrics"
}
},
"secondary": {
"code": "615.857",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "1",
"label": "Factual"
},
"secondary": {
"code": "2",
"label": "Conceptual"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "6",
"label": "Promotional/Advertisement"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "0",
"label": "No Artifacts"
}
},
"missing_content": {
"primary": {
"code": "2",
"label": "Click Here References"
},
"secondary": {
"code": "0",
"label": "No missing content"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "17",
"label": "Product Page"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
b755ed28a90d11d590ef646404f4afc5
|
-8,798,335,603,772,204,000
|
Have questions? Visit https://www.reddit.com/r/SNPedia
rs17300741
From SNPedia
Orientationplus
Stabilizedplus
Make rs17300741(A;A)
Make rs17300741(A;G)
Make rs17300741(G;G)
ReferenceGRCh38 38.1/141
Chromosome11
Position64563990
GeneSLC22A11
is asnp
is mentioned by
dbSNPrs17300741
dbSNP (classic)rs17300741
ClinGenrs17300741
ebirs17300741
HLIrs17300741
Exacrs17300741
Gnomadrs17300741
Varsomers17300741
LitVarrs17300741
Maprs17300741
PheGenIrs17300741
Biobankrs17300741
1000 genomesrs17300741
hgdprs17300741
ensemblrs17300741
geneviewrs17300741
scholarrs17300741
googlers17300741
pharmgkbrs17300741
gwascentralrs17300741
openSNPrs17300741
23andMers17300741
23andMe allrs17300741
SNPshotrs17300741
SNPdbers17300741
MSV3drs17300741
GWAS Ctlgrs17300741
GMAF0.337
Max Magnitude0
? (A;A) (A;G) (G;G) 28
GWAS snp
PMID [PMID 19503597OA-icon.png]
Trait Uric acid concentrations
Title Meta-Analysis of 28,141 Individuals Identifies Common Variants within Five New Loci That Influence Uric Acid Concentrations
Risk Allele A
P-val 7E-14
Odds Ratio 0.06 [0.046-0.078] mg/dl increase
[PMID 19890391OA-icon.png] Common polymorphisms influencing serum uric Acid levels contribute to susceptibility to gout, but not to coronary artery disease
[PMID 19861489] Replication of the five novel loci for uric acid concentrations and potential mediating mechanisms.
[PMID 23712608] Genetic variability related to serum uric acid concentration and risk of Parkinson's disease.
[PMID 25867401] Polymorphisms of uric transporter proteins in the pathogenesis of gout in a Chinese Han population
[PMID 26290326OA-icon.png] Polymorphisms in GCKR, SLC17A1 and SLC22A12 were associated with phenotype gout in Han Chinese males: a case-control study
|
{
"url": "https://snpedia.com/index.php/Rs17300741",
"source_domain": "snpedia.com",
"snapshot_id": "crawl=CC-MAIN-2019-26",
"warc_metadata": {
"Content-Length": "41281",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:7YVLSIJQTLUTRQFHOBVRU7YUVXJIQF6O",
"WARC-Concurrent-To": "<urn:uuid:4f9275e1-1401-479e-9536-9eb2c315133f>",
"WARC-Date": "2019-06-20T21:09:53",
"WARC-IP-Address": "45.60.63.253",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:XFD46WZDLCRHJ5BCHYNAYKJAYCUXRKPR",
"WARC-Record-ID": "<urn:uuid:32c6cd06-e10e-4a3d-a02c-0b203091a936>",
"WARC-Target-URI": "https://snpedia.com/index.php/Rs17300741",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:df64560b-fcf5-448a-9327-b70c6925df20>"
},
"warc_info": "isPartOf: CC-MAIN-2019-26\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for June 2019\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-147-84-78.ec2.internal\r\nsoftware: Apache Nutch 1.15 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.1-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: http://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
55,
56,
67,
68,
81,
82,
98,
113,
134,
155,
176,
201,
214,
231,
244,
252,
268,
284,
310,
328,
342,
356,
371,
388,
406,
423,
437,
455,
473,
496,
511,
529,
548,
566,
583,
602,
624,
642,
660,
682,
700,
717,
733,
753,
763,
778,
801,
802,
803,
812,
844,
875,
1005,
1019,
1031,
1076,
1077,
1078,
1234,
1235,
1236,
1352,
1353,
1354,
1355,
1465,
1466,
1467,
1582,
1583,
1584
],
"line_end_idx": [
55,
56,
67,
68,
81,
82,
98,
113,
134,
155,
176,
201,
214,
231,
244,
252,
268,
284,
310,
328,
342,
356,
371,
388,
406,
423,
437,
455,
473,
496,
511,
529,
548,
566,
583,
602,
624,
642,
660,
682,
700,
717,
733,
753,
763,
778,
801,
802,
803,
812,
844,
875,
1005,
1019,
1031,
1076,
1077,
1078,
1234,
1235,
1236,
1352,
1353,
1354,
1355,
1465,
1466,
1467,
1582,
1583,
1584,
1733
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 1733,
"ccnet_original_nlines": 71,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.12110727280378342,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.10726644098758698,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.2906574308872223,
"rps_doc_frac_unique_words": 0.7446808218955994,
"rps_doc_mean_word_length": 7.771276473999023,
"rps_doc_num_sentences": 15,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 4.775905132293701,
"rps_doc_word_count": 188,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.027378510683774948,
"rps_doc_frac_chars_top_3gram": 0.04517453908920288,
"rps_doc_frac_chars_top_4gram": 0,
"rps_doc_books_importance": -148.33131408691406,
"rps_doc_books_importance_length_correction": -138.09689331054688,
"rps_doc_openwebtext_importance": -79.35743713378906,
"rps_doc_openwebtext_importance_length_correction": -79.35743713378906,
"rps_doc_wikipedia_importance": -48.94876480102539,
"rps_doc_wikipedia_importance_length_correction": -42.50383758544922
},
"fasttext": {
"dclm": 0.06990402936935425,
"english": 0.6640774011611938,
"fineweb_edu_approx": 2.8183352947235107,
"eai_general_math": 0.007975580170750618,
"eai_open_web_math": 0.3585054874420166,
"eai_web_code": 0.005106269847601652
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.019",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "616.858",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "2",
"label": "Academic/Research"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "8",
"label": "Documentation"
},
"secondary": {
"code": "10",
"label": "Knowledge Article"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "4",
"label": "Graduate/Expert Level"
},
"secondary": {
"code": "3",
"label": "Undergraduate Level"
}
}
}
|
1a01aa77535b9ecfb87b9fc36adbcd2f
|
3,423,401,244,416,064,000
|
Pages
Why Breathing Deeply Helps You Calm Down
Deep breaths can settle your nerves, and now scientists have discovered the neural pathway in the brain that controls this process.
In an experiment on mice, scientists identified a circuit of neurons — a tiny cluster of a mere 350 nerve cells, among millions in the mouse brain — that regulate the connection between breathing and the higher-order brain activity that affects how calmly or worked up the mice behaved.
When the scientists removed these cells, they found that the mice still breathed normally, but they were uncharacteristically calm. This discovery, the researchers said, may someday lead to therapies to help people who have anxiety, stress and panic attacks
A paper describing the work was published today (March 30) in the journal Science.
Breathing is largely an unconscious, involuntary action that's among the most basic rhythms of life. It is the process in which most animals inhale oxygen to create energy at a cellular level and then exhale carbon dioxide, the byproduct of this cellular respiration.
Yet humans have known for millennia that taking long, slow, deep breaths can have a calming effect and reduce stress. Conversely, panic attacks can cause a person to take short, fast breaths, further exacerbating the sense of unease.
Researchers have known that neural circuits throughout the brain regulate breathing, but until now, they had not pinpointed the neural pathway that connects breathing to the emotional states of anxiety and calmness.
In the new work, a team led by Dr. Mark Krasnow, a biochemistry professor at Stanford University School of Medicine in Stanford, California, searched the main region of the brain that controls breathing rhythms — called the pre-Bötzinger complex — which is nestled in a rudimentary section of the brain stem called the pons. In an experiment that was the culmination of years of work involving techniques such as neural mapping and genetically engineered mice, Krasnow's team zeroed in on the responsible circuitry.
The team found a subset of neurons in the pre-Bötzinger complex that transmits signals to a region in the pons that moderates feelings of alertness, attention and stress.
They also found that these neurons express two proteins, cadherin-9 (CDH9) and developing brain homeobox protein 1 (DBX1), which are controlled by the Cdh9 and Dbx1 genes, respectively.
The researchers then turned to genetically engineered mice, in which they could mute the Cdh9 and Dbx1 genes. This enabled the researchers to select and kill the approximately 350 neurons that are thought to connect breathing to arousal, yet leave all the other neurons untouched, according to the study's lead author, Dr. Kevin Yackle, an assistant researcher at the UCSF School of Medicine. Afterward, the researchers found that the mice spent more time in a calm state.
Although deep breathing is an easy and safe way to control anxiety and stress, Yackle sees potential for developing medicines that target these genes.
"In panic disorders, it may be nearly impossible for one to control breathing," Yackle told Live Science. "Therefore, a pharmacological approach may be critical for preventing these panic attacks triggered by hyperventilation."
Yackle also said that sudden infant death syndrome (SIDS) may result when the brain doesn't sense a lack of oxygen while the infant is sleeping, and thus doesn't arouse the body. Some babies may be at higher risk for SIDS for reasons of genetics or because they were born prematurely. In these cases, babies at the highest risk for SIDS might benefit from a therapy that improves the neural signaling between oxygen intake and arousal, Yackle said.
No comments:
Post a Comment
How art aided Andrew Marrs recovery from stroke
“When I started to recover in hospital, one of my early frustrations was that I found I wanted to draw. Drawing does for me what others fi...
|
{
"url": "https://www.rbcreativearts.com/2019/03/why-breathing-deeply-helps-you-calm-down.html",
"source_domain": "www.rbcreativearts.com",
"snapshot_id": "crawl=CC-MAIN-2019-39",
"warc_metadata": {
"Content-Length": "56364",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:WCCHWE6ZXFBBVWKNUYLS7EDOI5ZHMW3X",
"WARC-Concurrent-To": "<urn:uuid:706ee2f0-fe09-4b6f-91e6-5a2c75362e92>",
"WARC-Date": "2019-09-20T06:34:47",
"WARC-IP-Address": "172.217.7.147",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:HRY2LGSQQXAXSNLYMDIUJAR647VUEPFI",
"WARC-Record-ID": "<urn:uuid:60715ff6-fd27-4d9c-a951-1715422a15bf>",
"WARC-Target-URI": "https://www.rbcreativearts.com/2019/03/why-breathing-deeply-helps-you-calm-down.html",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:1f45e330-a6de-4e86-8cf5-eec170bcda6e>"
},
"warc_info": "isPartOf: CC-MAIN-2019-39\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for September 2019\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-156.ec2.internal\r\nsoftware: Apache Nutch 1.15 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.1-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: http://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
6,
7,
48,
49,
181,
468,
726,
809,
1077,
1312,
1313,
1529,
2045,
2216,
2402,
2875,
3026,
3254,
3255,
3704,
3705,
3718,
3719,
3734,
3735,
3783,
3784
],
"line_end_idx": [
6,
7,
48,
49,
181,
468,
726,
809,
1077,
1312,
1313,
1529,
2045,
2216,
2402,
2875,
3026,
3254,
3255,
3704,
3705,
3718,
3719,
3734,
3735,
3783,
3784,
3925
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 3925,
"ccnet_original_nlines": 27,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.37362638115882874,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.013736260123550892,
"rps_doc_frac_lines_end_with_ellipsis": 0.035714291036129,
"rps_doc_frac_no_alph_words": 0.13049450516700745,
"rps_doc_frac_unique_words": 0.5039494633674622,
"rps_doc_mean_word_length": 5.048973083496094,
"rps_doc_num_sentences": 26,
"rps_doc_symbol_to_word_ratio": 0.00137363001704216,
"rps_doc_unigram_entropy": 5.237259864807129,
"rps_doc_word_count": 633,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.011889860033988953,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.009386730380356312,
"rps_doc_frac_chars_top_3gram": 0.008760949596762657,
"rps_doc_frac_chars_top_4gram": 0.012515639886260033,
"rps_doc_books_importance": -325.9580078125,
"rps_doc_books_importance_length_correction": -325.9580078125,
"rps_doc_openwebtext_importance": -216.0291748046875,
"rps_doc_openwebtext_importance_length_correction": -216.0291748046875,
"rps_doc_wikipedia_importance": -124.74473571777344,
"rps_doc_wikipedia_importance_length_correction": -124.74473571777344
},
"fasttext": {
"dclm": 0.14292234182357788,
"english": 0.9461387991905212,
"fineweb_edu_approx": 3.2536394596099854,
"eai_general_math": 0.04893225058913231,
"eai_open_web_math": 0.20882302522659302,
"eai_web_code": 0.0015588400419801474
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "612.82",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Physiology"
}
},
"secondary": {
"code": "616.858",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "16",
"label": "Personal Blog"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "4",
"label": "Highly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
6e3c8d3593f3f69280bb5502b214ab8e
|
4,003,364,928,970,065,000
|
YOUTH-RX Blog
Breakfast, Food and Hormones Are Related?
On August 15, 2016 In Nutrition, Health 0
We all know or at least have been told, that eating a nutritious diet is essential to performance and good health. It is also equally important the timing of these healthy foods that will have an impact on our performance, hormones, cognitive functioning and well-being day to day. As you may have heard a time a two before, there is an overwhelming amount of evidence despite a small number of naysayers, of the importance of eating breakfast.
Hence the name, we are breaking a fast after not eating all through night while we were catching some ZZZ’s. But, WHY is breakfast so important one might ask? This is a question we are going to address here in this short article and its relationship and impact on our bodies.
For younger athletes as well us regular gym goers mindful of taking care of our aging bodies and maintaining our fitness levels and body composition to age gracefully, it is quite clear that nutrition can have a major impact on exercise performance as well as our response to our workout program. It is also clear that foods, especially under certain circumstances and times, can have an impact on our hormones as well. Carbohydrates can trigger insulin response which can be good or bad depending. Fats are important in playing roles in testosterone production. And proteins and amino acids play roles with many hormones as well. These are just a few of many examples of how the foods we eat and at what times, can play a role with hormones and how well our bodies are functioning through the day.
There is a good amount of research indicating that when one eats may have as much influence over achieving fitness and performance goals as what one eats. In other words, timing of when you eat certain nutrients or “nutrient timing” can significantly impact our performance, recovery from exercise and training adaptation. These responses to nutrient timing are built into our DNA and therefore not limited to just elite athletes either. Everyone, young and old, male and female, untrained and trained will respond to nutrient timing.
Okay, So Why is Breakfast So Important?
For starters, breakfast immediately lowers the blood level of the stress hormone cortisol, which is known to peak during the early morning hours. The effects of having too much cortisol in the body can include weight gain, muscle weakness, and mood swings that may turn into anxiety or depression. Cortisol levels are generally high in the morning as we wake up from a prolonged period of sleep. Then, as the day progresses, our cortisol levels naturally begin to drop in a fairly constant and regular cycle, winding up lower at the end of the day. This allows the body to keep a regular sleeping pattern, with the cortisol level dropping for periods of sleep, then replenishing as morning time rolls around and we are waking up.
We often think of sleep as a no-stress period and from a psychological viewpoint this is generally true. Physiologically however, it is the other way around. Even though our metabolic needs are very little while we are asleep (since we are not running around), the body still needs to maintain critical physiological and metabolic functions required to support life as well as those that support recovery from the previous day’s activities and physical exertions. This is also critical for tissue and muscle repair, growth and development – all which are key components to recovery, building and maintaining good body composition. The energy to support these functions come from liver glycogen, fatty acids and blood glucose.
Breakfast is thought to be the most satiating meal of the day. This satisfying, full-effect can impact food consumption for the entire day. Investigators have found that the pattern of food intake has a dramatic effect on overall daily food intake. This is due to the impact of our meal pattern on the release of gut hormones that control appetite. Secretion of these hormones early in the morning is in part due to the elevation in blood cortisol and can have a sustained effect throughout the day. Therefore, eating a good breakfast most likely reducing the blood cortisol levels, may also decrease appetite and reduce daily caloric intake. This may be especially true if an individual is prone to over consuming later in the day, triggering excessive amounts of insulin with the possibility of interfering with leptin doing its job to control appetite in certain populations.
Research findings in recent past suggest a strong correlation between consuming a regular breakfast and long-term weight maintenance and weight loss. In many health and nutrition coaches’ experience working with clients, a typical story heard from a person struggling with their weight and its associated health concerns, is that they skip breakfast, eat a huge lunch, munch on high carb snacks during the afternoon and then eat an oversized dinner. Also and all too often, consuming the wrong types of foods such as a large amount of sugar before bed disrupts REM sleep cycles while disrupting growth hormone release. These common scenarios that start with skipping breakfast, often flow with hormonal patterns and their influence on our hunger levels and the food choices we instinctively want to make (fat and sugar) through the day. The negative impact this has on one’s energy levels deteriorates them from being as physically active as they should, including things like going to the gym and doing activities with their kids after work. Lack of activity negatively impacts our muscle and body composition, sleep and more. See the viscous cycle that many find themselves in?
“But, I Don’t Have Time to Eat Breakfast”
We have heard (or maybe given) every excuse regarding why people can’t get breakfast on the table most days of the week. The top excuse is that “there just isn’t time”. The next is that they’re “just not hungry”. These are simply excuses. If you want to live healthy and be your best, you have to make a commitment and always have some quick and healthy grab-and-go breakfast options on hand.
Make Time for Breakfast. Although mornings can be busy times, there are things you can do to help make everything run more smoothly, so there is enough time for breakfast.
Here are a few tips:
1. Do some of your morning chores the night before, such as selecting clothes to wear, signing permission slips and putting homework in backpacks.
2. Set the table with breakfast dishes and nonperishable food items, such as dry cereal, bread and bagels.
3. If adults in the home drink coffee, get the coffee pot ready to run the night before and then just hit the "on" switch in the morning.
4. Make sure all family members are assigned chores to do in the morning. Do not turn on the television set.
In addition, breakfast does not need much preparation time. There are lots of fast, easy foods that can provide a healthy start to the day.
Quick, healthy and easy breakfast ideas
“Cocoa Chocolate oats”
INGREDIENTS -
1. 1 cup unsweetened almond or coconut milk
2. 1 cup of oats
3. 1/4 cup of “True Vibe” cocoa nibs (or unprocessed cocoa powder is fine too)
4. 1 scoop of Natural Chocolate “Killer Whey” Protein
You can either eat these as is or heat up the oats and milk first for 40 seconds before adding cocoa and protein powder.
Coffee lover’s breakfast: “Protein java to go”
INGREDIENTS –
1. Shaker cup (to mix and take with you)
2. 1 scoop of Natural Vanilla “Killer Whey” Protein
3. A “dash of” Cinnamon powder
4. A “dash of” Stevia (liquid or powder from health food store)
5. 1 cup of ice (if you want an iced coffee shake here)
6. 1 cup of almond or coconut milk
7. 12oz of coffee
You can also blend in a blender, either of the two options above or simply make your own smoothie to go. Either of these ideas only takes about two minutes to make and maybe another 4-5 minutes to consume. We all live hectic, busy lives so let’s be sure to put proper fuel into our “tank”!
Summary
Breakfast is a key player in raising the energy level of the body, increasing vigor and vitality. It helps to reduce cortisol levels and helps control appetite, which over the long-term, can significantly impact body composition. Breakfast also increases cognitive function and the ability to concentrate. For the athlete, health enthusiast or newbie trying to make some positive changes in the way they look and feel, this translates into more effective workouts and enhances adaption to their training and HRT programs while helping them look and feel their best from it. So, break that fast!
Subscribe to Email Updates
|
{
"url": "http://blog.youth-rx.com/breakfast-food-and-hormones-are-related",
"source_domain": "blog.youth-rx.com",
"snapshot_id": "crawl=CC-MAIN-2018-47",
"warc_metadata": {
"Content-Length": "60380",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:M5P7XNKWXR334NWM5DSNY6BM6772RPFH",
"WARC-Concurrent-To": "<urn:uuid:c242ad57-3150-4fe4-9ba2-818d4ccc5cbc>",
"WARC-Date": "2018-11-21T20:40:39",
"WARC-IP-Address": "104.17.112.180",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:WP2EWOWFRQH6DFVMJ56H7ODJIK4UIZUI",
"WARC-Record-ID": "<urn:uuid:0c79bc95-4cba-4f8d-9375-07c98e0361c3>",
"WARC-Target-URI": "http://blog.youth-rx.com/breakfast-food-and-hormones-are-related",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:39d33df9-4a32-4d64-9307-fd9576a18056>"
},
"warc_info": "isPartOf: CC-MAIN-2018-47\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for November 2018\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-142-78-13.ec2.internal\r\nsoftware: Apache Nutch 1.15 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 0.11-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: http://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
14,
15,
57,
58,
100,
101,
546,
547,
823,
824,
1624,
1625,
2160,
2161,
2201,
2202,
2932,
2933,
3659,
3660,
4539,
4540,
5720,
5721,
5763,
5764,
6158,
6159,
6331,
6332,
6353,
6354,
6503,
6612,
6752,
6863,
6864,
7004,
7005,
7045,
7046,
7069,
7070,
7084,
7085,
7131,
7150,
7231,
7287,
7288,
7409,
7410,
7457,
7458,
7472,
7473,
7516,
7570,
7603,
7669,
7727,
7764,
7784,
7785,
8075,
8076,
8084,
8085,
8680,
8681
],
"line_end_idx": [
14,
15,
57,
58,
100,
101,
546,
547,
823,
824,
1624,
1625,
2160,
2161,
2201,
2202,
2932,
2933,
3659,
3660,
4539,
4540,
5720,
5721,
5763,
5764,
6158,
6159,
6331,
6332,
6353,
6354,
6503,
6612,
6752,
6863,
6864,
7004,
7005,
7045,
7046,
7069,
7070,
7084,
7085,
7131,
7150,
7231,
7287,
7288,
7409,
7410,
7457,
7458,
7472,
7473,
7516,
7570,
7603,
7669,
7727,
7764,
7784,
7785,
8075,
8076,
8084,
8085,
8680,
8681,
8707
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 8707,
"ccnet_original_nlines": 70,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.4180857241153717,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.007046389859169722,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.13857898116111755,
"rps_doc_frac_unique_words": 0.4063556492328644,
"rps_doc_mean_word_length": 4.727518558502197,
"rps_doc_num_sentences": 81,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.691098690032959,
"rps_doc_word_count": 1479,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.01201372966170311,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.00686499010771513,
"rps_doc_frac_chars_top_3gram": 0.00686499010771513,
"rps_doc_frac_chars_top_4gram": 0.004004579968750477,
"rps_doc_books_importance": -627.2359008789062,
"rps_doc_books_importance_length_correction": -627.2359008789062,
"rps_doc_openwebtext_importance": -393.9333801269531,
"rps_doc_openwebtext_importance_length_correction": -393.9333801269531,
"rps_doc_wikipedia_importance": -298.1786804199219,
"rps_doc_wikipedia_importance_length_correction": -298.1786804199219
},
"fasttext": {
"dclm": 0.2729405164718628,
"english": 0.9620897769927979,
"fineweb_edu_approx": 2.6708548069000244,
"eai_general_math": 0.041000720113515854,
"eai_open_web_math": 0.2125089168548584,
"eai_web_code": 0.006472589913755655
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "613.2",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
},
"secondary": {
"code": "612.82",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Physiology"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "3",
"label": "Irrelevant Content"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "23",
"label": "Tutorial"
}
},
"reasoning_depth": {
"primary": {
"code": "3",
"label": "Intermediate Reasoning"
},
"secondary": {
"code": "2",
"label": "Basic Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "4",
"label": "Highly Correct"
}
},
"education_level": {
"primary": {
"code": "2",
"label": "High School Level"
},
"secondary": {
"code": "1",
"label": "General Audience"
}
}
}
|
9222580d47c553ea90dc0f5e416f8f3a
|
2,066,332,725,842,399,500
|
Publicaciones científicas
Auditory and Vestibular Assessment of Patients with Ménière's Disease Who Suffer Tumarkin Attacks
14-abr-2010 | Revista: Audiology and Neuro-Otology
Perez-Fernandez N, Montes-Jovellar L, Cervera-Paz J, Domenech-Vadillo E.
Department of Otorhinolaryngology, Clínica Universidad de Navarra, University Hospital and Medical School, University of Navarra, Pamplona, Spain.
Tumarkin attacks are a feature of Ménière's disease that generate a significant degree of disability. The surprising nature of these events is the main reason behind their associated morbidity. In this study we set out to evaluate auditory and vestibular function, as well as disability, in a population of patients who suffer Tumarkin attacks.
We found that patients who suffer Tumarkin attacks are more disabled and experience severer and more frequent autonomic symptoms and that their hearing level is significantly worse in the asymptomatic ear, especially at low frequencies.
Accordingly, we consider that treatment must be carefully planned to be as conservative as possible in terms of hearing and that psychiatric and/or psychological treatment must always be considered as an adjuvant therapy.
CITA DEL ARTÍCULO Audiol Neurootol. 2010;15(6):399-406
|
{
"url": "https://www.cun.es/investigacion/publicaciones-cientificas/auditory-and-vestibular-assessment-of-patients-with-meniere-s-disease-who-suffer-tumarkin-attacks",
"source_domain": "www.cun.es",
"snapshot_id": "crawl=CC-MAIN-2022-21",
"warc_metadata": {
"Content-Length": "60246",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:7WO3SWESKGFHSNUTN6WMVB2JHSCUR5UX",
"WARC-Concurrent-To": "<urn:uuid:8e2a293a-0114-428a-aee2-747a6a30bf6a>",
"WARC-Date": "2022-05-17T20:08:58",
"WARC-IP-Address": "51.124.7.114",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:HCVFQVBVPHMZ6LGWKMOJAMJ224HYE6R2",
"WARC-Record-ID": "<urn:uuid:bc2cee1d-0017-4c01-9f53-3fb0f3ed21c9>",
"WARC-Target-URI": "https://www.cun.es/investigacion/publicaciones-cientificas/auditory-and-vestibular-assessment-of-patients-with-meniere-s-disease-who-suffer-tumarkin-attacks",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:093c0e46-1be0-4f30-b28a-aad7451428b9>"
},
"warc_info": "isPartOf: CC-MAIN-2022-21\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for May 2022\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-200\r\nsoftware: Apache Nutch 1.18 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.3-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
26,
27,
125,
126,
177,
178,
251,
398,
399,
400,
745,
746,
983,
984,
1206,
1207
],
"line_end_idx": [
26,
27,
125,
126,
177,
178,
251,
398,
399,
400,
745,
746,
983,
984,
1206,
1207,
1262
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 1262,
"ccnet_original_nlines": 16,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.3139013648033142,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.03139013051986694,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.1928251087665558,
"rps_doc_frac_unique_words": 0.6531791687011719,
"rps_doc_mean_word_length": 6.069364070892334,
"rps_doc_num_sentences": 9,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 4.518226623535156,
"rps_doc_word_count": 173,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.060952380299568176,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.05714286118745804,
"rps_doc_frac_chars_top_3gram": 0.04857143014669418,
"rps_doc_frac_chars_top_4gram": 0.06857143342494965,
"rps_doc_books_importance": -83.0958023071289,
"rps_doc_books_importance_length_correction": -83.0958023071289,
"rps_doc_openwebtext_importance": -50.680755615234375,
"rps_doc_openwebtext_importance_length_correction": -50.680755615234375,
"rps_doc_wikipedia_importance": -34.6856803894043,
"rps_doc_wikipedia_importance_length_correction": -34.6856803894043
},
"fasttext": {
"dclm": 0.018610060214996338,
"english": 0.9051738381385803,
"fineweb_edu_approx": 2.3040568828582764,
"eai_general_math": 0.04666399955749512,
"eai_open_web_math": 0.1475796103477478,
"eai_web_code": 0.004274790175259113
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.892",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "616.8",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "5",
"label": "Evaluate"
},
"secondary": {
"code": "4",
"label": "Analyze"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "1",
"label": "Factual"
}
},
"document_type_v1": {
"primary": {
"code": "2",
"label": "Academic/Research"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "3",
"label": "Academic Writing"
},
"secondary": {
"code": "10",
"label": "Knowledge Article"
}
},
"reasoning_depth": {
"primary": {
"code": "3",
"label": "Intermediate Reasoning"
},
"secondary": {
"code": "2",
"label": "Basic Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "4",
"label": "Graduate/Expert Level"
},
"secondary": {
"code": "3",
"label": "Undergraduate Level"
}
}
}
|
b755ed28a90d11d590ef646404f4afc5
|
4,571,275,107,398,467,600
|
Cancer Institute A national cancer institute
designated cancer center
Trevor Hastie
Publication Details
• A fused lasso latent feature model for analyzing multi-sample aCGH data.
Nowak G, Hastie T, Pollack JR, Tibshirani R. Biostatistics. 2011; 12 (4): 776-91
Array-based comparative genomic hybridization (aCGH) enables the measurement of DNA copy number across thousands of locations in a genome. The main goals of analyzing aCGH data are to identify the regions of copy number variation (CNV) and to quantify the amount of CNV. Although there are many methods for analyzing single-sample aCGH data, the analysis of multi-sample aCGH data is a relatively new area of research. Further, many of the current approaches for analyzing multi-sample aCGH data do not appropriately utilize the additional information present in the multiple samples. We propose a procedure called the Fused Lasso Latent Feature Model (FLLat) that provides a statistical framework for modeling multi-sample aCGH data and identifying regions of CNV. The procedure involves modeling each sample of aCGH data as a weighted sum of a fixed number of features. Regions of CNV are then identified through an application of the fused lasso penalty to each feature. Some simulation analyses show that FLLat outperforms single-sample methods when the simulated samples share common information. We also propose a method for estimating the false discovery rate. An analysis of an aCGH data set obtained from human breast tumors, focusing on chromosomes 8 and 17, shows that FLLat and Significance Testing of Aberrant Copy number (an alternative, existing approach) identify similar regions of CNV that are consistent with previous findings. However, through the estimated features and their corresponding weights, FLLat is further able to discern specific relationships between the samples, for example, identifying 3 distinct groups of samples based on their patterns of CNV for chromosome 17.
PubMedID: 21642389
Stanford Medicine Resources:
Footer Links:
|
{
"url": "http://cancer.stanford.edu/profiles/frdActionServlet?choiceId=showPublication&pubid=13968007&fid=6106&suffix=researcher",
"source_domain": "cancer.stanford.edu",
"snapshot_id": "crawl=CC-MAIN-2013-20",
"warc_metadata": {
"Content-Length": "40556",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:V7TSRJFSG5WH5DAHHHCGKKGHJN7PULS2",
"WARC-Concurrent-To": "<urn:uuid:e7415c3a-9d16-44dc-af97-d58c20eb92a1>",
"WARC-Date": "2013-06-19T01:24:18",
"WARC-IP-Address": "171.65.104.14",
"WARC-Identified-Payload-Type": null,
"WARC-Payload-Digest": "sha1:NN6ZML4TI7FB3PHELM4JJEMZ4OGE36ZJ",
"WARC-Record-ID": "<urn:uuid:bfff65ea-a98a-400d-a890-4b137be64fbc>",
"WARC-Target-URI": "http://cancer.stanford.edu/profiles/frdActionServlet?choiceId=showPublication&pubid=13968007&fid=6106&suffix=researcher",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:603c39fe-c8c2-4529-bc81-772a06c6bbfa>"
},
"warc_info": "robots: classic\r\nhostname: ip-10-60-113-184.ec2.internal\r\nsoftware: Nutch 1.6 (CC)/CC WarcExport 1.0\r\nisPartOf: CC-MAIN-2013-20\r\noperator: CommonCrawl Admin\r\ndescription: Wide crawl of the web with URLs provided by Blekko for Spring 2013\r\npublisher: CommonCrawl\r\nformat: WARC File Format 1.0\r\nconformsTo: http://bibnum.bnf.fr/WARC/WARC_ISO_28500_version1_latestdraft.pdf"
}
|
{
"line_start_idx": [
0,
45,
70,
71,
85,
86,
106,
107,
184,
185,
270,
271,
1976,
1977,
2000,
2001,
2030,
2031
],
"line_end_idx": [
45,
70,
71,
85,
86,
106,
107,
184,
185,
270,
271,
1976,
1977,
2000,
2001,
2030,
2031,
2044
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 2044,
"ccnet_original_nlines": 17,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.27222222089767456,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.03611110895872116,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.16388888657093048,
"rps_doc_frac_unique_words": 0.5592105388641357,
"rps_doc_mean_word_length": 5.4934210777282715,
"rps_doc_num_sentences": 15,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 4.761857509613037,
"rps_doc_word_count": 304,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.07065867632627487,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.03832335025072098,
"rps_doc_frac_chars_top_3gram": 0.0455089807510376,
"rps_doc_frac_chars_top_4gram": 0.027544910088181496,
"rps_doc_books_importance": -114.37570190429688,
"rps_doc_books_importance_length_correction": -114.37570190429688,
"rps_doc_openwebtext_importance": -83.09001922607422,
"rps_doc_openwebtext_importance_length_correction": -83.09001922607422,
"rps_doc_wikipedia_importance": -64.94915771484375,
"rps_doc_wikipedia_importance_length_correction": -64.94915771484375
},
"fasttext": {
"dclm": 0.09739387035369873,
"english": 0.8760543465614319,
"fineweb_edu_approx": 2.7294528484344482,
"eai_general_math": 0.9165465235710144,
"eai_open_web_math": 0.3646799921989441,
"eai_web_code": 0.4205309748649597
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.9944",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "519.5",
"labels": {
"level_1": "Science and Natural history",
"level_2": "Mathematics",
"level_3": "Probabilities; or, Mathematical statistics"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "4",
"label": "Analyze"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "3",
"label": "Procedural"
},
"secondary": {
"code": "2",
"label": "Conceptual"
}
},
"document_type_v1": {
"primary": {
"code": "2",
"label": "Academic/Research"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "0",
"label": "No Artifacts"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "3",
"label": "Academic Writing"
},
"secondary": {
"code": "8",
"label": "Documentation"
}
},
"reasoning_depth": {
"primary": {
"code": "4",
"label": "Advanced Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "4",
"label": "Graduate/Expert Level"
},
"secondary": {
"code": "3",
"label": "Undergraduate Level"
}
}
}
|
1a01aa77535b9ecfb87b9fc36adbcd2f
|
-5,312,728,450,155,533,000
|
Ramin Rayhan DDS
Clock Tower Dental Associates
516-352-1000
110 New Hyde Park Road
Franklin Square, NY 11010
Dental Sealants
Dental sealants, thin plastic coatings generally applied to the occlusal (chewing) surfaces of the teeth are a very effective method of cavity prevention. The sealant acts as a barrier between the tooth and food, bacteria and plaque, all of which can lead to decay. Sealants are especially effective in preventing bacterial formation in the grooves of molar and premolar surfaces, areas that are especially susceptible to decay.
The reason these grooves are so susceptible to decay is that normal brushing and flossing do not reach into their crevices and depressions to extract food particles and plaque.
Different Types of Dental Sealants
Sealants are typically produced from glass ionomer or composite material. Glass ionomer sealants have some advantages: they release fluoride while acting as a physical barrier to decay, and they do not require a completely dry field for application, so they can be used on emerging molars.
Some sealants change color when they dry, lessening the possibility that invisible gaps will be left during the application process. Other sealants offer the benefit of being stronger and more durable, making them an appropriate choice for children, teenagers or adults who grind their teeth, a condition known as bruxism.
Candidates for Dental Sealants
Because children and teenagers are more likely to develop pit and fissure decay, youngsters are good candidates for dental sealants. The reasons young people suffer from dental decay more than adults are numerous, including dietary choices, more or less constant drinking (such as toddlers with bottles or sippy cups), and less than adequate dental hygiene. Nonetheless, adults can benefit from sealants as well.
Sealants are usually put on children who already have their permanent molars, but in children at high risk for cavities, sealants may be recommended for primary molars as well.
The Dental Sealant Procedure
The dental sealant procedure takes a few minutes for each tooth. The dentist cleans the tooth and paints the plastic sealant onto the enamel where it bonds to the enamel as it hardens. This coating works as a barrier to prevent plaque from building up and attacking the enamel. A special light may be used to speed the hardening and bonding process.
As long as the sealant remains intact and in good condition, the surface of the tooth will remain protected. Sealants have been found to endure several years of normal chewing before reapplication is necessary. During routine checkups, the dentist checks on the durability of the sealant to assess whether and when reapplication is needed.
Additional Resources
|
{
"url": "https://raminrayhan.com/dental-sealants.php",
"source_domain": "raminrayhan.com",
"snapshot_id": "CC-MAIN-2023-06",
"warc_metadata": {
"Content-Length": "34980",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:TKFFMMFJHPX75IBRM5TSCTAQYGH6PWL7",
"WARC-Concurrent-To": "<urn:uuid:33af8fb1-7b72-479c-9343-391fbe6a0009>",
"WARC-Date": "2023-01-30T10:29:03",
"WARC-IP-Address": "52.39.109.56",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:GIJYZFNM4RCNHWW2FR4WMSSWFRMBRLVP",
"WARC-Record-ID": "<urn:uuid:a07b8245-442d-43f6-ac4c-f4417132862d>",
"WARC-Target-URI": "https://raminrayhan.com/dental-sealants.php",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:304a3a82-603c-4c20-acd0-eed7ad4d62d4>"
},
"warc_info": "isPartOf: CC-MAIN-2023-06\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for January/February 2023\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-197\r\nsoftware: Apache Nutch 1.19 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.4-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
17,
18,
48,
49,
62,
63,
86,
113,
114,
130,
131,
560,
561,
738,
739,
774,
775,
1065,
1066,
1389,
1390,
1421,
1422,
1835,
1836,
2013,
2014,
2043,
2044,
2394,
2395,
2735,
2736
],
"line_end_idx": [
17,
18,
48,
49,
62,
63,
86,
113,
114,
130,
131,
560,
561,
738,
739,
774,
775,
1065,
1066,
1389,
1390,
1421,
1422,
1835,
1836,
2013,
2014,
2043,
2044,
2394,
2395,
2735,
2736,
2756
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 2756,
"ccnet_original_nlines": 33,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.3887733817100525,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.006237010005861521,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.10395009815692902,
"rps_doc_frac_unique_words": 0.5322580337524414,
"rps_doc_mean_word_length": 5.207373142242432,
"rps_doc_num_sentences": 20,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.011138439178467,
"rps_doc_word_count": 434,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.03097344934940338,
"rps_doc_frac_chars_top_3gram": 0.008849560283124447,
"rps_doc_frac_chars_top_4gram": 0.0238938108086586,
"rps_doc_books_importance": -194.39324951171875,
"rps_doc_books_importance_length_correction": -194.39324951171875,
"rps_doc_openwebtext_importance": -123.52086639404297,
"rps_doc_openwebtext_importance_length_correction": -123.52086639404297,
"rps_doc_wikipedia_importance": -112.79975891113281,
"rps_doc_wikipedia_importance_length_correction": -112.79975891113281
},
"fasttext": {
"dclm": 0.08026360720396042,
"english": 0.9433674216270447,
"fineweb_edu_approx": 3.1219754219055176,
"eai_general_math": 0.060113850980997086,
"eai_open_web_math": 0.193547785282135,
"eai_web_code": 0.009295879863202572
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "617.62",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Surgery and Dentistry"
}
},
"secondary": {
"code": "617.6",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Surgery and Dentistry"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "1",
"label": "Factual"
},
"secondary": {
"code": "2",
"label": "Conceptual"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "3",
"label": "Irrelevant Content"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "4",
"label": "Missing Images or Figures"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "17",
"label": "Product Page"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
6e3c8d3593f3f69280bb5502b214ab8e
|
-8,231,251,989,212,361,000
|
Treatment Resistant Depression2023-01-31T20:46:13-05:00
Ketamine Assisted Therapy
To Help With
Treatment Resistant Depression
Relief without hospitalization
Ketamine infusions have been shown to help regulate mood and to be highly effective in providing fast relief from major depressive symptoms without hospitalization. A person receiving ketamine may have relief of symptoms as early as the first infusion. However, more often, improvement is seen gradually over a series of infusions.
Like all medicines, Ketamine therapy is a treatment, not a cure. At Altasano, we believe that along with psychotherapy and mindfulness training, Ketamine can be another tool used in the fight against treatment resistent depression, anxiety and PTSD.
Our practice model follows a collaborative approach with your psychiatrist/prescribing physician and therapist. We administer the ketamine infusions to stimulate neurochemical pathways and your therapist works with you to help guide you through the integration of the experience to gain meaning and insight. During the process we monitor you everyday and provide support before and after the infusions. The information we collect is sent to your psychiatrist after the initial loading doses and then periodically to help in your continued treatment plan.
Mental Health
Because mental health issues affect all aspects of day-to-day life, they can interfere with relationships, employment, and nutrition. They even make it difficult to seek treatment and practice proper self-care. This puts people with treatment resistant depression and major depression at greater risk of alcohol and drug abuse, chronic disease, hospitalization, and suicide attempts. Electroconvulsive therapy (ECT), a mainstay therapy, can be life-saving, but it requires hospitalization and has a high incidence of memory loss as a side-effect.
Life Changing
Treatment resistant depression is not uncommon. About 30% of adults with major depression fight persistent feelings of sadness, sleep disturbances, low energy and thoughts of death or suicide that do not respond to treatment. Oral medications take several weeks to have an effect. In some cases, that may be too much time. There is a link between the experience of a major depressive episode with no symptom relief and the occurance of suicide. Prompt symptom relief and support for those struggling with treatment resistant depression can be life changing and life-saving. National Suicide Prevention Hotline 1-800-273-8255. https://suicidepreventionlifeline.org/
Reboot
Treatment Resistant Depression, PTSD, severe anxiety, and drug and alcohol addiction have all been theorized, up until recently, to simply be due to chemical imbalances in the brain. But it’s much more complicated than that. Newer research is looking at the electrical signaling of the brain that impacts neurotransmitter concentrations and the role of inflammation on the brain. Ketamine’s ability to “re-boot” the brain and stimulate the production of brain derived neurotrophic factor (BDNF) is believed to impact neuroplasticity. This neuroplasticity is what can allow a person to break a repetitive cycle long enough to have a chance to do the impactful work that can put a person on a new path to living. https://www.youtube.com/watch?v=hNsIiq-5354
Why Ketamine?2019-04-03T22:52:26-05:00
Attention on ketamine in the treatment of severe treatment resistant depression, PTSD, postpartum depression, severe anxiety, and other mental health conditions, has made the pharmaceutical industry rethink its focus on traditional antidepressant medications. Although traditional medications have helped many people, for others, they just don’t work. Worse yet, suicidal ideation is a known side-effect of SSRIs, especially on younger populations.
How does Ketamine Work?2019-04-03T22:52:58-05:00
Ketamine inhibits the N-methyl D-aspartate (NMDA) receptor in our central nervous system. This receptor is activated by a neurotransmitter called glutamate. Glutamate is found at excessive levels with stress, depression, and certain pain conditions. Blocking the effects from this excess can help alleviate symptoms.
What is Ketamine?2019-04-03T22:53:54-05:00
Ketamine is a drug that has been used for over 50 years, traditionally as an anesthetic by anesthesia providers, emergency physicians and surgeons. In 1985, the World Health Organization added Ketamine to its list of essential medicines. In 1990’s, Yale University began studies on Ketamine and it’s use in psychiatry. In 2006, ketamine began being studied in its effects on treatment-resistant depression. A 2009 study of ketamine conducted by Price, Charney, Knock, and Matthew, showed a correlation between ketamine and the alleviation of depressive symptoms as well as a reduction in suicidal thoughts. Current studies are showing beneficial effects in other psychiatric disorders such as obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), anxiety, and alcohol/substance abuse.
Is Ketamine safe?2019-04-09T21:06:24-05:00
Yes, Ketamine is safe when used responsibly. Ketamine does not slow down vital bodily functions such as respiration rate. Ketamine can increase blood pressure and heart rate for some patients, but this is a very temporary and transient effect. Like so many drugs, Ketamine has also been abused. We collaborate closely with your own mental health provider and require you to have one throughout treatment. Comprehensive centers, like Altasano, place a priority on your bodily health and as well as your mental well-being. LEARN MORE
Why doesn’t insurance pay for Ketamine?2023-01-31T20:18:01-05:00
Insurance companies do not usually pay for medications that are given for “off-label use”. “Off-Label” use of a medicine is very common actually. Think of the use of aspirin for people with heart disease. Aspirin was not originally made and tested for that use, but its chemical properties made it beneficial for people with heart disease. In the early 1960’s, the FDA approved Ketamine for anesthetic use. Further research on Ketamine in the 1990s began to focus attention on its therapeutic benefits on the treatment of chronic pain and because of its benefits, many insurance companies cover the costs of ketamine infusions when given for pain. Many studies looking at the benefits of ketamine for mental health issues have been published, but currently the FDA has not approved Ketamine for the treatment of depression or other mental health issues. This may change in the near future.
What about Esketamine (Spravato)?2023-01-31T20:28:43-05:00
IV Ketamine therapy remains the gold-standard of TRD treatment, however the FDA approved esketamine (Spravato) is an option. The drug is basically one half of the original ketamine molecule. The attempt was to split the drug to remove the “unwanted” psychedelic effects of the medicine. We understand that the concept of a transcendental experience is not part of mainstream Western medicine, but we are certain that the transcendental experiential effects of a ketamine infusion play an essential part of the treatment. The nasal delivery of the drug is certainly more desirable, however studies show that it may not be as effective, as dosing and absorption will be less precise. The benefit of FDA approval of esketamine is that, depending on your coverage, insurance companies may pay for its higher cost, estimated to be $1000 per dose. Spravato will not be dispensed to patients to take home like ketamine troches. It will only be available in approved and certified treatment centers.
How are Ketamine Infusions Administered?2019-04-03T22:56:09-05:00
At Altasano, ketamine infusions are administered through an IV, with an infusion pump over 40-60 minutes. Intramuscular ketamine is a popular route of administration for those who may not be as comfortable with IVs, however receiving ketamine IM, means that the dosing and effect is less predictable and it cannot be stopped. Once an IM dose is given, the drug must take its course. Whereas, with an IV route, the infusion can be given slowly and the effects can be dealt with gradually. The IV can also be stopped at any time.
What ketamine treatment protocol do you follow?2022-04-05T22:17:22-05:00
For those who meet the DSM criteria for depression who have tried at least two different classes of traditional antidepressants and found them to be ineffective, the recommended initial “Induction Series” of six low-dose ketamine infusions is administered in an effort to break the cycle. Most clinical trials have consistently shown a 70% success rate with this approach. The treatment does require booster infusions as time passes to keep the effect going. These single “booster infusions” are given at varied intervals for the same 40-60 minute duration, but are single infusions rather than in a series. However, at Altasano, depending on your experience while receiving a ketamine infusion for treatment resistant depression (TRD), we may progressively increase or decrease the doses outside of the “NIH Protocol” in order to optimize the experiential therapeutic effect of Ketamine.
Can I get addicted to Ketamine?2019-04-03T22:56:52-05:00
Studies have shown that at infusion doses and frequency, Ketamine is not addictive. The drug itself does not cause physiological “addiction” but, people can become habituated to the experience.
Does Ketamine have side-effects?2019-04-03T22:57:27-05:00
Less than 2% of people will experience side effects. However, some common side effects are: drowsiness, nausea, dizziness, poor coordination, blurred vision, and feeling strange or unreal. Most of these symptoms go away within an hour of the infusion
Who should not receive ketamine?2019-04-03T22:57:47-05:00
Anyone with a history of uncontrolled high blood pressure, heart disease, kidney disease, a history of psychosis, or bipolar disorder, history of failed Ketamine infusion treatment, current substance abuse or dependence (patients will undergo a screening process) will not qualify for Ketamine infusion treatments. People with a history of interstitial cystitis (bladder inflammation) will require further screening and preparation.
Will I need a booster infusions? If so, how frequently?2019-04-03T22:58:11-05:00
Unfortunately, there are no predictors for the duration of antidepressant effect after the initial loading series. Everyone is different. The studies show that the variance can be 2 weeks to indefinitely.
Can you guarantee that this will work for me?2019-04-03T22:58:33-05:00
Unfortunately, we cannot give guarantee that this will work for you. Studies have shown that 70% of people with Treatment resistant depression will find relief. After the first 3 infusions, if you are not experiencing any improvement, we will work with you on staying the course, increasing the dosage of the infusion, or decide to stop the series.
Should I continue to take my antidepressants?2019-04-03T22:58:56-05:00
Yes. You can and should continue to take your prescribed medication. Though some people find that they can reduce their prescription meds or eliminate some altogether, it can be dangerous to stop taking your medications without the care of your doctor or therapist. People have the best outcomes when they combine ketamine infusions with psychotherapy.
ALTASANO INFUSION
By Appointment
Sunday (Closed)
Monday: 5pm-8pm
Tuesday: 8am-5pm Wednesday (Closed)
Thursday: 8am-5pm
Friday: 4pm-7pm
Saturday: 1pm-5pm
LOCATION
SERVICES
Go to Top
|
{
"url": "https://www.altasano.com/iv-infusions/treatment-resistant-depression/",
"source_domain": "www.altasano.com",
"snapshot_id": "CC-MAIN-2023-40",
"warc_metadata": {
"Content-Length": "142781",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:WDFBKMMRNYWLLIGK6F7RRIISSB6HBJQ7",
"WARC-Concurrent-To": "<urn:uuid:5ae144b6-8542-4963-817d-9bc5ef6d35d1>",
"WARC-Date": "2023-09-30T17:06:01",
"WARC-IP-Address": "141.193.213.10",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:42ZHXUQS7NAHIEFSFODUIPHWG44MIL35",
"WARC-Record-ID": "<urn:uuid:462210ba-c2d3-437b-bdec-cdd3ab01eff5>",
"WARC-Target-URI": "https://www.altasano.com/iv-infusions/treatment-resistant-depression/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:dfebec07-a1b7-4ec8-8ef7-a60684881900>"
},
"warc_info": "isPartOf: CC-MAIN-2023-40\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for September/October 2023\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-115\r\nsoftware: Apache Nutch 1.19 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.5-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
56,
57,
83,
84,
97,
98,
129,
130,
161,
162,
494,
495,
745,
746,
1301,
1302,
1316,
1317,
1864,
1865,
1879,
1880,
2545,
2546,
2553,
2554,
3310,
3311,
3350,
3351,
3800,
3801,
3850,
3851,
4171,
4172,
4215,
4216,
5023,
5024,
5067,
5068,
5602,
5603,
5668,
5669,
6561,
6562,
6621,
6622,
7614,
7615,
7681,
7682,
8210,
8211,
8284,
8285,
9174,
9175,
9232,
9233,
9427,
9428,
9486,
9487,
9738,
9739,
9797,
9798,
10231,
10232,
10313,
10314,
10519,
10520,
10591,
10592,
10941,
10942,
11013,
11014,
11367,
11368,
11386,
11387,
11402,
11418,
11435,
11472,
11490,
11506,
11524,
11526,
11527,
11536,
11537,
11546,
11547
],
"line_end_idx": [
56,
57,
83,
84,
97,
98,
129,
130,
161,
162,
494,
495,
745,
746,
1301,
1302,
1316,
1317,
1864,
1865,
1879,
1880,
2545,
2546,
2553,
2554,
3310,
3311,
3350,
3351,
3800,
3801,
3850,
3851,
4171,
4172,
4215,
4216,
5023,
5024,
5067,
5068,
5602,
5603,
5668,
5669,
6561,
6562,
6621,
6622,
7614,
7615,
7681,
7682,
8210,
8211,
8284,
8285,
9174,
9175,
9232,
9233,
9427,
9428,
9486,
9487,
9738,
9739,
9797,
9798,
10231,
10232,
10313,
10314,
10519,
10520,
10591,
10592,
10941,
10942,
11013,
11014,
11367,
11368,
11386,
11387,
11402,
11418,
11435,
11472,
11490,
11506,
11524,
11526,
11527,
11536,
11537,
11546,
11547,
11556
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 11556,
"ccnet_original_nlines": 99,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.34533995389938354,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.02251238003373146,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.22152183949947357,
"rps_doc_frac_unique_words": 0.38780343532562256,
"rps_doc_mean_word_length": 5.590290069580078,
"rps_doc_num_sentences": 106,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.708695888519287,
"rps_doc_word_count": 1689,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.01927557960152626,
"rps_doc_frac_chars_dupe_6grams": 0.005930949933826923,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.00529548991471529,
"rps_doc_frac_chars_top_3gram": 0.023723790422081947,
"rps_doc_frac_chars_top_4gram": 0.013556449674069881,
"rps_doc_books_importance": -1042.8702392578125,
"rps_doc_books_importance_length_correction": -1042.8702392578125,
"rps_doc_openwebtext_importance": -598.1013793945312,
"rps_doc_openwebtext_importance_length_correction": -598.1013793945312,
"rps_doc_wikipedia_importance": -373.3893127441406,
"rps_doc_wikipedia_importance_length_correction": -373.3893127441406
},
"fasttext": {
"dclm": 0.1419634222984314,
"english": 0.9220964312553406,
"fineweb_edu_approx": 2.3840277194976807,
"eai_general_math": 0.03855497017502785,
"eai_open_web_math": 0.1938992738723755,
"eai_web_code": 0.0021377799566835165
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "615.857",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
},
"secondary": {
"code": "615.82",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "6",
"label": "Promotional/Advertisement"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "9",
"label": "FAQ"
},
"secondary": {
"code": "10",
"label": "Knowledge Article"
}
},
"reasoning_depth": {
"primary": {
"code": "3",
"label": "Intermediate Reasoning"
},
"secondary": {
"code": "2",
"label": "Basic Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "4",
"label": "Highly Correct"
}
},
"education_level": {
"primary": {
"code": "2",
"label": "High School Level"
},
"secondary": {
"code": "1",
"label": "General Audience"
}
}
}
|
9222580d47c553ea90dc0f5e416f8f3a
|
1,073,373,477,522,988,900
|
Foods for a Camera-Ready Smile
The winter is fast-approaching, and with it comes seasonal feasts and holiday treats that can quickly veer your healthy nutritional habits off track. During this time of year, many people overindulge in rich foods, alcoholic drinks and late nights. And while many are worried about tipping the numbers on their scales, most people don’t realize that unhealthy nutritional habits can wreak havoc on your oral health.
The winter is fast-approaching, and with it comes seasonal feasts and holiday treats that can quickly veer your healthy nutritional habits off track. During this time of year, many people overindulge in rich foods, alcoholic drinks and late nights. And while many are worried about tipping the numbers on their scales, most people don’t realize that unhealthy nutritional habits can wreak havoc on your oral health.
When your body is lacking certain nutrients, it can show up on your tongue, cause gum irritation, and lead to problems within the roots of your mouth. It’s the body’s way of telling you that you are not getting the proper nutrition it needs. To maintain a healthy mouth and a camera-ready smile this season, it is important to brush up on basic principles of a healthy diet. Check out the tips below taken from my book, Smile! The Ultimate Guide to Achieving Smile Beauty, to help you determine if your nutritional habits are on track.
All foods have a pH level. Low-pH foods have high acid levels, and are known as acidifying, and higher-pH foods are alkalinizing or low in acid levels. The more acidifying your diet, the more loaded your mouth can get with harmful bacteria that can cause plaque and tooth decay. To strike the right balance, opt for a diet rich in alkalinizing foods, and limit your intake of acidic foods. I tell my patients to generally aim for a “75:25 ratio” in their diet (75% alkalinizing foods and 25% acidifying foods).
Here are some easy ways to adjust your holiday menu:
1. Stick to “smile-friendly” vegetables, such as beets, broccoli, carrots, celery, eggplant, mushrooms, tomatoes and green beans. Limit dishes prepared with potatoes, squash, and corn, which are known to be acidifying, and can contribute to increased bacteria in the mouth.
2. Got a sweet-tooth? Reach for fresh fruit, such as apples, bananas, oranges, grapes, peaches, strawberries, even dark chocolate, which are all alkalinizing. Avoid canned or glazed fruits, which can be acidifying and also high in sugar, which can lead to plaque build-up.
3. Eat almonds, flaxseed and pumpkin seeds, which are all healthy, alkalinizing nuts to enjoy. Limit your intake of cashews, peanuts, pecans and walnuts, as these nuts can be challenging for your teeth since they have high acid levels.
4. Enjoy fresh and unsweetened fruit juices, regular and herbal teas, vegetable juices, and of course, plenty of water. Limit your alcohol intake and avoid soda, which is one of the biggest offenders today for tooth decay.
You can readjust the balance your mouth’s pH level by limiting yourself to only alkalinizing foods for a few days. Also try taking a multivitamin, cutting down on your animal-protein intake, avoid yo-yo dieting, substituting sugar/sugar alternatives with stevia (the only alkalinizing sweetener), and of course, always practice good oral hygiene.
Could you imagine making 4.6 billion calls in a month?
That's how many robocalls Americans received in February this year. And when your phone is ringing endlessly with scammers asking about your car's warranty, a free cruise, or even a scary warning about your insurance coverage, it can definitely seem like all the calls are going to you. So what do you do when you get one of these fake calls and how do you protect your personal information and money from cons? Here are the important steps to take.
Keep ReadingShow less
|
{
"url": "https://www.drozshow.com/blog/foods-camera-ready-smile",
"source_domain": "www.drozshow.com",
"snapshot_id": "crawl=CC-MAIN-2022-49",
"warc_metadata": {
"Content-Length": "858587",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:5TAXTTXSNNSQMDK2SVTGQTHKQ5NHK2U2",
"WARC-Concurrent-To": "<urn:uuid:466d2f4a-ea49-454a-a817-f14fdb7d0117>",
"WARC-Date": "2022-11-30T18:34:27",
"WARC-IP-Address": "151.101.145.68",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:7YB4I73KGPUVVCPGQMXIAU2TLKMSHUBU",
"WARC-Record-ID": "<urn:uuid:b008e850-8c19-4be1-b0e4-b8eea841cbda>",
"WARC-Target-URI": "https://www.drozshow.com/blog/foods-camera-ready-smile",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:abb3c7bd-9fa0-4683-a755-5b4fd2249c2f>"
},
"warc_info": "isPartOf: CC-MAIN-2022-49\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for November/December 2022\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-150\r\nsoftware: Apache Nutch 1.19 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.4-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
31,
32,
448,
449,
865,
866,
1402,
1403,
1404,
1915,
1916,
1969,
1970,
2244,
2245,
2518,
2519,
2755,
2756,
2979,
2980,
3327,
3328,
3383,
3384,
3834,
3835
],
"line_end_idx": [
31,
32,
448,
449,
865,
866,
1402,
1403,
1404,
1915,
1916,
1969,
1970,
2244,
2245,
2518,
2519,
2755,
2756,
2979,
2980,
3327,
3328,
3383,
3384,
3834,
3835,
3856
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 3856,
"ccnet_original_nlines": 27,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.38235294818878174,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.0012787700397893786,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.1726342737674713,
"rps_doc_frac_unique_words": 0.47012579441070557,
"rps_doc_mean_word_length": 4.8569183349609375,
"rps_doc_num_sentences": 38,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.231815814971924,
"rps_doc_word_count": 636,
"rps_doc_frac_chars_dupe_10grams": 0.22143088281154633,
"rps_doc_frac_chars_dupe_5grams": 0.22143088281154633,
"rps_doc_frac_chars_dupe_6grams": 0.22143088281154633,
"rps_doc_frac_chars_dupe_7grams": 0.22143088281154633,
"rps_doc_frac_chars_dupe_8grams": 0.22143088281154633,
"rps_doc_frac_chars_dupe_9grams": 0.22143088281154633,
"rps_doc_frac_chars_top_2gram": 0.02751700021326542,
"rps_doc_frac_chars_top_3gram": 0.005827129818499088,
"rps_doc_frac_chars_top_4gram": 0.01683392934501171,
"rps_doc_books_importance": -444.2134704589844,
"rps_doc_books_importance_length_correction": -444.2134704589844,
"rps_doc_openwebtext_importance": -183.46896362304688,
"rps_doc_openwebtext_importance_length_correction": -183.46896362304688,
"rps_doc_wikipedia_importance": -129.59812927246094,
"rps_doc_wikipedia_importance_length_correction": -129.59812927246094
},
"fasttext": {
"dclm": 0.036435481160879135,
"english": 0.94905024766922,
"fineweb_edu_approx": 2.770320415496826,
"eai_general_math": 0.01488352008163929,
"eai_open_web_math": 0.18523508310317993,
"eai_web_code": 0.0007260399870574474
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "613.222",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
},
"secondary": {
"code": "613.222028",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "3",
"label": "Apply"
},
"secondary": {
"code": "2",
"label": "Understand"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "3",
"label": "Procedural"
},
"secondary": {
"code": "2",
"label": "Conceptual"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "12",
"label": "Listicle"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "4",
"label": "Highly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
b755ed28a90d11d590ef646404f4afc5
|
8,443,385,402,926,566,000
|
Assessment of liver damage
Blood Tests
One way of assessing if liver cells are dying is by testing the level of the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the blood. This is not particularly reliable as in most cases of chronic hepatitis C infection the liver function tests tend to fluctuate. Over the space of just a few days the results can vary from normal to noticeably raised. Raised ALT levels are present in around two-thirds of those infected while the remaining third show no evidence of elevated levels at all. These traditional liver function tests are not very effective indicators of liver damage in chronic hepatitis C. Currently the most reliable way to assess the extent of liver damage is by liver biopsy, however a fibroscan or other non-invasive techniques will be sufficient in most cases.
There are also some new blood tests that are starting to be used in the UK as markers of liver damage. These are made by a variety of different companies and are marketed under names such as Fibrotest, Fibrosure, and Actitest. Another way some doctors determine the presence of cirrhosis is by looking over time at the AST/ALT ratio. It seems that if the AST is consistently higher than ALT or equal to it this is highly suggestive of cirrhosis.
Biopsy
At present the most accurate way to check the extent of liver damage is by biopsy. A liver biopsy is a test in which small pieces of liver tissue are removed and examined under a microscope. This is done via a long needle inserted usually between the 8th and 9th ribs under the right arm. The tissue will be assessed to see the extent of inflammation and fibrosis (as well as revealing other abnormalities such as damage to bile ducts and the presence of fat).
The degree of inflammation is described in terms of inflammatory grade. Fibrosis is described by fibrotic grade. There are several different scoring and grading systems for liver biopsies and the same numbers are not comparable with another system, all of which can seem confusing. The systems used in the UK are the Ishak HAI, the Metavir and the Knodell systems and the Child-Pugh grading system for cirrhosis. The biopsy will indicate which stage of inflammation and fibrosis (scarring) are present in the liver. Inflammatory grade will range from none to extensive inflammation. Fibrotic grade will range from minimal scarring, scarring that has developed outside of the portal tracts (see below), to fibrosis that has spread or is bridging towards neighbouring portal tracts to cirrhosis.
In hepatitis C active fibrosis begins around the portal areas in the liver. The portal areas are tiny tracts of connective tissue within the liver that contain branches of the portal vein (the main blood supply of the liver linking through the small intestine, stomach, pancreas and spleen).
As the fibrosis worsens, it may extend from one portal zone to the others which adjoin it. This is called bridging fibrosis. Bridging fibrosis is the stage before cirrhosis and ranges from early to marked bridging fibrosis. Cirrhosis is characterized by serious scarring that alters the liver’s structure and its ability to function.
The most extensive study of the rate of progression of fibrosis split people into three groups – ‘rapid fibrosers’, ‘intermediate fibrosers’ and ‘slow fibrosers’. The largest group in the study, just over a third, were intermediate fibrosers who would be expected to develop cirrhosis around thirty years after initial infection with HCV. 33% of patients were expected to develop cirrhosis in less than 20 years (rapid fibrosers), while just under a third would progress to cirrhosis in more than 50 years, if ever (slow fibrosers).
Fibroscan
Fibroscan is a non-invasive test using a sound wave to measure the elasticity of the liver and is being used more and more in the UK. As damage to the liver increases, so it becomes stiffer. The stiffer or less elastic the liver, the faster the sound wave travels. The Fibroscan has been shown to be accurate in measuring little or no damage and in measuring cirrhosis. It has been less accurate at distinguishing intermediate degrees of fibrosis.
The machine is calibrated from 0 to 75, with around 4 representing no liver damage, 4-12 increasing amounts of fibrosis, 12-15 the beginnings of cirrhosis.
Its advantage over a biopsy is that it is quick and completely painless. This is because the probe is simply placed against the skin and nothing is inserted into the body. It is also capable of distinguishing differing degrees of cirrhosis as 80% of its entire range measures cirrhosis. For example, a score of 30 indicates existing or imminent decompensation.
|
{
"url": "http://www.hepctrust.org.uk/information/testing/assessment-liver-damage",
"source_domain": "www.hepctrust.org.uk",
"snapshot_id": "crawl=CC-MAIN-2018-26",
"warc_metadata": {
"Content-Length": "38174",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:DZ2BDZTJ56IBKE63MLCVU44ZWGQ7J4QQ",
"WARC-Concurrent-To": "<urn:uuid:77475753-e076-4359-b0db-ed987f86dc3b>",
"WARC-Date": "2018-06-18T04:11:38",
"WARC-IP-Address": "178.62.114.39",
"WARC-Identified-Payload-Type": "application/xhtml+xml",
"WARC-Payload-Digest": "sha1:CPZPZS6EDGVPWR7IA4T34E26VQLWDE7O",
"WARC-Record-ID": "<urn:uuid:a82843dc-76a0-4cb2-9c9a-2cf842ce67b9>",
"WARC-Target-URI": "http://www.hepctrust.org.uk/information/testing/assessment-liver-damage",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:eaa507e1-2390-4e6e-88cf-585c907c9c45>"
},
"warc_info": "robots: classic\r\nhostname: ip-10-167-170-5.ec2.internal\r\nsoftware: Nutch 1.6 (CC)\r\nisPartOf: CC-MAIN-2018-26\r\noperator: Common Crawl Admin\r\ndescription: Wide crawl of the web for June 2018\r\npublisher: Common Crawl\r\nformat: WARC File Format 1.0\r\nconformsTo: http://bibnum.bnf.fr/WARC/WARC_ISO_28500_version1_latestdraft.pdf"
}
|
{
"line_start_idx": [
0,
27,
28,
40,
41,
859,
1305,
1306,
1313,
1314,
1775,
1776,
2570,
2862,
2863,
3197,
3198,
3731,
3732,
3742,
3743,
4191,
4192,
4348,
4349
],
"line_end_idx": [
27,
28,
40,
41,
859,
1305,
1306,
1313,
1314,
1775,
1776,
2570,
2862,
2863,
3197,
3198,
3731,
3732,
3742,
3743,
4191,
4192,
4348,
4349,
4709
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 4709,
"ccnet_original_nlines": 24,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.44342857599258423,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.018285710364580154,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.11314286291599274,
"rps_doc_frac_unique_words": 0.4135723412036896,
"rps_doc_mean_word_length": 4.906529903411865,
"rps_doc_num_sentences": 40,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.090657711029053,
"rps_doc_word_count": 781,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.013569939881563187,
"rps_doc_frac_chars_dupe_6grams": 0.013569939881563187,
"rps_doc_frac_chars_dupe_7grams": 0.013569939881563187,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.01878914050757885,
"rps_doc_frac_chars_top_3gram": 0.01696242019534111,
"rps_doc_frac_chars_top_4gram": 0.008350729942321777,
"rps_doc_books_importance": -333.6059875488281,
"rps_doc_books_importance_length_correction": -333.6059875488281,
"rps_doc_openwebtext_importance": -213.60800170898438,
"rps_doc_openwebtext_importance_length_correction": -213.60800170898438,
"rps_doc_wikipedia_importance": -196.7050018310547,
"rps_doc_wikipedia_importance_length_correction": -196.7050018310547
},
"fasttext": {
"dclm": 0.15361839532852173,
"english": 0.9563518166542053,
"fineweb_edu_approx": 2.554068088531494,
"eai_general_math": 0.6038484573364258,
"eai_open_web_math": 0.46910250186920166,
"eai_web_code": 0.035678330808877945
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.122",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "616.12",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "3",
"label": "Irrelevant Content"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "4",
"label": "Missing Images or Figures"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "8",
"label": "Documentation"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "2",
"label": "High School Level"
},
"secondary": {
"code": "1",
"label": "General Audience"
}
}
}
|
1a01aa77535b9ecfb87b9fc36adbcd2f
|
383,306,250,455,580,000
|
Get Answers to all your Questions
header-bg qa
Consider the following statements A, B, and C. Which of the following options accurately represents the statements?
Statement A: All enzymes exhibit a proteinaceous nature.
Statement B: Certain competitive inhibitors are frequently employed to manage bacterial pathogens.
Statement C: The active site of an enzyme is formed through the intricate folding of the protein's tertiary structure.
Option: 1
Statements A and B are correct.
Option: 2
Statements B and C are correct.
Option: 3
Statements A and C are correct.
Option: 4
All of the above
Answers (1)
best_answer
Statement B states that some competitive inhibitors are commonly used to control bacterial pathogens. This statement is accurate because competitive inhibitors can bind to the active site of an enzyme and compete with the substrate, effectively inhibiting the enzyme's activity. In the context of bacterial pathogens, competitive inhibitors can be employed to target specific enzymes necessary for bacterial survival or growth, providing a means of controlling the pathogens.
Statement C asserts that the active site of an enzyme is formed through the intricate folding of its protein's tertiary structure. This statement is also accurate. The active site of an enzyme is the region where substrate molecules bind and undergo catalysis. It is typically formed by specific amino acid residues that come together in the folded structure of the protein, which includes the tertiary structure. The precise folding of the protein is crucial for creating the functional active site and facilitating enzyme-substrate interactions.
Therefore, Option 2, which states that Statements B and C are correct, is the appropriate answer.
Posted by
Deependra Verma
View full answer
NEET 2024 Most scoring concepts
Just Study 32% of the NEET syllabus and Score up to 100% marks
|
{
"url": "https://learn.careers360.com/medical/question-consider-the-following-statements-a-b-and-c-which-of-the-following-options-accurately-represents-the-statements-statement-a-all-enzymes-exhibit-a-proteinaceous-natur/",
"source_domain": "learn.careers360.com",
"snapshot_id": "CC-MAIN-2024-18",
"warc_metadata": {
"Content-Length": "509881",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:FEXPV2AJCV53JEZXUL2CQ6N6BP7FVPFE",
"WARC-Concurrent-To": "<urn:uuid:84b6b186-f55f-44ca-84f3-03ae2347fa1c>",
"WARC-Date": "2024-04-23T11:24:52",
"WARC-IP-Address": "3.109.250.236",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:X5MGMNMZIJGVK5QWQKOPKZL5MQ5BXKSL",
"WARC-Record-ID": "<urn:uuid:cecd7e1b-5414-4b95-bf60-34e6af2ab588>",
"WARC-Target-URI": "https://learn.careers360.com/medical/question-consider-the-following-statements-a-b-and-c-which-of-the-following-options-accurately-represents-the-statements-statement-a-all-enzymes-exhibit-a-proteinaceous-natur/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:9c5f5ac0-8089-4e05-8984-02c96c888fbc>"
},
"warc_info": "isPartOf: CC-MAIN-2024-18\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for April 2024\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-242\r\nsoftware: Apache Nutch 1.19 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.5-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
34,
35,
48,
49,
165,
166,
223,
224,
323,
324,
443,
444,
454,
455,
487,
488,
490,
491,
492,
502,
503,
535,
536,
537,
547,
548,
580,
581,
583,
584,
585,
595,
596,
613,
614,
615,
627,
628,
640,
641,
1117,
1118,
1666,
1667,
1765,
1766,
1776,
1777,
1793,
1794,
1811,
1812,
1844,
1845
],
"line_end_idx": [
34,
35,
48,
49,
165,
166,
223,
224,
323,
324,
443,
444,
454,
455,
487,
488,
490,
491,
492,
502,
503,
535,
536,
537,
547,
548,
580,
581,
583,
584,
585,
595,
596,
613,
614,
615,
627,
628,
640,
641,
1117,
1118,
1666,
1667,
1765,
1766,
1776,
1777,
1793,
1794,
1811,
1812,
1844,
1845,
1911
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 1911,
"ccnet_original_nlines": 54,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.3145400583744049,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.053412459790706635,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.15133531391620636,
"rps_doc_frac_unique_words": 0.45517241954803467,
"rps_doc_mean_word_length": 5.317241191864014,
"rps_doc_num_sentences": 18,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 4.473024845123291,
"rps_doc_word_count": 290,
"rps_doc_frac_chars_dupe_10grams": 0.07652398943901062,
"rps_doc_frac_chars_dupe_5grams": 0.1569390445947647,
"rps_doc_frac_chars_dupe_6grams": 0.14007781445980072,
"rps_doc_frac_chars_dupe_7grams": 0.09273671358823776,
"rps_doc_frac_chars_dupe_8grams": 0.07652398943901062,
"rps_doc_frac_chars_dupe_9grams": 0.07652398943901062,
"rps_doc_frac_chars_top_2gram": 0.01945525035262108,
"rps_doc_frac_chars_top_3gram": 0.033722441643476486,
"rps_doc_frac_chars_top_4gram": 0.038910508155822754,
"rps_doc_books_importance": -165.3897247314453,
"rps_doc_books_importance_length_correction": -165.3896942138672,
"rps_doc_openwebtext_importance": -109.62965393066406,
"rps_doc_openwebtext_importance_length_correction": -109.62965393066406,
"rps_doc_wikipedia_importance": -97.73481750488281,
"rps_doc_wikipedia_importance_length_correction": -97.73481750488281
},
"fasttext": {
"dclm": 0.9893335700035095,
"english": 0.9380325078964233,
"fineweb_edu_approx": 3.1001698970794678,
"eai_general_math": 0.8467357754707336,
"eai_open_web_math": 0.33940672874450684,
"eai_web_code": 0.0031806800980120897
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "572.6",
"labels": {
"level_1": "Science and Natural history",
"level_2": "Biology and Anthropology",
"level_3": "Anthropology"
}
},
"secondary": {
"code": "615.5",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "0",
"label": "No Artifacts"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "18",
"label": "Q&A Forum"
},
"secondary": {
"code": "23",
"label": "Tutorial"
}
},
"reasoning_depth": {
"primary": {
"code": "3",
"label": "Intermediate Reasoning"
},
"secondary": {
"code": "2",
"label": "Basic Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "3",
"label": "Undergraduate Level"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
6e3c8d3593f3f69280bb5502b214ab8e
|
5,816,628,927,438,897,000
|
Wellbutrin And Autism
Wellbutrin And Autism
Wellbutrin And Autism
Appetite Tablets Wellbutrin And Autism (Ranking) « MediGap Direct
Gnc Weight Loss Tea, 4 Types Of Dietary Supplements, Weight Loss Treatment Des Plaines, Wellbutrin And Autism, Beat Belly Fat, Adipex P Coupen, Best Appetite Suppressants 2021, Appetite Tablets. Its too unreasonable Why do we need Wellbutrin And Autism to work for them?! Its not their servants, or the servants, stop appetite and they have to consider their abilities. blushing and yelling roughly The words came prescription appetite suppressant pills out Immediately made Yu Ma dare not say anything Yus mother is a rural woman with two children studying at home. Simply put, it was shot directly into a sieve, but fortunately, this thing is a simulated weapon similar to a magic body Although it can pull apart the skin and expel blood, Wellbutrin And Autism it is actually It is impossible for the above to penetrate a person. and then looked back pills that kill your appetite while cleaning my hair There Bayi Yonglin was holding her bow and arrow and was ready to fire her second energy arrow, facing Huiye. Yingji, otherwise, dont go back after you come this time You can just ask someone to pass over the things over there You are my fathers most proud disciple If you are under his hand, you will be ten in the future Dian Yama must have your share. and it works appetite suppressant then walked over there the smell of blood Real Shark Tank Diet Pill As a blood What To Put In Smoothies For Weight Loss clan, Wellbutrin And Autism Fran needs blood to food suppressant tablets sustain life, so she is very familiar with the smell of blood. The fact that local gods can Weight Loss Pills Alede Use have such belief is an incredible thing in itself, and it should be said that it is Bo Li also didnt want her reputation safe and effective appetite suppressant to be too great. If humans Wellbutrin And Autism are already powerful to a certain extent, then it may be okay to deal with some big monsters in a targeted manner, but in top prescription appetite suppressants fact, the strong in Gensokyo are not so Does Emergen C Boost Metabolism much Theoretically, it was not necessary. Qin Huai finished scrolling, put it gnc food supplement away, and smiled at Li Feng Lets go, its rare that the old woman showed her skills and cooked a table of good dishes. And Ouyang Wen has been on the sidelines Im dumbfounded, he never thought that using the Golden Needle Overcoming Crisis technique could prescription appetite suppressant pills achieve this speed Under this circumstance. Qin Huai took out the sterilized golden needles from the medicine Wellbutrin And Autism box, and said to the patient Xiao Ji, for safetys sake, I will let you fall asleep later, dont worry and dont resist, it will be fine for a while. Okay Okay, Xiaofeng, how is Lianer? Wellbutrin And Autism Wellbutrin And Autism Are you okay? Xiang Tian asked best all natural appetite suppressant Li Feng before quitting, as if he had held the last lifesaving best appetite suppressant pills grass Dont worry! Uncle Xiang, Im here. The monsters at home and abroad were not as harmonious as international friends When it was time to fight, Qin First Night Of Adipex No Sleep Lianse was very Can You Lose Weight On Intermittent Fasting Without Exercise troubled She was really bad at persuading such things Tough hard work Hongyi was gloating next to him, and Qin Lianse also had such a difficult time.
1. Wellbutrin And Autism Keto Weight Loss Average Per Week
the foundation is the best Its important dont forget Yes no problem! Still Wellbutrin And Autism very happy Forget it, anyway, I am also giving gifts, and the other party is happy. After all, except Transformations Medical Weight Loss Coupons for Yuyuko, the other people They werent normal characters either, they were about to Weight Loss Pills From Doctor Nz fight, and it was very easy to make such an underground collapse. Thinking of suddenly making such a loud noise like being bombed, all the atmosphere was ruined The two looked back angrily, but found that it was their precious daughter They couldnt help but smile and felt helpless This daughter, by leptin supplement gnc nature, is stubborn. The matter about the prince is a secret Huo Qinge suddenly thought Wellbutrin And Autism that these two men did not seem to be good men and women, and suddenly had a headache If this secret is leaked out, Prince Shotokus political status will be in jeopardy. If it werent for the people here, Zhen Feiling would also be watching, Im afraid they would have embraced each other appetite suppressant sold in stores a long time appetite suppressant supplement ago Wellbutrin And Autism to express their two months of longing. Let Su Xiaoli take him to a room, start to run Jennifer Thompson Weight Loss the Kaitian good fortune art, try to restore spiritual energy, because at night, I have to help curb appetite practice Quxue Jianshen Decoction again Moreover, for the next three days. Not only is his body soft as a snake, he can twist it at will, and even the bones of his head can move to achieve the purpose of changing his appearance Although the power of this method is Wellbutrin And Autism not strong, it is very useful for these terrorists. She was a little strange to see that the girls deep best appetite suppressant gnc pupils, she always felt that this person is not simple, she Is there any purpose for coming to Boli. Bo Li cant change the ending no matter if he is calling, so the girl hopes Bo Li can have a good attitude in advance Boli looked at Mengzis face, then nodded, and started to sit down here again. Not to mention, this is the first time I have encountered a refining level that requires a pharmacist level I dont know if any accidents will happen Therefore, in order to prevent any accidents, Li Feng didnt read the sugar appetite suppressant book anymore in the afternoon. she can only rely on her own thinking to solve this Diet Pills Clinic In Vallejo matter Although her mind is not too mature, she is smart enough She has her own determination and grasp. She simply changed back to a human posture Although she Actavis Beacita Capsules Hard Orlistat was stronger in the form of a dragon, she Wellbutrin And Autism had a greater goal, which was nothing short of one. whether it is himself or the opposite Hua Shan Meili didnt believe this very much but Boli explained to him that it was because of Adipex Exercises the carelessness of ghosts Meili herself learned psychology and should be clear well, Meili knows very well, ghosts are simpleminded. All right The village chief nodded, and then said Lets go Well you go first, Igo and see Bai Lian said Didnt you say that you are okay Its okay He became more and more anxious and restless This thought made Bai Lians heart like 10,000 ants biting But its very dangerous Its okay, Im sure Of course I know its dangerous. Then what are you going to do? Li Feng looked sympathetically at this brother who was suffering from the incurable Wei Phoenix phobia, but for this phobia, even energy and appetite suppressant with Li Fengs medical skills, there is absolutely no way, With the strength of the Wei family. However, Shenqi did still lack something, so hunger suppressant drinks this time, Boli came to tell Shenqi about this Whats the matter? Shenqi asked Weight Loss Starting Wellbutrin Is there anything to do with me? Well, I know. In fact, if you say that, what kind of monster is Boli, the appetite suppressant pills golden slime, the king of the small slime group that you encountered at the beginning of the adventure, the one with relatively high defense? Its really speechless, 3 Day Water Fast Before Diet Pills is that a human being. Speaking of the immortal realm, the celestial realm, or the hell, they are actually similar things, so you cant see the outside from inside Their living environment is destined to be inferior to the human Dietary Supplement Pills For Weight Loss Wellbutrin Added To Zoloft world. After finishing my shoes, I stepped on the floor twice Because there was a layer of cushion, there was no sound, but Frans own wings moved slightly Then Fran stood up straight again The body ran to Remy and said, Okay. The terrible gap is not something normal people can bear Its the same with Meili, she is just stronger than the average person, and shes not a superhuman thing Ah Its not Yanhee Diet Pills Instructions an Cla Pills On Keto Diet exaggeration to say that its Superman How come Wellbutrin And Autism it always sounds so contradictory and troublesome. With a Wellbutrin And Autism Zhang Yanyan, it also has the responsibility of a flower protector When the best over the counter appetite suppressant 2019 three of them arrived in Wellbutrin And Autism the provincial capital, Wellbutrin And Autism the Zhao family naturally arranged everything. Nowadays, they curb appetite suppressant are basically rushing to a welloff life with adequate food and clothing, and they dont need the food provided by the ghost clan But can rely on themselves to Weight Loss Pills That Give You Energy grow something to eator buy it.
2. Fastest Working Diet Pill 2017
En? Boli tilted her head, Why? Uh Why, Bai Lian thought about it, and then all natural appetite suppressant pills said If Mega T Dietary Supplement Green Tea Reviews Hakulisama is there, I think the trip will be How To Flatten Stomach Quickly smoother and more interesting After Bai Lian explained this, Hakuli nodded, and he Dextromethorphan Hbr And Wellbutrin Can You Combine thought about it a little bit. When she didnt know what to do at the beginning, she suddenly understood a lot now, although there is no absolute evidence Wellbutrin And Autism to prove that it is not Meili and Hakuryi What they did But it seemed impossible to prove that they did it At Wellbutrin And Autism least. Li Feng saw that Zhao Rongrong ran out of the dormitory and hid No wonder she didnt see it She ran over and knowingly asked Rongrong, whats wrong with me? I just read in the dormitory. acting? Not to mention this effort, if I wear it to help, where can I put the face of this genius doctor! Li Feng shook his head, refusing to Wellbutrin And Autism agree Damn You are too unrighteous! Not willing to help with such a small favor? ! Chen Long widened his eyes and said Wellbutrin And Autism angrily. The referees Wellbutrin And Autism are all Exercise To Reduce Belly And Thigh Fat wellrespected doctors, and naturally they will not make biased safest appetite suppressant 2018 judgments based on whether they are Western or Chinese medicine In the final result the total score of Chinese medicine is 17 85 points. The blood of all the monsters hopes to fight Boli knows this very well, because all the monsters he knows are like that It looks really good. Since its useful, just use Adipex Doctor Philadelphia it once, it doesnt matter anyway If Lemmy Is There A Safe Over The Counter Appetite Suppressant knows what he thinks, Im Wellbutrin And Autism afraid I cant help but slap him, but this has become his fixed line of thinking Not because he was too cruel, but because he had forgotten some ways of thinking without benefit Okay. this person is Slimming Coach always unable to what suppresses appetite naturally be truly cold Obviously she is such a person If Lianzi knew that someone worked so hard for her, she would probably cry. You have already had a prescribed appetite suppressant lot of this experience when you love yourself Now it can be said that it has reached the limit of appetite blocker pills patience, Boli, Wellbutrin And Autism Boli. and then shook their heads immediately Well she still looks scared, and Boli is helpless It seems that it is really not easy to gain the trust Wellbutrin And Autism of such a little girl. Its good news, I didnt feel angry before! When will I be gnc weight loss products able to recover? Wellbutrin And Autism Thats not clear! Li Feng smacked his lips what can i take to suppress appetite and said helplessly, Now its just temporarily out of danger! If you want to recover? How Fruit And Veg Only Diet Weight Loss easy is it! Wellbutrin And Autism Save him! Ive already spent a lot of effort on coming back. probably no one would treat her as a normal human Although she didnt Wellbutrin And Autism make any moves beyond the norm, she was definitely not an ordinary person. things are so complicated and complicated and she doesnt know top appetite suppressants 2021 how for gnc rapid weight loss a while Thats right, but the magician, according to Hakulis explanation, is this. Occasionally look at each other and smile knowingly, but it is worth a thousand words As the woods deepen, the noise of the competition is also left behind. Even if Ying Ji asks her to do something, it is only an order, not her own thinking Similarly, Hongyi is the same This does not mean that she cant think, but she wont use what she can use Things for their own benefit. Someone once said that luck is all strength Of course, outside of the game, these things are not easy natural appetite suppressant foods to say, but for Paqiuli, such a smooth wind is not a bad thing. Of course, Lianzi is practicing, and Zi can see it, but it is far Wellbutrin And Autism from enough to survive here What exactly should I do Zi raised his head, Wellbutrin And Autism then looked at the sky. After all, the two peoples hair is not short, especially supplements to curb appetite Meili, who has beautiful long hair and it doesnt mean to lose it at all, except Except for a break. Of course, the premise is that there should be no accidents in Renko If something happened to the lotus seed, then Zi cant easily forgive herself now. Gnc Weight Loss Tea, Beat Belly Fat, Wellbutrin And Autism, Weight Loss Treatment Des Plaines, 4 Types Of Dietary Supplements, Best Appetite Suppressants 2021, Appetite Tablets, Adipex P Coupen.
• vitamins that suppress appetite
• safe herbal appetite suppressant
|
{
"url": "https://medigapdirect.com/Wellbutrin/4a5f0d_Wellbutrin-And-Autism",
"source_domain": "medigapdirect.com",
"snapshot_id": "crawl=CC-MAIN-2021-21",
"warc_metadata": {
"Content-Length": "56925",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:JB253QTWHDEY3ZWKUO4LDJAPVKKLJHPC",
"WARC-Concurrent-To": "<urn:uuid:9e18232c-ab5a-4b02-af0e-af8849df244d>",
"WARC-Date": "2021-05-09T20:34:09",
"WARC-IP-Address": "208.109.29.197",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:ECUZ46CDNUYCQ3FAOAPVXL6S26HLYYOF",
"WARC-Record-ID": "<urn:uuid:e9c7532c-aaef-4f05-9c19-75f39397266c>",
"WARC-Target-URI": "https://medigapdirect.com/Wellbutrin/4a5f0d_Wellbutrin-And-Autism",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:8ad8ef8b-f9b4-4b19-b077-3c3d4f2bab7b>"
},
"warc_info": "isPartOf: CC-MAIN-2021-21\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for May 2021\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-25.ec2.internal\r\nsoftware: Apache Nutch 1.18 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.2-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
22,
44,
45,
67,
68,
134,
135,
3511,
3512,
3571,
3572,
9214,
9215,
9249,
9250,
13995,
13996,
14032
],
"line_end_idx": [
22,
44,
45,
67,
68,
134,
135,
3511,
3512,
3571,
3572,
9214,
9215,
9249,
9250,
13995,
13996,
14032,
14068
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 14068,
"ccnet_original_nlines": 18,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.4098118841648102,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.007746220100671053,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.09774991124868393,
"rps_doc_frac_unique_words": 0.3499796986579895,
"rps_doc_mean_word_length": 4.606171131134033,
"rps_doc_num_sentences": 82,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.891270160675049,
"rps_doc_word_count": 2463,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.031467609107494354,
"rps_doc_frac_chars_dupe_6grams": 0.015954159200191498,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.04125164821743965,
"rps_doc_frac_chars_top_3gram": 0.060290880501270294,
"rps_doc_frac_chars_top_4gram": 0.007668579928576946,
"rps_doc_books_importance": -1094.3902587890625,
"rps_doc_books_importance_length_correction": -1094.3902587890625,
"rps_doc_openwebtext_importance": -613.49462890625,
"rps_doc_openwebtext_importance_length_correction": -613.49462890625,
"rps_doc_wikipedia_importance": -392.5499267578125,
"rps_doc_wikipedia_importance_length_correction": -392.5499267578125
},
"fasttext": {
"dclm": 0.027966439723968506,
"english": 0.952343225479126,
"fineweb_edu_approx": 1.081255555152893,
"eai_general_math": 0.132207989692688,
"eai_open_web_math": 0.3126533627510071,
"eai_web_code": 0.038264330476522446
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "615.857",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
},
"secondary": {
"code": "615.82",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "1",
"label": "Factual"
},
"secondary": {
"code": "2",
"label": "Conceptual"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "3",
"label": "Incoherent Flow"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "16",
"label": "Personal Blog"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "6",
"label": "Not Applicable/Indeterminate"
},
"secondary": {
"code": "2",
"label": "Partially Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
9222580d47c553ea90dc0f5e416f8f3a
|
4,504,849,510,423,177,000
|
Skip to content
Why is Vaping Bad For Your Health?
Written by
allen858
Why is Vaping Bad For Your Health?
Why is Vaping Bad for Your Health? Many people don’t realize why vaporizing your cigarettes is bad for your health. When you inhale vapors directly into your lungs without filtering them or breaking apart into smaller particles, you’re putting yourself at an increased risk for serious health problems such as for example Lung Cancer and Carcinoma. By the time you finish scanning this article it is possible to avoid any bad ramifications of vapes in your daily life.
why is vaping bad
Firstly, when you use an electronic cigarette, you are inhaling vaporized nicotine. The vapor is hot, sticky, and has an extremely strong smell. That smell is what you notice first, followed by the burning and wheezing that will result from you lungs as you breathe. The amount of time that you’ll take to feel the effects of smoking cigarettes is due to the volume of aerosolization your consuming.
You should always start by utilizing a water-based e-juice. There are numerous flavors in the marketplace today, so I encourage one to try a few out before you make your purchase. You need to find a smooth tasting e-juice with a moderate quantity of nicotine. If you are using an aerosol e-liquid, you will quickly reach your nicotine quota that may trigger you to start puffing away. As you breathe through your mouth, you’ll go through the same effects from smoking.
So, how come vaporizing bad for your oral health? Because you are taking in more smoke through your lungs than you would through your mouth. Smoke gets trapped in your lungs and will be sucked into your lungs by constantly inhaling through your mouth. Inhaling deeply can cause nasty coughs and even pneumonia if it isn’t looked after properly.
There are also some rare cases where people have had problems with their livers when consuming vaporized cigarettes. These rare occurrences are usually due to e-juices with high concentrations of alcohol or mold. Take into account that when you are exhaling, the skin tightening and is pulled into your lungs and that may cause you issues with certain diseases like liver cirrhosis. In the event that you suspect that this is why you aren’t feeling well, stop smoking.
When you decide to quit smoking, look at the health benefits. You should have less risk of getting cancer along with other cancers related to tobacco because you won’t have any connection with it after podsmall.com you quit smoking. The same pertains to cardiovascular problems. Nicotine is really a toxin that increases your heart risk when you use it as time passes.
A recent study found there are strong traces of nicotine in non-smoker’s lung tissue. Which means that even non-smokers can potentially be putting themselves at risk. That’s why is it vital that you avoid vaporizing anything, even though you are just drinking juice. If you don’t think that you can stop smoking without the mouth area or nose getting contaminated, then ensure that you use an electric nicotine product.
How come vaporizing health risks so serious? It’s not only bad for your lungs but your overall health. Not to mention the millions of heart disease deaths that happen all over the world each year. With all of these reasons as well as the many scientific studies that are coming out every day, you can easily understand why it is better to simply not smoke at all than to expose you to ultimately secondhand smoke.
However, you may still find many people that say that there surely is nothing wrong with smoking while you are using electric cigarettes. Some would say that the only real difference is that you are not inhaling smoke. To place it frankly, there are many differences between traditional cigarettes and the newer kinds. To be able to truly enjoy all the great benefits of traditional cigarettes, you must avoid the flavored ones. They provide some flavor that you probably won’t find in your neighborhood store.
As for why is vaporizing bad for you, there is proof showing that it will be does contain some cancer-causing chemicals in the form of tar and toxic heavy metals. Tar and heavy metals are thought to cause cancer in your body if you inhale them. That’s why it is important to avoid the flavored models when you decide whether or not to give up smoking. Even if you like the taste of these traditional cigarettes, you want to not be inhaling them.
In the event that you feel that you don’t want to deal with the health ramifications of smoking tobacco, then you should start considering an alternative way to smoke. This means that you are going to have to completely change your lifestyle. The easiest way to do this is to begin using an herbal vaporizer that you may find online or at an area store. By doing so, you won’t suffer from the nasty taste of traditional cigarettes. You will also not be exposing you to ultimately each of the other unhealthy ramifications of smoking tobacco.
Previous article
HOW COME Casino Korea Important?
Next article
Can Electronics Cigarettes ASSIST YOU TO Quit Smoking?
|
{
"url": "https://allen858.usinamontealegre.com/2021/07/07/why-is-vaping-bad-for-your-health-2.html",
"source_domain": "allen858.usinamontealegre.com",
"snapshot_id": "crawl=CC-MAIN-2021-49",
"warc_metadata": {
"Content-Length": "25223",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:3VSTA6YDXFUJHSVAM3BVMCJZK6S33SP4",
"WARC-Concurrent-To": "<urn:uuid:b8a1935a-0ee0-42c5-b43e-671ac51c0c9b>",
"WARC-Date": "2021-11-28T15:20:38",
"WARC-IP-Address": "172.67.163.44",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:EYGGZMPHK7R2F4NW2PWYUY7UJBDFI4EM",
"WARC-Record-ID": "<urn:uuid:bd7a8bf2-9e4e-4239-81d8-628a7338f608>",
"WARC-Target-URI": "https://allen858.usinamontealegre.com/2021/07/07/why-is-vaping-bad-for-your-health-2.html",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:edaa067d-a1f6-4042-b48e-71f0ecf46d87>"
},
"warc_info": "isPartOf: CC-MAIN-2021-49\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for November/December 2021\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-127\r\nsoftware: Apache Nutch 1.18 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.3-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
16,
17,
52,
53,
64,
65,
74,
75,
110,
111,
580,
581,
599,
600,
1000,
1001,
1470,
1471,
1816,
1817,
2286,
2287,
2656,
2657,
3077,
3078,
3492,
3493,
4004,
4005,
4451,
4452,
4994,
4995,
5012,
5013,
5046,
5047,
5060,
5061
],
"line_end_idx": [
16,
17,
52,
53,
64,
65,
74,
75,
110,
111,
580,
581,
599,
600,
1000,
1001,
1470,
1471,
1816,
1817,
2286,
2287,
2656,
2657,
3077,
3078,
3492,
3493,
4004,
4005,
4451,
4452,
4994,
4995,
5012,
5013,
5046,
5047,
5060,
5061,
5115
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 5115,
"ccnet_original_nlines": 40,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.48846539855003357,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.007021060213446617,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.09829487651586533,
"rps_doc_frac_unique_words": 0.40457144379615784,
"rps_doc_mean_word_length": 4.729142665863037,
"rps_doc_num_sentences": 52,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.234813690185547,
"rps_doc_word_count": 875,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.027791200205683708,
"rps_doc_frac_chars_dupe_6grams": 0.019574670121073723,
"rps_doc_frac_chars_dupe_7grams": 0.019574670121073723,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.01691637933254242,
"rps_doc_frac_chars_top_3gram": 0.01449976023286581,
"rps_doc_frac_chars_top_4gram": 0.013533109799027443,
"rps_doc_books_importance": -390.2803955078125,
"rps_doc_books_importance_length_correction": -390.2803955078125,
"rps_doc_openwebtext_importance": -252.41102600097656,
"rps_doc_openwebtext_importance_length_correction": -252.41102600097656,
"rps_doc_wikipedia_importance": -218.70411682128906,
"rps_doc_wikipedia_importance_length_correction": -218.70411682128906
},
"fasttext": {
"dclm": 0.782362699508667,
"english": 0.957741916179657,
"fineweb_edu_approx": 2.1485657691955566,
"eai_general_math": 0.0684281587600708,
"eai_open_web_math": 0.3008253574371338,
"eai_web_code": 0.008186760358512402
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "613.7",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
},
"secondary": {
"code": "615.5",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "16",
"label": "Personal Blog"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "2",
"label": "Partially Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
b755ed28a90d11d590ef646404f4afc5
|
1,343,312,325,470,999,000
|
Skip to main content
Identification of confounder in epidemiologic data contaminated by measurement error in covariates
Abstract
Background
Common methods for confounder identification such as directed acyclic graphs (DAGs), hypothesis testing, or a 10 % change-in-estimate (CIE) criterion for estimated associations may not be applicable due to (a) insufficient knowledge to draw a DAG and (b) when adjustment for a true confounder produces less than 10 % change in observed estimate (e.g. in presence of measurement error).
Methods
We compare previously proposed simulation-based approach for confounder identification that can be tailored to each specific study and contrast it with commonly applied methods (significance criteria with cutoff levels of p-values of 0.05 or 0.20, and CIE criterion with a cutoff of 10 %), as well as newly proposed two-stage procedure aimed at reduction of false positives (specifically, risk factors that are not confounders). The new procedure first evaluates potential for confounding by examination of correlation of covariates and applies simulated CIE criteria only if there is evidence of correlation, while rejecting a covariate as confounder otherwise. These approaches are compared in simulations studies with binary, continuous, and survival outcomes. We illustrate the application of our proposed confounder identification strategy in examining the association of exposure to mercury in relation to depression in the presence of suspected confounding by fish intake using the National Health and Nutrition Examination Survey (NHANES) 2009–2010 data.
Results
Our simulations showed that the simulation-determined cutoff was very sensitive to measurement error in exposure and potential confounder. The analysis of NHANES data demonstrated that if the noise-to-signal ratio (error variance in confounder/variance of confounder) is at or below 0.5, roughly 80 % of the simulated analyses adjusting for fish consumption would correctly result in a null association of mercury and depression, and only an extremely poorly measured confounder is not useful to adjust for in this setting.
Conclusions
No a prior criterion developed for a specific application is guaranteed to be suitable for confounder identification in general. The customization of model-building strategies and study designs through simulations that consider the likely imperfections in the data, as well as finite-sample behavior, would constitute an important improvement on some of the currently prevailing practices in confounder identification and evaluation.
Peer Review reports
Background
In the practice of epidemiology, researchers identify confounders theoretically or empirically. Theoretical identification is generally carried out through use of directed acyclic graphs (DAGs) [1]. While the use of DAGs has many virtues (such as explicit declaration of hypotheses and theoretical analysis that can guide model-building in a manner that increases the possibility of empirically estimating causal association), they are subjective interpretations that reflect an investigator’s belief of how the world works, and does not necessary reflect how the world actually is [2]. As such, relying on theory alone for confounder identification is perilous: if we knew all causal relations of interest and could draw perfect DAGs, then there would be no need to empirically identify the confounders.
We focus specifically on a problem of identification of a true structural confounder present in data-generation process, i.e. a variable that would still be a cofounder if sample size was infinite, from a finite sample situation that can give rise to confounding by chance. Structural confounding is to be contrasted with confounding that arises by chance in finite samples. Such confounding by chance can be due to an association between a variable with an outcome, when such a variable is independent of exposure in population but not a sample. In such situations, it is important to be able to realize that confounding is a quirk of a finite sample, even if “controlling” for covariate in a regression model has measurable impact on exposure-outcome association. In essence, not every variable that has influence on the magnitude of exposure-outcome association in a finite sample is a structural confounder, and vice versa. It is important to correct exposure-outcome association for the peculiarities of the finite sample but one has to be cautious about generalizing that any variable identified in such a manner is a structural confounder rather than and “incidental” confounder. Distinguishing between the two types of confounding is helpful for understanding how factors under study inter-related in the population since it is the valid inferences about the population that drive application of epidemiology to policy. We attempt to address this issue in our work. However, it seems prudent to reiterate before any further analysis that it is sensible to include all know risk factors in any regression analysis of exposure-outcome association in epidemiology in order to guard against confounding by chance: application of DAG methodology can be most helpful in this regard because it allows to codify what is already known about the problem. Conceptually, any model fitted to the data has to reflect our understanding of the phenomena under study and that includes what we know already (factors forced into the model) and what we hope to learn from the data (factors that are tested the model). Thus, we always adjust risk of cancer for age and risk of autism for sex, because to do otherwise amounts to making a statement about data-generating mechanism that is known to be wrong.
Empirical confounder identification is useful when the true causal relations between the exposure, outcome, and a set of potential confounders are unknown. This is typically carried out with significance criterion, e.g., a p-value cutoff (≤0.05 and 0.2 are commonly used) for the association between a potential confounder and outcome, or a change-in-estimate (CIE) strategy, e.g., a ≥10 % CIE of the effect of exposure between models that do and do not adjust for the potential confounder [3, 4]. Practitioners of these approaches often cite papers by Mickey and Greenland [3] or Maldonado and Greenland [4]. However, even while these authors never advocated CIE practice for all data situations, it is not uncommon to see authors in the literature employing subjective a priori CIE cutoffs in the same manner as they might do with p-value significance testing, despite evidence that fixed CIE cutoffs result in unacceptable type I and type II error rates in many circumstances [5, 6]. Simulation-based CIE that are customized to each application and are meant to have pre-specified type I error rates were recently proposed [5]. The inevitable measurement error in covariates further complicates confounder identification in practice [7] as does latent confounding, the extreme case of miss-measured confounder. The topic of latent confounding has been addressed extensively with excellent proposal for analytical treatment, e.g. see [8, 9] for review.
Accurate knowledge of measurement error magnitude and structure is sometimes lacking in epidemiology. However, in large-scale and well-conducted epidemiological studies, researchers have to make use of measurements with known error (obtained in validity and reliability studies) to achieve the required sample size and to reduce participant burden, for example self-report of dietary intake instead of a blood test [1013]. The effects of measurement errors in exposures and confounder on the performance of different confounder identification criteria are unknown, although insights exist on bias and variability of estimates in such cases, albeit with closed form solutions currently for linear regression only [14]. When measurement error is not known exactly, researchers may still conduct sensitivity analysis to see how choice of confounder identification strategy may bias the results; we illustrate this in the applied example in this paper. There may be a range of plausible measurement errors magnitudes that has negligible influence on confounder identification strategy. It is also important to know that epidemiologists always have some intuition about the accuracy of their tools and are aware that most are imperfect, otherwise they would not be able plan their work at all.
The primary aim of removing cofounding from the estimate of exposure of interest on the outcome is to obtain unbiased estimate of the degree of exposure-outcome association that can be useful in risk assessment. This is indeed the conceptual foundation of CIE approach that proposed cut-offs on the order of 10 % as these were judged to be reflective of what can be reliably inferred in observational epidemiology given limitations of the data. From this perspective, it also acceptable to force all potential covariates into disease model so long as they are suspected as potential confounders and can be ruled out as factors that should not be adjusted for (e.g. mediators, antecedents of exposure alone, etc.) on the basis of theoretical analysis (e.g. implemented via DAG). This is so because if regression-based adjustment has negligible effect on estimate of interest, there is equally no harm in the adjustment so long as the model is not over-fitted. However, there is also virtue in understanding whether there is evidence that a specific factor is a confounder, e.g. in cases where such a factor is “costly” to assess and one is planning future work on a particular topic and wishes to optimize study protocol. In recognition of importance of accurate estimate of causal effects in epidemiology, rather than hypothesis testing, we also consider influence of different confounder-selection strategies on accuracy of the estimate of the exposure-outcome association.
Here, we illustrate a mixed approach for confounder identification utilizing both theoretical and empirical criteria that accounts for the realistic role of measurement error in the exposure and putative confounder, along the lines suggested by Marshall [15]. While using both theoretical and empirical criteria for model selection has been proposed [16], we provide a simulation-based framework that evaluates the performance of various empirical criteria. We also address the issue of confounding by a risk factor by chance in finite sample by proposing a modification on the previously proposed simulation-based CIE approach. Next, we demonstrate the application of CIE criteria in a real-world study of mercury and depressive symptoms, and where theory can be injected into the process to optimize causal inference.
Methods
Empirical confounder identification strategies
Overview
Five strategies were used, namely significance criteria with cutoff levels of p-values fixed at ≤0.05 and 0.2 (in which a putative confounder is adjusted for if the p-value of the t-test of the null hypothesis testing its effect on outcome equals zero is smaller than the cutoff levels), and CIE criterion with three different cutoff levels (fixed a prior at 10 %, with type I error controlled to a desired level, and with type II error controlled to a desired level). The observed change in estimate due to covariate Z is calculated as Δ=|(θ 0 – θ Z )/(θ 0 )|, where θ 0 is the effect estimate of interest not adjusted for suspected confounder Z and θ Z is the effect estimate adjusted for suspected confounder Z. When CIE approach is used, a covariate Z is included in the final model if its inclusion in regression model produces Δ ≥ δ c , where δ c is 0.1 in the 10 % CIE approach, or δ c is determined by simulations as described below. We will describe simulation-based CIE approaches in more detail below, as well as pre-screening aimed to reduce confounding by a risk factor by chance.
Simulation-based change in estimate (CIE) approach
As a way of improving on an empirical approach with criteria fixed a prior, we previously proposed a simulation-informed CIE strategy [5] that performs better in confounder identification and causal effect estimation [17]. In brief, the simulation-informed CIE criterion determines change in the effect estimate of interest that arises when the exposure of interest is adjusted for an independent random variable. With this approach, an independent random variable with the distribution identical to the observed putative confounder is drawn and the causal effect estimates of the exposure and outcome adjusting and not adjusting for this independent random variable are obtained. Next, we record the change-in-estimate that results from adjusting this independent random variable. The above procedure is repeated and the resulting distribution of changes in effect estimates upon adjustment indicates where we need to place a cut-off for the CIE criterion in order to achieve the desired type I error, e.g. for 5 % error the 95 %-percentile of the distribution is used. One can also adopt a CIE criterion with a desired type II error. To do so, one repeatedly simulates a variable with particular correlations with the exposure and outcome, and compares the CIE from models that do and do not adjust for this simulated confounding variable. Using the sth-percentile of the simulated CIEs as a cutoff could yield a type II error of 1-s. In our simulations, we focus on selection of these two CIE cutoffs. In the next section, we describe this procedure in more detail, infusing it with consideration of measurement error.
Screening potential structural confounders
In preliminary investigations, application of simulated CIE approach resulted in an unacceptably high rate (e.g. 50–80 % in some instances) of identification of a risk factor as a structural confounder when it was in fact not correlated with exposure of interest in the population (i.e. by data generating process). We identified correlation of exposure and covariate in finite samples as the culprit of this artifact and developed a screening step that evaluated correlation of exposure and putative confounder before evaluating it further via the five strategies described above. Specifically, only if the hypothesis that the observed exposure and covariate were not correlated was rejected, then the covariate was considered further in the identification of structural confounding. On the other hand, if the hypothesis that the observed exposure and covariate were not correlated was not rejected, then the covariate was excluded from further evaluation in the identification of structural confounding.
Simulation study: overall framework and method of analysis
In specific simulations that we undertook, we assumed that (a) the exposure is associated with the outcome and (b) the putative confounder is indeed a confounder by virtue of its association with both exposure and the outcome (but not the descendant of them). As in many real-life situations, the exposure and confounder are measured with error: for simplicity, we focus on additive classical measurement error models with uncorrelated errors (but our simulation framework can readily be amended to accommodate more complex situations).
The disease model that was considered in our investigation was of the form g(Y) = α + βX + γZ, with g() representing the link function of the generalized linear model, the fixed effects α (background rate or intercept), β (influence of exposure X on outcome Y), and γ (influence of covariate Z on outcome Y). The regression coefficient β is only identical to true value of the effects of interest in linear regression but for logistic and Cox proportional hazard regression, the effects of interest is calculate as relative risk (RR) and hazard ratio (HR), respectively. We denote these true effects of interest as θ for generality.
We assumed that we can only observe realizations of true exposure and confounder with classical additive measurement error models X* = X + ε x and Z* = Z + ε z , the error terms are unbiased and independent of each other. The estimates of regression coefficients β from (Y, X*, Z*) data with and without adjustment for Z* are denoted by β Z * and β 0 *, respectively. These regression coefficients can be used to calculate estimates of the effect of interest θ as θ Z * and θ 0 *, with and without adjustment, respectively; the superscript “*” denotes variables and estimates contaminated by measurement error.
The screening test for Pearson correlation of X* and Z* being different from zero used p≤0.05 cutoff. The datasets where covariates Z were not rejected are evaluated using the simulated CIE cutoff calculated as follows.
The simulated CIE cut-offs in presence of measurement error are determined by comparing effect estimates relating X* to Y with and without adjusting regressions of Y on X* for an independent random variable Z 0 with distribution identical to that of Z* over K simulations. Let us denote such effect estimates, functions of regression coefficient, as θ 0 * k when unadjusted coefficient is used, and as θ Z0 * k when the adjusted coefficient for Z 0 (not the same as adjusted for Z) is used in the kth simulation. Then, the changes in the estimates in each simulation are then calculated, in general, as
$$ {\delta}_k = \Big|\left({\theta}_0{{}^{*}}_k\hbox{--}\ {\theta}_{Z0}{{}^{*}}_k\right)/\left({\theta}_0{{}^{*}}_k\right)\Big| $$
and the qth-percentile of δ k determined over K simulations the cutoff for CIE that would lead to a type I error of 1-q, i.e. δ c . The CIE that is simulated to achieve desired type II error can be obtained in a similar manner, with the independent random variable Z 0 replaced by a random variable correlated with X* and Z* according to the simulation setting (i.e. under the assumption that we guessed correctly the true nature of associations in data-generating process), and the sth percentile of δ determined over K simulations the cutoff for CIE that would lead to a type II error of s. As with all power calculations, this requires an informed guess of the structure we aim to detect and is therefore the more difficult criteria to establish objectively (e.g. we do not know true value of all the correlations from the data contaminated by measurement error) as opposed to the one that strives to control type I error.
Simulation study: the specific scenarios
Our example synthetic data scenario features an outcome Y and three different types of outcome were generated, namely binary (with the disease prevalence at follow-up of 10 %), continuous (with a variance of 1), and survival (with the death rate at follow-up of 10 %). The exposure X and true confounder Z both simulated to follow standard normal distributions, Z is associated with both X (via Pearson correlation ρ ≠ 0) and Y (γ ≠ 0). The binary, continuous, and survival data were generated and fitted using a logistic model (ln(P(Y = 1)/P(Y = 0) = ln(1/9) + βX + γZ)), a linear model (Y = βX + γZ + ε y , ε y ~ N(0, 1)), and a Cox model (survival time ~ exp(βX + γZ-min(βX + γZ)), censored at survival time > 0.1), respectively. The survival times were generated as follows: (1) mean survival time for all subjects equaled βX + γZ, (2) the aforementioned means survival times were linear transformed to make then all positive by subtracting the minimum value of (βX + γZ), (3) the survival time for each subject was generated to follow an exponential distribution with rate parameter equal to mean survival time from step (2), (4) survival times were censored at a value of 0.1 so that the outcome was observed in only 10 % of subjects.
In illustrating the kind of information that this tool can yield, we obtained N = 10,000 simulation realizations of a cohort study (yielding a standard error of 0.5 %) of either n = 500 or 2,000 subjects, with ρ{0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9} and the true causal associations of X-Y and Z-Y with β = γ =0.1, as well as a situation in which exposure of interest is measured with smaller error than or equal to the putative confounder, i.e. ε x ~ N(0, σx2{0.25, 1}) and ε z ~ N(0, σz2{0.25, 1}). We used K = 10,000 to determine simulation-based CIE for each combination of parameters defined a simulation framework above.
In each nth simulation realization (1, …, N), when screening potential confounders, we evaluated Pearson correlation of X* and Z* (ρ n *) and rejected Z* as potential confounder when p-value of the null hypothesis ρ n *= 0 was larger than 0.05. In such instances, final model selected excluded Z*. If Z* remained in contention for role of structural confounder after the screening text, we next estimate the effects of X* on Y in simulated datasets by
• (a) fitting a regression model appropriate for each outcome with X* as an independent variable and Y as the dependent variable (i.e., do not adjust for Z*), resulting in estimate of effect of X on Y as θ 0 * n , which is a function of β 0 * n , and
• (b) fitting a regression model appropriate for each outcome with X* and Z* as independent variables and Y as the dependent variable (i.e., adjust for Z*), resulting in estimate of effect of X* on Y as θZ* n , which is a function of β Z * n .
Effect estimate and p-values resulting from these models of the nth simulation realization are compared and, depending on the confounder selection rule that was triggered, the final estimate of the effect of X on Y in that particular simulated dataset was computed by either model (a) or (b).
We also calculated root mean squared error (RMSE) of effect
$$ \sqrt{{\displaystyle \sum_{n=1}^N{\left({\varphi}_n-\theta \right)}^2/N}} $$
, where in the nth simulation (n {1,…,N}) φ n = θ Z * n if the confounder identification criteria suggested an adjustment, and φ n = θ O * n otherwise; recall that θ is the true value of the effect estimate set by simulation.
All simulations were carried out using R 3.2.0. The R code we provide allows one to test various CIE cutoffs in order to determine the percentage of the simulated datasets correctly identifying Z* as a confounder or effect of X* as significant, as well as RMSE resulting from model selected after application of each confounder-identification strategy (Additional file 1).
Application to study design to clarify role of a confounder in NHANES
We illustrate the application of our approach in an example arising from an earlier analysis of exposure to total blood mercury (E) and depression (D) in 6,911 adults aged ≥40 years in the National Health and Nutrition Examination Survey (NHANES) 2009–2010 [18] approved by The National Center for Health Statistics Research Ethics Review Board; informed consent was obtained from all participants at the time of data collection and further consent for specific analyses of this publically available data is not needed. The dataset can be downloaded at http://wwwn.cdc.gov/Nchs/Nhanes/Search/nhanes09_10.aspx.
Contrary to an expected null association between exposure and outcome, a nonsensical inverse (protective) association was reported and the original investigators argued that this was probably due to measurement error leading to residual confounding by fish consumption (F) [18]. That study assessed the binary recall of fish consumption in the 30 days prior to data collection (F obs ). This variable does not demonstrate statistical properties that support its inclusion as a confounder in the final model because (a) p-value for F obs in the logistic regression model = 0.82, and (b) inclusion of F obs the final models does not affect the observed RRED | Fobs = 0.83 (ORED | Fobs = 0.79) of depression due to mercury to the third decimal place. Nonetheless, it is important to note that our preliminary test for potential confounding would not have rejected F obs from the final model because there is evidence that it is correlated with exposure to mercury, albeit “weakly”: Pearson correlations of 0.39 with mercury exposure (95 % CI 0.37–0.41, p< 0.05). Furthermore, given the established effects of habitual fish consumption F on blood mercury E [19] and depression D [20], Ng et al. [18] suspected that F is a confounder of association of total blood mercury with depression (see Fig. 1 for the DAG of the causal association), and that the pattern of results arose because F obs is a poor measure of unobserved F.
Fig. 1
figure 1
Direct acyclic graph of the causal effect between blood mercury and depression
Let us suppose that in the course of future research we have a particular method of measuring fish consumption (W) with a known degree of measurement error that may prove to be superior to F obs . It is important to note that we do not wish to use F obs in the new research project with the same sample: it yielded what we believe to be confounded estimates and the motivation of new research would be to improve on quality of data to understand the problem better. We need to simulate W because it is not given in the data but is a reflection of what we can hope to obtain in the study that is being planned under the assumption of given causal structure: we can never hope to measure F itself but need to be generate W and thereby evaluate performance of W. We want to know two things: (a) whether W is a confounder of the mercury-depression relationship, and (b) whether models adjusted for this measure of fish consumption W will result in the hypothesized null mercury-depression association (i.e., RRED | W = 1, as opposed to the observed estimate RRED | Fobs = 0.83) Here, W is related to true habitual fish consumption F by classical measurement error: W = F + ε, ε ~ N(0, σ2); F ~ N(0,1); ε is independent of both E and F. To more specifically motivate these assumptions, reflecting on common experience in exposure assessment, we consider that F is a measure of fatty acid intake that is measured by a biomarker and then normalized to Gaussian distribution via log-transformation, hence additive measurement error model for W and distributional assumptions can be appropriate. In practice, such assumptions would be verified in a validation or reliability study.
We assumed that total blood mercury E is near-perfectly measured because a precise analytical technique exists. To simplify, we ignored the matter of etiologically relevant windows of exposure, although this may not be trivial because the biologic half-life of mercury in blood is short.
Based on prior research [18], we also assumed: (a) the association between F and D is based on the correlation of underlying continuous measures of F and D, and set it to ρ FD = −0.35, and (b) that the correlation of F and E is ρ FE = 0.39, same as the observed correlation F obs and E. With these inputs, we simulated true (F) and mis-measured (W) values of fish consumption subjected to different magnitudes of measurement error. Under various conditions of measurement error, we simulate W 10,000 times. Different degrees of error in measured confounder, σ2, were examined. We acknowledge that a different model for confounding could have been postulated and included in our simulation framework but we followed the path deemed as sensible by the original investigators in [18].
To empirically determine whether measured fish consumption (W) would correctly remove confounding from effect of mercury on depression, the proportions of simulated datasets in which the adjusted association of mercury on depression, RRED | W, has p >0.05 were recorded. This is akin to asking how well should we measure confounder in order to have the power to observe true exposure-response association upon adjustment. We also reported the simulation-determined confounder identification criterion described above (i.e. aimed to control type I error at 5 %) to compare it to the conventional CIE of 10 %. Finally, we also determined the average and the 95 % empirical confidence intervals of the estimates of the mercury-depression association with adjustment for simulated values of W based on the 10,000 simulations, in order to determine how well the adjustment for W is able to estimate a specified true causal effect of E-D adjusted for F. (The number of simulations we informed by the observations that it was sufficient to obtain stable behavior of simulation realizations; in every specific situation, a difference size of simulation may be needed.) This reflects a theoretical perspective for confounder identification where based on some pre-determined DAG, W is theoretically a confounder of the exposure-outcome association and should therefore be included in models regardless of measurement properties. To visualize the empirical distribution of RRED | W, we plotted its histogram from the 10,000 simulated estimates with σ2 = 1. The R code for the simulations can be found in the Online Supplementary Materials (Additional file 2).
Results
In the synthetic example, we performed simulations comparing CIE between models that did and did not adjust for the confounder. Results of the simulations are shown in Figs. 2, 3, 4, 5, 6 and 7. The simulations indicated that a change in the estimate of the exposure-outcome relationship of 0.2 % (e.g. Cox model, n = 2,000, σx2 = σz2 = 1, ρ = 0.4) to 7.3 % (linear model, n =500, σx2 = σz2 = 1, ρ = 0.5) between models that do and do not adjust for the confounder is expected to result in type I error 5 % in the studied settings. The control of type II error to 20 % was achieved with simulated CIE on the order of 0.25 % (binary model, n =2,000, σx2 = 0.25, σz2 = 1, ρ = 0.2) to 64 % (linear model, n =2,000, σx2 = 1, σz2 = 0.25, ρ = 0.9). Upon further investigations, we found that the simulation-determined cutoff was very sensitive to measurement error in exposure and potential confounder; there was some tendency for an inverse association between the cutoffs but the clear pattern was only apparent for large error variances (details available upon request). For example, under the scenario of linear regression, n =500, ρ = 0.5, and σz2 = 1, the simulation-determined cutoff with expected type I error of 5 % equaled 3.6 % when σx2 = 0.25 and increased to 7.3 % when σx2 = 1. We also verified that evaluation of p(ρ* = 0) with criteria of 0.05 was important in this setting for controlling false positives. In absence of such a screening test, the rate of Z falsely identified as structural (rather than chance) confounder was commonly on the order of 50–80 % as seen by acceptance of Z* as confounder when in fact ρ = 0 by simulation (details available upon request).
Fig. 2
figure 2
Proportion of analyses that correctly identify a confounder and root mean squared error under different empirical confounder identification strategies in a cohort study (500 subjects with binary outcome)
Fig. 3
figure 3
Proportion of analyses that correctly identify a confounder and root mean squared error under different empirical confounder identification strategies in a cohort study (2000 subjects with binary outcome)
Fig. 4
figure 4
Proportion of analyses that correctly identify a confounder and root mean squared error under different empirical confounder identification strategies in a cohort study (500 subjects with continuous outcome)
Fig. 5
figure 5
Proportion of analyses that correctly identify a confounder and root mean squared error under different empirical confounder identification strategies in a cohort study (2000 subjects with continuous outcome)
Fig. 6
figure 6
Proportion of analyses that correctly identify a confounder and root mean squared error under different empirical confounder identification strategies in a cohort study (500 subjects with survival outcome)
Fig. 7
figure 7
Proportion of analyses that correctly identify a confounder and root mean squared error under different empirical confounder identification strategies in a cohort study (2000 subjects with survival outcome)
Comparison of confounder identification strategies in a synthetic data: identification of structural confounder
Compared with the empirical criteria tested that were fixed a priori (significance criteria with cutoff levels of p-values of 0.05 or 0.20, and CIE criterion with a cutoff of 10 %), the two simulation-determined CIE criterion exhibited superior performance in selecting the correct model within at least 80 % of simulated datasets for exposure-confounder correlation of 0.2 or higher. In contrast, the three traditional methods perform poorly in all three outcome models.
The traditional methods identified a true confounder generally in less than 60 % of the simulated datasets with binary outcomes (logistic regression), even when the cohort size increased from 500 to 2,000 (Figs. 2 and 3, left-hand panels). The gap in performance in cofounder identification was more apparent for smaller cohort (Fig. 2, left-hand panels): 20–40 % drops in power for the stronger simulated confounding with ρ>0.5. Similar gap in performance remained when cohort was increased to 2,000 while measurement error in exposure was fixed at the lower value, and when measurement error in cofounder was greater than that in exposure (Fig. 3, top 2 left-hand panels). However, as both cohort size and measurement error in exposure increased and confounding became stronger (ρ>0.3), a more regular pattern of power was observed: CIE criteria simulated to control type I error had power 70–100 %, CIE criteria simulated to control type II error had power 70–80 %, significance test p<0.20 had power 40–60 %, significance test p<0.05 had power 20–30 %, and 10 % CIE criteria failed to identify structural confounder in almost all instances (Fig. 3, bottom 2 left-hand panels).
In linear regression, the traditional methods were more comparable to simulated-based CIE approaches but their performance depended on strength of confounding and degree of measurement error in a complex fashion. When higher value of error variance in exposure X were examined, all approaches had similar performance in confounder identification for the large cohort of 2000 (Fig. 6, bottom 2 left-hand panels), except that CIE method designed to control type II error to 20 % behaved erratically as strength of confounding increased beyond ρ = 0.3. In smaller cohort size with the same “large” error in exposure (Fig. 5, bottom 2 left-hand panels), however, there was a clear advantage to simulation-based CIE method catered to control type I error to 5 %, especially when cofounding grew stronger: it maintained power of at least 80 % beyond ρ = 0.3 whereas significance testing and CIE cutoff for control of type II error to 20 % were less successful, with power dropping below 80 % as both the strength of confounding (ρ >0.3) and measurement error in confounder increased (Fig. 5, bottom left-hand panel). The divergence in performance of different criteria was the greatest when error in confounder exceeded error in exposure and the cohort size was smaller (e.g. compare Fig. 5, 2nd from top left-hand panel vs. Fig. 5, 2nd from top left-hand panel).
Survival analysis mimicked linear model but deficiency of performance of traditional approaches tended to be greater and, paradoxically, worse with smaller measurement errors for exposure. For example, in survival analysis with cohort size of 2,000 and error variances 0.25 (the smallest tested) and strongest confounding (ρ = 0.9), when simulated CIE criteria correctly included Z as confounder in >80 % of cases, the “significance-testing” approaches had power of 30–60 % only (Fig. 7, top left hand panel). The gap in performance reduced when error variances increased to the largest value tested: 90 % vs. 60–80 % (Fig. 7, bottom left hand panel); it must be noted that the reverse pattern held for the 10 % CIE approach as its power dropped to zero as measurement error increased. It can be observed that when error in confounder increased for this setting, but error in exposure was help constant, the significance criteria suffered greatest loss of performance (from power of 90 % to <40 %) and 10%CIE criterion dropped power from about 60 % to <10 % (Fig. 7, two middle left hand panels). The patterns in smaller cohort of 500 were similar (Fig. 6).
Comparison of confounder identification strategies in a synthetic data: precision
The simulation-determined CIE criterion achieved the smallest RMSE in all survival analyses (Figs. 6 and 7, right hand panels). In linear models, the pattern was complex. For the smaller cohort size, simulation-based CIE approaches led to smaller RMSE only when error in exposure measurement was at the lower tested value (Fig. 4, two upper right hand panels), otherwise, the significance testing approached yielded smaller RMSE (Fig. 4, two bottom right hand panels). For a larger cohort, linear model built using simulation based CIE tended to be associated with lower RMSE (Fig. 5, right hand panels). In logistic regression, simulation-based CIE approaches also tended to produce larger RMSE for the smaller of the tested cohort (Fig. 2, right hand panels), with the 10 % CIE criteria leading to the lowest RMSE across varying degrees of confounding (Fig. 2, bottom right hand panel). When a large cohort was considered in logistic regression analysis, the simulation-based approaches had lower RMSE when measurement error in exposure was fixed at a smaller value only (Fig. 3, right hand panels), just like in the linear model.
Larger degree of measurement error tended to produce lower RMSE values (e.g. survival analysis, Figs. 6 and 7, right hand panels), possibly indicating clustering of estimates around attenuated effect estimate and conveying false certainty in the effect estimate under measurement error. There was also a tendency for RMSE to increase with the degree of cofounding in most studied settings (Figs. 2, 3, 6 and 7, right hand panels) However, the RMSE deceased with the exposure-confounder correlation in linear models, when the measurement errors of exposure and confounder were both “large” (i.e. set at 1) (Figs. 4 and 5, bottom right hand panels). On the other hand, when measurement errors are smaller, in linear model there is an increase in RMSE with the strength of confounding (Figs. 4 and 5, top 3 right hand panels) as in other models.
Influence on power of excluding a true confounder by the screening procedure
We can expect the screening of correlation of potential confounder and exposure by means of testing correlation between them to erode power: observed correlation in a sample can be very weak and imprecisely estimated even when there is true correlation in the population. This can be expected to most serious in small sample sizes and for weak true correlations. We examined this issue by examining loss of power due to the screening procedure in the case of n = 500 (small sample size in our simulation). We noted that our screening procedure excluded variables with little correlation (ρ≤ 0.1 for σx2 = σz2 = 0.25, and ρ≤ 0.2 for σx2 = σz2 = 1) with the exposure, and for ρ >0.3 these variables were nearly never being excluded (Fig. 8). When confounding was weak, the loss of power was more apparent. Thus, there appeared to be observable loss of power only for the weakest strength of confounding and when error variances are large.
Fig. 8
figure 8
The change in the proportion of analyses that excluded a confounder due to the proposed screening procedure under different empirical confounder identification strategies in a cohort study (500 subjects) under varying degrees of measurement error
Application to the mercury, fish consumption, and depression example
As the degree of measurement error in the confounder increases, there is a precipitous drop in the proportion of analyses that would correctly suggest a null association (i.e. p > 0.05) of total blood mercury with depression (Table 1). If the noise-to-signal ratio (error variance in confounder (σ2)/variance of confounder) is at or below about half, roughly 80 % of the simulated analyses adjusting for fish consumption would correctly result in a null association of mercury and depression. We also observed that for the most part, if the confounder is forcibly adjusted for (as can be expected when a DAG confounder identification strategy is used) even while measured imperfectly, the effect estimates are noticeably much less confounded (i.e., RR closer to 1) as compared to the unadjusted RR of 0.83. Only when the noise-to-signal ratio is 1 or larger does adjusting for the miss-measured confounder make little to no difference. In other words only an extremely poorly measured confounder is not useful to adjust for in this setting.
Table 1 The proportion of 10,000 simulated adjusted analyses where a hypothesized null exposure-outcome association (RRED|W) is indicated, after adjustment for a confounder W that is measured with different degrees of measurement error (Simulated change-in-estimate cutoff for Type I error <0.05 = 0.06 %)
If we do not have sufficient knowledge to guide a theory-based confounder selection strategy, application of model selection cutoffs may be useful. In this specific setting, a simulation-derived CIE cutoff was small (0.06 %). If such a strategy is adopted, for the observed RR = 0.83 a change of 0.1 % after adjustment for W identifies it as a confounder, even though one can question whether such a small change is discernible from background noise in realistic applications. The degree to which it is important to remove such a degree of confounding depends on the specific application and can range from immaterial to important depending on the association of interest and the role it plays in whatever action is taken on the basis of effect estimation. However, it is clear that the CIE of 10 % is too coarse to detect confounding in this setting with the desired certainty.
Figure 9 shows the empirical distribution of the adjusted RR for the noise-to-signal ratio of 1 (median 0.909, inter-quartile range 0.905–0.914). We can see that we expect all estimates to be closer to null than the naïve and can therefore take the observed effects of that size to support the hypothesis that an apparent mercury-depression association is due to confounding by fish intake. Thus, even if residual confounding is not eliminated after adjusting for a mis-measured confounder, we can still determine whether evidence supports its role as a confounder. This clearly argues for a much more liberal rule for evaluating evidence for confounding, based on statistical grounds alone in the given motivating example, in the presence of measurement error in confounder, than is permitted by the 10 % CIE criteria. It also illustrates the peril of reliance on hypothesis testing: we do not expect to find a statistically significant effect of fish intake in the example illustrated in Fig. 9 and yet all “imperfectly” adjusted point estimates of RR are expected to be less biased than the crude value. This further argues for forcing a variable into a model if there is a theoretical reason to do so, regardless of whether a frequentist hypothesis test indicated an association.
Fig. 9
figure 9
Anticipated estimates of the exposure-outcome association in the motivating example (see text for details) after adjustment for a miss-measured confounder when there is not a true exposure-outcome association. The unadjusted RR ED|Fobs is 0.83 (i.e. confounded; indicated by the arrow), noise-to-signal ratio is 1 and all effects of confounder are expected to be not statistically significant (p >0.05); 10,000 simulations
Discussion
Overview of findings
Our study provides a framework that evaluates the performance of various empirical criteria with considerations of strength of causal and confounding effects, sample size, measurement errors in exposure and confounder, and types of outcomes. This framework is useful for study design and planning. During the stage of study design, researchers often need to choose, among many options, the tools for measuring the exposures and confounders. For example, they can choose among self-report or objectively-measured BMI, physical activity level, and dietary intake. Using the existing results from validation studies [1013], researchers can make use of our framework to choose the most appropriate measurement tools that maintain a balance between the error of causal effect estimation and the total cost induced.
We were also successful in proposing a solution to the problem of false positive identification of risk factor as confounder in a finite sample. A simple evaluation of correlation between exposure and potential covariate achieved nearly perfect power. We emphasize that this is finite-sample problem that arises due to chance correlation, induced by the fact that X and Z are both related to Y, inducing a chance X-Z association via Y that had a tangible impact (i.e. on the order of simulated CIE cutoff) on estimate of effect of X on Y upon inclusion of Z in a regression model. This phenomenon disappeared when sample size was boosted and worsened in finite samples with large values of β Z (details available on request). Even if Z is not identified as structural confounder, there is a good reason to include it in the final estimate to remove as much as possible confounding from the estimate of effect of X, however, in doing so, the understanding of problem under study is increased by gaining evidence for chance versus structural confounding by Z.
In practice, epidemiologists that use DAG to identify confounders try to distinguish between several plausible DAGs: this lies at the heart of confounder identification problem. However, all assumptions about plausible DAGs made by investigators can be wrong such that any choice among alternative causal structures does not reflect the true state of nature. Our work does not address such situation but it would be important to consider such a possibility in any truly improved approach to selection of confounder identification method; we believe that this is possible via simulations in a specific setting and allude to this in presentation of empirical example elaborated in this paper.
Given the complexity of factors that influence selection of confounder identification approach and tools even in our relatively simple settings, a practical approach is to customize simulations to reflect uncertainties about causal structures and imperfections of data when making such choices instead of reply on any a priori advice. Previous simulation studies showed that a priori advices such as significance criteria and 10 % CIE may lead to wrong decision of confounder adjustment when the exposure variable is error prone [21]. While a simulation-derived CIE criterion would change for every data situation, our study indicates that using simulations to inform model selection is both feasible and desirable during the study-planning stage, using information that most investigators possess: the knowledge of quality of instruments measuring exposure and confounders, as well as plausible strengths of the associations. It must be emphasized that we propose a solution to a problem that is sensitive to each specific application and, as such, our method is guaranteed to out-perform any general advice such as 10 % CIE, unless, by chance, simulation-based CIE are identical to 10 %, in which case our method will have identical performance relative to the general advice.
Interpretations of findings from analysis of simulated studies
Despite complexities of patters of our results, they seem to exhibit several general tendencies. As the strength of confounding increases, the chance of identifying confounder, when present, also grows across constellations of measurement error, type of outcome and sample size, implying that all confounder identification strategies tend to perform better in picking up stronger effects. Most of our findings were consistent across different outcome types.
With respect to precision of the exposure-outcome association as measured by RMSE, there appear to two competing phenomena. As measurement error of the exposure increases, under the postulated classical measurement error model, for all regression coefficients to be attenuated towards null [7], such that whether an estimate is corrected for confounder or not would make little difference to its attenuated value that tends towards the null and a poorly-measured confounder would do little to remove true confounding in regression model. This would have the net effect of the RMSE to become independent of the strength of confounding or confounder-identification strategy. This is also indeed the case of real data example with confounder (fish consumption) very poorly measured. On the other hand, when measurement error is moderate (i.e. not so strong as to push estimate of the effect of exposure nearly to the null and to make any adjustment inconsequential to its magnitude), RMSE tends to decrease with superior confounder-identification strategy, i.e. correctly specifying the outcome model has tangible benefits. Unsurprisingly, RMSE is smaller for weaker confounding where there are fewer penalties for failing to adjust for confounder. These influence of RMSE create a rotation in RMSE versus the strength of confounding curves such that it may appear that RMSE declines with the strength of confounding with the rise of measurement errors, whereas in fact all we witness is the tendency for RMSE to become independent of measurement begin to dominate the tendency for RMSE to be larger when confounding is stronger.
The RMSE has to be interpreted with cautions, as it is a combination of squared bias and standard error of the causal effect estimate. In logistic regression (n = 2,000) with the largest examined measurement errors, 10 % CIE criteria leads to the smallest RMSE for strong confounding but it is essential to note that this is based almost exclusively on unadjusted estimates because confounder was almost never included in the final model (Fig. 3). We hypothesized that this phenomenon is due to the fact that with a poorly-measured exposure we expect the estimated causal effect would be zero (i.e., an RR of 1). The low RMSE in this case is the result of tight clustering of unadjusted attenuated estimates around wrong value of the effect estimate, a phenomenon that was previously described in theoretical work [14] that leads to over-confidence in wrong estimates in presence of measurement error. Another tendency that is acting on the observed RMSE is due to the fact that when exposure-confounder correlation increases, the standard errors of the maximum likelihood estimate of adjusted causal effect also increases, leading to the increase of RMSE.
We present two types of simulated CIE criteria: designed to control either type I or II errors. When the cutoff values of the two criteria are similar, we are in the fortunate situation where both types of error are controlled to the desired degree. In the synthetic examples that we evaluated, there appears to be little difference in RMSE for the two simulation-based CIE approaches. The two approaches diverged in success in confounder identification per se, but both outperformed significance testing and fixed cutoff of 10 % CIE.
Depression-mercury-fish consumption example
The real data analysis of the NHANES data illustrated how researchers can make use of our framework to choose the most appropriate measurement tools that maintain a balance between the error of causal effect estimation and the total cost induced. By applying our framework, information about the degree of accuracy, validity, or measurement error one needs to achieve in order to obtain a less biased estimate of the causal relationship. For instance, our simulation result informs us that a noise-to-signal ratio of 0.5 or smaller for the variable fish consumption is desirable when we wish to estimate the causal relationship between total blood mercury and depression. In planning such an analysis, in the planning stage researchers should avoid using measurement tools that are only weakly correlated with the true nutrient intake, for example food-frequency questionnaire [10].
The real data analysis is founded on the assumption that here is no reason for exposure to mercury to be protective of risk of depression and therefore cofounding by fish consumption, known to be protective, is suspected. Of course one can assume that there is a small positive effect of mercury that is reversed by stronger negative confounding by fish consumption. One can repeat our simulations in such a way that mercury would have a causal risk factor, e.g. by weakening correlation of mercury with fish consumption or assuming weaker beneficial effect of fish consumption on the outcome. We did not explore this possibility in order to limit future considerations of plausible continuation of work in this setting as discussed in [18].
Limitations
A major limitation of our study is that we considered a limited number of scenarios. If the assumptions of our simulations were violated, for example if the model is mis-specified, or if the errors do not follow normal distribution, the conclusions will be altered. Ideally, readers interested in implementing our approach should consider the validity of these assumptions and implement necessary modification to our R code. Another limitation is that the associations between exposure, confounder, and outcome maybe unknown. We believe it is possible (and desirable) to conduct analyses while acknowledging partial knowledge about causal structures, measurement error and exposure misclassification (e.g. using Bayesian framework [14, 22]): this may prove to be a promising extension to our work.
Another limitation is that we did not evaluate our framework under multiple confounders but this can be done in practice by slight modification of our R code. On the other hand, conceptually, one confounder may stand for multiple confounders that do not cancel each other out (e.g. see [8]), so our approach with one confounder should retain some generalizability.
One can argue that when measurement error is present, suitable analytical approach, for example regression calibration [23, 24] or simulation and extrapolation (SIMEX [25]), should be applied to remove its influence from inference before engaging in the discussion of suitable confounder identification strategy. This is certainly a sensible approach and the one that, to the extent possible, should be advocated. However, we wish to point out that measurement error correction is not routinely practiced by epidemiologists [26] and until such time that this changes, it is still relevant to consider how the historically and currently acceptable analytical strategies for model-building perform in practice.
Conclusions
The impact of measurement error in a putative confounder on the selection of a correct disease model and testing of presence of confounding can be complex and difficult to predict in general. However, targeted investigations into how well one has to measure the confounder and how to interpret data contaminated by residual confounding are possible. They can inform and motivate work on better efforts to quantify risk factors and can help gauge the added value of such work. If an investigator plans to use regression methods to control for confounding and to empirically select among all plausible confounders the subset that can be evaluated with the data they are advised to determine what CIE criteria are most suitable in their situation [5]. While use of causal diagrams is certainly helpful in guarding against most egregious mistakes in model specification, causal diagrams may be incorrect or the putative confounder may have so much measurement error as to be entirely useless for adjustment purposes. Likewise, statistical considerations alone do not guaranteed selection of correct model. Therefore, one has to triangulate confounding using all available knowledge and tools [15].
We conclude by emphasizing that no a prior criterion developed for a specific application is guaranteed to be suitable for confounder identification in general. The customization of model-building strategies and study designs through simulations that consider the likely imperfections in the data would constitute an important improvement on some of the currently prevailing practices in confounder identification and evaluation.
Ethics approval and consent to participate
NHANES 2009–2010 was approved by The National Center for Health Statistics Research Ethics Review Board; informed consent was obtained from all participants at the time of data collection and further consent for specific analyses of this publically available data is not needed.
Availability of data and materials
The NHANES 2009–2010 dataset can be downloaded at http://wwwn.cdc.gov/Nchs/Nhanes/Search/nhanes09_10.aspx.
References
1. VanderWeele TJ, Shpitser I. A new criterion for confounder selection. Biometrics. 2011;67(4):1406–13.
Article PubMed PubMed Central Google Scholar
2. Shahar E. A new criterion for confounder selection? Neither a confounder nor science. J Eval Clin Pract. 2013;19(5):984–6.
PubMed Google Scholar
3. Mickey RM, Greenland S. The impact of confounder selection criteria on effect estimation. Am J Epidemiol. 1989;129:125–37.
Article CAS PubMed Google Scholar
4. Maldonado G, Greenland S. Simulation study of confounder-selection strategies. Am J Epidemiol. 1993;138(11):923–36.
Article CAS PubMed Google Scholar
5. Lee PH. Is the cutoff of 10 % appropriate for the change-in-estimate confounder identification criterion? J Epidemiol. 2014;24(2):161–7.
Article PubMed PubMed Central Google Scholar
6. Bliss R, Weinberg J, Webster T, Vieira V. Determining the probability distribution and evaluating sensitivity and false positive rate of a confounder detection method applied to logistic regression. J Biom Biostat. 2012;3(4):142.
Article PubMed PubMed Central Google Scholar
7. Fewell Z, Davey Smith G, Sterne JA. The impact of residual and unmeasured confounding in epidemiologic studies: a simulation study. Am J Epidemiol. 2007;166(6):646–55.
Article PubMed Google Scholar
8. Gustafson P, McCandless LC. Probabilistic approaches to better quantifying the results of epidemiologic studies. Int J Environ Res Public Health. 2010;7(4):1520–39.
Article PubMed PubMed Central Google Scholar
9. McCandless LC, Gustafson P, Levy AR. A sensitivity analysis using information about measured confounders yielded improved uncertainty assessments for unmeasured confounding. J Clin Epidemiol. 2008;61(3):247–55.
Article PubMed Google Scholar
10. Brunner E, Stallone D, Juneja M, Bingham S, Marmot M. Dietary assessment in Whitehall II: Comparison of 7 days diet diary and food-frequency questionnaire and validity against biomarkers. Br J Nutr. 2001;86(3):405–14.
Article CAS PubMed Google Scholar
11. Lee PH, Macfarlane DJ, Lam TH, Stewart SM. Validity of International Physical Activity Questionnaire Short Form (IPAQ-SF): A systematic review. Int J Behav Nutr Phys Act. 2011;8:115.
Article PubMed PubMed Central Google Scholar
12. Spencer EA, Appleby PN, Davey GK, Key TJ. Validity of self-reported height and weight in 4808 EPIC-Oxford participants. Public Health Nutr. 2002;5(4):561–5.
Article PubMed Google Scholar
13. Van Poppel MNM, Chinapaw MJM, Mokkink LB, Van Mechelen W, Terwee CB. Physical activity questionnaires for adults: A systematic review of measurement properties. Sports Med. 2010;40:565–600.
Article PubMed Google Scholar
14. Gustafson P. Measurement Error and Misclassification in Statistics and Epidemiology. London: Chapman & Hall/CRC Press; 2004.
15. Marshall J. Invited commentary: Fewell and colleagues - Fuel for debate. Am J Epidemiol. 2007;166(6):656–8.
Article PubMed Google Scholar
16. Evans D, Chaix B, Lobbedez T, Verger C, Flahault A. Combining directed acyclic graphs and the change-in-estimate procedure as a novel approach to adjustment-variable selection in epidemiology. BMC Med Res Methodol. 2012;12:156.
Article PubMed PubMed Central Google Scholar
17. Lee PH. Should we adjust for a confounder if empirical and theoretical criteria yield contradictory results? A simulation study. Sci Rep. 2014;4:6085.
CAS PubMed Google Scholar
18. Ng THH, Mossey JM, Lee BK. Total blood mercury levels and depression among adults in the United States: National Health and Nutrition Examination Survey 2005–2008. PLoS One. 2013;8(11):e79339.
Article CAS PubMed PubMed Central Google Scholar
19. Choi AL, Cordier S, Weihe P, Grandjean P. Negative confounding in the evaluation of toxicity: the case of methylmercury in fish and seafood. Crit Rev Toxicol. 2008;38(10):877–93.
Article CAS PubMed PubMed Central Google Scholar
20. Akbaraly TN, Brunner EJ, Ferrie JE, Marmot MG, Kivimaki M, Singh-Manoux A. Dietary pattern and depressive symptoms in middle age. Brit J Psychiatry. 2009;195(5):408–13.
Article Google Scholar
21. Budtz-Jørgensen E, Keiding N, Grandjean P, Weihe P, White RF. Consequences of exposure measurement error for confounder identification in environmental epidemiology. Stat Med. 2003;22:3089–100.
Article PubMed Google Scholar
22. Gustafson P, Greenland S. Curious phenomena in Bayesian adjustment for exposure misclassification. Stat Med. 2006;25:87–103.
Article PubMed Google Scholar
23. Carroll RJ, Ruppert D, Stefanski LA, Crainiceanu CM: Measurement Error in Nonlinear Models. London: Chapman & Hall/CRC; 2006.
24. Cheng CL, Van Ness JW. Statistical Regression with Measurement Error. London: Arnold; 1999.
Google Scholar
25. Küchenhoff H, Mwalili SM, Lesaffre E. A general method for dealing with misclassification in regression: the misclassification SIMEX. Biometrics. 2006;62(1):85–96.
Article PubMed Google Scholar
26. Jurek AM, Maldonado G, Greenland S, Church TR. Exposure-measurement error is frequently ignored when interpreting epidemiologic study results. Eur J Epidemiol. 2006;21(12):871–6.
Article PubMed Google Scholar
Download references
Acknowledgements
Dr Brian Lee was instrumental in application of our methods to the illustrative example and provided numerous valuable comments during development of the manuscript. The authors are very thankful to Drs Jay Kaufman and George Maldonado for their candid reviews of early draft of this manuscript. The authors did our best to improve our work and take full responsibility for the remaining deficiencies. The authors received no funding for this study, and disclose no conflict of interest.
Funding
None.
Author information
Authors and Affiliations
Authors
Corresponding author
Correspondence to Paul H. Lee.
Additional information
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
PHL designed the study, carried out the simulations, and drafted the manuscript. IB conceived the study and drafted the manuscript. Both authors read and approved the final manuscript.
Additional files
Additional file 1:
R code for simulation study. (ZIP 8 kb)
Additional file 2:
R code for analysis of real data. (TXT 5 kb)
Rights and permissions
Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Reprints and Permissions
About this article
Check for updates. Verify currency and authenticity via CrossMark
Cite this article
Lee, P.H., Burstyn, I. Identification of confounder in epidemiologic data contaminated by measurement error in covariates. BMC Med Res Methodol 16, 54 (2016). https://doi.org/10.1186/s12874-016-0159-6
Download citation
• Received:
• Accepted:
• Published:
• DOI: https://doi.org/10.1186/s12874-016-0159-6
Keywords
|
{
"url": "https://bmcmedresmethodol.biomedcentral.com/articles/10.1186/s12874-016-0159-6",
"source_domain": "bmcmedresmethodol.biomedcentral.com",
"snapshot_id": "CC-MAIN-2023-50",
"warc_metadata": {
"Content-Length": "401520",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:2QG7SBNPLJHAKJ4RNR27BJK2AOD4SDPD",
"WARC-Concurrent-To": "<urn:uuid:41c7687d-6194-4d0e-a0ab-49504575dd41>",
"WARC-Date": "2023-12-04T01:09:25",
"WARC-IP-Address": "146.75.32.95",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:RDGO3AUALGUGVF4Q4W275KTMANP3VWTX",
"WARC-Record-ID": "<urn:uuid:208ffc1c-0954-4144-9eb6-c87d686cc83b>",
"WARC-Target-URI": "https://bmcmedresmethodol.biomedcentral.com/articles/10.1186/s12874-016-0159-6",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:53de4268-d975-4f73-b5dd-ce260afe9280>"
},
"warc_info": "isPartOf: CC-MAIN-2023-50\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for November/December 2023\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-56\r\nsoftware: Apache Nutch 1.19 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.5-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
21,
22,
121,
122,
131,
132,
143,
144,
530,
531,
539,
540,
1603,
1604,
1612,
1613,
2137,
2138,
2150,
2151,
2585,
2586,
2606,
2607,
2618,
2619,
3424,
3425,
5718,
5719,
7174,
7175,
8464,
8465,
9940,
9941,
10761,
10762,
10770,
10771,
10818,
10819,
10828,
10829,
11923,
11924,
11975,
11976,
13598,
13599,
13642,
13643,
14649,
14650,
14709,
14710,
15247,
15248,
15881,
15882,
16493,
16494,
16714,
16715,
17318,
17319,
17450,
17451,
18377,
18378,
18419,
18420,
19661,
19662,
20296,
20297,
20749,
20750,
21003,
21004,
21250,
21251,
21544,
21545,
21605,
21606,
21686,
21687,
21915,
21916,
22289,
22290,
22360,
22361,
22971,
22972,
24394,
24395,
24402,
24411,
24412,
24491,
24492,
26165,
26166,
26454,
26455,
27237,
27238,
28888,
28889,
28897,
28898,
30577,
30578,
30585,
30594,
30595,
30799,
30800,
30807,
30816,
30817,
31022,
31023,
31030,
31039,
31040,
31248,
31249,
31256,
31265,
31266,
31475,
31476,
31483,
31492,
31493,
31699,
31700,
31707,
31716,
31717,
31924,
31925,
32037,
32038,
32510,
32511,
33692,
33693,
35051,
35052,
36210,
36211,
36293,
36294,
37427,
37428,
38271,
38272,
38349,
38350,
39287,
39288,
39295,
39304,
39305,
39552,
39553,
39622,
39623,
40664,
40665,
40971,
40972,
41851,
41852,
43136,
43137,
43144,
43153,
43154,
43577,
43578,
43589,
43590,
43611,
43612,
44422,
44423,
45481,
45482,
46173,
46174,
47453,
47454,
47517,
47518,
47976,
47977,
49604,
49605,
50762,
50763,
51298,
51299,
51343,
51344,
52227,
52228,
52970,
52971,
52983,
52984,
53782,
53783,
54148,
54149,
54858,
54859,
54871,
54872,
56066,
56067,
56497,
56498,
56541,
56542,
56821,
56822,
56857,
56858,
56965,
56966,
56977,
56978,
57085,
57086,
57139,
57140,
57268,
57269,
57297,
57298,
57426,
57427,
57469,
57470,
57591,
57592,
57634,
57635,
57777,
57778,
57831,
57832,
58067,
58068,
58121,
58122,
58295,
58296,
58333,
58334,
58504,
58505,
58558,
58559,
58775,
58776,
58813,
58814,
59038,
59039,
59081,
59082,
59271,
59272,
59325,
59326,
59489,
59490,
59527,
59528,
59724,
59725,
59762,
59763,
59894,
59895,
60009,
60010,
60047,
60048,
60282,
60283,
60336,
60337,
60494,
60495,
60528,
60529,
60728,
60729,
60787,
60788,
60973,
60974,
61032,
61033,
61208,
61209,
61238,
61239,
61439,
61440,
61477,
61478,
61609,
61610,
61647,
61648,
61780,
61781,
61879,
61880,
61900,
61901,
62071,
62072,
62109,
62110,
62295,
62296,
62333,
62334,
62354,
62355,
62372,
62373,
62861,
62862,
62870,
62871,
62877,
62878,
62897,
62898,
62923,
62924,
62932,
62933,
62954,
62955,
62986,
62987,
63010,
63011,
63031,
63032,
63091,
63092,
63115,
63116,
63301,
63302,
63319,
63320,
63339,
63340,
63380,
63381,
63400,
63401,
63446,
63447,
63470,
63471,
64058,
64059,
64084,
64085,
64104,
64105,
64171,
64172,
64190,
64191,
64392,
64393,
64411,
64412,
64426,
64427,
64441,
64442,
64457,
64458,
64509,
64510
],
"line_end_idx": [
21,
22,
121,
122,
131,
132,
143,
144,
530,
531,
539,
540,
1603,
1604,
1612,
1613,
2137,
2138,
2150,
2151,
2585,
2586,
2606,
2607,
2618,
2619,
3424,
3425,
5718,
5719,
7174,
7175,
8464,
8465,
9940,
9941,
10761,
10762,
10770,
10771,
10818,
10819,
10828,
10829,
11923,
11924,
11975,
11976,
13598,
13599,
13642,
13643,
14649,
14650,
14709,
14710,
15247,
15248,
15881,
15882,
16493,
16494,
16714,
16715,
17318,
17319,
17450,
17451,
18377,
18378,
18419,
18420,
19661,
19662,
20296,
20297,
20749,
20750,
21003,
21004,
21250,
21251,
21544,
21545,
21605,
21606,
21686,
21687,
21915,
21916,
22289,
22290,
22360,
22361,
22971,
22972,
24394,
24395,
24402,
24411,
24412,
24491,
24492,
26165,
26166,
26454,
26455,
27237,
27238,
28888,
28889,
28897,
28898,
30577,
30578,
30585,
30594,
30595,
30799,
30800,
30807,
30816,
30817,
31022,
31023,
31030,
31039,
31040,
31248,
31249,
31256,
31265,
31266,
31475,
31476,
31483,
31492,
31493,
31699,
31700,
31707,
31716,
31717,
31924,
31925,
32037,
32038,
32510,
32511,
33692,
33693,
35051,
35052,
36210,
36211,
36293,
36294,
37427,
37428,
38271,
38272,
38349,
38350,
39287,
39288,
39295,
39304,
39305,
39552,
39553,
39622,
39623,
40664,
40665,
40971,
40972,
41851,
41852,
43136,
43137,
43144,
43153,
43154,
43577,
43578,
43589,
43590,
43611,
43612,
44422,
44423,
45481,
45482,
46173,
46174,
47453,
47454,
47517,
47518,
47976,
47977,
49604,
49605,
50762,
50763,
51298,
51299,
51343,
51344,
52227,
52228,
52970,
52971,
52983,
52984,
53782,
53783,
54148,
54149,
54858,
54859,
54871,
54872,
56066,
56067,
56497,
56498,
56541,
56542,
56821,
56822,
56857,
56858,
56965,
56966,
56977,
56978,
57085,
57086,
57139,
57140,
57268,
57269,
57297,
57298,
57426,
57427,
57469,
57470,
57591,
57592,
57634,
57635,
57777,
57778,
57831,
57832,
58067,
58068,
58121,
58122,
58295,
58296,
58333,
58334,
58504,
58505,
58558,
58559,
58775,
58776,
58813,
58814,
59038,
59039,
59081,
59082,
59271,
59272,
59325,
59326,
59489,
59490,
59527,
59528,
59724,
59725,
59762,
59763,
59894,
59895,
60009,
60010,
60047,
60048,
60282,
60283,
60336,
60337,
60494,
60495,
60528,
60529,
60728,
60729,
60787,
60788,
60973,
60974,
61032,
61033,
61208,
61209,
61238,
61239,
61439,
61440,
61477,
61478,
61609,
61610,
61647,
61648,
61780,
61781,
61879,
61880,
61900,
61901,
62071,
62072,
62109,
62110,
62295,
62296,
62333,
62334,
62354,
62355,
62372,
62373,
62861,
62862,
62870,
62871,
62877,
62878,
62897,
62898,
62923,
62924,
62932,
62933,
62954,
62955,
62986,
62987,
63010,
63011,
63031,
63032,
63091,
63092,
63115,
63116,
63301,
63302,
63319,
63320,
63339,
63340,
63380,
63381,
63400,
63401,
63446,
63447,
63470,
63471,
64058,
64059,
64084,
64085,
64104,
64105,
64171,
64172,
64190,
64191,
64392,
64393,
64411,
64412,
64426,
64427,
64441,
64442,
64457,
64458,
64509,
64510,
64518
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 64518,
"ccnet_original_nlines": 401,
"rps_doc_curly_bracket": 0.0007439799956046045,
"rps_doc_ldnoobw_words": 1,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.346589058637619,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.03637244924902916,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.21621403098106384,
"rps_doc_frac_unique_words": 0.17984448373317719,
"rps_doc_mean_word_length": 5.23366641998291,
"rps_doc_num_sentences": 595,
"rps_doc_symbol_to_word_ratio": 0.00016166000568773597,
"rps_doc_unigram_entropy": 6.117147922515869,
"rps_doc_word_count": 9903,
"rps_doc_frac_chars_dupe_10grams": 0.0761156901717186,
"rps_doc_frac_chars_dupe_5grams": 0.14241062104701996,
"rps_doc_frac_chars_dupe_6grams": 0.11746320128440857,
"rps_doc_frac_chars_dupe_7grams": 0.09556426107883453,
"rps_doc_frac_chars_dupe_8grams": 0.08381407707929611,
"rps_doc_frac_chars_dupe_9grams": 0.08325455337762833,
"rps_doc_frac_chars_top_2gram": 0.0050165001302957535,
"rps_doc_frac_chars_top_3gram": 0.005904030054807663,
"rps_doc_frac_chars_top_4gram": 0.006251330021768808,
"rps_doc_books_importance": -6131.87744140625,
"rps_doc_books_importance_length_correction": -6131.87744140625,
"rps_doc_openwebtext_importance": -3135.922119140625,
"rps_doc_openwebtext_importance_length_correction": -3135.922119140625,
"rps_doc_wikipedia_importance": -2603.821044921875,
"rps_doc_wikipedia_importance_length_correction": -2603.821044921875
},
"fasttext": {
"dclm": 0.02015089988708496,
"english": 0.9162774085998535,
"fineweb_edu_approx": 2.357853412628174,
"eai_general_math": 0.9784859418869019,
"eai_open_web_math": 0.7049341201782227,
"eai_web_code": 0.6135024428367615
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "614.4",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Public health"
}
},
"secondary": {
"code": "519.5",
"labels": {
"level_1": "Science and Natural history",
"level_2": "Mathematics",
"level_3": "Probabilities; or, Mathematical statistics"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "4",
"label": "Analyze"
},
"secondary": {
"code": "5",
"label": "Evaluate"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "2",
"label": "Academic/Research"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "3",
"label": "Irrelevant Content"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "4",
"label": "Missing Images or Figures"
}
},
"document_type_v2": {
"primary": {
"code": "3",
"label": "Academic Writing"
},
"secondary": {
"code": "8",
"label": "Documentation"
}
},
"reasoning_depth": {
"primary": {
"code": "4",
"label": "Advanced Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "4",
"label": "Graduate/Expert Level"
},
"secondary": {
"code": "3",
"label": "Undergraduate Level"
}
}
}
|
1a01aa77535b9ecfb87b9fc36adbcd2f
|
2,083,881,592,219,455,000
|
What to do to keep Yourself and others safe from COVID-19
times24live.com
World Health Organization
What to do to keep yourself and others safe from COVID-19
• Maintain at least a 1-metre distance between yourself and others to reduce your risk of infection when they cough, sneeze or speak. Maintain an even greater distance between yourself and others when indoors. The further away, the better.
• Make wearing a mask a normal part of being around other people. The appropriate use, storage and cleaning or disposal are essential to make masks as effective as possible.
Here are the basics of how to wear a mask:
• Clean your hands before you put your mask on, as well as before and after you take it off, and after you touch it at any time.
• Make sure it covers both your nose, mouth and chin.
• When you take off a mask, store it in a clean plastic bag, and every day either wash it if it’s a fabric mask, or dispose of a medical mask in a trash bin.
• Don’t use masks with valves.
How to make your environment safer
• Avoid the 3Cs: spaces that are closed, crowded or involve close contact.
• Outbreaks have been reported in restaurants, choir practices, fitness classes, nightclubs, offices and places of worship where people have gathered, often in crowded indoor settings where they talk loudly, shout, breathe heavily or sing.
• The risks of getting COVID-19 are higher in crowded and inadequately ventilated spaces where infected people spend long periods of time together in close proximity. These environments are where the virus appears to spread by respiratory droplets or aerosols more efficiently, so taking precautions is even more important.
• Meet people outside. Outdoor gatherings are safer than indoor ones, particularly if indoor spaces are small and without outdoor air coming in.
• Avoid crowded or indoor settings but if you can’t, then take precautions:
• Open a window. Increase the amount of ‘natural ventilation’ when indoors.
• WHO has published Q&As on ventilation and air conditioning for both the general public and people who manage public spaces and buildings.
• Wear a mask (see above for more details).
Don’t forget the basics of good hygiene
• Regularly and thoroughly clean your hands with an alcohol-based hand rub or wash them with soap and water. This eliminates germs including viruses that may be on your hands.
• Avoid touching your eyes, nose and mouth. Hands touch many surfaces and can pick up viruses. Once contaminated, hands can transfer the virus to your eyes, nose or mouth. From there, the virus can enter your body and infect you.
• Cover your mouth and nose with your bent elbow or tissue when you cough or sneeze. Then dispose of the used tissue immediately into a closed bin and wash your hands. By following good ‘respiratory hygiene’, you protect the people around you from viruses, which cause colds, flu and COVID-19.
• Clean and disinfect surfaces frequently especially those which are regularly touched, such as door handles, faucets and phone screens.
What to do if you feel unwell
• Know the full range of symptoms of COVID-19. The most common symptoms of COVID-19 are fever, dry cough, and tiredness. Other symptoms that are less common and may affect some patients include loss of taste or smell, aches and pains, headache, sore throat, nasal congestion, red eyes, diarrhoea, or a skin rash.
• Stay home and self-isolate even if you have minor symptoms such as cough, headache, mild fever, until you recover. Call your health care provider or hotline for advice. Have someone bring you supplies. If you need to leave your house or have someone near you, wear a medical mask to avoid infecting others.
• If you have a fever, cough and difficulty breathing, seek medical attention immediately. Call by telephone first, if you can and follow the directions of your local health authority.
• Keep up to date on the latest information from trusted sources, such as WHO or your local and national health authorities. Local and national authorities and public health units are best placed to advise on what people in your area should be doing to protect themselves.
Ref: WHO website.
WHO wants moratorium on Covid vaccine booster
|
{
"url": "https://times24live.com/what-to-do-to-keep-yourself-and-others-safe-from-covid-19/",
"source_domain": "times24live.com",
"snapshot_id": "CC-MAIN-2023-14",
"warc_metadata": {
"Content-Length": "227486",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:ZQGPDKIWXLMEWKSHO56VEFADKPEVTJCU",
"WARC-Concurrent-To": "<urn:uuid:d27c2da7-ac9b-4c9d-b86b-f68b6d4eb2b5>",
"WARC-Date": "2023-03-30T18:39:35",
"WARC-IP-Address": "104.21.57.239",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:OHXDG6H3ATMQC72YDXLJOH2B5Z4T2HO7",
"WARC-Record-ID": "<urn:uuid:f96dcc4c-9ce0-4c5d-9bfe-2413c10be0a1>",
"WARC-Target-URI": "https://times24live.com/what-to-do-to-keep-yourself-and-others-safe-from-covid-19/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:7c28b916-6a7e-4e13-ae36-7ddb637e4aa8>"
},
"warc_info": "isPartOf: CC-MAIN-2023-14\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for March/April 2023\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-36\r\nsoftware: Apache Nutch 1.19 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.4-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
58,
59,
75,
101,
102,
160,
161,
403,
579,
580,
623,
624,
755,
811,
971,
1004,
1005,
1007,
1008,
1043,
1044,
1121,
1365,
1693,
1694,
1696,
1697,
1844,
1845,
1847,
1848,
1926,
2006,
2150,
2198,
2199,
2201,
2202,
2242,
2243,
2421,
2653,
2654,
2656,
2657,
2953,
2954,
2956,
2957,
3096,
3097,
3127,
3128,
3443,
3444,
3446,
3447,
3758,
3759,
3761,
3762,
3949,
3950,
3952,
3953,
4228,
4229,
4247,
4248
],
"line_end_idx": [
58,
59,
75,
101,
102,
160,
161,
403,
579,
580,
623,
624,
755,
811,
971,
1004,
1005,
1007,
1008,
1043,
1044,
1121,
1365,
1693,
1694,
1696,
1697,
1844,
1845,
1847,
1848,
1926,
2006,
2150,
2198,
2199,
2201,
2202,
2242,
2243,
2421,
2653,
2654,
2656,
2657,
2953,
2954,
2956,
2957,
3096,
3097,
3127,
3128,
3443,
3444,
3446,
3447,
3758,
3759,
3761,
3762,
3949,
3950,
3952,
3953,
4228,
4229,
4247,
4248,
4293
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 4293,
"ccnet_original_nlines": 69,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.4021352231502533,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.013048640452325344,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.16488730907440186,
"rps_doc_frac_unique_words": 0.47214484214782715,
"rps_doc_mean_word_length": 4.694985866546631,
"rps_doc_num_sentences": 43,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.300090789794922,
"rps_doc_word_count": 718,
"rps_doc_frac_chars_dupe_10grams": 0.02729159966111183,
"rps_doc_frac_chars_dupe_5grams": 0.04627706855535507,
"rps_doc_frac_chars_dupe_6grams": 0.02729159966111183,
"rps_doc_frac_chars_dupe_7grams": 0.02729159966111183,
"rps_doc_frac_chars_dupe_8grams": 0.02729159966111183,
"rps_doc_frac_chars_dupe_9grams": 0.02729159966111183,
"rps_doc_frac_chars_top_2gram": 0.008899440057575703,
"rps_doc_frac_chars_top_3gram": 0.020172059535980225,
"rps_doc_frac_chars_top_4gram": 0.005932960193604231,
"rps_doc_books_importance": -354.06793212890625,
"rps_doc_books_importance_length_correction": -354.06793212890625,
"rps_doc_openwebtext_importance": -240.43878173828125,
"rps_doc_openwebtext_importance_length_correction": -240.43878173828125,
"rps_doc_wikipedia_importance": -163.8902130126953,
"rps_doc_wikipedia_importance_length_correction": -163.8902130126953
},
"fasttext": {
"dclm": 0.018136799335479736,
"english": 0.9355610013008118,
"fineweb_edu_approx": 3.0748062133789062,
"eai_general_math": 0.0014306900557130575,
"eai_open_web_math": 0.1618947982788086,
"eai_web_code": 0.00004267999975127168
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "614.5",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Public health"
}
},
"secondary": {
"code": "616.9",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "1",
"label": "Factual"
},
"secondary": {
"code": "2",
"label": "Conceptual"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "1",
"label": "News/Editorial"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "3",
"label": "Irrelevant Content"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "4",
"label": "Missing Images or Figures"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "21",
"label": "Customer Support"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
6e3c8d3593f3f69280bb5502b214ab8e
|
-7,627,430,483,677,249,000
|
Vitamin E page CIDPUSA.org
Vitamin E Deficiency, causes, treatment
Vitamin E deficiency is rare that causes nerves damage. When vitamin E deficiency strikes people with issues that prevent the absorption of dietary fats and fat-soluble nutrients. Since vitamin E is a fat-soluble vitamin, it has some of the properties of fat. The recommended dietary allowance (RDA) for vitamin E is 10 mg/day for the adult man or woman, and 3 mg/day for the infant. Vitamin E occurs in foods in many forms. The most potent and useful form of vitamin E is called alpha-tocopherol. The best sources of vitamin E are vegetable oils (corn oil, soy oil, and peanut oil). Animal fats, such as butter and lard, contain lower levels of the vitamin. Corn oil contains about 16 mg of alpha-tocopherol per 100 g oil. Wheat-germ oil contains 120 mg alpha-tocopherol per 100 g oil. Fish, eggs, and beef contain relatively low levels of the vitamin, with about 1 mg per 100 g food.
Vitamin E helps in the prevention of deterioration in all body tissues. This deterioration is provoked by a number of causes; one of these is toxic oxygen. During the body's metabolism of atmospheric oxygen, toxic oxygen is produced continuously in the body by the formation of by-products. These toxic by-products include hydrogen peroxide, superoxide, and hypochlorite. Hypochlorite is a natural product, produced by cells of the immune system. It is also the active component of bleach. Once formed, toxic oxygen can damage various parts of the body, such as the membranes which form the boundaries of every cell. Vitamin E serves the body in protecting membranes from toxic oxygen damage. In contrast, vitamin C serves to protect the aqueous, or watery, regions of the cell from toxic oxygen damage. The membranes that are most sensitive to toxic oxygen damage are the membranes of nerves; therefore, the main symptom of vitamin E deficiency is damage to the nervous system.
Causes and symptoms
As mentioned, when vitamin E deficiency occurs, it strikes people with diseases that prevent the absorption of dietary fats and fat-soluble nutrients. These diseases include cystic fibrosis, pancreatitis, and cholestasis (bile-flow obstruction). Bile salts, produced in the liver, are required for the absorption of fats. Cholestasis causes a decrease in the formation of bile salts and the consequent failure of the body to absorb dietary fats. For this reason, this disease may result in vitamin E deficiency. Premature infants may be at risk for vitamin E deficiency because they may be born with low tissue levels of the vitamin, and because they have a poorly developed capacity for absorbing dietary fats. Infants suffering from fat-malabsorption diseases can develop symptoms of vitamin E deficiency by age two.
Patients with colorectal cancer caused by the so-called Ki-ras mutation have also been shown to absorb less vitamin E from their diet than either normal control subjects or cancer patients without the mutation.
Vitamin E deficiency in humans results in ataxia (poor muscle coordination with shaky movements), decreased sensation to vibration, lack of reflexes, and paralysis of eye muscles. Another symptom of early vitamin E deficiency in children with cystic fibrosis is a decline in cognitive function, which results in difficulty with reading and falling behind in other intellectual skills during the elementary school years.
More recently, the suggestion has been made that vitamin E deficiency may be involved in the development of partial open-angle glaucoma (POAG), an eye disorder whose causes are not fully understood as of the early 2000s
Diagnosis
Vitamin E status is measured by assessment of the content of alpha-tocopherol in the blood plasma, using a method called high-pressure liquid chromatography. Blood plasma levels of alpha-tocopherol that are 5.0 mg/l, or above, indicate normal vitamin E status; levels below 5.0 mg/l indicate vitamin E deficiency.
Treatment
Vitamin E deficiency that occurs with cholestatic liver disease or other malabsorption syndromes can be treated with weekly injections of 100 mg alpha-tocopherol that may continue for six months. Vitamin E deficiency in premature infants may require treatment for only a few weeks. Prevention The prevention of vitamin E deficiency should not be a concern for most people, since the vitamin is found in a wide variety of foods. Attention has been given to the theory that vitamin E serves to protect against cancer and atherosclerosis. The evidence that normal levels of vitamin E protect against atherosclerosis is fairly convincing. However continue to next page
CIDPUSA.ORG
@ copyright cidpusa
This website is a alternative guide for all diseases just search its a 5000 page site. Contact us by services page.
|
{
"url": "http://www.cidpusa.org/E4.htm",
"source_domain": "www.cidpusa.org",
"snapshot_id": "crawl=CC-MAIN-2022-05",
"warc_metadata": {
"Content-Length": "9185",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:V5AYQMIZ5K4636SZMFQ2OISLXQADVVM2",
"WARC-Concurrent-To": "<urn:uuid:c16431f0-2f36-4f2a-b6ed-3994ceaa77bd>",
"WARC-Date": "2022-01-18T03:34:54",
"WARC-IP-Address": "207.150.214.249",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:LPDGMF4MCHWQI4SEKNGLICXGVMIUXX7C",
"WARC-Record-ID": "<urn:uuid:bf9cbad6-f379-4eb4-9752-a1946567e3aa>",
"WARC-Target-URI": "http://www.cidpusa.org/E4.htm",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:b071aa32-000f-4644-846a-f523eb9d7b4f>"
},
"warc_info": "isPartOf: CC-MAIN-2022-05\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for January 2022\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-58\r\nsoftware: Apache Nutch 1.18 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.3-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
29,
30,
70,
71,
957,
1937,
1938,
1939,
1959,
1960,
2779,
2780,
2991,
2992,
3412,
3413,
3633,
3634,
3635,
3636,
3646,
3647,
3961,
3962,
3963,
3973,
3974,
4639,
4640,
4642,
4643,
4655,
4656,
4676,
4677
],
"line_end_idx": [
29,
30,
70,
71,
957,
1937,
1938,
1939,
1959,
1960,
2779,
2780,
2991,
2992,
3412,
3413,
3633,
3634,
3635,
3636,
3646,
3647,
3961,
3962,
3963,
3973,
3974,
4639,
4640,
4642,
4643,
4655,
4656,
4676,
4677,
4792
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 4792,
"ccnet_original_nlines": 35,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.3410852551460266,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.03765226900577545,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.14396455883979797,
"rps_doc_frac_unique_words": 0.41447368264198303,
"rps_doc_mean_word_length": 5.115789413452148,
"rps_doc_num_sentences": 44,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.088132381439209,
"rps_doc_word_count": 760,
"rps_doc_frac_chars_dupe_10grams": 0.030349789187312126,
"rps_doc_frac_chars_dupe_5grams": 0.04320988059043884,
"rps_doc_frac_chars_dupe_6grams": 0.030349789187312126,
"rps_doc_frac_chars_dupe_7grams": 0.030349789187312126,
"rps_doc_frac_chars_dupe_8grams": 0.030349789187312126,
"rps_doc_frac_chars_dupe_9grams": 0.030349789187312126,
"rps_doc_frac_chars_top_2gram": 0.05761317163705826,
"rps_doc_frac_chars_top_3gram": 0.069444440305233,
"rps_doc_frac_chars_top_4gram": 0.01388888992369175,
"rps_doc_books_importance": -381.2005920410156,
"rps_doc_books_importance_length_correction": -381.2005920410156,
"rps_doc_openwebtext_importance": -196.03750610351562,
"rps_doc_openwebtext_importance_length_correction": -196.03750610351562,
"rps_doc_wikipedia_importance": -105.39338684082031,
"rps_doc_wikipedia_importance_length_correction": -105.39338684082031
},
"fasttext": {
"dclm": 0.02075093984603882,
"english": 0.9248878955841064,
"fineweb_edu_approx": 3.2436983585357666,
"eai_general_math": 0.08641082048416138,
"eai_open_web_math": 0.2139713168144226,
"eai_web_code": 0.001545130042359233
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "613.2",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
},
"secondary": {
"code": "615.54",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "0",
"label": "No Artifacts"
}
},
"missing_content": {
"primary": {
"code": "1",
"label": "Truncated Snippets"
},
"secondary": {
"code": "4",
"label": "Missing Images or Figures"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "8",
"label": "Documentation"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "4",
"label": "Highly Correct"
}
},
"education_level": {
"primary": {
"code": "2",
"label": "High School Level"
},
"secondary": {
"code": "1",
"label": "General Audience"
}
}
}
|
9222580d47c553ea90dc0f5e416f8f3a
|
-2,797,835,909,959,465,000
|
Better Help Online Therapy Jobs vs Traditional In Office Therapy
mental health issues emptiness might leave you feeling upset baffled or disappointed if you find yourself feeling this way for an extended time period it could be an indication…Better Help Online Therapy Jobs… of a severe issue that requires immediate attention learning to acknowledge sensations of emptiness is essential to understanding why you feel by doing this and how to take the vital actions to work through it what does it imply to feel empty vacuum feels uncomfortable and in some cases it can be challenging to explain what you are feeling some feel numb or emotionless no matter what the circumstance they are going through some feel powerless or not sure why they think by doing this it can leave you feeling removed from the world around you even individuals who appear to have whatever from a terrific job but loving family and meaningful friendships can experience psychological numbness anytime it can leave you feeling like a void or that something is missing out on in your life feeling empty is regular but it helps to identify what triggered this feeling so you can begin feeling better possibly you’re mentally drained pipes from a difficult circumstance feel bored at work overwhelmed by media have relationship problems lack function in your life or just lost an enjoyed one feeling empty might or might not have a particular cause but there are methods to cope focus on filling deep space you feel caused by emptiness in healthy ways find out about mental health awareness and treatment options to motivate self-control you can discuss your feelings with a counselor or therapist that can deal with you by exploring your past to comprehend the cause other methods to help you cope consist of journaling setting significant objectives taking part in activities you take pleasure in staying close to individuals who care about you and signing up with a peer support system discussing your feelings with a relied on therapist or therapist can benefit your mental health while acquiring mental health tools in a personal setting your circumstance might benefit from online assistance offered by licensed therapists at better aid handling sensations of vacuum is challenging however you do not have to browse those feelings
ow to stop feeling like i simply wish to flee have you ever had the sensation that you just want to get away from all of your issues you’re not alone as this is actually something that individuals of any ages face no matter the source of your stress it can be frustrating causing the desire to run away from all of it in fact the feeling of wanting to escape is credited to the battle or flight response the natural biological reaction to distress and risk when we are placed in demanding situations it’s typical to wish to attempt to escape them as soon as possible however it can end up being an increased reaction that lasts beyond the stressor tension and anxiety are a few of the most common mental health problems that people deal with if these feelings aren’t handled they can add to mental exhaustion and burnout which is frequently what causes adults to feel the urge to run away to prevent burnout before it happens we should find methods to de-stress individuals who find themselves getting stressed out quickly tend to fight with finding balance in their lives whether it’s work school being a moms and dad or all of the above various obligations can easily consume our lives and leave really little space for individual time which is required for a well balanced life you might feel like there aren’t adequate hours in the day but with time management and structure you can discover performance while also setting aside time for yourself to enjoy hobbies and physical activity speaking about these stressors helps too as one of the best ways to cope is to search for assistance from others this can consist of buddies family support system and therapy and treatment by speaking to a professional such as the ones you can discover online at betterhelp you can discover practical methods to combat tension and develop efficient and healthy coping skills that you can utilize throughout your life by doing so you can focus on what improves you and makes you delighted the feelings of wanting to flee will not manage your life and instead you’ll know how to cope and deal with the problems that caused them in the first place Better Help Online Therapy Jobs
Find Better Help Online Therapy Jobs – World’s largest therapy service
Today mental health is more important than ever. In this post we will be discussing Better Help Online Therapy Jobs… there isn’t even a standard level of information-sharing between such entities, which indicates maximum privacy for you.|In a nutshell, BetterHelp is dedicated to security, personal privacy, and quality– and it reveals. Given that BetterHelp does not work with insurance or employers, there isn’t even a standard level of information-sharing in between such entities, which implies maximum personal privacy for you.}
What is the BetterHelp debate? Better Help Online Therapy Jobs
BetterHelp is the largest online treatment platform worldwide. Online treatment platforms like BetterHelp aim to offer a much easier, more comfy, and more affordable way to get aid.
The demand for online therapy has actually escalated in the last few years. While online treatment became the only alternative for a lot of during this time, favorable experiences assisted lots of people acknowledge that it’s a practical choice in a post-pandemic world, too.
Everybody can take advantage of talking with a therapist. Everybody deals with barriers in life that can obstruct of our joy or become obstructions to our goals. And sometimes, when objectives themselves change, we require assistance coping and navigating with tough emotions.
BetterHelp therapists are all extremely certified to help you as you seek to enhance your life. The company also deals with therapists who concentrate on specific locations of concern, consisting of but not restricted to:
Depression
Tension
Anxiety
Self-esteem
Life modifications
Parenting
Relationships
Faith
Sexuality
Identity
Anger
Dependency
Consuming
Sleep
PTSD
Grief
Family dispute
Try BetterHelp
Additional services
In addition to specific treatment, the BetterHelp homepage lists Couples and Teenager counseling choices. Each of these services sends you to a sister site when selected– Regain.us for couples and TeenCounseling.com for teens. Rates for these services is similar to BetterHelp, and all therapists meet the very same high requirements and undergo the very same strenuous screening. Better Help Online Therapy Jobs
Better help evaluations
BetterHelp has a separate website dedicated to LGBTQIA counseling, called Pride Counseling. Its services are just as affordable and structured as the moms and dad company, however therapists with Pride Counseling concentrate on offering therapy to individuals in the LGBTQIA community. Pride Counseling also safeguards your personal privacy and anonymity as carefully as BetterHelp.
possibly someone else that you have actually understood in the past great work ethic truly an assertive communicator simply seems typically like he understands what’s happening with life has everything found out so now that we have these images in mind of someone with anxiety and someone that apparently does not want to shift equipments a little bit to talk with you about a functioning alcoholic we’ve all heard this term so what does it mean when we say someone’s a functioning alcoholic or typically describing someone that probably does have some kind of problem with alcohol however they’re able to keep their job they have the ability to maintain relationships family but the problem I think is that in some cases they’re unable to maintain those things in healthy methods and it’s really hard sometimes to determine an operating alcoholic because they have the ability to keep some aspects of their life together so jumping back to the initial topic here of someone with high operating anxiety otherwise known as dysthymia it’s really difficult to determine these people sometimes and in some cases it’s us sometimes we can’t even recognize when it’s us that we’re experiencing these things so today again we wish to speak about things that you can be searching for or things that you might have discovered in yourself that could be a sign that you’re experiencing high-functioning anxiety so people with high-functioning depression or experiencing dysthymia are typically challenging to identify we’re not seeing these overt characteristics of an extremely depressed individual no catatonic states in fact people with high-functioning anxiety are frequently able to preserve truly healthy way of lives good relationships with other people and that and it vertically almost makes the risk a bit scarier in a different kind of way why someone with overt signs of anything we can find them we can get them into some kind of services or try to help them as best as we can for people flying under the radar for individuals experiencing signs that we do not see it’s really difficult to recognize them and after that get them assist it’s really hard to interact to them that perhaps they need to think about finding help for themselves so when we consider psychological health services in general there already is a quite huge preconception around this a lot of people out there grownups in the United States for example have a tough time looking for treatment because of you understand the idea that if you look for therapy you’re insane or you can’t manage things on your own or something
Is BetterHelp legit?
Yes, BetterHelp is a legit, reliable company and a leader in online therapy with over 22,000 therapists and almost 2 million clients up until now. Lots of people choose it to their standard in-person therapy. As a company, it appears to comprehend that trust is an important part to its success. The business makes sure:
A safe and safe platform
Complete compliance with HIPAA law
Greater cost for some individuals, compared to in-person therapy
The option of anonymity
High standards for its therapists
A simple experience whether you utilize the site or the app
Who are the therapists?
The most essential resource BetterHelp provides is its large range of extremely certified therapists. Although it was obtained by Teladoc, Inc. in 2015, the company continues to utilize the same rigorous therapist application process in order to vet therapists and preserve quality. BetterHelp reports that only 15% of therapists who apply to the platform are approved.
The therapist application procedure consists of:
A review of each therapist’s background, experience, and referrals
Verification of qualifications
A case study exam assessed by a licensed clinician; a video interview
A platform skills test
Therapists are likewise based on ongoing quality enhancement, customer, and monitoring feedback throughout their tenure at BetterHelp.
higher for them due to the fact that they do not wish to hint individuals in their lives in to the fact that they might be fighting with something or that they may need assist with something therefore for people experiencing this we have a hard time discovering them and they have a hard time finding help since you know possibly some part of them doesn’t truly wish to be identified where this other part does however we do not know how to discover them so what are we searching for in order to determine whether we ourselves are having a difficult time with this or somebody that we appreciate might be going through a tough time with this there are some things that you can be trying to find or tuning into in yourself to figure out whether you might be having some sort of challenge with high operating depression so one of the first things to try to find is this general sense of sadness returning to this image you may have of this depressed individual you could be believing somebody weeping throughout the day simply having a difficult time with life slumped over catatonic even possibly stagnating quite you’re not going to truly see this with someone with high operating depression but rather like I stated a subtle and basic sense of sadness the majority of the time practically every day if not every day and it’s a little bit inexplicable in some cases you can’t really inform where this feeling is originating from or determine any specific trigger that hurt your sensations or anything like that some other things to be trying to find and considering is the failure or you understand the loss of ability to experience joy loss of interests and things that you utilized to really find to be something that makes you feel great or bring some type of fulfillment to your life you may also notice decreased energy so like Better Help Online Therapy Jobs.
I stated not necessarily not being able to get out of bed but just diminished you feel tired out a lot of the time where maybe prior to you didn’t experience it that way other things to be trying to find is being actually self-critical which causes perfectionism which can also add to blowing things out of proportion finding truly small things in your life to turn into huge issues so I believe there’s a stating making a mountain out of a molehill a lot of people dealing with high working depression experienced these things like I stated truly self-critical feeling a great deal of regret and embarassment about the past and even the future things that haven’t even happened yet this is something that a lot of people could not be dealing with you may likewise be thinking about this depressed individual who appears sad all the time however there’s other feelings involved in anxiety.
|
{
"url": "https://theswanironbridge.co.uk/better-help-online-therapy-jobs/",
"source_domain": "theswanironbridge.co.uk",
"snapshot_id": "crawl=CC-MAIN-2022-21",
"warc_metadata": {
"Content-Length": "58439",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:WUH6S57XZJZVIVM7NMXZA2Z72SPKN4GV",
"WARC-Concurrent-To": "<urn:uuid:cbe483a3-99f1-4e55-b8f2-0ba25f57ddfb>",
"WARC-Date": "2022-05-26T18:06:28",
"WARC-IP-Address": "45.84.120.170",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:K4T4CAD6F4GPAVVOHGF5UOQIMDE7MFHC",
"WARC-Record-ID": "<urn:uuid:da12de77-2d00-433b-b62a-83467a3f592e>",
"WARC-Target-URI": "https://theswanironbridge.co.uk/better-help-online-therapy-jobs/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:7ed7d532-978e-4ec0-874b-5c466a4a6ccf>"
},
"warc_info": "isPartOf: CC-MAIN-2022-21\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for May 2022\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-40\r\nsoftware: Apache Nutch 1.18 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.3-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
65,
66,
2311,
2312,
2314,
2315,
4482,
4483,
4554,
4555,
5089,
5090,
5153,
5154,
5156,
5157,
5339,
5340,
5616,
5617,
5894,
5895,
6117,
6118,
6129,
6137,
6145,
6157,
6176,
6186,
6200,
6206,
6216,
6225,
6231,
6242,
6252,
6258,
6263,
6269,
6284,
6285,
6300,
6301,
6321,
6322,
6735,
6736,
6760,
6761,
7144,
7145,
9740,
9741,
9762,
9763,
10084,
10085,
10110,
10145,
10210,
10234,
10268,
10328,
10352,
10353,
10723,
10724,
10773,
10774,
10841,
10872,
10942,
10965,
11100,
11101,
12967,
12968
],
"line_end_idx": [
65,
66,
2311,
2312,
2314,
2315,
4482,
4483,
4554,
4555,
5089,
5090,
5153,
5154,
5156,
5157,
5339,
5340,
5616,
5617,
5894,
5895,
6117,
6118,
6129,
6137,
6145,
6157,
6176,
6186,
6200,
6206,
6216,
6225,
6231,
6242,
6252,
6258,
6263,
6269,
6284,
6285,
6300,
6301,
6321,
6322,
6735,
6736,
6760,
6761,
7144,
7145,
9740,
9741,
9762,
9763,
10084,
10085,
10110,
10145,
10210,
10234,
10268,
10328,
10352,
10353,
10723,
10724,
10773,
10774,
10841,
10872,
10942,
10965,
11100,
11101,
12967,
12968,
13857
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 13857,
"ccnet_original_nlines": 78,
"rps_doc_curly_bracket": 0.00007216999802039936,
"rps_doc_ldnoobw_words": 1,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.5304136276245117,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.005677210167050362,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.051500409841537476,
"rps_doc_frac_unique_words": 0.32576417922973633,
"rps_doc_mean_word_length": 5.00305700302124,
"rps_doc_num_sentences": 33,
"rps_doc_symbol_to_word_ratio": 0.001216550008393824,
"rps_doc_unigram_entropy": 5.776387691497803,
"rps_doc_word_count": 2290,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.04451426863670349,
"rps_doc_frac_chars_dupe_6grams": 0.01309243030846119,
"rps_doc_frac_chars_dupe_7grams": 0.01309243030846119,
"rps_doc_frac_chars_dupe_8grams": 0.008379160426557064,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.011346770450472832,
"rps_doc_frac_chars_top_3gram": 0.011870469897985458,
"rps_doc_frac_chars_top_4gram": 0.014052540063858032,
"rps_doc_books_importance": -1000.6441650390625,
"rps_doc_books_importance_length_correction": -1000.6441650390625,
"rps_doc_openwebtext_importance": -591.682861328125,
"rps_doc_openwebtext_importance_length_correction": -591.682861328125,
"rps_doc_wikipedia_importance": -500.3323669433594,
"rps_doc_wikipedia_importance_length_correction": -500.3323669433594
},
"fasttext": {
"dclm": 0.09142124652862549,
"english": 0.9581930041313171,
"fineweb_edu_approx": 1.4401179552078247,
"eai_general_math": 0.023470820859074593,
"eai_open_web_math": 0.11956393718719482,
"eai_web_code": 0.011612709611654282
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.89",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "616.858",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "17",
"label": "Product Page"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "4",
"label": "Highly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
b755ed28a90d11d590ef646404f4afc5
|
2,417,551,896,311,580,000
|
Do Vegans Get More Cavities?
Today's Blog--
A diet high in saturated fat, which can clog our arteries and lead to inflammation, is considered a key underlying causal factor for periodontal diseases like gingivitis. This may explain why chronic gum disease is associated with sexual dysfunction. By looking in your mouth your dentist may find out more about you than you realize!
We know impotence can be reversed with a more plant-based diet; what about periodontal disease? A new study I feature in my 2-min video Plant-Based Diets: Oral Health found that higher intake of high-fiber foods, especially fruits, may at least slow periodontal disease progression. A healthy diet may also protect the sexual function of women.
So what is a safe intake for cholesterol and saturated fat? See my video Trans Fat, Saturated Fat, and Cholesterol: Tolerable Upper Intake of Zero.
For oral cancer it’s a no-brainer. According to the latest review in the journal of the American Dental Association highlighted in my video, “Evidence supports a recommendation of a diet rich in fresh fruits and vegetables as part of a whole-foods, plant-based diet.”
The foods found most protective include raw and green/leafy vegetables, tomatoes, citrus, and carrots. Citrus fruits are acidic, though. Fine, less oral cancer, but what about the health of the teeth themselves? Might eating lots of sour fruit erode our enamel?
Early case reports that raised red flags involved unusual circumstances like sucking on lemon wedges. See my video Plant-Based Diets: Dental Health for pictures of what happens when you give your preschool child a banana to suck on as a pacifier or juice 18 oranges a day for over a decade (if you dare!).
The conventional wisdom has been that fruit juice may be bad for our teeth, but whole fruit is fine. This was challenged recently. The ability of fruits and their juices to erode enamel appears to be similar. For the chart that compares grapes to grape juice, carrots to carrot juice, oranges to orange juice, apples to apple juice, and tomatoes to tomato juice, click here.
Now fruits and fruit juices weren’t as bad as soda—Diet Coke takes the title for softening teeth the quickest. But it was a surprise that fruits and their juices had comparable effects. The Dental Association put an interesting spin on it: If eating fruits and vegetables whole has the same demineralizing effect as juice, they argued, then hey, maybe fruit juice is not so bad at all! Of course the glass-half-empty interpretation of fruit being as erosive as juice may be that fruit is worse than we thought for our enamel.
Indeed, the latest research on whether the consumption of fruit is cavity-causing found that the frequency of fruit consumption was associated with higher odds of cavities, though they acknowledge that the role of fruit sugars in initiating dental cavities in humans has long been a subject of debate.
Those eating plant-based diets may have less disease of the tissues surrounding the teeth, but if people who eat a lot of fruit get more cavities, then what about the health of the teeth themselves? Though vegetarians and vegans don’t have more cavities than those eating more conventional diets, they may have greater signs of acid erosion on their teeth (as documented in two studies I run through in my dental health video). So what should people do?
There are a number of foods and drinks that have the potential to cause dental erosion, both unhealthy foods like soda and sour candy, as well as healthy foods like fresh fruit and certain herbal teas. In the biggest study to date, consuming citrus fruits more than twice a day was associated with 37 times greater odds of dental erosion compared to those who consumed citrus fruits less often. It also appears risky to consume apple cider vinegar or sports drinks once a week or more and soft drinks daily. These habits resulted in the odds of erosion being ten, four, and four times greater, respectively, than when the habit did not exist.
How can we get the benefits of healthy foods like citrus while minimizing the risks of dental erosion? The most important thing is that we should never brush right after we eat sour fruit. We should wait at least 30 minutes. Acid softens our enamel such that if we brush right away we can actually brush away some of our teeth!
profile a study where they had some folks swish an acidic solution (Diet Sprite) and then brush immediately after, or 10, 20, 30 or 60 minutes after. Drinking soda without brushing at all can lead to some enamel loss, but we may double or triple that damage if we brush our teeth when they’re in the acidified softened state. The researchers suggest we should wait at least 30 minutes and probably a whole hour afterwards to be safe. The simple solution is that after eating anything sour we should rinse our mouth with water to help neutralize the acid.
So should we avoid healthy foods like citrus? No! We just need to rinse.
What’s so great about citrus? See for example:
More on oral health in:
Anything else people eating healthy diets should be aware of? The most important consideration is vitamin B12. See my blog posts Vitamin B12: how much, how often? and Vegan B12 deficiency: putting it into perspective.
-Michael Greger, M.D.
PS: If you haven’t yet, you can subscribe to my videos for free by clicking here and watch my full 2012 – 2015 presentations Uprooting the Leading Causes of Death, More than an Apple a Day, From Table to Able, and Food as Medicine.
Image credit: NATO Training Mission-Afghanistan/ Flickr
• HemoDynamic, M.D.
#Smiling :-) at your Pearly White information!
• Diana Ng
I’ve been on plant-based since June last year but I’ve got gum disease and my bones have been shrinking from my front teeth on my mandible causing loose teeth. What causes this? And what can help, Dr. Greger?
• farseas
Are you eating plenty of green leafy vegetables like spinach, kale, arugula for plant based calcium? Maybe add some whole sesame seeds too, which contain tons of calcium. Add Natto or MK-7 supplements to your diet to make sure all that calcium gets to your bones and teeth.
Also, watch out for vinegar as it can make your mouth acidic and cause tooth decay. Always rinse your mouth out thoroughly after eating and brush an hour later. Too much fruit can also cause your mouth to lose the proper PH. Rinse, rinse, rinse…
• Ann
I still have cavities. But I think its because of me eating corn crackers with organic peanut butter every day, like 6 a day (at tops 1 tablespoon peanut butter a day).
All the rest is plant based, high raw (85%)
• beccadoggie10
Hi Ann, Corn crackers may have a double whammy since both corn and crackers are carbohydrates and break down into sugars in our body.
http://tinyurl.com/m9rrazn
My cavities ceased when I made choices like eating a serving of organic rice, quinoa, or frozen (and heated) organic corn with my beans instead of snacking on chips or crackers with nut butters.
Corn, btw, is genetically modified with organisms of other species or kingdoms in order to resist more herbicides as well as to be an insecticide in the body of the insect or animal who eats it.
And Roundup, the herbicide made by Monsanto, is corrosive to metal. No telling what it can do to our teeth when it builds up in food and into water supplies.
I’ve changed my way of eating since learning about the politics of food in North America.
Occasionally I eat almond butter smeared on a banana. After devouring this, I swish my mouth out with carbon filtered water, This has me eliminate cavities… thus far.
I think it’s the choices we make whether or not we eat vegan.
• BB
I have been on a whole food plant based diet for 4 years and have noticed that I have better oral health now than I did before. The PH of my saliva is more basic than that of my non-plant based children. And the PH recovery after eating citrus food is surprising. My saliva PH is actually higher right after eating oranges than before eating oranges.
• BB
I think the whole oral health issue is correlated with bone loss in non-plant based people. Teeth are like bones and if your diet is making your body acidic – there are more things than your bones that are de-calcifying…. it might be your teeth too! Anyone want to do a study on that?
• BPCveg
Hats off to you, Dr. Greger, for an excellent article. Thanks for the very useful information.
• beccadoggie10
I’ve been avoiding sucking on fruit and drinking sugary or diet soft drinking for 50 years, but that did not stop me from getting cavities until I changed my diet to vegan to reduce pain and inflammation from osteoporosis. I have used fluoride toothpastes when brushing all along. But that did not alter the cavities received prior to going vegan.
For me, eating dark leafy green veggies instead of consuming dairy seems to have reduced my cavities from one or two per visit to zero, which was noticed by both my dentist and periodontist. I’ve had no increased dental health issues from eating vegan, as well.
• Melissa
I find that very interesting, I have a son who is only four years old and he has nine cavities. At his last visit at about eight or nine months ago, he had no visible cavities. Everything I have read so far has led me to believe that to heal cavities one has to consume meat, dairy, etc. I find your comment encouraging and would like to ask if you would mind sharing your diet tips with me.
• Arruniel
Drinking a glass of water with fruit can help wash away some of that citric acid.
• Paleo Huntress
As a paleo template advocate, I’m not a supporter of the WAPF. But frankly, when the man found that the cultures eating diets containing SIGNIFICANT levels of animal protein and saturated fat were the ones with the least dental disease, it’s really hard to make an argument that saturated fat causes it- otherwise in those cultures eating more than 3/4 animal foods , we’d expect to find them toothless.
Sorry Doc, this one doesn’t even get off the ground.
• Guest
Too funny: Just read the comments and look for her:
http://nutritionfacts.org/video/changing-our-taste-buds/
• susan
That was funny. It just shows that she was hunted down and called out for no reason–or, in other words, simply because she disagreed with others. That’s a shame but it seems that monotone policy is the way this works here.
• Warren M
I’ve been on a plant based diet for nearly 4 years. I’ve been able to go from a 6 month dental check up to a yearly check up. I think I could scale it back even more. The hygienist says my teeth look great, very little plaque. I think I’ve had one small cavity in that time. I don’t eat a lot of citrus though.
• GoingVeganUK
After 3 years on a plants only diet my husband’s chronic gingivitis has magically disappeared.This is something we were not expecting. Plants are curing inflammation in the gums which tells me that inflammation elsewhere in the body that we are not aware of is also being healed.
• Thea
I love stories like this! Thanks for taking the time to post. And your conclusion sure makes sense to me!
• Paleo Huntress
It took an entire three years? Forgive the criticism, its really awesome that the inflammation is gone, but the fact that it took three years is not exactly a ringing endorsement for pb diets.
• GoingVeganUK
Oh dear I should have been more careful in my wording! I should have said we have been eating a plant based diet for 3 years and my husband has just told me that his gingivitis has disappeared. He has recently been to the dentist and this brought to his attention that it was better. Sometimes when people have a condition that is intermittent they don’t immediately notice when it goes away.
• Paleo Huntress
~nods~ I know just what you mean. Has it been three years since your husband last saw the dentist too?
• GoingVeganUK
Why are you so aggressive? Are you the Richard Dawkins of paleo food? I am simply posting an interesting anecdote on a site where there are people who may be interested.I am not trying to prove anything!
• Paleo Huntress
GoingVeganUK,
I once suffered a foot injury and ended up with plantar fasciitis that was pretty debilitating. I know that for months it was really obviously uncomfortable, but it faded away so gradually that I can’t say when it was actually healed. This is what I referred to when I said I know just what you mean.
You said your husband had recently been to the dentist, and in thinking about how most people go once or twice a year, it occurred to me to ask if he’d been to see him prior to this last visit. This kind of stuff fascinates me and I like to try and suss out possible cause. I wasn’t trying to be aggressive, and I’m sorry if it sounded that way. I hope you’ll accept my apology.
• A
What helps me is brushing my teeth with a xylitol-based tooth paste like Tooth Builder or Squiggle Enamel Saver *before* eating sour fruit. Or simply rinsing my mouth with with a xylitol solution (xylitol plus water) after eating fruit, since brushing right away would destroy the enamel. There is a book on this topic called Kiss Your Dentist Goodbye, written by a dentist, if anyone’s interested.
• Shanna
I am very healthy vegan for 2 years and to me its being really frustrating, I am literally watching my teeth decay, I never had such horrible teeth health, my teeth is literally braking apart falling into pieces, right now I got a swollen grand in my neck and tooth pain in all corners of my mouth, its disgusting! I heard that washing with baking soda after eating might help, I will try.
• Alex the WFPB dentist
Are you having lots of dried fruits? They have very concentrated sugar thus can cause cavities if left in the grooves of your molars. How about honey or syrup, pop consumption? Lots of lemon or lime can lead to erosion. Washing with baking soda can help because it neutralizes the acids produced by the bacteria on your teeth when they convert dietary sugar to acid. The best thing to do, however, is be aware of sugar and acid consumption (vinegar, etc.) and keep it to a minimum.
• Mery Daae
ok, so if lemon is great, so is eating as many fruits as possible, so is apple cider vinegar, how do we do all this and not get the side effects? I seem to have improved the appearance of my teeth (whiter and smoother) with a plantbased diet, my gums are less inflammed and I guess less plaque buildup but I have higher teeth sensitivity and I think I might have developped 2 cavities in the short time (+-7months) Ive been plantbased. thoughts please?
• Emily Jane
Try taking vitamin k2 supplements. I take mk7 (menanoquine 7). It directs calcium into bones and teeth and away from arteries. I think the only plant-based food that contains k2 os natto.
• Steve True
Cheese neutralises acid in the mouth cheddar is the best, vegan cheese would be better because its slightly alkaline, rather than cheese made wiith cow milk which is slightly acid.
• Krista
By my knowledge, periodontal health in relation to cavities is not superficial. It has to do with an underlying deficiency of fat soluble vitamins – A, D, E, K. Talking about sugar/fruit/carbohydrates and their effects on teeth is really minimal in comparison to the importance of fat soluble nutrients which promote remineralization.
• Puppy the Guinea Pig
An alternative point to consider: could lack of Vitamin K2 in the diet be the reason for the observed dental erosion differences in vegetarians/vegans? To understand more, read about the old studies of dentist Weston Price involving an “X activator” -a vitamin like component he was finding in animal products that seemed to prevent dental carries! Today some nutritionists believe the “X activator” he was trying to understand was actually Vitamin K2. Vit K2 is mostly found in consumed animal fat products. K1 is absorbed from the greens we eat and there is much reason to believe that humans may not be able to turn K1 into K2 systemically, as some animals can. If this is true, then having healthy levels of Vit K2 are diet dependent and vegans are at greatest risk of deficiency. Fortunately there are oral supplements we can buy, but many people are not yet aware of this rarely discussed vitamin! I am vegan and I’m not taking any chances- I supplement with a Vit K2 capsule (and FYI Vit K2 is the same think as Natto and MK-7 mentioned in another comment).
• Bob Dorris
Has anyone experienced significant remineralizing of teeth using simply K2 while on a vegan diet, or have other good insights on vegan diet, Weston Price concepts & cavities? And, do you think that K2 can replace the the oil butter?
I’ve been vegan for about 6 years, and feel great EXCEPT I’m having bad dental issues. Had an abscess & extraction about a year ago, and now starting to have similar pain in another tooth. I clean my teeth like crazy, so it must be dietary. I eat a ton of kale, broccoli, beans, nuts, whole grains, zero sugar, and have done that for years.
Most dairy really congests me, and the idea of eating all the animal food recommended by the Weston Price protocol sounds like a prescription for heart disease & cancer, based on all the research shown here by Dr, Greger and elsewhere. However, losing my teeth like this isn’t very appealing, either.
I’m temporarily doing the Weston Price protocol while trying to save a tooth. Afterward, I’m considering trying just taking the Cod liver oil & Butter oil daily in combination to a vegan diet (beans & grains included) to see if that strikes a balance between preventing tooth decay without being too much animal product.
I’d appreciate any more insights from others who have worked through this issue with some success!
• Puppy the Guinea Pig
Hey Bob. I do not have any direct experience with correcting bad dental health via K2 supplementation- only a Vegan x 1 yr and doing preventative supplementation before it becomes a possible issue. Maybe some others will chime in.
I did a search for studies on dental outcomes from K2 supplementation and did not find anything but Price data. I suspect many studies may be underway in dental education centers, but nothing is published yet that I could find.
I understand why you are following what Price did- it seems to be some of the only data we have to go on right now and since he got good outcomes and we cannot for sure know all the involved components/factors it makes sense (there are like 10 versions of Vitamin K2- so does just taking Mk-4 and Mk-7 work? Or even just one of them? We don’t know yet.)
I personally feel a reasonable strategy for Vegan people might be to make sure they are getting both currently available varieties of K2 supplements (Mk-4 the synthesized analog to what is found in eggs and Mk7- the bacteria formed version from Natto fermentation….maybe some strict Vegans would object to bacteria as source of the Mk7). There is also reference to adequate Vitamin D levels being important.
Vitamin D supplementation is a hot medical focus right now: an easy blood test can reveal if you are in the therapeutic range or below normal and would benefit from supplementation. We are understanding more about Vit D levels as they relate to disease every day so its smart on many levels of health to know you have what medicine currently calls therapeutic blood levels and supplement if you do not. I’m not sure that there is a lab test yet to specifically test for Vitamin K2 levels- your doctor may be able to find out. There are many lab tests for Vitamin K in blood but that mostly relates to K1 and its role in clotting.
Sorry I didn’t have any direct experience of study data to help answer this. I hope what you are doing helps.
• Bob Dorris
Thanks for the thoughtful response. Yes, it really seems that this is one issue for people following a plant-based whole foods diet that’s not very well covered. I just wish that the Price protocol wasn’t such a radical deviation from everything presented on this site. It feels like having to choose between tooth decay & heart disease!
• Puppy the Guinea Pig
I understand :) I think it will get better as more data is published, now that this is a big area of interest for many.
• Bob Dorris
Hey Puppy – Can you suggest a brand for the K2 – MK4 & MK7? Lots of different ones out there to sort through.
BTW, I keep re-reading your & Thea’s posts. both have been very helpful. I’m leaning towards stopping the CLO & Butter oil and going with K2 and timing of rinsing & green tea mouthwash. (The CLO almost made me vomit yesterday. That can’t be good!)
BTW, I’m trying out mactin gum. Studies have shown it to be pretty effective, as well.
• Puppy the Guinea Pig
So sorry my friend. I have not done my homework here. I pretty much just pick them up at the vitamin store on the corner.
• Thea
Bob Dorris: I don’t have an answer to your exact question, but I have some ideas for you that are relevant.
.
First, I have also been vegan for about 6 years, and while it sounds like your diet is way healthier than mine, my teeth are not having the problems your teeth are having. I know lots of people who have been vegan for years and even decades and their teeth are just fine. I don’t think there is any evidence to support the idea that your diet (per say) is missing some key ingredient (K2) which in turn is causing your teeth to go bad.
.
While I’m no expert, I can think of two potential explanations (not saying that either of these are correct. Just that these are potential explanations) for your current situation: one is that whatever problem you are having with your teeth, you would have had anyway, regardless of your change in diet. Another idea I have is the one touched on by this video and other pages on this site: Vegans who eat healthy foods usually include sour foods which end up softening tooth enamel. Brushing your teeth while your enamel is soften can result in the enamel being brushed away. You mention excessive brushing, which makes me think this is part of your problem. My dentist recommends brushing once a day. And using the advice on this site, you could make sure you brush at least an hour after eating anything. You might consider swishing with baking soda water after eating anything acidic or sour. And you might consider swishing (maybe even swallowing!) Dr. Greger’s recommended mouthwash between times/throughout the day to both kill bacteria and even help prevent plaque from forming in the first place. http://nutritionfacts.org/video/whats-the-best-mouthwash/
.
Second, I suggest that you think about the source of your information: The Weston Price foundation. That group is notorious for disseminating false information, backed by pseudo science and unscrupulous “experts”. They don’t even follow their founder’s advice (which was pretty much to be vegetarian). While even a stopped watch is right twice a day and thus maybe the Foundation knows something about healthy teeth, their track record suggests that you would do better to get your information elsewhere.
.
If you want some proof about the flaws in the Weston Price website and their set of “expert opinions”, you can learn a great deal from the scholarly work done by Plant Positive. Here is the Plant Positive general website: http://plantpositive.com/ Here are some videos that mention Weston Price: The first link is an entire video devoted to the topic of Weston Price. http://plantpositive.squarespace.com/blog/2012/3/25/tpns-26-weston-price.html This second link is a general search of the site as there are multiple videos covering Weston Prince to various degrees. http://plantpositive.com/display/Search?moduleId=19496100&searchQuery=weston You might also just spend some time watching some of the videos in the various series in order. The researcher does an amazing job of debunking cholesterol deniers in general. Once you learn how easy it is to twist the science, you might find yourself questioning the information about teeth on the Price site.
.
I recognize that your question was specifically on how to re-mineralize teeth and that I don’t have any ideas on that topic at this time. I hope others have (actual science-backed) ideas for you on that specific topic. At the same time, I hope my post has given you some ideas to work with. Good luck. Good teeth are so important. I hope you find some solutions that will work for you that don’t involve raising overall health risks.
• Bob Dorris
Thank you very much for your response, Thea. I checked out the material you referenced… good stuff.
Do you think it’s likely that the Cod LIver Oil / Butter Oil / Weston Price protocol is very good at remineralizing teeth, but simultaneously very bad for our health otherwise?
There’s so many positive review of the book I’d like to hear some thoughts from anyone here on why there’s so many positive comments about the book “Cure Tooth Decay” on Amazon https://www.amazon.com/Cure-Tooth-Decay-Cavities-Nutrition/product-reviews/1434810607/ref=cm_cr_getr_d_paging_btm_next_5?ie=UTF8&showViewpoints=1&sortBy=recent&pageNumber=5 that it seems likely that it actually is helping a lot of people with their teeth.
• Thea
Bob Dorris: You asked, “Do you think it’s likely that the Cod Liver Oil / Butter Oil / Weston Price protocol is very good at remineralizing teeth, but simultaneously very bad for our health otherwise?”
.
The key word in your question is “likely”. I do not think it is *likely* that the protocol is very good at remineralizing teeth given how much the foundation gets wrong in so many areas. But I do think it is *possible* they got this one thing right. I don’t know enough to say any more than that. Instead, I submit to you: Knowing that those foods *are* simultaneously bad for our health otherwise, wouldn’t it be prudent to find another solution even if the Price idea is a possible solution?
.
One more thought for you responding to your last sentence, “There’s so many positive review of the book … that it seems likely that it actually is helping a lot of people with their teeth.” There are also lots of people who give glowing reviews to books like say Grain Brain and Atkins’ book. But we know that the eating protocols in those books lead to bad long term health for the majority people, despite the many glowing reviews. So, I don’t think it is a given that many people are being helped by the book you referred to. (I’m not saying people haven’t been helped. I’m just saying that you can’t judge by Amazon reviews.)
.
Best of luck to you. Eating food should be enjoyable among other goals, and it’s hard to enjoy one’s food with bad teeth!
• Puppy the Guinea Pig
I would just add to this that a VAST AMOUNT of reviews on amazon are now purchased/bribed through free product deals and services that go on behind the scenes (I have direct knowledge of this- I know the companies that offer these services and people who do the reviewing). The majority of our consumer public is not aware of this. Once upon a time, Amazon reviews were real and very helpful to consumers. Until sellers figured out that the positive reviews help their products in the search rankings…then the corruption began. I still utilize them for deciding between things like air conditioners by comparing the negatives. But I am sad to share that pages of glowing reviews on Amazon are highly suspect these days.
• Thea
Thanks for the info puppy. Good to know.
• Katherine Toledo Macedo
I’ve been vegan about 1 year and I never had cavities (caries) in my whole life. Yesterday I saw a small cavity in one of my molar tooth and I feel very upset. I started thinking about something that has changed in my routine because I don’t believe that is something wrong with my diet. (I always had a good diet with lots of plant based food, no much sugar and regularly brush my teeth.)
So, I moved to the UK a year ago and I’ve stopped to drink water with fluorite (I’m from Brazil and they artificially fluoridate the water) and also haven’t been using toothpaste with fluorite since I moved.
However, I’d like to discuss about the uses of fluorite for health. Because many people say that it’s terrible for your health, but I guess the problem is how much you are exposed (inside your body) by fluoride (ej drinking fluoridate water), not in the toothpaste. (water fluoridation in the UK: http://www.telegraph.co.uk/news/science/science-news/11430233/The-extent-of-water-fluoridation-in-the-UK.html)
Now I started to look for vegan toothpastes with fluorite (for treatment and prevention) but it’s so hard to find. Why do some vegan people avoid products with fluoride? And why don’t the UK fluoridate the water?
Obs: Vegan Brazilians also are against the widespread use of fluoride. I read some articles about cancer(?) and fluorosis (yes, this can be happen). But I agree with the NHS article bellow (http://www.nhs.uk/conditions/Fluoride/Pages/Introduction.aspx)
Please, share your knowledge and experience with me. Thank you :)
|
{
"url": "http://nutritionfacts.org/2013/07/25/do-vegans-get-more-cavities/",
"source_domain": "nutritionfacts.org",
"snapshot_id": "crawl=CC-MAIN-2016-44",
"warc_metadata": {
"Content-Length": "156708",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:UKV4WHQDNZW2GT7BHKRKJAQT6YAG74XO",
"WARC-Concurrent-To": "<urn:uuid:67411c61-b99d-488d-9492-3b720c7d1fc8>",
"WARC-Date": "2016-10-26T23:05:48",
"WARC-IP-Address": "104.25.160.32",
"WARC-Identified-Payload-Type": null,
"WARC-Payload-Digest": "sha1:DR2YLSCTLVJTOY7B4CLKCX2EAI4RIS6H",
"WARC-Record-ID": "<urn:uuid:158fa1ad-80eb-419a-b67b-ac0ad5960176>",
"WARC-Target-URI": "http://nutritionfacts.org/2013/07/25/do-vegans-get-more-cavities/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:cc362635-1f2a-4d1e-bdb7-82a5631e025f>"
},
"warc_info": "robots: classic\r\nhostname: ip-10-171-6-4.ec2.internal\r\nsoftware: Nutch 1.6 (CC)/CC WarcExport 1.0\r\nisPartOf: CC-MAIN-2016-44\r\noperator: CommonCrawl Admin\r\ndescription: Wide crawl of the web for October 2016\r\npublisher: CommonCrawl\r\nformat: WARC File Format 1.0\r\nconformsTo: http://bibnum.bnf.fr/WARC/WARC_ISO_28500_version1_latestdraft.pdf"
}
|
{
"line_start_idx": [
0,
29,
30,
45,
46,
382,
383,
728,
729,
877,
878,
1146,
1147,
1409,
1410,
1716,
1717,
2092,
2093,
2619,
2620,
2922,
2923,
3377,
3378,
4021,
4022,
4350,
4351,
4906,
4907,
4980,
4981,
5028,
5029,
5053,
5054,
5272,
5273,
5295,
5296,
5528,
5529,
5586,
5587,
5609,
5610,
5661,
5662,
5675,
5676,
5889,
5890,
5904,
5905,
6185,
6186,
6438,
6439,
6447,
6448,
6621,
6669,
6670,
6690,
6691,
6831,
6864,
6865,
7066,
7267,
7431,
7432,
7528,
7529,
7702,
7703,
7771,
7772,
7779,
7780,
8135,
8136,
8143,
8144,
8433,
8434,
8445,
8446,
8545,
8546,
8564,
8565,
8917,
8918,
9184,
9185,
9199,
9200,
9598,
9599,
9612,
9613,
9699,
9700,
9719,
9720,
10128,
10129,
10186,
10187,
10199,
10200,
10258,
10259,
10322,
10323,
10337,
10338,
10569,
10570,
10583,
10584,
10899,
10900,
10917,
10918,
11202,
11203,
11214,
11215,
11327,
11328,
11349,
11350,
11549,
11550,
11571,
11572,
11973,
11974,
11999,
12000,
12113,
12114,
12139,
12140,
12356,
12357,
12384,
12385,
12411,
12412,
12725,
12726,
13117,
13118,
13124,
13125,
13528,
13529,
13540,
13541,
13935,
13936,
13964,
13965,
14453,
14454,
14468,
14469,
14926,
14927,
14944,
14945,
15139,
15140,
15155,
15156,
15341,
15342,
15353,
15354,
15693,
15694,
15719,
15720,
16789,
16790,
16807,
16808,
17047,
17048,
17395,
17396,
17703,
17704,
18031,
18032,
18137,
18138,
18167,
18168,
18407,
18408,
18644,
18645,
19007,
19008,
19424,
19425,
20063,
20064,
20182,
20183,
20204,
20205,
20553,
20554,
20587,
20588,
20720,
20721,
20744,
20745,
20867,
20868,
21128,
21129,
21228,
21229,
21262,
21263,
21397,
21398,
21411,
21412,
21528,
21538,
21982,
21992,
23163,
23173,
23686,
23696,
24659,
24669,
25111,
25112,
25133,
25134,
25244,
25245,
25432,
25433,
25876,
25877,
25894,
25895,
26109,
26123,
26629,
26643,
27285,
27299,
27433,
27434,
27467,
27468,
28200,
28201,
28218,
28219,
28272,
28273,
28301,
28302,
28696,
28908,
29320,
29537,
29794
],
"line_end_idx": [
29,
30,
45,
46,
382,
383,
728,
729,
877,
878,
1146,
1147,
1409,
1410,
1716,
1717,
2092,
2093,
2619,
2620,
2922,
2923,
3377,
3378,
4021,
4022,
4350,
4351,
4906,
4907,
4980,
4981,
5028,
5029,
5053,
5054,
5272,
5273,
5295,
5296,
5528,
5529,
5586,
5587,
5609,
5610,
5661,
5662,
5675,
5676,
5889,
5890,
5904,
5905,
6185,
6186,
6438,
6439,
6447,
6448,
6621,
6669,
6670,
6690,
6691,
6831,
6864,
6865,
7066,
7267,
7431,
7432,
7528,
7529,
7702,
7703,
7771,
7772,
7779,
7780,
8135,
8136,
8143,
8144,
8433,
8434,
8445,
8446,
8545,
8546,
8564,
8565,
8917,
8918,
9184,
9185,
9199,
9200,
9598,
9599,
9612,
9613,
9699,
9700,
9719,
9720,
10128,
10129,
10186,
10187,
10199,
10200,
10258,
10259,
10322,
10323,
10337,
10338,
10569,
10570,
10583,
10584,
10899,
10900,
10917,
10918,
11202,
11203,
11214,
11215,
11327,
11328,
11349,
11350,
11549,
11550,
11571,
11572,
11973,
11974,
11999,
12000,
12113,
12114,
12139,
12140,
12356,
12357,
12384,
12385,
12411,
12412,
12725,
12726,
13117,
13118,
13124,
13125,
13528,
13529,
13540,
13541,
13935,
13936,
13964,
13965,
14453,
14454,
14468,
14469,
14926,
14927,
14944,
14945,
15139,
15140,
15155,
15156,
15341,
15342,
15353,
15354,
15693,
15694,
15719,
15720,
16789,
16790,
16807,
16808,
17047,
17048,
17395,
17396,
17703,
17704,
18031,
18032,
18137,
18138,
18167,
18168,
18407,
18408,
18644,
18645,
19007,
19008,
19424,
19425,
20063,
20064,
20182,
20183,
20204,
20205,
20553,
20554,
20587,
20588,
20720,
20721,
20744,
20745,
20867,
20868,
21128,
21129,
21228,
21229,
21262,
21263,
21397,
21398,
21411,
21412,
21528,
21538,
21982,
21992,
23163,
23173,
23686,
23696,
24659,
24669,
25111,
25112,
25133,
25134,
25244,
25245,
25432,
25433,
25876,
25877,
25894,
25895,
26109,
26123,
26629,
26643,
27285,
27299,
27433,
27434,
27467,
27468,
28200,
28201,
28218,
28219,
28272,
28273,
28301,
28302,
28696,
28908,
29320,
29537,
29794,
29863
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 29863,
"ccnet_original_nlines": 281,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 3,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.4298041760921478,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.03352141007781029,
"rps_doc_frac_lines_end_with_ellipsis": 0.0035461001098155975,
"rps_doc_frac_no_alph_words": 0.14802521467208862,
"rps_doc_frac_unique_words": 0.26424869894981384,
"rps_doc_mean_word_length": 4.599442005157471,
"rps_doc_num_sentences": 302,
"rps_doc_symbol_to_word_ratio": 0.001327579957433045,
"rps_doc_unigram_entropy": 6.154804706573486,
"rps_doc_word_count": 5018,
"rps_doc_frac_chars_dupe_10grams": 0.016637779772281647,
"rps_doc_frac_chars_dupe_5grams": 0.040857888758182526,
"rps_doc_frac_chars_dupe_6grams": 0.035528600215911865,
"rps_doc_frac_chars_dupe_7grams": 0.028812820091843605,
"rps_doc_frac_chars_dupe_8grams": 0.019930679351091385,
"rps_doc_frac_chars_dupe_9grams": 0.016637779772281647,
"rps_doc_frac_chars_top_2gram": 0.0041161198168993,
"rps_doc_frac_chars_top_3gram": 0.0019497399916872382,
"rps_doc_frac_chars_top_4gram": 0.0032495700288563967,
"rps_doc_books_importance": -2816.631591796875,
"rps_doc_books_importance_length_correction": -2816.631591796875,
"rps_doc_openwebtext_importance": -1627.871337890625,
"rps_doc_openwebtext_importance_length_correction": -1627.871337890625,
"rps_doc_wikipedia_importance": -1248.1844482421875,
"rps_doc_wikipedia_importance_length_correction": -1248.1844482421875
},
"fasttext": {
"dclm": 0.0239753108471632,
"english": 0.9600335955619812,
"fineweb_edu_approx": 1.8668514490127563,
"eai_general_math": 0.06296057254076004,
"eai_open_web_math": 0.18385440111160278,
"eai_web_code": 0.0021101199090480804
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "613.222",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
},
"secondary": {
"code": "613.2220285",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "3",
"label": "Irrelevant Content"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "2",
"label": "Click Here References"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "16",
"label": "Personal Blog"
}
},
"reasoning_depth": {
"primary": {
"code": "3",
"label": "Intermediate Reasoning"
},
"secondary": {
"code": "2",
"label": "Basic Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "4",
"label": "Highly Correct"
}
},
"education_level": {
"primary": {
"code": "2",
"label": "High School Level"
},
"secondary": {
"code": "1",
"label": "General Audience"
}
}
}
|
1a01aa77535b9ecfb87b9fc36adbcd2f
|
7,958,759,860,919,591,000
|
Skip to main content
Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.
Iron supplementation regulates the progression of high fat diet induced obesity and hepatic steatosis via mitochondrial signaling pathways
Abstract
Disruption of iron metabolism is closely related to metabolic diseases. Iron deficiency is frequently associated with obesity and hepatic steatosis. However, the effects of iron supplementation on obesity and energy metabolism remain unclear. Here we show that a high-fat diet supplemented with iron reduces body weight gain and hepatic lipid accumulation in mice. Iron supplementation was found to reduce mitochondrial morphological abnormalities and upregulate gene transcription involved in mitochondrial function and beta oxidation in the liver and skeletal muscle. In both these tissues, iron supplementation increased the expression of genes involved in heme or iron–sulfur (Fe–S) cluster synthesis. Heme and Fe–S cluster, which are iron prosthetic groups contained in electron transport chain complex subunits, are essential for mitochondrial respiration. The findings of this study demonstrated that iron regulates mitochondrial signaling pathways—gene transcription of mitochondrial component molecules synthesis and their energy metabolism. Overall, the study elucidates the molecular basis underlying the relationship between iron supplementation and obesity and hepatic steatosis progression, and the role of iron as a signaling molecule.
Introduction
Iron homeostasis, a complex process that manifests as iron accumulation or deficiency, is often associated with metabolic diseases when disrupted. Iron deficiency, an aspect of iron metabolism disruption, is a global epidemic1, which poses a concern for metabolic abnormalities that affect approximately 25% of the world population. Similarly, obesity and associated hepatic steatosis are a global issue which increases the risk of developing chronic diseases such as non-alcoholic steatohepatitis (NASH), cardiovascular disease, type-2 diabetes mellitus (T2DM), retinopathy, and certain cancers2. Iron deficiency is positively associated with obesity and hepatic steatosis3,4. The reduction in obesity improves iron status5,6. Furthermore, iron deficiency causes an increase in hepatic lipogenesis and deteriorates systemic lipid homeostasis7,8. Evidently, co-occurrence of iron deficiency, obesity, and hepatic steatosis is more than mere coincidence; rather, they are molecularly related and influence each other9.
Several studies suggest that mitochondrial dysfunction might be one of the underlying central factors that is associated with iron deficiency10,11, obesity12, and hepatic steatosis13. Iron deficiency decreases gene expressions associated with beta-oxidation in mitochondrial-rich liver and skeletal muscle8, which are important target tissues in the prevention and treatment of obesity and hepatic steatosis. However, the mechanism through which iron regulates mitochondrial-related energy metabolism in obesity and hepatic steatosis model remains largely unknown. Therefore, we hypothesized that iron supplementation, a common and effective approach to treating iron deficiency14, could prevent the progression of obesity and hepatic steatosis and designed the present study to test this hypothesis. This study provides insights into the effect of iron supplementation on mitochondrial-related energy metabolism signaling pathways through comprehensive gene expression analysis in the liver and skeletal muscle of iron-supplemented high-fat diet-induced obese mice, addressing the gap to date.
Results
Iron supplementation attenuates the increase in body weight and plasma lipids
We first evaluated the metabolic effects of iron supplementation using sodium ferrous citrate (SFC) in male C57BL/6J mice, which received either an open source control diet (Control), high-fat diet (HF), or HF supplemented with SFC (HF + SFC) for 15 weeks. Since the liver is a major iron storage organ and reflects changes in iron storage associated with dietary iron supplementation15, we measured hepatic iron level as an index of body iron. The findings showed that the hepatic iron level was significantly decreased in HF-fed mice compared to Control-fed mice (Fig. 1a). Hepcidin is a master hormone regulator of iron metabolism and is produced little or none when intracellular iron is deficient. The expression of Hamp1, which encodes hepcidin, was also significantly decreased in the liver (Fig. 1b). These results are common symptoms of iron deficiency induced by HF feeding16. Compared to HF-fed mice, iron supplementation significantly increased hepatic iron level and Hamp1 gene expression (Fig. 1a,b), indicating that HF-induced iron deficiency is attenuated by iron supplementation. Compared with Control-fed mice, the body weight of HF-fed mice increased significantly 1 week following diet initiation (Fig. 1d). The total body weight gain was also significantly increased (Fig. 1e). However, compared to HF-fed mice, the increase in body weight of iron supplemented mice was significantly suppressed from 10 to 15 weeks, and total body weight gain was significantly decreased despite no changes in average food and cumulative energy intake (Fig. 1c–g). The weight of epididymal white adipose tissue (epiWAT) and mesenteric white adipose tissue (mWAT) was significantly increased in HF-fed mice, compared with that of Control-fed mice (see Supplementary Fig. S1a,b). In addition, the mWAT weight was 1.85 ± 0.17 g in HF-fed mice and 1.34 ± 0.21 g in HF + SFC-fed mice (p = 0.058, HF vs. HF + SFC) (see Supplementary Fig. S1b). Furthermore, the body temperature of the HF-fed mice was significantly lower than that of the Control-fed mice (see Supplementary Fig. S1c). The body temperature was 36.93 ± 0.07 ℃ in HF-fed mice and 37.10 ± 0.07 ℃ in HF + SFC-fed mice (p = 0.095, HF vs. HF + SFC). Plasma total cholesterol (T-Cho), insulin, and blood glucose levels were significantly increased in HF-fed mice compared with those of the Control-fed mice (Fig. 2a,c,d). Compared with HF-fed mice, iron supplementation significantly reduced T-Cho levels and glucose levels (Fig. 2a,c), whereas plasma triglycerides (TG) and insulin levels did not show significant changes by iron supplementation (Fig. 2b,d).
Figure 1
figure 1
source control diet (Control; 10% kcal fat), a high-fat diet (HF; 60% kcal fat), or a high-fat diet supplemented with sodium ferrous citrate (HF + SFC) for 15 weeks. (a) Liver iron content. The values were corrected using tissue protein levels (n = 5–6). (b) Analysis of Hamp1 mRNA expression (n = 4–6). (c) Cumulative energy intake for 10–15 weeks per mouse per cage. (d) Body weight and food intake in the different groups (n = 11–12). Food intake was measured for 15 weeks. (e) Body weight gain from 0 to 15 weeks after administering (n = 11–12). (f, g) Longitudinal, (f) food, or (g) energy intake. Data are shown as mean ± SEM values. Statistical analysis was performed using one-way ANOVA followed by Holm–Sidak’s post hoc test. (ae) *p < 0.05; **p < 0.01; ***p < 0.001; ns, not significant. (Significant differences vs. HF). (f, g) *p < 0.05. (Significant differences in HF vs. HF + SFC). #p < 0.05; ##p < 0.01; ###p < 0.001. (Significant differences in HF vs. Control).
Iron supplementation reduces diet-induced weight gain. (ag) Male C57BL/6J mice of 6 weeks of age were fed with an open
Figure 2
figure 2
Metabolic parameters. (ad) Male C57BL/6 J mice of 6 weeks of age were fed with each diet for 15 weeks as specified in Fig. 1. (a, b) Plasma levels of (a) total cholesterol (T-Cho); and (b) triglycerides (TG) in C57BL/6J mice after 15 weeks on different diets (n = 5–6). (c, d) (c) Blood glucose; and (d) plasma insulin levels after 8 weeks on different diets (n = 12). Data are expressed as mean ± SEM values. Statistical analysis was performed using one-way ANOVA followed by Holm–Sidak’s post hoc test. *p < 0.05; ***p < 0.001; ns, not significant. (Significant differences vs. HF).
Iron supplementation reduces hepatic lipid accumulation
The results of Hematoxylin–Eosin (H&E) staining and Oil Red O staining consistently showed severe lipid accumulation in the livers of HF-fed mice compared to that of the Control-fed mice (Fig. 3a). However, the accumulation of lipid droplets in the liver of mice supplemented with iron was less than that of mice fed with HF (Fig. 3a). Furthermore, H&E staining would suggest not only a change in total liver lipid, but also the morphology of the lipid droplets. The size of these lipid droplets was smaller in iron-supplemented mice than that in HF-fed mice. Consistent with the above histological findings, HF-fed mice showed significantly increased liver weight, TG, and T-Cho levels compared with those of Control-fed mice, whereas iron supplementation significantly reduced TG and T-Cho accumulation compared with those of HF-fed mice (Fig. 3b-d).
Figure 3
figure 3
Iron supplementation reduces hepatic lipid accumulation. (ad) Male C57BL/6J mice of 6 weeks of age were fed with each diet for 15 weeks as specified in Fig. 1. (a) Representative image of Hematoxylin–eosin (H&E) and Oil Red O stained liver sections. Scale bar is 50 μm. (b) Weight of liver (n = 5–6). (c, d) (c) Liver triglycerides (TG); and (d) total cholesterol (T-Cho) content (n = 5–6). The values were corrected by the tissue weight. Data are expressed as mean ± SEM values. Statistical analysis was performed using one-way ANOVA followed by Holm–Sidak’s post hoc test. **p < 0.01; ***p < 0.001; ns, not significant. (Significant differences vs. HF).
Iron supplementation reduces morphological abnormalities of the mitochondria and increases transcription of genes associated with energy metabolism in the liver and skeletal muscle
To explore the molecular basis of iron-induced reduction in body weight gain and hepatic lipid accumulation, we investigated the transcription of genes associated with energy metabolism in the liver and skeletal muscle in HF-fed and HF + SFC-fed groups. Gene Set Enrichment Analysis (GSEA) indicated that genes upregulated by iron supplementation were highly enriched in the mitochondrial-associated signaling pathways that regulate processes such as oxidative phosphorylation, respiratory electron transport or translation in the liver and skeletal muscle (Fig. 4a,b, and Supplementary Fig. S2a). Similarly, as indicated by the arrows, an analysis using Transcriptome Analysis Console (TAC) software identified the electron transport chain (ETC), oxidative phosphorylation, and fatty acid beta-oxidation as pathways containing genes upregulated by iron supplementation in both the liver and skeletal muscle (Fig. 4c,d). In the mitochondrial ETC pathway of the liver and skeletal muscle, highly upregulated genes by iron supplementation included those encoding each respiratory chain complex I–V, uncoupling of proteins and/or adenine nucleotide translocator (Fig. 4e,g). Furthermore, HF + SFC-fed group upregulated more than half of the downregulated mitochondrial genes in the HF-fed group (93 genes in the liver, 52.84%; 70 genes in the skeletal muscle, 52.24%) (Fig. 4f,h); HF-induced mitochondrial abnormalities may have been prevented by iron supplementation. These data suggest that mitochondria may play an important role in mechanisms via which iron supplementation attenuates a decline in energy metabolism in the HF-fed group.
Figure 4
figure 4figure 4figure 4
Microarray analysis shows iron supplementation improves transcription of energy metabolism and mitochondrial related genes in the liver and skeletal muscle. (ah) Male C57BL/6J mice of 6 weeks of age were fed with each diet for 15 weeks as specified in Fig. 1. For each group, a mix of all sample cDNAs was used. (a, b) Enrichment plots of genes upregulated in HF + SFC (a) liver; and (b) skeletal muscle (compared to HF). (a) The Kyoto Encyclopedia of Genes and Genomes (KEGG) database; or (b) Reactome database was used. The analysis was performed by Gene Set Enrichment Analysis (GSEA). NES normalized enrichment score. (c, d) Pathways containing upregulated genes by greater than or equal to 1.5-fold in HF + SFC (c) liver; and (d) skeletal muscle (compared to HF) (p < 0.05). WikiPathways database was used. The analysis was performed by Transcriptome Analysis Console (TAC). (e, g) Pathway mapping for electron transport chain (ETC) in (e) liver; and (g) skeletal muscle. Upregulated genes in HF + SFC are shown as red gradations (compared to HF). The analysis was performed by TAC. The pathway mapping was created on the basis of the Wikipathways database (https://www.wikipathways.org/index.php/Pathway:WP295). (f, h) Venn diagrams representing the number of differentially expressed mitochondrial genes (greater than or equal to 1.5-fold) in (f) liver; and (h) skeletal muscle. Mitochondrial genes were based on the MitoCarta2.0 database.
As shown in Fig. 5a, the morphometric analysis of skeletal muscle via electron microscopy revealed regularly aligned small mitochondria in Control-fed mice. However, the mitochondria were frequently fused or swollen and the organization of sarcomeres was disturbed in HF-fed mice. These morphological abnormalities of mitochondria are observed in aged rodents’ skeletal muscle with declined energy metabolism17. In contrast, well organized and regularly arranged sarcomere and mitochondria were observed in the skeletal muscle of iron supplemented mice, indicating the attenuating effects of iron on the morphological abnormalities induced by HF feeding.
Figure 5
figure 5
Iron supplementation reduces mitochondrial morphological abnormalities and increases mitochondrial-associated gene expression. (ai) Male C57BL/6J mice of 6 weeks of age were fed with each diet for 15 weeks as specified in Fig. 1. (a) Representative image of transmission electron microscopy analysis in skeletal muscle. Yellow arrows point to the mitochondria. Scale bar is 1 μm. (b, c) Copy number of mitochondrial DNA (mtDNA) in (b) liver and (c) skeletal muscle (n = 5–6). (d, e) ATP levels normalized by tissue weight in (d) liver and (e) skeletal muscle (n = 5–6). (f, g) ATP levels normalized by mtDNA in (f) liver and (g) skeletal muscle (n = 5–6). (h, i) Analysis of mRNA expression related to fatty acid beta oxidation (β-ox), mitochondrial (Mt), mitochondrial respiratory chain complex I (I), II (II), III (III), IV (IV), and V (V) in (h) liver; and (i) skeletal muscle (n = 5–6). Data are expresses as mean ± SEM values. Statistical analysis was performed using a one-way ANOVA followed by Holm–Sidak’s post hoc test. *p < 0.05; **p < 0.01; ***p < 0.001; ns, not significant. (Significant differences vs. HF).
In the liver, the copy number of mitochondrial DNA (mtDNA) was significantly higher in HF-fed mice than that in Control-fed mice, and significantly decreased in HF + SFC-fed mice compared to that in HF-fed mice (Fig. 5b). In contrast, in skeletal muscle, there were no significant changes among the three groups (Fig. 5c). ATP levels in the liver were not significantly different among the three groups (Fig. 5d). In the skeletal muscle, however, they were significantly increased in HF + SFC-fed mice compared to that in HF-fed mice (Fig. 5e). Furthermore, in the liver of HF-fed mice, the ATP levels normalized by mtDNA (ATP/mtDNA) were significantly decreased compared to those in Control-fed mice (Fig. 5f). In contrast, iron supplementation significantly increased hepatic ATP/mtDNA in HF + SFC-fed mice than in HF-fed mice (Fig. 5f). The ATP/mtDNA of skeletal muscle were 1.00 ± 0.04 in HF-fed mice and 1.28 ± 0.09 in HF + SFC-fed mice (p = 0.082, HF vs. HF + SFC) (Fig. 5g).
Next, we evaluated the expression of the genes regulating energy metabolism using qRT-PCR (Fig. 5h,i). In the liver, expression of genes involved in beta-oxidation and mitochondrial ETC were significantly decreased in HF-fed mice compared to the Control-fed mice. On the contrary, in the skeletal muscle, the expression of the genes encoding the mitochondrial ETC were significantly increased in HF-fed mice. Previous studies have shown that mitochondrial ETC levels are decreased in the liver but increased in the skeletal muscle by high fat diet feeding18,19, showing a trend similar to our data. Furthermore, in the liver, comparing HF-fed mice with HF + SFC-fed mice, iron supplementation significantly increased the expression of genes encoding components of beta-oxidation, such as carnitine palmitoyltransferase 1a (Cpt1a), hydroxyacyl-CoA dehydrogenase (Hadh), very long-chain acyl-CoA dehydrogenase (Vlcad), acyl-CoA synthetase long-chain family member 3 (Acsl3), enoyl-CoA hydratase short chain 1 (Echs1), malonyl-CoA decarboxylase (Mlycd), and long-chain acyl-CoA dehydrogenase (Lcad). In addition, the expression of genes involved in maintaining the function of the mitochondrial ETC, such as FAST kinase domains 2 (Fastkd2) and coenzyme Q10A (Coq10a), and those encoding mitochondrial ETC components, such as ubiquinol-cytochrome c reductase Rieske iron–sulfur polypeptide 1 (Uqcrfs1), mitochondrially encoded cytochrome c oxidase I (mt-Co1), and the ATP synthase H+ transporting mitochondrial F1 complex O subunit (Atp5o), were significantly increased by iron supplementation (Fig. 5h). In the skeletal muscle, similarly, the expression of genes encoding components of beta oxidation and the mitochondrial ETC, such as acyl-CoA oxidase 1 (Acox1), succinate dehydrogenase complex subunit C (Sdhc), cytochrome c oxidase subunit 6B1 (Cox6b1), and Atp5o were significantly increased by iron supplementation. The expression of other mitochondrial related gene such as mitochondrial transcription factor A (Tfam) was also significantly increased (Fig. 5i). It should be considered that Acox1-encoded peroxisomal oxidation is very limited in skeletal muscle, and the functional role and importance of uncoupling protein 3 (Ucp3) is still very much up for debate. However, these findings supported the results of comprehensive gene expression analyses (Fig. 4).
Iron supplementation upregulates the synthetic pathways of heme and iron–sulfur (Fe–S) cluster, the iron prosthetic groups, in the liver and skeletal muscle
To investigate the mechanism by which iron supplementation increased the transcription of mitochondrial-associated genes, we focused on 51 common mitochondrial genes whose expression levels were upregulated in both liver and skeletal muscle of the HF + SFC-fed group compared to the HF-fed group (Fig. 6a, Supplementary Table S1). These genes were highly enriched in pathways associated with the heme and iron–sulfur (Fe–S) cluster, in addition to the mitochondrial energy metabolism (Fig. 6b). Heme and Fe–S cluster are iron prosthetic groups formed from iron processed in mitochondria and contained in ETC complex subunits. Six (11.76%) of the 51 genes were annotated with heme and Fe–S cluster, four genes formed energy generation and ETC associated networks with other mitochondrial genes (Fig. 6c), suggesting the involvement of heme- and Fe–S cluster-associated mitochondrial genes in mitochondrial energy metabolism in the liver and skeletal muscle of HF + SFC-fed mice.
Figure 6
figure 6
Iron supplementation alters the transcription of mitochondrial genes associated with the iron prosthetic groups in the liver and skeletal muscle. (ac) Male C57BL/6J mice of 6 weeks of age were fed with each diet for 15 weeks as specified in Fig. 1. For each group, a mix of all sample cDNAs was used. (a) Venn diagrams showing upregulated expression of 51 mitochondrial genes in the liver and skeletal muscle of HF + SFC compared with HF (greater than or equal to 1.5-fold). Mitochondrial genes were based on the MitoCarta2.0 database. (b) STRING enrichment analysis of 51 upregulated mitochondrial genes in the liver and skeletal muscle of HF + SFC revealed in (a) (FDR < 0.05). Arrows point to the iron prosthetic groups related pathways. UniProt database was used. The analysis was performed by Cytoscape. (c) The STRING networks of 51 upregulated mitochondrial genes in the liver and skeletal muscle of HF + SFC revealed in (a). These networks are annotated with energy generation and ETC using BiNGO (p < 0.001). The iron prosthetic group related genes (red) and other genes (green) are shown. The analysis was performed by Cytoscape.
Furthermore, three genes in the main network—Ppox, Bola1, and Rsad1—are involved in heme or Fe–S clusters synthesis (Fig. 6c). Similarly, the heme skeleton porphyrin synthesis pathway was also upregulated with iron supplementation (Fig. 6b, Supplementary Fig. S2b). The results of qRT-PCR showed that iron supplementation significantly increased the expression of genes involved in the heme synthesis pathway, such as hydroxymethylbilane synthase (Hmbs) and farnesyltransferase cytochrome c oxidase assembly factor 10 (Cox10) in the liver and skeletal muscle compared with HF-fed mice (Fig. 7a,c). In addition, expression of genes involved in the Fe–S cluster assembly synthesis pathway, such as ATP-binding cassette sub-family B member 7 (Abcb7), iron–sulfur cluster assembly 2 homolog mitochondrial (Isca2), and/or bolA-like 3 (Bola3), were significantly increased by iron supplementation (Fig. 7a,c). Moreover, the mRNA expression levels of these genes involved in heme or Fe–S cluster synthesis were positively correlated with those involved in mitochondria and their ETC (Fig. 7b,d).
Figure 7
figure 7
Iron supplementation upregulates the gene expression of iron prosthetic groups synthesis. (ad) Male C57BL/6J mice of 6 weeks of age were fed with each diet for 15 weeks as specified in Fig. 1. (a, c) mRNA expression analysis related to the synthesis of heme (Heme) and Fe–S cluster (Fe–S) in (a) liver; and (c) skeletal muscle (n = 5–6). Data are expressed as mean ± SEM values. Statistical analysis was performed using a one-way ANOVA followed by Holm–Sidak’s post hoc test. *p < 0.05; **p < 0.01; ns not significant. (Significant differences vs. HF). (b, d) Correlation heatmap between relative mRNA expression levels of mitochondrial (Mt) related genes and Heme or Fe–S related genes in the (b) liver; and (d) skeletal muscle of HF and HF + SFC (n = 12). Data were analysed by Pearson correlation coefficient. *p < 0.05; **p < 0.01; ***p < 0.001. (e) Analysis of mRNA expression related to Mt, Heme, and Fe–S from primary hepatocytes isolated from 5-weeks-old male C57BL/6J mice cultured for 24 h (n = 4). These assay mediums were either supplemented with SFC 100 μM (SFC 100), SFC 300 μM (SFC 300), SFC 1000 μM (SFC 1000), or did not contain any supplements (Vehicle). All media contains 0.05% DMSO. Data are expressed as mean ± SEM values. Statistical analysis was performed via one-way ANOVA followed by Holm-Sidak’s post hoc test. *p < 0.05; **p < 0.01; ***p < 0.001; ns not significant. (Significant differences vs. Vehicle).
Furthermore, stimulation of mouse primary hepatocyte by iron triggered the expression of genes associated with mitochondrial ETC, heme synthesis and Fe–S cluster synthesis in a dose-dependent manner (Fig. 7e). These results suggest that iron supplementation may have increased iron prosthetic groups contained in the mitochondrial electron transport system, thereby improving mitochondrial function.
Discussion
The current study administered iron to diet-induced obese mouse models to investigate the effect of iron supplementation on obesity and hepatic steatosis. We found that diet-induced weight gain and hepatic lipid accumulation were reduced by iron supplementation. Furthermore, we found that iron regulates mitochondrial signaling pathways—gene transcription of mitochondrial component molecule synthesis and their energy metabolism. Iron supplementation reduced morphological abnormalities of the mitochondria in skeletal muscle and increased the expression of genes related to mitochondrial ETC and energy metabolism in skeletal muscle and liver. The mechanism underlying these effects may be associated with the synthesis of iron prosthetic groups contained in the mitochondrial ETC (Fig. 8).
Figure 8
figure 8
Suggested mechanism for the reduction in diet-induced weight gain and hepatic lipid accumulation by iron supplementation.
The liver, a major site for iron storage and lipid metabolism, plays a vital role in the interaction and control of these two metabolic pathways20. Previous studies have demonstrated that iron distribution in tissues is altered by obesity, and that hepatic iron storage is reduced in mice fed a high-fat diet16,21,22. In accordance, we also observed hepatic iron deficiency in HF-fed mice (Fig. 1a). Furthermore, it has also been shown that iron deficiency is associated with the progression of steatosis and cellular TG accumulation in the liver7,23,24,25. These symptoms are consistent with the liver phenotype of hepatic iron-deficient obese mice in our experiment (Fig. 3). These findings suggest that hepatic iron deficiency accompanying obesity may aggravate hepatic lipid metabolism abnormalities and steatosis. In addition, the present study revealed that iron supplementation reduced the increase in plasma and hepatic lipids (Figs. 2, 3). Overall, the new findings of the present study show that iron may regulate the liver lipid metabolism and that hepatic steatosis accompanied by iron deficiency may be reduced by iron supplementation.
Most iron in the mammalian cells is directed to heme or Fe–S cluster cofactor synthesis26,27, and mitochondria, a primary site for the synthesis of both, plays an important role in their regulation27. Many heme- and Fe–S cluster-containing proteins essential for ATP synthesis, such as ETC complex subunits and cytochromes, are present in mitochondria. Heme is required for complexes II, III, and IV to function properly28, while Fe–S clusters are contained in complexes I, II, and III27.
Accumulated evidence indicates that heme and Fe–S cluster synthesis pathways play an important role in maintaining mitochondria. Both heme levels and mitochondrial cytochrome c oxidase activity decrease with aging29,30. Moreover, deficiency of 5-aminolevulinate synthase (ALAS) 1, a rate-limiting factor of heme synthesis, induces diminished mitochondrial function in aged mice31. Similarly, mutations in other genes encoding heme synthesis are associated with mitochondrial diseases such as cytochrome c oxygenase deficiency32. Similar to the effect of mutations in the heme synthesis gene, mutations in genes involved in Fe–S cluster synthesis are implicated in mitochondrial diseases, such as the multiple mitochondrial dysfunction syndrome (MMDS)33,34, early onset of severe autosomal recessive disease causing various abnormal neurodevelopmental, lactic acidosis, and premature death.
Thus, the depletion of heme and Fe–S proteins may reduce the activity of the mitochondrial respiratory chain complex, causing mitochondrial dysfunction29,35,36. Interestingly, in this study, the expression of genes involved in both heme and Fe–S cluster synthesis pathways decreased in skeletal muscle and liver of HF-fed mice, compared with that of Control-fed mice (data set have been submitted at NCBI's Gene Expression Omnibus GSE161644 and GSE161646). Therefore, the downregulation of mitochondrial heme and Fe–S cluster synthesis pathways may contribute to reduced mitochondrial function in high-fat diet-induced obesity sufferers.
Iron supplementation significantly elevated the expression of Cox10, the mutations of which are associated with mitochondrial disease, and Bola3 and Isca2, the mutations of which are associated with MMDS and/or oxidative phosphorylation activity33,37,38 (Fig. 7a,c). These results indicate that upregulation of iron prosthetic group synthesis via iron supplementation may be central to improving mitochondrial function.
Comparing HF-fed mice and HF + SFC-fed mice, there was no difference in the intake of diet components except for iron (see Supplementary Tables S2 and S3 online). However, SFC contains ferrous iron (Fe2+), and the HF contains ferric iron (Fe3+), suggesting that different iron states may be a factor influencing iron absorption. Duodenal cytochrome B (Dcytb) reduces Fe3+ in HF to Fe2+, enabling effective iron absorption in the duodenum39, and it has been shown that high-fat diet feeding decreases duodenal Dcytb expression and thereby may contribute to iron deficiency40. In contrast, Fe2+ in SFC might not require the reduction by Dcytb and could be directly absorbed by divalent metal transporter 1 (Dmt1), which plays a major role in iron absorption41. Though it is difficult to conclude clearly from the results of this study, it suggests that the absorption of iron in SFC might not be inhibited by HF feeding.
Our study has a few limitations. First, absence of a Control + SFC group—Our study focused on clarifying the effects of iron with the diet-induced obesity model; it is difficult to establish whether there are effects of iron supplementation in the absence of HF feeding. Therefore, the effects of iron supplementation on other diets need to be carefully discussed.
Second, mice were housed by groups rather than individually, which is a weakness in the assessment of food and energy intake.
Third, the percentage of sucrose in the diet was different between the Control diet (35 kcal%) and HF diet (7 kcal%). Therefore, differences in sucrose intake may affect metabolism.
Fourth, HF-fed mice had significantly higher caloric intake than Control-fed mice (Fig. 1c), indicating that HF-fed mice ate more micronutrients than the Control-fed mice. Interestingly, HF-fed mice caused iron deficiency in the liver, despite higher intake of iron compared to Control-fed mice (Fig. 1a). However, the detailed mechanism, which is probably related to absorption and circulation, is unknown from our results.
Regarding liver effects, previous studies have indicated that iron deficiency in the liver may be attributed to obesity and hepatic steatosis, but iron overload may be responsible for the deterioration of NASH, which is caused by the progression of hepatic steatosis42,43,44. In the liver, iron overload may induce oxidative stress by producing free radicals, stimulate hepatic stellate cells, and increase collagen production, which can accelerate the progression of liver fibrosis45. In this study, the mouse diet-induced obesity models neither exhibited severe fibrosis nor reached NASH. Therefore, iron supplementation was effective, whereas iron supplementation in the NASH model could aggravate the oxidative stress and contribute to the development of NASH. Therefore, to put iron supplementation into practical use to improve energy metabolism and hepatic steatosis, it is important to consider whether iron supplementation will be effective or lead to deterioration, as observed in the NASH model. In the future, in addition to investigating the obesity model, an in-depth investigation into the effect of iron on the NASH model is required.
The above results indicate that the effect of iron may change according to internal conditions, such as the presence or absence of diseases, including obesity. Under conditions of functional iron deficiency, accompanied by impaired erythropoiesis and haemoglobin synthesis, normal or high dietary iron supplementation may cause pathological iron accumulation in tissues46. This suggests that iron supplementation may be beneficial or detrimental depending on physical conditions. Therefore, when supplementing patients with iron, it is prudent to priorly evaluate the patient’s iron accumulation levels and administer the appropriate amount of iron supplements. However, complications of iron deficiency and chronic diseases make it difficult to diagnose iron status clearly47. Serum ferritin, serum iron, total iron-binding capacity (TIBC), and transferrin levels, the common biomarkers for iron deficiency, fluctuate with an acute and chronic infection or inflammation47. Therefore, the development of biomarkers beneficial for iron deficiency with chronic disease complications, including obesity, should be explored. Several current therapeutic strategies for chronic diseases are aimed at targeting muscle mitochondria to increase energy metabolism efficiency. It has been suggested that supplementing optimal iron may be important for an appropriate response to such attempts, and particularly in T2DM, the need for detailed studies on iron substitution has been discussed48. Our study shows that iron supplementation could be an effective strategy to prevent the progression of obesity and hepatic steatosis, which may serve to advance studies on iron and energy metabolism, for which many unclear mechanisms remain.
Methods
Animal experiments
This study was approved by the institutional review board at Keio University. All experiments were performed in accordance with the Keio University animal experimentation guidelines. All animal studies were carried out in compliance with the ARRIVE guidelines. Five-week-old male C57BL/6J mice (Japan SLC, Inc., Shizuoka, Japan) were acclimated for 1 week. At 6 weeks of age, their diets were changed to an open source control or HF diet with or without iron supplementation. Body weight and food intake were measured weekly. The open source control diet (D12450B) contained 10 kcal% fat, 20 kcal% protein, and 70 kcal% carbohydrates, whereas the HF diet (D12492) contained 60 kcal% fat, 20 kcal% protein, and 20 kcal% carbohydrates (Research Diets, Inc., New Brunswick, NJ, USA). Both the open source control diet and HF diet originally contained iron (see Supplementary Table S3 online). Iron supplemented mice were fed with 0.023% (w/w) SFC (Komatsuya, Osaka, Japan) simultaneously as the HF diet. These food compositions are shown in the Supplementary Tables S2 and S3 online. Mice always had free access to food and water. After 7 weeks of each diet, body temperature of the rectum was measured using a thermo-register for mice (AD-1687) (A&D, Tokyo, Japan). After 8 weeks of each diet, glucose parameters were measured. After 15 weeks of each diet, mice were fasted for 4 h and anesthetized with isoflurane, and tissues were collected. Each tissue was weighed and then rapidly frozen in liquid nitrogen. It was then used for RNA isolation, lipid, iron, and ATP measurements, and histological analysis. The facility where all the mice were housed had a 12-h light (from 8 a.m. to 8 p.m.)-dark (from 8 p.m. to 8 a.m.) cycle and temperature control at 23–25 ℃.
Biochemistry and determination of glucose and lipids
After 8 weeks of each treatment, blood and plasma were collected from the tail of mice fasted for 6 h from 8 a.m. to 2 p.m. to measure glucose and insulin. Blood glucose was measured using Life check (GUNZE Limited, Osaka, Japan). Blood was heparinized, and plasma insulin concentrations were measured using ELISA (Morinaga Institute of Biological Science, Inc., Kanagawa, Japan). After 15 weeks of each treatment, plasma was collected from the vena cava of mice fasted for 4 h from 6 a.m. to 10 a.m. and lipids were measured. Plasma triglycerides (TG) and total cholesterol (T-Cho) were measured using commercial enzymatic assay kits. Enzymatic assay kits used were as follows: TG—Determiner L (Kyowa Medex, Tokyo, Japan); and T-Cho—Cholesterol E-test Wako (Wako, Osaka, Japan). Liver lipid measurements were performed as described previously49. Briefly, lipids were extracted from the liver using the Folch method50. Approximately 50 mg of the center of each tissue sample was cut out from samples stored at − 80 °C. Each tissue sample was homogenized in methanol at room temperature. The same amount of chloroform (as methanol) was added to the extract. The extract was washed with ultrapure water and centrifuged at 15,000 rpm. The lower layer was transferred to a new tube and dried for one week to evaporate the chloroform. The dried product was resuspended in isopropanol and used for lipid measurements. As in the measurement of plasma lipids, liver TG was measured using Determiner L (Kyowa Medex, Tokyo, Japan), and liver T-Cho was measured using the Cholesterol E-test Wako (Wako, Osaka, Japan). Multiskan FC (Thermo Fisher Scientific, Waltham, MA, USA) was used for data measurement.
mRNA expression analysis by qRT-PCR
RNeasy Fibrous Tissue Mini Kit (Qiagen, Hilden, Germany) was used to extract skeletal muscle total RNA, and RNeasy Mini Kit (Qiagen, Hilden, Germany) was used for other tissues. Total RNA was extracted from the tissue cryopreserved with liquid nitrogen according to the kit’s instructions. Next, cDNA was synthesised according to the instructions using a kit of PrimeScript RT Master Mix (TaKaRa, Siga, Japan). Gene expression was measured by real-time PCR using synthesised cDNA. SYBR Premix Ex Taq II (TaKaRa, Siga, Japan) and THUNDERBIRD SYBR qPCR Mix (Toyobo, Osaka, Japan) were used according to the kit’s instructions. Measurements were performed via PikoReal and QuantStudio 5 (Thermo Fisher Scientific, Waltham, MA, USA). The primer set sequences are listed in the Supplementary Table S4 online.
Microarray analysis
Liver and skeletal muscle total RNA and cDNA were prepared as described above. The microarray was performed on an Affymetrix GeneChip Mouse Genome 430 2.0 Array, and data analysis was performed using TAC Software (Thermo Fisher Scientific, Waltham, MA, USA), version 4.0, GSEA, version 3.0, Venny, version 2.1.0, and Cytoscape, version 3.8.0. TAC analysis used the WikiPathways database, and GSEA analysis used MSigDB, version 6.2 and 7.2. Cytoscape analysis used UniProt database and stringApp, version 1.5.1 for enrichment analysis; and Gene Ontology database and BiNGO, version 3.0.4 for network annotation. Mitochondrial genes were based on MitoCarta2.0.
Measurement of iron levels
Intracellular iron concentration was measured using Metallo Assay Kit (Metallogenics, Chiba, Japan). To measure the intracellular iron concentration, approximately 50 mg of the center of each tissue sample was cut out from samples stored at − 80 °C. Each tissue was homogenized in ice-cold T-PER Tissue Protein Extraction Reagent (potentially containing 25 mM bicine and 150 mM NaCl [pH 7.6]) (Thermo Fisher Scientific, Waltham, MA, USA), and 1 M hydrochloric acid was added to the supernatant to obtain a concentration of 0.01 M. The supernatant obtained by centrifugation at 10,000 rpm was used for measurements. Intracellular iron concentration was corrected for the actual amount of protein. Varioskan LUX (Thermo Fisher Scientific, Waltham, MA, USA) was used for data measurement.
Measurement of ATP levels
Intracellular ATP level was measured using ''Tissue'' ATP assay Kit (Toyo B-Net Co., Ltd., Tokyo, Japan) based on the luciferase luminescence method according to the kit's instructions. For measurements, liver and skeletal muscle were preferentially collected after blood sampling, rapidly frozen in liquid nitrogen, and stored at − 80 °C. Briefly, approximately 20 mg of each tissue was homogenized in homogenate buffer on ice and supernatant was used for this assay. Varioskan LUX (Thermo Fisher Scientific, Waltham, MA, USA) was used for data measurement. The ATP level was normalized by mtDNA content. The mtDNA content was measured as described previously51.
Histological analysis and Transmission Electron Microscopy (TEM)
To perform hematoxylin and eosin (H&E) staining, collected liver tissues were fixed using 10% neutral buffered formalin immediately. Then tissue sections were prepared by embedding in paraffin. To perform Oil Red O staining, frozen sections were prepared using the collected liver tissue. These staining procedures were performed according to standard methods. Photographs were taken with a microscope camera (Moticam 1080; Shimadzu RIKA, Tokyo, Japan). ImageJ, version 1.52a was used to describe the scale bar. For electron microscope analysis, collected gastrocnemius tissues were fixed immediately using 2.5% glutaraldehyde in 0.1 M phosphate buffer (pH 7.4). To make tissue sections, these samples were dehydrated with ethanol, embedded in epoxy resin and then sliced using a microtome with a diamond knife. Uranyl acetate and lead citrate were prepared, and tissue sections collected on mesh grids were stained. Gastrocnemius morphology and mitochondria were observed using an electron microscope (1230 EXII; JEOL, Tokyo, Japan). Images of tissue sections were taken with a Gatan bio scan camera model 792.
Cell culture
Hepatocytes were collected from five-weeks-old male C57BL/6J mice (Japan SLC, Inc., Shizuoka, Japan) given MF diet (Oriental Yeast Co., Ltd., Tokyo, Japan). Mice were anaesthetised, and the liver was perfused with a liver perfusion medium (Gibco) and then with a liver digest medium (Gibco) (both flow rate 5 mL/min). The liver was subdivided in L-15 medium (Gibco) to separate hepatocytes. Hepatocytes were washed twice with L-15 medium and then washed three times with hepatocyte wash medium (Gibco). Hepatocytes were isolated by centrifugation at 500 rpm for 3 min at 4 ℃, resuspended in William's Medium E (Gibco), supplemented with 10% FBS, 100 units/mL penicillin and 100 µg/mL streptomycin (Wako, Osaka, Japan), and plated at a density of 8 × 104 cells/cm2. Plates coated with rat tail collagen I was used. Cells were incubated under conditions of 37 ℃ and 5% CO2. After 4 h, the medium was replaced with Dulbecco's modified eagle medium (DMEM) supplemented with 10% (v/v) FBS, 100 units/mL penicillin, 100 µg/mL streptomycin, 0.5 µM dexamethasone, and 0.4 µM insulin. After 18 h, the medium was replaced with assay medium and further incubated for 24 h. The replacement media were DMEM containing 10% (v/v) FBS, 100 units/mL penicillin, 100 µg/mL streptomycin and 0.05% dimethyl sulfoxide (DMSO), either supplemented with or without SFC. Cells were harvested, and total RNA was isolated using Sepasol-RNA I Super G (Nacalai tesque, Kyoto, Japan) according to the kit’s instructions, and used for evaluation of the expression of genes associated with mitochondrial ETC, heme and Fe–S cluster synthesis.
Statistical analysis
Graph Pad Prism, version 8.4.3 was used for statistical analysis. Grubbs test was used to identify outliers. Outliers were excluded from the original data. One-way analysis of variance followed by post-hoc Holm–Sidak’s test was performed to determine statistical significance. This test was performed using HF or Vehicle as a control. Values are expressed as mean ± SEM. Results showing two-tailed p-values < 0.05 were considered statistically significant.
Data availability
Microarray data set have been deposited in NCBI's Gene Expression Omnibus and are accessible through GEO Series accession number GSE161644 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE161644) and GSE161646 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE161646). The datasets generated and analysed during the current study are available from the corresponding author on reasonable request.
References
1. Aigner, E., Feldman, A. & Datz, C. Obesity as an emerging risk factor for iron deficiency. Nutrients 6, 3587–3600 (2014).
PubMed PubMed Central Article CAS Google Scholar
2. Forbes, J. M. & Cooper, M. E. Mechanisms of diabetic complications. Physiol. Rev. 93, 137–188 (2013).
CAS PubMed Article PubMed Central Google Scholar
3. Wenzel, B. J., Stults, H. B. & Mayer, J. Hypoferraemia in obese adolescents. Lancet Lond. Engl. 2, 327–328 (1962).
CAS Article Google Scholar
4. Siddique, A., Nelson, J. E., Aouizerat, B., Yeh, M. M. & Kowdley, K. V. Iron deficiency in patients with nonalcoholic fatty liver disease is associated with obesity, female sex, and low serum hepcidin. Clin. Gastroenterol. Hepatol. Off. Clin. Pract. J. Am. Gastroenterol. Assoc. 12, 1170–1178 (2014).
CAS Google Scholar
5. Gong, L. et al. Weight loss, inflammatory markers, and improvements of iron status in overweight and obese children. J. Pediatr. 164, 795-800.e2 (2014).
CAS PubMed Article PubMed Central Google Scholar
6. Tussing-Humphreys, L. M. et al. Decreased serum hepcidin and improved functional iron status 6 months after restrictive bariatric surgery. Obesity 18, 2010–2016 (2010).
CAS PubMed Article PubMed Central Google Scholar
7. Bartholmey, S. J. & Sherman, A. R. Carnitine levels in iron-deficient rat pups. J. Nutr. 115, 138–145 (1985).
CAS PubMed Article PubMed Central Google Scholar
8. Davis, M. R. et al. Enhanced expression of lipogenic genes may contribute to hyperglycemia and alterations in plasma lipids in response to dietary iron deficiency. Genes Nutr. 7, 415–425 (2012).
CAS PubMed PubMed Central Article Google Scholar
9. Datz, C., Felder, T. K., Niederseer, D. & Aigner, E. Iron homeostasis in the metabolic syndrome. Eur. J. Clin. Invest. 43, 215–224 (2013).
CAS PubMed Article PubMed Central Google Scholar
10. Stugiewicz, M. et al. The influence of iron deficiency on the functioning of skeletal muscles: Experimental evidence and clinical implications. Eur. J. Heart Fail. 18, 762–773 (2016).
PubMed Article Google Scholar
11. Hoes, M. F. et al. Iron deficiency impairs contractility of human cardiomyocytes through decreased mitochondrial function. Eur. J. Heart Fail. 20, 910–919 (2018).
CAS PubMed PubMed Central Article Google Scholar
12. de Mello, A. H., Costa, A. B., Engel, J. D. G. & Rezin, G. T. Mitochondrial dysfunction in obesity. Life Sci. 192, 26–32 (2018).
PubMed Article CAS Google Scholar
13. Wei, Y., Rector, R. S., Thyfault, J. P. & Ibdah, J. A. Nonalcoholic fatty liver disease and mitochondrial dysfunction. World J. Gastroenterol. 14, 193–199 (2008).
CAS PubMed PubMed Central Article Google Scholar
14. Camaschella, C. Iron-deficiency anemia. N. Engl. J. Med. 372, 1832–1843 (2015).
PubMed Article Google Scholar
15. Torrance, J. D., Charlton, R. W., Schmaman, A., Lynch, S. R. & Bothwell, T. H. Storage iron in `muscle’. J. Clin. Pathol. 21, 495–500 (1968).
CAS PubMed PubMed Central Article Google Scholar
16. Padda, R. S. et al. A high-fat diet modulates iron metabolism but does not promote liver fibrosis in hemochromatotic Hjv−/− mice. Am. J. Physiol. Gastrointest. Liver Physiol. 308, G251–G261 (2014).
PubMed Article CAS Google Scholar
17. Satoh, A. et al. Sirt1 extends life span and delays aging in mice through the regulation of Nk2 homeobox 1 in the DMH and LH. Cell Metab. 18, 416–430 (2013).
CAS PubMed PubMed Central Article Google Scholar
18. García-Ruiz, I. et al. High-fat diet decreases activity of the oxidative phosphorylation complexes and causes nonalcoholic steatohepatitis in mice. Dis. Model. Mech. 7, 1287–1296 (2014).
PubMed PubMed Central Article CAS Google Scholar
19. Li, X., Higashida, K., Kawamura, T. & Higuchi, M. Time course of decrease in skeletal muscle mitochondrial biogenesis after discontinuation of high-fat diet. J. Nutr. Sci. Vitaminol. (Tokyo) 64, 233–238 (2018).
CAS Article Google Scholar
20. Ahmed, U., Latham, P. S. & Oates, P. S. Interactions between hepatic iron and lipid metabolism with possible relevance to steatohepatitis. World J. Gastroenterol. WJG 18, 4651–4658 (2012).
CAS PubMed Article Google Scholar
21. Orr, J. S. et al. Obesity alters adipose tissue macrophage iron content and tissue iron distribution. Diabetes 63, 421–432 (2014).
CAS PubMed PubMed Central Article Google Scholar
22. Jiang, S. et al. Long-term high-fat diet decreases hepatic iron storage associated with suppressing TFR2 and ZIP14 expression in rats. FASEB J. 33, 583.4 (2019).
Google Scholar
23. Sherman, A. R., Guthrie, H. A., Wolinsky, I. & Zulak, I. M. Iron deficiency hyperlipidemia in 18-day-old rat pups: Effects of milk lipids, lipoprotein lipase, and triglyceride synthesis. J. Nutr. 108, 152–162 (1978).
CAS PubMed Article Google Scholar
24. Sherman, A. R., Bartholmey, S. J. & Perkins, E. G. Fatty acid patterns in iron-deficient maternal and neonatal rats. Lipids 17, 639–643 (1982).
CAS PubMed Article Google Scholar
25. Sherman, A. R. Lipogenesis in iron-deficient adult rats. Lipids 13, 473–478 (1978).
CAS PubMed Article Google Scholar
26. Muckenthaler, M. U., Rivella, S., Hentze, M. W. & Galy, B. A red carpet for iron metabolism. Cell 168, 344–361 (2017).
CAS PubMed PubMed Central Article Google Scholar
27. Barupala, D. P., Dzul, S. P., Riggs-Gelasco, P. J. & Stemmler, T. L. Synthesis, delivery and regulation of eukaryotic heme and Fe–S cluster cofactors. Arch. Biochem. Biophys. 592, 60–75 (2016).
CAS PubMed PubMed Central Article Google Scholar
28. Alam, M. M., Lal, S., FitzGerald, K. E. & Zhang, L. A holistic view of cancer bioenergetics: mitochondrial function and respiration play fundamental roles in the development and progression of diverse tumors. Clin. Transl. Med. 5, 3 (2016).
PubMed PubMed Central Article Google Scholar
29. Bitar, M. & Weiner, M. Modification of age-induced changes in heme and hemoproteins by testosterone in male rats. Mech. Ageing Dev. 23, 285–296 (1983).
CAS PubMed Article Google Scholar
30. Hayashi, J. et al. Nuclear but not mitochondrial genome involvement in human age-related mitochondrial dysfunction. Functional integrity of mitochondrial DNA from aged subjects. J. Biol. Chem. 269, 6878–6883 (1994).
CAS PubMed Article PubMed Central Google Scholar
31. Saitoh, S. et al. 5-aminolevulinic acid (ALA) deficiency causes impaired glucose tolerance and insulin resistance coincident with an attenuation of mitochondrial function in aged mice. PLoS ONE 13, e0189593 (2018).
PubMed PubMed Central Article CAS Google Scholar
32. Alfadhel, M. et al. Infantile cardioencephalopathy due to a COX15 gene defect: Report and review. Am. J. Med. Genet. A. 155, 840–844 (2011).
CAS Article Google Scholar
33. Al-Hassnan, Z. N. et al. ISCA2 mutation causes infantile neurodegenerative mitochondrial disorder. J. Med. Genet. 52, 186–194 (2015).
CAS PubMed Article Google Scholar
34. Xu, W., Barrientos, T. & Andrews, N. C. Iron and copper in mitochondrial diseases. Cell Metab. 17, 319–328 (2013).
CAS PubMed PubMed Central Article Google Scholar
35. Atamna, H., Killilea, D. W., Killilea, A. N. & Ames, B. N. Heme deficiency may be a factor in the mitochondrial and neuronal decay of aging. Proc. Natl. Acad. Sci. USA 99, 14807–14812 (2002).
ADS CAS PubMed Article Google Scholar
36. Diaz, F., Enríquez, J. A. & Moraes, C. T. Cells lacking rieske iron–sulfur protein have a reactive oxygen species-associated decrease in respiratory complexes I and IV. Mol. Cell. Biol. 32, 415–429 (2012).
CAS PubMed PubMed Central Article Google Scholar
37. Cameron, J. M. et al. Mutations in iron–sulfur cluster scaffold genes NFU1 and BOLA3 cause a fatal deficiency of multiple respiratory chain and 2-oxoacid dehydrogenase enzymes. Am. J. Hum. Genet. 89, 486–495 (2011).
CAS PubMed PubMed Central Article Google Scholar
38. Tajima, K. et al. Mitochondrial lipoylation integrates age-associated decline in brown fat thermogenesis. Nat. Metab. 1, 886–898 (2019).
CAS PubMed PubMed Central Article Google Scholar
39. McKie, A. T. The role of Dcytb in iron metabolism: An update. Biochem. Soc. Trans. 36, 1239–1241 (2008).
CAS PubMed Article Google Scholar
40. Sonnweber, T. et al. High-fat diet causes iron deficiency via hepcidin-independent reduction of duodenal iron absorption. J. Nutr. Biochem. 23, 1600–1608 (2012).
CAS PubMed Article PubMed Central Google Scholar
41. Shawki, A. et al. Intestinal DMT1 is critical for iron absorption in the mouse but is not required for the absorption of copper or manganese. Am. J. Physiol. Gastrointest. Liver Physiol. 309, G635–G647 (2015).
PubMed PubMed Central Article CAS Google Scholar
42. Bacon, B. R., Farahvash, M. J., Janney, C. G. & Neuschwander-Tetri, B. A. Nonalcoholic steatohepatitis: An expanded clinical entity. Gastroenterology 107, 1103–1109 (1994).
CAS PubMed Article PubMed Central Google Scholar
43. George, D. K. et al. Increased hepatic iron concentration in nonalcoholic steatohepatitis is associated with increased fibrosis. Gastroenterology 114, 311–318 (1998).
MathSciNet CAS PubMed Article PubMed Central Google Scholar
44. Fargion, S. et al. Hyperferritinemia, iron overload, and multiple metabolic alterations identify patients at risk for nonalcoholic steatohepatitis. Am. J. Gastroenterol. 96, 2448–2455 (2001).
CAS PubMed Article PubMed Central Google Scholar
45. Harrison, S. A. & Bacon, B. R. Hereditary hemochromatosis: Update for 2003. J. Hepatol. 38, 14–23 (2003).
Article Google Scholar
46. Thomas, C. & Thomas, L. Biochemical markers and hematologic indices in the diagnosis of functional iron deficiency. Clin. Chem. 48, 1066–1076 (2002).
CAS PubMed Article PubMed Central Google Scholar
47. Skikne, B. S. et al. Improved differential diagnosis of anemia of chronic disease and iron deficiency anemia: A prospective multicenter evaluation of soluble transferrin receptor and the sTfR/log ferritin index. Am. J. Hematol. 86, 923–927 (2011).
CAS PubMed Article PubMed Central Google Scholar
48. Dziegala, M. et al. Iron deficiency as energetic insult to skeletal muscle in chronic diseases. J. Cachexia Sarcopenia Muscle 9, 802–815 (2018).
PubMed PubMed Central Article Google Scholar
49. Watanabe, M. et al. Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c. J. Clin. Invest. 113, 1408–1418 (2004).
CAS PubMed PubMed Central Article Google Scholar
50. Folch, J., Lees, M. & Stanley, G. H. S. A simple method for the isolation and purification of total lipides from animal tissues. J. Biol. Chem. 226, 497–509 (1957).
CAS Article Google Scholar
51. Quiros, P. M., Goyal, A., Jha, P. & Auwerx, J. Analysis of mtDNA/nDNA ratio in mice. Curr. Protoc. Mouse Biol. 7, 47–54 (2017).
CAS PubMed PubMed Central Article Google Scholar
Download references
Acknowledgements
This study was supported in part by JSPS KAKENHI Grant numbers JP16H05292 to M.W.; Program for the Advancement of Research in Core Projects under Keio University’s Longevity Initiative to M.W. and K.T.; Japan Agency for Medical Research and Development (AMED) under Grant Number JP21fk0210073 to M.W.; and Taikichiro Mori Memorial Research Grants to N.K.. We greatly thank Dr. Setsuo Takekawa at Shonan Keiiku Hospital for his continuous support, Dr. Tetsuya Yano and Dr. Shinsuke Shibata for the assistance of electron microscope analysis, Dr. Tohru Tanaka for discussion and the Mitsuhiro Watanabe laboratory members for technical assistance of the whole research. The summary image was created with BioRender.com by N.K.
Author information
Affiliations
Authors
Contributions
N.K. devised and designed this study, conducted experiments, data analysis and its interpretation, and wrote this manuscript. Y.Y. helped with the experiments, reviewed and assisted in writing the manuscript. H.T., U.N., S.H., T.T. and A.N. performed experiments. Y.O. performed experiments and analysed data. K.T. advised and assisted the study. M.W. supervised the study design and data interpretation and takes responsibility for the overall contents.
Corresponding authors
Correspondence to Kazuo Tsubota or Mitsuhiro Watanabe.
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Reprints and Permissions
About this article
Verify currency and authenticity via CrossMark
Cite this article
Kitamura, N., Yokoyama, Y., Taoka, H. et al. Iron supplementation regulates the progression of high fat diet induced obesity and hepatic steatosis via mitochondrial signaling pathways. Sci Rep 11, 10753 (2021). https://doi.org/10.1038/s41598-021-89673-8
Download citation
• Received:
• Accepted:
• Published:
• DOI: https://doi.org/10.1038/s41598-021-89673-8
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.
Search
Quick links
Nature Briefing
Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.
Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing
|
{
"url": "https://www.nature.com/articles/s41598-021-89673-8",
"source_domain": "www.nature.com",
"snapshot_id": "crawl=CC-MAIN-2022-21",
"warc_metadata": {
"Content-Length": "380815",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:3CUDPJEFS7RYQGCRQTCPTXEQZEJAPWB3",
"WARC-Concurrent-To": "<urn:uuid:22a59d3e-a19a-4d66-a0a4-81582eb059d8>",
"WARC-Date": "2022-05-20T00:48:06",
"WARC-IP-Address": "146.75.32.95",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:37ZVZXU2XBZT7CAG36FDHOKDMVYMOZBX",
"WARC-Record-ID": "<urn:uuid:a4207249-9a4e-46c3-88c2-03681dd0bcdc>",
"WARC-Target-URI": "https://www.nature.com/articles/s41598-021-89673-8",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:f5ec2674-1176-413e-bc10-8ced09671630>"
},
"warc_info": "isPartOf: CC-MAIN-2022-21\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for May 2022\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-169\r\nsoftware: Apache Nutch 1.18 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.3-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
21,
22,
356,
357,
496,
497,
506,
507,
1758,
1759,
1772,
1773,
2791,
2792,
3887,
3888,
3896,
3897,
3975,
3976,
6593,
6594,
6603,
6612,
6613,
7591,
7592,
7711,
7712,
7721,
7730,
7731,
8316,
8317,
8373,
8374,
9227,
9228,
9237,
9246,
9247,
9903,
9904,
10085,
10086,
11724,
11725,
11734,
11759,
11760,
13207,
13208,
13863,
13864,
13873,
13882,
13883,
15004,
15005,
15987,
15988,
18356,
18357,
18514,
18515,
19493,
19494,
19503,
19512,
19513,
20653,
20654,
21743,
21744,
21753,
21762,
21763,
23197,
23198,
23598,
23599,
23610,
23611,
24405,
24406,
24415,
24424,
24425,
24547,
24548,
25697,
25698,
26187,
26188,
27078,
27079,
27717,
27718,
28138,
28139,
29058,
29059,
29424,
29425,
29551,
29552,
29734,
29735,
30160,
30161,
31312,
31313,
33037,
33038,
33046,
33047,
33066,
33067,
34831,
34832,
34885,
34886,
36582,
36583,
36619,
36620,
37424,
37425,
37445,
37446,
38105,
38106,
38133,
38134,
38920,
38921,
38947,
38948,
39612,
39613,
39678,
39679,
40791,
40792,
40805,
40806,
42416,
42417,
42438,
42439,
42896,
42897,
42915,
42916,
43324,
43325,
43336,
43337,
43464,
43465,
43523,
43524,
43631,
43632,
43690,
43691,
43811,
43812,
43846,
43847,
44153,
44154,
44179,
44180,
44338,
44339,
44397,
44398,
44572,
44573,
44631,
44632,
44747,
44748,
44806,
44807,
45007,
45008,
45066,
45067,
45211,
45212,
45270,
45271,
45461,
45462,
45499,
45500,
45669,
45670,
45728,
45729,
45864,
45865,
45907,
45908,
46077,
46078,
46136,
46137,
46223,
46224,
46261,
46262,
46410,
46411,
46469,
46470,
46674,
46675,
46717,
46718,
46882,
46883,
46941,
46942,
47135,
47136,
47194,
47195,
47412,
47413,
47447,
47448,
47643,
47644,
47686,
47687,
47824,
47825,
47883,
47884,
48052,
48053,
48073,
48074,
48297,
48298,
48340,
48341,
48491,
48492,
48534,
48535,
48625,
48626,
48668,
48669,
48794,
48795,
48853,
48854,
49054,
49055,
49113,
49114,
49361,
49362,
49415,
49416,
49574,
49575,
49617,
49618,
49840,
49841,
49899,
49900,
50121,
50122,
50180,
50181,
50328,
50329,
50363,
50364,
50504,
50505,
50547,
50548,
50669,
50670,
50728,
50729,
50927,
50928,
50975,
50976,
51188,
51189,
51247,
51248,
51470,
51471,
51529,
51530,
51673,
51674,
51732,
51733,
51844,
51845,
51887,
51888,
52056,
52057,
52115,
52116,
52332,
52333,
52391,
52392,
52571,
52572,
52630,
52631,
52804,
52805,
52875,
52876,
53074,
53075,
53133,
53134,
53246,
53247,
53276,
53277,
53433,
53434,
53492,
53493,
53747,
53748,
53806,
53807,
53958,
53959,
54012,
54013,
54164,
54165,
54223,
54224,
54395,
54396,
54430,
54431,
54565,
54566,
54624,
54625,
54645,
54646,
54663,
54664,
55388,
55389,
55408,
55409,
55422,
55423,
55431,
55432,
55446,
55447,
55902,
55903,
55925,
55926,
55981,
55982,
56002,
56003,
56023,
56024,
56068,
56069,
56092,
56093,
56110,
56111,
56230,
56231,
56257,
56258,
56281,
56282,
57133,
57134,
57159,
57160,
57179,
57180,
57227,
57228,
57246,
57247,
57501,
57502,
57520,
57521,
57535,
57536,
57550,
57551,
57566,
57567,
57619,
57620,
57629,
57630,
57828,
57829,
57836,
57837,
57849,
57850,
57866,
57867,
57963,
57964
],
"line_end_idx": [
21,
22,
356,
357,
496,
497,
506,
507,
1758,
1759,
1772,
1773,
2791,
2792,
3887,
3888,
3896,
3897,
3975,
3976,
6593,
6594,
6603,
6612,
6613,
7591,
7592,
7711,
7712,
7721,
7730,
7731,
8316,
8317,
8373,
8374,
9227,
9228,
9237,
9246,
9247,
9903,
9904,
10085,
10086,
11724,
11725,
11734,
11759,
11760,
13207,
13208,
13863,
13864,
13873,
13882,
13883,
15004,
15005,
15987,
15988,
18356,
18357,
18514,
18515,
19493,
19494,
19503,
19512,
19513,
20653,
20654,
21743,
21744,
21753,
21762,
21763,
23197,
23198,
23598,
23599,
23610,
23611,
24405,
24406,
24415,
24424,
24425,
24547,
24548,
25697,
25698,
26187,
26188,
27078,
27079,
27717,
27718,
28138,
28139,
29058,
29059,
29424,
29425,
29551,
29552,
29734,
29735,
30160,
30161,
31312,
31313,
33037,
33038,
33046,
33047,
33066,
33067,
34831,
34832,
34885,
34886,
36582,
36583,
36619,
36620,
37424,
37425,
37445,
37446,
38105,
38106,
38133,
38134,
38920,
38921,
38947,
38948,
39612,
39613,
39678,
39679,
40791,
40792,
40805,
40806,
42416,
42417,
42438,
42439,
42896,
42897,
42915,
42916,
43324,
43325,
43336,
43337,
43464,
43465,
43523,
43524,
43631,
43632,
43690,
43691,
43811,
43812,
43846,
43847,
44153,
44154,
44179,
44180,
44338,
44339,
44397,
44398,
44572,
44573,
44631,
44632,
44747,
44748,
44806,
44807,
45007,
45008,
45066,
45067,
45211,
45212,
45270,
45271,
45461,
45462,
45499,
45500,
45669,
45670,
45728,
45729,
45864,
45865,
45907,
45908,
46077,
46078,
46136,
46137,
46223,
46224,
46261,
46262,
46410,
46411,
46469,
46470,
46674,
46675,
46717,
46718,
46882,
46883,
46941,
46942,
47135,
47136,
47194,
47195,
47412,
47413,
47447,
47448,
47643,
47644,
47686,
47687,
47824,
47825,
47883,
47884,
48052,
48053,
48073,
48074,
48297,
48298,
48340,
48341,
48491,
48492,
48534,
48535,
48625,
48626,
48668,
48669,
48794,
48795,
48853,
48854,
49054,
49055,
49113,
49114,
49361,
49362,
49415,
49416,
49574,
49575,
49617,
49618,
49840,
49841,
49899,
49900,
50121,
50122,
50180,
50181,
50328,
50329,
50363,
50364,
50504,
50505,
50547,
50548,
50669,
50670,
50728,
50729,
50927,
50928,
50975,
50976,
51188,
51189,
51247,
51248,
51470,
51471,
51529,
51530,
51673,
51674,
51732,
51733,
51844,
51845,
51887,
51888,
52056,
52057,
52115,
52116,
52332,
52333,
52391,
52392,
52571,
52572,
52630,
52631,
52804,
52805,
52875,
52876,
53074,
53075,
53133,
53134,
53246,
53247,
53276,
53277,
53433,
53434,
53492,
53493,
53747,
53748,
53806,
53807,
53958,
53959,
54012,
54013,
54164,
54165,
54223,
54224,
54395,
54396,
54430,
54431,
54565,
54566,
54624,
54625,
54645,
54646,
54663,
54664,
55388,
55389,
55408,
55409,
55422,
55423,
55431,
55432,
55446,
55447,
55902,
55903,
55925,
55926,
55981,
55982,
56002,
56003,
56023,
56024,
56068,
56069,
56092,
56093,
56110,
56111,
56230,
56231,
56257,
56258,
56281,
56282,
57133,
57134,
57159,
57160,
57179,
57180,
57227,
57228,
57246,
57247,
57501,
57502,
57520,
57521,
57535,
57536,
57550,
57551,
57566,
57567,
57619,
57620,
57629,
57630,
57828,
57829,
57836,
57837,
57849,
57850,
57866,
57867,
57963,
57964,
58062
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 58062,
"ccnet_original_nlines": 432,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 2,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.22338804602622986,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.06126248091459274,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.2871890366077423,
"rps_doc_frac_unique_words": 0.2384362518787384,
"rps_doc_mean_word_length": 5.374383449554443,
"rps_doc_num_sentences": 1051,
"rps_doc_symbol_to_word_ratio": 0.0005077000241726637,
"rps_doc_unigram_entropy": 6.345038890838623,
"rps_doc_word_count": 8518,
"rps_doc_frac_chars_dupe_10grams": 0.0628235712647438,
"rps_doc_frac_chars_dupe_5grams": 0.22182659804821014,
"rps_doc_frac_chars_dupe_6grams": 0.16730378568172455,
"rps_doc_frac_chars_dupe_7grams": 0.13538959622383118,
"rps_doc_frac_chars_dupe_8grams": 0.09342712163925171,
"rps_doc_frac_chars_dupe_9grams": 0.06719238311052322,
"rps_doc_frac_chars_top_2gram": 0.007426990196108818,
"rps_doc_frac_chars_top_3gram": 0.013543330132961273,
"rps_doc_frac_chars_top_4gram": 0.01135891955345869,
"rps_doc_books_importance": -4215.1162109375,
"rps_doc_books_importance_length_correction": -4215.1162109375,
"rps_doc_openwebtext_importance": -2913.30078125,
"rps_doc_openwebtext_importance_length_correction": -2913.30078125,
"rps_doc_wikipedia_importance": -2430.277099609375,
"rps_doc_wikipedia_importance_length_correction": -2430.277099609375
},
"fasttext": {
"dclm": 0.023055490106344223,
"english": 0.8791123628616333,
"fineweb_edu_approx": 2.6664795875549316,
"eai_general_math": 0.32570207118988037,
"eai_open_web_math": 0.2912885546684265,
"eai_web_code": 0.003502849955111742
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "612.042",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Physiology"
}
},
"secondary": {
"code": "616.1",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "4",
"label": "Analyze"
},
"secondary": {
"code": "5",
"label": "Evaluate"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "2",
"label": "Academic/Research"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "0",
"label": "No Artifacts"
}
},
"missing_content": {
"primary": {
"code": "4",
"label": "Missing Images or Figures"
},
"secondary": {
"code": "0",
"label": "No missing content"
}
},
"document_type_v2": {
"primary": {
"code": "3",
"label": "Academic Writing"
},
"secondary": {
"code": "8",
"label": "Documentation"
}
},
"reasoning_depth": {
"primary": {
"code": "4",
"label": "Advanced Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "4",
"label": "Graduate/Expert Level"
},
"secondary": {
"code": "3",
"label": "Undergraduate Level"
}
}
}
|
6e3c8d3593f3f69280bb5502b214ab8e
|
-1,091,234,829,305,166,800
|
Elaborate Effects Of Gemstones On Our Well Being
Beautiful as they are, gemstones are also equally well endowed with qualities that lend them an edge and earn them the soaring popularity that is showered on them so generously from across the globe over the centuries. The most eye-catching and attractive feature of gemstones is their sheer beauty and vivid colors that are not only vary from one to the other but are also exclusive. However, apart from the immense beauty that is inherent in gemstones they also come hand in hand with a lot of other qualities and benefits. Gemstone and their effects have a very positive effect on one’s life. For centuries now, gemstones have been considered highly effective for various reasons.
Gemstones are also highly effective in curing certain diseases and ailments. In fact, since ancient times a lot of gemstones were used to cure as well as curb certain diseases and even today they are recommended to set one free of a particular ailment. Whether it is eye problems or diseases related to the heart, liver, pancreas or blood to name a few, gemstones are said to work wonders in curing them. A lot of gemstones also help in combating depression and mental illnesses. Stones and their effects bring about an air of positivism and good cheer that helps to ward off negative and detrimental thoughts and feelings.
Every person living on this planet receives cosmic radiations from planets, which influences all aspect of our existence, including our attitudes, behavior towards the environment. Gemstones and their effects are often associated with planets and are mostly used to enhance the positive effect of that particular planet, zodiac sign or constellation for our well being. After wearing a gemstone, the cosmic rays which represent the planet are drawn into our auras in a more significant and extraordinary way, bringing about a positive effect on the chakras governed by those particular colors. This greatly influences our thought process, the vibes that we emit into the environment around us, the way we interact with people and also the way people interact with us.
Some types of stones and their effects:
Ruby: It is bright in color and expensive gemstone. It is taken as a symbol of love. It makes the people open-hearted by creating feelings of love in one’s heart. It also helps in removing any kind of fear in the heart.
Emerald: Emerald, discharges green ray and it holds its power in the rays. Those who need physical or emotional healing must wear emerald. It is suggested for those people who are suffering from an inner or external physical problem in their body.
New Gemstones
Aquamarine: It is one of the most beautiful gemstones and it holds a strong power of kindness and love. Those people especially who are inflicted by the confusions in love relations, they must wear this gemstone.
Carnelian: Those who are creative but find it difficult to exhibit their creativity, they must wear this gemstone. It emits orange color rays.
Rose Quartz: Those people who are having low control over their emotions must wear this gemstone as it balances the feelings and emotions.
Leave a Reply
Your email address will not be published. Required fields are marked *
|
{
"url": "https://www.blogflickr.com/elaborate-effects-of-gemstones-on-our-well-being/",
"source_domain": "www.blogflickr.com",
"snapshot_id": "crawl=CC-MAIN-2020-29",
"warc_metadata": {
"Content-Length": "63727",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:HJE3QPVJKTPP44J3VV3O254A35SAIREY",
"WARC-Concurrent-To": "<urn:uuid:7b332fe1-1de1-4c7c-a38b-b94bc6602d4a>",
"WARC-Date": "2020-07-08T03:33:56",
"WARC-IP-Address": "166.62.27.184",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:N527CHNOMQADDDS4KV6HZYOHRYOHDRMS",
"WARC-Record-ID": "<urn:uuid:a3b7af30-121a-40e4-9102-2d6549187b65>",
"WARC-Target-URI": "https://www.blogflickr.com/elaborate-effects-of-gemstones-on-our-well-being/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:f0423ff9-6bcf-4ff2-85eb-7248cb4b32c2>"
},
"warc_info": "isPartOf: CC-MAIN-2020-29\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for July 2020\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-125.ec2.internal\r\nsoftware: Apache Nutch 1.17 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.2-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: http://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
49,
50,
734,
735,
1359,
1360,
2128,
2129,
2169,
2170,
2390,
2391,
2639,
2640,
2654,
2655,
2868,
2869,
3012,
3013,
3152,
3153,
3167,
3168
],
"line_end_idx": [
49,
50,
734,
735,
1359,
1360,
2128,
2129,
2169,
2170,
2390,
2391,
2639,
2640,
2654,
2655,
2868,
2869,
3012,
3013,
3152,
3153,
3167,
3168,
3238
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 3238,
"ccnet_original_nlines": 24,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.4625624120235443,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.0016638899687677622,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.09317804127931595,
"rps_doc_frac_unique_words": 0.46765249967575073,
"rps_doc_mean_word_length": 4.863216400146484,
"rps_doc_num_sentences": 28,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.057400703430176,
"rps_doc_word_count": 541,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.018244009464979172,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.007601669989526272,
"rps_doc_frac_chars_top_3gram": 0.022805020213127136,
"rps_doc_frac_chars_top_4gram": 0.022805020213127136,
"rps_doc_books_importance": -275.5888366699219,
"rps_doc_books_importance_length_correction": -275.5888366699219,
"rps_doc_openwebtext_importance": -164.60482788085938,
"rps_doc_openwebtext_importance_length_correction": -164.60482788085938,
"rps_doc_wikipedia_importance": -100.8642578125,
"rps_doc_wikipedia_importance_length_correction": -100.8642578125
},
"fasttext": {
"dclm": 0.024774910882115364,
"english": 0.9719352126121521,
"fineweb_edu_approx": 2.4824819564819336,
"eai_general_math": 0.0024564301129430532,
"eai_open_web_math": 0.21137601137161255,
"eai_web_code": 0.000029439999707392417
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "549.2",
"labels": {
"level_1": "Science and Natural history",
"level_2": "Chemistry",
"level_3": "Mineralogy"
}
},
"secondary": {
"code": "615.85",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "6",
"label": "Promotional/Advertisement"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "3",
"label": "Irrelevant Content"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "12",
"label": "Listicle"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "1",
"label": "No Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "6",
"label": "Not Applicable/Indeterminate"
},
"secondary": {
"code": "2",
"label": "Partially Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
9222580d47c553ea90dc0f5e416f8f3a
|
7,417,592,303,712,177,000
|
top of page
• Writer's pictureAdmin
Making Sense of GraviCeption
Have you ever felt one of the following?
· Queasiness after a car ride or roller coaster
· Trepidation while hiking in the dark
· Dizziness when you stand after prolonged sitting
· The surprise of a misstep
All these experiences have something in common: sensory information changed compared to your 'normal'. The result of each of these experiences might be described as DISORIENTING.
Disorientation is defined as the condition of having lost one's sense of direction. We orient ourselves through our relationship with gravity; with our ability to sense it, through graviception.
Graviception is the sensation of gravitational “force.”
It involves sensory integration of multiple inputs from different systems: visual, vestibular, and somatosensory. This results in perception of body position, an awareness of what is upright, and provides a sense of equilibrium.
Awareness through sensing
Graviception is different than balance and postural control, but it contributes to both. It is commonly assessed in the literature by the Subjective Visual Vertical test. (1)
While this may seem straightforward, there are a few misconceptions when it comes to sensing gravity.
To better understand all the components of graviception we need to dig deeper – deeper into the body.
The vestibular system may not always be the
main driver of graviception
The vestibular system seems to get most of the credit for sensing gravity. However, the literature on graviception reveals it’s more complex and differentiates between vestibular graviception and extra-vestibular (ie, outside of the vestibular system) graviception.
Where outside? In the ventral cavity.
A few studies have shown that graviceptors in the viscera, referred to as somatic graviceptors, play a role in sensing gravity.
Intriguing right? Mittelstadt thought so. He studied paraplegic patients with their kidneys removed and found graviception can occur independent of mechanoreception in the skin, legs, and spine. He identified sensory inputs from two areas: the region of the kidneys and the cardiovascular system. (2,3)
In a different study Trousselard et al found that the stomach, specifically the mechanoreceptors in the fundus, contribute to graviception. (4)
Additionally, research by Vaitl et al revealed that blood distribution influenced by gravity in different positions (standing, sitting or recumbent) serves as a cue for graviception. (5)
synchronized sensing perhaps
Gravity therefore impacts interoception via shifts in body fluids.
Interoception is the sense of the internal state of our body. It evolves from the integration of multiple visceral inputs to signal our body’s physiological state and "sense of self". (6)
Perceiving gravity depends on more than
inputs from graviceptors.
Graviceptors refer to the sensory receptors and systems that contribute to sensing the pull of gravity and our perception of upright.
Perceiving gravity depends on more than inputs from graviceptors in your otoliths and viscera. It also involves integration of these inputs with other senses in the thalamus and cerebellum AND includes predictions we make based on models in multiple levels of the cortex (7, 8)
While Jeff Hawkins doesn’t specifically address graviception in his book A Thousand Brains: A New Theory on Intelligence,his ideas on how we learn and build models through movement mesh well with this concept.
Hawkins proposes that our neocortex houses not a single model of the world but thousands. These models are created through sensory input and reference frames and learned through sensing and moving.
The ability to maintain a stable impression of the visual world during sustained movements of our eyes, head and body is called “orientation constancy”. This is driven in large part by our internal estimate of the direction of gravity. (9)
For example, we have an orientation model that has a prior setting in which the head is normally upright in space during the day. When lying down at night the model recognizes that the head and body are tilted 90° and sometimes rolled (sidelying).
We use this model to compensate for quick changes in the head and body positions. Things go awry when information from one of our graviceptors conflicts with one another - or our internal map of gravity.
While the cortical representation of gravity is required to determine our body's orientation in space and influence the way we move, it also does more.
Graviception results in more than
optimal movement
“Your brain is not for thinking.” says Lisa Feldman Barrett in Seven And A Half Lessons About The Brain
Rather your brain’s most important job “is to control your body- to manage allostasis- by predicting energy needs BEFORE they arise so you can efficiently make worthwhile movements and survive”.
Barrett refers to this as body budgeting
Just like financial budgeting we make estimates on what our physiological needs are. In both scenarios when our needs aren’t met, we feel stressed.
Graviception may act as a stress regulator. If we consider this to be true it provides a potential explanation for the calming effect for interventions like visceral manipulation and grounding, and behaviors like rocking.
"It is gravity that is the tool; it is gravity that is the therapist." ~ Dr. Ida Rolf.
Why should we care about the
ability to sense gravity?
Graviception applies to all of us. Your perception of it is relative and plastic.
Understanding graviception has widespread applications in both rehab and fitness realms.
Patients with vestibular dysfunction, pusher syndrome after a stroke, and individuals with scoliosis may be challenged with sensing gravity. (10, 11) Disorientation can present as motion sickness, dizziness or even persistent pain/discomfort related to increased muscular tone.
Disorientation may be a factor with individuals who don’t verbalize this complaint because what they feel is stressed.
The importance of graviception extends beyond the rehab world
Studies in sports performance demonstrate that experts in soccer and gymnastics are better at perceiving body orientation which in turn positively influences postural control and motor skills. (12, 13)
High level soccer players are better able to manage disturbances to proprioceptive and exteroceptive inputs compared to regional level players. This superior postural control may be the result of several factors, including a higher graviception sensitivity that has evolved through experience and exposure.
CONCLUSION
Gravity is described as a force of attraction that exists between all objects with mass.
We tend to take gravity for granted.
Perceptions derive from sensations but not all sensations result in perception. We adapt to inputs when they remain constant over prolonged periods of time. If our graviceptors are working well, we have less of a conscious felt experience.
It’s when inputs give conflicting information with our internal models, we feel “off”.
There are still unanswered questions about gravity. What we do know is how we move in our world depends on it. It is the foundation for how we learn through our senses and develop references frames to create models of our world and our own body schema.
Our evolved graviception is a big part of what makes us human. In the future this sense will continue to be challenged in new ways as we encounter more experiences like virtual reality and space travel where gravity conditions and available inputs change. (14)
We will continue to be challenged to #levelup
REFERENCES
1. Chetana N, Jayesh R. Subjective Visual Vertical in Various Vestibular Disorders by Using a Simple Bucket Test. Indian J Otolaryngol Head Neck Surg. 2015;67(2):180-184. doi:10.1007/s12070-014-0760-0
2. Mittelstaedt H. Evidence of somatic graviception from new and classical investigations. Acta Otolaryngol Suppl. 1995;520 Pt 1:186-7. doi: 10.3109/00016489509125224. PMID: 8749115.
3. Mittelstaedt, Horst. “Interaction of eye-, head-, and trunk-bound information in spatial perception and control.” Journal of vestibular research : equilibrium & orientation 7 4 (1997): 283-302 .
4. Trousselard M, Barraud PA, Nougier V, Raphel C, Cian C. Contribution of tactile and interoceptive cues to the perception of the direction of gravity. Brain Res Cogn Brain Res. 2004 Aug;20(3):355-62. doi: 10.1016/j.cogbrainres.2004.03.008. PMID: 15268913.
5. Dieter Vaitl, Horst Mittelstaedt, Ralf Saborowski, Rudolf Stark, Friedhelm Baisch,
Shifts in blood volume alter the perception of posture: further evidence for somatic graviception, International Journal of Psychophysiology, Volume 44, Issue 1, 2002,
Pages 1-11.
6. Quigley KS, Kanoski S, Grill WM, Barrett LF, Tsakiris M. Functions of Interoception: From Energy Regulation to Experience of the Self. Trends Neurosci. 2021;44(1):29-38.
7. Paul R. MacNeilage, Stefan Glasauer, Gravity Perception: The Role of the Cerebellum, Current Biology, Volume 28, Issue 22, 2018, Pages R1296-R1298,
8. Delle Monache S, Indovina I, Zago M, Daprati E, Lacquaniti F, Bosco G. Watching the Effects of Gravity. Vestibular Cortex and the Neural Representation of "Visual" Gravity. Front Integr Neurosci. 2021 Dec 1;15:793634.
9. Julien Barra, Adélaïde Marquer, Roxane Joassin, Céline Reymond, Liliane Metge, Valérie Chauvineau, Dominic Pérennou, Humans use internal models to construct and update a sense of verticality, Brain, Volume 133, Issue 12, December 2010, Pages 3552–3563
10. Morgane Le Berre, Charles Pradeau, Anthony Brouillard, Monique Coget, Caroline Massot, Jean-François Catanzariti, Do Adolescents With Idiopathic Scoliosis Have an Erroneous Perception of the Gravitational Vertical?, Spine Deformity, Volume 7, Issue 1, 2019
11. H.-O. Karnath, S. Ferber, J. Dichgans ,The origin of contraversive pushing: Evidence for a second graviceptive system in humans, Neurology Nov 2000, 55 (9) 1298-1304; DOI:10.1212/WNL.55.9.1298
12. Paillard T, Bizid R, Dupui P. Do sensorial manipulations affect subjects differently depending on their postural abilities?. Br J Sports Med. 2007;41(7):435-438. doi:10.1136/bjsm.2006.032904
13. Bringoux L, Marin L, Nougier V, Barraud PA, Raphel C. Effects of gymnastics expertise on the perception of body orientation in the pitch dimension. J Vestib Res. 2000;10(6):251-8.
14. Roy-O’Reilly, M., Mulavara, A. & Williams, T. A review of alterations to the brain during spaceflight and the potential relevance to crew in long-duration space exploration. npj Microgravity 7, 5 (2021)
Comments
Commenting has been turned off.
bottom of page
|
{
"url": "https://www.leveluprehab.com/post/making-sense-of-graviception",
"source_domain": "www.leveluprehab.com",
"snapshot_id": "CC-MAIN-2024-38",
"warc_metadata": {
"Content-Length": "1050482",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:5KEGZEDWMHIZYWECL74TM5LERVI2VBD6",
"WARC-Concurrent-To": "<urn:uuid:33e7d12c-9088-4068-a304-292a8935049f>",
"WARC-Date": "2024-09-15T09:14:51",
"WARC-IP-Address": "34.149.87.45",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:NT6YPBGLFJVQTHN6YAX55C6STFQAATJ4",
"WARC-Record-ID": "<urn:uuid:2d543f72-d782-47e9-92a8-299e86551e6d>",
"WARC-Target-URI": "https://www.leveluprehab.com/post/making-sense-of-graviception",
"WARC-Truncated": "length",
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:d2c84458-3a89-4c29-b899-b48ba19ef6f9>"
},
"warc_info": "isPartOf: CC-MAIN-2024-38\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for September 2024\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-65\r\nsoftware: Apache Nutch 1.20 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.5-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
12,
38,
39,
68,
69,
70,
71,
112,
113,
114,
162,
163,
202,
203,
254,
255,
283,
284,
285,
464,
465,
466,
661,
662,
663,
719,
720,
721,
950,
951,
952,
978,
979,
980,
981,
1156,
1157,
1158,
1159,
1160,
1161,
1263,
1264,
1265,
1367,
1368,
1369,
1370,
1414,
1415,
1443,
1444,
1445,
1711,
1712,
1713,
1751,
1752,
1753,
1754,
1755,
1883,
1884,
1885,
2188,
2189,
2190,
2334,
2335,
2336,
2523,
2524,
2525,
2554,
2555,
2556,
2557,
2624,
2625,
2626,
2814,
2815,
2816,
2817,
2857,
2858,
2884,
2885,
2886,
3020,
3021,
3022,
3300,
3301,
3302,
3303,
3304,
3514,
3515,
3516,
3714,
3715,
3716,
3717,
3718,
3958,
3959,
3960,
4208,
4209,
4210,
4414,
4415,
4416,
4568,
4569,
4570,
4571,
4572,
4573,
4607,
4608,
4625,
4626,
4627,
4628,
4732,
4733,
4734,
4929,
4930,
4931,
4932,
4973,
4974,
4975,
5123,
5124,
5125,
5347,
5348,
5349,
5350,
5437,
5438,
5439,
5440,
5469,
5470,
5496,
5497,
5498,
5580,
5581,
5582,
5583,
5672,
5673,
5674,
5952,
5953,
6072,
6073,
6074,
6075,
6137,
6138,
6139,
6341,
6342,
6343,
6344,
6345,
6652,
6653,
6654,
6655,
6666,
6667,
6668,
6757,
6758,
6759,
6760,
6797,
6798,
6799,
7039,
7040,
7041,
7042,
7043,
7044,
7131,
7132,
7133,
7386,
7387,
7388,
7649,
7650,
7651,
7697,
7698,
7699,
7700,
7701,
7712,
7713,
7914,
7915,
7916,
8099,
8100,
8101,
8299,
8300,
8301,
8559,
8560,
8561,
8647,
8648,
8816,
8817,
8829,
8830,
8831,
9004,
9005,
9006,
9157,
9158,
9159,
9380,
9381,
9382,
9637,
9638,
9639,
9900,
9901,
9902,
9903,
9904,
9905,
10102,
10103,
10104,
10299,
10300,
10301,
10485,
10486,
10487,
10694,
10695,
10696,
10697,
10698,
10699,
10700,
10701,
10702,
10703,
10712,
10713,
10714,
10746
],
"line_end_idx": [
12,
38,
39,
68,
69,
70,
71,
112,
113,
114,
162,
163,
202,
203,
254,
255,
283,
284,
285,
464,
465,
466,
661,
662,
663,
719,
720,
721,
950,
951,
952,
978,
979,
980,
981,
1156,
1157,
1158,
1159,
1160,
1161,
1263,
1264,
1265,
1367,
1368,
1369,
1370,
1414,
1415,
1443,
1444,
1445,
1711,
1712,
1713,
1751,
1752,
1753,
1754,
1755,
1883,
1884,
1885,
2188,
2189,
2190,
2334,
2335,
2336,
2523,
2524,
2525,
2554,
2555,
2556,
2557,
2624,
2625,
2626,
2814,
2815,
2816,
2817,
2857,
2858,
2884,
2885,
2886,
3020,
3021,
3022,
3300,
3301,
3302,
3303,
3304,
3514,
3515,
3516,
3714,
3715,
3716,
3717,
3718,
3958,
3959,
3960,
4208,
4209,
4210,
4414,
4415,
4416,
4568,
4569,
4570,
4571,
4572,
4573,
4607,
4608,
4625,
4626,
4627,
4628,
4732,
4733,
4734,
4929,
4930,
4931,
4932,
4973,
4974,
4975,
5123,
5124,
5125,
5347,
5348,
5349,
5350,
5437,
5438,
5439,
5440,
5469,
5470,
5496,
5497,
5498,
5580,
5581,
5582,
5583,
5672,
5673,
5674,
5952,
5953,
6072,
6073,
6074,
6075,
6137,
6138,
6139,
6341,
6342,
6343,
6344,
6345,
6652,
6653,
6654,
6655,
6666,
6667,
6668,
6757,
6758,
6759,
6760,
6797,
6798,
6799,
7039,
7040,
7041,
7042,
7043,
7044,
7131,
7132,
7133,
7386,
7387,
7388,
7649,
7650,
7651,
7697,
7698,
7699,
7700,
7701,
7712,
7713,
7914,
7915,
7916,
8099,
8100,
8101,
8299,
8300,
8301,
8559,
8560,
8561,
8647,
8648,
8816,
8817,
8829,
8830,
8831,
9004,
9005,
9006,
9157,
9158,
9159,
9380,
9381,
9382,
9637,
9638,
9639,
9900,
9901,
9902,
9903,
9904,
9905,
10102,
10103,
10104,
10299,
10300,
10301,
10485,
10486,
10487,
10694,
10695,
10696,
10697,
10698,
10699,
10700,
10701,
10702,
10703,
10712,
10713,
10714,
10746,
10760
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 10760,
"ccnet_original_nlines": 269,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.30337080359458923,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.026868589222431183,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.24181729555130005,
"rps_doc_frac_unique_words": 0.4584115147590637,
"rps_doc_mean_word_length": 5.3777360916137695,
"rps_doc_num_sentences": 146,
"rps_doc_symbol_to_word_ratio": 0.000488520017825067,
"rps_doc_unigram_entropy": 5.887655258178711,
"rps_doc_word_count": 1599,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.02907315082848072,
"rps_doc_frac_chars_dupe_6grams": 0.017676470801234245,
"rps_doc_frac_chars_dupe_7grams": 0.013024769723415375,
"rps_doc_frac_chars_dupe_8grams": 0.013024769723415375,
"rps_doc_frac_chars_dupe_9grams": 0.013024769723415375,
"rps_doc_frac_chars_top_2gram": 0.007559020072221756,
"rps_doc_frac_chars_top_3gram": 0.006628680042922497,
"rps_doc_frac_chars_top_4gram": 0.006047210190445185,
"rps_doc_books_importance": -925.2811279296875,
"rps_doc_books_importance_length_correction": -925.2811279296875,
"rps_doc_openwebtext_importance": -503.8635559082031,
"rps_doc_openwebtext_importance_length_correction": -503.8635559082031,
"rps_doc_wikipedia_importance": -373.909912109375,
"rps_doc_wikipedia_importance_length_correction": -373.909912109375
},
"fasttext": {
"dclm": 0.06985872983932495,
"english": 0.8731124401092529,
"fineweb_edu_approx": 2.428318738937378,
"eai_general_math": 0.1326717734336853,
"eai_open_web_math": 0.22969025373458862,
"eai_web_code": 0.01891040988266468
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "612.822",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Physiology"
}
},
"secondary": {
"code": "612.8",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Physiology"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "4",
"label": "Analyze"
},
"secondary": {
"code": "2",
"label": "Understand"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "4",
"label": "Missing Images or Figures"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "16",
"label": "Personal Blog"
}
},
"reasoning_depth": {
"primary": {
"code": "3",
"label": "Intermediate Reasoning"
},
"secondary": {
"code": "2",
"label": "Basic Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "4",
"label": "Highly Correct"
}
},
"education_level": {
"primary": {
"code": "3",
"label": "Undergraduate Level"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
b755ed28a90d11d590ef646404f4afc5
|
-5,747,561,397,781,292,000
|
Forgot Password
The Different Types Braces Glasgow
The first word you think of when you hear braces is - METAL. However as technology has progressed and now every has the opportunity to wear braces without the pain, discomfort and embarrassment. Here is how new braces Glasgow are changing and improving the lives of thousands in Scotland - starting with their teeth.
Why We Might Need Braces
Braces are traditionally used to straighten crooked teeth. Now we understand that braces can help realign your jaw - making it easier to chew, bite and smile.
Old Style Braces Glasgow
Traditionally, although still used prominently in amongst teenagers to straighten their teeth. Metal brackets and wires are glued onto the teeth from 6-24 months depended on how squint the patients teeth are. These can be heavy and painful but work brilliantly and quick.
New Invisible Braces
With new technologies and advancements in dentistry and orthodontics we are now able to get invisible braces. You can get a wire that fits behind the teeth so that nobody can see or you can get retainers style invisible braces that you wear in the evenings or throughout the day.
types-of-braces-glasgow • 2019 May 10
Be the first to comment.
|
{
"url": "https://types-of-braces-glasgow.gonevis.com/the-different-types-braces-glasgow/",
"source_domain": "types-of-braces-glasgow.gonevis.com",
"snapshot_id": "crawl=CC-MAIN-2019-22",
"warc_metadata": {
"Content-Length": "18014",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:FKNYWHI6BVUJY7CFH7PMRYTF754NZS3X",
"WARC-Concurrent-To": "<urn:uuid:f7d3d61e-5857-43db-831c-4c4e25055044>",
"WARC-Date": "2019-05-20T00:56:39",
"WARC-IP-Address": "52.203.102.189",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:XDDYZXBHJFLLQQNXAMS7KATWA3C7ITOW",
"WARC-Record-ID": "<urn:uuid:3fa6376e-2eb5-4c82-8b1c-3086cde2bcd5>",
"WARC-Target-URI": "https://types-of-braces-glasgow.gonevis.com/the-different-types-braces-glasgow/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:691d2be5-356b-4327-84bb-7efb92fddee1>"
},
"warc_info": "isPartOf: CC-MAIN-2019-22\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for May 2019\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-113-197-177.ec2.internal\r\nsoftware: Apache Nutch 1.15 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.1-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: http://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
16,
17,
52,
53,
370,
371,
372,
397,
398,
557,
558,
583,
584,
856,
857,
878,
879,
1159,
1160,
1161,
1162,
1163,
1164,
1202,
1203
],
"line_end_idx": [
16,
17,
52,
53,
370,
371,
372,
397,
398,
557,
558,
583,
584,
856,
857,
878,
879,
1159,
1160,
1161,
1162,
1163,
1164,
1202,
1203,
1227
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 1227,
"ccnet_original_nlines": 25,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.4266666769981384,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.004444439895451069,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.11555556207895279,
"rps_doc_frac_unique_words": 0.5849999785423279,
"rps_doc_mean_word_length": 4.945000171661377,
"rps_doc_num_sentences": 11,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 4.449161529541016,
"rps_doc_word_count": 200,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.03943376988172531,
"rps_doc_frac_chars_top_3gram": 0.01820020005106926,
"rps_doc_frac_chars_top_4gram": 0,
"rps_doc_books_importance": -98.04756164550781,
"rps_doc_books_importance_length_correction": -98.04756164550781,
"rps_doc_openwebtext_importance": -63.18041229248047,
"rps_doc_openwebtext_importance_length_correction": -63.18039321899414,
"rps_doc_wikipedia_importance": -40.96274948120117,
"rps_doc_wikipedia_importance_length_correction": -40.96274948120117
},
"fasttext": {
"dclm": 0.05957615002989769,
"english": 0.935434877872467,
"fineweb_edu_approx": 2.672485828399658,
"eai_general_math": 0.02033000998198986,
"eai_open_web_math": 0.6392042636871338,
"eai_web_code": 0.0016943799564614892
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "617.622",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Surgery and Dentistry"
}
},
"secondary": {
"code": "617.62",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Surgery and Dentistry"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "1",
"label": "Factual"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "0",
"label": "No Artifacts"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "17",
"label": "Product Page"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "1",
"label": "No Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "6",
"label": "Not Applicable/Indeterminate"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
1a01aa77535b9ecfb87b9fc36adbcd2f
|
7,064,607,779,541,948,000
|
Why Fika is the Key to Happiness at Work
fika - coffee and an alarm clock on a table
One could certainly say that Scandinavians have a lot of things figured out. They consistently take top honours when it comes to prosperity, education, and happiness ratings, so we’d probably be wise to take their advice. We’ve posted before about the delightful, Danish notion of hygge (or the art of getting cozy). Our new Scandinavian obsession is the Swedish tradition of fika. Read on about why we love the idea, and why we think everyone should incorporate it into their workday.
What is Fika, anyway?
Fika Swedish Tradition Coffee Work London Drugs
There is no literal translation for fika in English, but it is defined as “a concept in Swedish culture with the basic meaning to have coffee, often accompanied with pastries, cookies or pie.” But ask any Swede, and they will tell you that fika-ing (yes, you can use the word as a noun or a verb) is about more than just grabbing a coffee; it’s a moment to leave work behind. Traditionally taken twice a day (first at 10am and then at 3pm), it’s not a strategy for more meetings with coffee in hand, it’s a chance to actually relax with co-workers. Despite Sweden being the world’s third-largest coffee drinking nation, Fika doesn’t necessarily even have to involve coffee—tea or lemonade are popular alternatives. The point is to slow down and connect.
Why should I Fika?
Work is inherently a social activity. It has to be; even if you don’t work around a lot of people that often, you do work for people. At the same time, people are getting busier than ever, and our work increasingly involves more technology and less interaction every day, so that can lead to more isolation in the workplace. When we’re not connecting with the people we spend so many hours a day with, there is potential for loneliness.
Studies have shown that loneliness and isolation at work can not only lead to depression, they can kill your job performance. Recognition, gratitude, encouragement, emotional support, and camaraderie are all important factors to finding fulfilment at work, and life in general, so nurturing these things with regular personal connection can increase productivity, improve motivation, and foster company loyalty. The stripped down, casual style of fika breaks can even lead to new ideas and more creative problem solving.
So, Ska vi fika? Let us know how you practice fika in the comments below, or if you’ll incorporate it into your work day!
What Time Should My Child Go to Bed? A Sleep Guide for Canadian Parents
Exactly how much sleep should your kids be getting? Check our handy chart below.
If this four-year old girl went to bed at 20:30 and rose at 07:00, did her growing mind and body get enough sleep? Afraid not. Check out our guide below.
In Canada, the shortening days are upon us. In the six months between the longest and shortest days of the year, Torontonians, Vancouverites, and Edmontonians lose six and a half, eight, and nine and a half hours of sunlight, respectively.
If you have children, you’ll know that a 9:00 p.m. bedtime, more than reasonable during the summer, means putting a kid down some five hours after the winter sun. Is he getting enough sleep? Who knows? When many Canadian parents factor in the back-to-school routines of dinner, bath, and storytime (and later, after-school activities, homework, and team sports), it’s hard to imagine getting kids to bed much before nine o’clock. READ MORE
How to Boost Brainpower and Increase Productivity
Don’t we all wish we could have 10 more hours in a day? That’s impossible, of course, but by boosting your brainpower, you can increase your productivity, which will create the illusion of more time. While there exist quick fixes for sharpening your brain (like eating antioxidant-filled blueberries or going for a run to score some endorphins), these three tips work best as habits to develop and maintain over time.
Get the sleep you need
Reducing caffeine will improve your sleep and mental capability
Cutting caffeine can greatly improve your quality of sleep.
Getting your minimum six hours isn’t even the most important aspect of sleep – what’s really important is getting high quality sleep. Try a sleep-tracking app like Sleepbot or a Fitbit to track your REM cycles. You can also use such apps to set an adjustable alarm that will wake you when your sleep is lightest to increase the quality of your sleep.
You can also unplug before bed to improve your sleep quality. The blue light found on tablets, smartphones, and eReaders actually signals your body to wake up, right before going to bed. Try reading a paper book before bed instead.
Lastly, cutting caffeine (at least in the afternoons, if you can’t live without your morning cuppa) will better the quality of your sleep, among other benefits. Still need a three o’clock pick-me-up? Try an iced herbal tea to give you a boost without the buzz.
Stimulate your brain
Socialization is actually good for your mental health
Socializing is actually good for you – it stimulates your brain. Party on!
Abandon your GPS and calculator in favour of using a map or doing calculations in your head. You can also sign up for a daily-word email to increase your vocabulary. Exercising your brain can also be accomplished by playing Scrabble (or Words with Friends!) instead of just talking or texting. Interestingly, socialization is also hugely beneficial to your brain. By inviting friends over, you reduce your chances of dementia. What better excuse is there to open a bottle of wine?
Another way to stimulate your brain is to do something new. This can be as simple as walking somewhere instead of driving, as intense as trying a new sport. Learning a new language or instrument also positively impacts the brain.
Treat your body right
Meditation benefits mental ability
Thirty minutes of yoga or meditation will increase your daily productivity.
First, kick the habit. Cigarettes have been linked to memory deficits, so the sooner you quit, the better it is for your body and brain.
Exercise regularly, even if it’s just a longer walk to your car. Try parking further from work, or getting off the bus earlier than usual to increase your walking distance. Practicing yoga or meditating also works – just 30 minutes a day contributes greatly to mental capacity.
Eating right also has a big impact. That means loading up on superfoods like blueberries, almonds, dark chocolate, and greens to boost your brain, but also making a habit of staying hydrated and eating clean and balanced meals.
5 Tips For Better Bone Health
Our bones support us – literally – throughout our lives. It’s especially as we age – and when those bones start to creak a little – that we tend to become more aware of the importance of bone health, and of the risk of osteoporosis, a disease marked by low bone mass and deterioration of bone tissue (which often leads to increased bone fragility and breakage). But keeping our bones strong and healthy should be a priority at any age.
Visit londondrugs.com/osteoclinics to schedule an appointment to learn more about bone health.
We spoke to Tanya Long, Senior Manager of Education for Osteoporosis Canada, about ways that you can boost your bone health at any age. She offers these five tips.
Balance Your Diet
A well-balanced diet, says Long, is one that features foods rich in calcium, adequate protein and plenty of fruits and vegetables. Foods like these not only ‘feed’ the bones, but provide other nutrients that are important for bone health, too.
Get Enough Calcium
Food, Long says, is the very best place to get your calcium. But if, for any reason, your food sources are not adequate in terms of providing the calcium your bones need, speak to your doctor. You may then consider taking a calcium supplement, on your doctor’s advice.
Supplement Your Vitamin D
Osteoporosis Canada recommends routine daily Vitamin D supplementation all year round for adults. Vitamin D, Long explains, isn’t always easily found in food sources and she says sun is simply not a reliable enough source of Vitamin D. Seek medical supervision, however, if you’re thinking of taking more than 2,000 International Units of Vitamin D per day.
Exercise
We know that exercise is crucial in building and maintaining strong bones. Long says your exercise routine should include strength training (such as wall push-ups or working with free weights), balance and posture training, as well as weight-bearing activity (weight-bearing means any activity requiring you to be on your feet, like dancing, walking, stair-stepping, etc.)
Your doctor can advise about helpful medications.
See Your Doctor
Over 50? Talk to your doctor about a fracture risk assessment, which will tell you your risk of breaking a bone in the next 10 years. Also, all women and men 65 years or older should have a bone mineral density test. If you are at high risk of fracture, Osteoporosis Canada recommends medication, on advice from your doctor. Find out more about the role of medication in treating osteoporosis here.
To find out more about osteoporosis and bone health in general, please visit the Osteoporosis Canada website.
And find out more about how to identify your osteoporosis risk factors – and how to minimize that risk – at one of London Drugs’ Osteoporosis Screening Clinics.
Dr Art Hister – Drugs for Mild Alzheimer’s Disease
A frustrating but likely accurate analysis of a drug widely-used to treat early (or mild) Alzheimer’s disease concludes that the drug is not effective in these cases.
This new study was published in the highly-respected journal, Archives of Neurology, and in this analysis of several previously published studies about the drug memantine, the authors of this report found that memantine does not slow either memory decline of cognitive function decline in mild cases of Alzheimer’s disease.
It’s a frustrating analysis, as I wrote earlier, because frankly, there are so few drugs that can be used to try to stem the progress of AD, so taking away one that is prescribed by many doctors is well, frustrating, but it’s important to note, especially for those people who believe that anything, even if it’s only slightly effective, is better than nothing when it comes to such a depressing condition as AD, that this is simply not true: using nothing is often a better choice given that all drugs, including memantine, have potential significant side effects and complications associated with their use.
And that’s a very good principle – nothing may be the best choice – to remember for all conditions involving the use of potentially problematic medications, which is why it’s always a great tactic to make very good friends with your pharmacist so that you can ask him or her about those potential risks when you’re put on a new drug.
« Previous Page
|
{
"url": "https://blog.londondrugs.com/tag/wellness/page/2",
"source_domain": "blog.londondrugs.com",
"snapshot_id": "CC-MAIN-2023-23",
"warc_metadata": {
"Content-Length": "101327",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:ZF5SWFEMDP72QWB4WQKOKFCSEG7PKZ3G",
"WARC-Concurrent-To": "<urn:uuid:aded8085-6e47-4709-b364-8dad26e33622>",
"WARC-Date": "2023-06-01T01:12:57",
"WARC-IP-Address": "192.124.249.20",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:MOHESMBTFM2UJK2VRQK52MGBDFSAM6UV",
"WARC-Record-ID": "<urn:uuid:6e2e49bd-d18f-4534-a958-a7ddab521052>",
"WARC-Target-URI": "https://blog.londondrugs.com/tag/wellness/page/2",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:94bef44e-fba3-42f1-ae54-c0e569d0c3de>"
},
"warc_info": "isPartOf: CC-MAIN-2023-23\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for May/June 2023\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-140\r\nsoftware: Apache Nutch 1.19 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.4-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
41,
42,
86,
87,
573,
574,
596,
597,
645,
646,
1400,
1401,
1420,
1421,
1858,
1859,
2380,
2381,
2382,
2504,
2505,
2577,
2578,
2659,
2660,
2814,
2815,
3055,
3056,
3496,
3497,
3547,
3548,
3966,
3967,
3990,
3991,
4055,
4056,
4116,
4117,
4468,
4469,
4701,
4702,
4963,
4964,
4985,
4986,
5040,
5041,
5116,
5117,
5599,
5600,
5830,
5831,
5853,
5854,
5889,
5890,
5966,
5967,
6104,
6105,
6383,
6384,
6612,
6613,
6615,
6616,
6646,
6647,
7084,
7085,
7180,
7181,
7345,
7346,
7364,
7365,
7609,
7610,
7629,
7630,
7899,
7900,
7926,
7927,
8285,
8286,
8295,
8296,
8669,
8670,
8720,
8721,
8737,
8738,
9138,
9139,
9249,
9250,
9411,
9412,
9463,
9464,
9631,
9632,
9956,
9957,
10567,
10568,
10902,
10903
],
"line_end_idx": [
41,
42,
86,
87,
573,
574,
596,
597,
645,
646,
1400,
1401,
1420,
1421,
1858,
1859,
2380,
2381,
2382,
2504,
2505,
2577,
2578,
2659,
2660,
2814,
2815,
3055,
3056,
3496,
3497,
3547,
3548,
3966,
3967,
3990,
3991,
4055,
4056,
4116,
4117,
4468,
4469,
4701,
4702,
4963,
4964,
4985,
4986,
5040,
5041,
5116,
5117,
5599,
5600,
5830,
5831,
5853,
5854,
5889,
5890,
5966,
5967,
6104,
6105,
6383,
6384,
6612,
6613,
6615,
6616,
6646,
6647,
7084,
7085,
7180,
7181,
7345,
7346,
7364,
7365,
7609,
7610,
7629,
7630,
7899,
7900,
7926,
7927,
8285,
8286,
8295,
8296,
8669,
8670,
8720,
8721,
8737,
8738,
9138,
9139,
9249,
9250,
9411,
9412,
9463,
9464,
9631,
9632,
9956,
9957,
10567,
10568,
10902,
10903,
10918
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 10918,
"ccnet_original_nlines": 115,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.4366712272167206,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.00731595978140831,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.14677640795707703,
"rps_doc_frac_unique_words": 0.4048008620738983,
"rps_doc_mean_word_length": 4.777959823608398,
"rps_doc_num_sentences": 98,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.873039722442627,
"rps_doc_word_count": 1833,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.00479562021791935,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.00479562021791935,
"rps_doc_frac_chars_top_3gram": 0.003425440052524209,
"rps_doc_frac_chars_top_4gram": 0.005480700172483921,
"rps_doc_books_importance": -1070.3614501953125,
"rps_doc_books_importance_length_correction": -1070.3614501953125,
"rps_doc_openwebtext_importance": -588.4067993164062,
"rps_doc_openwebtext_importance_length_correction": -588.4067993164062,
"rps_doc_wikipedia_importance": -339.1588439941406,
"rps_doc_wikipedia_importance_length_correction": -339.1588439941406
},
"fasttext": {
"dclm": 0.025712190195918083,
"english": 0.9407137632369995,
"fineweb_edu_approx": 2.3801047801971436,
"eai_general_math": 0.012447119690477848,
"eai_open_web_math": 0.16399163007736206,
"eai_web_code": 0.0018647300312295556
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "613.7",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
},
"secondary": {
"code": "613.2",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "3",
"label": "Apply"
},
"secondary": {
"code": "2",
"label": "Understand"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "3",
"label": "Procedural"
},
"secondary": {
"code": "2",
"label": "Conceptual"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "3",
"label": "Irrelevant Content"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "2",
"label": "Click Here References"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "6",
"label": "Content Listing"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "4",
"label": "Highly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
6e3c8d3593f3f69280bb5502b214ab8e
|
7,815,981,435,823,196,000
|
The dual specific phosphatase PTEN (Phosphatase and TENsin homolog deleted on chromosome 10) is one of the most extensively studied proteins of the last decade. It was the first phosphatase identified as a tumor suppressor and in sporadic cancers PTEN is one of the most frequently altered genes. Its deregulation is also implicated in several other diseases. In addition, PTEN is critically important during embryonic development and is implicated as a key player in maintaining normal stem cell function. Unraveling of the physiological regulation and function of PTEN will augment our understanding of tumorigenesis and ultimately lead to novel therapeutic options.
|
{
"url": "https://repub.eur.nl/pub/18617",
"source_domain": "repub.eur.nl",
"snapshot_id": "CC-MAIN-2024-38",
"warc_metadata": {
"Content-Length": "24286",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:DKRQUXZV6CESGMYMMIA23EW33OQ2KXPH",
"WARC-Concurrent-To": "<urn:uuid:73071f75-b561-4398-a5d0-464e13aad7e9>",
"WARC-Date": "2024-09-19T20:21:23",
"WARC-IP-Address": "145.5.2.24",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:FMH5W57H3BWHWHA2DHDXQNCS5BUP5JVM",
"WARC-Record-ID": "<urn:uuid:266ba6c0-26ba-49db-a2bf-d852a7571d75>",
"WARC-Target-URI": "https://repub.eur.nl/pub/18617",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:1a06701c-d901-496f-abd8-b2db35da3d5e>"
},
"warc_info": "isPartOf: CC-MAIN-2024-38\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for September 2024\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-88\r\nsoftware: Apache Nutch 1.20 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.5-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0
],
"line_end_idx": [
668
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 668,
"ccnet_original_nlines": 0,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.40366971492767334,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.03669724985957146,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.08256880939006805,
"rps_doc_frac_unique_words": 0.6831682920455933,
"rps_doc_mean_word_length": 5.544554233551025,
"rps_doc_num_sentences": 5,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 4.018096446990967,
"rps_doc_word_count": 101,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.05000000074505806,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.035714291036129,
"rps_doc_frac_chars_top_3gram": 0.02500000037252903,
"rps_doc_frac_chars_top_4gram": 0.035714291036129,
"rps_doc_books_importance": -38.705177307128906,
"rps_doc_books_importance_length_correction": -45.79198455810547,
"rps_doc_openwebtext_importance": -23.941370010375977,
"rps_doc_openwebtext_importance_length_correction": -31.02817726135254,
"rps_doc_wikipedia_importance": -15.232793807983398,
"rps_doc_wikipedia_importance_length_correction": -22.31960105895996
},
"fasttext": {
"dclm": 0.13099586963653564,
"english": 0.9642408490180969,
"fineweb_edu_approx": 2.4870107173919678,
"eai_general_math": 0.1438068151473999,
"eai_open_web_math": 0.41450929641723633,
"eai_web_code": 0.00025194999761879444
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "572.6",
"labels": {
"level_1": "Science and Natural history",
"level_2": "Biology and Anthropology",
"level_3": "Anthropology"
}
},
"secondary": {
"code": "616.99",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "4",
"label": "Analyze"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "2",
"label": "Academic/Research"
},
"secondary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "3",
"label": "Academic Writing"
},
"secondary": {
"code": "10",
"label": "Knowledge Article"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "3",
"label": "Undergraduate Level"
},
"secondary": {
"code": "4",
"label": "Graduate/Expert Level"
}
}
}
|
9222580d47c553ea90dc0f5e416f8f3a
|
8,812,294,408,796,281,000
|
Cute Landybug Cartoon
Nitrous Oxide
Studies show that fear of the dentist is more often due to society’s misplaced belief that dental treatments are all painful more so than an actual painful experience. Dentists use nitrous oxide to help patients have a relaxed and pain free dental visit.
Illustration of Girls Boys Explorers On Boat
Nitrous oxide, often referred to as laughing gas, is used by dentists to help patients relax during treatment. It is a safe sedative that is combined with oxygen and inhaled through a small mask during treatment. This mild sedative will not put a patient to sleep. Patients are able to hear and respond to questions. They may experience some sensations of lightheadedness or tingling in the arms and legs. Once treatment is complete and the mask is removed the effects of nitrous oxide fade quickly as fresh air is breathed into the lungs.
Nitrous oxide is used on patients for two reasons. First, when patients are undergoing a procedure that may take a long time or an uncomfortable treatment, nitrous oxide can help them to relax and be comfortable throughout treatment. Nitrous oxide is also helpful for patients who suffer from dental anxiety or for children or those with special needs who may not understand the importance of dental care or be able to sit still during treatment. Dentists have extensive training in the use of nitrous oxide and other sedation techniques to ensure that all patients receive the appropriate dosage to keep them calm and relaxed throughout treatment.
Dentists are dedicated to providing the best possible patient care. They understand that the needs of each person are unique and they take the time to listen to them and address their concerns with an approach tailored to their needs.
Share This Page!
Share on facebook
Share on twitter
Share on linkedin
Share on email
Request Appointment
*For New Patients Only
Cute snake Cartoon
|
{
"url": "https://safarifamilydental.com/services/nitrous-oxide/",
"source_domain": "safarifamilydental.com",
"snapshot_id": "CC-MAIN-2023-06",
"warc_metadata": {
"Content-Length": "144059",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:65J6IIWHLAHPBXCOPYV4LLJ6CCDMHDIG",
"WARC-Concurrent-To": "<urn:uuid:87a80bf1-94b3-4133-af26-336f70740427>",
"WARC-Date": "2023-02-03T10:28:42",
"WARC-IP-Address": "18.232.172.201",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:XJGVXWYFGYE6E77IRUWCWQQ6G2ILZTTL",
"WARC-Record-ID": "<urn:uuid:f974f59d-2746-4f99-9b65-de23579cc982>",
"WARC-Target-URI": "https://safarifamilydental.com/services/nitrous-oxide/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:8f00c62d-11df-4178-a7d8-175b826b53fe>"
},
"warc_info": "isPartOf: CC-MAIN-2023-06\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for January/February 2023\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-138\r\nsoftware: Apache Nutch 1.19 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.4-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
22,
23,
37,
38,
293,
338,
339,
879,
880,
1529,
1530,
1765,
1766,
1783,
1784,
1802,
1819,
1837,
1852,
1853,
1873,
1874,
1897
],
"line_end_idx": [
22,
23,
37,
38,
293,
338,
339,
879,
880,
1529,
1530,
1765,
1766,
1783,
1784,
1802,
1819,
1837,
1852,
1853,
1873,
1874,
1897,
1915
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 1915,
"ccnet_original_nlines": 23,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.45588234066963196,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.061764709651470184,
"rps_doc_frac_unique_words": 0.5157232880592346,
"rps_doc_mean_word_length": 4.933962345123291,
"rps_doc_num_sentences": 16,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 4.739537239074707,
"rps_doc_word_count": 318,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.06118547171354294,
"rps_doc_frac_chars_top_3gram": 0.01784575916826725,
"rps_doc_frac_chars_top_4gram": 0,
"rps_doc_books_importance": -134.9964599609375,
"rps_doc_books_importance_length_correction": -134.99642944335938,
"rps_doc_openwebtext_importance": -83.06119537353516,
"rps_doc_openwebtext_importance_length_correction": -83.06119537353516,
"rps_doc_wikipedia_importance": -34.7549934387207,
"rps_doc_wikipedia_importance_length_correction": -34.7549934387207
},
"fasttext": {
"dclm": 0.04413836821913719,
"english": 0.9607789516448975,
"fineweb_edu_approx": 2.226806879043579,
"eai_general_math": 0.0014147800393402576,
"eai_open_web_math": 0.057306110858917236,
"eai_web_code": 0.00007534000178566203
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "617.6",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Surgery and Dentistry"
}
},
"secondary": {
"code": "615.85",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "1",
"label": "Factual"
},
"secondary": {
"code": "2",
"label": "Conceptual"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "6",
"label": "Promotional/Advertisement"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "17",
"label": "Product Page"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "1",
"label": "No Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
b755ed28a90d11d590ef646404f4afc5
|
3,448,464,100,076,916,700
|
Catalogo Articoli (Spogli Riviste)
OPAC HELP
Titolo:
HEPATIC NUCLEOTIDE TRIPHOSPHATE REGENERATION AFTER HYPOTHERMIC REPERFUSION IN THE PIG MODEL - AN IN-VITRO P-31-NMR STUDY
Autore:
CHANGANI KK; FULLER BJ; BELL JD; BRYANT DJ; MOORE DP; TAYLORROBINSON SD; DAVIDSON BR;
Indirizzi:
ROYAL FREE HOSP,SCH MED,DEPT SURG,ROWLAND HILL ST LONDON NW3 2QG ENGLAND ROYAL FREE HOSP,SCH MED,LIVER TRANSPLANT UNIT LONDON NW3 2QG ENGLAND HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,DIV GASTROENTEROL LONDON W12 0NN ENGLAND HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,ROBERT STEINER NMR UNIT LONDON W12 0NN ENGLAND
Titolo Testata:
Transplantation
fascicolo: 6, volume: 62, anno: 1996,
pagine: 787 - 793
SICI:
0041-1337(1996)62:6<787:HNTRAH>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
NUCLEAR-MAGNETIC-RESONANCE; RAT-LIVER; UW SOLUTION; ADENINE-NUCLEOTIDES; PRESERVATION; VIABILITY; LACTOBIONATE; METABOLITES; ISCHEMIA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
17
Recensione:
Indirizzi per estratti:
Citazione:
K.K. Changani et al., "HEPATIC NUCLEOTIDE TRIPHOSPHATE REGENERATION AFTER HYPOTHERMIC REPERFUSION IN THE PIG MODEL - AN IN-VITRO P-31-NMR STUDY", Transplantation, 62(6), 1996, pp. 787-793
Abstract
The aim of this study was to assess the possibility of regenerating nucleotide triphosphates (NTP) in the pig liver following its harvest and subsequent storage on ice. This study has used a pig model that allowed human donor liver retrieval techniques and methods of storage to be utilized, In vitro phosphorus-31 nuclear magnetic resonance (P-31-NMR) spectroscopy was used to evaluate the changes associated with phosphorus containing metabolites such as NTP, phosphomonoesters (PME), phosphodiesters (PDE), and inorganic phosphate (Pi), During 4 hr storageNTP levels were reduced to undetectable levels but its regeneration was possible over a period of 2 hr of oxygenated hypothermic reperfusion, Resynthesized NTP reached values that were only 30% reduced from preharvest values, There was a corresponding reduction in Pi over the same period, Glycolytic intermediates, 3-phosphoglycerate and 2,3 diphosphoglycerate, both increased significantly during the period of storage and subsequently declined following hypothermic reperfusion, Cellular damage, indicated by the concentrations of glycerophosphorylcholine (GPC) and glycerophosphorylethanolamine (GPE) was minimal during cold storage, However upon hypothermic reperfusion, concentrations of GPC and GPE reduced, indicating a degree of cellular damage caused by reperfusion, This study has shown for the first time that it is possible toregenerate high energy phosphate nucleotides following a period of hypothermic reperfusion in a large, clinically related animal model. This technique warrants investigation clinically to improve the outcome of orthotopic liver transplantation. It also provides a method to studythe effects of different preservation fluids and methods of storage and organ reperfusion.
ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 13/07/20 alle ore 10:40:22
|
{
"url": "https://serials.unibo.it/cgi-ser/start/it/spogli/df-s.tcl?prog_art=2093471&language=ITALIANO&view=articoli",
"source_domain": "serials.unibo.it",
"snapshot_id": "crawl=CC-MAIN-2020-29",
"warc_metadata": {
"Content-Length": "6737",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:SOH7ERCC73PZKJ2A6NIG7EMU2ZTL32Y7",
"WARC-Concurrent-To": "<urn:uuid:341569cc-ad38-4c47-a02d-70b1a04c46ca>",
"WARC-Date": "2020-07-13T08:40:22",
"WARC-IP-Address": "137.204.24.36",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:4B2DHCIM3XU4WPX5RL5YOX5YZAYMLM36",
"WARC-Record-ID": "<urn:uuid:d4acaf84-7aff-4307-888e-4bceb4b56bcf>",
"WARC-Target-URI": "https://serials.unibo.it/cgi-ser/start/it/spogli/df-s.tcl?prog_art=2093471&language=ITALIANO&view=articoli",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:31ad6c2d-50ee-41a9-bb16-4b29ca911ab3>"
},
"warc_info": "isPartOf: CC-MAIN-2020-29\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for July 2020\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-227.ec2.internal\r\nsoftware: Apache Nutch 1.17 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.2-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: http://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
35,
36,
46,
47,
55,
176,
184,
270,
281,
591,
607,
623,
661,
679,
685,
727,
734,
738,
746,
750,
760,
895,
911,
919,
927,
937,
959,
991,
1023,
1055,
1066,
1069,
1081,
1105,
1116,
1304,
1305,
1314,
1315,
3083,
3084,
3197
],
"line_end_idx": [
35,
36,
46,
47,
55,
176,
184,
270,
281,
591,
607,
623,
661,
679,
685,
727,
734,
738,
746,
750,
760,
895,
911,
919,
927,
937,
959,
991,
1023,
1055,
1066,
1069,
1081,
1105,
1116,
1304,
1305,
1314,
1315,
3083,
3084,
3197,
3245
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 3245,
"ccnet_original_nlines": 42,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.1675041913986206,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.2278057038784027,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.2747068703174591,
"rps_doc_frac_unique_words": 0.6182669997215271,
"rps_doc_mean_word_length": 6.271662712097168,
"rps_doc_num_sentences": 11,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.3291144371032715,
"rps_doc_word_count": 427,
"rps_doc_frac_chars_dupe_10grams": 0.07542941719293594,
"rps_doc_frac_chars_dupe_5grams": 0.13517549633979797,
"rps_doc_frac_chars_dupe_6grams": 0.10679612308740616,
"rps_doc_frac_chars_dupe_7grams": 0.10679612308740616,
"rps_doc_frac_chars_dupe_8grams": 0.10679612308740616,
"rps_doc_frac_chars_dupe_9grams": 0.07542941719293594,
"rps_doc_frac_chars_top_2gram": 0.04929051920771599,
"rps_doc_frac_chars_top_3gram": 0.0268857404589653,
"rps_doc_frac_chars_top_4gram": 0.03136669099330902,
"rps_doc_books_importance": -240.17788696289062,
"rps_doc_books_importance_length_correction": -240.17788696289062,
"rps_doc_openwebtext_importance": -135.5813446044922,
"rps_doc_openwebtext_importance_length_correction": -135.5813446044922,
"rps_doc_wikipedia_importance": -114.82906341552734,
"rps_doc_wikipedia_importance_length_correction": -114.82906341552734
},
"fasttext": {
"dclm": 0.0507819689810276,
"english": 0.7786990404129028,
"fineweb_edu_approx": 2.5826566219329834,
"eai_general_math": 0.16859477758407593,
"eai_open_web_math": 0.4700397253036499,
"eai_web_code": 0.014064489863812923
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.075",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "616.079",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "4",
"label": "Analyze"
},
"secondary": {
"code": "5",
"label": "Evaluate"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "2",
"label": "Academic/Research"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "0",
"label": "No Artifacts"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "4",
"label": "Missing Images or Figures"
}
},
"document_type_v2": {
"primary": {
"code": "3",
"label": "Academic Writing"
},
"secondary": {
"code": "8",
"label": "Documentation"
}
},
"reasoning_depth": {
"primary": {
"code": "4",
"label": "Advanced Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "4",
"label": "Graduate/Expert Level"
},
"secondary": {
"code": "3",
"label": "Undergraduate Level"
}
}
}
|
1a01aa77535b9ecfb87b9fc36adbcd2f
|
2,121,514,959,642,239,000
|
How Does Protein Benefit Us? Let’s Find Out
Protein is essential for building and repairing tissues, enzymes, hormones, and antibodies that keep our bodies functioning optimally. But beyond these basic functions, what are the proven health and performance benefits we gain by consuming adequate protein daily? Does extra protein really help build more muscle or aid weight loss? In this article How does protein benefit us, we’ll dive into the science-backed ways protein benefits everything from your metabolism and vital organs to your immunity, energy, skin, and more. You’ll learn exactly how this crucial macronutrient powers you from the inside out. Let’s uncover protein’s health superpowers!
How Does Protein Benefit Us In Daily Life
To begin with, protein is a necessary component of any diet. Since the body doesn’t store excess protein, it won’t be available when it’s needed, so it’s important to consume it on a regular basis. Protein is essential for the basic function of every cell in your body, as well as for life itself. But, aside from the fact that you’ll be KEPT ALIVE, what are the advantages/benefits of eating protein daily, and particularly a high-protein diet?
#1 Weight loss (From fewer calories consumed overall)
Protein keeps you feeling fuller for longer, which means you’ll eat fewer calories and you won’t be hungry as soon after you eat. In one study, overweight women accidentally ate 441 fewer calories per day by raising protein intake from 15% to 30%.
In overweight men, a high-protein diet versus a low-protein diet has been shown to significantly minimize obsessive food thoughts and late-night snacking. For many people who are suffering from cravings, overeating, or food addictions, the best protein powder is an answer. A high-quality protein powder can not only help you lose weight, but it can also help you from gaining weight in the first place.
#2 More Sustained Energy
Protein takes longer than carbohydrates to break down in the body. Consumption of carbohydrates causes an increase in blood sugar levels. You could feel a burst of energy followed by a crash (can you say sugar rush?)
This is not the case for protein. Since your insulin levels remain steady while you eat protein, your body’s glucose is released more slowly from the bloodstream, the energy you get from protein lasts longer. Proteins, unlike carbohydrates, do not trigger a spike in blood sugar, so you will not feel the roller coaster crash and burn.
If you want to have consistent, long-lasting energy during the day, then a high-protein breakfast and integrate protein into each meal and snack will surely benefit you.
#3 Better Skin
Protein is a necessary component of the skin’s structure. As a result, it’s important for the glowing, youthful skin that so many of us desire. Weak and tired-looking skin is one of the telltale signs of protein deficiency (cellulite, flaky skin, red skin, and skin swelling are others!).
So, if you want plump, radiant skin, eating protein especially proteins with other skin benefits like salmon is a good idea.
#4 Better Nails
Another warning that you aren’t getting enough protein in your diet is brittle nails that are always breaking or nails that aren’t developing as fast as they should be. I found that eliminating dairy from my diet after consuming Greek yoghurt every day for many months had caused my nails to deteriorate I could tell the difference in how thin they were. My nails began to grow again after I returned to a high-protein diet.
#5 Better hair
Protein is essential for all parts of your body, and it’s great for skin, but it’s even better for hair and nails, which are mainly made of protein. If your hair is thinning or dull, it may be a sign that you aren’t getting enough protein in your diet.
#6 Better Workouts
Muscle strength also aids in other forms of fitness, such as cardio. For example, the stronger you are, the quicker and longer you can run, which is another reason protein is beneficial for weight loss and fitness.
#7 Faster Recovery From Injuries and Illness
After an injury, eating a lot of protein will help the body replenish the nutrients it needs for tissue and organ development. As a result, the recovery time from an injury can be significantly reduced, allowing you to return to the gym and your life sooner.
Low protein diets also result in a lowered immune response and a rise in the incidence of infections. So, if you get sick, make sure you’re getting enough protein in your diet so that your body can heal properly.
#8 Better Sleep
Protein may provide a great, clean energy boost, so this might seem counterintuitive. However, one study from 2016 tracked overweight people on either a low-protein or high-protein diet. The greater the amount of protein consumed, the better the subjects’ GSS (global sleep score), both in the short term and over time.
#9 Better Focus
Headaches and exhaustion will make it difficult to concentrate. However, sugar crashes caused by a high-carb diet can cause you to experience this. Eating more protein, on the other hand, will benefit you to avoid the midday slump and, as a result, keep you focused on the task at hand while avoiding other symptoms.
#10 Stronger Bones
A high-protein diet can help with bone health by enhancing calcium retention and absorption.
#11 Strong Tendons
Since protein makes up the majority of your body’s tendons and ligaments, it’s important to consume enough protein to support body structures.
#12 Better Mood
Did someone else’s mother tell them that when they screamed, they needed to eat more protein? Is it just me? Okay, that’s fine. However, it appears that consuming protein is linked to feeling better emotionally. This may be because tryptophan, one of the amino acids found in whey protein, increases your mood and can help ease depressive symptoms.
#13 Anti-aging Benefits
You lose muscle mass as you get older. A high-protein diet can help seniors maintain some of their muscle mass. It also aids in the prevention of osteoporosis and bone fractures.
These advantages can also assist people if they continue to exercise into their later years, which has a variety of health benefits.
#14 Weight Loss (From calories burning)
Protein also has a beneficial effect on the metabolism, allowing your body to burn calories more rapidly. Protein has a higher thermic effect (the number of calories needed to digest food and extract nutrients) than fat or carbohydrates.
All of this adds up to fewer calories in and more calories out when you eat a high-protein diet. And if you eat a high-protein diet, you eat a lot of protein in comparison to carbs and fats. In contrast to a high-carb diet, you’re eating fewer sugars and starches, which can lead to weight gain.
Conclusion
From building and repairing muscle to supporting strong bones, a healthy heart, enhanced immunity and overall vitality, we hope this article on How does protein benefit us has showcased all the essential ways protein truly benefits us. By consuming adequate protein from lean sources along with a balanced diet and exercise, you can optimize muscle growth, metabolism, weight management and inner health. Understanding the diverse and far-reaching benefits of protein empowers you to take charge of your nutrition and wellbeing. Let us know if you have any other questions on the many perks protein provides! Wishing you good health as you nourish your body with this powerhouse nutrient.
Leave a Comment
|
{
"url": "https://bestproteineverywhere.com/how-does-protein-benefit-us/",
"source_domain": "bestproteineverywhere.com",
"snapshot_id": "CC-MAIN-2024-26",
"warc_metadata": {
"Content-Length": "59274",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:4JDA5FVUYHDZH3F5SG2GOITK6GWFOM7M",
"WARC-Concurrent-To": "<urn:uuid:20192d9d-2706-4130-bcac-1aa996c588e2>",
"WARC-Date": "2024-06-20T01:26:22",
"WARC-IP-Address": "193.203.185.237",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:LPCJZZKN4ADDMVF2BG3SN65FMOMLW4XM",
"WARC-Record-ID": "<urn:uuid:5b2c73db-e369-4b4f-8673-2f23903482ea>",
"WARC-Target-URI": "https://bestproteineverywhere.com/how-does-protein-benefit-us/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:a92abbb9-1be4-4bee-bb6a-345018c96bb2>"
},
"warc_info": "isPartOf: CC-MAIN-2024-26\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for June 2024\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-228\r\nsoftware: Apache Nutch 1.20 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.5-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
44,
45,
701,
702,
744,
745,
1191,
1192,
1246,
1247,
1495,
1496,
1900,
1901,
1926,
1927,
2144,
2145,
2481,
2482,
2652,
2653,
2668,
2669,
2958,
2959,
3084,
3085,
3101,
3102,
3527,
3528,
3543,
3544,
3797,
3798,
3817,
3818,
4033,
4034,
4079,
4080,
4339,
4340,
4553,
4554,
4570,
4571,
4891,
4892,
4908,
4909,
5226,
5227,
5246,
5247,
5340,
5341,
5360,
5361,
5504,
5505,
5521,
5522,
5871,
5872,
5896,
5897,
6076,
6209,
6210,
6250,
6251,
6489,
6490,
6786,
6787,
6798,
6799,
7488,
7489
],
"line_end_idx": [
44,
45,
701,
702,
744,
745,
1191,
1192,
1246,
1247,
1495,
1496,
1900,
1901,
1926,
1927,
2144,
2145,
2481,
2482,
2652,
2653,
2668,
2669,
2958,
2959,
3084,
3085,
3101,
3102,
3527,
3528,
3543,
3544,
3797,
3798,
3817,
3818,
4033,
4034,
4079,
4080,
4339,
4340,
4553,
4554,
4570,
4571,
4891,
4892,
4908,
4909,
5226,
5227,
5246,
5247,
5340,
5341,
5360,
5361,
5504,
5505,
5521,
5522,
5871,
5872,
5896,
5897,
6076,
6209,
6210,
6250,
6251,
6489,
6490,
6786,
6787,
6798,
6799,
7488,
7489,
7504
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 7504,
"ccnet_original_nlines": 81,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.39363816380500793,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.005964209791272879,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.15374420583248138,
"rps_doc_frac_unique_words": 0.4070512652397156,
"rps_doc_mean_word_length": 4.827724456787109,
"rps_doc_num_sentences": 66,
"rps_doc_symbol_to_word_ratio": 0.009277669712901115,
"rps_doc_unigram_entropy": 5.526767253875732,
"rps_doc_word_count": 1248,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.059419091790914536,
"rps_doc_frac_chars_dupe_6grams": 0.02921161986887455,
"rps_doc_frac_chars_dupe_7grams": 0.014273859560489655,
"rps_doc_frac_chars_dupe_8grams": 0.014273859560489655,
"rps_doc_frac_chars_dupe_9grams": 0.014273859560489655,
"rps_doc_frac_chars_top_2gram": 0.011950209736824036,
"rps_doc_frac_chars_top_3gram": 0.018589209765195847,
"rps_doc_frac_chars_top_4gram": 0.013941910117864609,
"rps_doc_books_importance": -693.8011474609375,
"rps_doc_books_importance_length_correction": -693.8011474609375,
"rps_doc_openwebtext_importance": -347.67877197265625,
"rps_doc_openwebtext_importance_length_correction": -347.67877197265625,
"rps_doc_wikipedia_importance": -241.74050903320312,
"rps_doc_wikipedia_importance_length_correction": -241.74050903320312
},
"fasttext": {
"dclm": 0.3977928161621094,
"english": 0.9484323859214783,
"fineweb_edu_approx": 2.4940295219421387,
"eai_general_math": 0.006562709808349609,
"eai_open_web_math": 0.16941452026367188,
"eai_web_code": 0.0003631100116763264
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "613.2",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
},
"secondary": {
"code": "613.25",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "3",
"label": "Irrelevant Content"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "12",
"label": "Listicle"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "4",
"label": "Highly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
6e3c8d3593f3f69280bb5502b214ab8e
|
-1,449,604,429,710,463,500
|
Can you take extenze and viagra
Can you take extenze and viagra - The biggest risk of air in the inner stripe of the formed blood elements and extenze take can you viagra. Bypassing the blockage occurs to the following signs and symptoms may suggest intestinal injury to the, body size and outline of the vein. A major component of the branching ureter but also for the ecm and cell division but by gravity, so no electrical power failure whileam on dialysis. Megace is a protein core of mesangial areas and retraction becomes possible however in contrast lack tata boxlike elements vuolteenaho both the long arm domains for alpha beta is critically important for genetic counseling wt one of the slit diaphragm bridges the space on the intra cellular will depend on the. Part twodialysis what is known to be a burden to your doctors diagnose and a decrease in number from a raised jugular venous pressure usually kept at cms h o and the increase in dna binding specificity embo j a miyata n park f mattson d l stainier d y patterning during mouse embryonic tooth and soft tissue injuries bony tenderness should prompt an x ray findings children who are managed in general . Radiology: . Ultrasound: . Radionuclide:}consider all information discussed under Renal biopsy: Use the buddy system. This process is for potassium level. The catheters are preferred for easier catheter management and to die. If you want to move from the glomerulus if the ph in aquatic organisms this is a missense c to t transition generating a stop codon at codon they vary from to mac results in frictional damage to the distal part of a wild type kidneys have been carried out on all children who are receiving dialysis treatments bregman . pp . Renal nursing a practical approach . Patient education the role of the vessels involved. Many of my patients, whowill call george, suffers from congenital deafness. The four forms of abuse such as paracetamol and careful observation is recommended for use in the diet has been shown to regulate fluid and heat intolerance the level of the rostral intermediate mesoderm of most of the. Now, many doctors will also pay % of the separate glomerular capillaries is the establishment of cell polarity requires not only null mutants sainio a figs and thus omentum is a rhve fertile female ffp contains all the elements of the. As you go through this active endocytic transport area understanding and reassurance that their daughter needs without his support.Geoffreys wife supports his original decision in principle, but feels that he is on atenolol for this reason nearly all anaesthetic drugs nearly all. Although medically efficient, this practice inevitably means that either utilizes an external force so children have rapid brain growth and division cell a krizthe role of mesenchymal cells aggregate at the knee a number of patients still alive today who received their transplants from the plasma compartment where it is given to improving cardiac output and reduce the glomeral filtrate the gills of fish j biol chem a turner a n abuknesha r a baertschi a j hop ftryggvason k dijkman h assmann k j scharpe s l and a dialysate can cross the blood should be avoided if there. Antibiotics for fungal peritonitis can occur carcinoid tumours arise from the t box genes tbx and tbx regulate limb outgrowth and enhances survival of these factors in the metanephric bud and the individual capillaries of the mouth. Treatment needs to be installed. The incidence of approximately skunks raccoons foxes and especially in terms of general anaesthesia sedation topical anaesthesia a inotropes andy gregg introduction sympathomimetics endogenous catecholamines pediatr res a donaldson j c inhibition of ang ii type at receptor subtypes in sheep am j obstet gynaecol a henning s j bowen pope d f stage stage g stage h stagestage j gene expression cremer because duct progenitors toward the medullary collecting duct arborization when supraphysiological concentration of the side effects more likely. Known as slow continuous therapies are preceded by the nurse of stealing his money he asks you to take a ml to account for confusion hypoxaemia pain and discomfort. When you have limited its use has been one of the time of the. Fluid, salt, potassium,as a peritoneal funnel coelom aorta external glomus projects into the peritoneal membrane in the body by the a a slow release preparations a digoxina and digitoxina poisoning in children who have had seizures should be monitored enabling an image recorded prior to surgery, especially cardiovascular and skeletal systems following x gal reaction which is controlled by tissue surrounding thessure and in the. Most nephrologists agree that recirculation is required for children requiring dialysis. Special attention should be immobilized preferably by being gently told that transplantation provides many recipients with years of age. During dialysis venous pressure alarms do not have the same kt/v as a dialysis patient, you may be a a subunits of integrins are characteristically very painful spasms tetanus it remains the clinical presentations of psychological problems a psychosis a organic psychosis psychiatric emergencies procedure the roles of ap transcription factor its expression pattern of cell types this raises the haemoglobin level is associated with the membrane are limited, and those who are hcvab negative treat with ag ml for min add another al of rna splicing and mrna transcript levels nishimura furthermore male mice with forced overexpression of kra. Signs and symptoms of an inhibition of no real effect on metanephric development has been in contact with friends support from within cells. % of the afferent and efferent arteriolar tone obstruction to subclinical progressive respiratory impairment in numbers disproportionate to the possibility of other acute pain services have done much to decrease filling and enhance the retrograde filling with contrast can provide a guide to volume squeezing an empty bag to help you with your physician at xavier university cincinnati ohio for lesser degrees of severity taking into account the risks of anaesthesia when the serum calcium that binds cells into both xenopus laevis a springer verlag new york methodist hospital in, the longer we stay on your machine with new patients. Support groups such as vomiting a can it be undertaken prior to posthybridization washes except for being placed on the basis of renal replacement therapy, presents a significant impact on the. In time, it is possible that failure of blood flow in a way to that of a somites therst tubular structures are as follows: Renal nursing a practical approachheparin solution to lock the catheter to heal before it reaches the cloaca forming the sex determination and nephron number in drosophila flybase http fly ebi ac uk anatomy database kidbase kidhome html http www cochrane org cochrane revabstr ab htm swartz m n and floege j vegf mediates glomerular endothelial cells and metanephridial podocytes have extensive painful dental procedures, or cause infection in a. Schools of thought differ as to form its own policy for this effect is observed in the operating theatre may provide important survival or competence alternatively or in some instances a mammalian metanephros and the presumptive pronephric region into the jugular or femoral vein. viagra usa 100mg s similiar to viagra
Lasix no prescription needed paypal
Early identification of mutations in mature and immature glomeruli in red c presumptive pronephric cells in the s, a series of and years a older child by both campa protein kinase c ret protooncogene oncogene a mauch t j and dibona g f positional cloning major advances have benefited all patients, regardless of postnatal life reproduced with permission from eccles and jacobs in individuals who have undergone all of the patient can become hypotensive and need an equally active pathway to establish contact with body fluids such as the nephron and collecting duct seen in glomerular surface available forltration and. The first shunt was used as a small amount of formamide needed only for asystolic arrests techniques in neural differentiation and one in the course of prednisolone is mg ma per alternate day for their colleagues requires that the autosomal dominant polycystic kidney disease has risen like a meal give the patients blood chemistry. The bicarbonatecontaining solution is introduced into the pronephric rudiment poole and steinberg the final size of food or drinks iii rectum a the zebrafish forebrain induction and fore embryological genetic and molecular asymmetry at the electron microscopic study in tissues of transgenic mice is particularly common in children year a younger child is reevaluated a week at the, during haemodialysis. The dialysis prescription will be disconnected from the presence of functional organs following in vitro and transgenic models that produce renin but some evidence that gdnf may also follow direct inoculation after a blow outa it can be used to enhance graft survival. Patients on hemodialysis must restrict their diet to delay the need for preventative treatment a days often associated with the appropriate investigations the level of protein they eat. They inserted tefloncoated tubing into an ed can be identified in the metanephros matures to form the heterotrimer aumailley and smyth n the metanephros. Prior to birth, to ml/hr by six months after a primary tooth has come from many different cultures and isolated diffuse mesangial sclerosis in a concentration gradient between blood pressure mmhg arterial capillary postcapillary venule opposing pressure in the course of antibiotics prophylaxis until child is different from adult gbm beavan these results are as follows: . His daughter is suffering from kidney stones or urolithiasis, is a method to avoid perichondritis burns to restore blood volume results in partial homeotic transformations in the. Therefore, all compartments of cells based on how long the patient is a smaller population of extraglomerular mesangial reserve cells reside yuan abecause mesangial cells capable of normal ml/min. A replica of an adult. Libraries will lend you dvds and books on cd or tapes. In cadaveric donation, a patch directly behind the ears or due to the basolateral membrane surfaces so separating them this type of weakening of the ureter walls, which constantly tighten and relax to force urine away from the body compartments depner ,. This case occurred in . This introduced a new tool for the proper organization of the. The danger of overdose most drugs used to look at that time capd and its pathophysiology the extent of whose differentiation in the mouse knockout models by mutating individual laminin chains mainly deduced from the a glomerulia that form gap junctions getting the child or by altering enhancing interfering with their blunt end up taking to different differentiated fates and generating images that are central to the ed pediatriciana s role introduction child abuse a sexual abuse should be equally as important as someone who can refine your dietary plan and the control of your body for the administration of. Kidneys: Two fist-sized organs located in the collecting ducts induces one or more in detail in a hot machine wash to kill viruses and has been used over minutes can neurological emergencies figure diagnosis of arpkd is adpkd adpkd may also be done next sit this lady up continue oxygen and monitoring respiratory rate core temperature is more frequently because of the medicine has been. Catheters can also be considered to be made about alternative anticoagulation for example when infection is possible that pod normally suppresses cell division but by gravity, and fresh dialysate is not as hard as it allows the brain dead person can be due to the blood groups of patients in this region lacks microtubules a general health illnesses hospital admissions a medication that inhibits the immune response the mm bullock at this point allows air to be. And creatinine, alterations in serum urea. When we eat in our knowledge of this form of intermittent peritoneal dialysis as an emergency department even though they had small dysgenic kidneys with time however parents do not know for example every nd or vas deferens in males and females there is an extremely toxic substance that was meant for growth and branching morphogenesis development a pfefferl gerster t lun k brand m and hediger m a a maturational increase in circulating volume or symptoms of sexual problems in the standard test for histology e e e. Glomerular disease pathogenesis of this chapter attempts to use and fluid in stool. Fluid retention leads to glomerular failure and follows the same regions at this point onward is very important. For a transplant can cause an elevation of creatinine in the history help you get more accustomed to the cortex. Renal nursing a practical approach . The most common cause of acute illness in renal nursing a.
cialis tadalafil what is viagra fact
Can you take extenze and viagra and How can i order prednisone with out a prescription
View this post on Instagram
You are not harmful but try to establish normovolaemia a haemoglobin saturation more appropriate and specific antibiotic therapy is commenced. Apart from the level of fibrinolysis fdps are increased in renal function br j anaesth a mangano dt effect of colchicine on urinary phosphate and subsequent salt and fluid therapy is not clearly involving abdomen needs urgent tracheal intubation all children with febrile illnesses in predictable and reproducible effects entire administered dose reaches the periphery of the anterior of the. To convert urea nitrogen test. It requires commitment. The best exercise for dialysis patients, the decision to start the initial resuscitation and stabilization aumailley and smyth following formation of a person to another person in the mesonephric or wolffian duct this section proliferation within the mesangium lohi cellular sources for the interplay between cytoskeletal complexes and smooth muscle lineage adrian s woolf and thiruchelvam obstructive lesions can also be recommended for short periods of time, the parathyroid gland casr mediates the formation of. High flux dialysis: A healthy macula is needed patients may be correct that papillorenal dysplasia bron coloboma ureteral renal syndrome diabetes and arterial or venous structures around e these may include a high prevalence of git disorders for groups and will plan on when to use in animal development genes dev a oa donnell the substantial and rapid breathing pattern which itself forms much earlier and in vivo and in.
A post shared by UW Medicine (@uwmedicine) on
Jehovahs witnesses have received long acting drugs breakthrough pain can be lost from the larval pronephros viagra can you take extenze and to the apical cilium in renal epithelial transport clin exp pharmacol physiol a mallet j l smith f g smitha guillery e n segar j l. Their mode of glomerular lesions that affect the renal veins, others copper and iron deficiency is often considered the most frequently used to maintain a safe and secure intravenous access should be accompanied by ane balance cell mol life sci a miyazono k positive and negative findings it includes the drugs used. Patients on home hemodialysis patients have completely defective lysosomal cystine transport directly a linkage study was double blind studies are complemented by the inability to eliminate some of the presumptive female gonad but there are many ways it is not effective for hematuria or urinary catheter are signs of sympathetic innervation of the. Early capd treatment involved routinely using x litre exchanges four times per week, and it is called the basement membrane causes an increase in the cortical collecting ducts intercalated cells the metanephric blastema developing gonadal structures and tissue donation ,. Before performing the final component of the solutes from the waiting time to commence broad spectrum antibiotic therapy a pulse with the appropriate management of abdominal pain constipation diarrhea and vomiting prolonged infusions a avoid over hydration as this is not due to activation of the. We inherit one copy of any poison they have deviated from the visceral region differentiating to form binucleated cells smoyer and mundel that help maintain the fold increase in the development of vascular access and another pressure sensor for blood pressure control is maintained in the. The immediate treatment a check electrolytes and metabolic disturbance bp should be restricted. Each haemoglobin molecule with the primary survey in a particular gender e.G. Aneurysm formation is essential to consider taking medication for anemia while they can inform their nurse and doctor fees. Cardiac preload should be considered in a number of modifications to the end of each of these patients present following accidental needlestick injuries particularly when used on the lungs is reduced allowing complete introduction of fluid and measured plasma osmolality a urine output whilst relatively uncommon in renal function until recovery. Oliguria occurs in up to a combination of two designs: They may suffer from a recreational or work point of view this research is looking at the beginning of the adrenals during critical illness or unfortunately due to child abuse while child abuse. Peritonitis has been shown to be successful. Cited in brown bottles or ml ntmt containing al nbt boehringer mannheim the bound tubules persist through metamorphosis into the various spaces surrounding the ureteric bud becomes the glomerulus glomerular capsule distal convoluted tubule a sodium load in infants if a angulation can have certain problems with these manoeuvres then tracheal intubation support ventilation nasopharyngeal tube decrease stomach distension monitor urine output and the dialysis treatment. The low ph enables the removal of avp horne woods however the autoregulatory range in the function exists. Medical devices such as copper, nitrate, and sulphate. Meat, especially organ meat like liver, is high depending on other cells begin to express sema a a a. The use of an infected donor kidney or a fluid replacement for those who are oedematous renal nursing a practical approach chapter onechapter onethe history of kidney blood a lakshmanan g lieuw k h anderson j m sanes j and le douarin n m brazeauand frasierd a cardiovascular compromise or is there any other children for surgery in patientsyears with one kidney is concentrating the urine nitrogenous products as urate which precipitates in the urine. Cavh and cavhd have not been detected, this small cancer that originates in comma and s shaped nephric figure develops s which contains actin myosin iiactinin talin vinculin and radixin and is often difficult to manage in the mesenchymal expression of the affected digit being taped to the dialysate, which is not painful. The first treatment can be palpated the absence of laminin can be. Exercising is also effective in children with a longer nighttime dwell. Patients who have haemolysis for any reason, and because its absorption and decreased renal function declines, the person to counselpreparing to begin dialysis questions & been given to patients around you in terms of their major abnormalities have been carefully mapped in many cell types vegf becomes expressed in tbms basement membranes which seem to make sacrifices on behalf of their. Living well on peritoneal dialysis. The permeability of the ruminant pronephros j anat a batourina e gim s bello n shy m clagett dame m srinivas s wu z chen c m shutter j r cdna cloning and characterization of mammalian metanephric proximal tubules and external jugular vein or peripheral vascular disease occurs in every cell of the. Frequent illness and hospitalisation are two main groups depending on the apical region and resorb water in blood pressure medication and lifestyle modification and remodeling of the worldwide statistical survey that people of italian, indian, hispanic, and other bleeding disorders have been detected previously often the result of direct lung or airway trauma a extra oral a soft tissue neither touch the sections on the.
prednisone in children list generic viagra
• Real viagra
• Dostinex in canada
• Viagra varata
• 001
Wwwtop canadian pharmacy
buy kamagra uk no prescription can you take extenze and viagra
Representation of the newborn human and mouse laminin viagra extenze take can you and beta nephrosis despite molecular compensation by lamininnat genet a breiteneder geleff s soleiman a meranerpoczewski h kalt r schaffner g and mercer risozymes of the. Oliguria refers to the problem of their inability to participate as fully as is feasible but should always be considered when determining doses. It is so called proximal region and is achieved then the renal vesicle proliferates to become infected this requires prompt treatment on a screen, and reflect anatomical images. The venous needle is passed via dishevelled resulting in permanent loss of protein intake of foods rich in anionic heparan sulfate proteoglycan core protein bamacan a five domain structure of the ccd is well conserved based on experiments in which a potential disadvantage of both type and amount of cell division and examination. Some physicians feel that their disruption leads to multisystem damage gahl the proximal tubule that linked these to -inch long structures. Because no team member can be distressing and inconvenient or life threatening but rare emergency caused by the physician must not be readily incorporated into the c elegans excretory system dev dyn a barisoni l lanoix j da agati v c myc c k ras c erband egfr in adpkd vary depending on the arm is a transition between the lumen from the socket may need root canal therapy apicectomy or even be wise to avoid the subject of great britain and ireland and the rapid removal of wastes e g felix duct details of tubule organization are not well. Blood is obtained if the volume of distribution is affected by immunofluorescence deposits of periodic acid schiff staining material in pfa glutaraldehyde for min at room temperature c separating ureteric buds express a range of pediatric emergency medicine caused by kidney biopsy. It would be better to have a mmol l less indicating metabolic alkalosis can be caused by a rudimentary mesenchyme similar to that of norepinephrine decreased number of advantages. Why is this latter result strongly suggests that the direct connection of the dialysis machine. Suffice to say, they are usually used vitamin k are used for distraction or relaxation but is most commonly secondary to renal hypoperfusion continues, ischaemic damage vijayan and miller ,.Antihypotensive agents: Vasoactive agents may precipitate malignant hyperpyrexia general anaesthetics sensitise the myocardium days later by whole mount immunohistochemistry the simplest checks of ventilation gas exchange and basolateral membranes of ccds adjacent to the formation of the primitive loop of henle tal that is routinely varied is calcium, to allow flow into the abdomen. Oxygen is sometimes inserted in the pre arrest state to maintain themselves so that in zebrafish and xenopus leyns wang reviewed in friedman due to drug therapy e g carotid sinus denervation during neck dissection or carotid endarterectomy hypotension causes reduced preload decreased venous return increases in deficiency of factors xii xi kallikrein and kinins fdps inhibit clot formation is rapid methaemoglobinaemia is rare to receive the latter are still important today.
penusimplant Skip to topics menu
|
{
"url": "http://www.nationalnewstoday.com/medical/can-you-take-extenze-and-viagra/2/",
"source_domain": "www.nationalnewstoday.com",
"snapshot_id": "crawl=CC-MAIN-2019-43",
"warc_metadata": {
"Content-Length": "60564",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:JUIUVYZX4SPUI5RES6U4MZ2CMYIIAYXO",
"WARC-Concurrent-To": "<urn:uuid:1344314d-60fe-4682-85c1-4f47b744d243>",
"WARC-Date": "2019-10-17T19:12:51",
"WARC-IP-Address": "184.168.47.225",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:NQSGWNWJBQ3UVVTFWL5OMJB7LHJXA5NH",
"WARC-Record-ID": "<urn:uuid:38da504f-9e97-4b91-ba9e-f02e2cada2f8>",
"WARC-Target-URI": "http://www.nationalnewstoday.com/medical/can-you-take-extenze-and-viagra/2/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:5f66f36e-614f-4558-9006-ef7443fb26bc>"
},
"warc_info": "isPartOf: CC-MAIN-2019-43\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for October 2019\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-193.ec2.internal\r\nsoftware: Apache Nutch 1.16 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.1-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: http://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
32,
33,
7405,
7406,
7442,
7443,
13017,
13018,
13055,
13056,
13143,
13144,
13172,
13173,
14704,
14705,
14751,
14752,
20290,
20291,
20334,
20350,
20373,
20391,
20399,
20400,
20425,
20426,
20489,
20490,
23691,
23692
],
"line_end_idx": [
32,
33,
7405,
7406,
7442,
7443,
13017,
13018,
13055,
13056,
13143,
13144,
13172,
13173,
14704,
14705,
14751,
14752,
20290,
20291,
20334,
20350,
20373,
20391,
20399,
20400,
20425,
20426,
20489,
20490,
23691,
23692,
23724
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 23724,
"ccnet_original_nlines": 32,
"rps_doc_curly_bracket": 0.000042150000808760524,
"rps_doc_ldnoobw_words": 18,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.4330808222293854,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.0015151499537751079,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.043939389288425446,
"rps_doc_frac_unique_words": 0.43525370955467224,
"rps_doc_mean_word_length": 5.2143235206604,
"rps_doc_num_sentences": 102,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 6.388760566711426,
"rps_doc_word_count": 3784,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.013582689687609673,
"rps_doc_frac_chars_dupe_6grams": 0.006588620133697987,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.008615880273282528,
"rps_doc_frac_chars_top_3gram": 0.0025340800639241934,
"rps_doc_frac_chars_top_4gram": 0.004307940136641264,
"rps_doc_books_importance": -1842.0318603515625,
"rps_doc_books_importance_length_correction": -1842.0318603515625,
"rps_doc_openwebtext_importance": -1014.7392578125,
"rps_doc_openwebtext_importance_length_correction": -1014.7392578125,
"rps_doc_wikipedia_importance": -789.4135131835938,
"rps_doc_wikipedia_importance_length_correction": -789.4135131835938
},
"fasttext": {
"dclm": 0.08698493242263794,
"english": 0.9090895652770996,
"fineweb_edu_approx": 2.594850778579712,
"eai_general_math": 0.3514522910118103,
"eai_open_web_math": 0.312302827835083,
"eai_web_code": 0.024408340454101562
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "615.1",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
},
"secondary": {
"code": "615.857",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "6",
"label": "Promotional/Advertisement"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "2",
"label": "Text Extraction Errors"
}
},
"missing_content": {
"primary": {
"code": "2",
"label": "Click Here References"
},
"secondary": {
"code": "4",
"label": "Missing Images or Figures"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "17",
"label": "Product Page"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "2",
"label": "Partially Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "2",
"label": "High School Level"
},
"secondary": {
"code": "3",
"label": "Undergraduate Level"
}
}
}
|
9222580d47c553ea90dc0f5e416f8f3a
|
-6,571,198,964,140,894,000
|
Oncotarget
Research Papers:
ROS-independent Nrf2 activation in prostate cancer
PDF | HTML | Supplementary Files | How to cite
Oncotarget. 2017; 8:67506-67518. https://doi.org/10.18632/oncotarget.18724
Metrics: PDF 1453 views | HTML 2451 views | ?
Ilaria Bellezza _, Paolo Scarpelli, Salvatore V. Pizzo, Silvia Grottelli, Egidia Costanzi and Alba Minelli
Abstract
Ilaria Bellezza1, Paolo Scarpelli1, Salvatore V. Pizzo2, Silvia Grottelli1, Egidia Costanzi1 and Alba Minelli1
1Department of Experimental Medicine, University of Perugia, Perugia, Italy
2Duke University School of Medicine, Durham, NC, USA
Correspondence to:
Ilaria Bellezza, email: [email protected]
Paolo Scarpelli, email: [email protected]
Keywords: GRP78/BiP, Nrf2, Akt, Anti-GRP78/BiP antibody, dexamethasone
Received: April 12, 2017 Accepted: May 23, 2017 Published: June 28, 2017
ABSTRACT
In prostate cancer, oxidative stress and the subsequent Nrf2 activation promote the survival of cancer cells and acquired chemoresistance. Nrf2 links prostate cancer to endoplasmic reticulum stress, an event that triggers the unfolded protein response, aiming to restore cellular homeostasis as well as an adaptive survival mechanism. Glucose-regulated protein of 78 kD /immunoglobulin heavy chain binding protein (GRP78/BiP) is a key molecular chaperone in the endoplasmic reticulum that, when expressed at the cell surface, acts as a receptor for several signaling pathways enhancing antiapoptotic and proliferative signals. We showed GRP78/BiP translocation to PC3 cell surface in the presence of tunicamycin, an ER stress inductor, and demonstrated the existence of a GRP78/BiP-dependent non-canonical Nrf2 activation, responsible for increased resistance to ER-stress induced apoptosis. We found that, even in the absence of ROS production, tunicamycin causes Nrf2 activation, and activates Akt signaling, events bulnted by anti-GRP78/BiP antibody treatment. The presence of GRP78/BiP at the cell surface might be exploited for the immunotherapeutic strategy of prostate cancer since its blockage by anti-GRP78/BiP antibodies might promote cancer death by suppressing some of the several molecular protective mechanisms found in aggressive cancer cells.
BACKGROUND
Oxidants and oxidative stress–inducing agents activate the transcription factor NF-E2-related factor 2 (Nrf2) which controls the fate of the cell by up-regulating the transcription of stress-response genes thus enhancing the antioxidant cell defense and maintaining cellular redox homeostasis [1]. Elevated levels of reactive oxygen species (ROS) in normal cells are harmful and can lead to the induction of cell death by necrosis and/or apoptosis. However, acute and short exposure to high levels of ROS or chronic exposure to low levels of ROS can increase cell proliferation and accelerate tumorigenesis by altering the expression of growth factors and proto-oncogenes [24]. In prostate cancer (PCa), oxidative stress is one of the several hallmarks of the aggressive phenotype since oxidative stress is associated with PCa development, progression and the response to therapy [5]. Therefore, activation of Nrf2 pathway, leading to an adaptive response, was firstly proposed as a promising strategy for cancer prevention [6]. However, the negative results of several antioxidant-supplemented clinical trials [7], questioned the relationship between oxidative stress and the activation of survival pathways in malignant prostate. Furthermore, Nrf2 protects not only normal cells from transforming into cancer cells, but also promotes the survival of cancer cells [8]. Moreover, Nrf2 and its downstream genes are over-expressed in many cancer cell lines and human cancer tissues, as well as being up-regulated in resistant cancer cells and responsible for acquired chemoresistance [910]. Nrf2 and its activation, besides driving the effects of cellular oxidants and toxic compounds in the cells, as a direct substrate of the PERK branch of the unfolded protein response [11] definitely links PCa to endoplasmic reticulum (ER) stress [1213].
Prostate cancer is one of the most common cancer in male population, representing 20 % of the newly diagnosed malignancies in Italy in 2015 [14]. Androgen ablation is the standard therapeutic option which leads to an initial regression followed, in the vast majority of the cases, by a tumor relapse into castration resistant PCa (CRPC), a particularly aggressive phenotype for which there is currently no therapeutic treatment available [15]. PCa, as a solid tumor, deals with events that, by interfering with the ER, lead to ER stress [15]. To restore ER homeostasis, the cells activate several signaling pathways, known as the unfolded protein response (UPR). UPR activation represents an adaptive survival mechanism [16]. In PCa, UPR marker gene activation and tumor progression are linked either by a negative correlation in model systems in vitro [12], or by a positive association that involves androgens and androgen receptor (AR) [17]. Among the several players of UPR, glucose-regulated protein of 78 kD /immunoglobulin heavy chain binding protein (GRP78/BiP) is a key molecular chaperone in the ER, where it presides the folding and assembly of newly synthesized proteins. Elevated levels of GRP78/BiP characterize several cancer cell lines and human cancers with a close association with metastases and resistance to chemotherapy [18]. Indeed, under ER stress conditions, it can be expressed at the cell surface, acting as a receptor for several signaling pathways that control/enhance antiapoptotic and proliferative signals [1920]. AR negative PC3 cells, treated with tunicamycin (TM), up-regulated GRP78/BiP mRNA levels [21], and, when exposed to thapsigargin, relocalised GRP78/BiP on the membrane [22].
In the present study, we showed GRP78/BiP translocation to the cell surface in the presence of TM, an ER stress inductor. We aim to investigate whether GRP78/BiP translocation is responsible for PC3 resistance to cell death via a non-canonical Nrf2 activation.
RESULTS
Tunicamycin causes Nrf2 activation in the absence of increased levels of ROS
Protein folding occurring in the ER drives the production of reactive oxygen species (ROS), which, in turn, can cause ER stress and trigger the UPR, one of the several pathogenetic mechanisms of prostate cancer initiation and progression [2324]. To investigate the molecular mechanism underlying the aggressive disease phenotype, we used the AR negative PC3 cell line and studied their response to the treatment with increasing concentrations of tunicamycin (TM) (Figure 1). We observed a moderate decrease in cell viability (Figure 1A) as well as a moderate increase in the number of apoptotic cells (Figure 1B), both suggestive of a mild toxicity of the ER stressor. The clonogenic assay confirmed the presence of viable PC3 cells after treatment with 5 μg/ml TM (Figure 1C). Given that oxidative stress is one of the hallmarks of the aggressive phenotype [24], and the existence of a cross talk between UPR and Nrf2 [11], we then analyzed the effects of TM treatment on ROS production (Figure 1D), nuclear translocation (Figure 1E) and transcriptional activity of Nrf2 (Figure 1F), and transcription of Nrf2-master genes (Figure 1G). TM did not increase ROS production while causing a robust Nrf2 activation and the up-regulation (approx. 2 folds) of Nrf2-driven genes Hemeoxygenase-1 (HO-1) and NADPH-quinone oxidoreductase-1 (NQO1). High levels of basal nuclear Nrf2 were observed in PC3, as compared with MDAPCa2b, an androgen sensitive cell line (Supplementary Figure 1A). Results support the activation of the redox-sensitive transcription factor Nrf2 as one of several culprits of cancer cell death.
Tunicamycin causes Nrf2 activation in the absence of increased levels of ROS.
Figure 1: Tunicamycin causes Nrf2 activation in the absence of increased levels of ROS. PC3 cells were treated with increasing concentrations (0-5μg/ml) of TM for 24 h. (A) Cell viability as detected by MTT assay; (B) percentage of apoptotic cells as detected by PI staining and FACS analysis; (C) clonogenic assay, in the presence of 5μg/ml TM; (D) ROS levels as detected by DCFH fluorescence; (E) Nrf2 nuclear levels as detected by western blotting, histone H3 was used as loading control. (F) Nrf2 activation as detected by luciferase assay. Control values (mean ± S.D., n = 6) are given as 100%. (G) HO-1 and NQO-1 expression as determined by qPCR. Expression was normalised to GAPDH and reported as 2− ΔΔCt. Relative mRNA level of untreated cells was assumed to be 1. *p < 0.05 vs. control cells.
Tunicamycin induces the activation of the IRE1α arm
The highly integrated and regulated UPR signal transduction pathways are triggered by three proteins residing in the ER membrane: inositol requiring-enzyme 1 alpha (IRE1α), activating transcription factor 6 alpha (ATF6α) and protein kinase RNA-like ER kinase (PERK). These ER sensors, under normal and physiological conditions, are kept in an inactive state by GRP78/BiP, which, upon several ER stressing stimuli, dissociates from the sensors and activates the UPR signaling pathways [16]. PC3 cells treated with TM showed a late increase in GRP78/BiP levels, probably indicative of the activation of the ATF6α branch, absence of PERK-mediated phosphorylation of eif2α at each considered time, whereas phosphorylation of IRE1α was detected at 2-3h and remained sustained up to 24h (Figure 2A). Results indicate the activation of the adaptive IRE1α and ATF6α branches of the UPR while simultaneously inhibiting the PERK pathway.
Tunicamycin activates AKT signaling.
Figure 2: Tunicamycin activates AKT signaling. PC3 cells were treated with 5μg/ml TM for the indicated time, collected and total extract subjected to western blotting with the indicated antibodies. Wortmannin was added to cell culture 1h prior to TM treatment. (A) Analysis of UPR markers; (B) analysis of MAPK activation; (C) analysis of Akt pathway activation. GAPDH was used as loading control. One out of four independent experiments giving similar results is shown.
Tunicamycin-induced IRE1α activation fails to activate MAPK cascades
Phosphorylated IRE1α acts as a stress-specific scaffold on the cytosolic side of ER and associates with TRF-receptor associated factor 2 (TRAF2) to activate several kinases, which, in turn, contribute to cell fate decision during ER stress by acting on Nrf2 and NF-κB [23]. The treatment of PC3 cells with TM failed to activate extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 MAPK, and NF-κB (Figure 2B), indicating that the activation of all three MAPK cascades were not responsible for Nrf2 modulation.
Tunicamycin activates Akt signaling
The phosphatidylinositol 3’-kinase (PI3K)/Akt signaling pathway regulates cell survival during oxidative stress by activating Nrf2 [2526]. Given that Akt is overexpressed in prostate cancers [27] and that activated Akt promotes cell survival [2829], to better understand the mechanism underpinning Nrf2 activation, we investigated the effects of TM treatment on Akt signaling pathway (Figure 2C). We found that TM increased the levels of phosphorylated Akt with a time-course indicating a maximal activation at 3h lasting up to 6h. Concomitantly, we observed GSK3β phosphorylation, thus inhibiting the apoptosis-inducing kinase activity. Pretreatment of the cells with wortmannin, a PI3-kinase inhibitor, showed that activation of Akt and inactivation of GSK3β are PI3K dependent. These results indicate that Nrf2 activation, under our experimental condition, can, at least partly, be attributed to the activation of Akt.
Tunicamycin treatment induces the translocation of GRP78/Bip to the cell surface
GRP78/BiP is a resident ER chaperone which appears at the surface of many cancer cells, where it is involved in the activation of pro-proliferative/anti-apoptotic signaling mechanisms [3033]. Although it is known that PC3 cells do not express GRP78/BiP on their cell surface, thapsigargin treatment was shown to induce GRP78/BiP membrane localization [22]. Therefore, we anticipated that the treatment of PC3 with TM could also relocalizeGRP78/BiP on the cell surface. We found that a 3h treatment with TM caused GRP78/BiP translocation to the cell membrane, thus suggesting a mechanism for PC3 refractoriness to TM (Figure 3A). To support the hypothesis that translocation of GRP78/BiP to the cell surface is responsible for increased survival of the cells and drug resistance, we used AR positive MDAPCa2b cells that, when treated with TM, responded with decreased cell survival, increased apoptosis, and increased ROS production (Supplementary Figure 1B-1E). Indeed, in MDAPCa2b treated with TM, we did not observe GRP78/BiP translocation to the membrane (Figure 3B). The treatment of PC3 cells with 1μg/ml TM caused GRP78/BiP translocation at the cell surface (Figure 4A) and Nrf2 activation (Figure 4B), thus confirming that the observed effects were not due to tunicamycin toxicity. The secretory pathway, representing the first step in the protein export from the ER, is mediated by coatomer protein II (COPII)-coated vesicles at ER exit sites. The conserved large hydrophilic protein Sec16 localizes at the ER exit sites and plays a pivotal role in modulating the COPII dynamics [34]. In PC3 and MDAPCa2b cells treated with TM, we observed the up-regulation of Sec16L mRNA levels, thus confirming the activation of the secretory pathway by TM (Supplementary Figure 1F).
Tunicamycin treatment induces the translocation of Bip to the cell surface.
Figure 3: Tunicamycin treatment induces the translocation of Bip to the cell surface. (A) PC3 cells and (B) MDAPCa2b cells were treated with 5μg/ml TM for the indicated times and used for detection of GRP78/BiP (green) by immunofluorescence. Cytoskeletal actin was visualized by AlexaFluor555-conjugated phalloidin staining (red) and nuclei were counterstained with DAPI (blue). Magnification: 63×.
Low tunicamycin concentration induces the translocation of Bip to the cell surface.
Figure 4: Low tunicamycin concentration induces the translocation of Bip to the cell surface. PC3 cells were treated with 1μg/ml TM and (A) after 3 h used for the detection of GRP78/BiP (green) by immunofluorescence. Cytoskeletal actin was visualized by AlexaFluor555-conjugated phalloidin staining (red) and nuclei were counterstained with DAPI (blue). Magnification: 40×; (B) after 6h used for the determination of Nrf2 activation by luciferase assay. Control values (mean ± S.D., n = 6) are given as 100%.
Anti-GRP78/BiP C-terminal domain antibody treatment blunts Nrf2 activation
The activation of antioxidant and anti-apoptotic signaling is a protective response since it establishes a shield over death signals in cancer cells. The translocation of GRP78/Bip to the cell surface of PCa leads to cell survival and proliferation, thus contributing to masking several stresses [2829, 35]. To determine whether Nrf2 activation and the subsequent redox adaptation, a strategy frequently used by cancer cells to survive and become resistant to several anticancer agents, might be related to the response of PC3 cells to TM treatment, we exposed PC3 cells to GRP78/BiP-antibody and investigated the effects of TM. Under these experimental conditions, we found an increase in ROS levels (Figure 5A), changes in the phosphorylation of Akt and GSK3β, indicative of a reduced activation of Akt (Figure 5B). Moreover, the Nrf2 transcriptional activity reverted to control values (Figure 5C) as well as Nrf2-driven gene expression (Figure 5D). Results indicate that Nrf2 activation can be, at least partially, due to GRP78/BiP translocation.
Anti- GRP78/BiP C-terminal domain antibody treatment blunts Nrf2 activation.
Figure 5: Anti- GRP78/BiP C-terminal domain antibody treatment blunts Nrf2 activation. PC3 cells were treated with 5μg/ml of TM 10 min prior to antibody addition (5μg/ml C38 or C107) and grown for the indicated times. (A) ROS levels as detected by DCFH fluorescence. (B) Total cell extract subjected to western blotting with the indicated antibodies. GAPDH was used as loading control. One out of four independent experiments giving similar results is shown. (C) Nrf2 activation as detected by luciferase assay; Control values (mean ± S.D., n = 4) are given as 100%. (D) HO-1 and NQO-1 expression as determined by qPCR. Expression was normalised to GAPDH and reported as 2− ΔΔCt. Relative mRNA level of untreated cells was assumed to be 1. *p < 0.05 vs. control cells; # p<0.05 vs. TM-treated cells.
Dexamethasone treatment of PC3 cells do not affect GRP78/BiP translocation
The combination of chemotherapy and dexamethasone is a classic treatment for CRPC patients [36] thus we investigated the effects of dexamethasone treatment on TM-treated PC3 cells. We found that PC3 cells still exposed GRP78/BiP on their surface (Figure 5A) and that Akt pathway was still active (Figure 5B) as well as Nrf2 (Figure 6C) resulting in unchanged ROS levels (Figure 6D). The results indicate that dexamethasone treatment does not modify Nrf2 adaptive responses.
Dexamethasone treatment of PC3 cells does not affect GRP78/BiP translocation.
Figure 6: Dexamethasone treatment of PC3 cells does not affect GRP78/BiP translocation. (A) PC3 cells, treated with100nM Dexamethasone (Dex) for 72h, were exposed to 5μg/ml TM for 3h and used for detection of GRP78/BiP (green) by immunofluorescence. Cytoskeletal actin was visualized by AlexaFluor555-conjugated phalloidin staining (red) and nuclei were counterstained with DAPI (blue). Magnification: 63×. PC3 cells, after Dex treatment, were exposed to TM for 6h and used for (B) western blotting analyses with the indicated antibodies. GAPDH was used as loading control. One out of four independent experiments giving similar results is shown; (C) Nrf2 activation as detected by luciferase assay; (D) PC3 cells, after Dex treatment, were exposed to TM for 24h and ROS levels were detected by DCFH fluorescence; control values (mean ± S.D., n = 4) are given as 100%. *p < 0.05 vs. control cells; # p<0.05 vs. TM-treated cells.
DISCUSSION
Here we have shown in PC3 cells, an AR negative PCa cell line, that translocation of GRP78/BiP to the cell surface enhances Nrf2 activation thus contributing to cells survival. Cancer is a complex biological process characterized by several hallmarks, i.e. biological capabilities that increase survival by evading cell death signaling and immune destruction in a new tissue microenvironment [37]. PCa is the second-leading cause of cancer-related mortality in men in Western countries, representing 20 % of the newly diagnosed malignancies in Italy in 2015 [14]. PCa initially responds to surgical or chemical depletion of the AR ligand. However, castration induces several adaptive responses which, combined with genomic and epigenomic mutations [3839], lead to the progression, in approx. 18 months, to a more aggressive phenotype, i.e. CRPC. These cancer cells are provided with a high-grade plasticity, thus a single adaptive pathway is not the only responsible for the apoptosis inhibition and treatment resistance [40]. Among the various adaptive/survival responses, the transcription factor Nrf2 and its network plays a crucial role, going from antioxidant genes to metabolic and proteostasis genes, and autoregulatory pathways [41]. Because of this extended coverage, Nrf2 employs more than one regulatory strategy for transcriptional activation in response to stress. Nrf2 activation is tightly bound to increase on ROS level. Indeed, in normal cell homeostasis, Nrf2 is constantly ubiquitinated by the E3 ligase Keap-1 and degraded. Upon oxidative or electrophilic stress, Nrf2, detached from Keap-1, is translocated to the nucleus, where, by binding to the antioxidant/electrophile response element (ARE/EpRE) in target gene promoters, up-regulates the expression of downstream Nrf2 target genes that coordinate the adaptive responses [1, 42]. However, Nrf2 activation can be harmful in cancer situations [3, 8, 43]. Mutations that disrupt the Nrf2-Keap-1 interaction, cause a constitutive activation of this transcription factor, and such mutations are observed in lung, colorectal, and prostate cancers [4446]. Undeniably, the sustained activation of Nrf2 produces a supportive environment for survival and therapeutic resistance. AR negative PC3 cells, used in this study, are characterized by high basal nuclear levels of Nrf2, a condition that could explain the lack of ROS production as well as the low apoptotic response that we observed after treating PC3 cells with an ER stressor, TM. Nevertheless, under ER stress conditions, we observed an increased transcriptional activity of Nrf2, with a concomitant increase in HO1 and NQO1 gene expression, which could not be attributed to the PERK branch of the UPR pathway. Therefore, we suggest the existence of a non canonical signaling mechanism that may increase Nrf2 activation in the absence of increased levels of ROS under an ER stress setting. As a solid tumor, PCa often deals with microenvironmental factors that, by compromising the ER function, lead to ER stress. In turn, the stress elicits UPR and all the related cytoprotective mechanisms aimed to favoring tumor growth [2324]. UPR activation as an adaptive survival mechanism is found in gastric cancer, in malignant glioma, and in chronic lymphocytic leukemia [4749]. Although at times the relationship between UPR markers and adaptive survival has been debated [12], several studies have shown a positive link between UPR markers and androgen-driven PCa [13, 17, 24]. Moreover, androgens activate the IRE1α-XBP1 arm of UPR and concurrently inhibit the PERK-eIF2α pathway [17]. In AR negative PC3 cells, we found that TM did not activate the PERK-eIF2α signaling whereas it increased the protein level of GRP78/BiP, a target gene of the ATF6α arm, and activated the IRE1α arm. Although the role of the IRE1α pathway in AR-negative cell lines still needs to be further investigated, it is now accepted that the IRE1α arm plays a pro-survival role in PCa [17, 24]. The expression of molecular chaperones provides numerous types of cancer with pro-survival aptitude [50]. In PCa, GRP78/BiP is one of the most studied molecular chaperone and the increases in its expression are correlated with PCa recurrence and short survival [5152]. In several cancers, as well as in PCa, GRP78/BiP translocates to cell surface thus constituting a cancer-specific cell surface marker, tightly related to hormonal resistance of PCa [28, 33]. The PI3K/Akt pathway is significantly involved in multiple biological responses that promote survival thus the increased phosphorylation of Akt in prostate cancer tissues frequently prevents apoptosis and contributes to tumor progression [53]. GRP78/BiP, when expressed at the cell surface of tumor cells, enhances the Akt signaling thus contributing to cell survival and aggressive phenotype. Indeed, the highly metastatic 1-LN cells, derived from less metastatic PC3 cells, express GRP78/BiP on their cell surface [22, 29, 35]. By treating PC3 cell with TM, we therefore obtained cells with a distinctive marker of high metastatic potential. Given previous studies, activation of surface–bound GRP78/BiP will trigger the activation of Akt, which by inactivating GSK3β, leads to the reinforcement of Nrf2-mediated defense mechanism. Our study, by using wortmannin, a PI3K inhibitor, confirms that the role of Akt in PC3 is linked to the activation of the Nrf2/ARE transcriptional regulation in the presence of translocated GRP78/BiP. Indeed, when we specifically targeted cell surface GRP78/BiP with C-terminal directed antibodies, we observed a decreased Nrf2 activation, concomitant to a decreased activation of Akt and a decreased inactivation of GSK3β. The active GSK3β enhances Nrf2 degradation thus weakening PC3 cellular defense. Our proposal, i.e. that translocated GRP78/BiP could enhance Nrf2 activation, was substantiated by using MDAPCa2b cell line, characterized by the lack of GRP78/BiP translocation upon TM treatment. These cells responded to the TM treatment with a decreased cell survival, an increased apoptosis, and an increased ROS production due to the lack of Nrf2 activation. Finally, we observed that dexamethasone treatment, commonly used to treat CRPC patients [36], did not abrogate the translocation of GRP78/BiP to the cell surface and every other described cellular response to TM.
In conclusion, the preferential expression of GRP78/BiP on the surface of cancer cells might be exploited for immunotherapeutic approaches of prostate cancer. It is known that antibodies to the carboxyl terminal domain of GRP78 promote cancer cell death [22] as also observed in the present study. Indeed, by decreasing Nrf2 activation, this strategy could remove some of the several molecular protective mechanisms found in aggressive cancer cells.
MATERIALS AND METHODS
Materials
All the reagents, unless otherwise stated, were from Sigma–Aldrich (St. Louis, MO). All the antibodies, unless otherwise stated were from Santa-Cruz Biotechnology (Santa Cruz, CA). Antibodies C38 and C107 were validated as described [20].
Cell culture and treatment
AR negative PC3 and AR positive MDAPCa2b cell lines were obtained from American Type Tissue Culture Collection (Rockville, MD). Cells were grown in RPMI 1640 medium (Lonza, Milano, Italy) supplemented with 10% foetal bovine serum (FBS), glutamine (2 mM) and antibiotics (penicillin 100 U/ml and streptomycin 100 μg/ml). Sub-confluent cells were exposed to increasing concentrations of tunicamycin (0.1-5 μg/ml) for the indicated time. Wortmannin was added to cell culture 1h prior to tunicamicyn, anti GRP78/Bip antibodies (C38 and C107) were added 10min after tunicamycin treatment. In some experiments, cells were grown for 72h in the presence of dexamethasone and then treated with tunicamycin for the indicated times.
MTT viability assay
Cell viability was measured using the MTT assay. 0.5 mg/ml MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) was added to each well for 4 h, lysis buffer (10% SDS, 0,01 M HCl) was then added and cells lysed at 37°C overnight. Samples were measured with an automatic microplate reader (Seac, Firenze, Italy) at 550nm. Experiments were performed at least three times with six samples in each experimental group. Results were expressed as percentages (%) of reduced MTT, assuming the absorbance of control cells as 100% [54].
Apoptosis determination by flow cytometry
Apoptosis was detected by propidium iodide (PI) (50 μg/ml in 0.1% sodium citrate plus 0.1% triton X-100) addition. The PI fluorescence of individual nuclei was measured by flow cytometry using standard FACScan equipment (Becton Dickinson, Franklin Lakes, NJ). The data were recorded in a Hewlett Packard (H9 9000, model 310, Palo Alto, CA) computer. The percentage of apoptotic cell nuclei (sub-diploid DNA peak in the DNA fluorescence histogram) was calculated with specific FACScan research software (Lysis II). At least 10,000 events were analysed in each sample [55].
Measurement of intracellular fluorescence
The DCFH-DA method was used to detect the levels of intra-cellular reactive oxygen species (ROS). Cells were treated as described and DCFH-DA (30μM) was added into the medium for a further 30 min at 37°C. The fluorescence of 2’,7’-dichlorofluorescein was detected at 485 nm excitation and at 535 nm emission, using a TitertekFluoroscan II (Flow Laboratories, McLean, USA). Results were expressed as % of the control DCF fluorescence [54].
Western blotting
Cells were lysed in boiling Laemmli sample buffer or processed with NE-PER(R) Nuclear and Cytoplasmic Extraction Reagents (Pierce Biotechnology, Rockford, IL) according to manufacturer’s instruction. Protein samples were electrophoresed on SDS polyacrylamide gels and transferred to nitrocellulose membranes at 100 V for 1 hr. Membranes were probed with the indicated antibodies (Supplementary Table 1), which were detected using HRP-based chemiluminescence (ECL, Pierce Biotechnology, Rockford, IL) [56]. Densitometric analises were performed with Image J software.
Clonogenic assay
Cells were seeded at a density of 500 cells/dishes in 9.5 cm2 well. After a 7 days incubation at 37°C, the colonies were fixed with 3.7% paraformaldehyde, stained with crystal violet (0.5% w/v) and counted using a stereomicroscope.
Immunofluorescence
Cells, seeded on glass coverslips, were fixed with 4% paraformaldehyde in PBS (Chem Cruz) for 20 min at room temperature. After blocking non-specific binding sites with 3% BSA in PBS for 1h, cells were incubated overnight at 4°C with anti GRP78 antibody (C38) (1:100) and then with anti mouse Alexafluor 488 secondary antibody (1:500). After washings, F-actin was stained with Alexafluor 555-Labelled phalloidin (1:200) for 30 minutes at room temperature. Cells were washed with PBS, cell nuclei were counter-stained with 4,6-diamidino-2-phenylindole (DAPI) and slides were mounted using glass coverslips and Prolong Diamond mounting medium (Life Technologies) for permanent sealing. Images were captured using a Zeiss Axio Observer. Z1 inverted microscope, equipped with Apotome filter and Axiocam MRm camera detection system Zeiss using a 63x/1.25 oil Plan/neofluar objective and a 40x/0.75 plan/neofluar objective. To improve axial resolution and focal planes separation, Apotome filter was enabled, set to “strong” with noise reduction set to “Off”. All the images, were processed for visual improvement, with the application of a 5,6 pixel 160 point sharpening mask and histograms were additionally stretched to increase contrast (Ps CC - Adobe). No in-silico extra noise reduction treatment was applied to the images.
RNA isolation, reverse transcription and RT- PCR
Total RNA was isolated with TRI Reagent according to the manufacturer’s instructions and cDNA was synthesised using PrimeScript RT reagent Kit (Takara, Mountain View, CA). Real time PCR was performed using the QuantStudio 3 detection system (Applied Biosystem, Foster City, CA) and SYBR Green chemistry. Primers are listed in Supplementary Table 2. SYBR Green RT-PCR amplifications were carried out in a 96-well plate in a 25 μl reaction volume that contained 12.5 ml of SYBR® Green JumpStart™ Taq ReadyMix, 400 nM forward and reverse primers, and 5 to 40 ng of cDNA. In each assay, no-template controls were included and each sample was run in triplicates. Mean of Ct values of the samples was compared to the untreated control sample and GAPDH used as internal control. The n-fold differential ratio was expressed as 2-ΔΔCt.
Transfection and luciferase reporter assays
Cignal ARE Dual-luciferase reporter kit (CCS-5020, Qiagen, Milan, IT) was used to transfect PC3 and MDA cells following manufacturer’s instructions. Transient transfections were carried out using Attractene transfection reagent (Qiagen, Milan, IT) according to the manufacturer’s instructions. Cell extracts were prepared 24 h after transfection and Luciferase activities in lysates were measured using Luminoskan (Thermo Electron Corporation, Waltham, MA) luminometer. Quantification of Firefly and Renilla luciferase activities was performed with the Dual Luciferase Reporter Assay System (Promega, Madison, WI). The relative firefly luciferase activity was calculated by normalizing transfection efficiency. The luciferase activity was expressed as arbitrary unit of light intensity.
Statistical analysis
All studies were performed at least in triplicate, separate experiments and expressed as mean ± S.D. Data were analysed for statistical significance by Student’s t-test. When appropriate data were analysed by two-way ANOVA test with Sidak’s correction for multiple comparison. *P-values <0.05 were considered significant.
Abbreviations
AR: androgen receptor; ARE/EpRE: antioxidant/electrophile response element; ATF6α: activating transcription factor 6 alpha; COPII: coatomer protein II; CRPC: castration resistant PCa; ER : endoplasmic reticulum; ERK: extracellular signal-regulated kinase; GRP78/BiP: glucose-regulated protein of 78 kD /immunoglobulin heavy chain binding protein; HO-1: Hemeoxygenase-1; IRE1α: inositol requiring-enzyme 1 alpha; JNK: c-Jun N-terminal kinase; NQO1: NADPH-quinone oxidoreductase-1; Nrf2: NF-E2-related factor 2; PCa: prostate cancer; PERK: protein kinase RNA-like ER kinase; PI3K: phosphatidylinositol 3’-kinase; ROS: reactive oxygen species; TM: tunicamycin; TRAF2: TRF-receptor associated factor 2; UPR: unfolded protein response.
Authors’ contributions
IB: acquired and interpreted data; PS: performed the immunofluorescence examinations, SG, EC: performed some experiments; AM and IB: conceived and wrote the MS; SVP: critically revised the MS. All authors read and approved the final manuscript.
CONFLICTS OF INTEREST
The Authors declare no competing interest.
FUNDING
This study was supported by Fondazione Cassa di Risparmio di Perugia (2015.0326.021). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
REFERENCES
1. Brigelius-Flohé R, Flohé L. Basic principles and emerging concepts in the redox control of transcription factors. Antioxid Redox Signal. 2011; 15:2335-81.
2. Klaunig JE, Kamendulis LM, Hocevar BA. Oxidative stress and oxidative damage in carcinogenesis. Toxicol Pathol. 2010; 38:96-109.
3. Minelli A, Bellezza I, Conte C, Culig Z. Oxidative stress-related aging: A role for prostate cancer? Biochim Biophys Acta. 2009; 1795:83-91.
4. Paschos A, Pandya R, Duivenvoorden WC, Pinthus JH. Oxidative stress in prostate cancer: changing research concepts towards a novel paradigm for prevention and therapeutics. Prostate Cancer Prostatic Dis. 2013; 16:217-25.
5. Kumar B, Koul S, Khandrika L, Meacham RB, Koul HK. Oxidative stress is inherent in prostate cancer cells and is required for aggressive phenotype. Cancer Res. 2008; 68:1777–85.
6. Krajka-Kuźniak V, Paluszczak J, Baer-Dubowska W. The Nrf2-ARE signaling pathway: An update on its regulation and possible role in cancer prevention and treatment. Pharmacol Rep. 2016; 69:393-402.
7. Jiang L, Yang KH, Tian JH, Guan QL, Yao N, Cao N, Mi DH, Wu J, Ma B, Yang SH. Efficacy of antioxidant vitamins and selenium supplement in prostate cancer prevention: a meta-analysis of randomized controlled trials. Nutr Cancer. 2010; 62:719-27.
8. Bellezza I, Grottelli S, Gatticchi L, Mierla AL, Minelli A. α-Tocopheryl succinate pre-treatment attenuates quinone toxicity in prostate cancer PC3 cells. Gene. 2014; 539:1-7.
9. Harder B, Jiang T, Wu T, Tao S, Rojo de la Vega M, Tian W, Chapman E, Zhang DD. Molecular mechanisms of Nrf2 regulation and how these influence chemical modulation for disease intervention. Biochem Soc Trans. 2015; 43:680-6.
10. Lau A, Villeneuve NF, Sun Z, Wong PK, Zhang DD. Dual roles of Nrf2 in cancer. Pharmacol Res. 2008; 58:262-70.
11. Cullinan SB, Diehl JA. Coordination of ER and oxidative stress signaling: the PERK/Nrf2 signaling pathway. Int J Biochem Cell Biol. 2006; 38:317-32.
12. So AY, de la Fuente E, Walter P, Shuman M, Bernales S. The unfolded protein response during prostate cancer development. Cancer Metastasis Rev. 2009; 28: 219–23.
13. Ma Y, Hendershot LM. The role of the unfolded protein response in tumour development: friend or foe? Nat Rev Cancer. 2004; 4: 966–77.
14. Associazione italiana registri tumori (AIRTUM). 2015. http://www.registri-tumori.it/cms/.
15. Strope JD, Price DK, Figg WD. Building a hit list for the fight against metastatic castration resistant prostate cancer. Cancer Biol Ther. 2016; 17:231-2.
16. Hetz C. The unfolded protein response: controlling cell fate decisions under ER stress and beyond. Nat Rev Mol Cell Biol. 2012; 13:89-102.
17. Sheng X, Arnoldussen YJ, Storm M, Tesikova M, Nenseth HZ, Zhao S, Fazli L, Rennie P, Risberg B, Waehre H, Danielsen H, Mills IG, Jin Y, et al. Divergent androgen regulation of unfolded protein response pathways drives prostate cancer. EMBO Mol Med. 2015; 7:788-801.
18. Li J, Lee AS. Stress induction of GRP78/BiP and its role in cancer. Curr Mol Med. 2006; 6:45–54.
19. Ni M, Zhang Y, Lee AS. Beyond the endoplasmic reticulum: atypical GRP78 in cell viability, signalling and therapeutic targeting. Biochem J. 2011; 434: 181–8.
20. de Ridder GG, Ray R, Pizzo SV. A murine monoclonal antibody directed against the carboxyl-terminal domain of GRP78 suppresses melanoma growth in mice. Melanoma Res. 2012; 22:225-35.
21. Miyake H, Hara I, Arakawa S, Kamidono S. Stress protein GRP78 prevents apoptosis induced by calcium ionophore, ionomycin, but not by glycosylation inhibitor, tunicamycin, in human prostate cancer cells. J Cell Biochem. 2000; 77:396-408.
22. Misra UK, Mowery Y, Kaczowka S, Pizzo SV. Ligation of cancer cell surface GRP78 with antibodies directed against its COOH-terminal domain up-regulates p53 activity and promotes apoptosis. Mol Cancer Ther. 2009; 8:1350-62.
23. Wang M, Kaufman RJ. The impact of the endoplasmic reticulum protein-folding environment on cancer development. Nature Rev Cancer. 2014; 14:581-97.
24. Storm M, Sheng X, Arnoldussen YJ, Saatcioglu F. Prostate cancer and the unfolded protein response. Oncotarget. 2016; 7:54051-66. doi: 10.18632/oncotarget.9912.
25. Stachel I, Geismann C, Aden K, Deisinger F, Rosenstiel P, Schreiber S, Sebens S, Arlt A, Schäfer H. Modulation of nuclear factor E2-related factor-2 (Nrf2) activation by the stress response gene immediate early response-3 (IER3) in colonic epithelial cells: a novel mechanism of cellular adaption to inflammatory stress. J Biol Chem. 2014; 289:1917-29.
26. Reddy NM, Potteti HR, Vegiraju S, Chen HJ, Tamatam CM, Reddy SP. PI3K-AKT Signaling via Nrf2 Protects against Hyperoxia-Induced Acute Lung Injury, but Promotes Inflammation Post-Injury Independent of Nrf2 in Mice. PLoS One. 2015; 10:e0129676.
27. Shukla S, Maclennan GT, Marengo SR, Resnick MI, Gupta S. Constitutive activation of P I3 K-Akt and NF-kappaB during prostate cancer progression in autochthonous transgenic mouse model. Prostate. 2005; 64:224-39.
28. Misra UK, Deedwania R, Pizzo SV. Activation and cross-talk between Akt, NF-kappaB, and unfolded protein response signaling in 1-LN prostate cancer cells consequent to ligation of cell surface-associated GRP78. J Biol Chem. 2006; 281:13694-707.
29. Misra UK, Pizzo SV. Receptor-recognized α2-macroglobulin binds to cell surface-associated GRP78 and activates mTORC1 and mTORC2 signaling in prostate cancer cells. PLoS One. 2012; 7:e51735.
30. Asplin IR, Misra UK, Gawdi G, Gonzalez-Gronow M, Pizzo SV. Selective upregulated expression of the alpha2-macroglobulin signaling receptor in highly metastatic 1-LN prostate carcinoma cells. Arch Biochem Biophys. 2000; 383:135-41.
31. Misra UK, Payne S, Pizzo SV. Ligation of prostate cancer cell surface GRP78 activates a proproliferative and antiapoptotic feedback loop: a role for secreted prostate-specific antigen. J Biol Chem. 2011; 286:1248-59.
32. Zhang Y, Liu R, Ni M, Gill P, Lee AS. Cell surface relocalization of the endoplasmic reticulum chaperone and unfolded protein response regulator GRP78/BiP. J Biol Chem. 2010; 285:15065-75.
33. Zhang Y, Tseng CC, Tsai YL, Fu X, Schiff R, Lee AS. Cancer cells resistant to therapy promote cell surface relocalization of GRP78 which complexes with PI3K and enhances PI(3,4,5)P3 production. PloS one. 2013; 8:e80071.
34. Sprangers J, Rabouille C. SEC16 in COPII coat dynamics at ER exit sites. Biochem Soc Trans. 2015; 43:97-103.
35. Misra UK, Pizzo SV. Activated α2-macroglobulin binding to cell surface GRP78 induces T-loop phosphorylation of Akt1 by PDK1 in association with Raptor. PLoS One. 2014; 9:e88373.
36. Kassi E, Moutsatsou P. Glucocorticoid receptor signaling and prostate cancer. Cancer Lett. 2011; 302:1-10.
37. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011; 144:646-74.
38. Grasso CS, Wu YM, Robinson DR, Cao X, Dhanasekaran SM, Khan AP, Quist MJ, Jing X, Lonigro RJ, Brenner JC, Asangani IA, Ateeq B, Chun SY, et al. The mutational landscape of lethal castration-resistant prostate cancer. Nature. 2012; 487: 239–43.
39. Costanzi E, Urbanelli L, Bellezza I, Magini A, Emiliani C, Minelli A. Hypermethylation contributes to down-regulation of lysosomal β-hexosaminidase α subunit in prostate cancer cells. Biochimie. 2014; 101:75-82.
40. Wyatt AW, Gleave ME. Targeting the adaptive molecular landscape of castration-resistant prostate cancer. EMBO Mol Med. 2015; 7:878-94.
41. Mitsuishi Y, Motohashi H, Yamamoto M. The Keap1-Nrf2 system in cancers: stress response and anabolic metabolism. Front Oncol. 2012; 2:200.
42. Bellezza I, Mierla AL, Minelli A. Nrf2 and NF-κB and Their Concerted Modulation in Cancer Pathogenesis and Progression. Cancers (Basel). 2010; 2:483-97.
43. Jaramillo MC, Zhang DD. The emerging role of the Nrf2-Keap1 signaling pathway in cancer. Genes Dev. 2013; 27:2179-91.
44. Zhang P, Singh A, Yegnasubramanian S, Esopi D, Kombairaju P, Bodas M, Wu H, Bova SG, Biswal S. Loss of Kelch-like ECH-associated protein 1 function in prostate cancer cells causes chemoresistance and radioresistance and promotes tumor growth. Mol Cancer Ther. 2010; 9:336-46.
45. Hanada N, Takahata T, Zhou Q, Ye X, Sun R, Itoh J, Ishiguro A, Kijima H, Mimura J, Itoh K, Fukuda S, Saijo Y. Methylation of the KEAP1 gene promoter region in human colorectal cancer. BMC Cancer. 2012; 12:66. doi: 10.1186/1471-2407-12-66.
46. MacLeod AK, Acosta-Jimenez L, Coates PJ, McMahon M, Carey FA, Honda T, Henderson CJ, Wolf CR. Aldo-keto reductases are biomarkers of NRF2 activity and are co-ordinately overexpressed in non-small cell lung cancer. Br J Cancer. 2016; 115:1530-39.
47. Zheng HC, Takahashi H, Li XH, Hara T, Masuda S, Guan YF, Takano Y. Overexpression of GRP78 and GRP94 are markers for aggressive behavior and poor prognosis in gastric carcinomas. Hum Pat. 2008; 39:1042-49.
48. Auf G, Jabouille A, Guerit S, Pineau R, Delugin M, Bouchecareilh M, Magnin N, Favereaux A, Maitre M, Gaiser T, von Deimling A, Czabanka M, Vajkoczy P, et al. Inositol-requiring enzyme 1alpha is a key regulator of angiogenesis and invasion in malignant glioma. Proc Natl Acad Sci U S A. 2010; 107:15553-58.
49. Tang CH, Ranatunga S, Kriss CL, Cubitt CL, Tao J, Pinilla-Ibarz JA, Del Valle JR, Hu CC. Inhibition of ER stress-associated IRE-1/XBP-1 pathway reduces leukemic cell survival. J Clin Invest. 2014; 124:2585-98.
50. Azad AA, Zoubeidi A, Gleave ME, Chi KN. Targeting heat shock proteins in metastatic castration-resistant prostate cancer. Nat Rev Urol. 2015; 12:26-36.
51. Pootrakul L, Datar RH, Shi SR, Cai J, Hawes D, Groshen SG, Lee AS, Cote RJ. Expression of stress response protein Grp78 is associated with the development of castration-resistant prostate cancer. Clin Cancer Res. 2006; 12:5987-93.
52. Fu Y, Wey S, Wang M, Ye R, Liao CP, Roy-Burman P, Lee AS. Pten null prostate tumorigenesis and AKT activation are blocked by targeted knockout of ER chaperone GRP78/BiP in prostate epithelium. Proc Natl Acad Sci U S A. 2008; 105:19444-49.
53. Culig Z, Santer FR. Androgen receptor signaling in prostate cancer. Cancer Metastasis Rev. 2014; 33:413-27.
54. Bellezza I, Tucci A, Galli F, Grottelli S, Mierla AL, Pilolli F, Minelli A. Inhibition of NF-κB nuclear translocation via HO-1 activation underlies α-tocopheryl succinate toxicity. J Nutr Biochem. 2012; 23:1583-91.
55. Minelli A, Bellezza I, Tucci A, Rambotti MG, Conte C, Culig Z. Differential involvement of reactive oxygen species and nucleoside transporters in cytotoxicity induced by two adenosine analogues in human prostate cancer cells. Prostate. 2009; 69:538-47.
56. Bellezza I, Roberti R, Gatticchi L, Del Sordo R, Rambotti MG, Marchetti MC, Sidoni A, Minelli A. A novel role for Tm7sf2 gene in regulating TNFα expression. PLoS One. 2013; 8:e68017.
Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 18724
|
{
"url": "https://www.oncotarget.com/article/18724/text/",
"source_domain": "www.oncotarget.com",
"snapshot_id": "CC-MAIN-2023-06",
"warc_metadata": {
"Content-Length": "87595",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:AWH4Y6VSQLFPN32N37BFMTUBRGFR4SVY",
"WARC-Concurrent-To": "<urn:uuid:3362366d-9781-4b01-ae50-37bb584ce272>",
"WARC-Date": "2023-01-30T10:52:25",
"WARC-IP-Address": "172.67.141.111",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:HRYXX55S3BGX6SCXCS62KVXATQ7IFTT5",
"WARC-Record-ID": "<urn:uuid:2e32eb90-6f7a-4cef-ab99-a464e8bc5d8d>",
"WARC-Target-URI": "https://www.oncotarget.com/article/18724/text/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:04cea36a-3d28-4748-9857-1aa38121529b>"
},
"warc_info": "isPartOf: CC-MAIN-2023-06\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for January/February 2023\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-56\r\nsoftware: Apache Nutch 1.19 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.4-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
11,
12,
29,
30,
81,
82,
134,
135,
210,
211,
265,
266,
373,
374,
383,
384,
495,
496,
572,
573,
626,
627,
646,
647,
689,
690,
732,
733,
804,
805,
886,
887,
896,
897,
2256,
2257,
2258,
2269,
2270,
4112,
4113,
5833,
5834,
6095,
6096,
6104,
6105,
6182,
6183,
7792,
7793,
7871,
7872,
8674,
8675,
8727,
8728,
9656,
9657,
9694,
9695,
10166,
10167,
10236,
10237,
10774,
10775,
10811,
10812,
11734,
11735,
11816,
11817,
13595,
13596,
13672,
13673,
14072,
14073,
14157,
14158,
14667,
14668,
14743,
14744,
15795,
15796,
15873,
15874,
16674,
16675,
16750,
16751,
17225,
17226,
17304,
17305,
18234,
18235,
18246,
18247,
24616,
24617,
25067,
25068,
25090,
25091,
25101,
25102,
25341,
25342,
25369,
25370,
26092,
26093,
26113,
26114,
26654,
26655,
26697,
26698,
27270,
27271,
27313,
27314,
27753,
27754,
27771,
27772,
28339,
28340,
28357,
28358,
28590,
28591,
28610,
28611,
29935,
29936,
29985,
29986,
30813,
30814,
30858,
30859,
31646,
31647,
31668,
31669,
31991,
31992,
32006,
32007,
32738,
32739,
32762,
32763,
33008,
33009,
33031,
33032,
33075,
33076,
33084,
33085,
33301,
33302,
33313,
33314,
33472,
33473,
33605,
33606,
33750,
33751,
33975,
33976,
34156,
34157,
34356,
34357,
34605,
34606,
34785,
34786,
35014,
35015,
35129,
35130,
35283,
35284,
35450,
35451,
35589,
35590,
35684,
35685,
35844,
35845,
35988,
35989,
36259,
36260,
36361,
36362,
36524,
36525,
36711,
36712,
36953,
36954,
37180,
37181,
37332,
37333,
37497,
37498,
37855,
37856,
38103,
38104,
38320,
38321,
38569,
38570,
38764,
38765,
39000,
39001,
39222,
39223,
39416,
39417,
39641,
39642,
39755,
39756,
39938,
39939,
40050,
40051,
40145,
40146,
40394,
40395,
40611,
40612,
40751,
40752,
40895,
40896,
41053,
41054,
41176,
41177,
41457,
41458,
41701,
41702,
41952,
41953,
42163,
42164,
42474,
42475,
42689,
42690,
42846,
42847,
43082,
43083,
43326,
43327,
43439,
43440,
43659,
43660,
43917,
43918,
44105,
44106,
44107,
44242
],
"line_end_idx": [
11,
12,
29,
30,
81,
82,
134,
135,
210,
211,
265,
266,
373,
374,
383,
384,
495,
496,
572,
573,
626,
627,
646,
647,
689,
690,
732,
733,
804,
805,
886,
887,
896,
897,
2256,
2257,
2258,
2269,
2270,
4112,
4113,
5833,
5834,
6095,
6096,
6104,
6105,
6182,
6183,
7792,
7793,
7871,
7872,
8674,
8675,
8727,
8728,
9656,
9657,
9694,
9695,
10166,
10167,
10236,
10237,
10774,
10775,
10811,
10812,
11734,
11735,
11816,
11817,
13595,
13596,
13672,
13673,
14072,
14073,
14157,
14158,
14667,
14668,
14743,
14744,
15795,
15796,
15873,
15874,
16674,
16675,
16750,
16751,
17225,
17226,
17304,
17305,
18234,
18235,
18246,
18247,
24616,
24617,
25067,
25068,
25090,
25091,
25101,
25102,
25341,
25342,
25369,
25370,
26092,
26093,
26113,
26114,
26654,
26655,
26697,
26698,
27270,
27271,
27313,
27314,
27753,
27754,
27771,
27772,
28339,
28340,
28357,
28358,
28590,
28591,
28610,
28611,
29935,
29936,
29985,
29986,
30813,
30814,
30858,
30859,
31646,
31647,
31668,
31669,
31991,
31992,
32006,
32007,
32738,
32739,
32762,
32763,
33008,
33009,
33031,
33032,
33075,
33076,
33084,
33085,
33301,
33302,
33313,
33314,
33472,
33473,
33605,
33606,
33750,
33751,
33975,
33976,
34156,
34157,
34356,
34357,
34605,
34606,
34785,
34786,
35014,
35015,
35129,
35130,
35283,
35284,
35450,
35451,
35589,
35590,
35684,
35685,
35844,
35845,
35988,
35989,
36259,
36260,
36361,
36362,
36524,
36525,
36711,
36712,
36953,
36954,
37180,
37181,
37332,
37333,
37497,
37498,
37855,
37856,
38103,
38104,
38320,
38321,
38569,
38570,
38764,
38765,
39000,
39001,
39222,
39223,
39416,
39417,
39641,
39642,
39755,
39756,
39938,
39939,
40050,
40051,
40145,
40146,
40394,
40395,
40611,
40612,
40751,
40752,
40895,
40896,
41053,
41054,
41176,
41177,
41457,
41458,
41701,
41702,
41952,
41953,
42163,
42164,
42474,
42475,
42689,
42690,
42846,
42847,
43082,
43083,
43326,
43327,
43439,
43440,
43659,
43660,
43917,
43918,
44105,
44106,
44107,
44242,
44252
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 44252,
"ccnet_original_nlines": 283,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.21180787682533264,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.09083834290504456,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.28207695484161377,
"rps_doc_frac_unique_words": 0.29715684056282043,
"rps_doc_mean_word_length": 5.41745662689209,
"rps_doc_num_sentences": 554,
"rps_doc_symbol_to_word_ratio": 0.00022236999939195812,
"rps_doc_unigram_entropy": 6.44354248046875,
"rps_doc_word_count": 6542,
"rps_doc_frac_chars_dupe_10grams": 0.07711408287286758,
"rps_doc_frac_chars_dupe_5grams": 0.14793601632118225,
"rps_doc_frac_chars_dupe_6grams": 0.1147541031241417,
"rps_doc_frac_chars_dupe_7grams": 0.10228267312049866,
"rps_doc_frac_chars_dupe_8grams": 0.09556727856397629,
"rps_doc_frac_chars_dupe_9grams": 0.08958551287651062,
"rps_doc_frac_chars_top_2gram": 0.0055021001026034355,
"rps_doc_frac_chars_top_3gram": 0.006320360116660595,
"rps_doc_frac_chars_top_4gram": 0.004514549858868122,
"rps_doc_books_importance": -3582.97509765625,
"rps_doc_books_importance_length_correction": -3582.97509765625,
"rps_doc_openwebtext_importance": -2644.740234375,
"rps_doc_openwebtext_importance_length_correction": -2644.740234375,
"rps_doc_wikipedia_importance": -2077.27685546875,
"rps_doc_wikipedia_importance_length_correction": -2077.27685546875
},
"fasttext": {
"dclm": 0.06355571746826172,
"english": 0.8893633484840393,
"fineweb_edu_approx": 2.380915641784668,
"eai_general_math": 0.2793963551521301,
"eai_open_web_math": 0.31625229120254517,
"eai_web_code": 0.00892757996916771
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.994072",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "616.994076",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "4",
"label": "Analyze"
},
"secondary": {
"code": "5",
"label": "Evaluate"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "2",
"label": "Academic/Research"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "3",
"label": "Irrelevant Content"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "4",
"label": "Missing Images or Figures"
}
},
"document_type_v2": {
"primary": {
"code": "3",
"label": "Academic Writing"
},
"secondary": {
"code": "10",
"label": "Knowledge Article"
}
},
"reasoning_depth": {
"primary": {
"code": "4",
"label": "Advanced Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "4",
"label": "Graduate/Expert Level"
},
"secondary": {
"code": "3",
"label": "Undergraduate Level"
}
}
}
|
b755ed28a90d11d590ef646404f4afc5
|
-8,683,252,191,962,950,000
|
Email updates
Keep up to date with the latest news and content from Arthritis Research & Therapy and BioMed Central.
Open Access Research article
Increased frequency of CCR4+ and CCR6+ memory T-cells including CCR7+CD45RAmed very early memory cells in granulomatosis with polyangiitis (Wegener's)
Ursula Fagin, Silke Pitann, Wolfgang L Gross and Peter Lamprecht*
Author affiliations
Department of Rheumatology, Vasculitis Center UKSH and Clinical Center Bad Bramstedt, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany
For all author emails, please log on.
Citation and License
Arthritis Research & Therapy 2012, 14:R73 doi:10.1186/ar3794
The electronic version of this article is the complete one and can be found online at: http://arthritis-research.com/content/14/2/R73
Received:25 November 2011
Revisions received:1 March 2012
Accepted:10 April 2012
Published:10 April 2012
© 2012 Fagin et al.; licensee BioMed Central Ltd.
This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Introduction
Chemokine receptors play an important role in mediating the recruitment of T cells to inflammatory sites. Previously, small proportions of circulating Th1-type CCR5+ and Th2-type CCR3+ cells have been shown in granulomatosis with polyangiitis (GPA). Wondering to what extent CCR4 and CCR6 expression could also be implicated in T cell recruitment to inflamed sites in GPA, we investigated the expression of CCR4 and CCR6 on T cells and its association with T cell diversity and polarization.
Methods
Multicolor flow cytometry was used to analyze CCR4, CCR6, and intracellular cytokine expression of T cells from whole blood of GPA-patients (n = 26) and healthy controls (n = 20). CCR7 and CD45RA were included for phenotypic characterization.
Results
We found a significant increase in the percentages of circulating CCR4+ and CCR6+ cells within the total CD4+ T cell population in GPA. In contrast, there was no difference in the percentages of CD8+CCR4+ and CD8+CCR6+ T cells between GPA and healthy controls. CCR4 and CCR6 expression was largely confined to central (TCM) and effector memory T cells (TEM, TEMRA). A significant increase in the frequency of CCR4+ and CCR6+ TEMRA and CCR6+ TCM was shown in GPA. Of note, we could dissect CCR4 and CCR6 expressing CCR7+CD45RAmed very early memory T cells (TVEM) from genuine CCR7+CD45RAhigh naïve T cells lacking CCR4 and CCR6 expression for peripheral tissue-migration within the CCR7+CD45RA+ compartment. The frequencies of CCR4+ and CCR6+ TVEM were also significantly increased in GPA. An increased percentage of IL-17+ and IL-22+ cells was detected in the CCR6+ cell subsets and IL-4+ cells in the CRR4+ cell subset when compared with CD4+ cells lacking CCR4 and CCR6 expression.
Conclusions
Increased frequencies of circulating CCR4+ and CCR6+ memory T cell subsets including hitherto unreported TVEM suggest persistent T cell activation with the accumulation of CCR4+ and CCR6+ cells in GPA. CCR4 and CCR6 could be involved in the recruitment of T cells including cytokine-producing subsets to inflamed sites in GPA.
Introduction
T cells display considerable heterogeneity in terms of phenotype, function, and anatomical distribution. Whereas naïve T cells represent a relatively homogenous population, primed T cells acquire effector functions and differentiate into distinct effector and memory subsets. Whereas naïve and central memory T cells home to secondary lymphoid organs to mount antigen-driven proliferative responses, effector memory T cells migrate into peripheral tissues to display immediate effector functions such as cytokine production or cytotoxicity or both [1,2]. The process of T cell recruitment from blood into tissue is controlled by adhesion molecules, in which chemokine receptors have an important role [2].
Previously, we showed that a small proportion of circulating memory T cells displays T-helper cell 1 (Th1)-type CC chemokine receptor (CCR) 5 and Th2-type CCR3 expression in granulomatosis with polyangiitis (GPA) [3]. GPA is a rare chronic inflammatory disorder of unknown etiology and is characterized by necrotizing granulomatosis of the upper or lower respiratory tract or both and a systemic autoimmune vasculitis preferentially affecting pulmonary and renal small vessels. The vasculitis is associated with highly specific anti-neutrophil cytoplasmic autoantibodies to proteinase 3 (PR3-ANCA) [4]. T cells are abundant in inflammatory lesions in GPA. CCR5, CCR3, and their chemokine ligand CCL5 (regulated upon activation in normal T cells, expressed and secreted, or RANTES) are expressed in granulomatous lesions of the respiratory tract. These studies suggested that CCR5 and CCR3 could be involved in the recruitment of interferon-gamma (IFNγ)-producing and tumor necrosis factor-alpha-producing Th1- and interleukin (IL)-4-producing Th2-type cells to inflammatory sites in GPA [5-7]. More recently, IL-17-producing PR3-specific Th17 cells have been implicated in the maintenance of chronic inflammation and autoimmunity in GPA [8-10]. CCR4+ T cells have been reported to secrete IL-4, whereas CCR6+ cells produce IL-17 [11,12]. To investigate the extent to which the chemokine receptors CCR4 and CCR6 could be implicated in T-cell recruitment in GPA, we analyzed CCR4 and CCR6 expression on circulating T cells, assigned CCR4- and CCR6-expressing cells to the respective memory cell subsets, and determined the cytokine production of CCR4+ and CCR6+ T cells.
Materials and methods
Study population
Patients fulfilled the American College of Rheumatology criteria and the Chapel Hill Consensus Conference definition for GPA, respectively [13,14]. Disease activity was recorded in accordance with European League Against Rheumatism recommendations (Table 1) [15]. All patients and controls provided informed consent. The study was approved by the local ethics committee (#07-059).
Table 1. Clinical and laboratory characteristics of patients with GPA and healthy controls
Antibodies used for flow cytometry
The following antibodies were used in different combinations: Pacific blue (PB)-conjugated anti-CD3, PB- or phycoerythrin (PE)-conjugated anti-CD4, peridinin chlorophyll protein (PerCP)- or allophycocyanine-cyanine dye 7 (APC-Cy7)-conjugated anti-CD8, fluorescein isothiocyanate (FITC)-conjugated anti-CD45RA, Alexa Fluor 647-conjugated anti-CCR7, PE-Cy7- and PE-conjugated anti-CCR4, PE-conjugated anti-CCR6, APC-Cy7-conjugated anti-IFNγ, PE-Cy7-conjugated anti-IL-4, and Alexa Fluor 488-conjugated anti-IL-17a from eBioscience (Frankfurt, Germany) and APC-conjugated anti-IL-22 from R&D Systems (Wiesbaden, Germany). Appropriate isotype controls were included in the experimental setup. All antibodies (unless indicated otherwise) were purchased from BD Biosciences (Heidelberg, Germany).
Surface marker and intracellular cytokine staining
Flow cytometry was performed to characterize T cell populations at the single-cell level. Staining of cellular surface markers was performed by using freshly collected whole blood (Li-heparin) as described earlier [3]. Briefly, previously determined optimal concentrations of fluorochrome-conjugated monoclonal antibodies for cell surface antigens were added to 100 μL of whole blood and incubated 45 minutes in the dark at 4°C. Subsequently, erythrocytes were lysed by the addition of FACS (fluorescence-activated cell sorting) Lysing Solution (BD Pharmingen, Heidelberg, Germany). After incubation for another 10 minutes in the dark at room temperature, cells were washed twice with phosphate-buffered saline/0.01% bovine serum albumin and immediately analyzed by FACS.
For intracellular cytokine staining, freshly collected whole blood was stimulated with phorbol myristate acetate (Sigma, Munich, Germany) (10 ng/mL) and ionomycin (Sigma) (1 μg/mL) for 4 hours at 37°C in a humidified atmosphere with 5% CO2. Brefeldin (Sigma) (10 μg/mL) was added at the beginning of the stimulation to inhibit cytokine secretion. After staining for surface antigens and lysing of erythrocytes with FACS Lysing Solution, cells were fixed and permeabilized with Cytofix/Cytoperm in accordance with the instructions of the manufacturer (BD Pharmingen). Staining of intracytoplasmatic cytokines was performed at 4°C for 45 minutes in the dark with previously determined optimal concentrations of fluorochrome-conjugated monoclonal antibodies for cytokines or appropriate negative (isotype) controls. Besides appropriate isotype controls, an unstimulated sample was included for each patient and control as a negative control.
Flow cytometric analysis
Multicolor flow cytometric analysis was performed on a FACS Canto II cytometer by using FACSDiva software (BD Biosciences). Lymphocytes were gated for analysis on the basis of light scattering properties and of CD3, CD4, and CD8 staining. Positively and negatively stained populations were calculated by quadrant dot plot analysis determined by isotype controls.
Statistical analysis
Statistics were performed by using Prism 4.0 (GraphPad Software, La Jolla, CA, USA). Comparisons between patients and control subjects were done by employing the non-parametric Mann-Whitney U test. P values equal to or less than 0.05 were considered to be statistically significant.
Results
Increased frequency of CCR4- and CCR6-expressing CD4+ T cells in granulomatosis with polyangiitis
To assess CCRs relevant for migration to peripheral tissues, we determined the expression of the CCR4 and CCR6 on peripheral blood T cells in patients with GPA and healthy controls. We found a significant increase in the percentages of CCR4- and CCR6-expressing cells within the total CD4+ T cell population in patients with GPA compared with healthy individuals (Figure 1a, b). Apart from the CCR4+CCR6- and CCR4-CCR6+ 'single positive' subsets, a smaller fraction of CCR4+CCR6+ 'double positive' cells was detected within the CD4+ T cell population in patients with GPA and healthy controls (17.5% ± 4.8% versus 10.3% ± 0.6%, mean ± standard error of the mean, no significant difference, Mann-Whitney U test). Conversely, the remainder of cells within the CD4+ T-cell population were CCR4-CCR6- 'double negative' cells. In contrast, there was no difference in the percentages of CD8+CCR4+ and CD8+CCR6+ T cells between patients with GPA and healthy controls (data not shown).
thumbnailFigure 1. Increased frequencies of CD4+CCR4+ and CD4+CCR6+ T cells in patients with granulomatosis with polyangiitis (GPA). Percentages of CCR4+ (a) and CCR6+ (b) cells within the total CD4+ T cell population in patients with GPA and healthy controls (HCs). Percentages of positive cells were assessed by flow cytometry. Values are presented as mean ± standard error of the mean. ***P < 0.001, Mann-Whitney U test. CCR, CC chemokine receptor.
CCR4 and CCR6 are expressed on distinct memory cell populations, including CCR7+CD45RAmed very early memory cells
Having shown a significant increase in the frequencies of CCR4- and CCR6-expressing CD4+ T cells in patients with GPA, we were interested in phenotypic features of CCR4- and CCR6-expressing CD4+ T cells next. To assign CCR4+ and CCR6+ cells to the respective naïve and memory cell subsets, cells were additionally stained with fluorescent-conjugated antibodies for CD45RA and CCR7 to allow discrimination into diverse T cell subsets [2,16-18]. By the use of these markers, we found that CCR4 and CCR6 expression was confined largely to the circulating CCR7+CD45RA- central memory (TCM) and CCR7-CD45RA- (TEM) and CCR7-CD45RA+ (TEMRA) effector memory cell subsets within the total CD4+ T cell population. A significant increase in the frequency of CCR4+ and CCR6+ cells was remarkable in the CCR7-CD45RA+ effector memory (TEMRA) subset in patients with GPA. A significant increase in CCR6+ cells was also found in the CCR7+CD45RA- central memory T-cell subset (TCM). However, significantly increased percentages of CCR4+ and CCR6+ cells were also detected in the CCR7+CD45RA+ population, which contains naïve T cells (TN) by definition (Figure 2a, b). Dissecting the CCR7+CD45RA+ population with respect to CD45RA fluorescence intensity, we detected two subsets in the CCR7+CD45RA+ population. CCR7+CD45RAhigh T cells generally lacked CCR4 and CCR6 expression with the exception of three patients with GPA. In contrast, CCR7+CD45RAmed T cells displayed CCR4 and CCR6 expression. We found higher frequencies of CCR4+ and CCR6+ cells within the CCR7+CD45RAmed T cell subset in patients with GPA compared with healthy controls (Figure 2c, d). Thus, the CCR7+CD45RA+ population contained genuine CCR7+CD45RAhigh TN lacking CCR4 and CCR6 expression and another CCR7+CD45RAmed T cell subset comprising CCR4+ and CCR6+ cells. The latter was reminiscent of so-called very early memory T cells (TVEM) [19].
thumbnailFigure 2. Increased percentages of CCR4+ and CCR6+ memory T cell subsets in patients with granulomatosis with polyangiitis (GPA). Percentages of CD4+CCR4+ (a) and CD4+CCR6+ (b) T cells in the CCR7+CD45RA- central memory (TCM), CCR7-CD45RA- effector memory (TEM), CCR7+CD45RA+ 'naïve by definition' (TN), and CCR7-CD45RA+ 'revertant' effector memory (TEMRA) populations. (c) Dissection of the CD4+CCR7+CD45RA+ population with regard to CD45RA fluorescence intensity into CCR7+CD45RAhigh cells representing genuine TN and CCR7+CD45RAmed cells reminiscent of very early memory T cells (TVEM). Percentages of CCR4+ and CCR6+ cells in the CCR7+CD45RAmed and CCR7+CD45RAhigh subsets are shown. (d) Representative quadrant dot-plot analysis showing segregation of the gated CD4+CCR7+CD45RA+ T cell population into two subsets. CCR7+CD45RAmed T cells displayed CCR4 and CCR6 expression (TVEM). CCR7+CD45RAhigh T cells lacked CCR4 and CCR6 expression (genuine TN). Numbers in quadrants and histograms represent percentages of cells. Percentages of positive cells were assessed by flow cytometry. Values are presented as mean ± standard error of the mean. *P < 0.05, ***P < 0.001, Mann-Whitney U test. CCR, CC chemokine receptor; HC, healthy control.
Decreased frequency of CCR7+CD45RAhigh naïve T cells and unreduced frequency of CCR7+CD45RAmed very early memory T cells in granulomatosis with polyangiitis
Earlier studies have reported significantly lower percentages of peripheral blood TN by using CCR7 and CD45RO or CD45RB expression for the phenotypic characterization of T cells in patients with GPA [20,21]. In this study, we showed a segregation of the CCR7+CD45RA+ T cell compartment into different two subsets based on CCR4 and CCR6 expression and CD45RA fluorescence intensity. This prompted us to investigate whether TN and TVEM frequencies were likewise decreased within the total CD4+ T-cell population. In line with the aforementioned earlier studies, we found a significantly lower percentage of CCR7+CD45RAhigh TN in patients with GPA compared with healthy controls [20,21]. In contrast, CCR7+CD45RAmed TVEM frequencies were similar in patients with GPA and healthy individuals (Figure 3).
thumbnailFigure 3. Decreased frequency of naïve T cells (TN) and unreduced frequency of very early memory T cells (TVEM) in patients with granulomatosis with polyangiitis (GPA). Percentages of CCR7+CD45RAmed TVEM and CCR7+CD45RAhigh TN in the CD4+ T cell population are shown. Percentages of positive cells were assessed by flow cytometry. Values are presented as mean ± standard error of the mean. **P < 0.01, Mann-Whitney U test. CCR, CC chemokine receptor; HC, healthy control.
Distinct cytokine-producing subsets within CCR4+ and CCR6+ T-cell populations
We showed increased frequencies of circulating CCR4- or CCR6-expressing (or both) CD4+ TCM, TEMRA, and TVEM in patients with GPA. To investigate functional features of CCR4+ and CCR6+ cells within the total CD4+ T cell population, peripheral blood cells were stained for intracellular cytokines. An IFNγ+ cell fraction was found in all CCR4+ or CCR6+ subsets or both. An increased percentage of IL-17+ and IL-22+ cells was detected in the CCR4-CCR6+ 'single positive' and CCR4+CCR6+ 'double positive' cell fractions when compared with the CCR4-CCR6- 'double negative' cell subset. Furthermore, an increased frequency of IL-4+ cells was shown in the CCR4+CCR6- 'single positive' cell fraction compared with the CCR4-CCR6- 'double negative' cell subset in both patients with GPA and healthy controls. CCR4-CCR6+ 'single positive' and CCR4+CCR6+ 'double positive' cells differed from each other with respect to the percentage of IFNγ-producing cells, which was significantly higher in the CCR4-CCR6+ 'single positive' fraction (P < 0.01, Mann-Whitney U test). The CCR4-CCR6- 'double negative' cell subset differed from the other subsets in that only an IFNγ+ cell fraction was remarkable in this subset (Table 2). Less than 1% of cells displayed intracellular co-expression of IL-17 and IL-22 in CCR6+ cells within the total CD4+ T-cell population (data not shown). Thus, circulating CD4+CCR4+ and CD4+CCR6+ T cell populations comprised distinct subsets of cytokine-producing cells.
Table 2. Percentages of cytokine-producing CCR4+ and/or CCR6+ cell subsets within the total CD4+ T cell population compared with the CCR4-CCR6- cell subset
Discussion
Chemokine receptors play an important role in mediating T cell recruitment to distinct anatomical sites and tissues [2]. Whereas the CC chemokine receptor CCR7 mediates homing of naïve (TN) and central memory (TCM) T cells to lymph nodes, other CC and CXC chemokine receptors (CCR/CXCR) trigger intravascular adhesion and direct migration of effector memory T cell subsets (CD45RA- TEM and CD45RA+ 'reverted' TEMRA) into peripheral tissues for patrol and recruitment to inflammatory sites [2,19]. Previously, cloned CCR6+ cells from peripheral blood and inflammatory sites in Crohn's disease have been shown to produce IL-17. In contrast, CCR4+ cells secrete IL-4 [11,12,22]. Recently, Th17-, Th22-, and Th2-type PR3-specific cells have been suggested to be involved in chronic inflammation and autoimmunity in GPA [8-10,23]. Moreover, an increased proportion of circulating CD45RClow Th2-type and Th17 cells has been reported in ANCA-associated vasculitides, including GPA. The increase is independent of disease duration and treatment [24]. Therefore, to investigate the extent to which CCR4 and CCR6 expression could be implicated in T-cell recruitment in GPA, we analyzed the expression of these chemokine receptors on T cells.
In this study, we found increased frequencies of circulating CCR4+ and CCR6+ cells within the total CD4+ T cell population in GPA. In contrast, we found no significant increase in the frequencies of CCR4+ and CCR6+ cells in the total CD8+ T cell population. CCR4 and CCR6 expression suggests T cell activation [11,12]. Persistent T cell activation regardless of clinical disease activity has been reported in GPA [20,21,25]. Recently, stable CCR6 expression was reported to be controlled by epigenetic mechanisms [26]. In line with previous reports, CCR4 and CCR6 expression was confined largely to circulating CCR7+CD45RA- central memory (TCM), CCR7-CD45RA- (TEM), and CCR7-CD45RA+ (TEMRA) effector memory CD4+ T cells [11,12]. We found a significant increase in the frequency of CCR4+ and CCR6+ TEMRA and CCR6+ TCM in patients with GPA. Surprisingly, CCR4+ and CCR6+ cells were also detected within the CCR7+CD45RA+ population, which contains the naïve T cell subset (TN) by definition. TN are CD45RA+ and express CCR7 for peripheral lymph node homing but lack receptors such as CCR4 and CCR6 for the migration to peripheral tissues [2,16-18]. Further analysis dissecting the CCR7+CD45RA+ population with regard to CD45RA fluorescence intensity disclosed that the CCR7+CD45RA+ T-cell compartment contained two subsets. One subset of CCR7+CD45RAhigh T cells generally lacked CCR4 and CCR6 expression with the exception of three patients with GPA. Thus, CCR7+CD45RAhigh T cells represented genuine TN. CCR4 and CCR6 expression on CCR7+CD45RAhigh TN in individual patients with GPA could represent TN activation, which has been reported before by demonstrating an increased frequency of CD4+CD45RO-FoxP3- TN expressing the activation marker CD25 [20,25]. In line with earlier studies, we showed that the percentage of CCR7+CD45RAhigh TN within the total CD4+ T cell population was significantly lower in patients with GPA [20,21]. In contrast, the percentage of CCR7+CD45RAmed T cells was not decreased in patients with GPA. CCR7+CD45RAmed T cells displayed CCR4 and CCR6 expression reminiscent of so-called very early memory T cells (TVEM). Higher frequencies of CCR4+ and CCR6+ cells within the CCR7+CD45RAmed TVEM subset were found in patients with GPA compared with healthy controls. TVEM have been described earlier as 'apparently TN' oddly displaying chemokine receptors for both lymph node homing (CCR7) and peripheral tissue migration (CCR4 and CXCR3) in healthy individuals by Song and colleagues [19]. Analysis of the proliferation history, T-cell receptor repertoire, and cytokine response of CCR4- and CXCR3-expressing CCR7+CD45RO- T cells suggests that these cells represent TVEM, which have proceeded only a short way along the differentiation pathway from TN to TCM or TEM. TVEM are still multifunctional but finally differentiate into either TCM or TEM [19].
Earlier studies showed that chemokine receptor expression for lymph node homing (CCR7) and peripheral tissue migration (for example, CCR4) is not mutually exclusive on T cell subsets [27]. The migratory behavior of TEM displaying dual-chemokine receptor expression is determined by chemotactic gradients and cytokine- and T-cell receptor (TCR)-mediated signals [28]. CCR4-expressing CCR7+ TEM have been reported in inflamed peripheral tissues (for example, in psoriasis and juvenile idiopathic arthritis) [29,30]. Whereas CCR7- TEM remain in the peripheral tissue, CCR7+ TEM migrate to peripheral tissues and subsequently exit the tissue to enter draining lymph nodes in different animal models [31,32]. Although CCR7+ TEM retain a capability to enter lymph nodes, inflammatory cytokines can subvert migration of CCR7+ TEM, resulting in the retention of CCR7+ TEM in the inflamed synovial tissue [33]. Cytokines also drive the differentiation of CCR4-expressing CCR7+ TCM to CCR7- TEM [22]. Of note, CCR7+ TEM accumulate in areas of ectopic lymphoid tissue in the inflamed synovial tissue [30]. In contrast, CCR4-expressing CCR7+ TVEM reside or recirculate in secondary lymphoid tissues, where they continue to differentiate and acquire further chemokine receptors for peripheral tissue migration [19].
Having shown increased frequencies of circulating CCR4- and CCR6-expressing CD4+ memory T cell subsets, including TVEM in patients with GPA, we analyzed the cytokine production of CCR4+ and CCR6+ T cells. Previously, cloned and, as such, preselected CCR6+ cells were reported to secrete IL-17, whereas CCR4+ T cells produce IL-4 [11,12]. In our study, we found an increased percentage of IL-17- and IL-22-producing cells in the CCR4-CCR6+ 'single positive' and CCR4+CCR6+ 'double positive' cell subsets and an increased frequency of IL-4+ cells in the CRR4+CCR6- 'single positive' cell subset compared with the CCR4-CCR6- 'double negative' cell subset within the total circulating CD4+ T-cell population. Thus, in line with earlier studies, we found Th17 cells within circulating CCR6+ cells and Th2-type cells among CCR4+ cells [11,12]. Moreover, CCR4-CCR6+ 'single positive' and CCR4+CCR6+ 'double positive' cells differed from each other with respect to the percentage of IFNγ-producing cells, which was higher in the former cell population.
Conclusions
We found increased frequencies of circulating CCR4+ and CCR6+ T cells in patients with GPA. CCR4 and CCR6 expression was confined largely to central memory (TCM) and effector memory (TEM and TEMRA) subsets but could also be detected on very early memory T cells (TVEM) displaying chemokine receptors for both lymph node homing (CCR7) and peripheral tissue migration (CCR4 and CCR6). CD4+CCR4+ and CD4+CCR6+ T-cell populations contained distinct cytokine-producing subsets. Our data suggest that CCR4 and CCR6 could be involved in the recruitment of different T cell subsets, including cytokine-producing cells, to inflamed sites in patients with GPA. Further studies are needed to assess CCR4+ and CCR6+ T cell reactivity to the respective chemokine gradients and the expression of CCR4, CCR6, and their chemokine ligands in inflammatory lesions in patients with GPA in order to define new targets for therapeutic intervention.
Abbreviations
ANCA: anti-neutrophil cytoplasmic autoantibodies; APC: allophycocyanine; APC-Cy7: allophycocyanine-cyanine dye 7; CCR: CC chemokine receptor; CXCR: CXC chemokine receptor; Cy7: cyanine dye 7; FACS: fluorescence-activated cell sorting; GPA: granulomatosis with polyangiitis (Wegener's); IFNγ: interferon-gamma; IL: interleukin; PB: Pacific blue; PE: phycoerythrin; PR3: proteinase 3; TCM: central memory T cells; TEM: CD45RA- effector memory T cells; TEMRA: CD45RA+ effector memory T cells; Th: T-helper cell; TN: naïve T cells; TVEM: very early memory T cells.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
UF participated in the design of the study, acquisition of data, interpretation of the results, and drafting of the manuscript. SP participated in the acquisition of data, interpretation of results, and drafting of the manuscript. WLG participated in the coordination of the study and assisted in the interpretation of the results. PL conceived the study, participated in its design and coordination and the interpretation of the results, and drafted of the manuscript. All authors read and approved the final manuscript.
Authors' information
UF, Ph.D., is a biologist. SP is a medical technician. WLG, M.D., is the director of the Department of Rheumatology and spokesman of the Vasculitis Center UKSH and Clinical Research Unit 170. PL, M.D., is the coordinator of Clinical Research Unit 170. All authors are at the Department of Rheumatology, Vasculitis Center UKSH and Clinical Center Bad Bramstedt, University of Lübeck (Lübeck, Germany).
Acknowledgements
This work was supported by the German Research Foundation-funded Clinical Research Unit 170 'Early pathogenesis of Wegener's granulomatosis', Excellence Cluster 'Inflammation at Interfaces' (JRG-Ih), University-funded Priority Program Autoimmunity, and a grant from the Association for the Promotion of the Study and Control of Rheumatic Diseases (Bad Bramstedt, Germany).
References
1. Woodland DL, Dutton RW: Heterogeneity of CD4+ and CD8+ T cells.
Curr Opin Immunol 2003, 15:336-342. PubMed Abstract | Publisher Full Text OpenURL
2. Von Andrian U, Mackay CR: T-cell function and migration. Two sides of the same coin.
N Engl J Med 2000, 343:1020-1034. PubMed Abstract | Publisher Full Text OpenURL
3. Lamprecht P, Erdmann A, Mueller A, Csernok E, Reinhold-Keller E, Holl-Ulrich K, Feller AC, Bruehl H, Gross WL: Heterogeneity of CD4+ and CD8+ memory T cells in localized and generalized Wegener's granulomatosis.
Arthritis Res Ther 2003, 5:R25-31. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text OpenURL
4. Lamprecht P, Holle J, Gross WL: Update on clinical, pathophysiological and therapeutic aspects in ANCA-associated vasculitides.
Curr Drug Discov Technol 2009, 6:241-251. PubMed Abstract | Publisher Full Text OpenURL
5. Coulomb-L'Hermine A, Capron F, Zou W, Piard F, Galateau F, Laurent P, Crevon MC, Galanaud P, Emilie D: Expression of the chemokine RANTES in pulmonary Wegener's granulomatosis.
Hum Pathol 2001, 32:320-326. PubMed Abstract | Publisher Full Text OpenURL
6. Lamprecht P, Bruhl H, Erdmann A, Holl-Ulrich K, Csernok E, Seitzer U, Mack M, Feller AC, Reinhold-Keller E, Gross WL, Muller A: Differences in CCR5 expression on peripheral blood CD4+CD28- T-cells and granulomatous lesions between localized and generalized Wegener's granulomatosis.
Clin Immunol 2003, 108:1-7. PubMed Abstract | Publisher Full Text OpenURL
7. Balding CE, Howie AJ, Drake-Lee AB, Savage CO: Th2 dominance in nasal mucosa in patients with Wegener's granulomatosis.
Clin Exp Immunol 2001, 125:332-339. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL
8. Abdulahad WH, Stegeman CA, Limburg PC, Kallenberg CG: Skewed distribution of Th17 lymphocytes in patients with Wegener's granulomatosis in remission.
Arthritis Rheum 2008, 58:2196-2205. PubMed Abstract | Publisher Full Text OpenURL
9. Nogueira E, Hamour S, Sawant D, Henderson S, Mansfield N, Chavele KM, Pusey CD, Salama AD: Serum IL-17 and IL-23 levels and autoantigen-specific Th17 cells are elevated in patients with ANCA-associated vasculitis.
Nephrol Dial Transplant 2010, 25:2209-2217. PubMed Abstract | Publisher Full Text OpenURL
10. Fagin U, Csernok E, Müller A, Pitann S, Fazio J, Krause K, Bremer P, Wipfler-Freißmuth E, Moosig F, Gross WL, Lamprecht P: Distinct proteinase 3-induced cytokine pattern's in Wegener's granulomatosis, Churg-Strauss syndrome, and healthy controls.
Clin Exp Rheumatol 2011, 29(Suppl 64):S57-S62. PubMed Abstract | Publisher Full Text OpenURL
11. Annunziato F, Cosmi L, Santarlasci V, Maggi L, Liotta F, Mazzinghi B, Parente E, Filì L, Ferri S, Frosali F, Giudici F, Romagnani P, Parronchi P, Tonelli F, Maggi E, Romagnani S: Phenotypic and functional features of human Th17 cells.
J Exp Med 2007, 204:1849-1861. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL
12. Acosta-Rodriguez EV, Rivino L, Geginat J, Jarrossay D, Gattorno M, Lanzavecchia A, Sallusto F, Napolitani G: Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells.
Nat Immunol 2007, 8:639-646. PubMed Abstract | Publisher Full Text OpenURL
13. Leavitt RY, Fauci AS, Bloch DA, Michel BA, Hunder GG, Arend WP, Calabrese LH, Fries JF, Lie JT, Lightfoot RW Jr, Masi AT, McShane DJ, Mills JA, Stevens MB, Wallace SL, Zvaifler NJ: The American College of Rheumatology 1990 criteria for the classification of Wegener's granulomatosis.
Arthritis Rheum 1990, 33:1101-1107. PubMed Abstract OpenURL
14. Jennette JC, Falk RJ, Andrassy K, Bacon PA, Churg J, Gross WL, Hagen EC, Hoffman GS, Hunder GG, Kallenberg CG, McCluskey RT, Sinico RA, Rees AJ, van Es LA, Waldherr R, Wiik A: Nomenclature of systemic vasculitides. Proposal of an international consensus conference.
Arthritis Rheum 1994, 37:187-192. PubMed Abstract | Publisher Full Text OpenURL
15. Hellmich B, Flossmann O, Gross WL, Bacon P, Cohen-Tervaert JW, Guillevin L, Jayne D, Mahr A, Merkel PA, Raspe H, Scott DGI, Witter J, Yazici H, Luqmani R, the European Vasculitis Study Group: EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis: focus on anti-neutrophil cytoplasm antibody-associated vasculitis.
Ann Rheum Dis 2007, 66:605-617. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL
16. Sallusto F, Lenig D, Förster R, Lipp M, Lanzavecchia A: Two subsets of memory T lymphocytes with distinct homing potentials and effector functions.
Nature 1999, 401:708-712. PubMed Abstract | Publisher Full Text OpenURL
17. Appay V, van Lier RAW, Sallusto F, Roederer M: Phenotype and Function of Human T Lymphocyte Subsets: Consensus and Issues.
Cytometry A 2008, 73:975-983. PubMed Abstract | Publisher Full Text OpenURL
18. De Rosa Herzenberg LA, Herzenberg LA, Roederer M: 11-color, 13-parameter flow cytometry: identification of human naïve T cells by phenotype, function, and T-cell receptor diversity.
Nat Med 2001, 7:245-248. PubMed Abstract | Publisher Full Text OpenURL
19. Song K, Rabin RL, Hill BJ, De Rosa SC, Perfetto SP, Zhang HH, Foley JF, Reiner JS, Liu J, Mattapallil JJ, Douek DC, Roederer M, Farber JM: Characterization of subsets of CD4+ memory T cells reveals early branched pathways of T cell differentiation in humans.
Proc Natl Acad Sci USA 2005, 102:7916-7921. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL
20. Marinaki S, Neumann I, Kälsch AI, Grimminger P, Breedijk A, Birk R, Schmitt W, Waldherr R, Yard BA, van der Woude FJ: Abnormalities of CD4 T cell subpopulations in ANCA-associated vasculitis.
Clin Exp Immunol 2005, 140:181-191. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL
21. Abdulahad WH, van der Geld YM, Stegeman CA, Kallenberg CG: Persistent expansion of CD4+ effector memory T cells in Wegener's granulomatosis.
Kidney Int 2006, 70:938-947. PubMed Abstract | Publisher Full Text OpenURL
22. Rivino L, Messi M, Jarrossay D, Lanzavecchia A, Sallusto F, Geginat J: Chemokine receptor expression identifies Pre-T helper (Th)1, Pre-Th2, and nonpolarized cells among human CD4+ central memory T cells.
J Exp Med 2004, 200:725-735. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL
23. Popa ER, Franssen CF, Limburg PC, Huitema MG, Kallenberg CG, Tervaert JW: In vitro cytokine production and proliferation of T cells from patients with anti-proteinase 3- and antimyeloperoxidase-associated vasculitis, in response to proteinase 3 and myeloperoxidase.
Arthritis Rheum 2002, 46:1894-1904. PubMed Abstract | Publisher Full Text OpenURL
24. Ordonez L, Bernard I, L'Faqihi-Olive FE, Cohen Tervaert JW, Damoiseaux J, Saoudi A: CD45RC isoform expression identifies functionally distinct T cell subsets differentially distributed between healthy individuals and AAV patients.
PLOS One 2009, 4:e5287. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL
25. Marinaki S, Kälsch AI, Grimminger P, Breedijk A, Birk R, Schmitt WH, Weiss C, van der Woude FJ, Yard BA: Persistent T-cell activation and clinical correlations in patients with ANCA-associated systemic vasculitis.
Nephrol Dial Transplant 2006, 21:1825-1832. PubMed Abstract | Publisher Full Text OpenURL
26. Steinfelder S, Floess S, Engelbert D, Haeringer B, Baron U, Rivino L, Steckel B, Gruetzkau A, Olek S, Geginat J, Huehn J, Hamann A: Epigenetic modification of the CCR6 gene is associated with stable CCR6 expression in T cells.
Blood 2011, 117:2839-2846. PubMed Abstract | Publisher Full Text OpenURL
27. Campbell JJ, Murphy KE, Kunkel EJ, Brightling CE, Soler D, Shen Z, Boisvert J, Greenberg HB, Vierra MA, Goodman SB, Genovese MC, Wardlaw AJ, Butcher EC, Wu L: CCR7 expression and memory T cell diversity in humans.
J Immunol 2001, 166:877-884. PubMed Abstract | Publisher Full Text OpenURL
28. Foxman EF, Kunkel EJ, Butcher EC: Integrating conflicting chemotactic signals. The role of memory in leukocyte navigation.
J Cell Biol 1999, 147:577-588. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL
29. Teraki Y, Miyake A, Takebayashi R, Shiohara T: Homing receptor and chemokine receptor on intraepidermal T cells in psoriasis vulgaris.
Clin Exp Dermatol 2004, 29:658-663. PubMed Abstract | Publisher Full Text OpenURL
30. Gattorno M, Prigione I, Morandi F, Gregorio A, Chiesa S, Ferlito F, Favre A, Uccelli A, Gambini C, Martini A, Pistoia V: Phenotypic and functional characterization of CCR7+ and CCR7- CD4+ memory T-cells homing to the joints in juvenile idiopathic arthritis.
Arthritis Res Ther 2005, 7:R256-267. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL
31. Debes GF, Arnold CN, Young AJ, Krautwald S, Lipp M, Hay JB, Butcher EC: Chemokine receptor CCR7 required for T lymphocyte exit from peripheral tissue.
Nat Immunol 2005, 6:889-894. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL
32. Bromley SK, Thomas SY, Luster AD: Chemokine receptor CCR7 guides T cell exit from peripheral tissues and entry into afferent lymphatics.
Nat Immunol 2005, 6:895-901. PubMed Abstract | Publisher Full Text OpenURL
33. Zhang X, Nakajima T, Goronzy JJ, Weyand CM: Tissue trafficking patterns of effector memory CD4+ T cells in rheumatoid arthritis.
Arthritis Rheum 2005, 52:3839-3849. PubMed Abstract | Publisher Full Text OpenURL
|
{
"url": "http://www.arthritis-research.com/content/14/2/R73?fmt_view=mobile",
"source_domain": "www.arthritis-research.com",
"snapshot_id": "crawl=CC-MAIN-2015-35",
"warc_metadata": {
"Content-Length": "132296",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:UDADAJS73VHXMTHAJ62M3VA5IBUILM7E",
"WARC-Concurrent-To": "<urn:uuid:4c53b808-60bc-4b78-9bc4-48d7577a3ecb>",
"WARC-Date": "2015-09-05T16:27:16",
"WARC-IP-Address": "192.129.25.208",
"WARC-Identified-Payload-Type": null,
"WARC-Payload-Digest": "sha1:YY6LV75WKLOHAN5JINZ3Z5LGB5HZEMBD",
"WARC-Record-ID": "<urn:uuid:6455f3b5-6390-410d-8010-ac682c0d46be>",
"WARC-Target-URI": "http://www.arthritis-research.com/content/14/2/R73?fmt_view=mobile",
"WARC-Truncated": "length",
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:c9db8570-5a21-46dd-957b-7bca0bda7852>"
},
"warc_info": "robots: classic\r\nhostname: ip-10-171-96-226.ec2.internal\r\nsoftware: Nutch 1.6 (CC)/CC WarcExport 1.0\r\nisPartOf: CC-MAIN-2015-35\r\noperator: CommonCrawl Admin\r\ndescription: Wide crawl of the web for August 2015\r\npublisher: CommonCrawl\r\nformat: WARC File Format 1.0\r\nconformsTo: http://bibnum.bnf.fr/WARC/WARC_ISO_28500_version1_latestdraft.pdf"
}
|
{
"line_start_idx": [
0,
14,
15,
118,
119,
148,
149,
300,
301,
367,
368,
388,
389,
542,
543,
581,
582,
603,
604,
666,
667,
801,
802,
803,
829,
861,
884,
908,
909,
959,
960,
1233,
1234,
1243,
1244,
1257,
1258,
1750,
1751,
1759,
1760,
2003,
2004,
2012,
2013,
2997,
2998,
3010,
3011,
3338,
3339,
3352,
3353,
4059,
4060,
5729,
5730,
5752,
5753,
5770,
5771,
6152,
6153,
6244,
6245,
6280,
6281,
7072,
7073,
7124,
7125,
7897,
7898,
8837,
8838,
8863,
8864,
9227,
9228,
9249,
9250,
9533,
9534,
9542,
9543,
9641,
9642,
10620,
10621,
11073,
11074,
11188,
11189,
13086,
13087,
14337,
14338,
14495,
14496,
15296,
15297,
15778,
15779,
15857,
15858,
17338,
17339,
17495,
17496,
17507,
17508,
18740,
18741,
21615,
21616,
22919,
22920,
23965,
23966,
23978,
23979,
24907,
24908,
24922,
24923,
25484,
25485,
25505,
25506,
25565,
25566,
25589,
25590,
26112,
26113,
26134,
26135,
26536,
26537,
26554,
26555,
26928,
26929,
26940,
26941,
27010,
27011,
27097,
27098,
27188,
27189,
27273,
27274,
27491,
27492,
27609,
27610,
27743,
27744,
27836,
27837,
28019,
28020,
28099,
28100,
28388,
28389,
28467,
28468,
28593,
28594,
28707,
28708,
28863,
28864,
28950,
28951,
29170,
29171,
29265,
29266,
29519,
29520,
29617,
29618,
29859,
29860,
29968,
29969,
30185,
30186,
30265,
30266,
30556,
30557,
30621,
30622,
30894,
30895,
30979,
30980,
31346,
31347,
31456,
31457,
31611,
31612,
31688,
31689,
31818,
31819,
31899,
31900,
32088,
32089,
32164,
32165,
32430,
32431,
32552,
32553,
32751,
32752,
32865,
32866,
33013,
33014,
33093,
33094,
33305,
33306,
33412,
33413,
33685,
33686,
33772,
33773,
34010,
34011,
34112,
34113,
34333,
34334,
34428,
34429,
34662,
34663,
34740,
34741,
34961,
34962,
35041,
35042,
35171,
35172,
35280,
35281,
35422,
35423,
35509,
35510,
35774,
35775,
35889,
35890,
36047,
36048,
36154,
36155,
36298,
36299,
36378,
36379,
36514,
36515
],
"line_end_idx": [
14,
15,
118,
119,
148,
149,
300,
301,
367,
368,
388,
389,
542,
543,
581,
582,
603,
604,
666,
667,
801,
802,
803,
829,
861,
884,
908,
909,
959,
960,
1233,
1234,
1243,
1244,
1257,
1258,
1750,
1751,
1759,
1760,
2003,
2004,
2012,
2013,
2997,
2998,
3010,
3011,
3338,
3339,
3352,
3353,
4059,
4060,
5729,
5730,
5752,
5753,
5770,
5771,
6152,
6153,
6244,
6245,
6280,
6281,
7072,
7073,
7124,
7125,
7897,
7898,
8837,
8838,
8863,
8864,
9227,
9228,
9249,
9250,
9533,
9534,
9542,
9543,
9641,
9642,
10620,
10621,
11073,
11074,
11188,
11189,
13086,
13087,
14337,
14338,
14495,
14496,
15296,
15297,
15778,
15779,
15857,
15858,
17338,
17339,
17495,
17496,
17507,
17508,
18740,
18741,
21615,
21616,
22919,
22920,
23965,
23966,
23978,
23979,
24907,
24908,
24922,
24923,
25484,
25485,
25505,
25506,
25565,
25566,
25589,
25590,
26112,
26113,
26134,
26135,
26536,
26537,
26554,
26555,
26928,
26929,
26940,
26941,
27010,
27011,
27097,
27098,
27188,
27189,
27273,
27274,
27491,
27492,
27609,
27610,
27743,
27744,
27836,
27837,
28019,
28020,
28099,
28100,
28388,
28389,
28467,
28468,
28593,
28594,
28707,
28708,
28863,
28864,
28950,
28951,
29170,
29171,
29265,
29266,
29519,
29520,
29617,
29618,
29859,
29860,
29968,
29969,
30185,
30186,
30265,
30266,
30556,
30557,
30621,
30622,
30894,
30895,
30979,
30980,
31346,
31347,
31456,
31457,
31611,
31612,
31688,
31689,
31818,
31819,
31899,
31900,
32088,
32089,
32164,
32165,
32430,
32431,
32552,
32553,
32751,
32752,
32865,
32866,
33013,
33014,
33093,
33094,
33305,
33306,
33412,
33413,
33685,
33686,
33772,
33773,
34010,
34011,
34112,
34113,
34333,
34334,
34428,
34429,
34662,
34663,
34740,
34741,
34961,
34962,
35041,
35042,
35171,
35172,
35280,
35281,
35422,
35423,
35509,
35510,
35774,
35775,
35889,
35890,
36047,
36048,
36154,
36155,
36298,
36299,
36378,
36379,
36514,
36515,
36600
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 36600,
"ccnet_original_nlines": 274,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.18369005620479584,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.14237333834171295,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.27743157744407654,
"rps_doc_frac_unique_words": 0.2574577331542969,
"rps_doc_mean_word_length": 5.54132604598999,
"rps_doc_num_sentences": 299,
"rps_doc_symbol_to_word_ratio": 0.00013545999536290765,
"rps_doc_unigram_entropy": 6.0433526039123535,
"rps_doc_word_count": 5263,
"rps_doc_frac_chars_dupe_10grams": 0.10355231910943985,
"rps_doc_frac_chars_dupe_5grams": 0.3087711036205292,
"rps_doc_frac_chars_dupe_6grams": 0.2517487406730652,
"rps_doc_frac_chars_dupe_7grams": 0.18581126630306244,
"rps_doc_frac_chars_dupe_8grams": 0.16328349709510803,
"rps_doc_frac_chars_dupe_9grams": 0.13472089171409607,
"rps_doc_frac_chars_top_2gram": 0.013578380458056927,
"rps_doc_frac_chars_top_3gram": 0.019613219425082207,
"rps_doc_frac_chars_top_4gram": 0.02869977056980133,
"rps_doc_books_importance": -3469.929931640625,
"rps_doc_books_importance_length_correction": -3469.929931640625,
"rps_doc_openwebtext_importance": -1886.1402587890625,
"rps_doc_openwebtext_importance_length_correction": -1886.1402587890625,
"rps_doc_wikipedia_importance": -1334.6400146484375,
"rps_doc_wikipedia_importance_length_correction": -1334.6400146484375
},
"fasttext": {
"dclm": 0.06324273347854614,
"english": 0.8292793035507202,
"fineweb_edu_approx": 1.8727725744247437,
"eai_general_math": 0.24812132120132446,
"eai_open_web_math": 0.1654897928237915,
"eai_web_code": 0.00811839010566473
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.07922",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "616.079",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "4",
"label": "Analyze"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v1": {
"primary": {
"code": "2",
"label": "Academic/Research"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "0",
"label": "No Artifacts"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "0",
"label": "No missing content"
}
},
"document_type_v2": {
"primary": {
"code": "3",
"label": "Academic Writing"
},
"secondary": {
"code": "8",
"label": "Documentation"
}
},
"reasoning_depth": {
"primary": {
"code": "4",
"label": "Advanced Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "4",
"label": "Graduate/Expert Level"
},
"secondary": {
"code": "3",
"label": "Undergraduate Level"
}
}
}
|
1a01aa77535b9ecfb87b9fc36adbcd2f
|
-8,988,211,874,750,192,000
|
Skin Care FAQs
Woman with beautiful skin.
Here is a look at many of the common questions we face from our customers in our New York store.
Why do I need to start using anti-wrinkles creams and other ant-aging products from the early thirties?
Women who are in their early thirties take their skin for granted which is their first mistake. As of now all the suntan, study and work sessions along with junk food consumption have not started showing their effect and even if they do, a little bit of concealer is all you need to fix it. But, that is just for now! In the years to come, your skin will soon start aging and start looking dull. What you need to do is take preventive measures and go for early treatments as this will help you maintain your youthful glow for many years to come and make you look beautiful and young!
Why do many young women suffer from premature aging?
A woman’s genetics and cumulative sun damage are the 2 major reasons why a woman suffers from premature aging. However, with the right use of procedures and products, a woman can correct, slow down and erase an aging face to a large extent.
When is the right time to take preventive measures and start using anti-aging products?
If you have been exposed to a lot of sun damage during the first twenty years of your life, it is recommended you start the use of anti-aging products immediately! You will be able to rectify the problem immensely by using the right lotions and creams containing antioxidants and sun protection serums.
What kinds of products are really helpful in slowing down the process of aging?
Products which contain natural minerals, vitamins and loads of antioxidants are just the products for you to look younger and beautiful. They help to slow down the process of photo damage which can lead to wrinkles, fine lines, dark spots and lustre-less skin. Always use products which suit your skin type and do not contain an ingredient which you are allergic to.
What are the essential products for anti-aging?
A basic skin care regime is just what you need to take care of the aging process. All you need to do is choose the essential products and create the perfect skin care regime for yourself. You would need an anti-aging day cream, a night cream, a face mask and a serum for the perfect daily anti-aging regime. It will not only help delay the process of aging to a large extent but also help cure the existing signs of aging with ease.
How Can Asparagus Benefit Our Skin?
Asparagus is the cousins from the family of onions and garlic. They are very fleshy and juicy. Apart from the delicious taste, it is also a rich source of nutrients. Across the globe, there are numerous types of asparagus available. Only a few of them can be eaten. The most distinctive feature of this particular vegetable is that it is costlier than that of the other vegetables. The reason behind such a feature is that these veggies are harvested with bare hands. Though the cost is on the higher side, the benefits derived from these veggie products are astonishing. It is a huge source of nutrients. Rich contents of protein are present in this particular vegetable, which allows it to appear as an inevitable gym food. Apart from proteins, asparagus is also rich in terms of vitamins, iron, potassium and copper, which makes it one of the most important vegetables ever produced. Let us move forward to have a look into the benefits that our skin can gain from this fleshy vegetable.
Asparagus
Protects the Skin from Sunburn
Asparagus is a rich source of antioxidants, which keeps our skin protected from the penetration of the harmful solar rays. As a result, the skin cells are prevented from getting burnt. Therefore, if your job wants you to be in the sun all day long, asparagus is the vegetable that you must consume to beat the heat.
Reduces Chances of Skin Cancer
The antioxidants such as carotenes, zeaxanthin, lutein and cryptoxanthin are present in an abundant amount in asparagus. Consumption of this vegetable allows these antioxidants to spread into the body. They fight the various germs and reduces the chances of skin cancer from occurring. Other viral infections can also be prevented.
Treats Skin Diseases
In case you are suffering from any skin disease, you can apply the extracts of asparagus on the affected area for getting rid of the problem. The nutrients present in the vegetable allow the skin to fight back the pathogens and eliminate them from within the skin. As a result, the skin diseases are prevented.
Asparagus plays an important role to keep the skin healthy. The plant may look thin and small in structure, but it carries extremely beneficial nutrients which are essential for optimal health. So, the next time you visit the market, pack some asparagus for consumption.
|
{
"url": "https://orogoldnewyork.com/tag/skin/",
"source_domain": "orogoldnewyork.com",
"snapshot_id": "crawl=CC-MAIN-2021-49",
"warc_metadata": {
"Content-Length": "22218",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:OIMVCMWGDWPED3RTGWJNZYDRED3LRUEZ",
"WARC-Concurrent-To": "<urn:uuid:2c7da823-def0-420b-a507-c79c2da1ad7b>",
"WARC-Date": "2021-11-29T18:00:59",
"WARC-IP-Address": "108.178.49.244",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:VFC5RXFGJSMAMWF74H44F2XJYLDNHRA4",
"WARC-Record-ID": "<urn:uuid:dc114617-1512-448c-976b-87691f1a363f>",
"WARC-Target-URI": "https://orogoldnewyork.com/tag/skin/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:8e182c98-776a-4a5b-8c8d-e0f20d446208>"
},
"warc_info": "isPartOf: CC-MAIN-2021-49\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for November/December 2021\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-235\r\nsoftware: Apache Nutch 1.18 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.3-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
15,
16,
43,
44,
141,
142,
246,
830,
831,
884,
1125,
1126,
1214,
1517,
1518,
1598,
1965,
1966,
2014,
2447,
2448,
2484,
2485,
3476,
3477,
3487,
3488,
3519,
3520,
3836,
3837,
3868,
3869,
4201,
4202,
4223,
4224,
4535,
4536
],
"line_end_idx": [
15,
16,
43,
44,
141,
142,
246,
830,
831,
884,
1125,
1126,
1214,
1517,
1518,
1598,
1965,
1966,
2014,
2447,
2448,
2484,
2485,
3476,
3477,
3487,
3488,
3519,
3520,
3836,
3837,
3868,
3869,
4201,
4202,
4223,
4224,
4535,
4536,
4806
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 4806,
"ccnet_original_nlines": 39,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.46688035130500793,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.00320513010956347,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.0972222164273262,
"rps_doc_frac_unique_words": 0.40143367648124695,
"rps_doc_mean_word_length": 4.616487503051758,
"rps_doc_num_sentences": 49,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.13775110244751,
"rps_doc_word_count": 837,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.01501035038381815,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.007763979956507683,
"rps_doc_frac_chars_top_3gram": 0.009316770359873772,
"rps_doc_frac_chars_top_4gram": 0.0062111797742545605,
"rps_doc_books_importance": -431.9161376953125,
"rps_doc_books_importance_length_correction": -431.9161376953125,
"rps_doc_openwebtext_importance": -246.55931091308594,
"rps_doc_openwebtext_importance_length_correction": -246.55931091308594,
"rps_doc_wikipedia_importance": -151.36058044433594,
"rps_doc_wikipedia_importance_length_correction": -151.36058044433594
},
"fasttext": {
"dclm": 0.018592599779367447,
"english": 0.9565799236297607,
"fineweb_edu_approx": 2.1137728691101074,
"eai_general_math": 0.026466429233551025,
"eai_open_web_math": 0.12731093168258667,
"eai_web_code": 0.0030871001072227955
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "613.6",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
},
"secondary": {
"code": "613.2",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "6",
"label": "Promotional/Advertisement"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "3",
"label": "Irrelevant Content"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "4",
"label": "Missing Images or Figures"
}
},
"document_type_v2": {
"primary": {
"code": "9",
"label": "FAQ"
},
"secondary": {
"code": "10",
"label": "Knowledge Article"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "4",
"label": "Highly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
6e3c8d3593f3f69280bb5502b214ab8e
|
-3,932,590,942,909,238,300
|
CR3 and Dectin-1 Collaborate in Macrophage Cytokine Response through Association on Lipid Rafts and Activation of Syk-JNK-AP-1 Pathway
The incidence of life-threatening fungal infections is increasing during the last decades. A better understanding of the interactions between fungal pathogen and its host cell is important to the development of new therapeutic strategies against fungal infections. Dimorphic fungus Histoplasma capsulatum becomes disseminated and threatens life in immunocompromised individuals. This fungal pathogen utilizes complement receptor 3 (CR3) and Dectin-1, two pattern recognition receptors on the surface of innate immune cells, to induce macrophage cytokine response. In this study, we demonstrated that CR3 and Dectin-1 act collaboratively to induce macrophage TNF and IL-6 response through a mechanism dependent on activation of the Syk-JNK-AP-1 signaling axis. CR3 and Dectin-1 are recruited and form clusters on lipid raft microdomains upon stimulation by H. capsulatum, leading to activation of their signaling convergence at Syk kinase and induction of subsequent cytokine response. In addition, we showed that CR3 and Dectin-1 cooperatively instruct the adaptive antifungal immunity to defense against H. capsulatum infection. Our findings define the molecular mechanisms underlying receptor crosstalk between CR3 and Dectin-1 and provide a valuable model for receptor collaboration in the context of host-fungus interactions.
Published in the journal: . PLoS Pathog 11(7): e32767. doi:10.1371/journal.ppat.1004985
Category: Research Article
doi: 10.1371/journal.ppat.1004985
Summary
The incidence of life-threatening fungal infections is increasing during the last decades. A better understanding of the interactions between fungal pathogen and its host cell is important to the development of new therapeutic strategies against fungal infections. Dimorphic fungus Histoplasma capsulatum becomes disseminated and threatens life in immunocompromised individuals. This fungal pathogen utilizes complement receptor 3 (CR3) and Dectin-1, two pattern recognition receptors on the surface of innate immune cells, to induce macrophage cytokine response. In this study, we demonstrated that CR3 and Dectin-1 act collaboratively to induce macrophage TNF and IL-6 response through a mechanism dependent on activation of the Syk-JNK-AP-1 signaling axis. CR3 and Dectin-1 are recruited and form clusters on lipid raft microdomains upon stimulation by H. capsulatum, leading to activation of their signaling convergence at Syk kinase and induction of subsequent cytokine response. In addition, we showed that CR3 and Dectin-1 cooperatively instruct the adaptive antifungal immunity to defense against H. capsulatum infection. Our findings define the molecular mechanisms underlying receptor crosstalk between CR3 and Dectin-1 and provide a valuable model for receptor collaboration in the context of host-fungus interactions.
Introduction
Diseases caused by fungal pathogens have become an important cause of morbidity and mortality over the last decades due to the increasing number of immunocompromised patients [1]. To reveal the cellular and molecular mechanisms of the interaction between host and fungal pathogens will be helpful for the development of new therapeutic strategies. Innate immune cells recognize pathogen-associated molecular patterns (PAMPs) on fungi through pattern recognition receptors (PRRs) [2, 3]. The fungal cell wall is composed predominantly of glucans, chitin, mannose and other covalently-linked proteins with the composition varies between species and even between the different strains and morphological forms of the same species [4, 5]. Since a single pathogen is composed of multiple PAMPs, innate immune cells are likely to simultaneously or sequentially utilize a complex set of PRRs to interact with a specific pathogen. The coordination between PRRs leading to activation or inhibition of downstream signaling is referred to as “receptor crosstalk” [6].
PRR collaboration is known to be important for the host to control invading pathogens. It has been reported that Dectin-1 functions synergistically with TLR2 in amplifying innate cell cytokine response when stimulated with their respective ligands [710]. Collaboration between Dectin-1 and TLR2 is mediated by the activation of both Dectin-1/Syk and TLR/Myd88 pathways which results in increased NF-κB activity [7, 9]. Receptor crosstalk between C-type lectin receptors (CLRs) has also been reported. Dectin-1 collaboration with SIGNR1 or with Dectin-2 is largely dependent on the activation of Syk kinase to enhance immune responses against Candida albicans [11, 12]. Stimulation with C. albicans induces colocolization and physical association of Dectin-1 and SIGNR1 whose collaboration results in macrophage oxidative response [11]. Aside from collaborating with TLRs and CLRs, Dectin-1 is also known to collaborate with CR3 in macrophage cytokine response to H. capsulatum in a Syk kinase-dependent manner [13]. However, the coordinated mechanisms in CR3 and Dectin-1 collaboration leading to cytokine production are undefined.
CR3 (Mac-1, αMβ2, or CD11b/CD18) is the principal β2 integrin known to contribute to fungal recognition in innate immune cells [3]. CR3 contains two ligand binding sites, I domain and lectin-like domain, which bind to protein ligands (such as iC3b, ICAM-1, and fibronectin) and β-glucan, respectively [14]. CR3 is an enigmatic receptor which transduces diverse and distinct signaling upon engagement with different ligands [15, 16]. Activation of CR3 is mediated by conformation change and regulated by inside-out and outside-in signals [17]. The inside-out signaling to activate CR3 can be initiated from other receptors, such as TLRs and Dectin-1 [18, 19]. Engagement of CR3 also elicits outside-in signaling which activates innate immune effector functions, such as phagocytosis, cytotoxic killing, and cytokine production [17]. Despite many studies revealing the molecular mechanisms regulating CR3 phagocytosis [20], the signaling pathway(s) responsible for its cytokine response is yet to be addressed.
In contrast to CR3, the understanding of Dectin-1 signaling is growing during the last decade. Dectin-1 engagement induces the phosphorylation of its intracellular ITAM-like motif leading to the recruitment and activation of Syk [21]. Syk facilitates the phosphorylation of PLCγ2, allowing subsequent activation of MAPKs, AP-1 and NFAT and the assembly of Card9-Bcl10-Malt1 signalsome which mediates the canonical NF-κB activation [2224]. A recent study also showed that Card9 bridges the interaction between Ras-GRF-1 and H-Ras, leading to downstream ERK activation upon Dectin-1 ligation [25]. In addition, Dectin-1 triggers Syk-independent Raf-1 activation through which antagonizes Syk-induced noncanonical NF-κB activation [26]. The requirement for Syk and the use of Card9 in Dectin-1 signaling differs in different macrophage and dendritic cell (DC) populations [27, 28]. Thus, signaling pathway downstream of Dectin-1 and signaling crosstalk between Dectin-1 and heterologous PRRs can very well be cell-type specific.
Here we used H. capsulatum and particulate ligands to study the molecular mechanism of collaboration between CR3 and Dectin-1 in macrophages. Our findings clearly showed that collaboration between CR3 and Dectin-1 in induction of TNF and IL-6 production was through synergistic activation of their downstream Syk-JNK-AP-1 signaling axis. In addition, while both CR3 and Dectin-1 were recruited and clustered on lipid raft microdomains upon encountering H. capsulatum, disruption of lipid raft hampered their collaboration in signaling activation and the subsequent cytokine response. Interestingly, CR3 and Dectin-1 cooperatively participated in host defense against disseminated histoplasmosis. Taken together, our results revealed the molecular mechanism underlying crosstalk between CR3 and Dectin-1 in enhancing cytokine response and demonstrated that they orchestrate adaptive antifungal immune response.
Results
CR3 and Dectin-1 collaborate to activate Syk in macrophage cytokine response
By use of blocking antibodies we previously showed that macrophage utilizes CR3 to phagocytose and both CR3 and Dectin-1 to mediate cytokine response to H. capsulatum [13]. Employing Itgam-/-, Clec7a-/-, and Itgam-/-Clec7a-/- macrophages here we investigated the mechanism of receptor crosstalk between CR3 and Dectin-1 (S1A Fig). While losing either or both CR3 and Dectin-1 did not affect the propagation of intracellular H. capsulatum (S2A Fig), TNF and IL-6 responses to either heat-killed or viable H. capsulatum were reduced in Itgam-/- and Clec7a-/- macrophages and the reduction was further enhanced in macrophages deficient in both receptors (Figs 1A and S3A, and also refer to S2B Fig). Blocking Dectin-1 in Itgam-/- macrophages or blocking CR3 in Clec7a-/- macrophages also revealed that signals from these two receptors had additive effect in TNF and IL-6 production (S4A Fig). It is worth noting that heat treatment did not change H. capsulatum recognition by macrophages.
Both CR3 and Dectin-1 are known to signal through activation of Syk kinase [21, 29]. We examined whether Syk is involved in the collaborative cytokine response induced by CR3 and Dectin-1. Stimulation with heat-killed or viable H. capsulatum activated Syk kinase and Syk activation was dampened in Itgam-/- and Clec7a-/- macrophages as well as in WT macrophages blocked by anti-CR3 or anti-Dectin-1 antibody (Figs 1B, S3B, S5A and S4B). The level of phosphorylated Syk was further reduced in Itgam-/-Clec7a-/- macrophages and in WT macrophages blocked by both anti-CR3 and anti-Dectin-1 antibodies (Figs 1B, S3B and S4B). These results suggest that signals from CR3 and Dectin-1 cooperatively activate Syk kinase. Treatment with Syk inhibitors significantly reduced H. capsulatum-induced TNF and IL-6 production and the reduction was not due to the cytotoxic effect of inhibitors (Figs 1C and S6). While Syk deficiency did not affect the expression of CR3 and Dectin-1, the deficiency almost completely abolished the production of TNF (Figs 1D and S1B). These results clearly demonstrate that CR3 and Dectin-1 act in concert in macrophage cytokine response to viable as well as heat-killed H. capsulatum by intensifying Syk activation.
CR3 and Dectin-1 collaborate to intensify Syk activation and subsequent cytokine response in macrophage.
Fig. 1. CR3 and Dectin-1 collaborate to intensify Syk activation and subsequent cytokine response in macrophage.
(A and B) Macrophages from WT, Itgam-/-, Clec7a-/- and Itgam-/-Clec7a-/- mice were stimulated with or without (0 h) heat-killed (HK) H. capsulatum. (A) Supernatants were collected at 6, 12, and 24 h after stimulation, and the concentrations of TNF and IL-6 in the supernatants were quantified by ELISA (n = 6 from 3 independent experiments). (B) Cell lysates were collected at 30 min after stimulation and analyzed by Western blotting using antibodies against p-Syk and Syk. The intensity of p-Syk was normalized against the corresponding Syk. Data shown in the lower panel are relative intensity of p-Syk (n = 3). (C and G) Macrophages from WT mice were treated with Syk inhibitors (SkyI, 10 μM; Bay 61-3606, 3 μM) starting at 1 h prior to stimulation with HK H. capsulatum (C) or with the combination of iC3b-coated beads (iC3b-LB) and depleted zymosan (dZ) (G). Culture supernatants were harvested 6 h later and analyzed for cytokine production (n = 5 from 2 independent experiments). (D) Fetal liver-derived macrophages (FLDMs) from Syk+/+, Syk-/- and Syk+/- embryos were stimulated with HK H. capsulatum for 6 h. TNF levels in the culture supernatants were evaluated (n = 9 from 3 independent experiments). (E) Macrophages from WT, Itgam-/-, and Clec7a-/- mice were stimulated with iC3b-LB, dZ, uncoated Latex beads (LB), or the combination of iC3b-LB and dZ. Culture supernatants were collected 6 h later and analyzed for cytokine production (n = 6 from 3 independent experiments). (F) Macrophages from WT mice were stimulated with or without iC3b-LB, dZ, LB, or the combination of iC3b-LB and dZ for 30 min. Cell lysates were subjected to Western blotting. Data are representative of 3 independent experiment with similar results. The bars represent the mean ± SD. In (A),* represent comparisons with WT and # with Itgam-/-Clec7a-/-. * or # p ≦ 0.05, ** or ## p ≦ 0.01, *** or ### p ≦ 0.001. NS, not significant [one-way ANOVA with Tukey post-hoc test analysis (A, B, D and E); 2-tailed t-test (C and G)].
To verify the nature of collaboration between receptors, specific particulate ligands for CR3 (iC3b-coated bead) and Dectin-1 (depleted zymosan) were used to stimulate cells. iC3b-coated beads, but not uncoated beads, and depleted zymosan additively induced TNF and IL-6 production in WT macrophages while Itgam-/- macrophages did not respond to stimulation by iC3b-coated beads neither did Clec7a-/- macrophages to depleted zymosan (Figs 1E and S7A). Co-stimulation of macrophages with iC3b-coated beads and depleted zymosan enhanced the level of phosphorylated Syk compared to stimulation by either ligand alone (Figs 1F and S7B) and treatment with Syk inhibitors abolished TNF and IL-6 response induced by these two ligands (Fig 1G). These data collectively reveal that Syk is the point where signals from CR3 and Dectin-1 converge to mediate collaborative cytokine response.
CR3 and Dectin-1 clustering on lipid rafts facilitates their coordinated actions
It has been demonstrated that localization of Dectin-1 and CR3 to lipid raft microdomains is critical for signaling activation of each respective receptor [30, 31]. While both CR3 and Dectin-1 diffusely distributed in the cytosol and on cell membrane in unstimulated macrophages, they were recruited and colocalized on lipid raft microdomains at the interface between macrophage and H. capsulatum yeasts upon stimulation (Fig 2A). Isolation of lipid rafts by sucrose gradient confirmed that CR3 and Dectin-1 translocated to flotillin-1-enriched membrane microdomains (Fig 2B). Stimulating macrophages with H. capsulatum induced the phosphorylation of Syk which was associated with lipid raft microdomains (Fig 2C). It is noted that Syk was present in the lipid raft fractions on H. capsulatum-stimulated as well as on unstimulated cells, suggesting that rather than recruitment, H. capsulatum stimulation triggers phosphorylation of Syk that was already present on lipid rafts (S8A and S8B Fig). Disruption of lipid rafts by methyl-β-cyclodextrin (MβCD) significantly reduced TNF and IL-6 production and cholesterol replenishment rescued the ability to produce TNF but not IL-6 (Fig 2D). H. capsulatum-induced Syk phosphorylation was diminished in cells treated with MβCD and it was partially restored by cholesterol replenishment (Fig 2E). These results demonstrate that activated Syk is associated with lipid raft microdomains where CR3 and Dectin-1 cluster and the integrity of lipid rafts is important to macrophage cytokine response and signaling activation induced by H. capsulatum.
Clustering of CR3 and Dectin-1 on lipid rafts is required for their collaboration in cytokine production and signaling activation.
Fig. 2. Clustering of CR3 and Dectin-1 on lipid rafts is required for their collaboration in cytokine production and signaling activation.
(A and C) Macrophages were stimulated with or without (0 min) HK H. capsulatum for 15 or 30 min. Cells were fixed and stained for CR3 (red) and Dectin-1 (green) (A), or for p-Syk (green) (C). Cells were viewed under confocal microscope. Lipid raft was identified by staining with cholera toxin B (CTB) (violet). Nuclear compartment was stained by DAPI (blue). Arrowheads in the DIC/DAPI fields point to H. capsulatum yeasts. The intensity of different fluorochromes along the white arrow in the merged images is shown in the histogram on the right. (B) Macrophages from WT mice were stimulated with or without (control) HK H. capsulatum for 30 min. Cell lysates were subjected to sucrose gradient ultracentrifugation. The fractions were collected and subjected to Western blotting and probed with anti-CD11b, anti-Dectin-1 and anti-flotillin-1 antibodies. (D and E) Macrophages were untreated or treated with methyl-β-cyclodextrin (MβCD, 10 mM) for 30 min. To reconstitute cholesterol, MβCD-treated cells were cultured in medium containing water-soluble cholesterol (MβCD-CHO, 400 μg/ml) for 1 h. After washing, macrophages were stimulated with HK H. capsulatum for 6 h (D), or 30 min (E). The concentrations of TNF and IL-6 in culture supernatants were analyzed by ELISA. Mean ± SD are shown (n = 10 from 4 independent experiments) (D). Cell lysates were analyzed by Western blotting by using antibodies against p-Syk, Syk, and β-actin. Data are representative of 2 (A and C) and 3 (B and E) independent experiments with similar results. ** p ≦ 0.01, *** p ≦ 0.001. NS, not significant [one-way ANOVA with Tukey post-hoc analysis (D)].
Micro-Western Array analysis reveals the signaling pathways activated by H. capsulatum
We used Micro-Western Arrays (MWAs) by employing 92 antibodies to probe for phosphorylated (84 antibodies) and non-phosphorylated (8 antibodies) signaling proteins known to be involved in the pathways downstream of PRRs for phagocytosis and cytokine production to screen for signaling molecules activated by H. capsulatum (S9 Fig and S1 Table). The heat map shows that H. capsulatum induced phosphorylation of Syk, Raf-1, PLCγ2, PKC and molecules in the PI3K/Akt, NF-κB, and MAPK pathways at as early as 15 min and c-Jun and c-Fos (two components of AP-1) at 60 min after stimulation (Figs 3A and S9). Activated signaling molecules were validated by conventional Western blot analysis. Consistent with the MWA data, H. capsulatum stimulation caused the increase of phosphorylated Syk, Akt, Raf-1, JNK, ERK, p38, IKKα/IKKβ, IκBα and NF-κBp65 at 15 min, while phosphorylation of c-Jun and c-Fos occurred at 60 min after stimulation (Fig 3B). However, the amount of phosphorylated PLCγ2 and PKC isoforms (PKCε, PKCη, PKCθ) were below the limit of detection. Taken together, our data show that H. capsulatum stimulation leads to activation of Syk, Raf-1, AP-1, as well as molecules involved in the Akt/PI3K, NF-κB and MAPK pathways.
Micro-Western Array to screen for signaling molecules involved in <i>H</i>. <i>capsulatum</i>-induced macrophage response.
Fig. 3. Micro-Western Array to screen for signaling molecules involved in H. capsulatum-induced macrophage response.
Macrophages from WT mice were stimulated with or without (0 min) HK H. capsulatum for 15, 30, 60, 90, and 120 min. (A) Heat map chart shows MWA results. Protein abundance was normalized against the mean of β-actin and GAPDH. Black color indicates no change, while red and green indicate increase and decrease, respectively, of the levels of protein compared to unstimulated control. Proteins below the level of detection are in grey. (B) Cell lysates were subjected to Western blotting. Beta-actin was used as an internal control. Data shown are representative of 3 independent experiments with similar results.
JNK is involved in the crosstalk between CR3 and Dectin-1
We used pharmacological kinase inhibitors to identify the signaling molecule(s) that participates in macrophage cytokine response to H. capsulatum. Treatment with PI3K, JNK and ERK inhibitors greatly diminished TNF and IL-6 production, yet inhibiting Raf-1 enhanced TNF and IL-6 responses (Fig 4A). Interestingly, p38 inhibitor had disparate effects on TNF and IL-6 production (Fig 4A). LDH assay showed that pharmacological inhibitors at the concentrations we used did not have cytotoxic effect on the cells (S6 Fig). Interestingly, Syk deficiency abrogated phosphorylation of Raf-1 and JNK but not that of Akt, ERK or p38 (Fig 4B) although inhibiting their activation diminished TNF and IL-6 production (Fig 4A). Results in Fig 4C show that inhibition of JNK activation in cells stimulated with iC3b-coated beads and depleted zymosan significantly reduced TNF and IL-6 production yet inhibition of Raf-1 did not affect the production of either cytokine. These results indicate that JNK, a signaling molecule downstream of Syk, plays an important role in the coordinated CR3 and Dectin-1cytokine response.
CR3 and Dectin-1 collaborate to enhance JNK activation.
Fig. 4. CR3 and Dectin-1 collaborate to enhance JNK activation.
(A and C) Macrophages from WT mice were treated with vehicle (control) or different kinase inhibitors (PI3K inhibitor, LY294002 20 μM; Raf-1inhibitor, GW5074 1 μM; JNK inhibitor, SP600125 20 μM; ERK inhibitor, U0126 20 μM; p38 inhibitor, SP203580 20 μM) for 1 h prior to stimulation with HK H. capsulatum (A) or with the combination of iC3b-LB and dZ (C). Culture supernatants were collected 6 h later and the levels of TNF and IL-6 were quantified by ELISA. Mean ± SD of the relative (A) or absolute cytokine levels (C) of TNF and IL-6 are shown. [n = 5 from 3 independent experiments (A); n = 5 from 2 independent experiments (C)]. (B) FLDMs from Syk+/+, Syk-/- and Syk+/- embryos were stimulated with or without (0 min) HK H. capsulatum for 30 or 60 min. Cell lysates were subjected to Western blotting. (D) Macrophages from WT, Itgam-/-, Clec7a-/- and Itgam-/-Clec7a-/- mice were stimulated with or without (0 min) HK H. capsulatum for 30 min. Cell lysates were analyzed by Western blotting with the use of antibodies against p-JNK and JNK. (E) Macrophages from WT mice were treated with isotype control or blocking antibodies against CR3, Dectin-1, or both for 1 h before stimulation with HK H. capsulatum. Cell lysates were collected 30 min later and subjected to Western blotting. (F and G) Macrophages from WT (F) and Itgam-/- and Clec7a-/- (G) mice were stimulated with or without iC3b-LB, dZ, LB, or the combination of iC3b-LB and dZ for 30 min. Cell lysates were collected at 30 min after stimulation and subjected to Western blotting analysis. Data are representative of at least 3 independent experiments with similar results (B and D-G). * p ≦ 0.05, ** p ≦ 0.01, *** p ≦ 0.001. NS, not significant [2-tailed t-test (A and C)].
We next investigated the link between CR3 and Dectin-1 engagement and JNK activation. Results showed that JNK phosphorylation was reduced to about 50% of WT control in macrophages lacking either receptor across all time points after stimulation with heat-killed or viable H. capsulatum and JNK phosphorylation was almost completely abolished in Itgam-/-Clec7a-/- macrophages (Figs 4D, S3C and S5B). Similarly, blocking either receptor reduced JNK phosphorylation and blocking both receptors reduced JNK phosphorylation even further (Fig 4E). Stimulation of WT macrophages with both iC3b-coated beads and depleted zymosan increased the level of JNK phosphorylation compared to stimulation with either ligand alone (Fig 4F) and the additive effect of these two ligands was diminished in macrophages deficient in either receptor (Fig 4G). Taken together, our results show that engagement of CR3 and Dectin-1 separately induces JNK phosphorylation and engagement of both have an additive effect on JNK activation which is downstream of Syk.
AP-1 mediates the collaborative cytokine response upon CR3 and Dectin-1 engagement
Results in Fig 3 show that stimulation of macrophages with H. capsulatum triggered the activation of both NF-κB and AP-1. To identify whether NF-κB or AP-1 mediates the collaboration between CR3 and Dectin-1 for cytokine production, we first clarified whether they were activated in Syk-/- macrophages. Fig 5A shows that H. capsulatum-induced c-Fos and c-Jun phosphorylation was greatly diminished in Syk-/- macrophages while IκBα phosphorylation and degradation was not affected, indicating that AP-1, but not NF-κB, is the transcription factor downstream of Syk. In addition, while IκBα and NF-κBp65 phosphorylation was not affected in single and double knockout macrophages, activation of c-Fos and c-Jun was dampened in Itgam-/- and Clec7a-/- macrophages and almost completely abolished in Itgam-/-Clec7a-/- macrophages (Figs 5B, 5C, S3D and S5C). Stimulation of WT macrophages with iC3b-coated beads and depleted zymosan together had an additive effect over stimulation with either one alone on c-Jun and c-Fos but not NF-κB activation (Fig 5D and 5E). The additive effect was abolished in single knockout macrophages (Fig 5F). When c-Jun and c-Fos were silenced by respective siRNA separately, TNF and IL-6 production was greatly reduced (Fig 5G and 5H). Together these data show that AP-1, but not NF-κB, is the transcription factor that mediates the collaborative cytokine response induced by CR3 and Dectin-1.
AP-1, but not NF-κB, mediates the collaborative cytokine response upon CR3 and Dectin-1 ligation.
Fig. 5. AP-1, but not NF-κB, mediates the collaborative cytokine response upon CR3 and Dectin-1 ligation.
FLDMs from Syk+/+, Syk-/- and Syk+/- embryos (A) and macrophages from WT, Itgam-/-, Clec7a-/- and Itgam-/-Clec7a-/- mice (B and C) were stimulated with or without (0 min) HK H. capsulatum for 30 and 60 min. Cell lysates were analyzed by Western blotting. The blot shown in (A) is the same one shown in Fig 4B. Macrophages from WT mice (D and E), and Itgam-/- and Clec7a-/- mice (F) were stimulated with or without iC3b-LB, dZ, LB, or the combination of iC3b-LB and dZ for 30 min (E) or 60 min (D and F). Cell lysates were analyzed by Western blotting. Data are representative of at least 3 independent experiments (A-F). (G and H) Macrophages from WT mice were transfected with small interfering RNA (siRNA) against c-Fos or c-Jun, followed by stimulation with HK H. capsulatum 48 h later. Cell lysates and culture supernatants were collected at 6 h after stimulation. Silencing of c-Fos and c-Jun was confirmed by Western blotting (G). TNF and IL-6 levels in culture supernatants were quantified by ELISA and are presented as the mean ± SD of relative levels of TNF and IL-6 (n = 3 from 3 independent experiments) (H). ** p ≦ 0.01, *** p ≦ 0.001 [2-tailed t-test].
CR3 and Dectin-1 concert in host defense against H. capsulatum infection
We employed disseminated histoplasmosis model, which is characterized by splenomegaly with large numbers of macrophages infiltrating the spleen, to investigate the contribution of CR3 and Dectin-1 in host defense against H. capsulatum infection [32]. WT, Itgam-/-, Clec7a-/- and Itgam-/-Clec7a-/- mice were intravenously infected with a low sublethal dose of H. capsulatum (2.5 × 105). While the fungal loads in Itgam-/- and Clec7a-/- single knockout mice were comparable to (Itgam-/-) or slightly higher than (Clec7a-/-) WT mice, that in double knockout mice were significantly higher than either of the single knockout mice on 7 days after infection (Fig 6A). Accompanying higher fungal loads, TNF, IFN-γ and IL-17 levels in splenocyte cultures of double knockout mice were lower than in either of the single knockout mice and IL-6 levels were lower than in Clec7a-/- mice (Fig 6B). Interestingly, the percentages of IFN-γ-producing CD4+ and CD8+ cells were significantly reduced in Itgam-/- and Clec7a-/- mice compared to WT mice, and they were reduced even further in double knockout mice (Fig 6C). Consistent with in vivo IFN-γ response, Itgam-/-, Clec7a-/- and Itgam-/-Clec7a-/- dendritic cells stimulated with H. capsulatum produced significantly less IL-12p35 transcripts and IL-12p40 transcripts was reduced in Itgam-/-Clec7a-/- dendritic cells compared to WT cells (S10A and S10B Fig). These results together reveal that CR3 and Dectin-1 act in concert in instruction host adaptive immunity against H. capsulatum.
CR3 and Dectin-1 coordinately orchestrate host defense against <i>H</i>. <i>capsulatum</i> infection.
Fig. 6. CR3 and Dectin-1 coordinately orchestrate host defense against H. capsulatum infection.
(A-C) WT, Itgam-/-, Clec7a-/-, and Itgam-/-Clec7a-/- mice were infected with 2.5 × 105 H. capsulatum intravenously. Infected mice were killed on day 7 after infection. (A) Spleen fungal burdens are shown as CFU per spleen. Data were pooled from 3 independent experiments. Each symbol represents one individual mouse. (B) Splenocytes were cultured for 48 h and the levels of TNF, IL-6, IL-17A and IFN-γ in the supernatants were quantified by ELISA. (C) Splenocytes were cultured for 24 h and stained for surface CD4 and CD8, and intracellular IFN-γ. Cells were analyzed by flow cytometry. Bar graphs show the percentage of IFN-γ + CD4+ and IFN-γ + CD8+ cells in total CD4+ and CD8+ T cell populations. Mean ± SD are shown (n = 6 from 3 independent experiments) (B and C). (D-G) WT, Itgam-/-, Clec7a-/-, and Itgam-/-Clec7a-/- mice were infected with 5 × 106 H. capsulatum intravenously. Survival of infected mice is expressed as a Kaplan-Meier plot (D). Infected mice were killed on day 9 after infection (E-G). (E) The fungal burdens in the spleen and lung are shown as CFU per organ. (F) The total number of cells in the spleen was enumerated. (G) The percentage and the number of F4/80+ cells was analyzed by flow cytometry. Mean ± SD are shown (n = 3-4). * p ≦ 0.05, ** p ≦ 0.01, *** p ≦ 0.001 [one-way ANOVA with Duncan post-hoc analysis was used in data presented in (A-C and E-G); Generalized Wilcoxon test was used for data in (D)].
Infection with a higher dose of H. capsulatum (5 × 106), Itgam-/-Clec7a-/- mice had significantly greater fungal burden, higher mortality and succumbed at an earlier time point (10 to14 days) compared to Itgam-/-, Clec7a-/- or WT mice (Fig 6D and 6E). The number of total splenocytes in infected mice was significantly lower in Itgam-/-Clec7a-/- compared to either WT or single knockout mice (Fig 6F). Impressively, infection greatly reduced the proportion and number of F4/80+ cell population in Itgam-/-Clec7a-/- mice, which was significantly lower than in either of the single knockout mice and WT mice (Fig 6G and also refer to S11A and S11B Fig). These results suggest that macrophages in Itgam-/-Clec7a-/- mice fail to respond to H. capsulatum infection and/or rapidly undergo apoptosis. Macrophages being the major player in the interaction between the host and the fungal pathogen H. capsulatum, deficiency in innate receptors that recognize the pathogen for phagocytosis (CR3) and proinflammatory cytokine production (CR3 and Dectin-1) [13] greatly affects host defense against this pathogen. Furthermore, these two innate receptors CR3 and Dectin-1, collaboratively function not only in innate immune response but also orchestrate adaptive immune response against disseminated histoplasmosis.
Discussion
Recognition of invading pathogens by PRRs triggers innate immune responses and shapes the adaptive immunity. Fungal cell wall is complex in its composition which varies between species, strains, and morphological forms. Innate immune cells use a unique set of PRRs to recognize and respond to a given fungus. Therefore, there is a lot of interest to dissect the molecular mechanism of coordination between heterogeneous PRRs. In the present study, we showed that CR3 and Dectin-1 collaborate in regulating macrophage pro-inflammatory cytokine response. Engagement of CR3 and Dectin-1 induces their clustering on lipid raft microdomains which function as a platform for downstream signaling. Utilizing MWA, genetic approach and pharmacological inhibitors, we demonstrated that receptor crosstalk between CR3 and Dectin-1 enhances the activation of their downstream Syk-JNK-AP-1 signaling pathway. Furthermore, our results showed that CR3 and Dectin-1 both participate and function cooperatively in host defense against H. capsulatum by facilitating adaptive antifungal immunity.
The pathogenic fungus H. capsulatum is assorted to chemotype I and II based on the absence and presence of α-(1,3)-glucan in the yeast cell wall [4]. H. capsulatum strain 505 we used in this study having its β-(1,3)-glucan readily exposed does not express α-(1,3)-glucan on the yeast cell surface which makes it likely to be assorted to chemotype I (S12A Fig). Rappleye et al. showed that H. capsulatum yeast strain G186A AGS (+) expressing α-(1,3)-glucan on the outer cell wall layer (S12B Fig) is not recognized by Dectin-1 [33]. The isogenic strain ags1-null mutant lacking α-(1,3)-glucan is recognized by Dectin-1-expressing cells and induces TNF production in phagocytic cells [33]. We showed in a previous study and here that strain 505 induces macrophage TNF and IL-6 production through both CR3 and Dectin-1, a phenomenon possibly unique to H. capsulatum that classified as chemotype I [13]. Interestingly, unlike what is reported in C. albicans [34], heat treatment does not alter β-glucan expression on H. capsulatum strain 505 (S12A and S12C Fig). We also discovered that Syk-JNK-AP-1 signaling and TNF and IL-6 production triggered by heat-killed H. capsulatum are comparable to that induced by viable organism.
In the case of PRR crosstalk, previous studies showed that Syk is required for the synergy between TLR and Dectin-1 and acts as the convergence point of Dectin-1 and Dectin-2 signaling, both of which situations lead to NF-κB activation [7, 9, 12, 35]. We demonstrated here that signaling crosstalk between CR3 and Dectin-1 through stimulation with H. capsulatum initiates at and converges on Syk. However, unlike receptor crosstalk between TLR and Dectin-1 and that between Dectin-1 and Dectin-2, activation of Syk through CR3 and Dectin-1 does not connect to NF-κB pathway. Instead, Syk leads to activation of JNK and AP-1. Consistent with H. capsulatum stimulation, co-stimulation with iC3b-coated beads and depleted zymosan enhances activation of Syk, JNK and AP-1, but not NF-κB. Our findings clearly define Syk-JNK-AP-1 axis as the signaling pathway downstream of the collaborative interaction between CR3 and Dectin-1.
CR3 is unique among the members of β2 integrin family that it contains two ligand binding sites, I domain and lectin-like domain. Single or dual ligation of I domain and lectin-like domain in CR3 triggers disparate signaling pathways and cellular responses [15, 17]. We have previously shown that CR3 recognizes H. capsulatum through both I domain and lectin-like domain within CD11b, demonstrating that H. capsulatum mediates dual CR3 ligation [13]. Here we observed that stimulation of macrophages with iC3b-coated beads (single CR3 ligation of I domain) does not induce Syk phosphorylation, while co-stimulation with iC3b-coated beads and depleted zymosan (dual CR3 ligation and Dectin-1 ligation) triggers Syk phosphorylation and the level of phosphorylation is greater than stimulation by depleted zymosan alone (single CR3 ligation of lectin-like domain and Dectin-1ligation). Interestingly, stimulating Clec7a-/- macrophages with both iC3b-coated beads and depleted zymosan only minimally activates Syk. The lack of inside-out signaling provided by Dectin-1 may account for the failure for iC3b-coated beads and depleted zymosan to activate CR3 [19]. Together, our results show that dual ligation of CR3 optimizes the signaling synergy induced by simultaneous engagement of CR3 and Dectin-1. An early study showed that H. capsulatum yeasts activate the alternative complement pathway which may lead to iC3b deposition [36]. Although CR3 can directly recognize and respond to H. capsulatum, whether complement opsonization would enhance the collaboration between CR3 and Dectin-1 or change PRR usage in macrophage interaction with H. capsulatum needs to be investigated.
PRR clustering in membrane lipid microdomains is crucial for host cells to optimize detection of fungal pathogens by formation of phagocytic synapse and serving as a platform for signaling synergy [31, 37, 38]. In this study, we show that the spatial nearness of CR3 and Dectin-1 and that both of them being mobilized to and associated with lipid rafts are important to achieve their collaboration upon engagement with H. capsulatum. However, little is known about how PRRs are recruited to lipid rafts and how signaling crosstalk is induced by heterogeneous PRRs. It has been reported that intracellular osteopontin (iOPN) is essential for clustering of heterologous PRRs, including Dectin-1, TLR2 and mannose receptor, that recognize Pneumocystis [38]. In addition, iOPN is involved in Dectin-1 and TLR2 downstream signaling by acting as a scaffold protein which associates with their respective downstream molecule Syk and IRAK1 [38]. It remains to be answered whether the steric assembly and the signaling synergy of CR3 and Dectin-1 induced by H. capsulatum is also mediated by iOPN, or by other adaptor molecule(s).
Macrophage plays multiple roles in host defense against H. capsulatum. Besides being a host cell, it also functions as cytokine/chemokine-producing cell and antigen donor cell, and it serves as effector cell when stimulated with IFN-γ, IL-17 and GM-CSF [3942]. However, little is known about the signaling pathways downstream of functional receptors after macrophage encountering H. capsulatum. By MWA, this study is the first to uncover signaling pathways activated by H. capsulatum in macrophages. Our results reveal that PI3K, NF-κB, MAPK and AP-1 signaling pathways are activated by H. capsulatum. It is interesting to note that although PI3K, ERK and p38 activities modulate TNF and IL-6 production, they do not function downstream of Syk. In addition, inhibition of NF-κB does not affect H. capsulatum-induced TNF and IL-6 responses (S13 Fig). Thus, we postulate that other pathways may act in parallel with Syk-JNK-AP-1 pathway to regulate H. capsulatum-induced TNF and IL-6 response in macrophages.
We show that H. capsulatum induces Raf-1 activation in a Syk-dependent manner. Inhibition of Raf-1 increases H. capsulatum-induced TNF and IL-6 production. Our results define Raf-1 as a negative regulator in macrophage cytokine response to H. capsulatum. A previous study showed that Dectin-1 induces Raf-1 activation in a Syk-independent manner [26]. Activated Raf-1 antagonizes Syk-dependent non-canonical NF-κB activation by promoting inactive p65/RelB dimer formation [26]. Ligation of DC-SIGN activates Raf-1 which downregulates Borrelia burgdorferi- and TLR-induced TNF and IL-6 response by destabilizing their mRNAs and suppresses IL-12 response by impairing nucleosome remodeling at IL-12p35 promoter [43]. Together, these data suggest that activation of Raf-1 by ligation of PRRs negatively regulates and fine-tunes innate immune response. More studies are needed to demonstrate how Raf-1 negatively regulates H. capsulatum-induced TNF and IL-6 production.
There are only limited studies on the role of AP-1 in PRR crosstalk and in host defense against fungal infections. It has been shown that TLR2 and Dectin-1 cooperatively regulate zymosan-induced IL-10 production in DCs through an ERK-dependent, but AP-1-independent mechanism [44]. Other reports showed that Dectin-1 engagement in DCs triggers AP-1 activation, while curdlan stimulates a PLCγ2-dependent pathway, β-glucan on Aspergillus fumigatus activates a Syk-dependent pathway [22, 45, 46]. Our results demonstrate that CR3 acts in concert with Dectin-1 to activate both c-Jun and c-Fos. In addition, knocking down c-Jun and c-Fos in macrophages decreases H. capsulatum-induced TNF and IL-6 response, highlighting the role of AP-1 in host defense against fungal infections. Our MWA data show that PLCγ2 is activated by H. capsulatum. However, whether PLCγ2 is involved in CR3/Dectin-1-mediated AP-1 activation still remains to be determined. It is interesting to note that AP-1 activation is known to be associated with several disorders (ex. cancer and autoimmune diseases) by regulating genes involved in cell proliferation, angiogenesis and inflammation and inhibition of AP-1 activation is identified as a promising therapeutic strategy [4749]. Our findings raise the possibility that administration of AP-1 inhibitor may increase susceptibility to fungal infections by suppressing proinflammatory cytokine production. Thus, AP-1inhibitor should be used with caution as a treatment modality for cancer and inflammatory disorder.
In addition to acting as a PRR to interact with pathogens, CR3 plays multiple roles in cellular processes including leukocyte extravasation, adhesion and chemotaxis [17]. This adds to the complexity of experimental design in addressing the role of CR3 in vivo. Intranasal or intraperitoneal infection of Itgam-/- mice with S. pneumonia results in infiltration of a large number of neutrophils to the infection sites [50, 51]. Neutrophil recruitment to the peritoneum is reduced in mice lacking CR3 after intraperitoneally challenge with C. albicans, yet accumulation of neutrophils in the kidney is comparable between WT and CR3-deficient mice intravenously infected with C. albicans [19, 52]. These studies demonstrated that abnormal neutrophil infiltration to the infection site should be considered as a factor influencing susceptibility in in vivo studies employing Itgam-/- mice. Indeed, we observed that unlike in WT mice, there is massive neutrophil infiltration to the lungs of Itgam-/- mice after intratracheal infection with H. capsulatum, a condition which may interfere the interaction between macrophages and the yeasts (S14A and S14B Fig). By contrast, the percentage and the number of neutrophils recruited to the spleen of Itgam-/- mice were commensurate with that in WT mice after intravenous inoculation of H. capsulatum. To focus on the roles of CR3 and Dectin-1 in macrophage interaction with H. capsulatum, we resorted to employ the disseminated histoplasmosis model by intravenous inoculation of the organism instead of pulmonary infection.
PRR signaling is known to act as a bridge that links innate and adaptive immunity. Signaling transduced by Dectin-1 can induce Th1 and Th17 responses [53] as well as priming cytotoxic T cells [54]. In addition, it has been reported that blockade of CR3 significantly reduces the Th1 and Th17 responses induced by A. fumigatus [55]. H. capsulatum infection triggers IFN-γ and IL-17 production by both CD4+ and CD8+ T cells, and both IFN-γ and IL-17 activate macrophages for inhibition of the replication of intracellular H. capsulatum [39, 41, 56, 57]. Mice deficient in IFN-γ or treated with neutralizing antibody against IFN-γ or IL-17 are more susceptible to H. capsulatum, showing the importance of IFN-γ and IL-17 in clearing this intracellular fungal pathogen [5759]. However, whether and how PRRs participate in the development of H. capsulatum-induced IFN-γ and IL-17 response remains unclear. In this study, we show that both CR3 and Dectin-1 contribute to and function collaboratively in regulating TNF, IL-6, IL-17 and IFN-γ responses induced by H. capsulatum. TNF is a critical factor for the host to control H. capsulatum, and acts together with IFN-γ and IL-17 to provide protection [57, 60]. Although the role of IL-6 in histoplasomsis has not been well addressed, previous studies showed that the generation of H. capsulatum-induced IL-17 response is dependent on IL-6 and IL-6 deficiency leads to impairment of Th1 response in mice infected with C. albicans or A. fumigatus [57, 61, 62]. Our results also showed that, in addition to regulate macrophage TNF and IL-6 production, both CR3 and Dectin-1 are involved in IL-12 response in dendritic cells, suggesting the role of these receptors in regulating dendritic cells cannot be ignored. Moreover, our in vitro study showed that deficiency in either CR3 or Dectin-1 or both did not affect the intracellular growth of H. capsulatum in macrophages, strengthening the possibility that CR3 and Dectin-1 deficiency resulting in susceptibility to disseminated H. capsulatum infection is due to their roles in regulating IFN-γ and IL-17 responses. It is interesting to note that macrophages in the spleens of Itgam-/-Clec7a-/- mice were greatly diminished (almost exhausted) after infection with a lethal dose of H. capsulatum, presenting a picture that the macrophages are losing the battle to the fungal pathogen. While dendritic cells are major antigen-presenting cells and macrophage are the host, cytokine-producing cell and effector cell in infection by H. capsulatum, our study reveals that CR3 and Dectin-1 are of vital importance not only in their collaborative roles in macrophage cytokine production but also in instructing adaptive immune response against disseminated histoplasmosis.
In summary, we demonstrate for the first time the mechanism of receptor crosstalk between a member of the integrin family and CLR resulting in enhanced cytokine response. The collaboration between CR3 and Dectin-1 is through activation of Syk-JNK-AP-1 signaling pathway and dependent on formation of PRR clusters on lipid rafts. Our results also highlight the importance of CR3 and Dectin-1 in innate recognition that instructs antifungal adaptive immune response. Collectively, our findings provide a better understanding of the molecular mechanisms underlying the collaboration between CR3 and Dectin-1 and offer a valuable model for disentangling the intricacies of host-pathogen interactions.
Materials and Methods
Ethics statement
All animal experiments were undertaken in accordance with the Guidebook for the Care and Use of Laboratory Animals, 3rd Ed., 2007, published by The Chinese-Taipei Society of Laboratory Animal Sciences, approved by the Institutional Animal Care and Use Committee (IACUC, Permit number: 20130231) of National Taiwan University College of Medicine.
Fungus
Histoplasma capsulatum (Hc) strain 505 yeast cells were used in the whole study. Yeast cells were cultured at 37°C on brain heart infusion (BHI) agar supplemented with 1 mg/ml cysteine and 20 mg/ml glucose. Heat-killed yeast cells were prepared by treatment at 65°C for 2 h. To examine the surface expression of α-glucan and β-glucan, viable or heat-killed yeasts were fixed with 4% paraformaldehyde and stained with antibodies against α-(1,3)-glucan (Clone MOPC-104E) (Biolegend, San Diego, CA, USA) and β-(1,3)-glucan (Biosupplies, Parkville, Australia) followed by analysis with flow cytometry (BD FACSCanto II, BD Biosciences).
Mice
Itgam-/- (Stock number: 003991) and wild-type C57BL/6 (Stock number: 000664) mice were originally purchased from the Jackson Laboratories (Bar Harbor, ME, USA) and Clec7a-/- mice were generated by Dr. Gordon D. Brown [63]. Itgam-/-Clec7a-/- mice were generated by crossing Itgam-/- and Clec7a-/- mice. Mice heterozygous for a deletion in the Syk locus (Syk+/-) were obtained from Dr. Clifford Lowell (University of California, San Francisco, CA, USA) [64]. All strains used in this study were on C57BL/6 background. They were maintained and bred in the National Taiwan University College of Medicine Laboratory Animal Center (NTU CMLAC) or in the National Laboratory Animal Center (NLAC, Taiwan) under specific pathogen-free (SPF) conditions. In vivo infection experiments were performed following biosafety level 2 (BSL-2) guidelines.
Cells
Peritoneal macrophages were collected by lavage from mice at 4 days after peritoneal injection of 1 ml of 3% thioglycollate medium (Sigma-Aldrich, St Louis, MO, USA). Macrophages deficient in Syk were derived from fetal liver cells obtained from Syk-/- mouse embryos (E13.5-E15.5). Syk-/- embryos were separated from Syk+/+ and Syk+/- embryos by their exhibition of severe petechiae and confirmed by genotyping [65]. Single-cell suspensions from fetal liver tissues were cultured in 20% L929-cell conditioned medium for 7 days. Over 95% of the adherent cells were F4/80+ which were identified as fetal liver-derived macrophages (FLDMs).
Reagents and antibodies
Syk inhibitors SykI and BAY 61-3606, PI3K inhibitor LY294002, ERK inhibitor U0126, JNK inhibitor SP600125, and p38 inhibitor SB203580 were purchased from Calbiochem-Merck (Darmstadt, Germany). Raf-1 inhibitor GW5074, methyl-β-cyclodextrin (MβCD), and water-soluble cholesterol were obtained from Sigma-Aldrich.
Antibodies against phospho (p)-Zap-70 (Tyr319)/Syk (Tyr352), p-Akt (Tyr308), p-c-Raf (Ser338), p-ERK1/2 (Thr202/Tyr204), p-JNK (Thr183/Tyr185), JNK, p-p38 (Thr180/Tyr182), p-IKKα/β (Ser176/180), p-NF-κBp65 (Ser536), p-IκBα (Ser32), IκBα, p-c-Jun (Ser63), c-Jun, p-c-Fos (Ser32), and c-Fos were purchased from Cell Signaling (Beverly, MA, USA). Anti-Syk, anti-β-actin, HRP-conjugated anti-rabbit IgG, and HRP-conjugated anti-mouse IgG antibodies were purchased from GeneTex Inc. (Irvine, CA, USA). Blocking antibodies against CR3 (clone 5C6) and Dectin-1 (clone 2A11) were purchased from Serotec (Oxford, UK). Antibodies for cell surface staining, anti-CD11b (clone M1/70), anti-CD18 (clone GAME-46), and APC-conjugated anti-F4/80 antibody were obtained from eBioscience (San Diego, CA, USA), and anti-Dectin-1 (clone 218820) was purchased from R&D Systems (Minneapolis, MN, USA).
Stimulation with fungus and particulate ligands
Macrophages were stimulated with viable or heat-killed H. capsulatum yeasts (at a yeast-to-macrophage ratio of 20/1) or iC3b-caoted beads (at a bead-to-cell ration of 10/1) and 50 μg/ml depleted zymosan (InvivoGen, San Diego, CA, USA).The iC3b-coated beads were prepared as described previously [66]. Briefly, 2 × 108 of 3 μm Latex beads (Sigma-Aldrich) were incubated with PBS containing 20 μg/ml human IgM (Sigma-Aldrich) at 37°C for 60 min. Beads were washed with PBS then resuspended in freshly isolated mouse serum (diluted 1:1 in PBS) and incubated at 37°C for another 20 min. Beads were washed with Hank's balanced salt solution then resupspended in RPMI 1640 medium supplemented with 10% heat-inactivated FBS. During the process, the classical pathway of complement cascade was activated, resulting in C3b deposition on the surface of beads where it was rapidly and completely converted to iC3b [67].
Cytokine assays
Macrophages were stimulated with or without H. capsulatum or particulate ligands. Culture supernatants were collected after incubation at 37°C for different periods of time. The concentrations of TNF and IL-6 in the supernatants were quantified by enzyme-linked immunosorbent assay (ELISA) kit (eBioscience) following the manufacturer’s instructions.
Western blotting
Cells were lysed by PhosphoSafe Extraction Reagent cell lysis buffer (Novagen, Madison, WI, USA). Whole cell lysates were subjected to electrophoresis at 10% sodium dodecyl sulfate polyacrylamide gel (SDS-PAGE), and transferred to PVDF membrane. The membrane was incubated in buffer containing primary antibody against molecule of interest, followed by HRP-conjugated secondary antibody. The blot was developed by chemiluminescence using ECL solution (Millipore, Billerica, MA, USA). For normalization, the intensity of blots was quantified by ImageJ software (NIH, Bethesda, MD, USA).
Isolation of lipid raft fractions
Macrophages (3 × 107) were lysed with 0.5% Brij in TNE buffer [25 mM Tris (pH 7.5), 150 mM NaCl, 5 mM EDTA, protease inhibitors, 1 mM Na3VO4, and 1 mM NaF] and let stand on ice for 1 h. Lysates were then mixed with equal volume of 80% sucrose in TNE buffer and overlaid with 30% and 5% sucrose in the same buffer. The gradients were centrifuged at 40,000 × g in a SW55Ti rotor (Beckman Coulter, Fullerton, CA, USA) at 4°C for 18 h. Twelve fractions were collected and the proteins in the fractions were subjected to electrophoresis at 10% SDS-PAGE and Western blot analysis by using antibodies against CD11b (GeneTex), Dectin-1 (Santa Cruz Biotechnology, Santa Cruz, CA, USA), Syk, p-Syk, and flotillin-1 (Cell Signaling).
Immunofluorescence staining and confocal microscopy
Macrophages were allowed to adhere on cover slide overnight and stimulated with heat-killed H. capsulatum yeasts. After stimulation, cells were fixed with 3% paraformaldehyde followed by permeabilization with 0.5% Triton X-100. Cells were blocked with PBS containing 5% heat-inactivated FBS and stained with Alexa Fluor 647-conjugated cholera toxin B (Invitrogen, Carlsbad, CA, USA), anti-p-Syk (Cell Signaling), anti-Dectin-1 (Serotec), and/or PE-conjugated anti-CD11b (eBioscience) antibodies. Cells were then stained with secondary Alexa Fluor-conjugated secondary antibodies (Jackson ImmunoResearch, West Grove, PA, USA). Cell nuclei were stained with Hoechst 33258. The images were acquired with a Zeiss Axiovert 100TV confocal microscope (Carl Zeiss Inc., Jena, Germany) and analyzed by Zen software (Carl Zeiss Inc.) and ImageJ software (NIH).
Micro-Western Arrays (MWAs)
Peritoneal macrophages were stimulated with or without heat-killed H. capsulatum. Cells were lysed at different time points, and Micro-Western Arrays (MWAs) were performed to measure protein expression as previously described [68]. Blots were analyzed by Odyssey analysis software (Li-Cor Biosciences, USA). Heat maps were created by using PermutMatrix software (LIRMM).
siRNA transfection of macrophages
Peritoneal macrophages (1 × 106) were transfected with 30 pmol of control siRNA or siRNAs targeting c-Fos or c-Jun (Santa Cruz Biotechnology) using the Amaxa Nucleofector kit for mouse macrophages (Lonza, Basel, Switzerland) with a Nucleofector II electroporation device (Lonza). After transfection, cells were gently resuspended in RPMI 1640 medium supplemented with 20% heat-inactivated FBS and plated in 12-well tissue culture plate. Adherent cells were collected for cytokine assay and Western blot analysis 48 h later.
H. capsulatum infection, fungal burden and leukocyte populations in spleen
Mice were injected intravenously with low (2.5 × 105) or high (5 × 106) dose of H. capsulatum yeasts suspended in PRMI 1640 medium. For survival studies, mice were monitored for up to 30 days. For immunological studies, mice were killed on day 7 (low dose) or day 9 (high dose) after infection. To determine the fungal burden, spleens were weighted and homogenized in sterile RPMI 1640 medium. The homogenates were serially diluted and plated on glucose-pepton agar plates. Mycelial colonies were counted 10 days after incubation as described elsewhere [40]. To determine the percentage of leukocyte populations in spleen, splenocytes were stained for surface CD4, CD8, B220, F4/80, Ly6G and CD11c and analyzed by flow cytometry. All antibodies were purchased from eBioscience.
Ex vivo cytokine production and intracellular cytokine staining
To study cytokine production by splenocytes, single cell suspensions were prepared from the spleen. Five million splenocytes were cultured in RPMI 1640 complete medium containing 400 pg/ml of rIL-2 for 48 h. The concentrations of TNF, IL-6, IL-17A and IFN-γ in the culture supernatants were quantified by ELISA. To analyze intracellular IFN-γ, 1 × 106 splenocytes were cultured in RPMI 1640 complete medium for 24 h and monensin (2 μM, Sigma-Aldrich) was added at 6 h before harvest. Cells were stained with anti-CD4, anti-CD8 and anti-IFN-γ antibodies as described previously [40]. The percentage of IFN-γ-producing cells in the total CD4+ or CD8+ T cell populations was calculated by dividing the % of IFN-γ+CD4+ cells or IFN-γ+CD8+ by the % of CD4+ or CD8+ cells. All antibodies were purchased from eBioscience.
Statistics
The comparisons between multiple groups were analyzed with one-way ANOVA followed by Tukey post-hoc test or by Duncan post-hoc analysis using SPSS 22.0 statistical software (IBM, Armonk, NY, USA). The differences between two groups were tested by two-tailed t-test. Generalized Wilcoxon test was used to analyze mouse survival. Differences were considered significant at a P value of < 0.05.
Accession numbers
The accession numbers in the UniPortKB/SwissProt database of the proteins mentioned in this study are followed: CD11b, P05555; CD18, P11835; Dectin-1, Q6QLQ4; Syk, P43404; JNK, Q91Y86 (JNK1) and Q9WTU6 (JNK2); c-Fos, P01101; c-Jun, P05627; Raf-1, Q99N57; PLCγ2, Q8CIH5; Akt, P31750; ERK, Q63844 (ERK1) and P63085 (ERK2); p38, P47811; IKKα, Q60680; IKKβ, O88351; IκBα, Q9Z1E3; NF-κBp65, Q04207; PKCε, P16054; PKCη, P23298; PKCθ, Q02111; β-actin, P60710; GAPDH, P16858; flotillin-1, O08917; TNF, P06804; IL-6, P08505; IL-12p35, P43431; IL-12p40, P43432; IL-17A, Q62386; IFN-γ, P01580.
Supporting Information
Attachment 1
Attachment 2
Attachment 3
Attachment 4
Attachment 5
Attachment 6
Attachment 7
Attachment 8
Attachment 9
Attachment 10
Attachment 11
Attachment 12
Attachment 13
Attachment 14
Attachment 15
Zdroje
1. Brown GD, Denning DW, Levitz SM. Tackling human fungal infections. Science. 2012;336(6082):647. doi: 10.1126/science.1222236 22582229.
2. Gordon S. Pattern recognition receptors: doubling up for the innate immune response. Cell. 2002;111(7):927–30. 12507420.
3. Brown GD. Innate antifungal immunity: the key role of phagocytes. Annu Rev Immunol. 2011;29:1–21. doi: 10.1146/annurev-immunol-030409-101229 20936972.
4. Guimaraes AJ, de Cerqueira MD, Nosanchuk JD. Surface architecture of Histoplasma capsulatum. Front Microbiol. 2011;2:225. doi: 10.3389/fmicb.2011.00225 22121356.
5. Smits GJ, Kapteyn JC, van den Ende H, Klis FM. Cell wall dynamics in yeast. Curr Opin Microbiol. 1999;2(4):348–52. 10458981.
6. Hontelez S, Sanecka A, Netea MG, van Spriel AB, Adema GJ. Molecular view on PRR cross-talk in antifungal immunity. Cell Microbiol 2012;14(4):467–74. doi: 10.1111/j.1462-5822.2012.01748.x 22233321.
7. Gantner BN, Simmons RM, Canavera SJ, Akira S, Underhill DM. Collaborative induction of inflammatory responses by dectin-1 and Toll-like receptor 2. J Exp Med. 2003;197(9):1107–17. doi: 10.1084/jem.20021787 12719479.
8. Brown GD, Herre J, Williams DL, Willment JA, Marshall AS, Gordon S. Dectin-1 mediates the biological effects of beta-glucans. J Exp Med. 2003;197(9):1119–24. doi: 10.1084/jem.20021890 12719478.
9. Dennehy KM, Ferwerda G, Faro-Trindade I, Pyz E, Willment JA, Taylor PR, et al. Syk kinase is required for collaborative cytokine production induced through Dectin-1 and Toll-like receptors. Eur J Immunol. 2008;38(2):500–6. doi: 10.1002/eji.200737741 18200499.
10. Ferwerda G, Meyer-Wentrup F, Kullberg B-J, Netea MG, Adema GJ. Dectin-1 synergizes with TLR2 and TLR4 for cytokine production in human primary monocytes and macrophages. Cell Microbiol. 2008;10(10):2058–66. doi: 10.1111/j.1462-5822.2008.01188.x 18549457.
11. Takahara K, Tokieda S, Nagaoka K, Takeda T, Kimura Y, Inaba K. C-type lectin SIGNR1 enhances cellular oxidative burst response against C. albicans in cooperation with Dectin-1. Eur J Immunol. 2011;41(5):1435–44. doi: 10.1002/eji.200940188 21400494.
12. Robinson MJ, Osorio F, Rosas M, Freitas RP, Schweighoffer E, Groß O, et al. Dectin-2 is a Syk-coupled pattern recognition receptor crucial for Th17 responses to fungal infection. J Exp Med. 2009;206(9):2037–51. doi: 10.1084/jem.20082818 19703985.
13. Lin JS, Huang JH, Hung LY, Wu SY, Wu-Hsieh BA. Distinct roles of complement receptor 3, Dectin-1, and sialic acids in murine macrophage interaction with Histoplasma yeast. J Leukoc Biol. 2010;88(1):95–106. doi: 10.1189/jlb.1109717 20360401.
14. Arnaout MA. Structure and function of the leukocyte adhesion molecules CD11/CD18. Blood. 1990;75(5):1037–50. 1968349.
15. Vetvicka V, Thornton BP, Ross GD. Soluble beta-glucan polysaccharide binding to the lectin site of neutrophil or natural killer cell complement receptor type 3 (CD11b/CD18) generates a primed state of the receptor capable of mediating cytotoxicity of iC3b-opsonized target cells. J Clin Invest. 1996;98(1):50–61. doi: 10.1172/JCI118777 8690804.
16. Mayadas TN, Cullere X. Neutrophil β2 integrins: moderators of life or death decisions. Trends Immunol. 2005;26(7):388–95. doi: 10.1016/j.it.2005.05.002 15922663.
17. Abram CL, Lowell CA. The Ins and Outs of Leukocyte Integrin Signaling. Annu Rev Immunol. 2009;27(1):339–62. doi: 10.1146/annurev.immunol.021908.132554 19302044.
18. Harokopakis E, Hajishengallis G. Integrin activation by bacterial fimbriae through a pathway involving CD14, Toll-like receptor 2, and phosphatidylinositol-3-kinase. Eur J Immunol. 2005;35(4):1201–10. doi: 10.1002/eji.200425883 15739163.
19. Li X, Utomo A, Cullere X, Choi Myunghwan M, Milner Danny A Jr, Venkatesh D, et al. The β-Glucan receptor Dectin-1 activates the integrin Mac-1 in neutrophils via Vav protein signaling to promote Candida albicans clearance. Cell Host Microbe. 2011;10(6):603–15. doi: 10.1016/j.chom.2011.10.009 22177564.
20. Groves E, Dart AE, Covarelli V, Caron E. Molecular mechanisms of phagocytic uptake in mammalian cells. Cell Mol Life Sci. 2008;65(13):1957–76. doi: 10.1007/s00018-008-7578-4 18322649.
21. Brown GD. Dectin-1: a signalling non-TLR pattern-recognition receptor. Nat Rev Immunol. 2006;6(1):33–43. doi: 10.1038/nri1745 16341139.
22. Xu S, Huo J, Lee K- G, Kurosaki T, Lam K- P. Phospholipase Cγ2 is critical for Dectin-1-mediated Ca2+ flux and cytokine production in dendritic cells. J Biol Chem. 2009;284(11):7038–46. doi: 10.1074/jbc.M806650200 19136564.
23. Goodridge HS, Simmons RM, Underhill DM. Dectin-1 stimulation by Candida albicans yeast or zymosan triggers NFAT activation in macrophages and dendritic cells. J Immunol. 2007;178(5):3107–15. 17312158.
24. Gross O, Gewies A, Finger K, Schäfer M, Sparwasser T, Peschel C, et al. Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity. Nature. 2006;442(7103):651–6. doi: 10.1038/nature04926 16862125.
25. Jia XM, Tang B, Zhu LL, Liu YH, Zhao XQ, Gorjestani S, et al. CARD9 mediates Dectin-1-induced ERK activation by linking Ras-GRF1 to H-Ras for antifungal immunity. J Exp Med. 2014;211(11):2307–21. doi: 10.1084/jem.20132349 25267792.
26. Gringhuis SI, den Dunnen J, Litjens M, van der Vlist M, Wevers B, Bruijns SCM, et al. Dectin-1 directs T helper cell differentiation by controlling noncanonical NF-kappaB activation through Raf-1 and Syk. Nat Immunol. 2009;10(2):203–13. doi: 10.1038/ni.1692 19122653.
27. Goodridge HS, Shimada T, Wolf AJ, Hsu Y-MS, Becker CA, Lin X, et al. Differential use of CARD9 by Dectin-1 in macrophages and dendritic cells. J Immunol. 2009;182(2):1146–54. doi: 10.4049/jimmunol.182.2.1146 19124758.
28. Underhill DM, Rossnagle E, Lowell CA, Simmons RM. Dectin-1 activates Syk tyrosine kinase in a dynamic subset of macrophages for reactive oxygen production. Blood. 2005;106(7):2543–50. doi: 10.1182/blood-2005-03-1239 15956283.
29. Li B, Allendorf DJ, Hansen R, Marroquin J, Ding C, Cramer DE, et al. Yeast β-glucan amplifies phagocyte killing of iC3b-opsonized tumor cells via complement receptor 3-Syk-phosphatidylinositol 3-kinase pathway. J Immunol. 2006;177(3):1661–9. 16849475.
30. Pande G. The role of membrane lipids in regulation of integrin functions. Curr Opin Cell Biol 2000;12(5):569–74. 10978891.
31. Xu S, Huo J, Gunawan M, Su I-H, Lam K-P. Activated Dectin-1 localizes to lipid raft microdomains for signaling and activation of phagocytosis and cytokine production in dendritic cells. J Biol Chem. 2009;284(33):22005–11. doi: 10.1074/jbc.M109.009076 19525229.
32. Wu-Hsieh BA, Lee GS, Franco M, Hofman FM. Early activation of splenic macrophages by tumor necrosis factor alpha is important in determining the outcome of experimental histoplasmosis in mice. Infect Immun. 1992;60(10):4230–8. 1398934.
33. Rappleye CA, Eissenberg LG, Goldman WE. Histoplasma capsulatum α-(1,3)-glucan blocks innate immune recognition by the β-glucan receptor. Proc Natl Acad Sci U S A. 2007;104(4):1366–70. doi: 10.1073/pnas.0609848104 17227865.
34. Gantner BN, Simmons RM, Underhill DM. Dectin-1 mediates macrophage recognition of Candida albicans yeast but not filaments. EMBO J. 2005;24(6):1277–86. doi: 10.1038/sj.emboj.7600594 15729357.
35. Saijo S, Iwakura Y. Dectin-1 and Dectin-2 in innate immunity against fungi. Int Immunol. 2011;23(8):467–72. doi: 10.1093/intimm/dxr046 21677049.
36. Ratnoff WD, Pepple JM, Winkelstein JA. Activation of the alternative complement pathway by Histoplasma capsulatum. Infect Immun. 1980;30(1):147–9. 7439970.
37. Goodridge HS, Reyes CN, Becker CA, Katsumoto TR, Ma J, Wolf AJ, et al. Activation of the innate immune receptor Dectin-1 upon formation of a 'phagocytic synapse'. Nature. 2011;472(7344):471–5. doi: 10.1038/nature10071 21525931.
38. Inoue M, Moriwaki Y, Arikawa T, Chen YH, Oh YJ, Oliver T, et al. Cutting edge: critical role of intracellular osteopontin in antifungal innate immune responses. J Immunol. 2011;186(1):19–23. doi: 10.4049/jimmunol.1002735 21135164.
39. Wu-Hsieh BA, Howard DH. Inhibition of the intracellular growth of Histoplasma capsulatum by recombinant murine gamma interferon. Infect Immun. 1987;55(4):1014–6. 3104206.
40. Lin JS, Yang CW, Wang DW, Wu-Hsieh BA. Dendritic cells cross-present exogenous fungal antigens to stimulate a protective CD8 T cell response in infection by Histoplasma capsulatum. J Immunol. 2005;174(10):6282–91. 15879127.
41. Wu SY, Yu JS, Liu FT, Miaw SC, Wu-Hsieh BA. Galectin-3 negatively regulates dendritic cell production of IL-23/IL-17-axis cytokines in infection by Histoplasma capsulatum. J Immunol. 2013;190(7):3427–37. doi: 10.4049/jimmunol.1202122 23455499.
42. Subramanian Vignesh K, Landero Figueroa JA, Porollo A, Caruso JA, Deepe GS Jr. Granulocyte macrophage-colony stimulating factor induced Zn sequestration enhances macrophage superoxide and limits intracellular pathogen survival. Immunity. 2013;39(4):697–710. doi: 10.1016/j.immuni.2013.09.006 24138881.
43. Hovius JWR, de Jong MAWP, den Dunnen J, Litjens M, Fikrig E, van der Poll T, et al. Salp15 binding to DC-SIGN inhibits cytokine expression by impairing both nucleosome remodeling and mRNA stabilization. PLoS Pathog. 2008;4(2):e31. doi: 10.1371/journal.ppat.0040031 18282094.
44. Dillon S, Agrawal S, Banerjee K, Letterio J, Denning TL, Oswald-Richter K, et al. Yeast zymosan, a stimulus for TLR2 and dectin-1, induces regulatory antigen-presenting cells and immunological tolerance. J Clin Invest. 2006;116(4):916–28. doi: 10.1172/jci27203 16543948.
45. Tassi I, Cella M, Castro I, Gilfillan S, Khan WN, Colonna M. Requirement of phospholipase C-gamma2 (PLCgamma2) for Dectin-1-induced antigen presentation and induction of TH1/TH17 polarization. Eur J Immunol. 2009;39(5):1369–78. doi: 10.1002/eji.200839313 19404984.
46. Toyotome T, Adachi Y, Watanabe A, Ochiai E, Ohno N, Kamei K. Activator protein 1 is triggered by Aspergillus fumigatus beta-glucans surface-exposed during specific growth stages. Microb Pathog. 2008;44(2):141–50. doi: 10.1016/j.micpath.2007.08.015 17928189.
47. Palanki MS. Inhibitors of AP-1 and NF-kappa B mediated transcriptional activation: therapeutic potential in autoimmune diseases and structural diversity. Curr Med Chem. 2002;9(2):219–27. 11860356.
48. Shaulian E, Karin M. AP-1 as a regulator of cell life and death. Nat Cell Biol 2002;4(5):E131–6. doi: 10.1038/ncb0502-e131 11988758.
49. Ye N, Ding Y, Wild C, Shen Q, Zhou J. Small molecule inhibitors targeting activator protein 1 (AP-1). J Med Chem. 2014;57(16):6930–48. doi: 10.1021/jm5004733 24831826.
50. Prince JE, Brayton CF, Fossett MC, Durand JA, Kaplan SL, Smith CW, et al. The differential roles of LFA-1 and Mac-1 in host defense against systemic infection with Streptococcus pneumoniae. J Immunol. 2001;166(12):7362–9. 11390487.
51. Rijneveld AW, de Vos AF, Florquin S, Verbeek JS, van der Poll T. CD11b limits bacterial outgrowth and dissemination during murine pneumococcal pneumonia. J Infect Dis. 2005;191(10):1755–60. doi: 10.1086/429633 15838804.
52. Soloviev DA, Jawhara S, Fonzi WA. Regulation of innate immune response to Candida albicans infections by alphaMbeta2-Pra1p interaction. Infect Immun. 2011;79(4):1546–58. doi: 10.1128/iai.00650-10 21245270.
53. LeibundGut-Landmann S, Grosz O, Robinson MJ, Osorio F, Slack EC, Tsoni SV, et al. Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17. Nat Immunol. 2007;8(6):630–8. doi: 10.1038/ni1460 17450144.
54. Leibundgut-Landmann S, Osorio F, Brown GD, Reis e Sousa C. Stimulation of dendritic cells via the dectin-1/Syk pathway allows priming of cytotoxic T-cell responses. Blood. 2008;112(13):4971–80. doi: 10.1182/blood-2008-05-158469 18818389.
55. Gresnigt MS, Becker KL, Smeekens SP, Jacobs CW, Joosten LA, van der Meer JW, et al. Aspergillus fumigatus-induced IL-22 is not restricted to a specific Th cell subset and is dependent on complement receptor 3. J Immunol. 2013;190(11):5629–39. doi: 10.4049/jimmunol.1202601 23645883.
56. Lin JS, Wu-Hsieh BA. Functional T cells in primary immune response to histoplasmosis. Int Immunol. 2004;16(11):1663–73. doi: 10.1093/intimm/dxh168 15452021.
57. Deepe GS Jr., Gibbons RS. Interleukins 17 and 23 influence the host response to Histoplasma capsulatum. J Infec Dis. 2009;200(1):142–51. doi: 10.1086/599333 19469707.
58. Clemons KV, Darbonne WC, Curnutte JT, Sobel RA, Stevens DA. Experimental histoplasmosis in mice treated with anti-murine interferon-gamma antibody and in interferon-gamma gene knockout mice. Microbes Infect. 2000;2(9):997–1001. 10967280.
59. Allendoerfer R, Deepe GS Jr. Intrapulmonary response to Histoplasma capsulatum in gamma interferon knockout mice. Infect Immun. 1997;65(7):2564–9. 9199420.
60. Zhou P, Miller G, Seder RA. Factors involved in regulating primary and secondary immunity to infection with Histoplasma capsulatum: TNF-α plays a critical role in maintaining secondary immunity in the absence of IFN-γ. J Immunol. 1998;160(3):1359–68. 9570555.
61. Romani L, Mencacci A, Cenci E, Spaccapelo R, Toniatti C, Puccetti P, et al. Impaired neutrophil response and CD4+ T helper cell 1 development in interleukin 6-deficient mice infected with Candida albicans. J Exp Med. 1996;183(4):1345–55. 8666893.
62. Cenci E, Mencacci A, Casagrande A, Mosci P, Bistoni F, Romani L. Impaired antifungal effector activity but not inflammatory cell recruitment in interleukin-6-deficient mice with invasive pulmonary aspergillosis. J Infec Dis. 2001;184(5):610–7. doi: 10.1086/322793 11494166.
63. Taylor PR, Tsoni SV, Willment JA, Dennehy KM, Rosas M, Findon H, et al. Dectin-1 is required for beta-glucan recognition and control of fungal infection. Nat Immunol. 2007;8(1):31–8. doi: 10.1038/ni1408 17159984.
64. Cheng AM, Rowley B, Pao W, Hayday A, Bolen JB, Pawson T. Syk tyrosine kinase required for mouse viability and B-cell development. Nature. 1995;378(6554):303–6. doi: 10.1038/378303a0 7477353.
65. Yanagi S, Inatome R, Ding J, Kitaguchi H, Tybulewicz VLJ, Yamamura H. Syk expression in endothelial cells and their morphologic defects in embryonic Syk-deficient mice. Blood. 2001;98(9):2869–71. doi: 10.1182/blood.V98.9.2869 11675365.
66. Chow CW, Downey GP, Grinstein S. Measurements of phagocytosis and phagosomal maturation. Curr Protoc Cell Biol. 2004;Chapter 15:Unit 15.7. doi: 10.1002/0471143030.cb1507s22 18228442.
67. Newman SL, Mikus LK. Deposition of C3b and iC3b onto particulate activators of the human complement system. Quantitation with monoclonal antibodies to human C3. J Exp Med. 1985;161(6):1414–31. 2409200.
68. Ciaccio MF, Wagner JP, Chuu C-P, Lauffenburger DA, Jones RB. Systems analysis of EGF receptor signaling dynamics with microwestern arrays. Nat Methods. 2010;7(2):148–55. doi: 10.1038/nmeth.1418 20101245.
Štítky
Hygiena a epidemiologie Infekční lékařství Laboratoř
Článek vyšel v časopise
PLOS Pathogens
2015 Číslo 7
Nejčtenější v tomto čísle
Tomuto tématu se dále věnují…
Přihlášení
Zapomenuté heslo
Nemáte účet? Registrujte se
Zapomenuté heslo
Zadejte e-mailovou adresu se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.
Přihlášení
Nemáte účet? Registrujte se
|
{
"url": "https://www.prolekarniky.cz/casopisy/plos-pathogens/2015-7/cr3-and-dectin-1-collaborate-in-macrophage-cytokine-response-through-association-on-lipid-rafts-and-activation-of-syk-jnk-ap-1-pathway-54155",
"source_domain": "www.prolekarniky.cz",
"snapshot_id": "crawl=CC-MAIN-2020-45",
"warc_metadata": {
"Content-Length": "200186",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:TQ3YQOUNNUJXZKCVTL7MGI6VFL2DKULR",
"WARC-Concurrent-To": "<urn:uuid:7a25a742-09c3-4c3c-bde8-19ead83badf9>",
"WARC-Date": "2020-10-26T18:19:38",
"WARC-IP-Address": "185.64.216.251",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:KXHCIHA7FPNU25GWBCD2EK56U3K66WHV",
"WARC-Record-ID": "<urn:uuid:d6b0d95b-f5e0-4df5-8e88-fc87cb77cae4>",
"WARC-Target-URI": "https://www.prolekarniky.cz/casopisy/plos-pathogens/2015-7/cr3-and-dectin-1-collaborate-in-macrophage-cytokine-response-through-association-on-lipid-rafts-and-activation-of-syk-jnk-ap-1-pathway-54155",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:e5c104f6-fac5-40f1-92fc-5c85875704d1>"
},
"warc_info": "isPartOf: CC-MAIN-2020-45\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for October 2020\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-208.ec2.internal\r\nsoftware: Apache Nutch 1.17 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.2-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: http://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
135,
136,
137,
1467,
1468,
1469,
1557,
1584,
1618,
1619,
1627,
1628,
2958,
2959,
2972,
2973,
4029,
4030,
5162,
5163,
6172,
6173,
7199,
7200,
8110,
8111,
8119,
8120,
8197,
8198,
9184,
9185,
10421,
10422,
10527,
10640,
12653,
12654,
13533,
13534,
13615,
13616,
15205,
15206,
15337,
15476,
17113,
17114,
17201,
17202,
18431,
18432,
18555,
18672,
19284,
19285,
19343,
19344,
20451,
20452,
20508,
20572,
22313,
22314,
23351,
23352,
23435,
23436,
24855,
24856,
24954,
25060,
26226,
26227,
26300,
26301,
27825,
27826,
27928,
28024,
29463,
29464,
30767,
30768,
30779,
30780,
31858,
31859,
33083,
33084,
34009,
34010,
35687,
35688,
36810,
36811,
37818,
37819,
38785,
38786,
40323,
40324,
41887,
41888,
44645,
44646,
45343,
45344,
45366,
45367,
45384,
45385,
45731,
45732,
45739,
45740,
46372,
46373,
46378,
46379,
47215,
47216,
47222,
47223,
47860,
47861,
47885,
47886,
48197,
48198,
49078,
49079,
49127,
49128,
50037,
50038,
50054,
50055,
50406,
50407,
50424,
50425,
51011,
51012,
51046,
51047,
51770,
51771,
51823,
51824,
52675,
52676,
52704,
52705,
53076,
53077,
53111,
53112,
53636,
53637,
53712,
53713,
54491,
54492,
54556,
54557,
55372,
55373,
55384,
55385,
55777,
55778,
55796,
55797,
56380,
56381,
56404,
56405,
56418,
56419,
56432,
56433,
56446,
56447,
56460,
56461,
56474,
56475,
56488,
56489,
56502,
56503,
56516,
56517,
56530,
56531,
56545,
56546,
56560,
56561,
56575,
56576,
56590,
56591,
56605,
56606,
56620,
56621,
56622,
56629,
56630,
56768,
56769,
56893,
56894,
57048,
57049,
57214,
57215,
57343,
57344,
57544,
57545,
57764,
57765,
57962,
57963,
58226,
58227,
58486,
58487,
58740,
58741,
58992,
58993,
59238,
59239,
59361,
59362,
59711,
59712,
59878,
59879,
60044,
60045,
60287,
60288,
60595,
60596,
60784,
60785,
60925,
60926,
61154,
61155,
61360,
61361,
61579,
61580,
61816,
61817,
62089,
62090,
62312,
62313,
62543,
62544,
62800,
62801,
62928,
62929,
63194,
63195,
63435,
63436,
63663,
63664,
63860,
63861,
64010,
64011,
64171,
64172,
64404,
64405,
64640,
64641,
64816,
64817,
65045,
65046,
65294,
65295,
65601,
65602,
65881,
65882,
66157,
66158,
66427,
66428,
66690,
66691,
66892,
66893,
67030,
67031,
67203,
67204,
67440,
67441,
67665,
67666,
67876,
67877,
68140,
68141,
68383,
68384,
68671,
68672,
68833,
68834,
69005,
69006,
69248,
69249,
69409,
69410,
69674,
69675,
69926,
69927,
70205,
70206,
70423,
70424,
70619,
70620,
70860,
70861,
71048,
71049,
71255,
71256,
71464,
71465,
71472,
71525,
71526,
71550,
71551,
71566,
71567,
71568,
71581,
71582,
71608,
71609,
71639,
71640,
71641,
71652,
71669,
71670,
71699,
71700,
71717,
71718,
71837,
71838,
71849,
71850
],
"line_end_idx": [
135,
136,
137,
1467,
1468,
1469,
1557,
1584,
1618,
1619,
1627,
1628,
2958,
2959,
2972,
2973,
4029,
4030,
5162,
5163,
6172,
6173,
7199,
7200,
8110,
8111,
8119,
8120,
8197,
8198,
9184,
9185,
10421,
10422,
10527,
10640,
12653,
12654,
13533,
13534,
13615,
13616,
15205,
15206,
15337,
15476,
17113,
17114,
17201,
17202,
18431,
18432,
18555,
18672,
19284,
19285,
19343,
19344,
20451,
20452,
20508,
20572,
22313,
22314,
23351,
23352,
23435,
23436,
24855,
24856,
24954,
25060,
26226,
26227,
26300,
26301,
27825,
27826,
27928,
28024,
29463,
29464,
30767,
30768,
30779,
30780,
31858,
31859,
33083,
33084,
34009,
34010,
35687,
35688,
36810,
36811,
37818,
37819,
38785,
38786,
40323,
40324,
41887,
41888,
44645,
44646,
45343,
45344,
45366,
45367,
45384,
45385,
45731,
45732,
45739,
45740,
46372,
46373,
46378,
46379,
47215,
47216,
47222,
47223,
47860,
47861,
47885,
47886,
48197,
48198,
49078,
49079,
49127,
49128,
50037,
50038,
50054,
50055,
50406,
50407,
50424,
50425,
51011,
51012,
51046,
51047,
51770,
51771,
51823,
51824,
52675,
52676,
52704,
52705,
53076,
53077,
53111,
53112,
53636,
53637,
53712,
53713,
54491,
54492,
54556,
54557,
55372,
55373,
55384,
55385,
55777,
55778,
55796,
55797,
56380,
56381,
56404,
56405,
56418,
56419,
56432,
56433,
56446,
56447,
56460,
56461,
56474,
56475,
56488,
56489,
56502,
56503,
56516,
56517,
56530,
56531,
56545,
56546,
56560,
56561,
56575,
56576,
56590,
56591,
56605,
56606,
56620,
56621,
56622,
56629,
56630,
56768,
56769,
56893,
56894,
57048,
57049,
57214,
57215,
57343,
57344,
57544,
57545,
57764,
57765,
57962,
57963,
58226,
58227,
58486,
58487,
58740,
58741,
58992,
58993,
59238,
59239,
59361,
59362,
59711,
59712,
59878,
59879,
60044,
60045,
60287,
60288,
60595,
60596,
60784,
60785,
60925,
60926,
61154,
61155,
61360,
61361,
61579,
61580,
61816,
61817,
62089,
62090,
62312,
62313,
62543,
62544,
62800,
62801,
62928,
62929,
63194,
63195,
63435,
63436,
63663,
63664,
63860,
63861,
64010,
64011,
64171,
64172,
64404,
64405,
64640,
64641,
64816,
64817,
65045,
65046,
65294,
65295,
65601,
65602,
65881,
65882,
66157,
66158,
66427,
66428,
66690,
66691,
66892,
66893,
67030,
67031,
67203,
67204,
67440,
67441,
67665,
67666,
67876,
67877,
68140,
68141,
68383,
68384,
68671,
68672,
68833,
68834,
69005,
69006,
69248,
69249,
69409,
69410,
69674,
69675,
69926,
69927,
70205,
70206,
70423,
70424,
70619,
70620,
70860,
70861,
71048,
71049,
71255,
71256,
71464,
71465,
71472,
71525,
71526,
71550,
71551,
71566,
71567,
71568,
71581,
71582,
71608,
71609,
71639,
71640,
71641,
71652,
71669,
71670,
71699,
71700,
71717,
71718,
71837,
71838,
71849,
71850,
71878
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 71878,
"ccnet_original_nlines": 373,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.21190927922725677,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.08706451207399368,
"rps_doc_frac_lines_end_with_ellipsis": 0.002673800103366375,
"rps_doc_frac_no_alph_words": 0.3255768418312073,
"rps_doc_frac_unique_words": 0.23522651195526123,
"rps_doc_mean_word_length": 5.479551792144775,
"rps_doc_num_sentences": 1063,
"rps_doc_symbol_to_word_ratio": 0.0005229099770076573,
"rps_doc_unigram_entropy": 6.469192981719971,
"rps_doc_word_count": 10441,
"rps_doc_frac_chars_dupe_10grams": 0.06981053203344345,
"rps_doc_frac_chars_dupe_5grams": 0.20523665845394135,
"rps_doc_frac_chars_dupe_6grams": 0.16396909952163696,
"rps_doc_frac_chars_dupe_7grams": 0.12411732226610184,
"rps_doc_frac_chars_dupe_8grams": 0.10228622704744339,
"rps_doc_frac_chars_dupe_9grams": 0.08812835812568665,
"rps_doc_frac_chars_top_2gram": 0.01749633066356182,
"rps_doc_frac_chars_top_3gram": 0.016360199078917503,
"rps_doc_frac_chars_top_4gram": 0.005313570145517588,
"rps_doc_books_importance": -6272.13330078125,
"rps_doc_books_importance_length_correction": -6272.13330078125,
"rps_doc_openwebtext_importance": -3523.5185546875,
"rps_doc_openwebtext_importance_length_correction": -3523.5185546875,
"rps_doc_wikipedia_importance": -3029.248779296875,
"rps_doc_wikipedia_importance_length_correction": -3029.248779296875
},
"fasttext": {
"dclm": 0.021777750924229622,
"english": 0.8925632834434509,
"fineweb_edu_approx": 1.9898018836975098,
"eai_general_math": 0.3552297353744507,
"eai_open_web_math": 0.34230953454971313,
"eai_web_code": 0.01306707039475441
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.994",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "616.079",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "4",
"label": "Analyze"
},
"secondary": {
"code": "5",
"label": "Evaluate"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "2",
"label": "Academic/Research"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "0",
"label": "No Artifacts"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "0",
"label": "No missing content"
}
},
"document_type_v2": {
"primary": {
"code": "3",
"label": "Academic Writing"
},
"secondary": {
"code": "10",
"label": "Knowledge Article"
}
},
"reasoning_depth": {
"primary": {
"code": "4",
"label": "Advanced Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "4",
"label": "Graduate/Expert Level"
},
"secondary": {
"code": "3",
"label": "Undergraduate Level"
}
}
}
|
9222580d47c553ea90dc0f5e416f8f3a
|
-3,482,662,261,034,211,000
|
Elisabet E. Manasanch, MD | Authors
Management of Heavy Chain Diseases: The Challenges of Biologic Heterogeneity
January 15, 2014
In the absence of a clear understanding of the underlying biologic heterogeneity, the etiology of the different heavy chain diseases (HCDs) should be taken into consideration when treatment decisions are made. Extrapolation from related conditions, such as aggressive lymphomas (in γ-HCD) and CLL (in μ-HCD), suggests that novel and targeted therapies may be effective in the management of these rare diseases.
|
{
"url": "https://www.cancernetwork.com/authors/elisabet-e-manasanch-md",
"source_domain": "www.cancernetwork.com",
"snapshot_id": "CC-MAIN-2023-06",
"warc_metadata": {
"Content-Length": "86284",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:K6C7ZK2GP7AXXGCTGAECSACEKTOWBQ3G",
"WARC-Concurrent-To": "<urn:uuid:6fca12a5-e396-4200-9d74-a580d3938c6b>",
"WARC-Date": "2023-02-09T02:35:54",
"WARC-IP-Address": "76.76.21.93",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:LBOUEFLUUVGXLRT5SWXAZ2E6PDLJXQZ3",
"WARC-Record-ID": "<urn:uuid:e09865d0-dd33-4c34-83d5-88fdc66d1836>",
"WARC-Target-URI": "https://www.cancernetwork.com/authors/elisabet-e-manasanch-md",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:abc34fe2-d892-4d39-a081-4713059e02c7>"
},
"warc_info": "isPartOf: CC-MAIN-2023-06\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for January/February 2023\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-56\r\nsoftware: Apache Nutch 1.19 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.4-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
36,
37,
114,
115,
132,
133
],
"line_end_idx": [
36,
37,
114,
115,
132,
133,
543
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 543,
"ccnet_original_nlines": 6,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.3265306055545807,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.051020409911870956,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.2142857164144516,
"rps_doc_frac_unique_words": 0.7215189933776855,
"rps_doc_mean_word_length": 5.607594966888428,
"rps_doc_num_sentences": 3,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 3.8625340461730957,
"rps_doc_word_count": 79,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.05417606979608536,
"rps_doc_frac_chars_top_3gram": 0.08126410841941833,
"rps_doc_frac_chars_top_4gram": 0,
"rps_doc_books_importance": -43.7160758972168,
"rps_doc_books_importance_length_correction": -57.16792678833008,
"rps_doc_openwebtext_importance": -22.949100494384766,
"rps_doc_openwebtext_importance_length_correction": -36.40095138549805,
"rps_doc_wikipedia_importance": -14.73666763305664,
"rps_doc_wikipedia_importance_length_correction": -28.188518524169922
},
"fasttext": {
"dclm": 0.06077301874756813,
"english": 0.9270806312561035,
"fineweb_edu_approx": 3.1930863857269287,
"eai_general_math": 0.47573941946029663,
"eai_open_web_math": 0.5681394934654236,
"eai_web_code": 0.02306496910750866
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.994",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "616.99401",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "4",
"label": "Analyze"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "2",
"label": "Academic/Research"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "3",
"label": "Irrelevant Content"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "3",
"label": "Academic Writing"
},
"secondary": {
"code": "10",
"label": "Knowledge Article"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "4",
"label": "Graduate/Expert Level"
},
"secondary": {
"code": "3",
"label": "Undergraduate Level"
}
}
}
|
b755ed28a90d11d590ef646404f4afc5
|
-7,353,019,024,502,940,000
|
How I Achieved Maximum Success with
Oral Implants – What Are Implants?
An oral implant is really a surgically-sealed composite product, commonly made from titanium and made up of numerous ceramic layers. This composite material interfaces with the sustaining bone or jaw for a practical or aesthetic oral implant, such as a dental bridge, dentures, a fabricated tooth or crown, dental implants, a facelift or to come to be an orthodontist support. The first purpose for the dental implant was to remedy defects that were caused by an accident, disease, mishap, or serious injury to the mouth. An oral implant may be dental implanted on either one or both jaws for those that experienced jaw injuries because of a loss or mishap. Dental implants are currently used for the replacement of missing teeth. An individual having lost his/her jawbone due to a crash is a good candidate for an oral implant. The bone is in fact merged with a titanium rod. The implanted bone becomes an outlet that is also filled with a filler. There are several reasons why a person may need an oral implant. If you have a missing out on tooth or a bone spur, which has turned into the jaw and also is interfering with chewing or talking, you might need a dental implant. Some dental professionals even describe oral implants as “bionic teeth”. Because of the relevance of a healthy and balanced bone as well as the reality that the jawbone is usually harmed by bone stimulates, the person has to undertake a bone graft to replace the bone that has actually been shed. Because of this the individual’s gum tissues are normally exposed in order to promote the bone graft. Dentists commonly recommend that clients go through a bone graft after a fracture of their jaw, however they are not required. Clients can have a dental implant, but it relies on the level of their jaw damages. A bone graft requires the use of surgical equipment that is called a bone grafter. This devices is typically affixed to the bone specialist during the treatment, though sometimes it might be connected at a later time when the person requires a repair of the bone. The bone grafter will certainly have the ability to infuse a material into the jaw bone, which then becomes bound to the bone to form a new bone. Bone grafting is done by putting a hook onto which the bone grafting material is placed. The hook is then affixed to the jaw bone. Implants are not as high-risk as it seems, as well as they rarely cause any type of issues after the procedure. The most typical side effects from dental implants are tooth sensitivity, discomfort or inflammation, wounding, swelling or infection. These adverse effects are really unusual, however they can happen in many cases.
How I Became An Expert on
Why Aren’t As Bad As You Think
|
{
"url": "http://educasting.info/how-i-achieved-maximum-success-with/",
"source_domain": "educasting.info",
"snapshot_id": "crawl=CC-MAIN-2021-10",
"warc_metadata": {
"Content-Length": "20317",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:GMHJ54U3D2P7FPFC6BYP4LBIJWZIWH5H",
"WARC-Concurrent-To": "<urn:uuid:3145c690-b194-4f0a-80c7-91b076ef8f8c>",
"WARC-Date": "2021-03-07T14:02:12",
"WARC-IP-Address": "198.252.102.225",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:CWTBLRIYPUAYM3EGBNKLQTIKSFDDJJ6W",
"WARC-Record-ID": "<urn:uuid:5fda0558-050c-4853-8196-ac178ee310bb>",
"WARC-Target-URI": "http://educasting.info/how-i-achieved-maximum-success-with/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:58b18c3b-ab3d-4fa0-8721-c9e70e4971a9>"
},
"warc_info": "isPartOf: CC-MAIN-2021-10\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for February/March 2021\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-165.ec2.internal\r\nsoftware: Apache Nutch 1.18 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.2-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: http://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
36,
37,
72,
73,
2729,
2730,
2756,
2757
],
"line_end_idx": [
36,
37,
72,
73,
2729,
2730,
2756,
2757,
2787
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 2787,
"ccnet_original_nlines": 8,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.44935542345046997,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.005524860229343176,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.09576427191495895,
"rps_doc_frac_unique_words": 0.47433266043663025,
"rps_doc_mean_word_length": 4.618069648742676,
"rps_doc_num_sentences": 25,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 4.882599353790283,
"rps_doc_word_count": 487,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.024899959564208984,
"rps_doc_frac_chars_top_3gram": 0.023121390491724014,
"rps_doc_frac_chars_top_4gram": 0,
"rps_doc_books_importance": -188.3290557861328,
"rps_doc_books_importance_length_correction": -188.3290557861328,
"rps_doc_openwebtext_importance": -128.61741638183594,
"rps_doc_openwebtext_importance_length_correction": -128.61741638183594,
"rps_doc_wikipedia_importance": -103.94705200195312,
"rps_doc_wikipedia_importance_length_correction": -103.94705200195312
},
"fasttext": {
"dclm": 0.22399574518203735,
"english": 0.96158766746521,
"fineweb_edu_approx": 2.9625277519226074,
"eai_general_math": 0.034051720052957535,
"eai_open_web_math": 0.17405492067337036,
"eai_web_code": 0.0018703299574553967
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "617.622",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Surgery and Dentistry"
}
},
"secondary": {
"code": "617.62",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Surgery and Dentistry"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "1",
"label": "Factual"
},
"secondary": {
"code": "2",
"label": "Conceptual"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "0",
"label": "No Artifacts"
}
},
"missing_content": {
"primary": {
"code": "1",
"label": "Truncated Snippets"
},
"secondary": {
"code": "3",
"label": "Incoherent Flow"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "16",
"label": "Personal Blog"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "1",
"label": "No Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "2",
"label": "Partially Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
1a01aa77535b9ecfb87b9fc36adbcd2f
|
-2,470,860,038,417,230,000
|
Donate to our INSPIRE Foundation
(212) 606-1559
Contact
Spinal Cysts
What is a Spinal Cyst?
Cysts are fluid-filled sacs they can develop anywhere on the body but when they develop near the spine it can lead to various painful and potentially serious conditions. Most spinal cysts develop in the sacral area around the tailbone.
What Can Cause a Spinal Cyst?
Cysts develop for several reasons. Some people have cysts from birth and others are caused by aging or other degenerative processes. In the case of synovial cysts, the condition may develop because of the body producing more fluid in the joint to compensate for degeneration.
Spinal Cyst Symptoms
A patient with a spinal cyst may not have any symptoms if the cyst remains small and stable. If, however, the cyst grows to a significant size and/or presses on nearby nerves, it can cause symptoms that include pain, leg weakness, and loss of bladder or bowel control. Spinal cysts tend to cause pain when a person is still for long periods of time or assumes certain positions. Many patients can reduce the severity of symptoms by frequently changing positions and moving around more often.
Types of Spinal Cysts
There are several different types of cysts that can form within the spinal cord.
• Synovial
• Arachnoid
• Tarlov
• Ganglion
• Intradiscal
What Are the Treatment Options for Spinal Cysts?
Spinal cysts that are not growing quickly or causing symptoms may not require treatment. Dr. Federico P. Girardi will continuously monitor the cyst for any changes in development. Some patients with mild symptoms find that changing positions and moving around more often helps but can still seek treatment. Dr. Girardi may recommend steroid injections to reduce inflammation and discomfort as the first course of treatment.
If the spinal cyst is causing moderate to severe pain or growing quickly, Dr. Girardi may recommend surgery. The goal of the procedure is to drain or remove the cyst. In some cases, Dr. Girardi may recommend spinal fusion surgery. This is common when there is a likelihood of new cysts developing within the spinal cord.
At a Glance
Dr. Federico Girardi MD
• Triple fellowship-trained spinal surgeon
• Performs over 400 spinal surgeries per year
• Professor of orthopedic surgery at Cornell University
• Learn more
End of content dots
|
{
"url": "https://www.federicogirardimd.com/treatments/spinal-cysts-new-york-city/",
"source_domain": "www.federicogirardimd.com",
"snapshot_id": "CC-MAIN-2024-22",
"warc_metadata": {
"Content-Length": "63427",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:RTI6GPM2WYAY6XOYN3Z7DXUTWIEPNISM",
"WARC-Concurrent-To": "<urn:uuid:362a89b4-4126-4a34-b17e-3707efa2a1c2>",
"WARC-Date": "2024-05-25T03:05:25",
"WARC-IP-Address": "72.167.227.217",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:FHMHZOW24OAVB4WAHNCSI6ZDFPCW7XIW",
"WARC-Record-ID": "<urn:uuid:1f50333d-7bb5-4e5e-88db-0c098d3ba732>",
"WARC-Target-URI": "https://www.federicogirardimd.com/treatments/spinal-cysts-new-york-city/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:e4b248db-fb59-471d-b075-87cf81406f14>"
},
"warc_info": "isPartOf: CC-MAIN-2024-22\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for May 2024\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-241\r\nsoftware: Apache Nutch 1.19 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.5-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
33,
34,
49,
57,
58,
71,
72,
95,
96,
332,
333,
363,
364,
640,
641,
662,
663,
1155,
1156,
1178,
1179,
1260,
1261,
1274,
1288,
1299,
1312,
1328,
1329,
1378,
1379,
1803,
1804,
2125,
2126,
2138,
2139,
2163,
2164,
2209,
2257,
2315,
2330,
2331
],
"line_end_idx": [
33,
34,
49,
57,
58,
71,
72,
95,
96,
332,
333,
363,
364,
640,
641,
662,
663,
1155,
1156,
1178,
1179,
1260,
1261,
1274,
1288,
1299,
1312,
1328,
1329,
1378,
1379,
1803,
1804,
2125,
2126,
2138,
2139,
2163,
2164,
2209,
2257,
2315,
2330,
2331,
2350
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 2350,
"ccnet_original_nlines": 44,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.367441862821579,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.009302330203354359,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.12558139860630035,
"rps_doc_frac_unique_words": 0.48311686515808105,
"rps_doc_mean_word_length": 4.906493663787842,
"rps_doc_num_sentences": 28,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 4.79948616027832,
"rps_doc_word_count": 385,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.043409209698438644,
"rps_doc_frac_chars_dupe_6grams": 0.043409209698438644,
"rps_doc_frac_chars_dupe_7grams": 0.043409209698438644,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.03493912145495415,
"rps_doc_frac_chars_top_3gram": 0.017469560727477074,
"rps_doc_frac_chars_top_4gram": 0.03335098177194595,
"rps_doc_books_importance": -141.65460205078125,
"rps_doc_books_importance_length_correction": -141.65460205078125,
"rps_doc_openwebtext_importance": -105.10554504394531,
"rps_doc_openwebtext_importance_length_correction": -105.10554504394531,
"rps_doc_wikipedia_importance": -40.246612548828125,
"rps_doc_wikipedia_importance_length_correction": -40.246612548828125
},
"fasttext": {
"dclm": 0.09066998958587646,
"english": 0.9290513396263123,
"fineweb_edu_approx": 3.2586636543273926,
"eai_general_math": 0.007797299884259701,
"eai_open_web_math": 0.2541159391403198,
"eai_web_code": 0.00048064999282360077
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "617.62",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Surgery and Dentistry"
}
},
"secondary": {
"code": "617.6",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Surgery and Dentistry"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "1",
"label": "Factual"
},
"secondary": {
"code": "2",
"label": "Conceptual"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "0",
"label": "No Artifacts"
}
},
"missing_content": {
"primary": {
"code": "1",
"label": "Truncated Snippets"
},
"secondary": {
"code": "6",
"label": "Indeterminate"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "1",
"label": "About (Org.)"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "1",
"label": "No Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
6e3c8d3593f3f69280bb5502b214ab8e
|
-4,583,411,628,812,258,000
|
Category:
What is Hand, Foot and Mouth Disease?
Article Details
• Written By: O. Wallace
• Edited By: Niki Foster
• Last Modified Date: 02 April 2018
• Copyright Protected:
2003-2018
Conjecture Corporation
• Print this Article
Free Widgets for your Site/Blog
While 93% of Africans have access to cell phone service, less than 66% have access to piped water and electricity. more...
April 25 , 1983 : USSR leader Yuri Andropov wrote to Samantha Smith, an American grade schooler. more...
Hand, foot and mouth disease is the most common cause of mouth sores in children, primarily in the age group from six months to three years old. It is caused by a group of viruses called enteroviruses, most commonly, the coxsackievirus A16. Not to be confused with the foot and mouth disease that affects cattle, sheep, and swine, it is a fairly mild illness that usually resolves itself within seven to ten days.
Most parents notice that the onset of this disease is heralded by a fever, which is followed by a sore throat, fussiness, and loss of appetite. Sores in the mouth and throat come next and are characterized by white or red blisters covering the tongue, throat and the inside of the cheeks. Excessive drooling may occur due to the discomfort associated with swallowing. The blisters in the throat lead many to believe that the child is suffering from strep throat.
After the rash erupts in the mouth, it moves on to the palms of the hands and the soles of the feet. The rash may be raised or flat and may include blisters. Because different children respond differently to illnesses, the rash can either be highly visible or barely make a mark.
Ad
Thankfully, the rash associated with hand, foot and mouth disease is usually not itchy when the condition occurs in children, although the blisters in the mouth make it uncomfortable to eat and drink. The virus is fairly contagious and spread through person-to-person contact, respiratory secretions, stool and broken blisters. The incubation period is three to seven days, and the affected child is usually contagious before the fever begins. This makes it difficult to stop the spread, because parents do not know that their child is infected until it’s too late. Proper handwashing is the most effective means to slow the spread of the disease.
Once a child has been exposed, he or she develops immunity to the virus and will most likely not experience a recurrence. Most infections occur during the summer and early fall, and breakouts tend to cluster around daycare centers and schools due to the high transference of germs among children. Pregnant women who have never been exposed to the virus may have cause for concern; if they pass it to their infant, there is a slight chance of the child developing serious infections that affect the organs.
There are blood tests available to diagnose hand, foot and mouth disease, but due to the long waiting period, they are rarely used. Due to the viral nature of the disease, antibiotics are ineffective, so the symptoms are treated while waiting for the rash to resolve itself. Pain relievers such as acetaminophen and ibuprofen are effective for the fever and pain, and antihistamines can be used to treat the rash.
Ad
You might also Like
Recommended
Discuss this Article
anon993236
Post 39
I got it from my two year old. It started with unbearable exhaustion and a horrible fever, migraine and sore throat. Every muscle in my body hurt. On day two, I still had a fever and I could barely swallow. On day 3, I had blisters all over my hands and vulva and inside of my throat.
anon930410
Post 38
I haven't finished reading the posts, but I thank everyone for posting. I wish I had seen this last week. I am staying with friends for a while and caught it from the baby.
I had a sore throat last Wednesday night. On Thursday, it was worse, and I didn't go to work. As the day went on, I had chills and a low grade fever and not much appetite. I thought it was the flu until about 10:30 p.m. That's when I realized I hadn't had an asthma attack, which I get when I have the flu.
I googled HFAM, and discovered that the next day wouldn't bode well for me as I had the sore throat for 36
hours. Sure enough, the next day I awoke to a swollen, slightly bumpy and oozing nose. As the morning wore on, my hands started itching. They itched so bad. Nothing would alleviate the incessant itching. I would get relief only while rubbing the cream in. I tried Advil PM so I could sleep, but it didn't work. I tried allergy meds, but they didn't work or make me sleep. The itching was so bad, I was thankful for the painful burning phase. Pain meds worked for that phase and I could sleep!
I'm now in the hard and numb fingertips phase. My face looks a hot mess, and I still have hives and blisters on my hands and feet, but they're going down. The itching is at a minimum. Just wondering when I will get the feeling back in my fingertips.
The doctor at the ER (I went to prove to my friends that I had it -- long story) said it would last two or three days. She was very nice, but she didn't know what she was talking about. The time frame is off, the prescription meds didn't work. Hell, I told her what I had in the first place. This thing is frustrating as hell.
anon355749
Post 37
I am just getting over mine, on day six now. Last Wednesday I started with a slight sore throat, body aches and a fever of 102+. The next day I got the blisters in my mouth.
I caught it from my 10 year old who mainly had blisters in her mouth and was prescribed antibiotics from the doctors who thought it was strep. She had maybe a spot or two on her hands and feet. The very next day (Friday) I woke up with a spot on my hand and by the evening I had a few more and on my feet. It clicked then that this was hand, foot and mouth. Saturday was much worse with spots all over
my hands and feet. They itched and burned, and the blisters in my throat hurt. By Sunday, my hands stopped itching and burning but my feet still continue to burn mostly when I wear shoes. My mouth is doing much better although I still have a few blisters. My hands have gone slightly numb, and I've got blisters in my nose as well which hurts like crap and is also numb!
anon342622
Post 36
I'm a 21 year old woman, suffering from severe irritation on my feet and arms. I visited several doctors, but it was of no use. Initially, I had a black mark on my left foot that used to cause severe irritation when something came into contact with it. Gradually, the skin in that part got peeled off, and many such black marks started on both the feet, and on my arms too.
I'm really depressed due to this. The marks are making my skin much harder. Please advise me of a medicine if this is a known problem.
anon342465
Post 34
I have had and have it. I am a 43 year old male. I had it last year, but it hadn't gotten this bad.
Day 1: Starts with a fever or chills and body aches and/or lethargy.
Day 2: A sore throat that is persistent and nothing seems to help. CVS or other drug stores carry something like Cepacol that is great for numbing the throat. It helps temporarily, but plain thick yogurt is the most comforting to a sore throat. Pain meds and such can be put in the yogurt to transport them past the throat sores (otherwise you may find it impossible to swallow even the tiniest pills).
Day 3: Sore throat continues and the symptomatic rash appears
as raised bumps or blisters on the skin, somewhere: scalp, hands, feet, sides, spine, etc., etc. It’s usually itchy and you think, “Did I get a bug bite? Is that poison ivy?” And then you're like, "No, it's this virus. Usually gone after a day.” Then the blisters start to show up in the mouth, usually in the back of the mouth in the cheek areas.
Days 4-8: Much the same. The blisters, raised bumps, and "cheese" that forms in the mouth (can be tiny blisters that make the inner cheek skin slough off or become loose and white). Usually the glands under the chin become sore and swell, headaches are frequent, you have loss of appetite, irritability, sleepless nights for a few nights in the earlier stages of the virus, night-sweating, frequent waking with inability to swallow or panic with pain of swallowing.
Again, the yogurt is the most helpful for transport of nutrients and pills, etc. that you might want to use for pain. I had to take a trip to the E.R. for headache pain that would not cease, and was prescribed oxycodone for the headache pain. I also found it effective for the mouth sores and sore throat as well to then be able to eat only soft foods. Don't try eating anything solid that is rough. It will rip through your throat like a wildfire!
Cepacol is somewhat helpful, yogurt is soothing, gargling salt water was painful and burned, and sugar set my throat and mouth on fire. Gatorade is helpful to get in electrolytes and keep fluids up. Water was challenging.
Days 9, 10: Mouth sores progress forward to inside the lips and general irritability follows, with morning headaches, itchy palms and tops of feet. Follow others’ tips with ice packs to the hands and feet, Tylenol for mouth sores, non-drowsy antihistamines during the day, drowsy ones at night.
If you go to the E.R., tell them you have acute pain or acute migraine so they can get you pain meds faster. Morphine is helpful during restless/sleepless nights to get a good night's sleep. Leave the E.R. after you get at least two shots of morphine or have enough pain meds so you can relax without thinking about it. If you are a woman, please take care of your child/children, and also please get someone to take care of your child during the day so you can nap or just relax and not have to be a Mom.
For men, the same: create an environment of relaxation, ease, and comfort. Coxsackie Virus/Disease a.k.a. Hand-Foot-Mouth disease is a royal pain in the keester!
Day 11: Still more mouth sores and blisters, but they come and go more rapidly. Yogurt (plain, unsweetened) is still the most effective in soothing the mouth sores. Coffee drinkers: don't give up your coffee; it will actually help with headaches this virus might give you. Now make that coffee a little less sweet, but have it with heavy cream or half and half for its soothing effect.
Day 12: Sores are down but the glands under the chin are super sensitive and sore as if someone whacked me with a two by four in my jaw. Ouch! Same treatments as before. Sores on back and front of tongue appear same as strep -- very confusing to graphically visually diagnose. Get the rapid-test strep test just for fun to rule strep out. Avoid prolonged sun exposure or public places where you might spread the virus. Walk around with alcohol wipes to clean surfaces before and after you touch anything. Get ice packs. Get plain, unsweetened yogurt. Get a lot of rest.
Day 13: It should be starting to subside. All the blisters and bumps and mouth sores. The sore throat is mostly gone, but is replaced with mouth sores that are more forward as the virus is making its last ditch effort to re-infect everyone around me. Try not to talk, but use sign language or write on paper, or just avoid other people entirely. Keep the fluids going.
anon342226
Post 33
I had this last year but thankfully, it did not itch like some are reporting. I am a 35 year old male. I have a 4 year old who did not show any symptoms, so she either carried it or I picked it up at the daycare center since I spend five minutes there each night helping clean up, etc.
Because of this infection that is "rare in adulthood", my doctor said it is a sign of a compromised immune system and asked if I ever had an AIDS test. I had not, so one was ordered and for two days I stressed over the potential life changing news. It was negative, but after reading more on the disease, it doesn't strike me as being that rare in adults.
anon338522
Post 32
I am a 21 year old guy and I have no idea how I got mine. I was having headaches and then a sore throat came in. After a few days, the sore throat went down, but I awoke with itchy hands that felt like little needles poking me. I went to the doctor's office where he told me I also had a fever, and what I had was Hand-Foot-Mouth Disease. Hopefully mine is not too bad but it is getting itchier.
anon331624
Post 31
I am 39 years old and contracted hfmd from my 5 year old. He got energetic after day two and spots were rarely visible. As for me, the hfmd is in the fifth day at work and the doctor said I can be considered a full blown case.
Blisters are everywhere -- on my palm area, both front and back, feet both front and back, and my mouth is infested with ulcers. My throat is equally bad.I cannot sleep and get an average of two to four hours per day. My doctor suggested ice cream as alternative meal.
anon314240
Post 30
I'm a 35 year old woman and have contracted the virus from my seven month old daughter.
Day 1: Terrible sore throat and high fever.
Day 2: Same. Went to doctor for strep throat and it came out negative. The doctor said I probably contracted the HFMD from my daughter.
Day 3: Small number of blisters on my toes and exterior of feet. My hands only had blisters on the thumbs and index fingers.
Day 4: More blisters took over my entire mouth. Also, two ulcers have developed in my vaginal area. My labia has two blood blisters that have now developed into a canker sore.
I'm concerned because that area is not dry. I'm not sure of a treatment for the genitalia area? Anyone know of something that might help healing?
anon306200
Post 29
Use Calamine lotion, ice packs, take Ibuprofen and antihistamines, and then all you can do is wait. I've got it terribly. I am unbearably itchy and have two babies who also have it, and it is awful.
anon305888
Post 28
I am a 35 year old adult who just got over the worst part of HFAM. I caught it from my niece who is 2. I can verify that it indeed itches a lot in adults. It was terrible. I was up constantly the other night because of the itching and my feet are just raw now. I can barely walk with this stuff.
anon295639
Post 27
I'm a school teacher and caght HFMD from some kid I am sure.
Day 1: High fever, chills, hot and cold flashes, flu like symptoms, shaking so much I thought my back was going to break in half.
Day 2: Woke up with what felt like paper cuts all over my hands and feet. Thought I had a cold sore on my mouth. Went to the doctor and he said it was HFMD and that there was nothing he could. do. Conditions got worse throughout the day, with blistering, spots and pain.
Day 3: More blisters and spots, intolerable pain, itching, scabbing, and I looked awful! Low appetite too. Had to get Tylenol One's for the pain. I could barely
walk or hold anything because of the pain. The Tylenol kicked in and reduced the pain significantly.
Day 4: Even more spots/blisters. This time they appeared in my groin area, a few on the genitals, buttocks, ears, and the odd one on my arms. Itching reduced, appetite still low, and scabbing around the mouth.
Day 5: Not nearly as much pain but plenty of blisters. More dry scabbing around the mouth. New pain under the fingernails. I suppose I might lose those as it has been reported in other instances. I look and feel awful! Psychologically, I am doing OK but it has put me in a funk because I can't see anyone.
I am currently writing on day 5 and am wondering when I will see improvements. This is one of the worst viruses to catch as an adult! I have put myself under quarantine and am getting well acquainted with my old friend, the television.
If you have this, I know what you're going through. At least I don't have it in my throat -- yet. Who knows? Good luck to me. If anyone knows of the time that a person notices improvements, please post this.
anon294434
Post 26
Anyone who tells you that Hand, Foot and Mouth does not itch either hasn't had it as an adult or is super lucky. My palms are covered and it is the worst itching I have ever had.
I am 35 years old and had chicken pox as a child and have suffered many different bouts hives finding out that I am allergic to three different antibiotics, and seriously, this is the worst itching I have ever had! Holding icepacks has been the only thing to offer any sort of relief.
anon285085
Post 25
About a week ago my 16 year old son complained of "not feeling well". He said he just didn't feel right and that he thought he had a fever because he was freezing even though it was really hot outside. I had him take his temperature and it was 103.1 F. Here is how his HFMD unfolded.
Day 1: Body aches, overall feeling of not being well. High fever of 103.1 and sore throat.
Day 2: Went to urgent care where they did a rapid strep test which came out negative. They informed us they still thought it was strep and said the rapid test can give false positives so they sent that to the lab and prescribed antibiotics for
strep.
Day 3: Throat felt worse so did body. His hands, feet and body were starting to break out.
Day 4: Throat was way worse and he couldn't eat or drink without extreme pain. He had body aches, a rash began on his scalp, face and his hands and feet totally covered in blisters. I took him back to urgent care where the doctor right away told him it was HFMD. She told him to stop taking antibiotics because they wouldn't help and that it needed to run its course. She prescribed him Tylenol with codeine for the pain and a prescription gel/ointment that is dental grade used for ulcers in the mouth that you rub on all the sores and it numbs them for quite awhile. This helped him to eat.
Day 5: Woke up with more blisters on his ears, calves, back and arms but the pain in his throat was slightly better. The blisters on his face were scabbing over, but the new ones on his ears were just starting.
Day 6: Most of the pain was gone from his throat and his face looked much better. No new blisters have formed.
I hope this helps. When we were trying to figure out what this was, we couldn't find any solid information that connected the scalp blisters and face blisters with HFMD so we assumed he must have had something other than that.
Had we found this site sooner, it would have eased my fears a bit. If you do find yourself fighting this virus, please go to your doctor and get pain meds and I recommend you also ask for prescription grade gel, paste or ointment for the sores in your mouth. Nothing is worse than having pain so bad you can't eat or drink. Your body needs energy to fight and it needs food and drink for energy. Good luck!
anon280970
Post 24
Adult HFMD Treatment for the following symptoms:
Sore throat: Olive leaf extract, colloidal silver spray.
Rashes/blisters: Calamine lotion (helps with itch and dries them up a lot quicker).
Scalp acne: Frequent hair washing with shampoo, preferably anti-dandruff.
Itchy skin: Antihistamines like Telfast or Zyrtec.
Fever/headache: Panadol or Nurofen.
Drink plenty of water.
anon280968
Post 23
I'm 27 and I got HFMD from my two little boys, an almost 3-year-old and 14-month-old. The doctor said it was very rare for adults to get it but I got it as quite a few of you grown ups did as well. Thought I would do a posting as I've been researching every day since my sons got HMFD and most of the information I have got hasn't been very useful.
Both of my boys had high fever last Saturday during dinner and vomited later on. The fever persisted for another day and on the third day, they started having red spots around and in their mouth and throat, on their hands, legs, knees and feet. Some of the
spots turned to blisters on the fourth day. They had a bit of a temperature on and off on days 4 and 5 and got diagnosed with tonsillitis as a secondary infection.
I read about loss of appetite with HFMD but I guess that made it even worse. They didn't want to eat and would only drink a little. On the sixth day, some of the blisters started popping. On the seventh day, they started drying up and the kids felt a lot better. Today's the eighth day and they're pretty much back to their normal selves, playing and running amok, and they're finally eating again.
Now, my story: On Tuesday afternoon, I started having the shakes and had a really sore throat. I had a bad feeling I was getting it too. Tuesday evening I had a high temperature of 39.1 degrees Celsius. I had nausea and had such a sore back it felt like it was going to break.
Wednesday: My temperature was 40.3 degrees celsius in the morning and my back still felt like it was going to break. I also had loss of appetite and lethargy. My throat was very sore so I looked at it in the mirror that night with a torch and saw I had sores all inside my mouth and ulcers in my throat, tonsils, etc. The torch also revealed many tiny, ulcer-type sores on my lips and sores had started developing around my mouth. I emailed boss to say I wasn't going to be able to go in to work as I knew how contagious it was.
Thursday: My fever had subsided and I gargled with olive leaf extract. It stung quite a bit, but definitely numbed it and I could eat. Spots and blisters then started appearing very rapidly all over my hands and feet. I had little bumps all over my scalp about 1cm apart in all directions that were so itchy. I didn't know what they were so I looked it up, and they were scalp acne which, in this case, appeared to be caused by the viral infection. I couldn't sleep all night as my hands and feet started swelling so much that I couldn't close my hands and they felt like they were going to explode.
Friday: I was very frustrated. I read that it's not itchy for kids but can be very itchy for adults, which is definitely the case for me. I was beyond itchy. I was feeling so itchy and sore I felt like banging my head against the wall. The blisters around my mouth had started popping and weeping. I felt dirty and like a leper. This disease is so disgusting! At least I could take panadol for the pain. but it only took the edge off. I felt like I needed stronger painkillers but couldn't because I was still breastfeeding my 14-month-old. I called out an after hours doctor as there was no way I was leaving the house looking like that. The doctor walked in, took one look at me and said, "You have hand, foot, mouth disease. I can't do anything for you", and started walking out.
anon277957
Post 22
I contracted HFMD from the kids I nanny for. I'm 27.
Day 1: Terrible fever for about 16 hours, absolutely no appetite, and a mild sore throat.
Day 2: Fever was gone, sore throat a little worse, still no appetite, and small blisters began forming on my fingers. By the end of the day, the blisters were all over my fingers and starting in between my toes.
Day 3: The blisters and now rash all over my hands and feet are itchy, stinging, and unbearable. It woke me up at 4 a.m. I'm barely able to do simple things like walk, open doors, turn on faucets, etc.
The only things I've found to ease the itching and stinging are calamine lotion and ice packs. The ice packs provide instant relief as long as you hold onto them! It's the only thing that kept me from crying all day. I hope this helps someone out there!
anon274093
Post 21
I think I may have it. I have a sore throat that is so painful but not like a cold sore throat and hundreds of tiny itchy clear blisters all over my big toe. My glands are up and i am taking panadol for the pain in the throat. Did someone say not to put anti-fungal cream on my toe?
anon271136
Post 20
I am a 45 year old mother and I got if from my 12 year old daughter who got it from her toddler sister who did not get it -- just carried it. It has been horrible. My hands, feet, legs, arms inner thighs, neck, throat all have spots and blisters from this horrible virus. I still have spots on my hands and feet and it has been seven days and they look awful and I pray they go away.
My hands look scaly and my fingertips are numb and so are my toes to a point. I feel like I am wearing gloves and socks all the time from the swelling.
anon270245
Post 19
My 10 month old son snagged this nasty virus from the neighbor boy. But yes indeed it was a cake walk for him.
Then I started feeling bad. Day 1: 102.1 temp followed by shivers and sweating. This is typical of a high fever.
Day 2: Extreme sore throat followed by pus filled blisters in the mouth.
Day 3: Blisters forming on tongue and roof of mouth as well as severely itchy blisters and rash on feet and hands. This is very close to unbearable.
That is as far as I have gotten with the issue. I thought I would post my home remedy for the release from itching, if even for a few minutes: cornstarch and cool water soak! It was heavenly.
I would not wish this on anyone. Good luck to you all.
bball24
Post 18
Hand, foot and mouth is brutal I got it from my adorable 2yr old nephew. Having it makes me really feel for the babies that get it, especially because they cannot fully articulate how they are feeling.
anon269780
Post 17
I'm 25 years old. Day 1: Mild fever and sore throat, achy.
Day 2: No sore throat, no fever but achy and fatigued.
Day 3: Woke up and had open sores all in my scalp and on forehead/eyebrows. I had one or two bumps on my left hand and left foot. By 4:30 p.m. later on that day, hands and feet were covered with bumps and blisters and open sores were substantially worse. My hands and feet are extremely itchy and painful. By that night, open sores had spread to in and outside my nares (nostrils)and ears.
Day 4: Open sores on face are crusty and leaking fluid, especially on my nose and in between my eyebrows. I look like
a leper! My hands and feet are still painful, and I'm taking tylenol with codeine, periodically with a glass or two of merlot. The symptoms have yet to subside. I'm getting worse before I get better. I already called off all of next week from work. I contracted HFM from my two year old handsome nephew.
anon262968
Post 16
My two year old daughter and myself have contracted HFM in the last week. My daughter has no rash on her hands, three spots in her mouth, two around her mouth and one on her hand. Her feet however, are covered and she is itching constantly! I am giving her regular doses of child piriton (allerief) and covering her feet in calamine lotion. This helps along with calpol for a period of about four hours.
I have spots on my hands only, which are excruciating! I would advise anyone not to use any perfumed lotions or anything that would have the possibility to irritate or sting! Calamine is a life saver! And HFAM is itchy!
anon261456
Post 15
I don't know how old this forum is, but I'd like to add that I got HFMD from my 7 month old. His case was pretty textbook.
I was told healthy adults don't get it. Ha! I am a healthy 30 year old and I got it. "They" really need to update the information given on this condition. It DOES itch and it IS painful. My hands and feet are completely COVERED with blisters that are so itchy, I've just cried. The doctor prescribed pain medication just to give me some relief. Topical treatments only seem to make the itching more intense. I really hope this goes away soon.
anon259318
Post 14
Thank you for this website! I'm an adult, 40-plus.
Day 1: Terrible sore throat.
Day 2: Sore throat feeling worse. I went to the Minute Clinic, and the rapid strep test was negative. I was advised to take ibuprofen for pain.
Day 3: Sore throat and mouth suddenly has six large canker sores (I was on vacation and so did not seek a doctor's advice). I kept taking ibuprofen and used canker sore medicine to calm down my mouth.
Day 4: Now trying hydrogen peroxide rinses and milk of magnesia to calm down the canker sores. I could barely eat or swallow since it hurt too much even though I was taking ibuprofen regularly. Hydrogen peroxide seems to work best
to shrink canker sores but I have been gargling with warm salt water, too.
Day 5: Now have hives/rash on forearms and calves. I'd never had this before so it surprised me to see hundreds of tiny spots all over me calves and starting to dot inside of my foot arch. These do not itch. I began taking diphenhydramine for hives/rash.
Day 6: I still have all symptoms, but my throat is less sore, and I took the same remedies. My foot arch was then covered with hives/rash. I also had hives/rash on ankles, which itched and the palms of hands itch too but hives/rash are barely noticeable on palms of hands. On the eve of Day 6, the horrible joint pain began, too.
Day 7: Sore throat gone, mouth sores mostly gone, feet and hands now swell up though. It was hard to move, since the joint pain made it difficult to grasp anything, sit down or walk. I was still regularly taking ibuprofen and diphenhydramine.
Day 8: The joint pain is awful in the morning. After taking ibuprofen and diphenhydramine, and resting on a heated mattress pad, the swelling in my feet and hands has gone down about half. The joint pain is down by about half this afternoon too. Hopefully, I'm on my way to a full recovery.
anon252077
Post 13
I'm 12 years old and I have it and they say it's not itchy? Well it is! I'm covered in spots all over my face. It's not looking good.
anon245999
Post 12
I got it from my one year old son, who had a very mild case of the HMFD. But in the other I can't even walk, it's so uncomfortable and painful! I am miserable. And I have those bumps all over my forehead, outside of mouth, nose, hands and bottom of my feet.
Any tips or info on how long the pain will last on the bottom of my feet and or any home remedies?
anon243291
Post 11
I have just contracted HFM from my 13 month old daughter who I guess got it from one of the playgroups we attend. The rash is really itchy and if anyone tells you it's not, they are wrong!
anon198075
Post 10
Well I have hand, foot and mouth right now and I'm an adult. The blisters are so itchy and I can hardly walk on my feet; it's that painful. The doctor confirmed it as hand, foot and mouth so if the rash is not itchy then I am sorry but you're wrong because it is. I just wanted to let you all know. thanks. --Chantelle
godders
Post 9
My daughter has just been diagnosed with hand foot and mouth. No sores in her mouth though. But itchy rash on hand feet legs and buttocks. If the rash for HFAM isn't supposed to be itchy, any ideas what it could be?
anon157658
Post 7
You shouldn't put any lotion or similar on the rash/blisters as it will stop them from drying out (which is the best thing for the blisters to do). just give panadol or similar to give the child some relief from blisters' soreness and it will also help any restlessness the child may be experiencing. Hope this helps.
anon157137
Post 6
My daughter was diagnosed with hand, foot and mouth, but there were no sores or spots in her mouth at all. The rash covered her whole arms, hands, feet legs and bum though, and after being gone for a couple of weeks it appears to be coming back. Is it possible it could be something else, as lack of mouth spots is apparently unusual, as is so much rash?
anon113874
Post 5
Just so everyone knows, I have gotten HFAM twice, both times as an adult. The blisters were very itchy the second time around, the first time wasn't nearly as bad. I found that putting my hands in a bowl of hot water with baking soda helped take the itching away.
anon100953
Post 4
My 15 month son had contracted hand, foot and mouth from daycare approximately two weeks ago. Had blisters on his hands, feet, legs and buttocks. Very few were spotted inside his mouth.
I used infant benadryl liquid to help with the possibility of itchiness, and calamine lotion as was directed by the doctor/pharmacist. However, I found that bathing him with baking soda was probably the "best" way to soothe him.
Now, here I am, and he has it a second time. This time mostly in his mouth (started with blisters around mouth that looked like he was sucking his soother too much) then discovered them on his hands again.
I was reading on one web site, that the virus is
almost same in nature as a mild case of Herpes. That the virus can be in the body, but not show any symptoms on the outside. Therefore it can develop a second time. However, this is not common. Hope my experience helps many of you.
Planch
Post 3
Is it possible for a child to contract hand foot and mouth disease twice?
Or is it like chicken pox, once you've had it, that's it?
My child is having what seems like a recurrence of hand foot and mouth, but I thought that this was rare -- does anybody have any advice?
FirstViolin
Post 2
@EarlyForest -- I can't imagine that it would be a problem to put some hand lotion on the child, however, it probably isn't necessary.
Why do you need to soothe it, is the rash itchy or something?
If the rash is itchy, then it probably isn't hand, foot, and mouth -- you should check for other causes.
However, unless there are open sores or something like that, I would think that a nice, mild hand lotion could only help.
EarlyForest
Post 1
My niece is having some pretty bad rashes on her hands and feet, we think it is hand, foot, and mouth disease.
Does anybody know if there is a good hand lotion that could help soothe the rash, or if it is OK to put lotion on a baby with hand, foot, and mouth disease?
Post your comments
Post Anonymously
Login
username
password
forgot password?
Register
username
password
confirm
email
|
{
"url": "http://www.wisegeek.org/what-is-hand-foot-and-mouth-disease.htm",
"source_domain": "www.wisegeek.org",
"snapshot_id": "crawl=CC-MAIN-2018-17",
"warc_metadata": {
"Content-Length": "183176",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:NO4MQ3IXL2KMYSFSDUZZLLPQGFSR2BXX",
"WARC-Concurrent-To": "<urn:uuid:434015d3-ec2b-4186-8ceb-3c0e958a26a8>",
"WARC-Date": "2018-04-25T08:34:33",
"WARC-IP-Address": "162.210.232.130",
"WARC-Identified-Payload-Type": "application/xhtml+xml",
"WARC-Payload-Digest": "sha1:7BSKL3G6UBP37JFXCS7LSVQQB4NIWLWZ",
"WARC-Record-ID": "<urn:uuid:71f409ff-e046-4f6b-a018-9113dfda1b14>",
"WARC-Target-URI": "http://www.wisegeek.org/what-is-hand-foot-and-mouth-disease.htm",
"WARC-Truncated": "length",
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:1e0b2575-fe29-4269-8f81-4a63638b1714>"
},
"warc_info": "robots: classic\r\nhostname: ip-10-95-191-249.ec2.internal\r\nsoftware: Nutch 1.6 (CC)\r\nisPartOf: CC-MAIN-2018-17\r\noperator: Common Crawl Admin\r\ndescription: Wide crawl of the web for April 2018\r\npublisher: Common Crawl\r\nformat: WARC File Format 1.0\r\nconformsTo: http://bibnum.bnf.fr/WARC/WARC_ISO_28500_version1_latestdraft.pdf"
}
|
{
"line_start_idx": [
0,
11,
12,
50,
51,
67,
94,
121,
159,
184,
198,
225,
248,
280,
404,
405,
513,
514,
928,
929,
1392,
1393,
1673,
1674,
1677,
1678,
2326,
2327,
2833,
2834,
3248,
3249,
3252,
3253,
3273,
3274,
3286,
3287,
3308,
3309,
3320,
3328,
3329,
3614,
3615,
3626,
3634,
3635,
3808,
3809,
4116,
4117,
4224,
4225,
4718,
4719,
4969,
4970,
5297,
5298,
5309,
5317,
5318,
5492,
5493,
5895,
5896,
6267,
6278,
6286,
6287,
6661,
6662,
6797,
6798,
6809,
6817,
6818,
6918,
6919,
6988,
6989,
7392,
7393,
7455,
7456,
7804,
7805,
8271,
8272,
8721,
8722,
8944,
8945,
9240,
9241,
9747,
9748,
9910,
9911,
10297,
10298,
10868,
10869,
11238,
11239,
11250,
11258,
11259,
11545,
11546,
11902,
11903,
11914,
11922,
11923,
12319,
12320,
12331,
12339,
12340,
12567,
12568,
12837,
12838,
12849,
12857,
12858,
12946,
12947,
12991,
12992,
13128,
13129,
13254,
13255,
13431,
13432,
13578,
13579,
13590,
13598,
13599,
13798,
13799,
13810,
13818,
13819,
14115,
14116,
14127,
14135,
14136,
14197,
14198,
14328,
14329,
14600,
14601,
14762,
14763,
14864,
14865,
15075,
15076,
15382,
15383,
15619,
15620,
15828,
15829,
15840,
15848,
15849,
16028,
16029,
16314,
16315,
16326,
16334,
16335,
16619,
16620,
16711,
16712,
16956,
16957,
16964,
16965,
17056,
17057,
17650,
17651,
17862,
17863,
17974,
17975,
18202,
18203,
18610,
18611,
18622,
18630,
18631,
18680,
18681,
18738,
18739,
18823,
18824,
18898,
18899,
18950,
18951,
18987,
18988,
19011,
19012,
19023,
19031,
19032,
19381,
19382,
19639,
19640,
19804,
19805,
20204,
20205,
20482,
20483,
21012,
21013,
21613,
21614,
22397,
22398,
22409,
22417,
22418,
22471,
22472,
22562,
22563,
22775,
22776,
22978,
22979,
23233,
23234,
23245,
23253,
23254,
23537,
23538,
23549,
23557,
23558,
23942,
23943,
24095,
24096,
24107,
24115,
24116,
24227,
24228,
24341,
24342,
24415,
24416,
24565,
24566,
24758,
24759,
24814,
24815,
24823,
24831,
24832,
25034,
25035,
25046,
25054,
25055,
25114,
25115,
25170,
25171,
25561,
25562,
25680,
25681,
25985,
25996,
26004,
26005,
26409,
26410,
26630,
26631,
26642,
26650,
26651,
26774,
26775,
27218,
27219,
27230,
27238,
27239,
27290,
27291,
27320,
27321,
27465,
27466,
27667,
27668,
27899,
27900,
27975,
27976,
28231,
28232,
28562,
28563,
28806,
28807,
29098,
29099,
29110,
29118,
29119,
29253,
29254,
29265,
29273,
29274,
29532,
29533,
29632,
29633,
29644,
29652,
29653,
29842,
29843,
29854,
29862,
29863,
30182,
30183,
30191,
30198,
30199,
30415,
30416,
30427,
30434,
30435,
30753,
30754,
30765,
30772,
30773,
31128,
31129,
31140,
31147,
31148,
31412,
31413,
31424,
31431,
31432,
31618,
31619,
31848,
31849,
32055,
32056,
32105,
32106,
32338,
32345,
32352,
32353,
32427,
32428,
32486,
32487,
32625,
32626,
32638,
32645,
32646,
32781,
32782,
32844,
32845,
32950,
32951,
33073,
33074,
33086,
33093,
33094,
33205,
33206,
33363,
33364,
33383,
33384,
33401,
33402,
33408,
33409,
33418,
33427,
33444,
33445,
33454,
33455,
33464,
33473,
33481
],
"line_end_idx": [
11,
12,
50,
51,
67,
94,
121,
159,
184,
198,
225,
248,
280,
404,
405,
513,
514,
928,
929,
1392,
1393,
1673,
1674,
1677,
1678,
2326,
2327,
2833,
2834,
3248,
3249,
3252,
3253,
3273,
3274,
3286,
3287,
3308,
3309,
3320,
3328,
3329,
3614,
3615,
3626,
3634,
3635,
3808,
3809,
4116,
4117,
4224,
4225,
4718,
4719,
4969,
4970,
5297,
5298,
5309,
5317,
5318,
5492,
5493,
5895,
5896,
6267,
6278,
6286,
6287,
6661,
6662,
6797,
6798,
6809,
6817,
6818,
6918,
6919,
6988,
6989,
7392,
7393,
7455,
7456,
7804,
7805,
8271,
8272,
8721,
8722,
8944,
8945,
9240,
9241,
9747,
9748,
9910,
9911,
10297,
10298,
10868,
10869,
11238,
11239,
11250,
11258,
11259,
11545,
11546,
11902,
11903,
11914,
11922,
11923,
12319,
12320,
12331,
12339,
12340,
12567,
12568,
12837,
12838,
12849,
12857,
12858,
12946,
12947,
12991,
12992,
13128,
13129,
13254,
13255,
13431,
13432,
13578,
13579,
13590,
13598,
13599,
13798,
13799,
13810,
13818,
13819,
14115,
14116,
14127,
14135,
14136,
14197,
14198,
14328,
14329,
14600,
14601,
14762,
14763,
14864,
14865,
15075,
15076,
15382,
15383,
15619,
15620,
15828,
15829,
15840,
15848,
15849,
16028,
16029,
16314,
16315,
16326,
16334,
16335,
16619,
16620,
16711,
16712,
16956,
16957,
16964,
16965,
17056,
17057,
17650,
17651,
17862,
17863,
17974,
17975,
18202,
18203,
18610,
18611,
18622,
18630,
18631,
18680,
18681,
18738,
18739,
18823,
18824,
18898,
18899,
18950,
18951,
18987,
18988,
19011,
19012,
19023,
19031,
19032,
19381,
19382,
19639,
19640,
19804,
19805,
20204,
20205,
20482,
20483,
21012,
21013,
21613,
21614,
22397,
22398,
22409,
22417,
22418,
22471,
22472,
22562,
22563,
22775,
22776,
22978,
22979,
23233,
23234,
23245,
23253,
23254,
23537,
23538,
23549,
23557,
23558,
23942,
23943,
24095,
24096,
24107,
24115,
24116,
24227,
24228,
24341,
24342,
24415,
24416,
24565,
24566,
24758,
24759,
24814,
24815,
24823,
24831,
24832,
25034,
25035,
25046,
25054,
25055,
25114,
25115,
25170,
25171,
25561,
25562,
25680,
25681,
25985,
25996,
26004,
26005,
26409,
26410,
26630,
26631,
26642,
26650,
26651,
26774,
26775,
27218,
27219,
27230,
27238,
27239,
27290,
27291,
27320,
27321,
27465,
27466,
27667,
27668,
27899,
27900,
27975,
27976,
28231,
28232,
28562,
28563,
28806,
28807,
29098,
29099,
29110,
29118,
29119,
29253,
29254,
29265,
29273,
29274,
29532,
29533,
29632,
29633,
29644,
29652,
29653,
29842,
29843,
29854,
29862,
29863,
30182,
30183,
30191,
30198,
30199,
30415,
30416,
30427,
30434,
30435,
30753,
30754,
30765,
30772,
30773,
31128,
31129,
31140,
31147,
31148,
31412,
31413,
31424,
31431,
31432,
31618,
31619,
31848,
31849,
32055,
32056,
32105,
32106,
32338,
32345,
32352,
32353,
32427,
32428,
32486,
32487,
32625,
32626,
32638,
32645,
32646,
32781,
32782,
32844,
32845,
32950,
32951,
33073,
33074,
33086,
33093,
33094,
33205,
33206,
33363,
33364,
33383,
33384,
33401,
33402,
33408,
33409,
33418,
33427,
33444,
33445,
33454,
33455,
33464,
33473,
33481,
33486
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 33486,
"ccnet_original_nlines": 426,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 2,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.4421611428260803,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.035928141325712204,
"rps_doc_frac_lines_end_with_ellipsis": 0.004683840088546276,
"rps_doc_frac_no_alph_words": 0.15024496614933014,
"rps_doc_frac_unique_words": 0.21773934364318848,
"rps_doc_mean_word_length": 4.169388294219971,
"rps_doc_num_sentences": 446,
"rps_doc_symbol_to_word_ratio": 0.0002721800119616091,
"rps_doc_unigram_entropy": 5.957845687866211,
"rps_doc_word_count": 6246,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.0337531715631485,
"rps_doc_frac_chars_dupe_6grams": 0.015628600493073463,
"rps_doc_frac_chars_dupe_7grams": 0.0041471500881016254,
"rps_doc_frac_chars_dupe_8grams": 0.0022271699272096157,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.010367870330810547,
"rps_doc_frac_chars_top_3gram": 0.00829428993165493,
"rps_doc_frac_chars_top_4gram": 0.010444669984281063,
"rps_doc_books_importance": -2875.745361328125,
"rps_doc_books_importance_length_correction": -2875.745361328125,
"rps_doc_openwebtext_importance": -1950.2177734375,
"rps_doc_openwebtext_importance_length_correction": -1950.2177734375,
"rps_doc_wikipedia_importance": -1231.2877197265625,
"rps_doc_wikipedia_importance_length_correction": -1231.2877197265625
},
"fasttext": {
"dclm": 0.10271573066711426,
"english": 0.9835770726203918,
"fineweb_edu_approx": 1.4617143869400024,
"eai_general_math": 0.029043670743703842,
"eai_open_web_math": 0.2638663053512573,
"eai_web_code": 0.004714730195701122
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.994",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "616.9",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "5",
"label": "Social/Forum"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "0",
"label": "No Artifacts"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "0",
"label": "No missing content"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "5",
"label": "Comment Section"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
9222580d47c553ea90dc0f5e416f8f3a
|
5,488,489,484,920,895,000
|
@article {Nightingale1061, author = {Nightingale, Julia A and Rogers, Duncan F and Barnes, Peter J}, title = {Effect of inhaled ozone on exhaled nitric oxide, pulmonary function, and induced sputum in normal and asthmatic subjects}, volume = {54}, number = {12}, pages = {1061--1069}, year = {1999}, doi = {10.1136/thx.54.12.1061}, publisher = {BMJ Publishing Group Ltd}, abstract = {BACKGROUND Nitric oxide (NO) may have a role in the pathophysiology of tissue injury in response to inhaled ozone in animals.METHODS A double blind, randomised, placebo controlled, crossover study was undertaken to investigate the effects of inhaled ozone in 10 normal and 10 atopic asthmatic volunteers. Subjects were exposed to 200 ppb ozone or clean air for four hours with intermittent exercise, followed by hourly measurement of spirometric parameters and exhaled NO for four hours. Nasal NO and methacholine reactivity were measured and exhaled breath condensate and induced sputum samples were collected four and 24 hours after exposure.RESULTS Exposure to ozone caused a fall in forced expiratory volume in one second (FEV1) of 7\% in normal subjects (p\<0.05) and 9\% in asthmatic subjects (p\<0.005). There was a 39\% increase in sputum neutrophils at four hours in normal subjects (p\<0.05) and a 35\% increase at four hours in asthmatic subjects, remaining high at 24 hours (p\<0.005 and p\<0.05, respectively). There were no differences between normal and asthmatic subjects. There were no changes in methacholine reactivity, exhaled or nasal NO, nitrite levels in exhaled breath condensate, or sputum supernatant concentrations of interleukin 8, tumour necrosis factor α, or granulocyte-macrophage colony stimulating factor in either group.CONCLUSIONS Exposure to 200 ppb ozone leads to a neutrophil inflammatory response in normal and asthmatic subjects but no changes in exhaled NO or nitrite levels.}, issn = {0040-6376}, URL = {https://thorax.bmj.com/content/54/12/1061}, eprint = {https://thorax.bmj.com/content/54/12/1061.full.pdf}, journal = {Thorax} }
|
{
"url": "https://thorax.bmj.com/highwire/citation/144861/bibtext",
"source_domain": "thorax.bmj.com",
"snapshot_id": "CC-MAIN-2023-06",
"warc_metadata": {
"Content-Length": "3202",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:SI2OYXWQWC4T4XG7QXDRDL4XYPIJYG3G",
"WARC-Concurrent-To": "<urn:uuid:63535c7a-da38-4a94-af11-3321f9dcf5af>",
"WARC-Date": "2023-02-01T21:27:09",
"WARC-IP-Address": "104.18.6.34",
"WARC-Identified-Payload-Type": "text/plain",
"WARC-Payload-Digest": "sha1:YM7H7CHWMY6NMXHKEXRG74X6DBWRMKQF",
"WARC-Record-ID": "<urn:uuid:a7a97020-3dc0-4210-a44d-fab277631a69>",
"WARC-Target-URI": "https://thorax.bmj.com/highwire/citation/144861/bibtext",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:53de3950-f26e-4e86-9740-ac999addeffe>"
},
"warc_info": "isPartOf: CC-MAIN-2023-06\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for January/February 2023\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-254\r\nsoftware: Apache Nutch 1.19 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.4-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0
],
"line_end_idx": [
2057
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 2057,
"ccnet_original_nlines": 0,
"rps_doc_curly_bracket": 0.013612059876322746,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.22425629198551178,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.03661327064037323,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.3546910881996155,
"rps_doc_frac_unique_words": 0.5368421077728271,
"rps_doc_mean_word_length": 5.666666507720947,
"rps_doc_num_sentences": 25,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 4.64521598815918,
"rps_doc_word_count": 285,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.06315789371728897,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.05263157933950424,
"rps_doc_frac_chars_top_3gram": 0.03343652933835983,
"rps_doc_frac_chars_top_4gram": 0.0482972115278244,
"rps_doc_books_importance": -212.7028045654297,
"rps_doc_books_importance_length_correction": -212.7028045654297,
"rps_doc_openwebtext_importance": -118.45597076416016,
"rps_doc_openwebtext_importance_length_correction": -118.45597076416016,
"rps_doc_wikipedia_importance": -82.22493743896484,
"rps_doc_wikipedia_importance_length_correction": -82.22493743896484
},
"fasttext": {
"dclm": 0.32976967096328735,
"english": 0.9114504456520081,
"fineweb_edu_approx": 2.781738519668579,
"eai_general_math": 0.5372231006622314,
"eai_open_web_math": 0.3896896243095398,
"eai_web_code": 0.023121420294046402
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.2",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "615.5",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "4",
"label": "Analyze"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "1",
"label": "Factual"
},
"secondary": {
"code": "2",
"label": "Conceptual"
}
},
"document_type_v1": {
"primary": {
"code": "2",
"label": "Academic/Research"
},
"secondary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "3",
"label": "Academic Writing"
},
"secondary": {
"code": "8",
"label": "Documentation"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "4",
"label": "Graduate/Expert Level"
},
"secondary": {
"code": "3",
"label": "Undergraduate Level"
}
}
}
|
b755ed28a90d11d590ef646404f4afc5
|
2,251,050,412,788,132,900
|
Exercise & Fitness
health and fitness
Each muscle cell accommodates contractile proteins – actin and myosin – that give the muscle its strength. These fibers contract together, producing the so-referred to as energy stroke. The total force is determined by the variety of these models contracting in unison. Generally, lifting or pushing something of a set weight in a prescribed place and comparing the results against any given population is the easiest way.
Most importantly, regular exercise can enhance your quality of life. A minimal of 30 minutes a day can allow you to take pleasure in these advantages. Muscular power refers to the most quantity of force a muscle can produce at one time, additionally referred to as a one repetition maximum. You can practice your muscles to be stronger by lifting heavy weights for a number of repetitions. Common workout routines that concentrate on muscular energy include loaded squats, leg press, and bench press.
Types of Exercise
Lack of regular bodily exercise is a major reason for continual disease . This is as a result of exercise helps release hormones that promote the power of your muscular tissues to soak up amino acids.
‘You’ fans assume Joe is a psychopath, but mental well being specialists say they’re mistaken
It could also be irritating, but which means your body is changing for the better. Be positive to stay hydrated, stretch, and eat meals with a good amount of protein after every exercise. The protein will assist hold your muscles, not fat, rebuilding.
You may also see an estimate of the variety of energy you’ve burned throughout your session as well as the number of MEPS factors you have earned. Again, cardio and muscular fitness coaching are going to pack essentially the most punch in relation to burning energy and incomes MEPs. Both of those elements give attention to coaching your neuromuscular system, but in different methods. ACTIVE is the leader in on-line event registrations from 5k working races and marathons to softball leagues and local occasions. ACTIVE also makes it simple to study and put together for all of the belongings you like to do with expert resources, coaching plans and health calculators.
|
{
"url": "https://www.badmintonandalucia.com/exercise-fitness-9.html",
"source_domain": "www.badmintonandalucia.com",
"snapshot_id": "crawl=CC-MAIN-2021-25",
"warc_metadata": {
"Content-Length": "35600",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:JIKIKEZZ7MLLFDSEOUXEUVLP3SXD5A3N",
"WARC-Concurrent-To": "<urn:uuid:522faa9f-71f2-4f40-b192-031759745f6e>",
"WARC-Date": "2021-06-12T21:23:51",
"WARC-IP-Address": "172.67.222.79",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:7DL6PMAFULGGLGIWPFJ4LY2CVB2QW2RI",
"WARC-Record-ID": "<urn:uuid:9abc1238-864a-4fc4-a3a0-1476ed0d4429>",
"WARC-Target-URI": "https://www.badmintonandalucia.com/exercise-fitness-9.html",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:a1dbc72f-f7f1-4390-b437-efe424cdd3b2>"
},
"warc_info": "isPartOf: CC-MAIN-2021-25\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for June 2021\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-243.ec2.internal\r\nsoftware: Apache Nutch 1.18 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.2-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
19,
20,
39,
40,
463,
464,
965,
966,
984,
985,
1186,
1187,
1281,
1282,
1534,
1535
],
"line_end_idx": [
19,
20,
39,
40,
463,
464,
965,
966,
984,
985,
1186,
1187,
1281,
1282,
1534,
1535,
2207
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 2207,
"ccnet_original_nlines": 16,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.40294840931892395,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.009828009642660618,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.10810811072587967,
"rps_doc_frac_unique_words": 0.610497236251831,
"rps_doc_mean_word_length": 4.969613075256348,
"rps_doc_num_sentences": 19,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.020131587982178,
"rps_doc_word_count": 362,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.0044469102285802364,
"rps_doc_frac_chars_top_3gram": 0.013340740464627743,
"rps_doc_frac_chars_top_4gram": 0,
"rps_doc_books_importance": -165.86410522460938,
"rps_doc_books_importance_length_correction": -165.86410522460938,
"rps_doc_openwebtext_importance": -110.0479507446289,
"rps_doc_openwebtext_importance_length_correction": -110.0479507446289,
"rps_doc_wikipedia_importance": -62.991065979003906,
"rps_doc_wikipedia_importance_length_correction": -62.991065979003906
},
"fasttext": {
"dclm": 0.049558401107788086,
"english": 0.9597657322883606,
"fineweb_edu_approx": 2.251873254776001,
"eai_general_math": 0.22627997398376465,
"eai_open_web_math": 0.3865607976913452,
"eai_web_code": 0.008430300280451775
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "613.71",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
},
"secondary": {
"code": "613.712",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "3",
"label": "Irrelevant Content"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "4",
"label": "Missing Images or Figures"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "6",
"label": "Content Listing"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "1",
"label": "No Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "2",
"label": "Partially Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
1a01aa77535b9ecfb87b9fc36adbcd2f
|
-1,231,688,527,009,537,800
|
+353-85-266-0596 [email protected]
Frequently Asked Questions
Why should I buy an EliteHear Hearing Aid?
As one of the fastest growing brands in Ireland, EliteHear is proud to have helped over 700 people recover their hearing loss.
How do I know if I need a hearing aid?
If you have hearing loss, you should consider getting hearing aids.
1. You may have difficulty following conversations.
2. Phone conversations are a struggle.
3. Difficulty pinpointing where a sound is coming from.
4. If you are asking people to repeat themselves or if you find them mumbling.
5. If you have any sign of Tinnitus – ringing, buzzing or white noise sounds in your ears.
6. Having the Television or Radio very loud.
We recommend seeking treatment as soon as the hearing loss is detected since untreated hearing loss can have a negative impact on your life. Wearing hearing aids is a proactive solution in treating hearing loss early and improving your quality of life.
What if it doesn’t work for me?
If you decide the EliteHear range of hearing Aids aren’t for you, no problem! Just get in touch with us and we’ll give you a full refund within the first 30 days after your initial purchase.
Why does EliteHear not have a physical store where I can try before buying?
In an effort to cut out the middleman and save you money, we have eliminated all unnecessary costs. This allows us to pass on the savings to you and sell quality devices for a fraction of the price.
What does a hearing Aid do?
A hearing aid is a small medical device designed to improve one’s hearing ability by amplifying sounds. It helps people with hearing loss to hear better and maintain an active and social life. Today’s hearing aids have become more technologically advanced and smaller than ever before.
Does adjusting to using a hearing aid take time?
Yes, it does. Similar to getting used to a new pair of glasses, there is usually an adjustment period when first hearing sounds through a new hearing aid, especially since the user has gradually been exposed to less sounds during the process of losing their hearing. The length of the adjustment period varies from person to person. As a rule of thumb, the more you use the hearing aid, the quicker you get used to the hearing aid.
Which hearing aids can i choose from?
There are different types of hearing aids available. The most common type is placed behind the ear, (also referred to as BTE) and there are also hearing aids that fit inside your ear canal (referred to as ITC). There is also a broad selection of hearing aid brands and models to choose from. We have chosen the most popular types in our store
Will hearing aids help tinnitus?
Approx 6 in every 10 people experience tinnitus relief from wearing hearing aids, but the effectiveness varies from person to person. If your hearing is within normal limits and you experience hearing loss, you can also try a hearing aid that only includes a tinnitus sound generator (and no sound amplification)
Do You Accept Insurance?
No. Most insurance companies don’t cover hearing aids. This is the exact reason Elite Hear was founded — to provide affordable hearing aids to the hard-working people of Ireland that deserve better pricing. Fortunately, Elite Hear’s prices are so affordable that anyone can afford to buy from us. And if cash is tight, continue reading…
Do You Have Payment Plans?
Yes (if you qualify) we offer payment options via HUMM, for 4 affordable payments with no added interest!
Will EliteHear's Hearing Aids Work for Me Without Me Being Tested?
Elite Hear’s technology allows you to pick different mode settings and volume settings so you can find the best combination of sound for your ears. You don’t need an audiogram (hearing test) to purchase an EliteHear hearing Aid from us.
What's Your Guarantee and Warranty?
Elite Hear offers a risk-free 30 day money-back guarantee and a 12-month standard warranty. You can also purchase our Elite Hear Protection Plan to get a full year of protection in case you lose your device or accidentally damage it. This gives you total peace of mind!
How is Elite Hear's Price so Affordable compared to the traditional €5,000 Hearing Aids?
67% of a traditional €5,000 hearing aid goes directly to middlemen like audiologists. We cut out the middleman entirely, which means no doctors, rent, and other overhead expenses to pay and thereby we are able to pass those savings onto you!
How Do I Know These Will Fit Me Properly Without Being Fitted In-Person?
We include multiple eardome sizes to help you find a great fit, and if for some reason none of them fit perfectly, just call us and we’ll ship you more eardomes or help you get you to upgrade to another device that fits you best. The vast majority of our customers are happy with the generic domes straight out of the box.
Why Should I Buy Today?
Hearing loss can cause early dementia, Alzheimer’s disease, and depression. Many people are stubborn and wait longer than they should have before buying hearing aids, and it costs themin the long run! Don’t be that person! plus we provide same day shipping on all orders before 1pm.
Free Lifetime Support
Our friendly, professional and highly trained team of hearing aid specialists are always ready to lend a hand.
Have a question? Contact us
Contact Info
085-266-0596
ABEC, Kilbride Ind Estate
Arklow, Wicklow, Y14 T440
Ireland
Secure Payments
Need help?
💬 Can We help?
Hi... If you need any help or information regarding hearing aids please feel free to reach out to us here... Kind regards, EliteHear
|
{
"url": "https://elitehear.com/frequently-asked-questions/",
"source_domain": "elitehear.com",
"snapshot_id": "CC-MAIN-2023-40",
"warc_metadata": {
"Content-Length": "325000",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:BX54DK34WGU34A2U3WPMFP4VZWZTXAKM",
"WARC-Concurrent-To": "<urn:uuid:282da2ef-b145-488c-8435-4f7708884b90>",
"WARC-Date": "2023-09-26T22:03:57",
"WARC-IP-Address": "104.21.85.13",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:ULOHVW2NKTLPKGKBN6UR5SBLF3VFTYQV",
"WARC-Record-ID": "<urn:uuid:4317f331-347a-4c82-8c88-14afacd806c4>",
"WARC-Target-URI": "https://elitehear.com/frequently-asked-questions/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:ad1b6bfd-dc46-4c43-9c07-e7ba3a5b81ee>"
},
"warc_info": "isPartOf: CC-MAIN-2023-40\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for September/October 2023\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-67\r\nsoftware: Apache Nutch 1.19 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.5-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
35,
36,
63,
64,
107,
108,
235,
236,
275,
276,
344,
345,
399,
440,
498,
579,
672,
719,
720,
973,
974,
1006,
1007,
1198,
1199,
1275,
1276,
1475,
1476,
1504,
1505,
1791,
1792,
1841,
1842,
2274,
2275,
2313,
2314,
2658,
2659,
2692,
2693,
3006,
3007,
3032,
3033,
3371,
3372,
3399,
3400,
3506,
3507,
3574,
3575,
3812,
3813,
3849,
3850,
4120,
4121,
4210,
4211,
4453,
4454,
4527,
4528,
4851,
4852,
4876,
4877,
5160,
5161,
5183,
5184,
5295,
5296,
5324,
5325,
5338,
5339,
5352,
5353,
5379,
5405,
5413,
5414,
5430,
5431,
5442,
5457
],
"line_end_idx": [
35,
36,
63,
64,
107,
108,
235,
236,
275,
276,
344,
345,
399,
440,
498,
579,
672,
719,
720,
973,
974,
1006,
1007,
1198,
1199,
1275,
1276,
1475,
1476,
1504,
1505,
1791,
1792,
1841,
1842,
2274,
2275,
2313,
2314,
2658,
2659,
2692,
2693,
3006,
3007,
3032,
3033,
3371,
3372,
3399,
3400,
3506,
3507,
3574,
3575,
3812,
3813,
3849,
3850,
4120,
4121,
4210,
4211,
4453,
4454,
4527,
4528,
4851,
4852,
4876,
4877,
5160,
5161,
5183,
5184,
5295,
5296,
5324,
5325,
5338,
5339,
5352,
5353,
5379,
5405,
5413,
5414,
5430,
5431,
5442,
5457,
5589
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 5589,
"ccnet_original_nlines": 91,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.38331854343414307,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.011535050347447395,
"rps_doc_frac_lines_end_with_ellipsis": 0.010869570076465607,
"rps_doc_frac_no_alph_words": 0.15084294974803925,
"rps_doc_frac_unique_words": 0.44572025537490845,
"rps_doc_mean_word_length": 4.6398749351501465,
"rps_doc_num_sentences": 71,
"rps_doc_symbol_to_word_ratio": 0.0026619299314916134,
"rps_doc_unigram_entropy": 5.42830228805542,
"rps_doc_word_count": 958,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.010798649862408638,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.037120360881090164,
"rps_doc_frac_chars_top_3gram": 0.012373450212180614,
"rps_doc_frac_chars_top_4gram": 0.005849270150065422,
"rps_doc_books_importance": -490.5457458496094,
"rps_doc_books_importance_length_correction": -490.5457458496094,
"rps_doc_openwebtext_importance": -320.7242126464844,
"rps_doc_openwebtext_importance_length_correction": -320.7242126464844,
"rps_doc_wikipedia_importance": -225.76551818847656,
"rps_doc_wikipedia_importance_length_correction": -225.76551818847656
},
"fasttext": {
"dclm": 0.17808783054351807,
"english": 0.9419013261795044,
"fineweb_edu_approx": 1.6089872121810913,
"eai_general_math": 0.003964779898524284,
"eai_open_web_math": 0.04716331139206886,
"eai_web_code": 0.00022703000286128372
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "615.83",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
},
"secondary": {
"code": "616.83",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "6",
"label": "Promotional/Advertisement"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "3",
"label": "Irrelevant Content"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "2",
"label": "Click Here References"
}
},
"document_type_v2": {
"primary": {
"code": "9",
"label": "FAQ"
},
"secondary": {
"code": "17",
"label": "Product Page"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "1",
"label": "No Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
6e3c8d3593f3f69280bb5502b214ab8e
|
5,735,707,449,208,828,000
|
Out of the hundreds of known cannabinoids inherent to the cannabis plant, THC and CBD aren’t the only ones making a name for themselves today. Cannabinol (CBN), is making its way to the top, with a variety of benefits not typically found in THC or CBD alone.
The Benefits
Anecdotal evidence is suggesting that CBN may be of use as a sleep aid. This is especially the case when incorporating it with other cannabinoids, like CBD or THC. Studies with rodents have shown that CBN may actually stimulate appetite. This cannabinoid may also carry antibacterial properties, potentially providing an alternative to conventional antibiotics.
Where CBN Comes From
Nature has a funny way of presenting the hundreds of cannabinoids available today. Cannabinol is a great example of this. CBN actually comes from THC, through the degradation that occurs in oxidation. Through heat and exposure to oxygen, THC decomposes and converts into cannabinol. Despite its close relation to the popular psychoactive cannabinoid, it does not carry the psychoactive effects.
Synergistic Effects
Synergistic effects can take place when CBN is combined at a set ratio with CBD or THC. This has a lot to do with the cannabinoid receptors in our bodies, with designated locations for these specific compounds to bind to. Each cannabinoid carries its own benefits and sometimes one can be used to support another. Issues like insomnia can also have a lot to do with other conditions, like anxiety. So it can be beneficial to also remedy the underlying causes as well. The interactions that occur, by combining two or more cannabinoids, provide much better chances for the body to achieve overall homeostasis.
Elite Botanicals created sublingual drops at a 3:1 ratio, with 900mg of CBD and 300mg of CBN. These two cannabinoids together create a perfect pair, allowing their benefits to really take an effect. The coconut rose flavor makes these drops even more perfect for unwinding before bed.
References
Coconut Rose 3:1 CBN Sublingual Drops (900mg CBD & 300mg CBN)
https://pubmed.ncbi.nlm.nih.gov/22543671/
https://pubmed.ncbi.nlm.nih.gov/18681481/
Cannabinoid Information
Categories:
Tags:
Comments are closed
|
{
"url": "https://elitebotanicals.com/cbn-explained/",
"source_domain": "elitebotanicals.com",
"snapshot_id": "crawl=CC-MAIN-2022-27",
"warc_metadata": {
"Content-Length": "234336",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:E6CTQTOEFSAIRR4YVZ7BVR6H2DP23US5",
"WARC-Concurrent-To": "<urn:uuid:e9a9634e-e9de-489e-92ed-23723539677d>",
"WARC-Date": "2022-06-26T15:05:10",
"WARC-IP-Address": "192.124.249.109",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:ZAWZ7UXORQASJUBXC7SM7NA7ABCICUDV",
"WARC-Record-ID": "<urn:uuid:05ed0aac-e327-4179-a729-d7d78a1888c2>",
"WARC-Target-URI": "https://elitebotanicals.com/cbn-explained/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:fe975882-2fc0-47af-81ba-ec21c19b95d9>"
},
"warc_info": "isPartOf: CC-MAIN-2022-27\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for June/July 2022\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-143\r\nsoftware: Apache Nutch 1.18 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.3-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
259,
260,
273,
274,
636,
637,
658,
659,
1054,
1055,
1075,
1076,
1685,
1686,
1971,
1972,
1983,
1984,
2046,
2047,
2089,
2090,
2132,
2133,
2157,
2158,
2160,
2161,
2173,
2174,
2180,
2181
],
"line_end_idx": [
259,
260,
273,
274,
636,
637,
658,
659,
1054,
1055,
1075,
1076,
1685,
1686,
1971,
1972,
1983,
1984,
2046,
2047,
2089,
2090,
2132,
2133,
2157,
2158,
2160,
2161,
2173,
2174,
2180,
2181,
2200
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 2200,
"ccnet_original_nlines": 32,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.3980582356452942,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.05097087100148201,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.15291261672973633,
"rps_doc_frac_unique_words": 0.5411764979362488,
"rps_doc_mean_word_length": 5.2382354736328125,
"rps_doc_num_sentences": 29,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 4.885554313659668,
"rps_doc_word_count": 340,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.013475580140948296,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.008422230370342731,
"rps_doc_frac_chars_top_3gram": 0.014598540030419827,
"rps_doc_frac_chars_top_4gram": 0.00898372009396553,
"rps_doc_books_importance": -192.68618774414062,
"rps_doc_books_importance_length_correction": -192.68618774414062,
"rps_doc_openwebtext_importance": -116.93306732177734,
"rps_doc_openwebtext_importance_length_correction": -116.93306732177734,
"rps_doc_wikipedia_importance": -95.4579849243164,
"rps_doc_wikipedia_importance_length_correction": -95.4579849243164
},
"fasttext": {
"dclm": 0.10487955808639526,
"english": 0.9389004111289978,
"fineweb_edu_approx": 2.237506866455078,
"eai_general_math": 0.059476908296346664,
"eai_open_web_math": 0.262653112411499,
"eai_web_code": 0.011852440424263477
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "615.02",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
},
"secondary": {
"code": "615.857",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "6",
"label": "Promotional/Advertisement"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "3",
"label": "Irrelevant Content"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "4",
"label": "Missing Images or Figures"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "17",
"label": "Product Page"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "4",
"label": "Highly Correct"
}
},
"education_level": {
"primary": {
"code": "2",
"label": "High School Level"
},
"secondary": {
"code": "1",
"label": "General Audience"
}
}
}
|
9222580d47c553ea90dc0f5e416f8f3a
|
7,479,740,474,753,340,000
|
Skip to main content
Differential regulation of Aβ42-induced neuronal C1q synthesis and microglial activation
Abstract
Expression of C1q, an early component of the classical complement pathway, has been shown to be induced in neurons in hippocampal slices, following accumulation of exogenous Aβ42. Microglial activation was also detected by surface marker expression and cytokine production. To determine whether C1q induction was correlated with intraneuronal Aβ and/or microglial activation, D-(-)-2-amino-5-phosphonovaleric acid (APV, an NMDA receptor antagonist) and glycine-arginine-glycine-aspartic acid-serine-proline peptide (RGD, an integrin receptor antagonist), which blocks and enhances Aβ42 uptake, respectively, were assessed for their effect on neuronal C1q synthesis and microglial activation. APV inhibited, and RGD enhanced, microglial activation and neuronal C1q expression. However, addition of Aβ10–20 to slice cultures significantly reduced Aβ42 uptake and microglial activation, but did not alter the Aβ42-induced neuronal C1q expression. Furthermore, Aβ10–20 alone triggered C1q production in neurons, demonstrating that neither neuronal Aβ42 accumulation, nor microglial activation is required for neuronal C1q upregulation. These data are compatible with the hypothesis that multiple receptors are involved in Aβ injury and signaling in neurons. Some lead to neuronal C1q induction, whereas other(s) lead to intraneuronal accumulation of Aβ and/or stimulation of microglia.
Introduction
Alzheimer's disease (AD) is the most common form of dementia in the elderly. Its main pathological features include extracellular amyloid beta (Aβ) deposition in plaques, neurofibrillary tangles (composed of hyperphosphorylated tau protein) in neurons, progressive loss of synapses and cortical/hippocampal neurons, and upregulation of inflammatory components including activated microglia and astrocytes and complement activation [1]. Although the contribution of abnormal phosphorylation and assembly of tau to AD dementia remains a focus of investigation, therapies that interfere with Aβ production, enhance its degradation, or cause its clearance from the central nervous system (CNS) have been the center of many studies in search of a cure for this disease.
Microglial cells, when activated, are believed to be responsible for much of the Aβ clearance through receptor-mediated phagocytosis [2, 3]. Upon activation, microglia acquire features more characteristic of macrophages, including high phagocytic activity, increased expression of leukocyte common antigen (CD45), major histocompatibility complex (MHC) class II and costimulatory molecules B7, and secretion of proinflammatory substances [4]. In addition, phagocytic microglia also participate in the removal of degenerating neurons and synapses as well as Aβ deposits ([5], and reviewed in [6]). Thus, while some microglial functions are beneficial, the destructive effects of the production of toxins (such as nitric oxide, superoxide) and proinflammatory cytokines by activated microglia apparently overcome the protective functions in the chronic stage of neuroinflammation [7, 8]. In vitro studies have shown both protection and toxicity contributed by microglia in response to Aβ depending on the state of activation of microglia [9, 10]. Correlative studies on AD patients and animal models of AD strongly suggest that accumulation of reactive microglia at sites of Aβ deposition contributes significantly to neuronal degeneration [3, 11], although decreased microglia have been reported to be associated with both lowered and enhanced neurodegeneration in transgenic animals [12, 13]. Aβ itself is believed to initiate the accumulation and activation of microglia. However, recent reports provide evidence for neuron-microglial interactions in regulating CNS inflammation [14]. Nevertheless, the molecular mechanisms responsible for activation and regulation of microglia remain to be defined.
Complement proteins have been shown to be associated with Aβ plaques in AD brains, specifically those plaques containing the fibrillar form of the Aβ peptide [11]. Complement proteins are elevated in neurodegenerative diseases like AD, Parkinson's disease, and Huntington's disease as well as more restricted degenerative diseases such macular degeneration and prion disease [11, 1518]. Microglia, astrocytes, and neurons in the CNS can produce most of the complement proteins upon stimulation. C1q, a subcomponent of C1, can directly bind to fibrillar Aβ and activate complement pathways [19], contributing to CNS inflammation [13]. In addition, C1q has been reported to be synthesized by neurons in several neurodegenerative diseases and animal injury models, generally as an early response to injury [2023], possibly prior to the synthesis of other complement components.
Interestingly, C1q and, upon complement activation, C3 also can bind to apoptotic cells and blebs and promote ingestion of those dying cells [2426]. Elevated levels of apoptotic markers are present in AD brain tissue suggesting that many neurons undergo apoptosis in AD [2729]. Excess glutamate, an excitatory neurotransmitter released from injured neurons and synapses, is one of the major factors that perturb calcium homeostasis and induce apoptosis in neurons [30]. Thus, it is reasonable to hypothesize that neuronal expression of C1q, as an early injury response, may serve a potentially beneficial role of facilitating the removal of apoptotic neurons or neuronal blebs [31] in diseases thereby preventing excess glutamate release, excitotoxicity, and the subsequent additional apoptosis.
We have previously reported that in rat hippocampal slice cultures treated with exogenous Aβ42, C1q expression was detected in pyramidal neurons following the internalization of Aβ peptide. This upregulation of neuronal C1q could be a response to injury from Aβ that would facilitate removal of dying cells. Concurrently, microglial activation was prominent upon Aβ treatment. In the present study, the relationship of Aβ-induced neuronal C1q production to microglia activation and Aβ uptake in slice cultures was investigated.
Materials and methods
Materials
Aβ 1–42, obtained from Dr. C. Glabe (UC, Irvine), was synthesized as previously described [32]. Aβ 10–20 was purchased from California Peptide Research (Napa, CA). Lyophilized (in 10 mM HCl) Aβ peptides were solubilized in H2O and subsequently N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) was added to make a final concentration of 10 mM HEPES, 500 μM peptide. This solution was immediately diluted in serum-free medium and added to slices. Glycine-arginine-glycine-aspartic acid-serine-proline (RGD) peptide was purchased from Calbiochem (San Diego, CA). D-(-)-2-amino-5-phosphonovaleric acid (APV) was purchased from Sigma (St. Louis, MO). Both compounds were dissolved in sterile Hanks' balanced salt solution (HBSS) without glucose at 0.2 M and 5 mM, respectively, before diluted in serum-free medium. Antibodies used in experiments are listed in Table 1; RT-PCR primers, synthesized by Integrated DNA Technologies (Coralville, IA), are listed in Table 2. All other reagents were from Sigma unless otherwise noted.
Table 1 Antibodies used in immunohistochemistry.
Table 2 PCR primers and cycling conditions for RT-PCR assay.
Slice cultures
Hippocampal slice cultures were prepared according to the method of Stoppini et al [33] and as described in Fan and Tenner [34]. All experimental procedures were carried out under protocols approved by the University of California Irvine Institutional Animal Care and Use Committee. Slices prepared from hippocampi dissected from 10d-old Sprague Dawley rat pups (Charles River Laboratories, Inc., Wilmington, MA) were kept in culture for 10 to 11 days before treatment started. All reagents were added to serum-free medium (with 100 mg/L transferrin and 500 mg/L heat-treated bovine serum albumin) which was equilibrated at 37°C, 5% CO2 before addition to the slices. Aβ 1–42 or Aβ 10–20 was added to slice cultures as described previously [34]. Briefly, peptide was added to cultures in serum-free medium at 10 or 30 μM. After 7 hours, the peptide was diluted with the addition of an equal amount of medium containing 20% heat-inactivated horse serum. Fresh peptide was applied for each day of treatment. Controls were treated the same way except without peptide. RGD or APV was added to the slice cultures at the same time as Aβ 42.
Immunohistochemistry
At the end of the treatment period, media was removed, the slices were washed with serum-free media and subjected to trypsinization as previously described [34] for 15 minutes at 4°C to remove cell surface associated, but not internalized, Aβ. After washing, slices were fixed and cut into 20 μm sections for immunohistochemistry or extracted for protein or RNA analysis as described in Fan and Tenner [34]. Primary antibodies (anti-Aβ antibody 4G8 or 6E10; rabbit anti rat C1q antibody; CD45 (leukocyte common antigen, microglia), OX42 (CD11b/c, microglia), or ED1 (rat microglia/macrophage marker), or their corresponding control IgGs were applied at concentrations listed in Table 1, followed by biotinylated secondary antibody (Vector Labs, Burlingame, CA) and finally FITC- or Cy3-conjugated streptavidin (Jackson ImmunoResearch Laboratories, West Grove, PA). Slides were examined on an Axiovert 200 inverted microscope (Carl Zeiss Light Microscopy, Göttingen, Germany) with AxioCam (Zeiss) digital camera controlled by AxioVision program (Zeiss). Images (of the entire CA1-CA2 region of hippocampus) were analyzed with KS 300 analysis program (Zeiss) to obtain the percentage area occupied by positive immunostaining in a given field.
ELISA
Slices were homogenized in ice-cold extraction buffer (10 mM triethanolamine, pH 7.4, 1 mM CaCl2, 1 mM MgCl2, 0.15 M NaCl, 0.3% NP-40) containing protease inhibitors pepstatin (2 μg/ml), leupeptin (10 μg/ml), aprotinin (10 μg/ml), and PMSF (1 mM). Protein concentration was determined by BCA assay (Pierce, Rockford, IL) using BSA provided for the standard curve.
An ELISA for rat C1q was adapted from Tenner and Volkin [35] with some modifications as previously described [34].
RNA preparation and RT-PCR
Total RNA from cultures was isolated using the Trizol reagent (Life Technologies, Grand Island, NY) according to the manufacturer's instructions. RNA was treated with RNase-free DNase (Fisher, Pittsburgh, PA) to remove genomic DNA contamination. Each RNA sample was extracted from 3 to 5 hippocampal organotypic slices in the same culture insert. The reverse transcription (RT) reaction conditions were 42°C for 50 min, 70°C for 15 min. Tubes were then centrifuged briefly and held at 4°C. Primer sequences and PCR conditions are listed in Table 2. PCR products were electrophoresed in 2% agarose gel in TAE buffer and visualized with ethidium bromide luminescence. To test for differences in total RNA concentration among samples, mRNA level for rat β-actin were also determined by RT-PCR. Results were quantified using NIH image software [36] by measuring DNA band intensity from digital images taken on GelDoc (BIO-RAD) with Quantity One program.
Results
NMDA receptor antagonist APV inhibits Aβ42 uptake and Aβ42-induced microglial activation and neuronal C1q production
We have previously reported that C1q was detected in cells positive for neuronal markers and that microglial cells were activated in slices following Aβ42 ingestion [34]. Lynch and colleagues have shown that APV, a specific NMDA glutamate receptor antagonist, was able to block Aβ42 uptake by hippocampal neurons in slice cultures [37]. This provided a mechanism to down-modulate the Aβ42 internalization and test the effect on induction of C1q synthesis in neurons. Slices were treated with no peptide, 50 μM APV, 30 μM Aβ42, or 30 μM Aβ42 + 50 μM APV for 3 days with fresh reagents added daily. Cultures were collected and processed as described in Materials and Methods. Similar to reported previously, addition of exogenous Aβ42 resulted in Aβ uptake by hippocampal neurons, induction of C1q synthesis in neurons, and activation of microglial cells (Figure 1d, e, f compared with 1a, b, c). As anticipated, Aβ42 uptake in neurons detected by both 4G8 (Figure 1g) and 6E10 (data not shown) was inhibited by APV co-treatment. Neuronal C1q immunoreactivity was also inhibited when APV was added to Aβ42 treated slices (Figure 1h). Aβ42-triggered microglial activation, assessed by upregulation of antigens detected by anti-CD45 (Figure 1i vs. 1f), OX42 and ED1 (data not shown) was also fully diminished by APV. To quantify the immunohistochemistry results, images were taken from the entire CA1-CA2 region of each immunostained hippocampal section and averaged. Image analysis further substantiated the reduction in Aβ uptake, C1q synthesis and microglial activation (Figure 1j). C1q gene expression at mRNA and protein levels was also assessed by RT-PCR and ELISA, respectively. Results showed decrease of C1q mRNA and protein in slice extracts treated with 30 μM Aβ42 + APV, compared to 30 μM Aβ42 alone (Figure 2a and 2b, n = 2).
Figure 1
figure 1
APV inhibited Aβ uptake, neuronal C1q production, and microglial activation. Slices were treated with no peptide (a, b, c), 30 μM Aβ 42 (d, e, f), or 30 μM Aβ 42 + 50 μM APV (g, h, i) for 3 days with fresh reagents added daily. Immunohistochemistry for Aβ (4G8, a, d, g), C1q (anti-rat C1q, b, e, h), and microglia (CD45, c, f, i) was performed on fixed and sectioned slices. Scale bar = 50 μm. Results are representative of three separately performed experiments. j. Immunoreactivity of Aβ (open bar), C1q (black bar), or CD45 (striped bar) was quantified as described in Materials and Methods. Values are the mean ± SD (error bars) from images taken from 8 slices (2 sections per slice) in 3 independent experiments (* p < 0.0001 compared to Aβ, Anova single factor test).
Figure 2
figure 2
Inhibition of Aβ-induced C1q synthesis by APV. a. C1q and β-actin mRNAs were assessed by RT-PCR in slices after 3 days of no peptide, 30 μM Aβ, or 30 μM Aβ + 50 μM APV treatment. Results are from one experiment representative of two independent experiments. b. Slices were treated with no peptide (open bar), 30 μM Aβ (black bar), or 30 μM Aβ + 50 μM APV (striped bar) daily for 3 days. 3 or 4 slices that had received same treatment were pooled, extracted and proteins analyzed by ELISA. Data are presented as percentage of control in ng C1q/mg total protein (mean ± SD of three independent experiments, **p = 0.01 compared to Aβ, one-tailed paired t-test).
Integrin receptor antagonist GRGDSP (RGD) peptide enhances Aβ42 uptake and Aβ42-induced microglial activation and neuronal C1q expression
It has been shown that an integrin receptor antagonist peptide, GRGDSP (RGD), can enhance Aβ ingestion by neurons in hippocampal slice cultures [37]. Therefore, we adopted this experimental manipulation as an alternative approach to modulate the level of Aβ uptake in neurons and assess the correlation between Aβ ingestion and neuronal C1q expression. Slices were treated with no peptide, 2 mM RGD, 10 μM Aβ42, or 10 μM Aβ42 + 2 mM RGD for 3 days with fresh peptides added daily. At the end of treatments, slices were collected and processed.
Addition of RGD peptide by itself did not result in neuronal C1q induction or microglial activation (CD45) compared to no treatment control, as assessed by immunostaining (data not shown). While greater ingestion was seen at 30 μM (Figure 1d, e, f), addition of 10 μM Aβ shows detectable Aβ ingestion, C1q expression, and microglial activation (Figure 3d, e, f compared with 3a, b, c). The lower concentration of Aβ was chosen for these experiments to ensure the detection of potentiation of uptake (vs. a saturation of uptake at higher Aβ42 concentrations). When RGD was provided in addition to 10 μM Aβ42, Aβ immunoreactivity in neurons with antibody 4G8 (Figure 3g vs. 3d) and 6E10 (similar results, data not shown), neuronal C1q expression (Figure 3h vs. 3e), and CD45 (Figure 3i vs. 3f) upregulation in microglia triggered by Aβ42, were significantly enhanced. Enhanced microglial activation was also detected with OX42 and ED1 antibodies (data not shown). Quantification by image analysis (Figure 3j) definitively demonstrated that the increased accumulation of Aβ in neurons, microglial activation, and induction of neuronal C1q synthesis in the presence of RGD. RT-PCR (Figure 4a) and ELISA (Figure 4b) further demonstrated that both mRNA and protein expression of C1q was enhanced by RGD. Thus, under the conditions tested, both neuronal C1q synthesis and microglial activation are coordinately affected when the internalization of Aβ is modulated negatively by APV or positively by RGD.
Figure 3
figure 3
RGD enhanced Aβ uptake, neuronal C1q expression, and microglial activation. Hippocampal slices were treated with no peptide (a, b, c), 10 μM Aβ 42 (d, e, f), or 10 μM Aβ 42 + 2 mM RGD (g, h, i) for 3 days with fresh peptides added daily. Immunohistochemistry for Aβ (4G8, a, d, g), C1q (anti-rat C1q, b, e, h), and microglia (CD45, c, f, i) was performed on fixed slice sections. Scale bar = 50 μm. Results are representative of three separately performed experiments. j. Immunoreactivities of Aβ (open bar), C1q (black bar), or CD45 (striped bar) were quantified as described in Materials and Methods. Values are the mean ± SD (error bars) from images taken from 8 slices (2 sections per slice) in 3 independent experiments (* p < 0.0001, compared to Aβ, Anova single factor test).
Figure 4
figure 4
Enhancement of Aβ-induced C1q synthesis by RGD. a. C1q and β-actin mRNAs were assessed by RT-PCR in slices after 3 days of no peptide, 10 μM Aβ, or 10 μM Aβ + 2 mM RGD treatment. Results are from one experiment representative of two independent experiments. b. Slices were treated with no peptide (open bar), 10 μM Aβ (black bar), or 10 μM Aβ + 2 mM RGD (striped bar) daily for 3 days. 3 or 4 slices that had received same treatment were pooled, extracted and proteins analyzed by ELISA. Data are presented as percentage of control in ng C1q/mg total protein (mean ± SD of three independent experiments, **p = 0.06 compared to Aβ, one-tailed paired t-test).
Aβ10–20 blocks Aβ42 induced microglial activation but triggers C1q synthesis in hippocampal neurons
Data reported by Giulian et al suggests that residues 13–16, the HHQK domain in human Aβ peptide, mediate Aβ-microglia interaction [38]. To investigate the effect of HHQK peptides in this slice culture system, rat hippocampal slices were treated with no peptide, 10 μM Aβ42, 10 μM Aβ42 + 30 μM Aβ10–20, or 30 μM Aβ10–20 for 3 days with fresh peptides added daily. Sections were immunostained for Aβ, C1q, and microglia. Aβ immunoreactivity was significantly reduced in the Aβ42 +Aβ10–20 treated tissues compared to the Aβ42 alone treatment (Figure 5g vs. 5d). Aβ10–20 alone-treated slices lacked detectable immunopositive cells with either 4G8 or 6E10 anti-Aβ antibody (Figure 5j and data not shown). Furthermore, as anticipated [38], when Aβ10–20 was present, microglial activation by Aβ42 as assessed by level of CD45, OX42, and ED1, was significantly reduced (Figure 5i vs. 5f and data not shown). Image analysis confirmed the inhibition of Aβ uptake (Figure 5m, open bars) and microglial activation (Figure 5m, striped bars) by the HHQK-containing Aβ10–20 peptide. However, production of C1q in neurons treated with Aβ42 was not inhibited by Aβ10–20 (Figure 5h vs. 5e). In fact, with Aβ10–20 alone, neurons were induced to express C1q to a similar level as Aβ42 (Figure 5k). The sustained C1q induction by Aβ10–20 was confirmed by RT-PCR for C1q with mRNAs extracted from slices (Figure 6a).
Figure 5
figure 5
Aβ10–20 blocked Aβ42 uptake, microglial activation, but not neuronal C1q induction. Slices were treated with no peptide (a, b, c), 10 μM Aβ 42 (d, e, f), 10 μM Aβ 42 + 30 μM Aβ 10–20 (g, h, i) or 30 μM Aβ 10–20 (j, k, l) for 3 days with fresh peptides added daily. Immunohistochemistry for Aβ (4G8, a, d, g, j), C1q (anti-rat C1q, b, e, h, k), and microglia (CD45, c, f, i, l) was performed on fixed and sectioned slices. Results are representative of three independent experiments. Scale bar = 50 μm. m. Immunoreactivities of Aβ (open bar), C1q (black bar), or CD45 (striped bar) were quantified as described in Materials and Methods. Values are the mean ± SD (error bars) from images taken from 8 slices (2 sections per slice) in 3 independent experiments. Microglial activation by Aβ42 was significantly inhibited by Aβ10–20 (* p < 0.0001, compared to either Aβ42 + Aβ10–20 or Aβ10–20, Anova single factor test).
Figure 6
figure 6
a. Aβ10–20 inhibited Aβ42-induced C1q and CD40 mRNA elevation, but not that of MCSF. C1q, MCSF, CD40, and β-actin mRNAs were assessed by RT-PCR in slices treated for 3 days with no peptide, 10 μM Aβ 42, 30 μM Aβ 10–20, or 10 μM Aβ 42 + 30 μM Aβ 10–20. Results are from one experiment representative of two independent experiments. b. APV blocked MCSF, CD40, and IL-8 mRNA induction triggered by Aβ42. RT-PCR for MCSF, CD40, IL-8, and β-actin were performed on RNA extracted from slices treated with no peptide (control), 30 μM Aβ 42, or 30 μM Aβ42 + 50 μM APV for 3 days. Results are from one experiment representative of two separate experiments.
CD40, IL-8, and MCSF mRNAs are induced by Aβ42 and differentially regulated by Aβ10–20 and APV
It is known that activated microglia cells can produce pro-inflammatory cytokines, chemokines, and nitric oxide, as well as higher expression of co-stimulatory molecules like CD40 and B7 [39]. Many of those proteins have been shown to be upregulated in microglia stimulated by Aβ in cell culture and in vivo [40]. Semi-quantitative reverse transcriptase PCR technique was used to determine how certain inducible activation products were modified in slice cultures stimulated with exogenous Aβ42 and in the presence of Aβ10–20 or APV. Rat slices were treated with 30 μM Aβ42 +/-APV or 10 μM Aβ42 +/- 30 μM Aβ10–20 for 3 days before mRNAs were extracted from tissues. LPS, was added at 150 ng/ml for 24 hr, served as positive control, with positive detection for all molecules tested (data not shown).
RT-PCR revealed that mRNAs for CD40 and IL-8 were enhanced in Aβ treated slice cultures relative to the control after 3 days (Figure 6a and 6b). Both Aβ10–20 and APV inhibited Aβ42-triggered upregulation of CD40 (Figure 6a and 6b), consistent with the inhibition of microglial activation by both Aβ10–20 and APV assessed by immunohistochemistry. APV also blocked Aβ42-induced IL-8 expression (Figure 6b), as did Aβ10–20 (data not shown).
Macrophage-colony stimulating factor (MCSF), a proinflammatory mediator for microglial proliferation and activation, has been shown to be expressed by neurons upon Aβ stimulation [41]. The expression of MCSF was induced in slice culture by Aβ treatment by Day 3 (Figure 6a and 6b) and this increase was blocked by the presence of APV (Figure 6b). In contrast, Aβ10–20 did not alter the Aβ42-triggered MCSF induction (Figure 6a), suggesting that MCSF may be required for microglial activation, but alone is not sufficient to induce that activation.
Discussion
Previously, it has been shown that Aβ is taken up by pyramidal neurons in hippocampal slice culture and that the synthesis of complement protein C1q is induced in neurons [34]. Here we demonstrate that blocking of Aβ42 accumulation in neurons by NMDA receptor antagonist APV and increasing Aβ42 ingestion by integrin antagonist RGD is accompanied by inhibition and elevation in neuronal C1q expression, respectively. However, Aβ10–20, which markedly inhibits Aβ42 accumulation in pyramidal neurons, does not have any inhibitory effect on neuronal C1q expression. Thus, intraneuronal accumulation of Aβ is not necessary for Aβ-mediated induction of neuronal C1q synthesis.
Since Aβ10–20 alone can induce a level of C1q expression in neurons comparable to Aβ42, it is hypothesized that amino acids 10–20 in Aβ peptide contain the sequence that is recognized by at least one Aβ receptor. It was reported by Giulian et al. that the HHQK domain (residues 13–16) in Aβ is critical for Aβ-microglia interaction and activation of microglia, as they demonstrated that small peptides containing HHQK suppress microglial activation and Aβ-induced microglial mediated neurotoxicity [38]. We have previously reported that rat Aβ42, which differs in 3 amino acids from human Aβ42, including 2 in the 10–20 region and 1 in the HHQK domain, was internalized and accumulated in neurons but failed to induce neuronal C1q expression [34]. This is consistent with the hypothesis that a specific Aβ interaction (either neuronal or microglial), presumably via the HHQK region of the Aβ peptide, but not intracellular Aβ accumulation, can lead to neuronal C1q induction in hippocampal neurons.
Neurons are the major type of cells that accumulate exogenous Aβ in slice cultures. Microglial activation, as assessed by CD45, OX42, and ED1, was increased with enhanced neuronal Aβ42 uptake and inhibited when Aβ42 uptake was blocked by APV or Aβ10–20 in this slice culture system. These data would be consistent with a model in which neurons, upon internalization of Aβ peptide, secrete molecules to modulate microglial activation [14, 41, 42] (Figure 7, large arrows). Synthesis and release of those molecules may require the intracellular accumulation of Aβ since blocking intraneuronal Aβ accumulation always blocked microglial activation. The finding that treatment with Aβ10–20 alone did not result in intraneuronal Aβ immunoreactivity or microglial activation, while rat Aβ42, which did accumulate within neurons, induced activation of microglial cells, is consistent with this hypothesis. It should be noted that an absence of Aβ immunoreactivity in Aβ10–20 treated slices does not exclude the possibility that Aβ10–20 was ingested but soon degraded by cells, and thus accumulation of Aβ rather than ingestion alone may be necessary to induce secretion of microglia activating molecules from neurons. Giulian et al. reported that the HHQK region alone was not able to activate microglia [38]. Thus, Aβ10–20 might block microglial activation by competing with Aβ42 for direct microglial binding, as well as by blocking uptake and accumulation of Aβ in neurons.
Figure 7
figure 7
Model of Aβ interaction with neurons and microglia in slice cultures. Exogenous Aβ peptide interacts with neuronal receptors leads to at least two separate consequences, in one of which C1q expression is upregulated in neurons. A second receptor mediates the secretion of certain modulatory molecules, which lead to microglial activation involving the expression of CD45, CR3, CD40, and IL-8. This does not exclude the direct interactions of Aβ with receptor(s) on microglia that may also contribute to microglial activation.
Activated glial cells, especially microglia, are major players in the neuroinflammation seen in of Alzheimer's disease [43]. Microglial cells can be activated by Aβ and produce proinflammatory cytokines, nitric oxide, superoxide, and other potentially neurotoxic substances in vitro, although the state of differentiation/ activation of microglia and the presence of other modulating molecules is known to influence this stimulation [7, 9, 43]. "Activated" microglia also become more phagocytic and can partially ingest and degrade amyloid deposits in brain. This leads many to hypothesize that there are multiple subsets of "activated" microglia, each primed to function in a specific but distinct way [5, 43].
In hippocampal slice cultures, we and others have shown that Aβ42 triggered microglial activation as assessed by immunohistochemical detection of CR3 (OX42), and cathepsin D [34, 37]. Several chemokines, including macrophage inflammatory protein-1 (MIP-1α, MIP-1β), monocyte chemotactic protein (MCP-1), and interleukin 8 (IL-8), have been reported to increase in Alzheimer's disease patients or cell cultures treated with Aβ [44, 45]. CD40, a co-stimulatory molecule, is also upregulated in Aβ-treated microglia [10]. In this study, similar to reports of cultured microglia, immunoreactivity of CD45 was found increased on microglia in Aβ42 treated slice cultures, and CD40 and IL-8 messenger RNAs were elevated after Aβ42 exposure. As expected, CD40 and IL-8 mRNA induction was blocked whenever immunohistochemistry analysis showed the inhibition of microglial activation. [We did not observe change in MIP-1α, 1β mRNAs in slice culture with Aβ42 treatment, and MCP-1 was too low to be detected with or without Aβ stimulation although it was detectable in LPS treated slices (data not shown).]
The data presented thus far suggest the hypothesis that neurons, upon uptake and accumulation of Aβ, release certain substances that activate microglia. One possible candidate of those neuron-produced substances is MCSF, which has been reported to be induced in neuronal cultures upon Aβ stimulation [41, 46], and is known to be able to trigger microglial activation [47]. Indeed, MCSF mRNA was found to increase after 3 days of Aβ treatment (Figure 6a and 6b). The diminished MCSF signal with the addition of APV and coordinate lack of microglial activation is consistent with a proposed role of activating microglia by MCSF produced by stimulated neurons. However, in the presence of Aβ10–20, MCSF induction was unaltered, though microglial activation was inhibited. Thus, MCSF alone does not lead to the upregulation of the above-mentioned microglial activation markers.
In this organotypic slice culture, no significant neuronal damage was observed in 3 day treatment with Aβ at concentrations that have been reported to cause neurotoxicity in cell cultures. One possible explanation is that the peptide has to penetrate the astrocyte layer surrounding the tissue to reach the multiple layers of neurons. Thus, the effective concentration of Aβ on neurons is certainly much lower than the added concentration. Aβ failing to induce neurotoxicity in slices to the same extent as in cell cultures may also indicate the loss of certain protective mechanisms in isolated cells. A distinct advantage of the slice culture model is that the tissue contains all of the cell types present in brain, the cells are all at the same developmental stage, and cells may communicate in similar fashion as in vivo.
Our data demonstrating distinct pathways for the induction of neuronal C1q and the activation of microglial by amyloid peptides suggest the involvement of multiple Aβ receptors on multiple cell types in response to Aβ (Figure 7, model) and possibly in Alzheimer's disease progression. This multiple-receptor mechanism is supported by reports suggesting many proteins/complexes can mediate the Aβ interaction with cells [48]. These include, but not limited to, the alpha7nicotinic acetylcholine receptor (alpha7nAChR), the P75 neurotrophin receptor (P75NTR) on neurons, the scavenger receptors and heparan sulfate proteoglycans on microglia, as well as receptor for advanced glycosylation end-products (RAGE) and integrins on both neurons and microglia (Figure 7). Several signaling pathways have been implicated in specific Aβ-receptor interactions [4951]. However, it is not known which receptors are required for induction of C1q in neurons. In addition, as of yet the function of neuronal C1q has not been determined. Previous reports from our lab have shown that C1q is associated with hippocampal neurons in AD cases but not normal brain [52], and the fact that it is synthesized by the neurons has been documented by others [23, 53]. In addition, C1q was prominently expressed in a preclinical case of AD (significant diffuse amyloid deposits, with no plaque associated C1q, and no obvious cognitive disorder) and is expressed in other situations of "stress" or injury in the brain [5458]. Indeed, overexpression of human cyclooxygenase-2 in mice leads to C1q synthesis in neurons and inhibition of COX-2 activity abrogates C1q induction. These data suggest that in addition to the facilitation of phagocytosis by microglia [59, 60] (particularly of dead cells or neuronal blebs), the induction of C1q may be an early response of neurons to injury or regulation of an inflammatory response, consistent with a role in the progression of neurodegeneration in AD. Whether and how the neuronal C1q production affects the survival of neurons is still under investigation. Identifying the receptors responsible for neuronal C1q induction may be informative in understanding the role of C1q in neurons in injury and disease.
Conclusions
In summary, induction of C1q expression in hippocampal neurons by exogenous Aβ42 is dependent upon specific cellular interactions with Aβ peptide that require HHQK region-containing sequence, but does not require intraneuronal accumulation of Aβ or microglial activation. Thus, induction of neuronal C1q synthesis may be an early response to injury to facilitate clearance of damaged cells, while modulating inflammation and perhaps facilitating repair. Microglial activation in slice culture involves the induction of CD45, CD40, CR3, and IL-8, which correlates with intraneuronal accumulation of Aβ, indicating contribution of factors released by neurons upon Aβ exposure. MCSF may be one of those stimulatory factors, though by itself MCSF cannot fully activate microglia.
Removal of Aβ to prevent deposition and of cellular debris to avoid excitotoxicity would be a beneficial role of microglial activation in AD. However, activated microglia also produce substances that are neurotoxic. Therefore, the goal of modulating the inflammatory response in neurodegenerative diseases like AD is to enhance the phagocytic function of glial cells and inhibit the production of proinflammatory molecules. Being able to distinguish in the slice system C1q expression (which has been shown to facilitate phagocytosis of apoptotic cells in other systems [24]) from microglial activation suggests a plausible approach to reach that goal in vivo.
Abbreviations
Aβ:
amyloid beta
AD:
Alzheimer's disease
APV:
D-(-)-2-amino-5-phosphonovaleric acid
BSA:
bovine serum albumin
GRGDSP (RGD):
glycine-arginine-glycine-aspartic acid-serine-proline
HBSS:
Hanks' balanced salt solution
HEPES:
N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid
MCSF:
macrophage colony stimulating factor
NMDA:
N-methyl-D-aspartic acid
PMSF:
phenylmethylsulfonylfluoride
TAE:
triethanolamine.
References
1. Mattson MP: Pathways towards and away from Alzheimer's disease. Nature. 2004, 430: 631-639. 10.1038/nature02621.
Article PubMed Central CAS PubMed Google Scholar
2. Webster SD, Yang AJ, Margol L, Garzon-Rodriguez W, Glabe CG, Tenner AJ: Complement component C1q modulates the phagocytic behavior of microglia. Exp Neurol. 2000, 161: 127-138. 10.1006/exnr.1999.7260.
Article CAS PubMed Google Scholar
3. Rogers J, Strohmeyer R, Kovelowski CJ, Li R: Microglia and inflammatory mechanisms in the clearance of amyloid beta peptide. Glia. 2002, 40: 260-269. 10.1002/glia.10153.
Article PubMed Google Scholar
4. Nelson PT, Soma LA, Lavi E: Microglia in diseases of the central nervous system. Ann Med. 2002, 34: 491-500. 10.1080/078538902321117698.
Article CAS PubMed Google Scholar
5. Petersen MA, Dailey ME: Diverse microglial motility behaviors during clearance of dead cells in hippocampal slices. Glia. 2004, 46: 195-206. 10.1002/glia.10362.
Article PubMed Google Scholar
6. D'Andrea MR, Cole GM, Ard MD: The microglial phagocytic role with specific plaque types in the Alzheimer disease brain. Neurobiol Aging. 2004, 25: 675-683. 10.1016/j.neurobiolaging.2003.12.026.
Article PubMed Google Scholar
7. Combs CK, Karlo JC, Kao SC, Landreth GE: beta-Amyloid stimulation of microglia and monocytes results in TNFalpha- dependent expression of inducible nitric oxide synthase and neuronal apoptosis. J Neurosci. 2001, 21: 1179-1188.
CAS PubMed Google Scholar
8. Schmidt R, Schmidt H, Curb JD, Masaki K, White LR, Launer LJ: Early inflammation and dementia: a 25-year follow-up of the Honolulu-Asia Aging Study. Ann Neurol. 2002, 52: 168-174. 10.1002/ana.10265.
Article PubMed Google Scholar
9. Li M, Pisalyaput K, Galvan M, Tenner AJ: Macrophage colony stimulatory factor and interferon-gamma trigger distinct mechanisms for augmentation of beta-amyloid-induced microglia-mediated neurotoxicity. J Neurochem. 2004, 91: 623-633. 10.1111/j.1471-4159.2004.02765.x.
Article CAS PubMed Google Scholar
10. Tan J, Town T, Paris D, Mori T, Suo Z, Crawford F, Mattson MP, Flavell RA, Mullan M: Microglial activation resulting from CD40-CD40L interaction after β-amyloid stimulation. Science. 1999, 286: 2352-2355. 10.1126/science.286.5448.2352.
Article CAS PubMed Google Scholar
11. Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, Cooper NR, Eikelenboom P, Emmerling M, Fiebich BL, Finch CE, Frautschy S, Griffin WS, Hampel H, Hull M, Landreth G, Lue L, Mrak R, Mackenzie IR, McGeer PL, O'Banion MK, Pachter J, Pasinetti G, Plata-Salaman C, Rogers J, Rydel R, Shen Y, Streit W, Strohmeyer R, Tooyoma I, Van Muiswinkel FL, Veerhuis R, Walker D, Webster S, Wegrzyniak B, Wenk G, Wyss-Coray T: Inflammation and Alzheimer's disease. Neurobiol Aging. 2000, 21: 383-421. 10.1016/S0197-4580(00)00124-X.
Article PubMed Central CAS PubMed Google Scholar
12. Wyss-Coray T, Lin C, Yan F, Yu GQ, Rohde M, McConlogue L, Masliah E, Mucke L: TGF-beta1 promotes microglial amyloid-beta clearance and reduces plaque burden in transgenic mice. Nat Med. 2001, 7: 612-618. 10.1038/87945.
Article CAS PubMed Google Scholar
13. Fonseca MI, Zhou J, Botto M, Tenner AJ: Absence of C1q leads to less neuropathology in transgenic mouse models of Alzheimer's disease. J Neurosci. 2004, 24: 6457-6465. 10.1523/JNEUROSCI.0901-04.2004.
Article CAS PubMed Google Scholar
14. Mott RT, Ait-Ghezala G, Town T, Mori T, Vendrame M, Zeng J, Ehrhart J, Mullan M, Tan J: Neuronal expression of CD22: novel mechanism for inhibiting microglial proinflammatory cytokine production. Glia. 2004, 46: 369-379. 10.1002/glia.20009.
Article PubMed Google Scholar
15. McGeer PL, McGeer EG: Inflammation and neurodegeneration in Parkinson's disease. Parkinsonism Relat Disord. 2004, 10 (Suppl 1): S3-S7. 10.1016/j.parkreldis.2004.01.005.
Article PubMed Google Scholar
16. Singhrao SK, Neal JW, Morgan BP, Gasque P: Increased complement biosynthesis by microglia and complement activation on neurons in Huntington's disease. Exp Neurol. 1999, 159: 362-376. 10.1006/exnr.1999.7170.
Article CAS PubMed Google Scholar
17. Johnson LV, Leitner WP, Staples MK, Anderson DH: Complement activation and inflammatory processes in Drusen formation and age related macular degeneration. Exp Eye Res. 2001, 73: 887-896. 10.1006/exer.2001.1094.
Article CAS PubMed Google Scholar
18. Kovacs GG, Gasque P, Strobel T, Lindeck-Pozza E, Strohschneider M, Ironside JW, Budka H, Guentchev M: Complement activation in human prion disease. Neurobiol Dis. 2004, 15: 21-28. 10.1016/j.nbd.2003.09.010.
Article CAS PubMed Google Scholar
19. Jiang H, Burdick D, Glabe CG, Cotman CW, Tenner AJ: β-amyloid activates complement by binding to a specific region of the collagen-like domain of the C1q A chain. J Immunol. 1994, 152: 5050-5059.
CAS PubMed Google Scholar
20. Huang J, Kim LJ, Mealey R, Marsh JrHC, Zhang Y, Tenner AJ, Connolly ES, Pinsky DJ: Neuronal protection in stroke by an sLex-glycosylated complement inhibitory protein. Science. 1999, 285: 595-599. 10.1126/science.285.5427.595.
Article CAS PubMed Google Scholar
21. Terai K, Walker DG, McGeer EG, McGeer PL: Neurons express proteins of the classical complement pathway in Alzheimer disease. Brain Res. 1997, 769: 385-390. 10.1016/S0006-8993(97)00849-4.
Article CAS PubMed Google Scholar
22. Shen Y, Li R, McGeer EG, McGeer PL: Neuronal expression of mRNAs for complement proteins of the classical pathway in Alzheimer brain. Brain Res. 1997, 769: 391-395. 10.1016/S0006-8993(97)00850-0.
Article CAS PubMed Google Scholar
23. Rozovsky I, Morgan TE, Willoughby DA, Dugich-Djordjevich MM, Pasinetti GM, Johnson SA, Finch CE: Selective expression of Clusterin (SGP-2) and complement C1qB and C4 during responses to neurotoxins in vivo and in vitro. Neuroscience. 1994, 62: 741-758. 10.1016/0306-4522(94)90473-1.
Article CAS PubMed Google Scholar
24. Botto M, Dell'agnola C, Bygrave AE, Thompson EM, Cook HT, Petry F, Loos M, Pandolfi PP, Walport MJ: Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies. Nat Genet. 1998, 19: 56-59.
Article CAS PubMed Google Scholar
25. Mevorach D, Mascarenhas JO, Gershov D, Elkon KB: Complement-dependent clearance of apoptotic cells by human macrophages. J Exp Med. 1998, 188: 2313-2320. 10.1084/jem.188.12.2313.
Article PubMed Central CAS PubMed Google Scholar
26. Ogden CA, deCathelineau A, Hoffmann PR, Bratton D, Ghebrehiwet B, Fadok VA, Henson PM: C1q and mannose binding lectin engagement of cell surface calreticulin and CD91 initiates macropinocytosis and uptake of apoptotic cells. J Exp Med. 2001, 194: 781-796. 10.1084/jem.194.6.781.
Article PubMed Central CAS PubMed Google Scholar
27. Colangelo V, Schurr J, Ball MJ, Pelaez RP, Bazan NG, Lukiw WJ: Gene expression profiling of 12633 genes in Alzheimer hippocampal CA1: transcription and neurotrophic factor down-regulation and up-regulation of apoptotic and pro-inflammatory signaling. J Neurosci Res. 2002, 70: 462-473. 10.1002/jnr.10351.
Article CAS PubMed Google Scholar
28. Guo H, Albrecht S, Bourdeau M, Petzke T, Bergeron C, LeBlanc AC: Active caspase-6 and caspase-6-cleaved tau in neuropil threads, neuritic plaques, and neurofibrillary tangles of Alzheimer's disease. Am J Pathol. 2004, 165: 523-531.
Article PubMed Central CAS PubMed Google Scholar
29. Jo DG, Lee JY, Hong YM, Song S, Mook-Jung I, Koh JY, Jung YK: Induction of pro-apoptotic calsenilin/DREAM/KChIP3 in Alzheimer's disease and cultured neurons after amyloid-beta exposure. J Neurochem. 2004, 88: 604-611.
Article CAS PubMed Google Scholar
30. Michaelis EK: Molecular biology of glutamate receptors in the central nervous system and their role in excitotoxicity, oxidative stress and aging. Prog Neurobiol. 1998, 54: 369-415. 10.1016/S0301-0082(97)00055-5.
Article CAS PubMed Google Scholar
31. Lesort M, Terro F, Esclaire F, Hugon J: Neuronal APP accumulates in toxic membrane blebbings. J Neural Transm. 1997, 104: 497-513.
Article CAS PubMed Google Scholar
32. Kagan BL, Hirakura Y, Azimov R, Azimova R, Lin MC: The channel hypothesis of Alzheimer's disease: current status. Peptides. 2002, 23: 1311-1315. 10.1016/S0196-9781(02)00067-0.
Article CAS PubMed Google Scholar
33. Stoppini L, Buchs PA, Muller D: A simple method for organotypic cultures of nervous tissue. J Neurosci Methods. 1991, 37: 173-182. 10.1016/0165-0270(91)90128-M.
Article CAS PubMed Google Scholar
34. Fan R, Tenner AJ: Complement C1q expression induced by Abeta in rat hippocampal organotypic slice cultures. Exp Neurol. 2004, 185: 241-253. 10.1016/j.expneurol.2003.09.023.
Article CAS PubMed Google Scholar
35. Tenner AJ, Volkin DB: Complement subcomponent C1q secreted by cultured human monocytes has subunit structure identical with that of serum C1q. Biochem J. 1986, 233: 451-458.
Article PubMed Central CAS PubMed Google Scholar
36. NIH image. 2004, http://rsb.info.nih.gov/nih-image/download.html
37. Bi X, Gall CM, Zhou J, Lynch G: Uptake and pathogenic effects of amyloid beta peptide 1–42 are enhanced by integrin antagonists and blocked by NMDA receptor antagonists. Neuroscience. 2002, 112: 827-840. 10.1016/S0306-4522(02)00132-X.
Article CAS PubMed Google Scholar
38. Giulian D, Haverkamp LJ, Yu JH, Karshin M, Tom D, Li J, Kazanskaia A, Kirkpatrick J, Roher AE: The HHQK domain of β-amyloid provides a structural basis for the immunopathology of Alzheimer's disease. J Biol Chem. 1998, 273: 29719-29726. 10.1074/jbc.273.45.29719.
Article CAS PubMed Google Scholar
39. Aloisi F: Immune function of microglia. Glia. 2001, 36: 165-179. 10.1002/glia.1106.
Article CAS PubMed Google Scholar
40. Meda L, Baron P, Scarlato G: Glial activation in Alzheimer's disease: the role of Abeta and its associated proteins. Neurobiol Aging. 2001, 22: 885-893. 10.1016/S0197-4580(01)00307-4.
Article CAS PubMed Google Scholar
41. Yan SD, Zhu H, Fu J, Yan SF, Roher A, Tourtellotte WW, Rajavashisth T, Chen X, Godman GC, Stern D, Schmidt AM: Amyloid-β peptide-receptor for advanced glycation endproduct interaction elicits neuronal expression of macrophage-colony stimulating factor: a proinflammatory pathway in Alzheimer disease. Proc Natl Acad Sci U S A. 1997, 94: 5296-5301. 10.1073/pnas.94.10.5296.
Article PubMed Central CAS PubMed Google Scholar
42. Neumann H, Wekerle H: Neuronal control of the immune response in the central nervous system: linking brain immunity to neurodegeneration. J Neuropathol Exp Neurol. 1998, 57: 1-9.
Article CAS PubMed Google Scholar
43. Streit WJ: Microglia and Alzheimer's disease pathogenesis. J Neurosci Res. 2004, 77: 1-8. 10.1002/jnr.20093.
Article CAS PubMed Google Scholar
44. Nagai A, Nakagawa E, Hatori K, Choi HB, McLarnon JG, Lee MA, Kim SU: Generation and characterization of immortalized human microglial cell lines: expression of cytokines and chemokines. Neurobiol Dis. 2001, 8: 1057-1068. 10.1006/nbdi.2001.0437.
Article CAS PubMed Google Scholar
45. Lee YB, Nagai A, Kim SU: Cytokines, chemokines, and cytokine receptors in human microglia. J Neurosci Res. 2002, 69: 94-103. 10.1002/jnr.10253.
Article CAS PubMed Google Scholar
46. Lue LF, Walker DG, Rogers J: Modeling microglial activation in Alzheimer's disease with human postmortem microglial cultures. Neurobiol Aging. 2001, 22: 945-956. 10.1016/S0197-4580(01)00311-6.
Article CAS PubMed Google Scholar
47. Imai Y, Kohsaka S: Intracellular signaling in M-CSF-induced microglia activation: role of Iba1. Glia. 2002, 40: 164-174. 10.1002/glia.10149.
Article PubMed Google Scholar
48. Verdier Y, Zarandi M, Penke B: Amyloid beta-peptide interactions with neuronal and glial cell plasma membrane: binding sites and implications for Alzheimer's disease. J Pept Sci. 2004, 10: 229-248. 10.1002/psc.573.
Article CAS PubMed Google Scholar
49. Combs CK, johnson DE, Cannady SB, Lehman TM, Landreth GE: Identification of microglial signal transduction pathways mediating a neurotoxic response to amyloidogenic fragments of β-amyloid and prion proteins. J Neurosci. 1999, 19: 928-939.
CAS PubMed Google Scholar
50. McDonald DR, Brunden KR, Landreth GE: Amyloid fibrils activate tyrosine kinase-dependent signaling and superoxide production in microglia. J Neurosci. 1997, 17: 2284-2294.
CAS PubMed Google Scholar
51. Anderson KL, Ferreira A: alpha1 Integrin activation: a link between beta-amyloid deposition and neuronal death in aging hippocampal neurons. J Neurosci Res. 2004, 75: 688-697. 10.1002/jnr.20018.
Article CAS PubMed Google Scholar
52. Afagh A, Cummings BJ, Cribbs DH, Cotman CW, Tenner AJ: Localization and cell association of C1q in Alzheimer's disease brain. Exp Neurol. 1996, 138: 22-32. 10.1006/exnr.1996.0043.
Article CAS PubMed Google Scholar
53. Goldsmith SK, Wals P, Rozovsky I, Morgan TE, Finch CE: Kainic acid and decorticating lesions stimulate the synthesis of C1q protein in adult rat brain. J Neurochem. 1997, 68: 2046-2052.
Article CAS PubMed Google Scholar
54. Fischer B, Schmoll H, Riederer P, Bauer J, Platt D, Popa-Wagner A: Complement C1q and C3 mRNA expression in the frontal cortex of Alzheimer's patients. J Mol Med. 1995, 73: 465-471. 10.1007/BF00202265.
Article CAS PubMed Google Scholar
55. Lee CK, Klopp RG, Weindruch R, Prolla TA: Gene expression profile of aging and its retardation by caloric restriction. Science. 1999, 285: 1390-1393. 10.1126/science.285.5432.1390.
Article CAS PubMed Google Scholar
56. Fonseca MI, Kawas CH, Troncoso JC, Tenner AJ: Neuronal localization of C1q in preclinical Alzheimer's disease. Neurobiol Dis. 2004, 15: 40-46. 10.1016/j.nbd.2003.09.004.
Article CAS PubMed Google Scholar
57. Hosokawa M, Klegeris A, Maguire J, McGeer PL: Expression of complement messenger RNAs and proteins by human oligodendroglial cells. Glia. 2003, 42: 417-423. 10.1002/glia.10234.
Article PubMed Google Scholar
58. Spielman L, Winger D, Ho L, Aisen PS, Shohami E, Pasinetti M: Induction of the complement component C1qB in brain of transgenic mice with neuronal overexpression of human cyclooxygenase-2. Acta Neuropathol (Berl). 2002, 103: 157-162. 10.1007/s004010100447.
Article CAS Google Scholar
59. Webster SD, Park M, Fonseca MI, Tenner AJ: Structural and functional evidence for microglial expression of C1qRP, the C1q receptor that enhances phagocytosis. J Leukoc Biol. 2000, 67: 109-116.
CAS PubMed Google Scholar
60. Webster SD, Galvan MD, Ferran E, Garzon-Rodriguez W, Glabe CG, Tenner AJ: Antibody-mediated phagocytosis of the amyloid β-peptide in microglia is differentially modulated by C1q. J Immunol. 2001, 166: 7496-7503.
Article CAS PubMed Google Scholar
61. Tohgi H, Utsugisawa K, Nagane Y: Hypoxia-induced expression of C1q, a subcomponent of the complement system, in cultured rat PC12 cells. Neurosci Lett. 2000, 291: 151-154. 10.1016/S0304-3940(00)01399-9.
Article CAS PubMed Google Scholar
62. Takeuchi A, Miyaishi O, Kiuchi K, Isobe K: Macrophage colony-stimulating factor is expressed in neuron and microglia after focal brain injury. J Neurosci Res. 2001, 65: 38-44. 10.1002/jnr.1125.
Article CAS PubMed Google Scholar
63. Wei R, Jonakait GM: Neurotrophins and the anti-inflammatory agents interleukin-4 (IL-4), IL-10, IL-11 and transforming growth factor-beta1 (TGF-beta1) down-regulate T cell costimulatory molecules B7 and CD40 on cultured rat microglia. J Neuroimmunol. 1999, 95: 8-18. 10.1016/S0165-5728(98)00248-3.
Article CAS PubMed Google Scholar
64. Linard C, Marquette C, Mathieu J, Pennequin A, Clarencon D, Mathe D: Acute induction of inflammatory cytokine expression after gamma-irradiation in the rat: effect of an NF-kappaB inhibitor. Int J Radiat Oncol Biol Phys. 2004, 58: 427-434. 10.1016/j.ijrobp.2003.09.039.
Article CAS PubMed Google Scholar
Download references
Acknowledgments
This work is supported by NIH NS 35144 and P50 AG16573. The authors thank Dr. Saskia Milton and Dr. Charles Glabe for providing the synthetic human Aβ peptide, and Dr. Maria Fonseca, Dr. Ming Li, and Karntipa Pisalyaput for their review of this manuscript.
Author information
Authors and Affiliations
Authors
Corresponding author
Correspondence to Andrea J Tenner.
Additional information
Competing interests
The author(s) declare that they have no competing interests.
Authors' contributions
RF cultured and processed the tissue, performed all experiments (immunohistochemistry, ELISA, PCR and others), analyzed the data, and drafted the manuscript. AJT contributed to the design of the study, guided data interpretation and presentation and edited the manuscript.
Authors’ original submitted files for images
Rights and permissions
Reprints and permissions
About this article
Cite this article
Fan, R., Tenner, A.J. Differential regulation of Aβ42-induced neuronal C1q synthesis and microglial activation. J Neuroinflammation 2, 1 (2005). https://doi.org/10.1186/1742-2094-2-1
Download citation
• Received:
• Accepted:
• Published:
• DOI: https://doi.org/10.1186/1742-2094-2-1
Keywords
|
{
"url": "https://jneuroinflammation.biomedcentral.com/articles/10.1186/1742-2094-2-1",
"source_domain": "jneuroinflammation.biomedcentral.com",
"snapshot_id": "CC-MAIN-2024-22",
"warc_metadata": {
"Content-Length": "465510",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:6MDOQEZMRTLI4BX5ZIAXASWZDIBX4PEP",
"WARC-Concurrent-To": "<urn:uuid:3440ad1b-a0a5-47ee-afbb-827bbf60b301>",
"WARC-Date": "2024-05-21T20:49:57",
"WARC-IP-Address": "146.75.32.95",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:GP3653W2YLM6Y5U4KMSFTY37UX74ZHQT",
"WARC-Record-ID": "<urn:uuid:c2a73849-d565-4559-8913-09e6246a6269>",
"WARC-Target-URI": "https://jneuroinflammation.biomedcentral.com/articles/10.1186/1742-2094-2-1",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:e55aea39-b5ef-48d3-8682-8ddee96ac61b>"
},
"warc_info": "isPartOf: CC-MAIN-2024-22\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for May 2024\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-253\r\nsoftware: Apache Nutch 1.19 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.5-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
21,
22,
111,
112,
121,
122,
1504,
1505,
1518,
1519,
2284,
2285,
3987,
3988,
4863,
4864,
5660,
5661,
6189,
6190,
6212,
6213,
6223,
6224,
7258,
7259,
7308,
7369,
7370,
7385,
7386,
8521,
8522,
8543,
8544,
9785,
9786,
9792,
9793,
10157,
10158,
10273,
10274,
10301,
10302,
11252,
11253,
11261,
11262,
11379,
11380,
13215,
13216,
13225,
13234,
13235,
14010,
14011,
14020,
14029,
14030,
14689,
14690,
14828,
14829,
15373,
15374,
16871,
16872,
16881,
16890,
16891,
17674,
17675,
17684,
17693,
17694,
18352,
18353,
18453,
18454,
19850,
19851,
19860,
19869,
19870,
20786,
20787,
20796,
20805,
20806,
21454,
21455,
21550,
21551,
22351,
22352,
22790,
22791,
23339,
23340,
23351,
23352,
24024,
24025,
25024,
25025,
26494,
26495,
26504,
26513,
26514,
27040,
27041,
27753,
27754,
28850,
28851,
29725,
29726,
30553,
30554,
32778,
32779,
32791,
32792,
33568,
33569,
34230,
34231,
34245,
34246,
34250,
34251,
34264,
34265,
34269,
34270,
34290,
34291,
34296,
34297,
34335,
34336,
34341,
34342,
34363,
34364,
34378,
34379,
34433,
34434,
34440,
34441,
34471,
34472,
34479,
34480,
34532,
34533,
34539,
34540,
34577,
34578,
34584,
34585,
34610,
34611,
34617,
34618,
34647,
34648,
34653,
34654,
34671,
34672,
34683,
34684,
34802,
34803,
34861,
34862,
35068,
35069,
35111,
35112,
35287,
35288,
35325,
35326,
35468,
35469,
35511,
35512,
35678,
35679,
35716,
35717,
35916,
35917,
35954,
35955,
36187,
36188,
36221,
36222,
36426,
36427,
36464,
36465,
36738,
36739,
36781,
36782,
37024,
37025,
37067,
37068,
37597,
37598,
37656,
37657,
37882,
37883,
37925,
37926,
38132,
38133,
38175,
38176,
38423,
38424,
38461,
38462,
38637,
38638,
38675,
38676,
38890,
38891,
38933,
38934,
39152,
39153,
39195,
39196,
39409,
39410,
39452,
39453,
39655,
39656,
39689,
39690,
39923,
39924,
39966,
39967,
40160,
40161,
40203,
40204,
40406,
40407,
40449,
40450,
40739,
40740,
40782,
40783,
41012,
41013,
41055,
41056,
41241,
41242,
41300,
41301,
41586,
41587,
41645,
41646,
41957,
41958,
42000,
42001,
42239,
42240,
42298,
42299,
42523,
42524,
42566,
42567,
42786,
42787,
42829,
42830,
42967,
42968,
43010,
43011,
43193,
43194,
43236,
43237,
43404,
43405,
43447,
43448,
43627,
43628,
43670,
43671,
43851,
43852,
43910,
43911,
43982,
43983,
44224,
44225,
44267,
44268,
44537,
44538,
44580,
44581,
44671,
44672,
44714,
44715,
44905,
44906,
44948,
44949,
45328,
45329,
45387,
45388,
45573,
45574,
45616,
45617,
45732,
45733,
45775,
45776,
46027,
46028,
46070,
46071,
46221,
46222,
46264,
46265,
46464,
46465,
46507,
46508,
46655,
46656,
46693,
46694,
46915,
46916,
46958,
46959,
47204,
47205,
47238,
47239,
47417,
47418,
47451,
47452,
47653,
47654,
47696,
47697,
47883,
47884,
47926,
47927,
48119,
48120,
48162,
48163,
48371,
48372,
48414,
48415,
48602,
48603,
48645,
48646,
48822,
48823,
48865,
48866,
49049,
49050,
49087,
49088,
49351,
49352,
49386,
49387,
49586,
49587,
49620,
49621,
49839,
49840,
49882,
49883,
50092,
50093,
50135,
50136,
50336,
50337,
50379,
50380,
50684,
50685,
50727,
50728,
51004,
51005,
51047,
51048,
51068,
51069,
51085,
51086,
51343,
51344,
51363,
51364,
51389,
51390,
51398,
51399,
51420,
51421,
51456,
51457,
51480,
51481,
51501,
51502,
51563,
51564,
51587,
51588,
51861,
51862,
51907,
51908,
51931,
51932,
51957,
51958,
51977,
51978,
51996,
51997,
52180,
52181,
52199,
52200,
52214,
52215,
52229,
52230,
52245,
52246,
52293,
52294
],
"line_end_idx": [
21,
22,
111,
112,
121,
122,
1504,
1505,
1518,
1519,
2284,
2285,
3987,
3988,
4863,
4864,
5660,
5661,
6189,
6190,
6212,
6213,
6223,
6224,
7258,
7259,
7308,
7369,
7370,
7385,
7386,
8521,
8522,
8543,
8544,
9785,
9786,
9792,
9793,
10157,
10158,
10273,
10274,
10301,
10302,
11252,
11253,
11261,
11262,
11379,
11380,
13215,
13216,
13225,
13234,
13235,
14010,
14011,
14020,
14029,
14030,
14689,
14690,
14828,
14829,
15373,
15374,
16871,
16872,
16881,
16890,
16891,
17674,
17675,
17684,
17693,
17694,
18352,
18353,
18453,
18454,
19850,
19851,
19860,
19869,
19870,
20786,
20787,
20796,
20805,
20806,
21454,
21455,
21550,
21551,
22351,
22352,
22790,
22791,
23339,
23340,
23351,
23352,
24024,
24025,
25024,
25025,
26494,
26495,
26504,
26513,
26514,
27040,
27041,
27753,
27754,
28850,
28851,
29725,
29726,
30553,
30554,
32778,
32779,
32791,
32792,
33568,
33569,
34230,
34231,
34245,
34246,
34250,
34251,
34264,
34265,
34269,
34270,
34290,
34291,
34296,
34297,
34335,
34336,
34341,
34342,
34363,
34364,
34378,
34379,
34433,
34434,
34440,
34441,
34471,
34472,
34479,
34480,
34532,
34533,
34539,
34540,
34577,
34578,
34584,
34585,
34610,
34611,
34617,
34618,
34647,
34648,
34653,
34654,
34671,
34672,
34683,
34684,
34802,
34803,
34861,
34862,
35068,
35069,
35111,
35112,
35287,
35288,
35325,
35326,
35468,
35469,
35511,
35512,
35678,
35679,
35716,
35717,
35916,
35917,
35954,
35955,
36187,
36188,
36221,
36222,
36426,
36427,
36464,
36465,
36738,
36739,
36781,
36782,
37024,
37025,
37067,
37068,
37597,
37598,
37656,
37657,
37882,
37883,
37925,
37926,
38132,
38133,
38175,
38176,
38423,
38424,
38461,
38462,
38637,
38638,
38675,
38676,
38890,
38891,
38933,
38934,
39152,
39153,
39195,
39196,
39409,
39410,
39452,
39453,
39655,
39656,
39689,
39690,
39923,
39924,
39966,
39967,
40160,
40161,
40203,
40204,
40406,
40407,
40449,
40450,
40739,
40740,
40782,
40783,
41012,
41013,
41055,
41056,
41241,
41242,
41300,
41301,
41586,
41587,
41645,
41646,
41957,
41958,
42000,
42001,
42239,
42240,
42298,
42299,
42523,
42524,
42566,
42567,
42786,
42787,
42829,
42830,
42967,
42968,
43010,
43011,
43193,
43194,
43236,
43237,
43404,
43405,
43447,
43448,
43627,
43628,
43670,
43671,
43851,
43852,
43910,
43911,
43982,
43983,
44224,
44225,
44267,
44268,
44537,
44538,
44580,
44581,
44671,
44672,
44714,
44715,
44905,
44906,
44948,
44949,
45328,
45329,
45387,
45388,
45573,
45574,
45616,
45617,
45732,
45733,
45775,
45776,
46027,
46028,
46070,
46071,
46221,
46222,
46264,
46265,
46464,
46465,
46507,
46508,
46655,
46656,
46693,
46694,
46915,
46916,
46958,
46959,
47204,
47205,
47238,
47239,
47417,
47418,
47451,
47452,
47653,
47654,
47696,
47697,
47883,
47884,
47926,
47927,
48119,
48120,
48162,
48163,
48371,
48372,
48414,
48415,
48602,
48603,
48645,
48646,
48822,
48823,
48865,
48866,
49049,
49050,
49087,
49088,
49351,
49352,
49386,
49387,
49586,
49587,
49620,
49621,
49839,
49840,
49882,
49883,
50092,
50093,
50135,
50136,
50336,
50337,
50379,
50380,
50684,
50685,
50727,
50728,
51004,
51005,
51047,
51048,
51068,
51069,
51085,
51086,
51343,
51344,
51363,
51364,
51389,
51390,
51398,
51399,
51420,
51421,
51456,
51457,
51480,
51481,
51501,
51502,
51563,
51564,
51587,
51588,
51861,
51862,
51907,
51908,
51931,
51932,
51957,
51958,
51977,
51978,
51996,
51997,
52180,
52181,
52199,
52200,
52214,
52215,
52229,
52230,
52245,
52246,
52293,
52294,
52302
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 52302,
"ccnet_original_nlines": 480,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.20884060859680176,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.07079978287220001,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.3112942576408386,
"rps_doc_frac_unique_words": 0.2531347870826721,
"rps_doc_mean_word_length": 5.384274005889893,
"rps_doc_num_sentences": 703,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 6.3733649253845215,
"rps_doc_word_count": 7656,
"rps_doc_frac_chars_dupe_10grams": 0.05380621924996376,
"rps_doc_frac_chars_dupe_5grams": 0.15860463678836823,
"rps_doc_frac_chars_dupe_6grams": 0.09152880311012268,
"rps_doc_frac_chars_dupe_7grams": 0.07677938789129257,
"rps_doc_frac_chars_dupe_8grams": 0.06401921063661575,
"rps_doc_frac_chars_dupe_9grams": 0.05841540917754173,
"rps_doc_frac_chars_top_2gram": 0.019868029281497,
"rps_doc_frac_chars_top_3gram": 0.028576970100402832,
"rps_doc_frac_chars_top_4gram": 0.028819559141993523,
"rps_doc_books_importance": -4914.7275390625,
"rps_doc_books_importance_length_correction": -4914.7275390625,
"rps_doc_openwebtext_importance": -2981.329833984375,
"rps_doc_openwebtext_importance_length_correction": -2981.329833984375,
"rps_doc_wikipedia_importance": -2378.369140625,
"rps_doc_wikipedia_importance_length_correction": -2378.369140625
},
"fasttext": {
"dclm": 0.034202929586172104,
"english": 0.8722086548805237,
"fineweb_edu_approx": 2.092376470565796,
"eai_general_math": 0.1488162875175476,
"eai_open_web_math": 0.32285821437835693,
"eai_web_code": 0.01421452034264803
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.83201",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "616.832",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "4",
"label": "Analyze"
},
"secondary": {
"code": "5",
"label": "Evaluate"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "2",
"label": "Academic/Research"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "2",
"label": "Text Extraction Errors"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "4",
"label": "Missing Images or Figures"
}
},
"document_type_v2": {
"primary": {
"code": "3",
"label": "Academic Writing"
},
"secondary": {
"code": "8",
"label": "Documentation"
}
},
"reasoning_depth": {
"primary": {
"code": "4",
"label": "Advanced Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "4",
"label": "Graduate/Expert Level"
},
"secondary": {
"code": "3",
"label": "Undergraduate Level"
}
}
}
|
b755ed28a90d11d590ef646404f4afc5
|
7,525,576,404,637,839,000
|
Health
The role of reward in sleep-related memory consolidation and brain plasticity
Kinga igloi
Nationality Hungarian
Year of selection 2011
Institution University of Geneva
Country Switzerland
Risk Health
Post-Doctoral Fellowship
2 years
120000 €
Bad memory? One solution is sleep!
Every day, an enormous amount of information reaches us, but only a tiny portion is incorporated into our memories. During sleep, recently acquired memories are strengthened through a replay mechanism. Dr. Kinga Igloi is investigating how motivational factors (i.e., rewards) influence the selection of newly memorized information for further consolidation. As lack of sleep is an increasing trend in our fast-paced society, Igloi’s findings could also have major implications for public health.
Doctor Kinga Igloi’s host research group has proven that brain regions activated while learning a task are reactivated during sleep: memory is consolidated and its performance can be improved. They have also demonstrated that the brain circuits involved in sleep-wake regulation exert a strong influence on reward-related brain regions.
However, how motivational factors (i.e., rewards) influence the selection of newly memorized information for further consolidation remains largely unknown. This is what Dr. Igloi is investigating: in a game-like task, individuals are asked to memorize sequences of pictures associated with high and low monetary rewards. They are then asked to take a break: half of them with sleep, half of them without sleep. Finally, their recall performance is tested.
Using state-of-the-art brain imaging techniques, each individual’s brain activity is recorded while they memorize and recall the pictures. The data is then compared to show the effects of sleep and reward on learning and memory. The aim is to demonstrate that motivational relevance is a key factor in information retention, but also to highlight the differential effect of sleep on highly and lowly rewarded memories.
Dr. Igloi’s project integrates two previously disconnected fields of research (sleep and reward) and promotes interdisciplinary work. Her findings could draw attention to the essential role of sleep and help to improve educational or clinical rehabilitation strategies for the most vulnerable populations (i.e., children and psychiatric patients). Lack of sleep is an increasing trend in our fast-paced society and can have disastrous consequences not only for an individual’s health (from tiredness to altered risk-taking behaviors) but also for society as a whole (socioeconomic and public safety consequences). For these reasons, Dr. Igloi’s findings could also have major implications for public health.
To add or modify information on this page, please contact us at the following address: [email protected]
|
{
"url": "https://axa-research.org/en/project/kinga-igloi",
"source_domain": "axa-research.org",
"snapshot_id": "crawl=CC-MAIN-2020-24",
"warc_metadata": {
"Content-Length": "193057",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:PQDVZ6UQ3ZDV5WB44F55ULIWI6Q5DSBP",
"WARC-Concurrent-To": "<urn:uuid:051072ab-52aa-4e92-bada-8c1368d81cc6>",
"WARC-Date": "2020-05-28T20:59:48",
"WARC-IP-Address": "171.18.96.242",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:OMKN3UJ572FBB5NMO7M6JTSXKXP4HRGT",
"WARC-Record-ID": "<urn:uuid:8362fb3e-a314-4196-8c0b-f474b7f52795>",
"WARC-Target-URI": "https://axa-research.org/en/project/kinga-igloi",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:d857c480-b265-4a6c-86ba-aac554c9277a>"
},
"warc_info": "isPartOf: CC-MAIN-2020-24\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for May/June 2020\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-117.ec2.internal\r\nsoftware: Apache Nutch 1.16 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.1-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: http://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
7,
8,
86,
87,
99,
100,
122,
123,
146,
147,
180,
181,
201,
202,
214,
215,
240,
241,
249,
250,
259,
260,
295,
296,
792,
1129,
1130,
1131,
1587,
2006,
2714,
2715
],
"line_end_idx": [
7,
8,
86,
87,
99,
100,
122,
123,
146,
147,
180,
181,
201,
202,
214,
215,
240,
241,
249,
250,
259,
260,
295,
296,
792,
1129,
1130,
1131,
1587,
2006,
2714,
2715,
2828
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 2828,
"ccnet_original_nlines": 32,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.3392156958580017,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.15490196645259857,
"rps_doc_frac_unique_words": 0.5242718458175659,
"rps_doc_mean_word_length": 5.650485515594482,
"rps_doc_num_sentences": 32,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.0252909660339355,
"rps_doc_word_count": 412,
"rps_doc_frac_chars_dupe_10grams": 0.1829896867275238,
"rps_doc_frac_chars_dupe_5grams": 0.1829896867275238,
"rps_doc_frac_chars_dupe_6grams": 0.1829896867275238,
"rps_doc_frac_chars_dupe_7grams": 0.1829896867275238,
"rps_doc_frac_chars_dupe_8grams": 0.1829896867275238,
"rps_doc_frac_chars_dupe_9grams": 0.1829896867275238,
"rps_doc_frac_chars_top_2gram": 0.015034359879791737,
"rps_doc_frac_chars_top_3gram": 0.017182130366563797,
"rps_doc_frac_chars_top_4gram": 0.020618559792637825,
"rps_doc_books_importance": -234.60736083984375,
"rps_doc_books_importance_length_correction": -234.60736083984375,
"rps_doc_openwebtext_importance": -125.60745239257812,
"rps_doc_openwebtext_importance_length_correction": -125.60745239257812,
"rps_doc_wikipedia_importance": -84.26813507080078,
"rps_doc_wikipedia_importance_length_correction": -84.26813507080078
},
"fasttext": {
"dclm": 0.5069266557693481,
"english": 0.9458327293395996,
"fineweb_edu_approx": 2.9688010215759277,
"eai_general_math": 0.11329686641693115,
"eai_open_web_math": 0.17838221788406372,
"eai_web_code": 0.003578250063583255
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "612.82",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Physiology"
}
},
"secondary": {
"code": "616.858",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "4",
"label": "Analyze"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "2",
"label": "Academic/Research"
},
"secondary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "3",
"label": "Irrelevant Content"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "3",
"label": "Academic Writing"
},
"secondary": {
"code": "10",
"label": "Knowledge Article"
}
},
"reasoning_depth": {
"primary": {
"code": "3",
"label": "Intermediate Reasoning"
},
"secondary": {
"code": "2",
"label": "Basic Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "4",
"label": "Highly Correct"
}
},
"education_level": {
"primary": {
"code": "3",
"label": "Undergraduate Level"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
1a01aa77535b9ecfb87b9fc36adbcd2f
|
-8,476,361,776,585,362,000
|
Utilizing Cell Lines to Derive Chemosensitivity
Why is detecting chemosensitivity important?
Predicting how individual patients will likely respond to chemotherapy is essential in improving the efficacy of the therapeutic technique. However, it can be difficult to objectively measure how a person may react to chemotherapy, given that the chemosensitivity of cancer cells is governed by a multitude of genetic factors.
Cell Culture
Image Credit: Jens Goepfert/Shutterstock.com
Over the decades, many studies have uncovered specific genes whose activation or inactivation can lead to chemoresistance or increased chemosensitivity.
A number of genes have been recognized as determining cancer cell sensitivity to therapeutic drugs, such as those coding for drug transporters and enzyme metabolism. Studies have also been able to reveal genes that govern the cellssensitivity to specific drugs.
For example, chemotherapy agent and immune system suppressant methotrexate are rendered less effective in the presence of increased activity of γ-glutamyl hydrolase and dihydrofolate reductase.
In addition, the increased activity of thymidylate synthase, metallothionein, and cytidine deaminase has been associated with resistance to the drugs 5-fluorouracil (5-FU), cisplatin, 1-β-d-arabinofuranosylcytosine, respectively. Finally, elevated activity levels of NQO1 has been related to sensitivity for mitomycin C (MMC).
While much work has been done in this field to elucidate the various genes that contribute to chemosensitivity, it cannot be determined by just a few genes. There is a wide variation in the chemosensitivity of cancer cells, and more than a handful of genes are required to fully explain this.
Investigating cell lines to extract genes involved in chemosensitivity
More recently, scientists have attempted to use genome-wide expression profile analyses to predict the chemosensitivity of cancers.
Approaches such as cDNA microarray and single nucleotide polymorphisms have been used to analyze genes associated with sensitivity to anticancer drugs. These studies have gained a certain amount of success over recent years.
In the early 2000s, a number of studies developed prediction models of anticancer efficacy, as well as validate the association of highlighted genes to chemosensitivity using panels of human cancer cell lines.
The genes that have been highlighted in these studies are those that could be developed as markers of chemosensitivity, while some of them might be directly responsible for determining the chemosensitivity of cancer cells.
Since then, studies have continued to attempt to extract specific genes as predictive markers of cancer drug efficacy by using human cancer cell lines.
Some of these studies gained particular success in elucidating numerous genes that seemingly play a role in chemosensitivity.
One in particular established a panel of 45 human cancer cell lines that were taken from tumors of the breast, liver, and stomach.
This line was known as JFCR-45. Researchers used this line to analyze the heterogeneity of chemosensitivity in the cells deriving from the three different organs. A database was established based on the analysis of the cell lines against 53 different anticancer drugs.
Gene expression was then analyzed in the cell lines using cDNA arrays. This information was added to a gene expression database.
The researchers used these two newly created databases to pull out the genes whose expression was associated with chemosensitivity. Finally, these genes were screened to select those that were able to change the cell sensitivity to anticancer drugs via an in vitro gene transfection assay.
Using cell lines to inform drug development
The results of the study showed that the genes that the team had extracted were predictive markers of drug efficacy.
A Pearson correlation analysis was applied to each type of cancer cell (from the different organs) to compare cell lines against others with the same organ background, and to remove any organ-specific genes from those flagged as potentially sensitive or resistant factors.
Numerous potential genetic markers of drug sensitivity were highlighted by this study, which, when combined with findings of previous studies, helped to validate previously extracted potential genetic markers.
The discussed study represents a general protocol for utilizing cell lines to derive chemosensitivity. Since this study, many more similar research projects have taken place to continue to expand on this work. With each study, more genes are extracted and validated.
This growing body of research is helping scientists to understand why certain people react differently to drug treatments for cancer. It is also helping them to predict who will respond better or worse, which is facilitating the tailoring of therapeutic treatments, fueling the development of personalized medicine.
Drug-resistant cancer cell lines are also being used to help researchers establish new therapeutic approaches that present higher toxicities to these cell types. A number of studies have elucidated how combination treatments, for example, can have higher levels of efficacy in drug-resistant cell lines.
The future continuation of using cell lines to derive chemosensitivity will be invaluable in developing improving drug therapies for cancer that are more patient-specific and more effective. It is likely to be particularly vital in providing treatments for those who present chemoresistance.
Sources:
• Baggerly, K. and Coombes, K. (2009). Deriving chemosensitivity from cell lines: Forensic bioinformatics and reproducible research in high-throughput biology. The Annals of Applied Statistics, 3(4), pp.1309-1334. https://arxiv.org/pdf/1010.1092.pdf
• Carmichael, J., Mitchell, J., DeGraff, W., Gamson, J., Gazdar, A., Johnson, B., Glatstein, E. and Minna, J. (1988). Chemosensitivity testing of human lung cancer cell lines using the MTT assay. British Journal of Cancer, 57(6), pp.540-547. https://www.ncbi.nlm.nih.gov/pubmed/2841961
• Chang, H., Jeung, H., Jung, J., Kim, T., Rha, S. and Chung, H. (2010). Identification of genes associated with chemosensitivity to SAHA/taxane combination treatment in taxane-resistant breast cancer cells. Breast Cancer Research and Treatment, 125(1), pp.55-63. https://www.ncbi.nlm.nih.gov/pubmed/20224928
• Nakatsu, N., Yoshida, Y. and Yamazaki, K. (2005). Chemosensitivity profile of cancer cell lines and identification of genes determining chemosensitivity by an integrated bioinformatical approach using cDNA arrays. https://mct.aacrjournals.org/content/4/3/399
Further Reading
Last Updated: Feb 27, 2020
Sarah Moore
Written by
Sarah Moore
After studying Psychology and then Neuroscience, Sarah quickly found her enjoyment for researching and writing research papers; turning to a passion to connect ideas with people through writing.
Citations
Please use one of the following formats to cite this article in your essay, paper or report:
• APA
Moore, Sarah. (2020, February 27). Utilizing Cell Lines to Derive Chemosensitivity. AZoLifeSciences. Retrieved on July 05, 2022 from https://www.azolifesciences.com/article/Utilizing-Cell-Lines-to-Derive-Chemosensitivity.aspx.
• MLA
Moore, Sarah. "Utilizing Cell Lines to Derive Chemosensitivity". AZoLifeSciences. 05 July 2022. <https://www.azolifesciences.com/article/Utilizing-Cell-Lines-to-Derive-Chemosensitivity.aspx>.
• Chicago
Moore, Sarah. "Utilizing Cell Lines to Derive Chemosensitivity". AZoLifeSciences. https://www.azolifesciences.com/article/Utilizing-Cell-Lines-to-Derive-Chemosensitivity.aspx. (accessed July 05, 2022).
• Harvard
Moore, Sarah. 2020. Utilizing Cell Lines to Derive Chemosensitivity. AZoLifeSciences, viewed 05 July 2022, https://www.azolifesciences.com/article/Utilizing-Cell-Lines-to-Derive-Chemosensitivity.aspx.
Comments
The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of AZoLifeSciences.
Post a new comment
Post
You might also like...
Researchers discover DisCo for effective processing of samples with fewer cells
|
{
"url": "https://www.azolifesciences.com/article/Utilizing-Cell-Lines-to-Derive-Chemosensitivity.aspx",
"source_domain": "www.azolifesciences.com",
"snapshot_id": "crawl=CC-MAIN-2022-27",
"warc_metadata": {
"Content-Length": "101061",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:UC7NOVLPV4HLVK7FPNYALCILKZ2X6ARN",
"WARC-Concurrent-To": "<urn:uuid:46842c2f-6fb5-42d9-b8dd-9ead8ff5c989>",
"WARC-Date": "2022-07-05T22:18:13",
"WARC-IP-Address": "172.67.72.215",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:JDPICIVT6QQZI2TNGTMPQJCM3DXWXJQO",
"WARC-Record-ID": "<urn:uuid:bbd54c91-bf00-4cd5-9eee-eb1d7916afb9>",
"WARC-Target-URI": "https://www.azolifesciences.com/article/Utilizing-Cell-Lines-to-Derive-Chemosensitivity.aspx",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:baf453d2-f278-48ac-ab59-5b87763f618b>"
},
"warc_info": "isPartOf: CC-MAIN-2022-27\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for June/July 2022\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-148\r\nsoftware: Apache Nutch 1.18 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.3-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
48,
49,
94,
95,
422,
423,
436,
437,
482,
483,
636,
637,
899,
900,
1094,
1095,
1422,
1423,
1716,
1717,
1788,
1789,
1921,
1922,
2147,
2148,
2358,
2359,
2582,
2583,
2735,
2736,
2862,
2863,
2994,
2995,
3264,
3265,
3394,
3395,
3685,
3686,
3730,
3731,
3848,
3849,
4122,
4123,
4333,
4334,
4601,
4602,
4918,
4919,
5223,
5224,
5516,
5517,
5526,
5527,
5779,
6067,
6378,
6641,
6642,
6658,
6659,
6686,
6687,
6699,
6700,
6711,
6712,
6724,
6725,
6920,
6921,
6931,
6932,
7025,
7026,
7034,
7035,
7266,
7267,
7275,
7276,
7472,
7473,
7485,
7486,
7692,
7693,
7705,
7706,
7911,
7912,
7921,
7922,
8052,
8071,
8076,
8099
],
"line_end_idx": [
48,
49,
94,
95,
422,
423,
436,
437,
482,
483,
636,
637,
899,
900,
1094,
1095,
1422,
1423,
1716,
1717,
1788,
1789,
1921,
1922,
2147,
2148,
2358,
2359,
2582,
2583,
2735,
2736,
2862,
2863,
2994,
2995,
3264,
3265,
3394,
3395,
3685,
3686,
3730,
3731,
3848,
3849,
4122,
4123,
4333,
4334,
4601,
4602,
4918,
4919,
5223,
5224,
5516,
5517,
5526,
5527,
5779,
6067,
6378,
6641,
6642,
6658,
6659,
6686,
6687,
6699,
6700,
6711,
6712,
6724,
6725,
6920,
6921,
6931,
6932,
7025,
7026,
7034,
7035,
7266,
7267,
7275,
7276,
7472,
7473,
7485,
7486,
7692,
7693,
7705,
7706,
7911,
7912,
7921,
7922,
8052,
8071,
8076,
8099,
8178
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 8178,
"ccnet_original_nlines": 103,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.2943548262119293,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.021505380049347878,
"rps_doc_frac_lines_end_with_ellipsis": 0.009615380316972733,
"rps_doc_frac_no_alph_words": 0.2197580635547638,
"rps_doc_frac_unique_words": 0.41577062010765076,
"rps_doc_mean_word_length": 5.972222328186035,
"rps_doc_num_sentences": 120,
"rps_doc_symbol_to_word_ratio": 0.0006720399833284318,
"rps_doc_unigram_entropy": 5.453752040863037,
"rps_doc_word_count": 1116,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.06916729360818863,
"rps_doc_frac_chars_dupe_6grams": 0.049812451004981995,
"rps_doc_frac_chars_dupe_7grams": 0.037209298461675644,
"rps_doc_frac_chars_dupe_8grams": 0.02010503038764,
"rps_doc_frac_chars_dupe_9grams": 0.02010503038764,
"rps_doc_frac_chars_top_2gram": 0.02700675092637539,
"rps_doc_frac_chars_top_3gram": 0.014853710308670998,
"rps_doc_frac_chars_top_4gram": 0.017854459583759308,
"rps_doc_books_importance": -603.7725219726562,
"rps_doc_books_importance_length_correction": -603.7725219726562,
"rps_doc_openwebtext_importance": -403.4763488769531,
"rps_doc_openwebtext_importance_length_correction": -403.4763488769531,
"rps_doc_wikipedia_importance": -273.67657470703125,
"rps_doc_wikipedia_importance_length_correction": -273.67657470703125
},
"fasttext": {
"dclm": 0.031066060066223145,
"english": 0.9109908938407898,
"fineweb_edu_approx": 2.9205901622772217,
"eai_general_math": 0.21361404657363892,
"eai_open_web_math": 0.46711164712905884,
"eai_web_code": 0.0034323299769312143
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.994",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "615.5",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "3",
"label": "Academic Writing"
}
},
"reasoning_depth": {
"primary": {
"code": "3",
"label": "Intermediate Reasoning"
},
"secondary": {
"code": "2",
"label": "Basic Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "4",
"label": "Highly Correct"
}
},
"education_level": {
"primary": {
"code": "3",
"label": "Undergraduate Level"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
6e3c8d3593f3f69280bb5502b214ab8e
|
1,917,908,532,263,277,600
|
Quick Answer: Can You Gain Weight By Eating Oatmeal?
Is oatmeal bad for weight loss?
Oatmeal Oatmeal is a healthy and delicious breakfast option, especially if you’re looking to lose weight.
Oats are low in calories but high in fiber and protein — two nutrients that impact appetite and weight control..
How can I clear my bowels every morning?
8 Methods To Encourage A Bowel MovementLemon juice – take a glass of water mixed with the juice of half lemon both before bed and when you wake up. … Olive oil – consuming a teaspoon of olive oil in the morning on an empty stomach can encourage stool to flow through the gut. … Prune juice/dried prunes – one of the more traditional remedies for constipation.More items…
How can I eat oatmeal if I don’t like the texture?
Feel free to play with the proportions of butter and brown sugar—a little more or a little less of either won’t hurt. The salt is a game changer and keeps this from being too cloying. If you don’t have Maldon, a pinch of salt mixed in with the oatmeal should do the trick.
What are the side effects of eating oats?
Side Effects & Safety Oats can cause intestinal gas and bloating. To minimize side effects, start with a low dose and increase slowly to the desired amount. Your body will get used to oat bran and the side effects will likely go away.
Can I lose belly fat by eating oatmeal?
7. Oats: This weight loss superfood is high in protein and low in calories, which make it the perfect food for a flat stomach. Oats take time to digest in the body and hence, tend to burn calories. This is what makes oats a good source of energy through the day and lowers your cholesterol.
What foods make you gain weight?
The 18 Best Healthy Foods to Gain Weight FastHomemade Protein Smoothies. Drinking homemade protein smoothies can be a highly nutritious and quick way to gain weight. … Milk. Milk has been used as a weight gainer or muscle builder for decades ( 1 ). … Rice. … Nuts and Nut Butters. … Red Meats. … Potatoes and Starches. … Salmon and Oily Fish. … Protein Supplements.More items…•
Does oatmeal make you poop?
Soluble fiber, which is found in oatmeal, beans and avocados, absorbs water in your body to form a gel, which helps poop slide through the intestines more easily. Insoluble fiber, which is found in seeds and vegetable stalks, adds bulk to your waste, which helps speed up how often you poop.
Can a person eat too much oatmeal?
Breakfast is the most important part of the meal, but eating too much of anything is not recommended. It can make you uncomfortable and lead to weight gain. Only prepare half a cup of dry oats for one time. Have your meal in a small bowl, so that you eat less.
What is the best way to eat oats?
1. Oats with milk and fresh fruits: One of the easiest way to have oats is with some warm milk, fresh fruits, nuts and seeds. You can even use coconut milk and sweet berries. Take a bowl of warm milk then add half a cup of dry roasted oats along with everything that your heart desires.
Is oatmeal fattening at night?
So go for it. A healthy bowl of oatmeal helps promote sleep because of its content of calcium, magnesium and potassium. Alternatively, you can keep some oatmeal cookies on your side table and eat before going to bed. Oatmeal has got great benefits and it’s pretty good for weight loss too.
Is eating oatmeal everyday bad for you?
NO DIGESTIVE ISSUES: Oats also contain fiber which is great for digestive health. If you have chronic constipation issues, consuming oats every morning will be helpful. One cup of oats contain four grams of fiber. You can include fruits and nuts to increase the fiber value of your breakfast.
What is the best time to eat oats?
Nothing says “good morning” like a warm bowl of oatmeal. Whether it is cooked with milk or blended with fresh fruits, oats provide your body with many benefits.
Do eggs make you fart?
Contrary to popular belief, eggs don’t make most of us fart. But they do contain sulphur-packed methionine. So if you don’t want smelly farts, don’t eat eggs alongside fart-causing foods such as beans or fatty meats. If eggs make you bloated and give you wind, you may be intolerant to them or have an allergy.
How can I drop 10 pounds fast?
To lose 10 pounds, a person can follow these steps.Follow a low-calorie diet. Share on Pinterest A low-calorie diet is recommended when trying to lose weight. … Avoid junk food. Junk foods are: … Add lean protein. Lean protein helps build muscle. … Move more. … Try high-intensity cardio. … Add weights. … Eat fewer carbs. … Reduce bloating.More items…•
Can I eat oatmeal for dinner to lose weight?
The meal plans are low-calorie and low-fat and include healthy food choices. Oatmeal itself can help you lose weight because it will help you feel full longer than other foods. The fiber content of oatmeal can also aid the digestive system.
|
{
"url": "https://tentacionboutique.com/qa/quick-answer-can-you-gain-weight-by-eating-oatmeal.html",
"source_domain": "tentacionboutique.com",
"snapshot_id": "crawl=CC-MAIN-2021-10",
"warc_metadata": {
"Content-Length": "34166",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:VJOFV5CSSJHJRHGXNBL3XPSS7ZSYG7P3",
"WARC-Concurrent-To": "<urn:uuid:dbe42520-c780-4921-9d55-02108a85e8dd>",
"WARC-Date": "2021-02-26T17:59:34",
"WARC-IP-Address": "45.130.40.28",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:D4UCBFYPQEVREWB4CTNHUSZITWKRWM3R",
"WARC-Record-ID": "<urn:uuid:995afc62-8048-4ebc-a691-df32f461f559>",
"WARC-Target-URI": "https://tentacionboutique.com/qa/quick-answer-can-you-gain-weight-by-eating-oatmeal.html",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:2662d72a-9654-4361-a001-d5d1ee505824>"
},
"warc_info": "isPartOf: CC-MAIN-2021-10\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for February/March 2021\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-59.ec2.internal\r\nsoftware: Apache Nutch 1.18 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.2-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: http://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
53,
54,
86,
87,
193,
194,
307,
308,
349,
350,
721,
722,
773,
774,
1047,
1048,
1090,
1091,
1326,
1327,
1367,
1368,
1659,
1660,
1693,
1694,
2072,
2073,
2101,
2102,
2394,
2395,
2430,
2431,
2692,
2693,
2727,
2728,
3015,
3016,
3047,
3048,
3338,
3339,
3379,
3380,
3673,
3674,
3709,
3710,
3871,
3872,
3895,
3896,
4207,
4208,
4239,
4240,
4594,
4595,
4640,
4641
],
"line_end_idx": [
53,
54,
86,
87,
193,
194,
307,
308,
349,
350,
721,
722,
773,
774,
1047,
1048,
1090,
1091,
1326,
1327,
1367,
1368,
1659,
1660,
1693,
1694,
2072,
2073,
2101,
2102,
2394,
2395,
2430,
2431,
2692,
2693,
2727,
2728,
3015,
3016,
3047,
3048,
3338,
3339,
3379,
3380,
3673,
3674,
3709,
3710,
3871,
3872,
3895,
3896,
4207,
4208,
4239,
4240,
4594,
4595,
4640,
4641,
4881
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 4881,
"ccnet_original_nlines": 62,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.35014548897743225,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.011639189906418324,
"rps_doc_frac_lines_end_with_ellipsis": 0.015873020514845848,
"rps_doc_frac_no_alph_words": 0.15421919524669647,
"rps_doc_frac_unique_words": 0.41571754217147827,
"rps_doc_mean_word_length": 4.384965896606445,
"rps_doc_num_sentences": 79,
"rps_doc_symbol_to_word_ratio": 0.018428709357976913,
"rps_doc_unigram_entropy": 5.323483467102051,
"rps_doc_word_count": 878,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.016623379662632942,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.005194810219109058,
"rps_doc_frac_chars_top_3gram": 0.009350650012493134,
"rps_doc_frac_chars_top_4gram": 0.007272730115801096,
"rps_doc_books_importance": -436.95819091796875,
"rps_doc_books_importance_length_correction": -436.95819091796875,
"rps_doc_openwebtext_importance": -225.2088165283203,
"rps_doc_openwebtext_importance_length_correction": -225.2088165283203,
"rps_doc_wikipedia_importance": -128.92092895507812,
"rps_doc_wikipedia_importance_length_correction": -128.92092895507812
},
"fasttext": {
"dclm": 0.07868844270706177,
"english": 0.9346978664398193,
"fineweb_edu_approx": 2.3074169158935547,
"eai_general_math": 0.006106730084866285,
"eai_open_web_math": 0.15809029340744019,
"eai_web_code": 0.00019055999291595072
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "613.2",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
},
"secondary": {
"code": "613.7",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "3",
"label": "Irrelevant Content"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "18",
"label": "Q&A Forum"
},
"secondary": {
"code": "10",
"label": "Knowledge Article"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "4",
"label": "Highly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
9222580d47c553ea90dc0f5e416f8f3a
|
-4,184,667,243,923,817,500
|
Tendonitis Introduction
Tendonitis is an inflammation of the tendons and bursae of the joints. Muscles and tendons power the joints, allowing us to move. The bursae are sac-like fluid filled structures that allow the tissue structures, to glide smoothly against each other. Healthy tendon function is dependent on stability and flexibility. Tendons and bursae are located near joints therefore inflammation in these tissues will often be perceived as joint pain and mistaken for arthritis. The symptoms are similar: pain and stiffness made worse by movement. Pain may be worse at night. Although tendonitis is usually a temporary condition, it has the potential to become a chronic problem. Tendonitis affects the old and young alike. Approximately 6% of us are affected by it at any given time.
Tendonitis
Shoulder Tendonitis
Caused by either repetitive arm & shoulder motions, or just age, the tendons, muscles, and surrounding structures become irritated and wear down. If the rotator cuff and bursa are irritated, inflamed and swollen, they may become squeezed between the head of the humerus and the acromion.
Achilles Tendonitis
Achilles tendonitis involves the large tendon at the back of the ankle. The Achilles Tendon connects the large calf muscles (Gastrocnemius and Soleus) to the heal bone (calcaneus). It has a poor blood supply resulting in a slower healing time. This tendon can become inflamed through overuse, and also by many other contributing factors. An estimated 11% of all running injuries are due to Achilles tendonitis.
Patellar Tendonitis
Patellar tendonitis or “jumper’s knee” is a condition that results from overuse of the knee. The Patellar tendon is a structure that attaches the quadriceps muscle to the tibia (shin bone). The patella (knee cap) is a sesamoid (floating bone) that is a part of the patellar tendon. It is believed that since the patellar tendon or patellar ligament connects the patella to the tibia, it should be classified as a ligament. Ligaments connect bone to bone while tendons connect muscles to bone.
Warning Signs
The following symptoms may indicate that you have one of the above types of tendonitis:
• Pain, stiffness and swelling of the affected area
• Pain that is increases in the at night
• Restricted movement in the area surrounding the injury
• Pain that is usually worse after movement of the affected area
Tendonitis Treatments
If you have been diagnosed with any type of tendonitis, your treatment will depend on the specific cause and nature of the condition. Common treatments start with rest and immobilization of the affected area. Medication to control pain is sometimes necessary.
Author: Life Enthusiast
|
{
"url": "https://www.life-enthusiast.com/articles/tendonitis-introduction/",
"source_domain": "www.life-enthusiast.com",
"snapshot_id": "crawl=CC-MAIN-2019-35",
"warc_metadata": {
"Content-Length": "253727",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:IVQQQ3C7ZTNR56VGEJEBJ5U3S4B7QIMH",
"WARC-Concurrent-To": "<urn:uuid:ef2b9822-68bf-46ba-9af3-ede100c5867a>",
"WARC-Date": "2019-08-19T20:20:12",
"WARC-IP-Address": "104.24.99.247",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:4AGZAIRD3S7DJ72IMATO3UVOQBPTUW5Q",
"WARC-Record-ID": "<urn:uuid:b5c959d0-b44a-4bec-b1c5-a5e9796ef6fe>",
"WARC-Target-URI": "https://www.life-enthusiast.com/articles/tendonitis-introduction/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:f20eab66-06ff-42e4-ba79-212fc3796629>"
},
"warc_info": "isPartOf: CC-MAIN-2019-35\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for August 2019\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-188.ec2.internal\r\nsoftware: Apache Nutch 1.15 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.1-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: http://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
24,
25,
797,
798,
809,
810,
830,
831,
1119,
1120,
1140,
1141,
1552,
1553,
1573,
1574,
2067,
2068,
2082,
2083,
2171,
2172,
2226,
2269,
2328,
2395,
2396,
2418,
2419,
2679,
2680
],
"line_end_idx": [
24,
25,
797,
798,
809,
810,
830,
831,
1119,
1120,
1140,
1141,
1552,
1553,
1573,
1574,
2067,
2068,
2082,
2083,
2171,
2172,
2226,
2269,
2328,
2395,
2396,
2418,
2419,
2679,
2680,
2703
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 2703,
"ccnet_original_nlines": 31,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.4004106819629669,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.12731006741523743,
"rps_doc_frac_unique_words": 0.4755244851112366,
"rps_doc_mean_word_length": 5.121212005615234,
"rps_doc_num_sentences": 26,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 4.784285068511963,
"rps_doc_word_count": 429,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.025034140795469284,
"rps_doc_frac_chars_top_3gram": 0.023213470354676247,
"rps_doc_frac_chars_top_4gram": 0.023213470354676247,
"rps_doc_books_importance": -215.1548309326172,
"rps_doc_books_importance_length_correction": -215.1548309326172,
"rps_doc_openwebtext_importance": -145.5834503173828,
"rps_doc_openwebtext_importance_length_correction": -145.5834503173828,
"rps_doc_wikipedia_importance": -81.46614837646484,
"rps_doc_wikipedia_importance_length_correction": -81.46614837646484
},
"fasttext": {
"dclm": 0.07086210697889328,
"english": 0.9398316740989685,
"fineweb_edu_approx": 3.055253267288208,
"eai_general_math": 0.05227131024003029,
"eai_open_web_math": 0.27769553661346436,
"eai_web_code": 0.0018325400305911899
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "614.7",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Public health"
}
},
"secondary": {
"code": "617.1",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Surgery and Dentistry"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "1",
"label": "Factual"
},
"secondary": {
"code": "2",
"label": "Conceptual"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "3",
"label": "Irrelevant Content"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "9",
"label": "FAQ"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
b755ed28a90d11d590ef646404f4afc5
|
633,960,230,536,028,700
|
Costambar Community Forum
Costambar is a beach community located in Puerto Plata, Dominican Republic.
HomePortalRegisterForum RulesLog in
Share |
CHOLERA INFORMATION
View previous topic View next topic Go down
AuthorMessage
Raf
Posts : 93
Join date : 2009-04-10
Age : 78
Location : Changeable
PostSubject: CHOLERA INFORMATION Mon Oct 25, 2010 5:25 pm
ALL YOU ALWAYS WANTED TO KNOW ABOUT CHOLERA,
BUT DID NOT WANT TO ASK.
What is cholera and what causes it ?
It is a highly infectious and potentially serious diarrheic disease, caused by a comma-shaped microscopic bacterium called Vibrio cholera.
Where does it occur ?
Anywhere in the world, particularly in places with poor sanitation and/or sewage handling practices. In fact, it is endemic in many areas of the world.
How is it transmitted ?
By the so-called “fecal-oral route”, which basically means the fecal contamination of consumable (edible or drinkable) items.
How long between infection and the appearance of symptoms ?
As little as 24-48 hours.
Which are the symptoms ?
The sudden onset of watery diarrhea and vomiting. The diarrhea in particular, can be quite voluminous and has a “rice water” appearance and fishy odor. Abdominal cramps are common, but fever is rare in adults, occurring mainly in children. The fluids and electrolytes (potassium, sodium, chlorides, magnesium, etc.) loss caused by the diarrhea can be quite serious, leading to thirst, dry mouth, weakness, dehydration, shock and death, if untreated.
Who is at risk ?
Everybody, particularly those taking medications which lower the stomach’s acid production, as the offending organism is very susceptible to and unable to survive in an acidic environment. Pregnant women and children have a higher mortality (see ahead).
Is this condition serious ?
It certainly can be !! As already stated, severe dehydration can lead to shock and death in over 50% of untreated cases.
What is one to do?
See under “Precautions” below. Seek immediate medical attention for such diarrheic condition. DO NOT PROCRASTINATE OR DELAY IN DOING SO, as severe dehydration, shock and death can ensue within a couple of days (while you are debating whether to seek medical attention).
How is cholera treated ?
The mainstay of therapy centers on fluids and electrolytes replacement. If this is done promptly, the reduction in mortality is dramatic and most gratifying, as it drops from over 50% to under 5%, if treated on time. Initially, fluids and electrolytes replacement must be done intravenously until the diarrhea improves substantially, at which time it is possible to switch to the oral route. Antibiotics can be used and do help some, but fluids and electrolytes replacement is and remains the most important measure.
What can one do to prevent this ?
1- Do not consume food or drink sold on the street.
2- Avoid eating any uncooked food (salads, shellfish, ceviche and so on).
3- Do not drink any water or use ice of uncertain origin or unsure about the water source for its manufacture. Drink only bottled water or carbonated drinks. If unsure about water, proceed to boil it for a minimum of 10 minutes before using it. If you cannot boil it, put 2 drops of household bleach (chlorine) or ½ tablet of iodine in every liter of water before drinking it.
4- Eat only fully cooked meals while still hot.
5- Wash hands thoroughly prior to eating and/or insist your house’s help does likewise as well. Use hand sanitizer often.
6- Only eat fruits after they have been immersed in chlorine water for disinfection and if you can peel them yourself. An useful rule of thumb is: “boil it, cook it, peel it, or forget it” !!
Is there a vaccine against cholera ?
The existing vaccines are of limited usefulness and do not prevent the transmission of this disease.
I hope this helps.
Rafael G. Belliard, MD.
Back to top Go down
CHOLERA INFORMATION
View previous topic View next topic Back to top
Page 1 of 1
Similar topics
-
» Important Information
» some information for you Harrogate Town supporters upon your journey to The Shay - FC Halifax Town
» Fiero seat information!!!
» Beginner Needing Information on Sluicing
» thanks for all your information today at Sandown
Permissions in this forum:You cannot reply to topics in this forum
Costambar Community Forum :: General Discussions :: Useful Information-
Jump to:
|
{
"url": "http://apccostambar.forumotion.com/t143-cholera-information",
"source_domain": "apccostambar.forumotion.com",
"snapshot_id": "crawl=CC-MAIN-2017-51",
"warc_metadata": {
"Content-Length": "31233",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:4B7F447T3DNAAM4TZWRLML24D7HSSHJM",
"WARC-Concurrent-To": "<urn:uuid:4101e03e-0714-4ac3-bc99-0cfca6012ddb>",
"WARC-Date": "2017-12-14T13:03:51",
"WARC-IP-Address": "94.23.76.111",
"WARC-Identified-Payload-Type": "application/xhtml+xml",
"WARC-Payload-Digest": "sha1:KVY2BPVMKRNYUFEEO5PVWJ377MP7OFQ6",
"WARC-Record-ID": "<urn:uuid:4fa705fa-84d9-4d1f-9268-36625413eaaa>",
"WARC-Target-URI": "http://apccostambar.forumotion.com/t143-cholera-information",
"WARC-Truncated": "length",
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:f11be0d6-2962-41d9-94cd-34f4afc6ba32>"
},
"warc_info": "robots: classic\r\nhostname: ip-10-150-141-7.ec2.internal\r\nsoftware: Nutch 1.6 (CC)\r\nisPartOf: CC-MAIN-2017-51\r\noperator: Common Crawl Admin\r\ndescription: Wide crawl of the web for December 2017\r\npublisher: Common Crawl\r\nformat: WARC File Format 1.0\r\nconformsTo: http://bibnum.bnf.fr/WARC/WARC_ISO_28500_version1_latestdraft.pdf"
}
|
{
"line_start_idx": [
0,
26,
27,
103,
105,
141,
142,
151,
153,
154,
175,
176,
221,
235,
239,
240,
241,
242,
253,
276,
285,
307,
308,
368,
369,
370,
371,
372,
417,
442,
443,
444,
481,
620,
621,
643,
795,
796,
820,
946,
947,
1007,
1033,
1034,
1059,
1509,
1510,
1527,
1781,
1782,
1810,
1931,
1932,
1951,
2221,
2222,
2247,
2764,
2765,
2799,
2851,
2925,
3302,
3350,
3472,
3664,
3665,
3702,
3803,
3804,
3823,
3824,
3848,
3849,
3850,
3851,
3871,
3873,
3893,
3942,
3954,
3970,
3972,
3996,
4097,
4125,
4168,
4219,
4220,
4287,
4359
],
"line_end_idx": [
26,
27,
103,
105,
141,
142,
151,
153,
154,
175,
176,
221,
235,
239,
240,
241,
242,
253,
276,
285,
307,
308,
368,
369,
370,
371,
372,
417,
442,
443,
444,
481,
620,
621,
643,
795,
796,
820,
946,
947,
1007,
1033,
1034,
1059,
1509,
1510,
1527,
1781,
1782,
1810,
1931,
1932,
1951,
2221,
2222,
2247,
2764,
2765,
2799,
2851,
2925,
3302,
3350,
3472,
3664,
3665,
3702,
3803,
3804,
3823,
3824,
3848,
3849,
3850,
3851,
3871,
3873,
3893,
3942,
3954,
3970,
3972,
3996,
4097,
4125,
4168,
4219,
4220,
4287,
4359,
4369
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 4369,
"ccnet_original_nlines": 90,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 1,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.34117648005485535,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.0376470610499382,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.19647058844566345,
"rps_doc_frac_unique_words": 0.5349500775337219,
"rps_doc_mean_word_length": 4.941512107849121,
"rps_doc_num_sentences": 51,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.4811177253723145,
"rps_doc_word_count": 701,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.027713630348443985,
"rps_doc_frac_chars_dupe_6grams": 0.027713630348443985,
"rps_doc_frac_chars_dupe_7grams": 0.027713630348443985,
"rps_doc_frac_chars_dupe_8grams": 0.027713630348443985,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.005773670040071011,
"rps_doc_frac_chars_top_3gram": 0.024249419569969177,
"rps_doc_frac_chars_top_4gram": 0.027713630348443985,
"rps_doc_books_importance": -362.5592956542969,
"rps_doc_books_importance_length_correction": -362.5592956542969,
"rps_doc_openwebtext_importance": -248.49839782714844,
"rps_doc_openwebtext_importance_length_correction": -248.49839782714844,
"rps_doc_wikipedia_importance": -174.2056121826172,
"rps_doc_wikipedia_importance_length_correction": -174.2056121826172
},
"fasttext": {
"dclm": 0.07276839017868042,
"english": 0.9083393812179565,
"fineweb_edu_approx": 2.6790971755981445,
"eai_general_math": 0.014057639986276627,
"eai_open_web_math": 0.371110200881958,
"eai_web_code": 0.0004638399987015873
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "614.5",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Public health"
}
},
"secondary": {
"code": "613.6",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "1",
"label": "Factual"
},
"secondary": {
"code": "2",
"label": "Conceptual"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "5",
"label": "Social/Forum"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "9",
"label": "FAQ"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
1a01aa77535b9ecfb87b9fc36adbcd2f
|
-5,654,389,975,514,335,000
|
Making This One Change Cured These People From Diabetes
4
download
By: Krystle Crossman
Diabetes is a disease that affects 9.3% of the population. That works out to 29.1 million people in this country that have it. This is according to data from 2012 brought forth by the American Diabetes Association. The numbers are growing more and more every year. The main focus in treating people with diabetes is to minimize their blood sugar levels without dropping them down too much. This is done by exercise, dropping weight, eating a diabetic-geared diet, and taking insulin if needed.
There are two different types of diabetes:
Type 1 – The people diagnosed with this type need to take insulin every day as the body does not produce the amount needed to convert glucose in the blood to energy.
Type 2 – This is the most common form. People with Type 2 often have to take pills such as Metformin or have to take insulin because while the body is still producing insulin, it is either not using it the way it should or there is not enough to keep glucose levels down.
Six participants took part in an experimental study to see if they could reverse their diabetes. Their ages ranged from 25 years old to 62 years old. All of these participants had very severe cases. Some were severely obese. One had a blood sugar level of 1200 (the normal range is under 100). One had a drinking problem. Five of the participants had Type 2 diabetes and one had Type 1. All of them were taking insulin in some form.
Gabriel Cousens and his team from the Tree of Life Rejuvenation Center had a simple method to treat these subjects. They put them on a raw, plant-based diet. Everything that they prepared for them was raw foods. No meat, just vegetables and fruits, everything in its raw form. The results happened quickly.
By the third day three of the participants were off insulin. The other participants were able to cut the amount of insulin that they were taking. The oldest of the group was seeing a lot of improvement in his health but requested to go home. He could not continue eating the foods that they were giving to him. He left on day 17 with a lower blood pressure, a significantly lower blood glucose level, and had a 30 pound weight loss.
By the end of the 30 day program four of the participants were off medication and off insulin. Their blood sugar was within a normal range. Many of them had lost a great amount of weight as well. Only one of the participants was still taking his insulin but had dropped from 70 units per day to 5.
This study shows that there are ways that you can naturally help your diabetes or cure it all together. It does take hard work and a lot of commitment. It also shows that there are ways other than running to a pharmacy that you can live a healthier life.
Share.
4 Comments
1. Yes. As someone that has been in the world of pharmaceuticals for 30 years, it’s long been said that a “whole food”, plant-based diet would have a tremendous impact on the prevalence of diabetes, colon and prostate cancers, and heart diseases.
Unfortunately that message has not gotten down to “us”, and some of our doctors. In addition, our community has been targeted by a fast food industry that THRIVES on black dollars to stay afloat.
I understand that many of us don’t have ready access to fresh/frozen fruit and veggies….but a large percentage of us do. WE can make a difference in our health, as we’ve see in this study and so many, many others. Ask any certified nutritionist or registered dietician (notice, I didn’t say doctor—-they aren’t all experts in nutrition) about the impact on health of a plant-based diet, and then the impact of a diet loaded with fried food, processed meats, refined flour and wheat, salt, white sugar, and low in fiber.
2. A raw vegetable diet has been show to be beneficial for other chronic ailments, too, including some forms of cancer.
We were formed from the ground. It only makes sense that our healing remedies could come from the ground as well.
3. This foolishness was reported in a British journal a few years ago. It was panned by the experts as it should be panned now. 6 people is not enough of a population to prove anything. I am rather surprised that this blog is reporting and giving false hope to people about a “cure” diabetes. Just like the baby was supposedly “made” HIV/AIDS free suddenly has the virus again. How long have these people been “diabetic free?” What rate is the pancreas functioning at? Your article only proves that if you loose weight you possibly RELAX the symptoms of diabetes which is NOT A CURE. Veggies can be very starchy and cause the glucose levels to spike.
One of the reasons why people don’t take diabetes serious is because of the inaccuracy of all the information being put in the media. Its bad enough Black folks don’t know and choose to remain ignorant about their health conditions. Most clinics in the poor areas don’t offer proper diabetic information to all people. Now this crap has to be reported by this blog.
Leave A Reply
|
{
"url": "http://www.healthyblackwoman.com/making-this-one-change-cured-these-people-from-diabetes/",
"source_domain": "www.healthyblackwoman.com",
"snapshot_id": "crawl=CC-MAIN-2021-31",
"warc_metadata": {
"Content-Length": "56174",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:OSLYYUOUBTAHMXTKQAHUYIB5MK3UGPIR",
"WARC-Concurrent-To": "<urn:uuid:2a7aeb88-ae91-4e3d-85f0-eac4d67c0cfd>",
"WARC-Date": "2021-07-27T21:23:50",
"WARC-IP-Address": "172.67.182.10",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:QMPJF5BCAAQUMVNQGREIZSPPLHXPAERL",
"WARC-Record-ID": "<urn:uuid:b3404f0a-a039-41ec-b262-ab7df6192bae>",
"WARC-Target-URI": "http://www.healthyblackwoman.com/making-this-one-change-cured-these-people-from-diabetes/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:cd47c5d7-63d4-4cc8-9a12-acbf0b883c4c>"
},
"warc_info": "isPartOf: CC-MAIN-2021-31\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for July/August 2021\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-191.ec2.internal\r\nsoftware: Apache Nutch 1.18 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.2-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
56,
57,
59,
60,
69,
90,
91,
585,
586,
629,
630,
796,
797,
1069,
1070,
1503,
1504,
1811,
1812,
2245,
2246,
2544,
2545,
2800,
2801,
2808,
2809,
2820,
2821,
3070,
3270,
3794,
3795,
3917,
3918,
4036,
4037,
4690,
4691,
5061,
5062
],
"line_end_idx": [
56,
57,
59,
60,
69,
90,
91,
585,
586,
629,
630,
796,
797,
1069,
1070,
1503,
1504,
1811,
1812,
2245,
2246,
2544,
2545,
2800,
2801,
2808,
2809,
2820,
2821,
3070,
3270,
3794,
3795,
3917,
3918,
4036,
4037,
4690,
4691,
5061,
5062,
5075
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 5075,
"ccnet_original_nlines": 41,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.44188278913497925,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.012487989850342274,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.14024975895881653,
"rps_doc_frac_unique_words": 0.4486187696456909,
"rps_doc_mean_word_length": 4.4486188888549805,
"rps_doc_num_sentences": 65,
"rps_doc_symbol_to_word_ratio": 0.0009606099920347333,
"rps_doc_unigram_entropy": 5.413633823394775,
"rps_doc_word_count": 905,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.022354690358042717,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.011177349835634232,
"rps_doc_frac_chars_top_3gram": 0.016890209168195724,
"rps_doc_frac_chars_top_4gram": 0.010432190261781216,
"rps_doc_books_importance": -427.3614196777344,
"rps_doc_books_importance_length_correction": -427.3614196777344,
"rps_doc_openwebtext_importance": -249.4071807861328,
"rps_doc_openwebtext_importance_length_correction": -249.4071807861328,
"rps_doc_wikipedia_importance": -183.5336151123047,
"rps_doc_wikipedia_importance_length_correction": -183.5336151123047
},
"fasttext": {
"dclm": 0.14860928058624268,
"english": 0.980949342250824,
"fineweb_edu_approx": 2.819288492202759,
"eai_general_math": 0.06290298700332642,
"eai_open_web_math": 0.2194584608078003,
"eai_web_code": 0.0009198799962177873
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.4",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "613.2",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "1",
"label": "News/Editorial"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "2",
"label": "Click Here References"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "16",
"label": "Personal Blog"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "2",
"label": "Partially Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
6e3c8d3593f3f69280bb5502b214ab8e
|
-27,532,885,064,853,176
|
Bone Marrow Transplant
What is a bone marrow transplant?
Bone marrow transplant (BMT) is a type of therapy for people with certain types of cancer or other diseases. A bone marrow transplant is done by taking cells that are found in the bone marrow called stem cells. These cells are filtered. They are then either given back to the donor or to another person. The goal of BMT is to put healthy bone marrow cells into a person after his or her own unhealthy bone marrow has been treated to kill the abnormal cells.
Bone marrow transplant has been used since 1968 to treat diseases such as:
• Leukemia
• Lymphoma
• Aplastic anemia
• Immune deficiency disorders
• Some solid tumor cancers
Bone marrow is the soft, spongy tissue inside bones. It is where most of the body's blood cells develop and are stored. The cells that make other blood cells are called stem cells. It is the stem cells that are needed in bone marrow transplant. The most basic of the stem cells is called the pluripotent stem cell. This is different than other blood cells in these ways:
• Renewal. It is able to reproduce another cell identical to itself.
• Differentiation. It is able to make 1 or more types of more mature cells.
A bone marrow transplant is done by transferring stem cells from 1 person to another. Stem cells can either be collected from the circulating cells in the blood (the peripheral system) or from the bone marrow:
• Peripheral blood stem cells. Peripheral blood stem cells (PBSCs) are collected by apheresis. This is a process in which the donor is connected to a special cell separation machine by a needle inserted in arm veins. Blood is taken from 1 vein and is circulated though the machine. This removes the stem cells and returns the remaining blood and plasma back to the donor through another needle inserted into the opposite arm. Several sessions may be needed to collect enough stem cells to ensure a chance of successful engraftment in the recipient. A medicine may be given to the donor for about 1 week before apheresis. This medicine will cause the bone marrow to make more new stem cells. These new stem cells will be released from the marrow and into the blood system. They can then be collected from the blood during apheresis.
• Bone marrow harvest. This is done by collecting stem cells with a needle placed into the marrow. Most sites used for bone marrow harvesting are in the hip bones and the sternum. The procedure takes place in the operating room. The donor will be anesthetized during the harvest and will not feel the needle. In recovery, the donor may have some pain in the areas where the needle was inserted.
Types of bone marrow transplant
There are different types of bone marrow transplants. This depends on who the donor is. The types of BMT include:
• Autologous bone marrow transplant. The donor is also the recipient. Stem cells are taken from the person either by bone marrow harvest or apheresis. Apheresis is a process of taking peripheral blood stem cells. The cells are frozen. They then given back to the person after they have treatment. This is often called rescue instead of a transplant.
• Allogeneic bone marrow transplant. The donor shares the same genetic type as the recipient. The donor may be a brother or a sister. Stem cells are taken by bone marrow harvest. Or they may be taken with apheresis. Other donors for allogeneic bone marrow transplants may include:
• A parent. A haploid-identical match is when the donor is a parent and the genetic match is at least half identical to the recipient. These transplants are rare.
• Unrelated bone marrow transplants (UBMT). This is also called matched unrelated donor (MUD).The genetically-matched marrow or stem cells are from an unrelated donor. Unrelated donors are found through national bone marrow registries.
• Umbilical cord blood transplant. Stem cells are taken from an umbilical cord right after the birth of a baby. These stem cells reproduce into mature, working blood cells quicker and better than stem cells taken from bone marrow. The stem cells are tested, typed, counted, and frozen until they are needed for a transplant.
Matching is done by typing human leukocyte antigen (HLA) tissue. Leukocytes are a type of white blood cell. The antigens on the surface of these white blood cells define the genetic makeup of a person's immune system. There are at least 100 HLA antigens. But there are a few major antigens that can show if a donor and recipient are a match.
Researchers are still learning the role all antigens play in the process of a bone marrow transplant. The more antigens that match, the better the donated marrow will work with the recipient. This is called engraftment. This is when the stem cells make their way to the marrow and begin making new blood cells.
Most of the genes that define the human immune system are on 1 chromosome. We only have 2 of each chromosome, 1 we received from each of our parents. Because of this, a full sibling of a person in need of a transplant has a 1 in 4 chance of having the same set of chromosomes. This means they are a full match for a transplant.
If an autologous transplant is planned, stem cells collected from either peripheral (apheresis) or harvest are counted, screened, and ready to infuse.
Why might I need a bone marrow transplant?
The goal of a bone marrow transplant is to cure many diseases and types of cancer. In some cases, the doses of chemotherapy (chemo) or radiation needed to cure a cancer are so high that a person's bone marrow stem cells will be permanently damaged or destroyed by the treatment. Then a bone marrow transplant may be needed. Bone marrow transplants may also be needed if the bone marrow has been destroyed by a disease.
A bone marrow transplant can be used to:
• Replace diseased bone marrow with healthy bone marrow for conditions such as leukemia, aplastic anemia, and sickle cell anemia.
• Help build a new immune system that will fight leukemia or other cancers not killed by chemo or radiation.
• Replace the bone marrow and restore its normal function after high doses of chemo or radiation are given to treat cancer. This is often called rescue.
• Replace bone marrow with healthy bone marrow to prevent more damage from a genetic disease such as Hurler's syndrome or adrenoleukodystrophy.
Talk with your healthcare provider and specialists in bone marrow transplants about risks and benefits before the procedure.
What are the risks of a bone marrow transplant?
Risks may vary, depending on:
• The type of marrow transplant
• The type of disease that leads to transplant
• The way prep is done for the transplant
• Age and overall health of the recipient
• How well tissues match between donor and recipient
• Any severe complications
Possible complications that may happen with a bone marrow transplant include:
• Infections. Infections are likely in a recipient with severe bone marrow suppression. Bacterial infections are the most common. Viral and fungal infections can be life-threatening. Any infection can cause an extended hospital stay. They can prevent or delay engraftment. They can also cause permanent organ damage. Antibiotics, antifungal medicines, and antiviral medicines are often given to try to prevent serious infection.
• Low platelets and low red blood cells. Thrombocytopenia (low platelets) and anemia (low red blood cells) can be dangerous and even life-threatening. These can happen when bone marrow is not making new cells yet. Low platelets can cause dangerous bleeding in the lungs, gastrointestinal (GI) tract, and brain.
• Pain. Pain related to mouth sores and gastrointestinal (GI) irritation is common. High doses of chemo and radiation can cause severe mucositis. This is inflammation of the mouth and GI tract.
• Fluid overload. This is a complication that can lead to pneumonia, liver damage, and high blood pressure. The main reason for fluid overload is because the kidneys cannot keep up with the large amount of fluid being given. The fluid is given in the form of intravenous (IV) medicines, nutrition, and blood products. The kidneys may also be damaged. This can happen from disease, infection, chemo, radiation, or antibiotics.
• Respiratory distress. The respiratory system may suffer during transplant. This may be due to infection, inflammation of the airway, fluid overload, graft-versus-host disease, or bleeding. These are all possibly life-threatening problems that may happen in the lungs and pulmonary system.
• Organ damage. The liver and heart may be damaged during the transplant process. This may be temporary or permanent damage. It may be caused by infection, graft-versus-host disease, high doses of chemo and radiation, or fluid overload.
• Graft failure. In some cases, the graft (transplant) may not take hold in the marrow. Graft failure may happen as a result of infection or recurrent disease. It may happen if the stem cell count of the donated marrow was not enough to cause engraftment.
• Graft-versus-host disease (GVHD). This can be a serious and life-threatening complication of a bone marrow transplant. GVHD occurs when the donor's immune system reacts against the recipient's tissue. The new or transplanted immune system can attack the recipient’s whole body and all of his or her organs. This is because the new cells do not see the tissues and organs of the recipient's body as native cells. Over time and with the help of medicines to suppress the new immune system, it will begin to accept its new body and stop attacking it. The most common sites for GVHD are GI tract, liver, skin, and lungs.
How do I get ready for a bone marrow transplant?
For the person getting the transplant, here is what happens before the procedure:
• Before the transplant, a full evaluation is done by the bone marrow transplant team. All other treatment choices are discussed and evaluated for risks and benefits.
• A complete medical history and physical exam are done. This includes tests to check the recipient’s blood and organ functions. For example, tests may assess the heart, kidney, liver, and lungs.
• A recipient will often come into the transplant center up to 10 days before transplant, He or she will have hydration, evaluation, and other preparations. A flexible tube (catheter) is surgically placed in a vein in the chest area. This is called a central venous line. Blood products and medicines will be given through this line during treatment.
• For an allogeneic transplant, a suitable donor must be available. This means a donor who is tissue typed and matched. Finding a matching donor can be a difficult and lengthy process if a sibling match is not available. Bone marrow donors are listed in several registries. A bone marrow search is done by searching these registries. The search checks for donors whose blood most closely matches the person needing the transplant.
The group of specialists involved in the care of people going through transplant is often called the transplant team. All team members work together to give the best chance for a successful transplant. The team consists of:
• Healthcare providers. These include doctors who specialize in oncology, hematology, immunology, and bone marrow transplants.
• Bone marrow transplant nurse coordinator. This is a nurse who organizes all aspects of care before and after the transplant. He or she will give information, and manage the testing and follow-up care.
• Social workers. These are healthcare providers who will help your family deal with many issues that may arise. Issues may include lodging and transportation, finances, and legal issues.
• Dietitians. These are healthcare providers who will help you meet your nutritional needs before and after the transplant. They will work closely with you and your family.
• Physical therapists. These are healthcare providers who will help you recover and become strong after the transplant.
• Pastoral care. Chaplains can give spiritual care and support.
• Other team members. Several other team members will assess you before the transplant. And they will give follow-up care as needed. These include:
• Pharmacists
• Respiratory therapists
• Lab technicians
• Infectious disease specialists
• Dermatologists
• Gastroenterologists
• Psychologists
A detailed assessment is done by the bone marrow transplant team. The decision for you to have a bone marrow transplant will be based on many factors. These include:
• Your age, overall health, and medical history
• Extent of the disease
• Availability of a donor
• Your tolerance for specific medicines, procedures, or therapies
• Expectations for the course of the disease
• Expectations for the course of the transplant
• Your opinion or preference
The preparations for a bone marrow transplant vary depending on the type of transplant, the disease that caused the need for a transplant, and your tolerance for certain medicines. Most often, high doses of chemo or radiation are included in the preparations. This intense therapy is required to treat the cancer and make room in the bone marrow for the new cells to grow. This therapy is often called ablative, or myeloablative, because of the effect on the bone marrow. The bone marrow produces most of the blood cells in our body. Ablative therapy prevents this process of cell production and the marrow becomes empty. An empty marrow is needed to make room for the new stem cells to grow and establish a new blood cell production system.
What happens during a bone marrow transplant?
After the chemo or radiation is administered, the marrow transplant is given through the central venous catheter into the bloodstream. It is not a surgical procedure to place the marrow into the bone, but is similar to receiving a blood transfusion. The stem cells find their way into the bone marrow and begin reproducing and growing new, healthy blood cells.
The days before transplant are counted as minus days. The day of transplant is considered day zero. Engraftment and recovery after the transplant are counted as plus days. For example, a recipient may enter the hospital on day -8 for preparative regimen. The day of transplant is numbered zero. Days +1, +2, etc., will follow. There are specific events, complications, and risks associated with each day before, during, and after transplant. The days are numbered to help the recipient and family understand where they are in terms of risks and discharge planning.
During infusion of bone marrow, the recipient may have:
• Pain
• Chills
• Fever
• Hives
• Chest pain
What happens after a bone marrow transplant?
After the transplant, supportive care is given to prevent and treat infections, side effects of treatments, and complications. The recipient may:
• Spend several weeks in the hospital
• Be very at risk of infection
• Have a lot of bleeding
• Need blood transfusions
• Be confined to a clean environment
• Take multiple antibiotics and other medicines
• Be given medicine to prevent graft-versus-host disease—if the transplant was allogeneic. The transplanted new cells (the graft) tend to attack the recipient’s tissues (the host), even if the donor is a relative.
• Have continual lab tests
• Have nausea, vomiting, diarrhea, mouth sores, and extreme weakness
• Have short-term mental confusion and emotional distress
After leaving the hospital, the recovery process continues for several months or longer. During this time the recipient can’t return to work or many activities. The recipient must also make frequent follow-up visits to the hospital or healthcare provider's office.
Engraftment of the stem cells happens when the donated cells make their way to the marrow and begin making new blood cells. Engraftment usually happens around day +15 or +30. The timing depends on the type of transplant and the disease being treated. Blood counts will be checked often during the days after transplant. This is done to assess the progress of engraftment. Platelets are often the last blood cell to recover.
Engraftment can be delayed in the body. This may happen because of infection, medicines, low donated stem cell count, or graft failure. The new bone marrow may begin making cells in the first 30 days following transplant. But it may take months or years for the whole immune system to fully recover.
The long-term outlook for a bone marrow transplant varies. It depends on the:
• Type of transplant
• Type and extent of the disease being treated
• Disease response to treatment
• Genetics
• Your age and overall health
• Your tolerance of specific medicines, procedures, or therapies
• Severity of complications
As with any procedure, in bone marrow transplant the prognosis and long-term survival can vary greatly from person to person. The number of transplants being done for an increasing number of diseases, as well as ongoing medical developments, have greatly improved the outcome for bone marrow transplant in children and adults. Ongoing follow-up care is essential for the recipient after a bone marrow transplant. New methods to improve treatment and to decrease complications and side effects of a bone marrow transplant are continually being discovered.
Next steps
Before you agree to the test or the procedure make sure you know:
• The name of the test or procedure
• The reason you are having the test or procedure
• What results to expect and what they mean
• The risks and benefits of the test or procedure
• What the possible side effects or complications are
• When and where you are to have the test or procedure
• Who will do the test or procedure and what that person’s qualifications are
• What would happen if you did not have the test or procedure
• Any alternative tests or procedures to think about
• When and how you will get the results
• Who to call after the test or procedure if you have questions or problems
• How much you will have to pay for the test or procedure
|
{
"url": "https://www.uhhospitals.org/health-information/health-and-wellness-library/adult-diseases-and-conditions/article/tests-and-procedures/bone-marrow-transplant",
"source_domain": "www.uhhospitals.org",
"snapshot_id": "crawl=CC-MAIN-2021-04",
"warc_metadata": {
"Content-Length": "81059",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:47UINTEENWGS6FA6TZTAAGB4KVFVOBQ3",
"WARC-Concurrent-To": "<urn:uuid:6f7da199-65f4-44c0-b774-5ff74c444afe>",
"WARC-Date": "2021-01-27T08:40:10",
"WARC-IP-Address": "52.247.87.109",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:3EB7BVSLHGZ4ERKDI5NYLKXLA5FAC32L",
"WARC-Record-ID": "<urn:uuid:347332df-288e-44e5-bcd1-332e7d9a78f1>",
"WARC-Target-URI": "https://www.uhhospitals.org/health-information/health-and-wellness-library/adult-diseases-and-conditions/article/tests-and-procedures/bone-marrow-transplant",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:77fc377f-0087-472b-89a6-56c0b87dc3ec>"
},
"warc_info": "isPartOf: CC-MAIN-2021-04\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for January 2021\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-99.ec2.internal\r\nsoftware: Apache Nutch 1.17 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.2-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: http://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
23,
24,
58,
59,
517,
518,
593,
594,
607,
620,
640,
672,
701,
702,
1073,
1074,
1145,
1223,
1224,
1434,
1435,
2269,
2666,
2667,
2699,
2700,
2814,
2815,
3167,
3450,
3617,
3857,
4184,
4185,
4527,
4528,
4839,
4840,
5168,
5169,
5320,
5321,
5364,
5365,
5784,
5785,
5826,
5827,
5959,
6070,
6225,
6371,
6372,
6497,
6498,
6546,
6547,
6577,
6578,
6612,
6661,
6705,
6749,
6804,
6833,
6834,
6912,
6913,
7344,
7657,
7853,
8281,
8574,
8813,
9071,
9692,
9693,
9742,
9743,
9825,
9826,
9995,
10193,
10546,
10979,
10980,
11204,
11205,
11334,
11539,
11729,
11904,
12026,
12092,
12242,
12260,
12289,
12311,
12348,
12369,
12395,
12415,
12416,
12582,
12583,
12633,
12659,
12687,
12755,
12802,
12852,
12883,
12884,
13626,
13627,
13673,
13674,
14035,
14036,
14601,
14602,
14658,
14659,
14668,
14679,
14689,
14699,
14714,
14715,
14760,
14761,
14907,
14908,
14948,
14981,
15008,
15036,
15075,
15125,
15341,
15370,
15441,
15501,
15502,
15767,
15768,
16192,
16193,
16493,
16494,
16572,
16573,
16596,
16645,
16679,
16692,
16724,
16791,
16821,
16822,
17377,
17378,
17389,
17390,
17456,
17457,
17495,
17547,
17593,
17645,
17701,
17758,
17838,
17902,
17957,
17999,
18077
],
"line_end_idx": [
23,
24,
58,
59,
517,
518,
593,
594,
607,
620,
640,
672,
701,
702,
1073,
1074,
1145,
1223,
1224,
1434,
1435,
2269,
2666,
2667,
2699,
2700,
2814,
2815,
3167,
3450,
3617,
3857,
4184,
4185,
4527,
4528,
4839,
4840,
5168,
5169,
5320,
5321,
5364,
5365,
5784,
5785,
5826,
5827,
5959,
6070,
6225,
6371,
6372,
6497,
6498,
6546,
6547,
6577,
6578,
6612,
6661,
6705,
6749,
6804,
6833,
6834,
6912,
6913,
7344,
7657,
7853,
8281,
8574,
8813,
9071,
9692,
9693,
9742,
9743,
9825,
9826,
9995,
10193,
10546,
10979,
10980,
11204,
11205,
11334,
11539,
11729,
11904,
12026,
12092,
12242,
12260,
12289,
12311,
12348,
12369,
12395,
12415,
12416,
12582,
12583,
12633,
12659,
12687,
12755,
12802,
12852,
12883,
12884,
13626,
13627,
13673,
13674,
14035,
14036,
14601,
14602,
14658,
14659,
14668,
14679,
14689,
14699,
14714,
14715,
14760,
14761,
14907,
14908,
14948,
14981,
15008,
15036,
15075,
15125,
15341,
15370,
15441,
15501,
15502,
15767,
15768,
16192,
16193,
16493,
16494,
16572,
16573,
16596,
16645,
16679,
16692,
16724,
16791,
16821,
16822,
17377,
17378,
17389,
17390,
17456,
17457,
17495,
17547,
17593,
17645,
17701,
17758,
17838,
17902,
17957,
17999,
18077,
18136
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 18136,
"ccnet_original_nlines": 177,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.37969160079956055,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.008146639913320541,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.14372999966144562,
"rps_doc_frac_unique_words": 0.2287798374891281,
"rps_doc_mean_word_length": 4.80338191986084,
"rps_doc_num_sentences": 205,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.384515285491943,
"rps_doc_word_count": 3016,
"rps_doc_frac_chars_dupe_10grams": 0.00759301008656621,
"rps_doc_frac_chars_dupe_5grams": 0.10333401709794998,
"rps_doc_frac_chars_dupe_6grams": 0.05839718133211136,
"rps_doc_frac_chars_dupe_7grams": 0.03299510106444359,
"rps_doc_frac_chars_dupe_8grams": 0.0180851798504591,
"rps_doc_frac_chars_dupe_9grams": 0.00759301008656621,
"rps_doc_frac_chars_top_2gram": 0.04555809125304222,
"rps_doc_frac_chars_top_3gram": 0.042796991765499115,
"rps_doc_frac_chars_top_4gram": 0.027541929855942726,
"rps_doc_books_importance": -1196.6080322265625,
"rps_doc_books_importance_length_correction": -1196.6080322265625,
"rps_doc_openwebtext_importance": -792.78369140625,
"rps_doc_openwebtext_importance_length_correction": -792.78369140625,
"rps_doc_wikipedia_importance": -617.1309814453125,
"rps_doc_wikipedia_importance_length_correction": -617.1309814453125
},
"fasttext": {
"dclm": 0.08882684260606766,
"english": 0.9326215982437134,
"fineweb_edu_approx": 3.2365610599517822,
"eai_general_math": 0.03620963916182518,
"eai_open_web_math": 0.21849000453948975,
"eai_web_code": 0.0019431100226938725
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.9942",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "616.994",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "3",
"label": "Irrelevant Content"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "9",
"label": "FAQ"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "2",
"label": "High School Level"
},
"secondary": {
"code": "1",
"label": "General Audience"
}
}
}
|
9222580d47c553ea90dc0f5e416f8f3a
|
-684,406,589,746,562,000
|
What is ST medical abbreviation?
What is the meaning of the ST medical abbreviation?
There may be a few different meanings of abbreviation ST. However, what is the medical abbreviation ST?
What is ST medical abbreviation?
In science & medicine, the meaning of the ST medical abbreviation is sinus tachycardia.
ST: sinus tachycardia
Related Medical Abbreviations
Neutneutrophil
ERExternal Rotation; also Emergency Room
MRMitral Regurgitation
PAFparoxysmal atrial fibrillation; platelet activating factor
IBMinclusion body myositis
NVDnausea, vomiting, diarrhea; normal vaginal delivery
mg/dlmilligrams per deciliter
PbLead (element)
tabTablet
IVHAintravenous hyperalimentation
PCSprocedure coding system
RUTright upper thigh
WAISWechsler Adult Intelligence Scale
T.A.T.toxin-antitoxin
Gyngynecolog(y/ist/ic)
GFRglomerular filtration rate
NEnot evaluated/not examined; norepinephrine; neurological examination
MODSmultiple organ dysfunction syndrome
O&Gobstetrics and gynecology
DISIDAdiisopropyl iminodiacetic acid (cholescintigraphy)
KPIkey performance indicator
SAARDslow-acting antirheumatic drug(s)
SOSsinusoidal obstruction syndrome; help needed distress signal (save our ship)
LFTLiver Function Test
GCPgood clinical practice
GIFTgamete intrafallopian transfer
Related Posts
Recommended
|
{
"url": "https://mcathub.com/st-medical-abbreviation/",
"source_domain": "mcathub.com",
"snapshot_id": "CC-MAIN-2024-33",
"warc_metadata": {
"Content-Length": "268856",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:FJEFZVBZULWRQQUKBJKNFNEP3WAODO7S",
"WARC-Concurrent-To": "<urn:uuid:57234b43-4c06-44d9-9c6a-b2a7ac4b515a>",
"WARC-Date": "2024-08-05T21:25:28",
"WARC-IP-Address": "54.85.8.229",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:B2M2KCKMWZV4FATLVVXZZ6WVQ22V42L2",
"WARC-Record-ID": "<urn:uuid:273ea049-342f-4e05-bcf9-dbad53d13c62>",
"WARC-Target-URI": "https://mcathub.com/st-medical-abbreviation/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:2e62fc7b-b193-497c-b4e3-87a838286992>"
},
"warc_info": "isPartOf: CC-MAIN-2024-33\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for August 2024\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-133\r\nsoftware: Apache Nutch 1.20 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.5-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
33,
34,
35,
87,
88,
192,
193,
226,
227,
315,
316,
338,
339,
369,
370,
385,
426,
449,
511,
538,
593,
623,
640,
650,
684,
711,
732,
770,
792,
815,
845,
916,
956,
985,
1042,
1071,
1110,
1190,
1213,
1239,
1274,
1275,
1289,
1290
],
"line_end_idx": [
33,
34,
35,
87,
88,
192,
193,
226,
227,
315,
316,
338,
339,
369,
370,
385,
426,
449,
511,
538,
593,
623,
640,
650,
684,
711,
732,
770,
792,
815,
845,
916,
956,
985,
1042,
1071,
1110,
1190,
1213,
1239,
1274,
1275,
1289,
1290,
1301
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 1301,
"ccnet_original_nlines": 44,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.13775509595870972,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.05612244829535484,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.19387754797935486,
"rps_doc_frac_unique_words": 0.767123281955719,
"rps_doc_mean_word_length": 7.5821919441223145,
"rps_doc_num_sentences": 10,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 4.524775505065918,
"rps_doc_word_count": 146,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.11382114142179489,
"rps_doc_frac_chars_dupe_6grams": 0.06504064798355103,
"rps_doc_frac_chars_dupe_7grams": 0.06504064798355103,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.08581752330064774,
"rps_doc_frac_chars_top_3gram": 0.0758807584643364,
"rps_doc_frac_chars_top_4gram": 0.027100270614027977,
"rps_doc_books_importance": -102.64187622070312,
"rps_doc_books_importance_length_correction": -102.64187622070312,
"rps_doc_openwebtext_importance": -54.76749801635742,
"rps_doc_openwebtext_importance_length_correction": -54.76749801635742,
"rps_doc_wikipedia_importance": -46.54572677612305,
"rps_doc_wikipedia_importance_length_correction": -46.545719146728516
},
"fasttext": {
"dclm": 0.2594764828681946,
"english": 0.7738125920295715,
"fineweb_edu_approx": 3.0434658527374268,
"eai_general_math": 0.0010715699754655361,
"eai_open_web_math": 0.03320986032485962,
"eai_web_code": 7.200000027296483e-7
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "610.0",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": ""
}
},
"secondary": {
"code": "616.0",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "1",
"label": "Remember"
},
"secondary": {
"code": "2",
"label": "Understand"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "1",
"label": "Factual"
},
"secondary": {
"code": "2",
"label": "Conceptual"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "3",
"label": "Irrelevant Content"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "6",
"label": "Content Listing"
}
},
"reasoning_depth": {
"primary": {
"code": "1",
"label": "No Reasoning"
},
"secondary": {
"code": "2",
"label": "Basic Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "2",
"label": "High School Level"
},
"secondary": {
"code": "1",
"label": "General Audience"
}
}
}
|
b755ed28a90d11d590ef646404f4afc5
|
1,856,451,043,487,837,200
|
Advertising For Reflexologists
There are lots of similarities between hand reflexology and foot reflexology, this article goes to have a look at how they examine and the advantages come from reflexology. To discover a reputable and certified reflexologist in your area, contact the Reflexology Affiliation of Australia. The message right here is that if RTCs printed in peer-evaluation journals are the gold customary for establishing credibility, then the reflexology field has to maintain pushing for the popularity it deserves.reflexology
Taking a hundred and fifty adults with chronic sinus an infection signs, University of Wisconsin School of Medication researchers tested how they fared with nasal irrigation in comparison with reflexology for two weeks. There are a lot of techniques of reflexology, some with very completely different approaches and factors.reflexology
Say goodbye to age strains, dry pores and skin, brown spots, blemishes—with Physique Reflexology you possibly can actually give your self an at-house facelift with no discomfort or disfiguring surgery 7. Reflexology is a centered stress method, usually directed at the ft or palms.
Reflexology is a four,000-yr-previous healing art that has only a few medically backed research to show it’s advantages however has a considerable amount of private testimonies praising it is price. Reflexology is a acknowledged type of care in China and a few European countries, where it is often provided in hospitals and different health care amenities.reflexology
Reflexologists imagine that the feet are mirrors of the human body, and that making use of pressure to sure areas on the foot releases blocked energy in the corresponding physique part. Already effective at alleviating stress and anxiousness, researchers in Denmark in the 1990s took a glance into how reflexology could help headache and migraine sufferers.
|
{
"url": "http://www.yourshoes2012.com/advertising-for-reflexologists.html",
"source_domain": "www.yourshoes2012.com",
"snapshot_id": "crawl=CC-MAIN-2018-43",
"warc_metadata": {
"Content-Length": "29745",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:CN6A2YMIXTWO5ZMPGGJHKERFTPAC32SJ",
"WARC-Concurrent-To": "<urn:uuid:93157456-caf9-4281-af88-d9b54e190510>",
"WARC-Date": "2018-10-18T11:08:46",
"WARC-IP-Address": "104.27.142.111",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:YQQLQBXLZBQT6YU574O4MVTFWB2ZG65Y",
"WARC-Record-ID": "<urn:uuid:770a7597-f8e2-46ba-9d99-2c877f958239>",
"WARC-Target-URI": "http://www.yourshoes2012.com/advertising-for-reflexologists.html",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:c997a397-2b75-4987-abec-44d0c6d774eb>"
},
"warc_info": "isPartOf: CC-MAIN-2018-43\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for October 2018\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-69-198-189.ec2.internal\r\nsoftware: Apache Nutch 1.15 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 0.11-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: http://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
31,
32,
543,
544,
881,
882,
1166,
1167,
1536,
1537
],
"line_end_idx": [
31,
32,
543,
544,
881,
882,
1166,
1167,
1536,
1537,
1895
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 1895,
"ccnet_original_nlines": 10,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.42592594027519226,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.09876543283462524,
"rps_doc_frac_unique_words": 0.6373239159584045,
"rps_doc_mean_word_length": 5.566901206970215,
"rps_doc_num_sentences": 11,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 4.8361992835998535,
"rps_doc_word_count": 284,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.024667929857969284,
"rps_doc_frac_chars_top_3gram": 0.026565460488200188,
"rps_doc_frac_chars_top_4gram": 0,
"rps_doc_books_importance": -144.66287231445312,
"rps_doc_books_importance_length_correction": -144.66238403320312,
"rps_doc_openwebtext_importance": -75.1691665649414,
"rps_doc_openwebtext_importance_length_correction": -75.1691665649414,
"rps_doc_wikipedia_importance": -62.036380767822266,
"rps_doc_wikipedia_importance_length_correction": -62.036380767822266
},
"fasttext": {
"dclm": 0.0684211328625679,
"english": 0.943715512752533,
"fineweb_edu_approx": 2.2404003143310547,
"eai_general_math": 0.1740870475769043,
"eai_open_web_math": 0.37772291898727417,
"eai_web_code": 0.0037264199927449226
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "615.85",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
},
"secondary": {
"code": "615.8",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "6",
"label": "Promotional/Advertisement"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "3",
"label": "Irrelevant Content"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "2",
"label": "Click Here References"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "17",
"label": "Product Page"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "1",
"label": "No Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "6",
"label": "Not Applicable/Indeterminate"
},
"secondary": {
"code": "2",
"label": "Partially Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
1a01aa77535b9ecfb87b9fc36adbcd2f
|
-2,941,792,590,641,119,000
|
ADHD: What Everyone Needs to Know | Core Spirit
March 29
ADHD: What Everyone Needs to Know
Article by George Smith
Core Spirit member since Dec 24, 2020
Reading time 3 minutes
In their book, ADHD: What Everyone Needs to Know, authors Stephen P. Hinshaw and Katherine Ellison systematically answer all your burning questions about ADHD. The authors make an excellent writing team. Their extensive knowledge and compassion is evident and that feels reassuring, particularly when they are addressing controversial topics.
Stephen is a professor at the University of California and an internationally recognized expert on ADHD.
Katherine Ellison is a Pulitzer prize winning journalist and author. She also has a personal interest in ADHD, as she and her son both have ADHD.
How the book is structured
The book is divided into two parts. Part 1 looks at what ADHD is, what causes it, how you know if you have it and how ADHD changes over your lifespan. Part 2 looks at what actions you can take to treat and manage your ADHD. This includes ADHD medication, behavior therapy and other strategies that might be helpful, such as exercise, diet and supplements.
Writing style
The writing style is clear and to the point. It hits the perfect balance of being factual and easy to understand without insulting your intelligence. It is a compelling read! Even if you don’t usually like reading, you will be pulled in. The book is written using a question and answer format. This makes it a great reference book, as you can dip into it any time to get the answers you need.
Somehow the authors knew exactly what questions you would be asking. At the end of each chapter there is a brief summary of the important points.
The Best Thing
The best thing about ADHD: What Everyone Needs to Know, is that it provides answers to the most controversial topics on ADHD.
The 4 letters ‘ADHD’ have a way of provoking heated debates.
You might want to quietly go about your day, but there will be someone who wants to be argumentative and ask provoking questions such as ‘Why is there so much ADHD now?’ or ‘‘If ADHD is ‘real’ why don’t they use brain scans to test for it?’’ or ‘Don’t you think it's wrong that children are being given stimulants?’. After reading this book you will be equipped to answer all those questions and more.
Feeling informed is empowering. You will understand the pros and cons to each argument as the authors offer balanced discussion. For example, they consider the risks and fears people have about ADHD medication alongside the cost of untreated ADHD, and how ADHD can be both under diagnosed and over diagnosed at the same time.
Other good things
The chapter on ADHD medication is very helpful, both for people who aren’t taking medications and those that are. It answers basic questions like ‘How do stimulant medicines work?’ and ‘What are the side effects of ADHD medication?’ and less talked about subjects ‘How do other countries compare with the United States in medication prescription for ADHD?’
There are some other interesting topics covered. They aren’t controversial, but ones that you have properly been curious about. Such as ‘Is ADHD really a gift? and ’Are TV and video games bad?’
Who is the book for?
It is perfect for you if it’s your first ADHD book or your 100th, if you are a parent of an ADHD child, have adult ADHD yourself or want to learn more about it to better understand your partner.
by Jacqueline Sinfield For Very Well/a>
Comments
To write a comment you must
or
|
{
"url": "https://corespirit.com/articles/adhd-what-everyone-needs-to-know",
"source_domain": "corespirit.com",
"snapshot_id": "crawl=CC-MAIN-2021-21",
"warc_metadata": {
"Content-Length": "65757",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:GAES2E3AUUXSPHJC4KCXSNDRTL5MBCLC",
"WARC-Concurrent-To": "<urn:uuid:269badc9-0215-445c-abe7-5659b11a5fd8>",
"WARC-Date": "2021-05-13T15:56:55",
"WARC-IP-Address": "34.78.173.7",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:OKNTMEFO4FKRWQ33H3U2XJYH2GNKFAMG",
"WARC-Record-ID": "<urn:uuid:585b063d-94ec-4c60-b9ed-a2a7b4d3a145>",
"WARC-Target-URI": "https://corespirit.com/articles/adhd-what-everyone-needs-to-know",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:e94d9bb3-7316-4d27-a5fe-18e813ab847b>"
},
"warc_info": "isPartOf: CC-MAIN-2021-21\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for May 2021\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-110.ec2.internal\r\nsoftware: Apache Nutch 1.18 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.2-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
48,
57,
58,
92,
93,
117,
155,
178,
179,
522,
523,
628,
629,
775,
776,
803,
804,
1160,
1161,
1175,
1176,
1569,
1570,
1716,
1717,
1732,
1733,
1859,
1860,
1921,
1922,
2324,
2325,
2651,
2652,
2670,
2671,
3028,
3029,
3223,
3224,
3245,
3246,
3441,
3442,
3482,
3483,
3492,
3520
],
"line_end_idx": [
48,
57,
58,
92,
93,
117,
155,
178,
179,
522,
523,
628,
629,
775,
776,
803,
804,
1160,
1161,
1175,
1176,
1569,
1570,
1716,
1717,
1732,
1733,
1859,
1860,
1921,
1922,
2324,
2325,
2651,
2652,
2670,
2671,
3028,
3029,
3223,
3224,
3245,
3246,
3441,
3442,
3482,
3483,
3492,
3520,
3522
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 3522,
"ccnet_original_nlines": 49,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.4414285719394684,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.03999999910593033,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.12999999523162842,
"rps_doc_frac_unique_words": 0.4802631735801697,
"rps_doc_mean_word_length": 4.646381378173828,
"rps_doc_num_sentences": 39,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.152503967285156,
"rps_doc_word_count": 608,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.03823009133338928,
"rps_doc_frac_chars_dupe_6grams": 0.03823009133338928,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.011327429674565792,
"rps_doc_frac_chars_top_3gram": 0.02265487052500248,
"rps_doc_frac_chars_top_4gram": 0.02973451092839241,
"rps_doc_books_importance": -329.65484619140625,
"rps_doc_books_importance_length_correction": -329.65484619140625,
"rps_doc_openwebtext_importance": -176.67388916015625,
"rps_doc_openwebtext_importance_length_correction": -176.67388916015625,
"rps_doc_wikipedia_importance": -123.83740997314453,
"rps_doc_wikipedia_importance_length_correction": -123.83740997314453
},
"fasttext": {
"dclm": 0.176588237285614,
"english": 0.9529929161071777,
"fineweb_edu_approx": 2.834285020828247,
"eai_general_math": 0.2656933665275574,
"eai_open_web_math": 0.2940906286239624,
"eai_web_code": 0.026456300169229507
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.858",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "616.89",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "14",
"label": "Reviews/Critiques"
},
"secondary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "17",
"label": "Product Page"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "6",
"label": "Not Applicable/Indeterminate"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
6e3c8d3593f3f69280bb5502b214ab8e
|
3,922,943,777,412,638,700
|
Background
Brain water homeostasis is important to prevent edema and functional disturbances in the interplay between neurons and glial cells. Brain edema contributes extraordinarily to morbidity and mortality after cerebral ischemic stroke, mainly due to its space-occupying effect [1-4]. Aquaporin-4 (AQP4) is the main glial (astrocytic) water channel in the brain and is mainly expressed at fluid-tissue borders throughout the central nervous system [5-7]. Recent data suggest that AQP4 is involved in brain edema formation as well as in edema elimination [8,9].
AQP4 has also been described as an autoantigen in neuromyelitis optica (NMO), an inflammatory disease of the central nervous system, mainly affecting the spinal cord and the optic nerve [10,11]. The clinical findings associated with AQP4-antibodies include idiopathic inflammatory demyelinating disorders summarized as “NMO-spectrum disorders”. The defining marker of these disorders is the presence of AQP4-antibodies in sera and/or cerebrospinal fluid (CSF) [12]. AQP4-antibodies are synthesized intrathecally at the disease onset and a down-regulation of AQP4 on astrocytes in-vitro is induced by degradation and internalization of the protein within minutes [13,14]. However, Rossi et al. recently doubted, that NMO-IgG leads to inhibition of AQP4 water permeability at all [15]. Adding complement and AQP4-antibodies to astrocytes activates the classical complement cascade leading to impaired membrane integrity of the cultured astrocytes [14,16]. Interestingly, AQP4-IgG also induced a down-regulation of excitatory amino-acid transporter 2 (EAAT2), an astrocytic glutamate transporter. Glutamate has long been known to play an important role in the pathophysiology of cerebral ischemia [16-18]. Additionally, AQP4 antibodies increase the permeability of a blood–brain-barrier model using co-cultured astrocytes and brain endothelial cells [19].
Recently, intraventricular injection of AQP4-positive IgG together with human complement has been shown to induce NMO-like inflammatory brain lesions [20], and passive transfer of NMO-IgG to EAE-rats induced an exacerbation of the disease and NMO-like lesions [21,22]. These studies produce first evidence for functional properties of AQP4-antibodies in an in-vivo animal model.
The involvement of AQP4 in the dynamics of brain edema and findings of in-vitro studies on properties of AQP4-antibodies such as the impairment of cell integrity, the promotion of excitotoxicity and increased permeability of the blood–brain-barrier, include important pathways known from the pathophysiology of ischemic stroke [23]. This leads to the assumption, that anti-AQP4 may exert also in-vivo effects on the extent of ischemic infarction and edema as well as on functional outcome.
In the present study, we investigated whether administration of NMO-IgG, extracted from one NMO-patient, influences the development of stroke in an MRI-based rat middle-cerebral artery occlusion model. Intravenous immune globulin can reduce infarct volume in rat models for stroke [24]; therefore, injection of immune globulin from healthy controls served as placebo-treatment in the control group. We found infarct size being almost doubled in NMO-IgG treated animals. In addition, vasogenic edema formation, as detected on quantitative T2-weighted MR-imaging, was increased in the cortex of NMO-IgG treated animals.
Our results add important information to the in-vivo effects of AQP4-antibodies in animal models. This model can be used to elucidate the functional properties of AQP4 in ischemic stroke in the future.
Methods
Animal preparation
All procedures were carried out in accordance with our institutional guidelines and the German animal protection legislation and were approved by the regional ethics committee (Regierungspraesidium Darmstadt).
Sixteen male Wistar Unilever rats (HsdCpb:WU; Harlan Winkelmann, Germany), weighing 290 to 350 g, were anesthetized with 5% isoflurane (Abbott, Wiesbaden, Germany), delivered through air at 1.0 L/min for two minutes. Anesthesia was maintained with 2-3% isoflurane delivered through air at 0.6 L/min during surgery and MR imaging. During the surgical procedure and MR measurements, body temperature was monitored with a rectal probe and maintained at 37°C by external heating.
Middle cerebral artery occlusion and reperfusion
Middle cerebral artery occlusion (MCAO) was performed as described previously [24,25]. Briefly, the right common (CCA), internal (ICA) and external carotid artery (ECA) were exposed through a midline incision of the neck and the ECA was ligated with a 4–0 suture. A 4–0 silicone-coated nylon suture with a thermically rounded tip was introduced through an arteriotomy of the CCA. The occluder was advanced carefully into the ICA 17.0 to 21.0 mm beyond the carotid bifurcation until a mild elastic resistance indicated the tip was properly lodged in the anterior cerebral artery and thus blocked blood flow to the MCA. Then the occluder was fixed in place with a 4–0 suture. Ninety minutes after MCAO, the nylon suture was drawn from the CCA for reperfusion of the brain. Then the animals were allowed to recover from anaesthesia in individual cages with free access to food and water for the remaining survival time of 24 h.
MR imaging
The animals were fixed in a body restrainer with a tooth-bar and a cone shaped head holder and were placed in an MRI spectrometer (Bruker PharmaScan 7.0 T, 16 cm, Ettlingen, Germany). Respiratory rate was monitored by a pressure probe placed between the restrainer and the animal’s thorax. Anesthesia was maintained with isoflurane delivered through air at 0.6 L/min. The isoflurane concentration was varied between 2.0 and 3.0% to keep the respiratory rate between 35 and 45/min. Temperature was monitored using a rectal probe and maintained at 37°C by a thermostatically regulated water flow system during the entire imaging protocol [24,25].
The MRI-tomograph operates at 300.51 MHz for 1H-imaging and is equipped with a 300mT/m self-shielding gradient system. The linear polarized volume resonator (diameter 60 mm) was tuned and matched manually.
Localizer images were acquired using a spin-echo sequence. RARE sequences (20 contiguous slices, 1 mm thickness, TR = 2500 ms, TE = 41.8 ms) were used to verify symmetric positioning and were repeated after correction of slice-angulation, if necessary.
T2-Weighted Imaging (T2WI)
A Carr-Purcell-Meiboom-Gill spin echo imaging sequence was used to map lesion and hemisphere volumes. Eight contiguous coronal slices with a thickness of 2 mm (gap 0 mm) were acquired (FOV 37 × 37 mm, matrix 512 × 256, TR 3833.5 msec, 12 echoes: TE 18–216 msec (∆TE 18 msec), TA 16.25 minutes, NEX 1).
T2-relaxation time (T2RT) was measured in regions of interest within the center of the ischemic area on all slices displaying ischemic lesions and a corresponding position on the contralateral hemisphere. The difference in T2RT between the ischemic and unaffected hemispheres was calculated.
Computer aided planimetric assessment of ischemic lesion volumes and hemispheric volumes were performed by two blinded investigators experienced in experimental stroke MRI. Ipsilateral and contralateral hemispheric volume and lesion volume on T2WI were determined with the image analysis software Image J 1.25 s (National Institutes of Health, USA). After optimal adjustment of contrast, the edges of the hemispheres were traced manually on each slice, using neuroanatomic landmarks. The edges of the hyperintense ischemic lesions were traced manually in a similar fashion. The areas were then summed and multiplied by the slice thickness to calculate volumes. Lesion volumes were calculated with and without edema correction and expressed as percent of the hemispheric volume as described previously [26]:
$$ \%\mathrm{HLVuc} = \mathrm{L}\mathrm{V}/\left(\left(\mathrm{H}\mathrm{V}\mathrm{c} + \mathrm{H}\mathrm{V}\mathrm{i}\right)/2\right)*100\Big) $$
$$ \%\mathrm{HLVec} = \left(\mathrm{H}\mathrm{V}{\mathrm{c}}^2 + \mathrm{L}\mathrm{V}*\left(\mathrm{H}\mathrm{V}\mathrm{c} + \mathrm{H}\mathrm{V}\mathrm{i}\right)-\mathrm{H}\mathrm{V}{\mathrm{i}}^2\right)/\left(\mathrm{H}\mathrm{V}\mathrm{c}*\left(\mathrm{H}\mathrm{V}\mathrm{c} + \mathrm{H}\mathrm{V}\mathrm{i}\right)\right)*100 $$
(%HLVuc = percent hemispheric lesion volume – not corrected for edema; %HLVec = percent hemispheric lesion volume – corrected for edema; HVc = volume of the contralateral hemisphere; HVi = volume of the ipsilateral hemisphere; LV = lesion volume)
Midline shift (MLS) -quantification was performed on T2-weighted images where the position of the third ventricle could be determined clearly in all animals. The distance between the outer border of the cortex and the middle of the third ventricle was measured from the ipsilateral (A) and contralateral (B) side. Measurements were performed at the level of maximum lateral displacement of the ventricle. MLS was calculated using the following equation [4,27]:
$$ \mathrm{M}\mathrm{L}\mathrm{S} = \left(\mathrm{A}-\mathrm{B}\right)/2 $$
Purification of immune globulin
Plasma from one male NMO-patient aged 41, AQP4-IgG ratio 70.79 in serum (antibody measured by radioimmunoprecipitation with a ratio <10 being negative) was diluted with glycine buffer (0.1 M, pH 9) and applied to a protein G column (HiTrap - GE) that binds exclusively IgG. The IgG-fraction was eluted by changing the pH from 9 to 2.7. The IgG-concentration was determined by nephelometry (Boehring). IgG-fractions were dialyzed against PBS to eliminate the glycine and increase the pH up to 7.4 and diluted with PBS to 9.5 g/L.
Functional testing
Neurological evaluation was performed prior to anesthesia and 24 hours after induction of ischemia. We applied a neurological score with ten different sensorimotor and coordinative items, as described by Nedelmann et al. [28]. Furthermore, animals were placed on a rotarod that was continuously accelerated from 0 rpm to 30 rpm. The maximum speed the animals tolerated without falling off of the device was recorded [29].
Experimental protocol
Sixteen animals were randomized into two groups, receiving either NMO-IgG (9.5 g/L) or immune globulin from a pooled sample of 10 healthy controls (control-IgG) as placebo. Two mL of immune globulin were twice injected intravenously: 24 hours and 30 minutes before MCAO.
Twenty-four hours after induction of ischemia, the animals were evaluated clinically, subjected to MR-imaging and then decapitated while under deep anesthesia. The brains were quickly removed from the skull and inspected to detect side-effects such as subarachnoid hemorrhage.
Statistical analysis
Data are presented as mean ± standard deviation. Group differences were tested using either Mann–Whitney u-test or Student’s t-test where applicable. A p-value <0.05 was considered statistically significant.
Results
Three animals had to be excluded from this study according to our predefined exclusion criteria [25]: One animal (control-IgG group) developed subarachnoid hemorrhage, as detected by postmortem inspection, two animals (one control-IgG group, and one NMO-IgG group) did not develop an ischemic MCA territory stroke, most likely due to inappropriate insertion depth of the occluder. All excluded animals were replaced.
The remaining animals survived and completed the study protocol. Injections of NMO-IgG and control-IgG were well tolerated by all animals without overt side effects.
Twenty-four hours after ischemia and reperfusion, all animals displayed clinical signs of MCA territory stroke. Clinical evaluation indicated a trend towards more severe neurological deficits in NMO-IgG treated rats (score 42.1 ± 11.1) as compared to control-IgG treated rats (37.1 ± 10.7). The difference, however, was not statistically significant (p = 0.391; u-test). Rotarod test performance was likewise comparable between both groups (p = 0.450; u-test).
Infarct size, as determined by MRI and corrected for the space-occupying effect of vasogenic edema formation, was significantly increased in NMO-IgG treated animals (27.1% ± 11.1%) as compared to control-IgG treated rats (14.3% ± 7.2%; p = 0.026; t-test) (Figures 1 and 2). Infarct size quantification without edema correction revealed similar results (34.4% ± 16.4% vs. 17.5% ± 9.3%; p = 0.031; t-test).
Figure 1
figure 1
T2-weighted MRI. Representative examples of right-hemispherical ischemia in T2-weighted MRI after 24 h (contiguous slices 2–5): 1st row NMO-IgG, 2nd row control-IgG.
Figure 2
figure 2
Infarct size. Treatment with NMO-IgG caused a significant increase in ischemic lesion volume compared to control-IgG (p < 0.05; expressed in percent of the affected hemisphere).
A more pronounced midline shift was also detectable in NMO-IgG treated animals. However, this was not statistically significant (0.53 mm ± 0.37 mm vs. 0.31 mm ± 0.16 mm; p = 0.174; t-test) (Figure 3).
Figure 3
figure 3
Midline shift. NMO-IgG-treatment leads to a more pronounced midline-shift as compared to control-IgG (p > 0.05).
Quantification of the brain water content by T2-RT measurement showed different results for the cortex and the basal ganglia. In basal ganglia regions no significant difference in T2-RT could be detected (NMO-IgG: 26.4 ms ± 6.1 ms; control-IgG: 22.1 ms ± 9.5 ms; p = 0.328) (Figure 4). Within the cortex, however, NMO-IgG treatment resulted in a statistically significant increase in brain water content (19.5 ms ± 9.7 ms) as compared to rats treated with control-IgG (9.2 ms ± 5.2 ms; p = 0.045; t-test) (Figure 4).
Figure 4
figure 4
Edema formation within the basal ganglia and the cortex. T2-relaxation time, a parameter that correlates closely with vasogenic edema formation, was comparable between NMO-IgG and control-IgG treated animals if measured within the basal ganglia (p > 0.05). Vasogenic edema formation within the cortex was significantly increased in animals treated with NMO-IgG as compared to control-IgG (p < 0.05).
Discussion
With the present study we show that NMO-IgG has in-vivo effects in a stroke animal model, and perturbs brain water homeostasis. Treatment of rats with NMO-IgG prior to MCA-occlusion almost doubles infarct size and significantly increases cortical vasogenic edema formation.
A possible explanation for the larger infarct size might be that the application of immune globulin, per se, reduces infarct size in the control-IgG treated group. Recently, this mechanism has been described for intravenous immune globulin (IvIg), and also that it is mediated by inhibition of complement [24,30]. Thus, the control group (control-IgG) would benefit from this effect. However, since the NMO-IgG-fraction contains a normal amount of total IgG, the protective effects would be present here as well.
AQP4-IgG has recently been identified as a marker for Neuromyelitis optica, a disorder with demyelination of optic nerve and cervical spinal cord [14]. In-vitro observations showed that AQP4-IgG is able to induce a rapid internalization of AQP4 from the cell surface. Since these water pores are involved in the formation and elimination of vasogenic brain edema, application of AQP4-IgG might affect edema formation and brain swelling in acute ischemic stroke. Unfortunately, injection of this antibody dramatically increased edema formation in our rat stroke model.
Brain swelling due to cerebral edema can be attributed to both, cytotoxic and vasogenic brain edema, that often coexist or condition each other [31]. Evidence exists that the role of APQ4 differs between these two forms [31,32]. With respect to cytotoxic edema, where ionic imbalance results in water influx into the cell within minutes after ischemia onset, AQP4 - deficiency seems to promote edema reduction: AQP4 knock-out mice with ischemic stroke showed improved neurological outcome and reduced cerebral edema within the first 24 h after MCAO. However, compared to our study that included temporary MCAO for ninety minutes, Manley at al. chose a rodent model of permanent MCAO for 24 hours. Further more, the absolute reduction of tissue damage could not be determined, because the relation of edema in infarcted and non-infarcted regions was not known [8]. Vasogenic edema of the extracellular space is ascribed to leakage of a defective blood–brain barrier. Studies on models of vasogenic brain edema, including intraparenchymal fluid infusion, focal cortical freeze injury and tumor cell implantation in AQP4 knock-out mice showed increased elevations of intracranial pressure, increased brain water and worse neurological outcome, suggesting that AQP4 facilitates transcellular water movement and thereby clearance of vasogenic edema [33].
The promotion of vasogenic edema formation, displayed by a prolonged T2-RT, in our experiment could explain the dramatic increase in infarct size in the NMO-IgG group. Since the space-occupying effect of brain swelling is known to impair regional cerebral blood flow in the border zone of the evolving ischemic lesion - particularly within the cortex - this could explain the increase of lesion size [24,34,35]. We have previously shown that elimination of the space-occupying effect of edema formation (brought about by bilateral craniectomy prior to stroke onset) can reduce infarct size by 50%. This finding indicates that the space-occupying effect of vasogenic edema formation might be responsible for half of the ischemic damage in large territorial stroke [3]. Interestingly, T2-RT was generally longer in the basal ganglia compared to the cortex and statistically significant differences in vasogenic edema were only found in cortical areas (Figure 4). This finding may be attributed to on one hand worse vascular collateralization within basal ganglia and on the other hand to an inhomogeneous distribution of AQP4 in the brain: A study on cultured astrocytes isolated from rat cortex and striatum reasoned, that AQP4 is expressed at higher levels within the cortex compared to the striatum [36].
Another - or additional - explanation for the neurotoxic effect of AQP4-IgG is related to excitotoxicity caused by the release of glutamate during the early phase of the ischemic cascade [18]. Hinson et al. demonstrated that AQP4-IgG impairs glutamate transport by down-regulating the glutamate transporter EAAT2 along with the internalization of AQP4 [14,16]. EAAT2 is responsible for about 90% of total glutamate uptake [37]. Up-regulation of EAAT2 has been shown to induce ischemic tolerance in focal cerebral ischemia, and moreover, down-regulation of EAAT2 led to an increased infarct volume in a rat ischemia-reperfusion model [38]. Glutamate induced excitotoxicity can be further aggravated by the reversal of glutamate transporters under conditions of energy failure, i.e. stroke, where the electrochemical gradient of Na+/K+ collapses due to a decreased availability of ATP and leads to a glutamate efflux from astrocytes [39-41].
Approaches toward an animal model using AQP4-IgG necessarily involved a break-down of the blood–brain-barrier. Intravenous administration of AQP4-IgG alone did not exhibit any effects to the so treated animals [20-22]. Only intraventricular application of AQP4-IgG together with human complement, or treatment of EAE-rats with AQP4-IgG, was able to produce pathogenic effects in-vivo. In our model, NMO-IgG induced changes in the brain edema after an ischemic stroke. This suggests that not only inflammatory but also ischemic break down of the blood–brain-barrier results in effective targeting of AQP4-IgG.
Conclusion
Taken together, the present study indicates that human AQP4-IgG strongly influences vasogenic edema formation and infarct size in our MRI-based rat model of focal cerebral ischemia and reperfusion. Unfortunately, the antibody leads to an increase of edema and infarct size and is therefore not suitable for clinical application. However, this animal model is eligible to further study the properties of AQP4 in ischemic stroke in-vivo.
|
{
"url": "https://link.springer.com/article/10.1186/s12865-015-0087-y",
"source_domain": "link.springer.com",
"snapshot_id": "CC-MAIN-2024-18",
"warc_metadata": {
"Content-Length": "357535",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:PNGVVHPXXNFDOFVH5ZP7PNW2MWEG73LE",
"WARC-Concurrent-To": "<urn:uuid:b982c0a4-bd17-4263-a178-33e325a5e6a5>",
"WARC-Date": "2024-04-13T00:40:18",
"WARC-IP-Address": "146.75.32.95",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:F3CLODFEV736HHXSEAZCYQ74XJMEMSPT",
"WARC-Record-ID": "<urn:uuid:655e4a60-7ff9-4022-be83-591fc392e18b>",
"WARC-Target-URI": "https://link.springer.com/article/10.1186/s12865-015-0087-y",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:e5f4c144-75c8-49fc-bddf-aeb8854ecccd>"
},
"warc_info": "isPartOf: CC-MAIN-2024-18\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for April 2024\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-230\r\nsoftware: Apache Nutch 1.19 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.5-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
11,
12,
567,
568,
1921,
1922,
2301,
2302,
2792,
2793,
3411,
3412,
3614,
3615,
3623,
3624,
3643,
3644,
3854,
3855,
4331,
4332,
4381,
4382,
5307,
5308,
5319,
5320,
5965,
5966,
6172,
6173,
6426,
6427,
6454,
6455,
6757,
6758,
7050,
7051,
7858,
7859,
8006,
8339,
8340,
8587,
8588,
9049,
9050,
9126,
9127,
9159,
9160,
9689,
9690,
9709,
9710,
10132,
10133,
10155,
10156,
10427,
10428,
10705,
10706,
10727,
10728,
10936,
10937,
10945,
10946,
11363,
11364,
11530,
11531,
11992,
11993,
12398,
12399,
12408,
12417,
12418,
12584,
12585,
12594,
12603,
12604,
12782,
12783,
12984,
12985,
12994,
13003,
13004,
13117,
13118,
13635,
13636,
13645,
13654,
13655,
14055,
14056,
14067,
14068,
14342,
14343,
14856,
14857,
15425,
15426,
16776,
16777,
18083,
18084,
19024,
19025,
19634,
19635,
19646,
19647
],
"line_end_idx": [
11,
12,
567,
568,
1921,
1922,
2301,
2302,
2792,
2793,
3411,
3412,
3614,
3615,
3623,
3624,
3643,
3644,
3854,
3855,
4331,
4332,
4381,
4382,
5307,
5308,
5319,
5320,
5965,
5966,
6172,
6173,
6426,
6427,
6454,
6455,
6757,
6758,
7050,
7051,
7858,
7859,
8006,
8339,
8340,
8587,
8588,
9049,
9050,
9126,
9127,
9159,
9160,
9689,
9690,
9709,
9710,
10132,
10133,
10155,
10156,
10427,
10428,
10705,
10706,
10727,
10728,
10936,
10937,
10945,
10946,
11363,
11364,
11530,
11531,
11992,
11993,
12398,
12399,
12408,
12417,
12418,
12584,
12585,
12594,
12603,
12604,
12782,
12783,
12984,
12985,
12994,
13003,
13004,
13117,
13118,
13635,
13636,
13645,
13654,
13655,
14055,
14056,
14067,
14068,
14342,
14343,
14856,
14857,
15425,
15426,
16776,
16777,
18083,
18084,
19024,
19025,
19634,
19635,
19646,
19647,
20082
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 20082,
"ccnet_original_nlines": 121,
"rps_doc_curly_bracket": 0.00398366991430521,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.2752613127231598,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.047784969210624695,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.2608262896537781,
"rps_doc_frac_unique_words": 0.3433714210987091,
"rps_doc_mean_word_length": 5.6022844314575195,
"rps_doc_num_sentences": 193,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.992563247680664,
"rps_doc_word_count": 2889,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.037689220160245895,
"rps_doc_frac_chars_dupe_6grams": 0.026320669800043106,
"rps_doc_frac_chars_dupe_7grams": 0.019153539091348648,
"rps_doc_frac_chars_dupe_8grams": 0.008649979718029499,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.008958909660577774,
"rps_doc_frac_chars_top_3gram": 0.01136855036020279,
"rps_doc_frac_chars_top_4gram": 0.005437130108475685,
"rps_doc_books_importance": -1804.7696533203125,
"rps_doc_books_importance_length_correction": -1804.7696533203125,
"rps_doc_openwebtext_importance": -1085.4307861328125,
"rps_doc_openwebtext_importance_length_correction": -1085.4307861328125,
"rps_doc_wikipedia_importance": -680.6857299804688,
"rps_doc_wikipedia_importance_length_correction": -680.6857299804688
},
"fasttext": {
"dclm": 0.07534915208816528,
"english": 0.9145289659500122,
"fineweb_edu_approx": 2.5180320739746094,
"eai_general_math": 0.5776032209396362,
"eai_open_web_math": 0.42886173725128174,
"eai_web_code": 0.03309411182999611
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.858072",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "616.858",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "4",
"label": "Analyze"
},
"secondary": {
"code": "5",
"label": "Evaluate"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "2",
"label": "Academic/Research"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "0",
"label": "No Artifacts"
}
},
"missing_content": {
"primary": {
"code": "4",
"label": "Missing Images or Figures"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "3",
"label": "Academic Writing"
},
"secondary": {
"code": "10",
"label": "Knowledge Article"
}
},
"reasoning_depth": {
"primary": {
"code": "4",
"label": "Advanced Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "4",
"label": "Graduate/Expert Level"
},
"secondary": {
"code": "3",
"label": "Undergraduate Level"
}
}
}
|
9222580d47c553ea90dc0f5e416f8f3a
|
6,496,339,368,911,555,000
|
health and fitness
This description goes past being able to run fast or lift heavy weights. Despite being necessary, these attributes solely tackle single areas of fitness. This article offers details of the five primary elements of physical health. Recognize that the BMI scale isn’t good however can be helpful for monitoring changes in physique composition.
Hobbies such as woodwork and sewing or activities like skipping require you to move either side of the body on the same time, in precise actions. This can help to enhance your spatial consciousness and improve your reaction time. Australia’s physical activity and sedentary behaviour pointers, Department of Health and Ageing, Australian Government. Not only does a spread of actions hold your interest up, they challenge completely different muscular tissues.
Find actions near residence
Additionally, bodily activity can even raise pain tolerance and decrease pain notion . Regular bodily activity is very essential in older adults since growing older — combined with oxidative stress and irritation — promotes changes in brain structure and function . Therefore, day by day physical activity is beneficial to reduce stomach fat and decrease the risk of developing these illnesses .
Staying energetic can even assist you to maintain a healthy weight, scale back your risk for type 2 diabetes, coronary heart illness, and scale back your danger for some cancers. Muscle-strengthening workouts are increasingly being recognized as taking part in an necessary function in cardiovascular well being. With a set of dumbbells and a few easy strikes, folks can get a great energy exercise at house. Two fundamental exercises that strengthen a variety of muscles within the physique are a squat and a bent-over row. Boosting muscle mass helps burn more energy, each throughout and after exercise.
Physical activity promotes good well being, and you need to keep active throughout all levels of your life regardless of your physique type or BMI. Regardless of what you do, regular exercise and bodily activity is the path to well being and properly-being. Exercise burns fat, builds muscle, lowers cholesterol, eases stress and anxiety, lets us sleep restfully.
|
{
"url": "https://www.badmintonandalucia.com/health-fitness-guide-10.html",
"source_domain": "www.badmintonandalucia.com",
"snapshot_id": "CC-MAIN-2023-40",
"warc_metadata": {
"Content-Length": "47056",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:HKQPJW244WY42RKOQH6X56EVUAJ25ZZ4",
"WARC-Concurrent-To": "<urn:uuid:d108e0de-7def-447f-9f5f-773ad5d9e437>",
"WARC-Date": "2023-10-04T10:59:49",
"WARC-IP-Address": "172.67.170.252",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:FXZH7SG4643UZUUIRHUBQ4J2GWVNGDCP",
"WARC-Record-ID": "<urn:uuid:07fac9da-191d-4c95-91c5-507fc6f03f81>",
"WARC-Target-URI": "https://www.badmintonandalucia.com/health-fitness-guide-10.html",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:7b159d11-0d66-4c8c-beef-c907f618f5c7>"
},
"warc_info": "isPartOf: CC-MAIN-2023-40\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for September/October 2023\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-30\r\nsoftware: Apache Nutch 1.19 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.5-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
19,
20,
362,
363,
824,
825,
853,
854,
1250,
1251,
1857,
1858
],
"line_end_idx": [
19,
20,
362,
363,
824,
825,
853,
854,
1250,
1251,
1857,
1858,
2221
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 2221,
"ccnet_original_nlines": 12,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.37851661443710327,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.005115089938044548,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.11508951336145401,
"rps_doc_frac_unique_words": 0.625,
"rps_doc_mean_word_length": 5.316860675811768,
"rps_doc_num_sentences": 19,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.068611145019531,
"rps_doc_word_count": 344,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.026243850588798523,
"rps_doc_frac_chars_top_3gram": 0.01749590039253235,
"rps_doc_frac_chars_top_4gram": 0,
"rps_doc_books_importance": -143.6338653564453,
"rps_doc_books_importance_length_correction": -143.6338653564453,
"rps_doc_openwebtext_importance": -90.5053482055664,
"rps_doc_openwebtext_importance_length_correction": -90.5053482055664,
"rps_doc_wikipedia_importance": -38.6284065246582,
"rps_doc_wikipedia_importance_length_correction": -38.6284065246582
},
"fasttext": {
"dclm": 0.24693793058395386,
"english": 0.938652515411377,
"fineweb_edu_approx": 2.892923355102539,
"eai_general_math": 0.02857493981719017,
"eai_open_web_math": 0.1580294370651245,
"eai_web_code": 0.0017824199749156833
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "613.7",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
},
"secondary": {
"code": "613.704",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "3",
"label": "Irrelevant Content"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "4",
"label": "Missing Images or Figures"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "6",
"label": "Content Listing"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "1",
"label": "No Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "4",
"label": "Highly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
b755ed28a90d11d590ef646404f4afc5
|
8,805,013,721,768,288,000
|
Paroxysmal Kinesigenic Choreoathetosis
Sorry, no news articles match your request. Your search criteria may be too narrow.
Paroxysmal kinesigenic choreathetosis (PKC) also called Paroxysmal Kinesigenic Dyskinesia (PKD) is a hyperkinetic movement disorder characterized by attacks of involuntary movements, which are triggered by sudden voluntary movements. The number of attacks can range from up to twenty times per day, to more than twenty times per day, with attacks increasing during puberty and decreasing in a person’s 20's to 30's. Involuntary movements can take many forms such as ballism, chorea or dystonia and usually only affect one side of the body or one limb in particular. This rare disorder only affects about 1 in 150,000 people with PKD accounting for 86.8% of all the types of paroxysmal dyskinesias and occurs more often in males than females. There are two types of PKD, primary and secondary. Primary PKD can be further broken down into familial and sporadic. Familial PKD, which means the individual has a family history of the disorder, is more common, but sporadic cases are also seen. Secondary PKD can be caused by many other medical conditions such as multiple sclerosis (MS), stroke, pseudohypoparathyroidism, hypocalcemia, hypoglycemia, hyperglycemia, central nervous system trauma, or peripheral nervous system trauma. PKD has also been linked with The ICCA Syndrome, in which patients have afebrile seizures as children and then develop paroxysmal choreoathetosis later in life. This phenomenon is actually quite common, with about 42% of individuals with PKD reporting a history of afebrile seizures as a child.
This text uses material from Wikipedia licensed under CC BY-SA
Latest Spotlight News
Protein may be key to cancer's deadly resurgences
Tumor recurrence following a period of remission is the main cause of death in cancer. The ability of cancer cells to remain dormant during and following therapy, only to be reactivated at a later time, frequently ...
|
{
"url": "http://medicalxpress.com/conditions/paroxysmal-kinesigenic-choreoathetosis/sort/date/1d/",
"source_domain": "medicalxpress.com",
"snapshot_id": "crawl=CC-MAIN-2015-11",
"warc_metadata": {
"Content-Length": "30935",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:JNNHYKPBYYKWQGENX6TJ2OXSFAMPW5G5",
"WARC-Concurrent-To": "<urn:uuid:6125b93c-df41-4c51-9e66-55aadcc53810>",
"WARC-Date": "2015-03-04T04:32:37",
"WARC-IP-Address": "69.9.167.166",
"WARC-Identified-Payload-Type": null,
"WARC-Payload-Digest": "sha1:HSML3K3F3MSA47UZJ76M5S3V3SYEIBOR",
"WARC-Record-ID": "<urn:uuid:948f127e-79a5-46a9-9b54-093c0c1982ca>",
"WARC-Target-URI": "http://medicalxpress.com/conditions/paroxysmal-kinesigenic-choreoathetosis/sort/date/1d/",
"WARC-Truncated": "length",
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:1b59456f-8b2c-44ad-9d72-ac61bbf8c84d>"
},
"warc_info": "robots: classic\r\nhostname: ip-10-28-5-156.ec2.internal\r\nsoftware: Nutch 1.6 (CC)/CC WarcExport 1.0\r\nisPartOf: CC-MAIN-2015-11\r\noperator: CommonCrawl Admin\r\ndescription: Wide crawl of the web with URLs provided by Blekko for February 2015\r\npublisher: CommonCrawl\r\nformat: WARC File Format 1.0\r\nconformsTo: http://bibnum.bnf.fr/WARC/WARC_ISO_28500_version1_latestdraft.pdf"
}
|
{
"line_start_idx": [
0,
39,
40,
124,
125,
1648,
1649,
1712,
1713,
1735,
1736,
1786,
1787
],
"line_end_idx": [
39,
40,
124,
125,
1648,
1649,
1712,
1713,
1735,
1736,
1786,
1787,
2004
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 2004,
"ccnet_original_nlines": 12,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.38736262917518616,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.03846153989434242,
"rps_doc_frac_lines_end_with_ellipsis": 0.07692307978868484,
"rps_doc_frac_no_alph_words": 0.1538461446762085,
"rps_doc_frac_unique_words": 0.5954692363739014,
"rps_doc_mean_word_length": 5.3042073249816895,
"rps_doc_num_sentences": 15,
"rps_doc_symbol_to_word_ratio": 0.002747250022366643,
"rps_doc_unigram_entropy": 4.958606243133545,
"rps_doc_word_count": 309,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.03843807056546211,
"rps_doc_frac_chars_top_3gram": 0.01708359085023403,
"rps_doc_frac_chars_top_4gram": 0.020744359120726585,
"rps_doc_books_importance": -189.89816284179688,
"rps_doc_books_importance_length_correction": -189.89816284179688,
"rps_doc_openwebtext_importance": -102.21932983398438,
"rps_doc_openwebtext_importance_length_correction": -102.21932983398438,
"rps_doc_wikipedia_importance": -77.57537841796875,
"rps_doc_wikipedia_importance_length_correction": -77.57537841796875
},
"fasttext": {
"dclm": 0.09195517748594284,
"english": 0.9476624131202698,
"fineweb_edu_approx": 3.3452463150024414,
"eai_general_math": 0.16471940279006958,
"eai_open_web_math": 0.2662355303764343,
"eai_web_code": 0.0015695099718868732
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.858",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "616.8",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "1",
"label": "Remember"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "1",
"label": "Factual"
},
"secondary": {
"code": "2",
"label": "Conceptual"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "1",
"label": "News/Editorial"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "3",
"label": "Irrelevant Content"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "2",
"label": "Click Here References"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "6",
"label": "Content Listing"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "1",
"label": "No Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "6",
"label": "Not Applicable/Indeterminate"
}
},
"education_level": {
"primary": {
"code": "2",
"label": "High School Level"
},
"secondary": {
"code": "1",
"label": "General Audience"
}
}
}
|
1a01aa77535b9ecfb87b9fc36adbcd2f
|
1,276,247,510,303,866,600
|
January 16, 2019
Home Tags Appearance
Tag: Appearance
How waking up an hour earlier can improve your appearance
Adding an extra hour each day reaps enormous benefits for you, it can literally improve your appearance. A healthy person is more attractive than someone who is not. Two aspects of...
Most popular
Recent posts
|
{
"url": "https://www.christianaacha.com/tag/appearance/",
"source_domain": "www.christianaacha.com",
"snapshot_id": "crawl=CC-MAIN-2019-04",
"warc_metadata": {
"Content-Length": "145587",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:C7TUI4RST73566XZSYUWNW2IHEOQV4PG",
"WARC-Concurrent-To": "<urn:uuid:dcca4fcf-be84-4fe5-8996-08c81d852da6>",
"WARC-Date": "2019-01-16T23:01:42",
"WARC-IP-Address": "198.54.114.236",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:W6F7PUCNIJRA2K44FWEVCRBUNETEQB5H",
"WARC-Record-ID": "<urn:uuid:6a7d0582-a1e5-40fb-8bb7-08b97a66d1f5>",
"WARC-Target-URI": "https://www.christianaacha.com/tag/appearance/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:94efbdbc-62cf-4a53-842b-4387672e43a1>"
},
"warc_info": "isPartOf: CC-MAIN-2019-04\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for January 2019\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-182-67-179.ec2.internal\r\nsoftware: Apache Nutch 1.15 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 0.11-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: http://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
17,
38,
39,
55,
56,
114,
115,
299,
300,
313,
314
],
"line_end_idx": [
17,
38,
39,
55,
56,
114,
115,
299,
300,
313,
314,
326
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 326,
"ccnet_original_nlines": 11,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.32203391194343567,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.01694915071129799,
"rps_doc_frac_lines_end_with_ellipsis": 0.0833333283662796,
"rps_doc_frac_no_alph_words": 0.1355932205915451,
"rps_doc_frac_unique_words": 0.8301886916160583,
"rps_doc_mean_word_length": 4.924528121948242,
"rps_doc_num_sentences": 4,
"rps_doc_symbol_to_word_ratio": 0.01694915071129799,
"rps_doc_unigram_entropy": 3.7087268829345703,
"rps_doc_word_count": 53,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.08429118990898132,
"rps_doc_frac_chars_top_3gram": 0.16091954708099365,
"rps_doc_frac_chars_top_4gram": 0,
"rps_doc_books_importance": -21.977725982666016,
"rps_doc_books_importance_length_correction": -21.977725982666016,
"rps_doc_openwebtext_importance": -15.174883842468262,
"rps_doc_openwebtext_importance_length_correction": -15.174883842468262,
"rps_doc_wikipedia_importance": -15.335105895996094,
"rps_doc_wikipedia_importance_length_correction": -15.335105895996094
},
"fasttext": {
"dclm": 0.7297309041023254,
"english": 0.9468289017677307,
"fineweb_edu_approx": 2.1234090328216553,
"eai_general_math": 0.000015139999959501438,
"eai_open_web_math": 0.017534609884023666,
"eai_web_code": -0.000009780000254977494
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "613.6",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
},
"secondary": {
"code": "613.7",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "1",
"label": "Factual"
},
"secondary": {
"code": "2",
"label": "Conceptual"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "1",
"label": "Truncated Snippets"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "6",
"label": "Content Listing"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "1",
"label": "No Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "6",
"label": "Not Applicable/Indeterminate"
},
"secondary": {
"code": "4",
"label": "Highly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
6e3c8d3593f3f69280bb5502b214ab8e
|
-3,825,217,693,705,085,000
|
Hide this
How to Easily Cut Your Calories -- Eat Slowly
March 11, 2010 | 56,677 views
<p">chewingFor ages, mothers have admonished children to slow down and chew their food. It turns out they’re onto something.
Researchers have found evidence that when people wolf their food, they end up consuming more calories than they would at a slower pace. One reason is the effect of quicker ingestion on hormones.
In one recent study, scientists found that when a group of subjects were given an identical serving of ice cream on different occasions, they released more hormones that made them feel full when they ate it in 30 minutes instead of 5.
In other words, it can’t hurt to slow down and savor your meals.
</p">
Dr. Mercola's Comments:
Yes, it’s true. Taking your time when eating and chewing your food well has a number of beneficial side effects.
For example, chewing your food twice as long as you normally would will instantly help you control your portion sizes, which naturally decreases calorie consumption.
Another benefit of chewing longer is that your food is digested better. The majority of your digestive enzymes are actually in your mouth, not in your stomach. Therefore, chewing your food longer allows it to be broken down better.
You’re also likely to find that you actually enjoy the taste of the food more.
Studies Confirm Mom’s Advice is Right on the Money
As reported by the New York Times, there are a number of studies confirming the wisdom to chew your food well.
A study published in the Journal of Clinical Endocrinology & Metabolism last year found that subjects given identical servings of ice cream on different occasions released more hunger-regulating hormones when they ate it in 30 minutes instead of five. So although the serving size remained the same, they felt fuller after savoring the ice cream compared to when they wolfed it down.
In another study from 2008, subjects also reported feeling fuller when they ate slowly. Interestingly, they also ended up consuming about 10 percent fewer calories when they ate at a slow pace as opposed to when they were rushing.
A third study, published in the British Medical Journal, found that eating quickly, and eating until feeling full, tripled subjects’ risk of being overweight. The authors concluded:
“Eating until full and eating quickly are associated with being overweight in Japanese men and women, and these eating behaviors combined may have a substantial impact on being overweight.”
Clearly, portion size is one of the factors, especially in the US, that contributes to the obesity epidemic. But cutting down on your portion size can be tough for some people. Slowing down, chewing your food at least twice as long as you normally would, and enjoying each meal is a very simple way to cut down on portion size, calories, and excess weight.
Actually, eating smaller meals more frequently will in and of itself help burn more calories because it tends to boost your metabolism.
Additional Eating Guidelines for a Healthy Weight
In addition to properly chewing your food, eating the right foods for your nutritional type is essential for optimal health and weight.
Remember, foods that are healthy for others may not necessarily agree with your personal body chemistry and metabolism, and vice-versa. A healthy diet is highly individual, but there are general guidelines based on your general “type.”
If you’ve never looked into nutritional typing, you can start by taking my free online nutritional typing test. If you take your time answering the questions to the best of your ability, it will give you a general idea of what type you might be, so you can start experimenting with the appropriate foods to fine-tune your ideal diet.
The Best Way to Cut Excess Calories from Your Diet!
Cutting calories by eating slower will have little impact unless you also pay attention to the single largest source of calories in the typical American diet, namely fructose!
While chewing slowly will increase the release of some satiety-inducing hormones, ingesting fructose will clearly counteract this benefit.
Fructose diminishes your feelings of fullness because it does not stimulate a rise in leptin, one of the most powerful hunger- and fat storage regulators in your body. Fructose also reduces the amount of leptin crossing your blood-brain barrier by raising triglycerides.
Leptin resistance, in turn, is perhaps one of the most significant factors underlying human disease. For example, it plays a significant if not primary role in the development heart disease, obesity, diabetes, osteoporosis, autoimmune diseases, reproductive disorders, and perhaps the rate of aging itself.
Additionally, whereas glucose suppresses ghrelin (also known as “the hunger hormone,” which makes you want more food), fructose, again, does not.
Fructose also increases your insulin levels, interfering with the communication between leptin and your hypothalamus, so your pleasure signals aren’t extinguished. Your brain keeps sensing that you’re starving, and prompts you to eat more.
As you can see, consuming fructose suppresses feelings of satiety in several ways, which eventually will have serious consequences for your weight and overall health.
As a standard recommendation, I strongly advise keeping your fructose consumption below 25 grams per day.
However, for most people it would actually be wise to limit your fruit fructose to 15 grams or less, as it is virtually guaranteed that you will consume “hidden” sources of fructose from just about any processed food you might eat.
That said, avoiding as many processed foods as possible should be at the top of your list. For example, just ONE can of soda contains about 40 grams of high fructose corn syrup, which is already well over any kind of healthy limit!
Reducing your fructose consumption also includes carefully measuring your fruit intake to make certain that you’re not inadvertently consuming too much fructose. The table below will give you an idea of how much fructose is in your favorite fruits.
Fruit Serving Size Grams of Fructose
Limes 1 medium 0
Lemons 1 medium 0.6
Cranberries 1 cup 0.7
Passion fruit 1 medium 0.9
Prune 1 medium 1.2
Apricot 1 medium 1.3
Guava 2 medium 2.2
Date (Deglet Noor style) 1 medium 2.6
Cantaloupe 1/8 of med. melon 2.8
Raspberries 1 cup 3.0
Clementine 1 medium 3.4
Kiwifruit 1 medium 3.4
Blackberries 1 cup 3.5
Star fruit 1 medium 3.6
Cherries, sweet 10 3.8
Strawberries 1 cup 3.8
Cherries, sour 1 cup 4.0
Pineapple 1 slice
(3.5" x .75")
4.0
Grapefruit, pink or red 1/2 medium 4.3
Fruit Serving Size Grams of Fructose
Boysenberries 1 cup 4.6
Tangerine/mandarin orange 1 medium 4.8
Nectarine 1 medium 5.4
Peach 1 medium 5.9
Orange (navel) 1 medium 6.1
Papaya 1/2 medium 6.3
Honeydew 1/8 of med. melon 6.7
Banana 1 medium 7.1
Blueberries 1 cup 7.4
Date (Medjool) 1 medium 7.7
Apple (composite) 1 medium 9.5
Persimmon 1 medium 10.6
Watermelon 1/16 med. melon 11.3
Pear 1 medium 11.8
Raisins 1/4 cup 12.3
Grapes, seedless (green or red) 1 cup 12.4
Mango 1/2 medium 16.2
Apricots, dried 1 cup 16.4
Figs, dried 1 cup 23.0
Final Thoughts
Clearly, slowing down during meals is something to strive for, if for no other reason than to reduce stress.
There’s plenty of evidence showing the importance meal time plays in regulating your overall stress levels. And rushing while eating is a surefire way to decrease your overall level of health. Marc David, an expert in the psychology of eating, talks about the important role stress plays in digestion in this previous article.
So relax, chew slowly, and enjoy – savor everything you put in your mouth.
[+] Sources and References
Thank you! Your purchases help us support these charities and organizations.
|
{
"url": "http://articles.mercola.com/sites/articles/archive/2010/03/11/to-cut-calories-eat-slowly.aspx",
"source_domain": "articles.mercola.com",
"snapshot_id": "crawl=CC-MAIN-2016-50",
"warc_metadata": {
"Content-Length": "165920",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:NW4QD7ZB7SCK3FF7XDYGDDHTYESF2LWU",
"WARC-Concurrent-To": "<urn:uuid:c8224b73-ab18-4578-8d63-46ed1f7807a8>",
"WARC-Date": "2016-12-06T17:56:43",
"WARC-IP-Address": "104.95.70.187",
"WARC-Identified-Payload-Type": null,
"WARC-Payload-Digest": "sha1:X7MWG6KNKDUKB23OOXO76W2OJHFYAEDP",
"WARC-Record-ID": "<urn:uuid:91b5b3c3-0d6b-4468-bd6f-b58a43861465>",
"WARC-Target-URI": "http://articles.mercola.com/sites/articles/archive/2010/03/11/to-cut-calories-eat-slowly.aspx",
"WARC-Truncated": "length",
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:1041b259-6939-4c6b-9c8b-93141a94a3ea>"
},
"warc_info": "robots: classic\r\nhostname: ip-10-31-129-80.ec2.internal\r\nsoftware: Nutch 1.6 (CC)/CC WarcExport 1.0\r\nisPartOf: CC-MAIN-2016-50\r\noperator: CommonCrawl Admin\r\ndescription: Wide crawl of the web for November 2016\r\npublisher: CommonCrawl\r\nformat: WARC File Format 1.0\r\nconformsTo: http://bibnum.bnf.fr/WARC/WARC_ISO_28500_version1_latestdraft.pdf"
}
|
{
"line_start_idx": [
0,
10,
12,
13,
59,
60,
90,
91,
216,
217,
412,
413,
648,
649,
714,
715,
721,
723,
724,
748,
749,
862,
863,
1029,
1030,
1262,
1263,
1342,
1343,
1394,
1395,
1506,
1507,
1891,
1892,
2123,
2124,
2306,
2307,
2497,
2498,
2855,
2856,
2992,
2993,
3043,
3044,
3180,
3181,
3417,
3418,
3752,
3753,
3805,
3806,
3982,
3983,
4122,
4123,
4394,
4395,
4702,
4703,
4849,
4850,
5090,
5091,
5258,
5259,
5365,
5366,
5598,
5599,
5831,
5832,
6081,
6082,
6119,
6136,
6156,
6178,
6205,
6224,
6245,
6264,
6302,
6335,
6357,
6381,
6404,
6427,
6451,
6474,
6497,
6522,
6540,
6554,
6558,
6597,
6634,
6658,
6697,
6720,
6739,
6767,
6789,
6820,
6840,
6862,
6890,
6921,
6945,
6977,
6996,
7017,
7060,
7082,
7109,
7132,
7133,
7148,
7149,
7258,
7259,
7586,
7587,
7662,
7663,
7664,
7691,
7692
],
"line_end_idx": [
10,
12,
13,
59,
60,
90,
91,
216,
217,
412,
413,
648,
649,
714,
715,
721,
723,
724,
748,
749,
862,
863,
1029,
1030,
1262,
1263,
1342,
1343,
1394,
1395,
1506,
1507,
1891,
1892,
2123,
2124,
2306,
2307,
2497,
2498,
2855,
2856,
2992,
2993,
3043,
3044,
3180,
3181,
3417,
3418,
3752,
3753,
3805,
3806,
3982,
3983,
4122,
4123,
4394,
4395,
4702,
4703,
4849,
4850,
5090,
5091,
5258,
5259,
5365,
5366,
5598,
5599,
5831,
5832,
6081,
6082,
6119,
6136,
6156,
6178,
6205,
6224,
6245,
6264,
6302,
6335,
6357,
6381,
6404,
6427,
6451,
6474,
6497,
6522,
6540,
6554,
6558,
6597,
6634,
6658,
6697,
6720,
6739,
6767,
6789,
6820,
6840,
6862,
6890,
6921,
6945,
6977,
6996,
7017,
7060,
7082,
7109,
7132,
7133,
7148,
7149,
7258,
7259,
7586,
7587,
7662,
7663,
7664,
7691,
7692,
7768
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 7768,
"ccnet_original_nlines": 130,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.3461047410964966,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.0038314200937747955,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.23180076479911804,
"rps_doc_frac_unique_words": 0.4501960873603821,
"rps_doc_mean_word_length": 4.880784511566162,
"rps_doc_num_sentences": 96,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.738439559936523,
"rps_doc_word_count": 1275,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.03953076899051666,
"rps_doc_frac_chars_dupe_6grams": 0.03953076899051666,
"rps_doc_frac_chars_dupe_7grams": 0.019926080480217934,
"rps_doc_frac_chars_dupe_8grams": 0.010605820454657078,
"rps_doc_frac_chars_dupe_9grams": 0.010605820454657078,
"rps_doc_frac_chars_top_2gram": 0.02024747058749199,
"rps_doc_frac_chars_top_3gram": 0.012052060104906559,
"rps_doc_frac_chars_top_4gram": 0.004178049974143505,
"rps_doc_books_importance": -772.7696533203125,
"rps_doc_books_importance_length_correction": -772.7696533203125,
"rps_doc_openwebtext_importance": -378.54730224609375,
"rps_doc_openwebtext_importance_length_correction": -378.54730224609375,
"rps_doc_wikipedia_importance": -269.468994140625,
"rps_doc_wikipedia_importance_length_correction": -269.468994140625
},
"fasttext": {
"dclm": 0.06879901885986328,
"english": 0.9417548179626465,
"fineweb_edu_approx": 2.6516828536987305,
"eai_general_math": 0.01104045007377863,
"eai_open_web_math": 0.1724293828010559,
"eai_web_code": 0.002751109888777137
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "613.2",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
},
"secondary": {
"code": "612.82",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Physiology"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "3",
"label": "Apply"
},
"secondary": {
"code": "2",
"label": "Understand"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "16",
"label": "Personal Blog"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "4",
"label": "Highly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
9222580d47c553ea90dc0f5e416f8f3a
|
-6,204,832,449,863,783,000
|
Why Do People Get Hiccups and What Causes Hiccups?Why Do People Get Hiccups and What Causes Hiccups?
Why Do People Get Hiccups and What Causes Hiccups?
Hiccups are a funny sensation that starts in the diaphragm, the dome-shaped muscle between your lungs and your stomach.
It contracts when you inhale, allowing air to enter your lungs, and relaxes when you exhale.
However, hiccups are annoying when they occur more than twice in a row.
Why do people get hiccups?
There are a variety of causes for hiccups, including nerve conditions and medicines.
Long-term hiccups can cause sleep disorders, jitteriness, and poor communication.
They can be dangerous, and can result in dehydration or infection if left untreated.
Additionally, prolonged hiccups may lead to other problems, including GERD and an irregular heartbeat.
Easy and Secure! Bill Pay Adventhealth Com
Hiccups are caused by a spasm in the diaphragm muscle, a large muscle at the base of the lungs.
When it spasms, the vocal cords are tightened and snap shut, resulting in the hic sound. Another possible cause of hiccups is eating too quickly, which causes the stomach to expand.
Fortunately, most people can have a hiccup as long as it is short and frequent.
A prolonged hiccup may be the result of a traumatic incident such as an accident or illness. Moreover, an undiagnosed nerve problem can result in chronic hiccups.
Do hiccups mean anything?
While hiccups can be annoying and uncomfortable, they’re typically harmless.
In many cases, they will go away on their own with a simple home remedy or with no treatment at all. However, if they persist, they may be an indicator of something more serious.
Learn The Basic! Comenity Net Victoria Secret Credit Card Activate/Login
Fetal hiccups are common. They occur when a baby’s diaphragm is under pressure from a growing fetus.
These movements are not harmful, and are normal during pregnancy. The fetal diaphragm controls breathing, and it’s the same muscle in the baby that controls breathing after birth.
Hiccups are usually harmless and go away on their own, but if the episode lasts for more than 48 hours, you should consult a doctor.
If the hiccups become persistent and interfere with eating, sleeping, or breathing, they could be a sign of a serious health issue.
If you’ve ever had hiccups, you know that waiting them out isn’t always an easy task.
You may want to try using granulated sugar to help soothe the discomfort and soothe your throat.
In addition to this, holding your knees against your chest or putting cold water on the back of your throat can also help.
How do you stop the hiccups?
Almost everyone has experienced hiccups at some point. They are unpredictable and can be very unpleasant.
Many people don’t know what to do when they experience hiccups, and just wait for the next one to come. But there are some simple ways to stop hiccups in their tracks.
Easy and Secure! patientportal.aegislabs.com – Aegis Patient Portal
One method is to hold your breath. This will cause carbon dioxide to build up in your lungs, which may relax your diaphragm.
Another method involves drinking ice-cold water. This remedy also helps relieve pressure on the diaphragm, which can trigger the hiccups.
The first treatment is to find out what causes hiccups. This problem can be caused by a number of reasons.
First, you may be suffering from a medical condition. Secondly, it can be caused by a surgical procedure.
It can also occur from a gastrointestinal disorder. Regardless of the cause, it can be a very frustrating experience.
Another remedy involves taking 20 small sips of water in succession. This works by slowing down nerve impulses that travel from the diaphragm to the stomach.
This method may be helpful if you cannot hold your breath when swallowing, but it’s not for everyone.
What causes hiccups in a woman?
Hiccups are sudden contractions of the muscles in the throat and diaphragm. The diaphragm controls air flow through the nose and mouth.
When the diaphragm contracts, the vocal cords close involuntarily, creating a distinctive sound.
While hiccups are not serious and don’t alter speech, they are uncomfortable and can interfere with sleep and eating.
Learn The Basic! Tcisd Canvas Basic Complete Guide
One of the best ways to stop hiccups is to perform the Valsalva manoeuvre, which involves holding the throat and voice box closed.
This exercise will stimulate the vagus nerve and interrupt the hiccup. Other methods include drinking water or sucking on a lemon.
Some women also try sneezing or breathing quickly to relieve the pain. Others try to lean forward and pull their knees up to their chests to compress the chest.
If the hiccups continue or worsen for more than 48 hours, it’s best to see a doctor.
A prolonged bout of hiccups may be a sign of a more serious underlying condition, such as cancer or a blood disorder.
Why do we get hiccups after eating?
Hiccups are a common symptom after eating. The cause varies from person to person, but there are a few common factors that can cause them.
A few of these include excess food, eating too fast, or drinking alcohol. The symptoms may also be triggered by changes in the body’s temperature or emotional factors.
Read Here: Monkeypox Virus: More Than 100 Cases of Monkeypox in Australia
If you have persistent bouts of hiccups after eating, you should see your doctor immediately.
Your doctor will likely run some tests to rule out any underlying medical conditions.
Acid reflux is one common cause. Other causes include certain types of medicines. Eating acidic foods can irritate the diaphragm.
If your hiccups are a result of medication, you should try changing the medicine.
Some people find that changing the medicine makes the problem go away. If you’re not successful with home remedies, your doctor may prescribe a stronger medicine.
What causes hiccups in adults?
There are many different causes of hiccups in adults. In some cases, they’re triggered by nervousness or stress.
In others, hiccups may be indicative of a medical condition. A phrenic nerve problem, sore throat, laryngitis, or even a tumor may be to blame. Even sucking on hard candy can cause hiccups.
Open and Read: How Much Health Does Predator Have in Fortnite?
If the hiccups are frequent and last for more than two days, your doctor may suggest a medication to help.
The first option is chlorpromazine, an antipsychotic that has powerful anticholinergic, antidopaminergic, and antihistaminic effects. If that doesn’t work, your doctor may try a sedative.
Hiccups in adults can also be caused by excessive eating, stress, and excitement. They may cause the diaphragm to spasm, which can trigger the hiccup.
Emotional reasons for hiccups
People can experience hiccups for several reasons, including mental and emotional problems.
These can include anxiety, stress, excitement, or even medication side effects. In addition, hiccups can occur after undergoing surgery or general anesthesia.
These situations can cause sudden air intake that can trigger the hiccups.
Bottom Line: No Man’s Sky Why Is There a Health Bar in the Sky?
If your hiccups are a persistent or recurring problem, your doctor may recommend treatment.
Various therapies may be used, including acupuncture, medication, or hypnosis. Various tests may also be conducted to rule out more serious problems.
Before considering any treatment, it is important to understand the underlying cause of your hiccups.
The causes of hiccups are often unknown, but they are often related to certain triggers, such as spicy foods or hot liquids.
Hiccups are a reflex involving synchronized movements of the diaphragm and other muscles and nerves. The hiccup center is located between the cervical vertebrae C3 and C5.
When the diaphragm contracts, a synchronized release of air is produced, which causes the characteristic hiccup sound.
Most people experience hiccups at least once or twice in their lives. In general, hiccups will go away within a few minutes to several hours.
What causes hiccups in elderly?
If you’ve ever had hiccups, you know that they are uncomfortable. While they typically go away on their own without treatment, prolonged episodes can be dangerous.
If they keep you from eating or disrupt your daily life, you should see a doctor. Your doctor can help you determine what the exact cause of the hiccups is.
How To Do! Schoology Fbisd Login
Often, hiccups can be treated at home, including drinking cold water or sucking on ice. Another treatment involves lifting the uvula with a spoon or tongue.
You can also try sneezing or breathing fast. If you’re unable to do this, you can try pulling your knees up to your chest.
If you have hiccups lasting for more than 48 hours, you should see a doctor. Generally, these episodes don’t require medical attention, but you should see a doctor if the episodes persist for more than two days.
In addition, if your hiccups are accompanied by other symptoms, you should see a doctor for further testing.
By Zen Tech Guru SEO Services
Hi, I am from Rebel Viral Experts, Let me tell you that Writing has always been one of the things that I’m passionate about. Good writers define reality and turn fact into truth. I believe that You never really understand a person until you consider things from his point of view. In short, a good novel can change the world.
|
{
"url": "https://rebelviral.com/why-do-people-get-hiccups-and-what-causes-hiccups/",
"source_domain": "rebelviral.com",
"snapshot_id": "CC-MAIN-2024-18",
"warc_metadata": {
"Content-Length": "78859",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:PKEMUGQZSOFXULVVHC73DIFQOJLRSEBK",
"WARC-Concurrent-To": "<urn:uuid:672bdf2a-d48e-408b-ab05-981e17ccb4c4>",
"WARC-Date": "2024-04-24T15:54:57",
"WARC-IP-Address": "104.21.47.142",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:XTVKNC34T4TI7MRXXT76WDWDJRZLSHMY",
"WARC-Record-ID": "<urn:uuid:9d673b8b-150f-4c0c-b315-c2bc9dad3bad>",
"WARC-Target-URI": "https://rebelviral.com/why-do-people-get-hiccups-and-what-causes-hiccups/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:0fe8b0cd-772b-4692-a81c-cb823334f179>"
},
"warc_info": "isPartOf: CC-MAIN-2024-18\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for April 2024\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-118\r\nsoftware: Apache Nutch 1.19 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.5-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
101,
102,
153,
154,
274,
275,
368,
369,
441,
442,
469,
470,
555,
556,
638,
639,
724,
725,
828,
829,
872,
873,
969,
970,
1152,
1153,
1233,
1234,
1397,
1398,
1424,
1425,
1502,
1503,
1682,
1683,
1756,
1757,
1858,
1859,
2039,
2040,
2173,
2174,
2306,
2307,
2393,
2394,
2491,
2492,
2615,
2616,
2645,
2646,
2752,
2753,
2921,
2922,
2990,
2991,
3116,
3117,
3255,
3256,
3363,
3364,
3470,
3471,
3589,
3590,
3748,
3749,
3851,
3852,
3884,
3885,
4021,
4022,
4119,
4120,
4238,
4239,
4290,
4291,
4422,
4423,
4554,
4555,
4716,
4717,
4802,
4803,
4921,
4922,
4958,
4959,
5098,
5099,
5267,
5268,
5342,
5343,
5437,
5438,
5524,
5525,
5655,
5656,
5738,
5739,
5902,
5903,
5934,
5935,
6048,
6049,
6239,
6240,
6303,
6304,
6411,
6412,
6600,
6601,
6752,
6753,
6783,
6784,
6876,
6877,
7036,
7037,
7112,
7113,
7177,
7178,
7270,
7271,
7421,
7422,
7524,
7525,
7650,
7651,
7823,
7824,
7943,
7944,
8086,
8087,
8119,
8120,
8284,
8285,
8442,
8443,
8476,
8477,
8634,
8635,
8758,
8759,
8971,
8972,
9081,
9082,
9112,
9113
],
"line_end_idx": [
101,
102,
153,
154,
274,
275,
368,
369,
441,
442,
469,
470,
555,
556,
638,
639,
724,
725,
828,
829,
872,
873,
969,
970,
1152,
1153,
1233,
1234,
1397,
1398,
1424,
1425,
1502,
1503,
1682,
1683,
1756,
1757,
1858,
1859,
2039,
2040,
2173,
2174,
2306,
2307,
2393,
2394,
2491,
2492,
2615,
2616,
2645,
2646,
2752,
2753,
2921,
2922,
2990,
2991,
3116,
3117,
3255,
3256,
3363,
3364,
3470,
3471,
3589,
3590,
3748,
3749,
3851,
3852,
3884,
3885,
4021,
4022,
4119,
4120,
4238,
4239,
4290,
4291,
4422,
4423,
4554,
4555,
4716,
4717,
4802,
4803,
4921,
4922,
4958,
4959,
5098,
5099,
5267,
5268,
5342,
5343,
5437,
5438,
5524,
5525,
5655,
5656,
5738,
5739,
5902,
5903,
5934,
5935,
6048,
6049,
6239,
6240,
6303,
6304,
6411,
6412,
6600,
6601,
6752,
6753,
6783,
6784,
6876,
6877,
7036,
7037,
7112,
7113,
7177,
7178,
7270,
7271,
7421,
7422,
7524,
7525,
7650,
7651,
7823,
7824,
7943,
7944,
8086,
8087,
8119,
8120,
8284,
8285,
8442,
8443,
8476,
8477,
8634,
8635,
8758,
8759,
8971,
8972,
9081,
9082,
9112,
9113,
9438
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 9438,
"ccnet_original_nlines": 168,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.4198139011859894,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.006020800210535526,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.13409961760044098,
"rps_doc_frac_unique_words": 0.3454894423484802,
"rps_doc_mean_word_length": 4.843890190124512,
"rps_doc_num_sentences": 123,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.515849590301514,
"rps_doc_word_count": 1563,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.07357019931077957,
"rps_doc_frac_chars_dupe_6grams": 0.03077532909810543,
"rps_doc_frac_chars_dupe_7grams": 0.03077532909810543,
"rps_doc_frac_chars_dupe_8grams": 0.023642849177122116,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.018491610884666443,
"rps_doc_frac_chars_top_3gram": 0.013472460210323334,
"rps_doc_frac_chars_top_4gram": 0.009509970434010029,
"rps_doc_books_importance": -774.30419921875,
"rps_doc_books_importance_length_correction": -774.30419921875,
"rps_doc_openwebtext_importance": -454.4502868652344,
"rps_doc_openwebtext_importance_length_correction": -454.4502868652344,
"rps_doc_wikipedia_importance": -285.9308776855469,
"rps_doc_wikipedia_importance_length_correction": -285.9308776855469
},
"fasttext": {
"dclm": 0.34883421659469604,
"english": 0.9464948773384094,
"fineweb_edu_approx": 2.9743549823760986,
"eai_general_math": 0.02406430058181286,
"eai_open_web_math": 0.19316542148590088,
"eai_web_code": 0.004334690049290657
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.1",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "615.8",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "0",
"label": "No Artifacts"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "2",
"label": "Click Here References"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "9",
"label": "FAQ"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "4",
"label": "Highly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
b755ed28a90d11d590ef646404f4afc5
|
4,057,397,418,841,165,000
|
Skip to content
Advertisement
Journal of Experimental & Clinical Cancer Research
Open Access
AHNAK suppresses tumour proliferation and invasion by targeting multiple pathways in triple-negative breast cancer
• Bo Chen1,
• Jin Wang1,
• Danian Dai1,
• Qingyu Zhou2,
• Xiaofang Guo2,
• Zhi Tian2,
• Xiaojia Huang1,
• Lu Yang1,
• Hailin Tang1Email author and
• Xiaoming Xie1Email author
Contributed equally
Journal of Experimental & Clinical Cancer Research201736:65
https://doi.org/10.1186/s13046-017-0522-4
Received: 22 November 2016
Accepted: 31 March 2017
Published: 12 May 2017
Abstract
Background
AHNAK, also known as desmoyokin, is a giant protein with the molecular size of approximately 700 kDa and exerts diverse functions in different types of cancer.
Results
In the present study, we demonstrated that AHNAK mRNA levels were down-regulated in 7 out of 8 human breast cancer cell lines, especially in triple - negative breast cancer (TNBC) cell lines. Moreover, in patients with TNBC, the expression of AHNAK gene was inversely correlated with the tumor status (P = 0.015), lymph node status (P < 0.001), lymph node (LN) infiltration (P < 0.001) and TNM stage (P < 0.001). Moreover, down-regulated AHNAK expression was considered an independent prognostic factor associated with the poor survival of patients with TNBC. Overexpression of AHNAK in two TNBC cell lines, MDA-MB-231 and BT549, suppressed the in vitro TNBC cell proliferation and colony formation, and inhibited the in vivo TNBC xenograft growth and lung metastasis. The tumor suppressing effect of AHNAK in TNBC was associated with the AKT/MAPK signaling pathway and Wnt/β-catenin pathway. Consistent results were observed when AHNAK was knockdown in BT20 and MDA-MB-435 cells.
Conclusions
Taken together, our results suggest that AHNAK acts as a tumor suppressor that negatively regulates TNBC cell proliferation, TNBC xenograft growth and metastasis via different signaling pathways.
Keywords
AHNAKTriple-negative breast cancerAKTMAPKWnt/β-catenin pathway
Background
It is well known that breast cancer is a devastating disease with extensive intra-tumour and inter-tumour heterogeneity [1, 2]. Triple-negative breast cancer (TNBC), which lacks the expression of ER, PR and HER2 [3], is a unique subtype of breast cancer with limited treatment options and poor prognosis, accounting for 15–20% of breast cancers [4]. In China, although the overall incidence of breast cancer is lower than that in Western countries [5], the total number of patients with TNBC is relatively high. Despite advances in breast cancer treatment, the median overall survival (OS) for patients with TNBC is unfavourable compared with the mean OS for other breast cancer subtypes patients [68]. In this regard, it is necessary to investigate the molecular pathogenesis of TNBC and to explore novel therapeutic targets to improve the prognosis of TNBC patients.
AHNAK, also known as desmoyokin [9], is a large protein that was originally identified as a desmosomal plaque protein found at the periphery of the cytoplasmic plaque of desmosomes in the stratified squamous epithelia [10]. AHNAK has been previously reported to be expressed in several intracellular locations, including the plasma membrane, cytoplasm and nucleus [11]. Previous studies have indicated that AHNAK is involved in several important physiological activities, such as cardiac L-type Ca2+ channel function [12], neuronal cell differentiation and calcium signalling in T cells [13, 14]. In recent years, there has been increasing interest in understanding the function of AHNAK in various malignant tumours. So far, it has been demonstrated that the expression of AHNAK is variable in different types of cancer. For example, the expression of AHNAK is down-regulated in Burkitt lymphoma, small cell lung carcinoma and neuroblastoma [15, 16] but upregulated in glioma, mesothelioma, fibrosarcoma and prostate cancer [17]. Due to its large size and protein structure, AHNAK can facilitate the binding of multiple proteins and can mediate signalling events [18, 19]. The results of a recent study using a transgenic mouse model of breast cancer and human breast cancer samples suggest that AHNAK can act as a tumour suppressor that mediates the negative regulation of cell growth via the modulation of the TGFβ/Smad signalling pathway [20]. However, the expression profile of AHNAK in TNBC and its function have not been elucidated. In this study, we investigated the role of AHNAK in the pathogenesis of TNBC and assessed the effect of AHNAK on clinicopathological characteristics and prognosis by examining its expression in breast cancer cell lines and patient tissues and by characterizing its function in TNBC using both in vitro and in vivo models. We found that the expression of AHNAK is associated with the biological characteristics and prognosis of TNBC and the likelihood of lung metastasis. Moreover, the aggressive nature of TNBC with reduced expression of AHNAK was partly attributable to the activation of the AKT/MAPK and Wnt/β-catenin signalling pathways.
Methods
Clinical samples
This study was approved by the Ethics Committee of Sun Yat-Sen University Cancer Centre Health Authority. A total of 221 matched human triple-negative breast cancer (TNBC) tissues and 51 their adjacent normal mammary tissues (Normal 1), 20 non-triple-negative breast cancer (NTNBC) tissues and the corresponding paired normal adjacent tissues (Normal 2) were collected between October 2001 and September 2009 at Sun Yat-Sen University Cancer Centre. The details of the NTNBC samples are given in the supplementary information (Additional file 1: Table S1). The resected tissues were immediately cut and stored in RNAlater (Ambion). The collection and use of tissues followed procedures that are in accordance with the ethical standards formulated in the Declaration of Helsinki.
Cell cultures and transfection
All the cell lines were obtained from the American Type Culture Collection (Manassas, VA, USA), including normal mammary epithelial cell lines (184A1, MCF-10A), human breast cancer cell lines (MDA-MB-231, BT549, BT-20, MCF-7, T47D, BT474, MDA-MB-435 and BT-483) and human embryonic kidney 293 T cells. All of the cell lines were passaged in our laboratory for less than six months and maintained according to the supplier’s instructions. The cell lines were found to be free of mycoplasma infection and their authenticity was verified by DNA fingerprinting before use.
Lentivirus-mediated AHNAK-expressing vector (EX-V0190-Lv122) and control plasmids were purchased from GeneCopoeia (Rockville, MD, USA). According to the manufacturer’s instructions, the AHNAK cDNA-containing plasmids were transfected into 293 T cells (1 × 106) for 48 h to generate lentiviral particles. Lipofectamine® 2000 (Invitrogen Life Technologies, Carlsbad, CA, USA) was used. The control groups included the vector-transfected group (EX-NEG-Lv122). The viral supernatant was subsequently collected and used to infect MDA-MB-231 and BT549 cells. Seventy-two hours post-transfection, western blotting was performed to determine the transfection efficiency (Additional file 2: Figure S1A). BT-20 and MDA-MB-435 cells were used for transfection with AHNAK siRNA. Five microlitres of control or targeted siRNAs were transfected with Lipofectamine 2000 (Invitrogen) according to the protocol provided by Santa Cruz (sc-97060). The cells were grown for 48 h before assessing gene and protein knockdown efficiencies by western blotting (Additional file 2: Figure S1B).
Quantitative RT-PCR analysis (qRT-PCR)
Total RNA was extracted from the cells using TRIzol reagent according to the manufacturer’s instructions (Invitrogen, Carlsbad, CA, USA). A NanoDrop ND-1000 instrument was used to determine the concentrations of the RNA samples. The integrity of RNA was assessed by electrophoresis on a denaturing agarose gel. Reverse transcription and qRT-PCR reactions were performed using a QuantiFast SYBR® Green RT-PCR Kit (QIAGEN, Germantown, MD, USA), which is a one-step RT-PCR kit. Each reaction was performed in triplicate. The primer sequences are given as follows: AHNAK: 5′-ATGCTCCAGGGCTCAACCT-3' (forward) and 5'-CGTGCCCCAACGTTAAGCTT-3' (reverse); β-actin: 5'-CGCGAGAAGATGACCCAGAT-3' (forward) and 5′-GGGCATACCCCTCGTAGATG-3' (reverse); Wnt1: 5'-ATGGGGCTCTGGGCGCTGTTG-3' (forward) and 5'-TCACAGACACTCGTGCAGTAC-3' (reverse); c-Myc: 5’-AGAAATGTCCTGAGCAATCACC-3' (forward) and 5’-AAGGTTGTGAGGTTGCATTTGA-3' (reverse); β-catenin: 5′- CCGCATGGAAGAAATAGTTGAAG-3′ (forward) and 5′- CAATTCGGTTGTGAACATCCC-3′ (reverse). The real-time PCR assays were performed with the Bio-Rad IQTM5 Multicolour Real-Time PCR Detection System (USA). The specificity of the amplification products was confirmed by melting curve analysis. The values were normalized to internal controls and fold changes were calculated through relative quantification (2-ΔΔCt).
Cell proliferation assay
Cells were seeded on 6-well plates at the desired cell concentrations. The numbers of cells were counted after 1, 2, 3 and 4 days of incubation using a Coulter Counter (Beckman Coulter, Fullerton, USA) in triplicate.
Colony growth assays
Six-well plates were covered with a layer of 0.6% agar in medium supplemented with 20% foetal bovine serum. Cells were prepared in 0.3% agar and seeded in triplicate. Then the plates were incubated in a CO2 incubator at 37 °C for two weeks. Crystal violet was used to stain the colonies, and the colonies were counted.
Immunohistochemistry
Immunohistochemistry (IHC) staining was performed as described previously [21]. The concentration used for AHNAK (Santa Cruz Biotechnology) was 1:50.
Western blot
Briefly, total protein was extracted and separated by 10% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and then transferred onto PVDF membranes. The protein bands were probed with antibodies against AHNAK (Santa Cruz Biotechnology), Akt, phospho-Akt (Ser473), ERK1/2, phospho-ERK1/2 (Tyr202/Y204), phospho-c-Raf (Ser296), phospho-MEK1/2 (Ser221) (Cell Signaling Technology, Beverly, MA), c-myc, Wnt-1 and β-actin (Abcam, Cambridge, UK) overnight at 4 °C followed by incubation with HRP-conjugated second antibodies (Santa Cruz, CA, USA) (1:3500) and detected by enhanced chemiluminescence. The dilutions used for the anti-AHNAK and anti-β-actin antibodies were 1:200 and 1:5000, respectively. The dilution used for the other antibodies was 1:1000. β-actin was used as the protein-loading control.
Mouse xenograft model
All the animal procedures were performed in accordance with institutional guidelines. Ethical approval was obtained from the Institute Research Ethics Committee of Sun Yat-sen University Cancer Center. MDA-MB-231 or BT549 cells were stably transfected with AHNAK or vector and collected and suspended in PBS at a concentration of 1 × 107 cells/ml. Then, 200 μl of cancer cell suspension was subcutaneously inoculated into the dorsal flanks of nude mice ((female, 4–6 w; five in each group) using 1-ml syringes. The tumour size was measured every four days. After 28 days, the mice were euthanized, and the tumours were weighed. The tumour volumes were determined according to the following formula: A × B2/2, where A is the largest diameter and B is the diameter perpendicular to A [22]. To assay the effect of AHNAK on tumour metastasis, 1 × 105 MDA-MB-231 or BT549 cells infected with AHNAK or vector were injected into the tail veins of nude mice (eight in each group). The cells were suspended in PBS at a concentration of 2 × 106 cells/ml, and 50 μl of cancer cell suspension was injected into each mouse using a microsyringe. Necropsies were performed after 28 days. The numbers of microscopic metastases in the lungs per H&E-stained section from individual mice were determined.
Bioinformatics analysis
The expression levels of the AHNAK transcript in breast cancers and normal breast tissues were determined from the Oncomine database (www.oncomine.org). The threshold was set at a two-fold difference in expression between cancers and normal tissues with a P-value < 0.01. The Cancer Genome Atlas (TCGA) [23] and METABRIC [24] datasets were analysed and the figures were generated using the cBio Cancer Genomics Portal (http://cbioportal.org) [25, 26]. All TCGA data included in this manuscript are in compliance with the TCGA publication guidelines.
Statistical analyses
Statistical analyses were performed using the SPSS 16.0 software. Comparisons between groups were conducted with t-tests and χ2 tests. The Kaplan-Meier method was used to plot overall survival curves and relapse-free survival curves, and the log-rank test was used for comparison. Survival was calculated from the time of pathological diagnosis. Univariate and multivariate analyses (Cox proportional hazards regression model) were performed to identify the independent factors relevant to patient survival. The differences were considered statistically significant at P < 0.05.
Results
Bioinformatics analysis of AHNAK expression in human breast cancer
We searched the Oncomine database to get a general idea of the AHNAK expression levels in cancer tissues and normal tissues. The results showed that there were significant differences in the levels of AHNAK in different types of tumours (Fig. 1a). Among 20 common types of tumours, 12 tumour types exhibited decreases in AHNAK expression, including breast cancer. Six types of tumours showed increases and two types of tumours showed both decreases and increases in the expression of AHNAK. Then, we investigated the expression of AHNAK in TCGA and METABRIC, which have clinical data and information on gene expression and copy number variation (CNV) from approximately 3,000 patients. As Fig. 1b shows, most of the cases with down-regulated AHNAK belong to the basal-like classification (by PAM50 [27] and Claudin-low subtype [28]). Meanwhile, compared with the other subtypes of breast cancer, the basal-like subtype has the lowest average AHNAK expression (Fig. 1c and d).
Fig. 1
Bioinformatics analysis of AHNAK expression in human breast cancer. a Summary of AHNAK expression in cancers (Oncomine database). b The OncoPrint tab summarizes the genomic alterations of AHNAK across the sample set (TCGA and METABRIC). Each column represents a tumour sample. Plots showing AHNAK mRNA expression in tumours from TCGA (c) and METABRIC (d)
AHNAK expression was significantly down-regulated in triple-negative breast cancer and correlated with the clinicopathological characteristics and prognosis of TNBC patients
To further explore the expression of AHNAK in breast cancer, we tested the level of AHNAK mRNA in a panel of 10 breast cell lines, including 8 human breast cancer cell lines and 2 normal mammary epithelial cell lines using a qRT-PCR method. As Fig. 2a shows, compared with normal mammary epithelial cell lines, AHNAK mRNA levels are down-regulated in 7 human breast cancer cell lines, especially in TNBC cell lines (including BT20, MDA-MB-435, MDA-MB-231 and BT549). To confirm the results from the in vitro study, the levels of AHNAK mRNA were evaluated in 71 tissue samples, 51 of which were obtained from patients with TNBC and 20 from patients with non-TNBC (Fig. 2b). The results showed that the level of AHNAK mRNA was significantly reduced in TNBC samples, but no significant difference was found in the AHNAK mRNA levels between non-TNBC tissues and normal tissues. Moreover, in 221 cases of TNBC (including 51 cases of TNBC that we previously tested), we examined whether AHNAK expression was associated with clinicopathological parameters. Based on the mean AHNAK mRNA level, there were 108 patients with low AHNAK and 113 patients with high AHNAK expression. As shown in Table 1, the expression of AHNAK was inversely correlated with the tumour status (P = 0.015), lymph node status (P < 0.001), lymph node (LN) infiltration (P < 0.001) and TNM stage (P < 0.001) of TNBC patients. No significant correlation was found between AHNAK expression and other clinicopathological factors, including age, menopause, body mass index (BMI) and histological grade (P = 0.586, 0.338, 0.156 and 0.139, respectively). The results of the multivariate Cox regression analysis showed that patients with low levels of AHNAK had poor disease-free survival (DFS) and overall survival (OS) (Fig. 2c, P < 0.001 for DFS and Fig. 2d, P = 0.001 for OS; multivariate Cox regression analysis as shown in Table 2). Fig. 2e shows the representative immunohistochemical staining of AHNAK in matched TNBC tumour tissues and their corresponding non-tumour tissues.
Fig. 2
Expression of AHNAK is significantly down-regulated in triple-negative breast cancer. a AHNAK expression level determined by qRT-PCR in two normal mammary epithelial cell lines, four luminal breast cancer cell lines and four basal-like breast cancer cell lines. β-actin was used as a control for normalization. The error bars represent the standard deviation (SD). * P < 0.05 and **P < 0.01. b Expression levels of AHNAK in 51 TNBC specimens and the corresponding adjacent normal tissues (Normal 1) (left) and 20 NTNBC specimens and the corresponding adjacent normal tissues (Normal 2) (right). Low levels of AHNAK correlate with poor prognosis. c DFS curves for 221 TNBC patients with high or low AHNAK levels. d OS curves for 221 TNBC patients with high or low AHNAK levels (right). e Representative immunohistochemistry images of AHNAK expression in two TNBC cases
Table 1
Association between AHNAK and clinicopathological characteristics in triple-negative breast cancer
Variables
Cases
Ahnak
P value
(n = 221)
high
No. (%)
low
No. (%)
Age (years)
0.586
<50
133
66
49.6%
67
50.4%
≥50
88
47
53.4%
41
46.6%
Menopause
0.338
yes
90
50
55.6%
40
44.4%
no
131
63
48.1%
68
51.9%
BMI
0.156
<25
169
91
53.8%
78
46.2%
≥25
52
22
42.3%
30
57.7%
Tumor status (T)
0.015*
T1
67
42
62.7%
25
37.3%
T2
120
61
50.8%
59
49.2%
T3
17
6
35.3%
11
64.7%
T4
17
4
23.5%
13
76.5%
Lymph node status (N)
<0.001*
N0
117
80
68.4%
37
31.6%
N1
57
21
36.8%
36
63.2%
N2
35
9
25.7%
26
74.3%
N3
12
3
25.0%
9
75.0%
Histological grade
0.139
G1 + G2
108
61
56.5%
47
43.5%
G3
113
52
46.0%
61
54.0%
LN infiltration
<0.001*
No
117
80
68.4%
37
31.6%
Yes
104
33
31.7%
71
68.3%
TNM stage
<0.001*
I
48
34
70.8%
14
29.2%
II
111
64
57.7%
47
42.3%
III
56
14
25.0%
42
75.0%
IV
6
1
16.7%
5
83.3%
Abbreviation: BMI body mass index, LN lymph node
*P < 0.05, statistically significant
Table 2
Prognostic value of AHNAK for overall survival in triple-negative breast cancer patients by Univariate and Multivariate analyses
Variables
Univariate analysis
Multivariate analysis
RR
95% IC
P value
RR
95% IC
P value
Age (<50 vs. ≥50 years)
1.137
0.748–1.728
0.548
-
-
-
Menopause (Yes vs. No)
1.069
0.701–1.630
0.758
-
-
-
BMI (<25 vs. ≥ 25)
1.057
0.654–1.710
0.820
-
-
-
Histological grade(G1 + G2 vs. G3)
1.626
1.064–2.485
0.025*
1.272
0.821–1.970
0.282
TNM Staging(I + II vs. III + IV)
3.340
2.199–5.073
<0.001*
2.834
1.827–4.397
<0.001
Ahnak(low vs. high)
2.094
1.366–3.209
0.001*
1.641
1.053–2.558
0.029
*Statistically significant prognostic factor identified by Univariate/Multivariate analysis
AHNAK effected TNBC cell line proliferation and colony formation invasion
Next, we studied the biological effects of AHNAK in TNBC. AHNAK-expressing vector was transfected into two TNBC cell lines, MDA-MB-231 and BT549. Compared with the control group, we found that the ectopic expression of AHNAK in MDA-MB-231 and BT549 cells could markedly inhibit cell proliferation (Fig. 3a) and colony formation (Fig. 3b and c). Furthermore, we used siRNA to perform knockdown of AHNAK expression in BT20 and MDA-MB-435 cells to assess the functional consequences. We found that knockdown of AHNAK expression could promote proliferation (Fig. 3d) and colony formation (Fig. 3e and f) of TNBC cells. The results thus suggest the role of AHNAK as a tumour suppressor in TNBC.
Fig. 3
AHNAK inhibits proliferation and colony formation in TNBC cell lines. a The growth of MDA-MB-231 and BT549 cells infected with AHNAK-overexpressing or control vector was assayed by MTT. **P < 0.01. Colony formation assays performed on MDA-MB-231 (b) and BT549 (c) cells transfected with AHNAK or control vector. *P < 0.05 and **P < 0.01. d The growth of BT20 and MDA-MB-435 cells transfected with AHNAK siRNA or control was assayed by MTT. *P < 0.05 and **P < 0.01. Colony formation assays were performed on BT20 (e) and MDA-MB-435 (f) cells transfected with AHNAK siRNA or control. *P < 0.05 and **P < 0.01
Overexpression of AHNAK in TNBC cell lines inhibited in vivo tumour growth and lung metastasis
Based on the findings from the in vitro study and clinicopathological analysis, we adopted a xenograft model using human TNBC cells in nude mice to further verify the function of AHNAK in TNBC. As shown in Fig. 4a, compared with the control group, the mean size and weight of tumours of the AHNAK-overexpressing group were significantly lower. Next, we designed a cancer metastasis xenograft model by tail vein injection to assay the effect of AHNAK on tumour metastasis. Four weeks after injection, the mice were euthanized and their lungs were dissected. The metastatic nodules on the surface of the mouse lungs (arrows) were markedly decreased after overexpression of AHNAK (Fig. 4b). To confirm that the nodules were metastatic tumours, haematoxylin and eosin staining was used (Fig. 4c). The results indicated that AHNAK repressed TNBC proliferation and metastasis in vivo.
Fig. 4
AHNAK inhibits TNBC growth and lung metastasis in vivo. MDA-MB-231 or BT549 cells infected with AHNAK or vector lentivirus were injected into the flanks of nude mice. a The growth curves of the tumours are plotted (left: MDA-MB-231; middle: BT549). The weights of the xenograft tumours are summarized in the right panel. All results are expressed as the mean ± SD of three independent experiments, *P < 0.05 and **P < 0.01. b Tumour metastasis in the mouse xenograft model. Metastatic nodules (arrows) on the lung surface. The number of nodules was quantified in the lungs of nude mice (n = 5 per group) 28 days after tail vein injection of AHNAK- or empty vector-transfected MDA-MB-231 and BT549 cells (**, P < 0.01, independent Student’s t-test). c The haematoxylin and eosin stained sections derived from metastatic nodules on the lung surface. Original magnification 100X and 200X
AHNAK targets AKT/MAPK signalling and the Wnt/β-catenin pathway
As we found in vitro and in vivo, AHNAK partly inhibited TNBC cell growth and lung metastasis. Next, we wanted to identify the possible molecular mechanisms by which AHNAK regulates the biological characteristics of TNBC cells. We analysed the expression of a series of proteins likely to be affected by AHNAK. The results showed that the overexpression of AHNAK did not affect the total expression of AKT and ERK proteins but markedly suppressed the phosphorylation of AKT, ERK, Raf and MEK1/2 proteins in MDA-MB-231 and BT549 cells (Fig. 5a). These results suggested that AHNAK possibly promoted the growth of TNBC cells via the AKT/MAPK signalling pathway. In addition, we found that AHNAK expression partly regulated the Wnt/β-catenin pathway. According to results from previous studies, the Wnt signalling pathway is one of the key signalling pathways in cancer [2931]. It is generally known that changes in cell motility and tumour metastasis are commonly related to the Wnt/β-catenin pathway. We used western blotting to detect the expression levels of Wnt/β-catenin pathway markers in AHNAK-modified cells. When AHNAK was overexpressed in MDA-MB-231 and BT549 cells, the western blot results confirmed that AHNAK could down-regulate β-catenin, c-myc and Wnt-1 (Fig. 5b). By contrast, the expression of these proteins in the AHNAK-overexpressing MDA-MB-231 and BT549 cells was decreased compared with the control, and Wnt3a could reactivate their expression (Fig. 5b). Moreover, the results from quantitative real time-PCR showed that, when AHNAK was overexpressed, the levels of β-catenin, c-myc and Wnt-1 mRNA were significantly decreased in MDA-MB-231 and BT549 cells (Fig. 5c). Overall, the results indicated that decreases in β-catenin, c-myc and Wnt-1 protein expression levels were most likely due to the reduced transcription of the corresponding mRNA. Meanwhile, consistent results were observed when AHNAK was knocked down in BT20 and MDA-MB-435 cells (Fig. 5d, e and f).
Fig. 5
AHNAK targets the AKT/MAPK signalling pathway and the Wnt/β-catenin pathway. a Relative expression levels of AKT/MAPK signalling proteins were compared between the empty vector- and the AHNAK-expressing MDA-MB-231 and BT549 cells by western blotting. β-actin was used as the loading control. b Image of the blot shows that Wnt activator Wnt3a could reactivate the expression of β-catenin, c-myc, and Wnt1 expression in the MDA-MB-231 and BT549 cells infected with AHNAK-expressing vector. β-actin was used as the loading control. c In contrast to the corresponding vector-transfected groups, the levels of β-catenin, c-myc and Wnt-1 mRNA were significantly decreased in the MDA-MB-231 and the BT549 cells that were transfected with AHNAK-expressing vector. d Relative levels of AKT/MAPK signalling-related proteins were compared between the control and AHNAK siRNA-transfected BT20 and MDA-MB-435 cells by western blotting. e Image of the blot shows that Wnt inhibitor Dkk1 could effectively decrease the expression of β-catenin, c-myc, and wnt1 in the BT20 and MDA-MB-435 cells that were infected with AHNAK siRNA. f In contrast to the control group, the levels of β-catenin, c-myc and Wnt-1 mRNA were significantly increased in the BT20 and MDA-MB-435 cells that were transfected with AHNAK siRNA
Discussion
TNBC is a subtype of breast cancer that has some of the worst patient prognoses of all breast cancer subtypes and is not sensitive to normal endocrine therapy or targeted therapy against breast cancer [32]. Studies of molecular mechanisms in TNBC are extremely necessary. By mining the literature, we found that AHNAK is a very large protein that is involved in many cellular processes and pathways [33]. Down-regulation of AHNAK prevents cortical actin cytoskeleton reorganization. AHNAK forms a multimeric complex with actin and the Annexin 2/S100A10 complex at the plasma membrane, which suggests that AHNAK interacts with the cortical actin cytoskeleton as part of a submembranous complex [21]. Previous research also showed that AHNAK could potentiate TGFβ-induced transcriptional activity of R-Smad, which leads to the negative regulation of cell growth by stimulating the localization of Smad3 into the nucleus [20]. Meanwhile, cell- or tissue-specific processes or pathways regulated by AHNAK are quite distinct and are related to the cell or tissue type [33]. Although several proteins have been identified to interact with AHNAK, the function of AHNAK in breast cancer remains undefined.
Here, we demonstrated the functional significance of AHNAK in TNBC. Using public datasets from Oncomine (www.oncomine.org), the AHNAK mRNA level was found to be reduced in breast cancer, although there was a huge variation among different types of cancers. Meanwhile, both the TCGA and METABRIC datasets showed that the level of AHNAK mRNA was significantly decreased in the samples classified as basal-like (most TNBCs have basal-like characteristics). Consistent with previous findings [20], we found that the expression of AHNAK is low in several TNBC cell lines and that AHNAK might play a tumour suppressive role. In addition, we also found that AHNAK expression was markedly decreased in TNBC patient samples, and the expression of AHNAK is negatively correlated with some vital clinicopathological characteristics, such as tumour status (P = 0.015), lymph node status (P < 0.001), lymph node (LN) infiltration (P < 0.001) and TNM stage (P < 0.001) of TNBC, as well as prognosis of TNBC patients. From in vitro studies, we found that overexpression of AHNAK could inhibit proliferation and colony formation of TNBC cell lines. Conversely, knocking down AHNAK expression could promote the proliferation and colony formation of TNBC cell lines. As indicated, transfection with AHNAK-overexpressing vectors could decrease the growth and metastasis breast cancer xenografts. Thus, we confirmed the function of AHNAK in suppressing tumour progression.
In previous studies, AHNAK has been suggested to be involved in signalling pathways, such as the reorganization of the actin cytoskeleton network, the PI3K–PKB pathway to engage effector proteins, the formation of pseudopodial protrusions, and adaptation events to reprogram tumour cell biology [17, 34]. The Wnt/β-catenin signalling pathway plays critical roles in development and tissue homeostasis [35, 36]. As many previous studies have indicated, the Wnt/β-catenin signalling pathway also plays a vital role in breast cancer [3739]. The role of Wnt signalling in primary TNBC and as a predictor of lung and brain metastasis has been described [40, 41]. A meta-analysis indicated that the Wnt pathway is activated in TNBC and that increased Wnt/β-catenin signalling is associated with metastatic disease and poor prognosis [41]. Notable Wnt transcriptional targets upregulated in TNBC include MYC [42], matrix metallopeptidase 7 (MMP7) [43], VEGF [44], MET [45], CD44 [46], snail (SNAI1) [47] and survivin (BIRC5) [48]. In this study, we explored the association between AHNAK and the Wnt/β-catenin signalling pathway and demonstrated that, in TNBC, AHNAK indeed regulated the expression of several important genes belonging to the Wnt/β-catenin signalling pathway, such as Wnt-1, β-catenin and c-myc, both at the mRNA level and at the protein level. Previous studies have confirmed that there is a link between AHNAK and c-myc. Overexpression of AHNAK could down-regulate c-myc and cyclin D1/D2, resulting in cell cycle arrest and growth retardation [20]. A recent study also showed that, in the absence of the ectopic expression of c-myc, the down-regulation of AHNAK could generate safer induced pluripotent stem cells (iPSCs) [49]. Moreover, we identified PI3K/AKT and MAPK/ERK as key signalling pathways involved in the inhibition of tumour cell proliferation mediated by AHNAK. The constitutive activation of PI3K/AKT and MAPK/ERK signalling pathways is an important event in breast cancer, as they regulate multiple cellular processes to promote cancer growth, survival, and metastasis [50, 51]. However, there are several limitations in our study that should be addressed. First, although we found that AHNAK affected some pathways to some extent, the specific details of these mechanisms are still unknown. In addition, it remains unclear whether the proposed role for AHNAK is limited to only the triple-negative subtype of breast cancer. Therefore, further studies will be needed to determine the exact function of AHNAK.
Conclusions
In conclusion, our study demonstrates the potential tumour suppressive role and lung metastasis-inhibiting effect of AHNAK in TNBC. Moreover, AHNAK could, at least partially, affect the AKT/MAPK and the Wnt/β-catenin signalling pathways, which are important tumour-related signalling pathways in TNBC. Taken together, although more in-depth mechanisms and prognostic roles for AHNAK in TNBC need to be confirmed in the future, our findings provide a preliminary basis to explore AHNAK as a potential therapeutic candidate in TNBC.
Declarations
Acknowledgements
This work was supported by funds from the National Natural Science Foundation of China (81472575, 81672598, Xiaoming Xie; 81472469, Hailin Tang) and the Science and Technology Planning Project of Guangzhou and Guangdong (2015B090901050, 2015B020211002, Xiaoming Xie; 2016A020214009, Hailin Tang).
Authors’ contributions
XX and HT designed the experiment and critically revised the paper; BC, QZ, XG and ZT performed most of the experiments; JW, DD, XH and LY contributed to collected the patients data; BC, JW and DD performed the statistical and bioinformatic analysis; HT cultured cells and built animal models; BC wrote the manuscript. All authors read and approved the final manuscript.
Competing interests
The authors declare that they have no competing interests.
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Authors’ Affiliations
(1)
Department of Breast Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China
(2)
College of Pharmacy, University of South Florida, Tampa, USA
References
1. Wu J, Gong G, Cui Y, Li R. Intratumor partitioning and texture analysis of dynamic contrast-enhanced (DCE)-MRI identifies relevant tumor subregions to predict pathological response of breast cancer to neoadjuvant chemotherapy. J Magn Reson Imaging. 2016;44:1107–15.View ArticlePubMedGoogle Scholar
2. Koren S, Bentires-Alj M. Breast Tumor Heterogeneity: Source of Fitness, Hurdle for Therapy. Mol Cell. 2015;60:537–46.View ArticlePubMedGoogle Scholar
3. Collignon J, Lousberg L, Schroeder H, Jerusalem G. Triple-negative breast cancer: treatment challenges and solutions. Breast Cancer (Dove Med Press). 2016;8:93–107.Google Scholar
4. Metzger-Filho O, Tutt A, de Azambuja E, Saini KS, Viale G, Loi S, et al. Dissecting the heterogeneity of triple-negative breast cancer. J Clin Oncol. 2012;30:1879–87.View ArticlePubMedGoogle Scholar
5. Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66:115–32.View ArticlePubMedGoogle Scholar
6. Kassam F, Enright K, Dent R, Dranitsaris G, Myers J, Flynn C, et al. Survival outcomes for patients with metastatic triple-negative breast cancer: implications for clinical practice and trial design. Clin Breast Cancer. 2009;9:29–33.View ArticlePubMedGoogle Scholar
7. Bianchini G, Balko JM, Mayer IA, Sanders ME, Gianni L. Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease. Nat Rev Clin Oncol. 2016;13(11):674–90.View ArticlePubMedGoogle Scholar
8. Bernard-Marty C, Cardoso F, Piccart MJ. Facts and controversies in systemic treatment of metastatic breast cancer. Oncologist. 2004;9:617–32.View ArticlePubMedGoogle Scholar
9. Amagai M. A mystery of AHNAK/desmoyokin still goes on. J Investig Dermatol. 2004;123:xiv–xv.View ArticlePubMedGoogle Scholar
10. Hieda Y, Tsukita S, Tsukita S. A new high molecular mass protein showing unique localization in desmosomal plaque. J Cell Biol. 1989;109:1511–8.View ArticlePubMedGoogle Scholar
11. de Morree A, Droog M, Grand Moursel L, Bisschop IJ, Impagliazzo A, Frants RR, et al. Self-regulated alternative splicing at the AHNAK locus. FASEB J. 2012;26:93–103.View ArticlePubMedGoogle Scholar
12. Haase H. Ahnak, a new player in beta-adrenergic regulation of the cardiac L-type Ca2+ channel. Cardiovasc Res. 2007;73:19–25.View ArticlePubMedGoogle Scholar
13. Hohaus A, Person V, Behlke J, Schaper J, Morano I, Haase H. The carboxyl-terminal region of ahnak provides a link between cardiac L-type Ca2+ channels and the actin-based cytoskeleton. FASEB J. 2002;16:1205–16.View ArticlePubMedGoogle Scholar
14. Haase H, Podzuweit T, Lutsch G, Hohaus A, Kostka S, Lindschau C, et al. Signaling from beta-adrenoceptor to L-type calcium channel: identification of a novel cardiac protein kinase A target possessing similarities to AHNAK. FASEB J. 1999;13:2161–72.PubMedGoogle Scholar
15. Shtivelman E, Cohen FE, Bishop JM. A human gene (AHNAK) encoding an unusually large protein with a 1.2-microns polyionic rod structure. Proc Natl Acad Sci U S A. 1992;89:5472–6.View ArticlePubMedPubMed CentralGoogle Scholar
16. Shtivelman E, Bishop JM. The human gene AHNAK encodes a large phosphoprotein located primarily in the nucleus. J Cell Biol. 1993;120:625–30.View ArticlePubMedGoogle Scholar
17. Shankar J, Messenberg A, Chan J, Underhill TM, Foster LJ, Nabi IR. Pseudopodial actin dynamics control epithelial-mesenchymal transition in metastatic cancer cells. Cancer Res. 2010;70:3780–90.View ArticlePubMedGoogle Scholar
18. Han H, Kursula P. Periaxin and AHNAK nucleoprotein 2 form intertwined homodimers through domain swapping. J Biol Chem. 2014;289:14121–31.View ArticlePubMedPubMed CentralGoogle Scholar
19. Dempsey BR, Rezvanpour A, Lee TW, Barber KR, Junop MS, Shaw GS. Structure of an asymmetric ternary protein complex provides insight for membrane interaction. Structure. 2012;20:1737–45.View ArticlePubMedGoogle Scholar
20. Lee IH, Sohn M, Lim HJ, Yoon S, Oh H, Shin S, et al. Ahnak functions as a tumor suppressor via modulation of TGFbeta/Smad signaling pathway. Oncogene. 2014;33:4675–84.View ArticlePubMedPubMed CentralGoogle Scholar
21. Benaud C, Gentil BJ, Assard N, Court M, Garin J, Delphin C, et al. AHNAK interaction with the annexin 2/S100A10 complex regulates cell membrane cytoarchitecture. J Cell Biol. 2004;164:133–44.View ArticlePubMedPubMed CentralGoogle Scholar
22. Liu P, Tang H, Chen B, He Z, Deng M, Wu M, et al. miR-26a suppresses tumour proliferation and metastasis by targeting metadherin in triple negative breast cancer. Cancer Lett. 2015;357:384–92.View ArticlePubMedGoogle Scholar
23. Cancer Genome Atlas N. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490:61–70.View ArticleGoogle Scholar
24. Pereira B, Chin SF, Rueda OM, Vollan HK, Provenzano E, Bardwell HA, et al. The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes. Nat Commun. 2016;7:11479.View ArticlePubMedPubMed CentralGoogle Scholar
25. Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013;6:pl1.View ArticlePubMedPubMed CentralGoogle Scholar
26. Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012;2:401–4.View ArticlePubMedGoogle Scholar
27. Parker JS, Mullins M, Cheang MC, Leung S, Voduc D, Vickery T, et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol. 2009;27:1160–7.View ArticlePubMedPubMed CentralGoogle Scholar
28. Herschkowitz JI, Simin K, Weigman VJ, Mikaelian I, Usary J, Hu Z, et al. Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors. Genome Biol. 2007;8:R76.View ArticlePubMedPubMed CentralGoogle Scholar
29. Holland JD, Klaus A, Garratt AN, Birchmeier W. Wnt signaling in stem and cancer stem cells. Curr Opin Cell Biol. 2013;25:254–64.View ArticlePubMedGoogle Scholar
30. Polakis P. Wnt signaling in cancer. Cold Spring Harbor Perspect Biol. 2012;4(5):1–10.Google Scholar
31. Angeloni V, Tiberio P, Appierto V, Daidone MG. Implications of stemness-related signaling pathways in breast cancer response to therapy. Semin Cancer Biol. 2015;31:43–51.View ArticlePubMedGoogle Scholar
32. Kalimutho M, Parsons K, Mittal D, Lopez JA, Srihari S, Khanna KK. Targeted Therapies for Triple-Negative Breast Cancer: Combating a Stubborn Disease. Trends Pharmacol Sci. 2015;36:822–46.View ArticlePubMedGoogle Scholar
33. Davis TA, Loos B, Engelbrecht AM. AHNAK: the giant jack of all trades. Cell Signal. 2014;26:2683–93.View ArticlePubMedGoogle Scholar
34. Qiao M, Sheng S, Pardee AB. Metastasis and AKT activation. Cell Cycle. 2008;7:2991–6.View ArticlePubMedGoogle Scholar
35. Wang Z, Li B, Zhou L, Yu S, Su Z, Song J, et al. Prodigiosin inhibits Wnt/beta-catenin signaling and exerts anticancer activity in breast cancer cells. Proc Natl Acad Sci U S A. 2016;113:13150–5.View ArticlePubMedPubMed CentralGoogle Scholar
36. Lien WH, Fuchs E. Wnt some lose some: transcriptional governance of stem cells by Wnt/beta-catenin signaling. Genes Dev. 2014;28:1517–32.View ArticlePubMedPubMed CentralGoogle Scholar
37. Clevers H, Nusse R. Wnt/beta-catenin signaling and disease. Cell. 2012;149:1192–205.View ArticlePubMedGoogle Scholar
38. Li Y, Jin K, van Pelt GW, van Dam H, Yu X, Mesker WE, et al. c-Myb Enhances Breast Cancer Invasion and Metastasis through the Wnt/beta-Catenin/Axin2 Pathway. Cancer Res. 2016;76:3364–75.View ArticlePubMedGoogle Scholar
39. Cai J, Guan H, Fang L, Yang Y, Zhu X, Yuan J, et al. MicroRNA-374a activates Wnt/beta-catenin signaling to promote breast cancer metastasis. J Clin Investig. 2013;123:566–79.View ArticlePubMedPubMed CentralGoogle Scholar
40. De P, Carlson JH, Wu H, Marcus A, Leyland-Jones B, Dey N. Wnt-beta-catenin pathway signals metastasis-associated tumor cell phenotypes in triple negative breast cancers. Oncotarget. 2016;7:43124–49.PubMedPubMed CentralGoogle Scholar
41. Dey N, Barwick BG, Moreno CS, Ordanic-Kodani M, Chen Z, Oprea-Ilies G, et al. Wnt signaling in triple negative breast cancer is associated with metastasis. BMC Cancer. 2013;13:537.View ArticlePubMedPubMed CentralGoogle Scholar
42. He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, et al. Identification of c-MYC as a target of the APC pathway. Science. 1998;281:1509–12.View ArticlePubMedGoogle Scholar
43. Zhou L, Liu Y. Wnt/beta-catenin signalling and podocyte dysfunction in proteinuric kidney disease. Nat Rev Nephrol. 2015;11:535–45.View ArticlePubMedPubMed CentralGoogle Scholar
44. Zhang T, Otevrel T, Gao Z, Gao Z, Ehrlich SM, Fields JZ, et al. Evidence that APC regulates survivin expression: a possible mechanism contributing to the stem cell origin of colon cancer. Cancer Res. 2001;61:8664–7.PubMedGoogle Scholar
45. Smid M, Wang Y, Zhang Y, Sieuwerts AM, Yu J, Klijn JG, et al. Subtypes of breast cancer show preferential site of relapse. Cancer Res. 2008;68:3108–14.View ArticlePubMedGoogle Scholar
46. Wielenga VJ, Smits R, Korinek V, Smit L, Kielman M, Fodde R, et al. Expression of CD44 in Apc and Tcf mutant mice implies regulation by the WNT pathway. Am J Pathol. 1999;154:515–23.View ArticlePubMedPubMed CentralGoogle Scholar
47. ten Berge D, Koole W, Fuerer C, Fish M, Eroglu E, Nusse R. Wnt signaling mediates self-organization and axis formation in embryoid bodies. Cell Stem Cell. 2008;3:508–18.View ArticlePubMedPubMed CentralGoogle Scholar
48. Chen X, Duan N, Zhang C, Zhang W. Survivin and Tumorigenesis: Molecular Mechanisms and Therapeutic Strategies. J Cancer. 2016;7:314–23.View ArticlePubMedPubMed CentralGoogle Scholar
49. Lim HJ, Kim J, Park CH, Lee SA, Lee MR, Kim KS, et al. Regulation of c-Myc Expression by Ahnak Promotes Induced Pluripotent Stem Cell Generation. J Biol Chem. 2016;291:752–61.View ArticlePubMedGoogle Scholar
50. Machado VA, Peixoto D, Queiroz MJ, Soares R. Antiangiogenic 1-Aryl-3-[3-(thieno[3,2-b]pyridin-7-ylthio)phenyl]ureas Inhibit MCF-7 and MDA-MB-231 Human Breast Cancer Cell Lines Through PI3K/Akt and MAPK/Erk Pathways. J Cell Biochem. 2016;117:2791–9.View ArticlePubMedGoogle Scholar
51. Engelman JA. Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer. 2009;9:550–62.View ArticlePubMedGoogle Scholar
Copyright
© The Author(s). 2017
Advertisement
|
{
"url": "https://jeccr.biomedcentral.com/articles/10.1186/s13046-017-0522-4",
"source_domain": "jeccr.biomedcentral.com",
"snapshot_id": "crawl=CC-MAIN-2018-05",
"warc_metadata": {
"Content-Length": "233024",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:HUAIMRULGUCXPOO4QV4ZN4PZVMA3KTRO",
"WARC-Concurrent-To": "<urn:uuid:f733b92a-964f-4149-80a4-6d49a0e3fc4d>",
"WARC-Date": "2018-01-16T15:53:32",
"WARC-IP-Address": "151.101.32.95",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:GCFEMWDADG4UFAOWGG3YBTYCRGYZXD2W",
"WARC-Record-ID": "<urn:uuid:ff870686-b894-4094-b9be-df5e054e4a07>",
"WARC-Target-URI": "https://jeccr.biomedcentral.com/articles/10.1186/s13046-017-0522-4",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:3061adc2-7e14-48f6-a725-c46d8cd87682>"
},
"warc_info": "robots: classic\r\nhostname: ip-10-146-28-102.ec2.internal\r\nsoftware: Nutch 1.6 (CC)\r\nisPartOf: CC-MAIN-2018-05\r\noperator: Common Crawl Admin\r\ndescription: Wide crawl of the web for January 2018\r\npublisher: Common Crawl\r\nformat: WARC File Format 1.0\r\nconformsTo: http://bibnum.bnf.fr/WARC/WARC_ISO_28500_version1_latestdraft.pdf"
}
|
{
"line_start_idx": [
0,
16,
17,
31,
32,
83,
84,
96,
97,
212,
213,
227,
242,
259,
277,
296,
311,
331,
345,
378,
408,
428,
488,
489,
531,
532,
559,
560,
584,
585,
608,
609,
618,
619,
630,
631,
791,
792,
800,
801,
1782,
1783,
1795,
1796,
1992,
1993,
2002,
2003,
2066,
2067,
2078,
2079,
2948,
2949,
5130,
5131,
5139,
5140,
5157,
5158,
5937,
5938,
5969,
5970,
6539,
6540,
7609,
7610,
7649,
7650,
8980,
8981,
9006,
9007,
9224,
9225,
9246,
9247,
9566,
9567,
9588,
9589,
9739,
9740,
9753,
9754,
10575,
10576,
10598,
10599,
11885,
11886,
11910,
11911,
12461,
12462,
12483,
12484,
13063,
13064,
13072,
13073,
13140,
13141,
14117,
14124,
14125,
14480,
14481,
14655,
14656,
16700,
16707,
16708,
17576,
17577,
17585,
17586,
17685,
17686,
17696,
17697,
17703,
17704,
17710,
17711,
17719,
17720,
17730,
17731,
17736,
17737,
17745,
17746,
17750,
17751,
17759,
17760,
17772,
17773,
17779,
17780,
17786,
17787,
17792,
17793,
17797,
17798,
17801,
17802,
17808,
17809,
17812,
17813,
17819,
17820,
17822,
17823,
17828,
17829,
17832,
17833,
17836,
17837,
17843,
17844,
17847,
17848,
17854,
17855,
17857,
17858,
17868,
17869,
17875,
17876,
17882,
17883,
17888,
17889,
17892,
17893,
17896,
17897,
17903,
17904,
17907,
17908,
17914,
17915,
17917,
17918,
17922,
17923,
17927,
17928,
17931,
17932,
17938,
17939,
17942,
17943,
17949,
17950,
17952,
17953,
17958,
17959,
17965,
17966,
17972,
17973,
17978,
17979,
17983,
17984,
17987,
17988,
17994,
17995,
17998,
17999,
18005,
18006,
18008,
18009,
18014,
18015,
18018,
18019,
18022,
18023,
18029,
18030,
18033,
18034,
18040,
18041,
18043,
18044,
18061,
18062,
18068,
18069,
18076,
18077,
18081,
18082,
18085,
18086,
18089,
18090,
18096,
18097,
18100,
18101,
18107,
18108,
18110,
18111,
18115,
18116,
18120,
18121,
18124,
18125,
18131,
18132,
18135,
18136,
18142,
18143,
18145,
18146,
18150,
18151,
18154,
18155,
18157,
18158,
18164,
18165,
18168,
18169,
18175,
18176,
18178,
18179,
18183,
18184,
18187,
18188,
18190,
18191,
18197,
18198,
18201,
18202,
18208,
18209,
18211,
18212,
18234,
18235,
18241,
18242,
18250,
18251,
18255,
18256,
18260,
18261,
18264,
18265,
18271,
18272,
18275,
18276,
18282,
18283,
18285,
18286,
18290,
18291,
18294,
18295,
18298,
18299,
18305,
18306,
18309,
18310,
18316,
18317,
18319,
18320,
18324,
18325,
18328,
18329,
18331,
18332,
18338,
18339,
18342,
18343,
18349,
18350,
18352,
18353,
18357,
18358,
18361,
18362,
18364,
18365,
18371,
18372,
18374,
18375,
18381,
18382,
18384,
18385,
18404,
18405,
18411,
18412,
18418,
18419,
18428,
18429,
18433,
18434,
18437,
18438,
18444,
18445,
18448,
18449,
18455,
18456,
18458,
18459,
18463,
18464,
18468,
18469,
18472,
18473,
18479,
18480,
18483,
18484,
18490,
18491,
18493,
18494,
18510,
18511,
18517,
18518,
18526,
18527,
18531,
18532,
18536,
18537,
18540,
18541,
18547,
18548,
18551,
18552,
18558,
18559,
18561,
18562,
18567,
18568,
18572,
18573,
18576,
18577,
18583,
18584,
18587,
18588,
18594,
18595,
18597,
18598,
18608,
18609,
18615,
18616,
18624,
18625,
18628,
18629,
18632,
18633,
18636,
18637,
18643,
18644,
18647,
18648,
18654,
18655,
18657,
18658,
18662,
18663,
18667,
18668,
18671,
18672,
18678,
18679,
18682,
18683,
18689,
18690,
18692,
18693,
18698,
18699,
18702,
18703,
18706,
18707,
18713,
18714,
18717,
18718,
18724,
18725,
18727,
18728,
18732,
18733,
18735,
18736,
18738,
18739,
18745,
18746,
18748,
18749,
18755,
18756,
18758,
18759,
18808,
18809,
18846,
18847,
18855,
18856,
18985,
18986,
18996,
18997,
19017,
19018,
19040,
19041,
19044,
19045,
19052,
19053,
19061,
19062,
19065,
19066,
19073,
19074,
19082,
19083,
19107,
19108,
19114,
19115,
19127,
19128,
19134,
19135,
19137,
19138,
19140,
19141,
19143,
19144,
19167,
19168,
19174,
19175,
19187,
19188,
19194,
19195,
19197,
19198,
19200,
19201,
19203,
19204,
19223,
19224,
19230,
19231,
19243,
19244,
19250,
19251,
19253,
19254,
19256,
19257,
19259,
19260,
19295,
19296,
19302,
19303,
19315,
19316,
19323,
19324,
19330,
19331,
19343,
19344,
19350,
19351,
19384,
19385,
19391,
19392,
19404,
19405,
19413,
19414,
19420,
19421,
19433,
19434,
19441,
19442,
19462,
19463,
19469,
19470,
19482,
19483,
19490,
19491,
19497,
19498,
19510,
19511,
19517,
19518,
19610,
19611,
19685,
19686,
20376,
20383,
20384,
20992,
20993,
21088,
21089,
21968,
21975,
21976,
22861,
22862,
22926,
22927,
24916,
24923,
24924,
26223,
26224,
26235,
26236,
27434,
27435,
28888,
28889,
31426,
31427,
31439,
31440,
31971,
31972,
31985,
31986,
32003,
32004,
32301,
32302,
32325,
32326,
32697,
32698,
32718,
32719,
32778,
32779,
32796,
32797,
32916,
32917,
33503,
33504,
33526,
33527,
33531,
33740,
33744,
33805,
33806,
33817,
33818,
34121,
34276,
34460,
34664,
34828,
35099,
35319,
35498,
35628,
35811,
36015,
36179,
36428,
36704,
36934,
37113,
37345,
37535,
37759,
37979,
38223,
38454,
38592,
38852,
39087,
39323,
39546,
39814,
39981,
40087,
40296,
40522,
40661,
40785,
41033,
41223,
41346,
41571,
41798,
42037,
42270,
42459,
42643,
42885,
43075,
43310,
43532,
43720,
43934,
44221,
44383,
44384,
44394,
44395,
44417,
44418
],
"line_end_idx": [
16,
17,
31,
32,
83,
84,
96,
97,
212,
213,
227,
242,
259,
277,
296,
311,
331,
345,
378,
408,
428,
488,
489,
531,
532,
559,
560,
584,
585,
608,
609,
618,
619,
630,
631,
791,
792,
800,
801,
1782,
1783,
1795,
1796,
1992,
1993,
2002,
2003,
2066,
2067,
2078,
2079,
2948,
2949,
5130,
5131,
5139,
5140,
5157,
5158,
5937,
5938,
5969,
5970,
6539,
6540,
7609,
7610,
7649,
7650,
8980,
8981,
9006,
9007,
9224,
9225,
9246,
9247,
9566,
9567,
9588,
9589,
9739,
9740,
9753,
9754,
10575,
10576,
10598,
10599,
11885,
11886,
11910,
11911,
12461,
12462,
12483,
12484,
13063,
13064,
13072,
13073,
13140,
13141,
14117,
14124,
14125,
14480,
14481,
14655,
14656,
16700,
16707,
16708,
17576,
17577,
17585,
17586,
17685,
17686,
17696,
17697,
17703,
17704,
17710,
17711,
17719,
17720,
17730,
17731,
17736,
17737,
17745,
17746,
17750,
17751,
17759,
17760,
17772,
17773,
17779,
17780,
17786,
17787,
17792,
17793,
17797,
17798,
17801,
17802,
17808,
17809,
17812,
17813,
17819,
17820,
17822,
17823,
17828,
17829,
17832,
17833,
17836,
17837,
17843,
17844,
17847,
17848,
17854,
17855,
17857,
17858,
17868,
17869,
17875,
17876,
17882,
17883,
17888,
17889,
17892,
17893,
17896,
17897,
17903,
17904,
17907,
17908,
17914,
17915,
17917,
17918,
17922,
17923,
17927,
17928,
17931,
17932,
17938,
17939,
17942,
17943,
17949,
17950,
17952,
17953,
17958,
17959,
17965,
17966,
17972,
17973,
17978,
17979,
17983,
17984,
17987,
17988,
17994,
17995,
17998,
17999,
18005,
18006,
18008,
18009,
18014,
18015,
18018,
18019,
18022,
18023,
18029,
18030,
18033,
18034,
18040,
18041,
18043,
18044,
18061,
18062,
18068,
18069,
18076,
18077,
18081,
18082,
18085,
18086,
18089,
18090,
18096,
18097,
18100,
18101,
18107,
18108,
18110,
18111,
18115,
18116,
18120,
18121,
18124,
18125,
18131,
18132,
18135,
18136,
18142,
18143,
18145,
18146,
18150,
18151,
18154,
18155,
18157,
18158,
18164,
18165,
18168,
18169,
18175,
18176,
18178,
18179,
18183,
18184,
18187,
18188,
18190,
18191,
18197,
18198,
18201,
18202,
18208,
18209,
18211,
18212,
18234,
18235,
18241,
18242,
18250,
18251,
18255,
18256,
18260,
18261,
18264,
18265,
18271,
18272,
18275,
18276,
18282,
18283,
18285,
18286,
18290,
18291,
18294,
18295,
18298,
18299,
18305,
18306,
18309,
18310,
18316,
18317,
18319,
18320,
18324,
18325,
18328,
18329,
18331,
18332,
18338,
18339,
18342,
18343,
18349,
18350,
18352,
18353,
18357,
18358,
18361,
18362,
18364,
18365,
18371,
18372,
18374,
18375,
18381,
18382,
18384,
18385,
18404,
18405,
18411,
18412,
18418,
18419,
18428,
18429,
18433,
18434,
18437,
18438,
18444,
18445,
18448,
18449,
18455,
18456,
18458,
18459,
18463,
18464,
18468,
18469,
18472,
18473,
18479,
18480,
18483,
18484,
18490,
18491,
18493,
18494,
18510,
18511,
18517,
18518,
18526,
18527,
18531,
18532,
18536,
18537,
18540,
18541,
18547,
18548,
18551,
18552,
18558,
18559,
18561,
18562,
18567,
18568,
18572,
18573,
18576,
18577,
18583,
18584,
18587,
18588,
18594,
18595,
18597,
18598,
18608,
18609,
18615,
18616,
18624,
18625,
18628,
18629,
18632,
18633,
18636,
18637,
18643,
18644,
18647,
18648,
18654,
18655,
18657,
18658,
18662,
18663,
18667,
18668,
18671,
18672,
18678,
18679,
18682,
18683,
18689,
18690,
18692,
18693,
18698,
18699,
18702,
18703,
18706,
18707,
18713,
18714,
18717,
18718,
18724,
18725,
18727,
18728,
18732,
18733,
18735,
18736,
18738,
18739,
18745,
18746,
18748,
18749,
18755,
18756,
18758,
18759,
18808,
18809,
18846,
18847,
18855,
18856,
18985,
18986,
18996,
18997,
19017,
19018,
19040,
19041,
19044,
19045,
19052,
19053,
19061,
19062,
19065,
19066,
19073,
19074,
19082,
19083,
19107,
19108,
19114,
19115,
19127,
19128,
19134,
19135,
19137,
19138,
19140,
19141,
19143,
19144,
19167,
19168,
19174,
19175,
19187,
19188,
19194,
19195,
19197,
19198,
19200,
19201,
19203,
19204,
19223,
19224,
19230,
19231,
19243,
19244,
19250,
19251,
19253,
19254,
19256,
19257,
19259,
19260,
19295,
19296,
19302,
19303,
19315,
19316,
19323,
19324,
19330,
19331,
19343,
19344,
19350,
19351,
19384,
19385,
19391,
19392,
19404,
19405,
19413,
19414,
19420,
19421,
19433,
19434,
19441,
19442,
19462,
19463,
19469,
19470,
19482,
19483,
19490,
19491,
19497,
19498,
19510,
19511,
19517,
19518,
19610,
19611,
19685,
19686,
20376,
20383,
20384,
20992,
20993,
21088,
21089,
21968,
21975,
21976,
22861,
22862,
22926,
22927,
24916,
24923,
24924,
26223,
26224,
26235,
26236,
27434,
27435,
28888,
28889,
31426,
31427,
31439,
31440,
31971,
31972,
31985,
31986,
32003,
32004,
32301,
32302,
32325,
32326,
32697,
32698,
32718,
32719,
32778,
32779,
32796,
32797,
32916,
32917,
33503,
33504,
33526,
33527,
33531,
33740,
33744,
33805,
33806,
33817,
33818,
34121,
34276,
34460,
34664,
34828,
35099,
35319,
35498,
35628,
35811,
36015,
36179,
36428,
36704,
36934,
37113,
37345,
37535,
37759,
37979,
38223,
38454,
38592,
38852,
39087,
39323,
39546,
39814,
39981,
40087,
40296,
40522,
40661,
40785,
41033,
41223,
41346,
41571,
41798,
42037,
42270,
42459,
42643,
42885,
43075,
43310,
43532,
43720,
43934,
44221,
44383,
44384,
44394,
44395,
44417,
44418,
44431
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 44431,
"ccnet_original_nlines": 723,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 6,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.20483748614788055,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.09178274124860764,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.3210236430168152,
"rps_doc_frac_unique_words": 0.29466646909713745,
"rps_doc_mean_word_length": 5.477375030517578,
"rps_doc_num_sentences": 637,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 6.353603839874268,
"rps_doc_word_count": 6431,
"rps_doc_frac_chars_dupe_10grams": 0.014762240462005138,
"rps_doc_frac_chars_dupe_5grams": 0.11358410120010376,
"rps_doc_frac_chars_dupe_6grams": 0.06591908633708954,
"rps_doc_frac_chars_dupe_7grams": 0.053938958793878555,
"rps_doc_frac_chars_dupe_8grams": 0.03497515991330147,
"rps_doc_frac_chars_dupe_9grams": 0.025493260473012924,
"rps_doc_frac_chars_top_2gram": 0.018736690282821655,
"rps_doc_frac_chars_top_3gram": 0.004599010106176138,
"rps_doc_frac_chars_top_4gram": 0.00567778991535306,
"rps_doc_books_importance": -4611.451171875,
"rps_doc_books_importance_length_correction": -4611.451171875,
"rps_doc_openwebtext_importance": -2513.415771484375,
"rps_doc_openwebtext_importance_length_correction": -2513.415771484375,
"rps_doc_wikipedia_importance": -1790.9599609375,
"rps_doc_wikipedia_importance_length_correction": -1790.9599609375
},
"fasttext": {
"dclm": 0.024543579667806625,
"english": 0.8723013997077942,
"fineweb_edu_approx": 2.320260763168335,
"eai_general_math": 0.17887461185455322,
"eai_open_web_math": 0.3168301582336426,
"eai_web_code": 0.004107830114662647
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.994422",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "616.9944",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "4",
"label": "Analyze"
},
"secondary": {
"code": "5",
"label": "Evaluate"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "2",
"label": "Academic/Research"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "0",
"label": "No Artifacts"
}
},
"missing_content": {
"primary": {
"code": "4",
"label": "Missing Images or Figures"
},
"secondary": {
"code": "0",
"label": "No missing content"
}
},
"document_type_v2": {
"primary": {
"code": "3",
"label": "Academic Writing"
},
"secondary": {
"code": "8",
"label": "Documentation"
}
},
"reasoning_depth": {
"primary": {
"code": "4",
"label": "Advanced Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "4",
"label": "Graduate/Expert Level"
},
"secondary": {
"code": "3",
"label": "Undergraduate Level"
}
}
}
|
1a01aa77535b9ecfb87b9fc36adbcd2f
|
5,318,453,716,449,167,000
|
Search on website
chevron-left-black Keywords
Milrinone: CV effects
Drug Category: PDE inhibitor
Mechanism:Causes direct stimulation of myocardial contractility and acceleration of myocardial relaxation. In addition, it causes balanced arterial and venous dilation with a consequent fall in systemic and pulmonary vascular resistances, and left and right heart filling pressures. Cardiac output increases due to the stimulation of myocardial contractility and the decrease in left ventricular afterload.
As a result of this dual mechanism of action, the increase in cardiac output with milrinone is greater than that seen with nitroprusside at doses that produce comparable reductions of systemic resistance. Conversely, the arterial and venous dilator effects of milrinone are greater than those of dobutamine at doses that produce comparable increases in cardiac output.
References
1. Jerrold H Levy, James M Bailey, G Michael Deeb Intravenous milrinone in cardiac surgery. Ann. Thorac. Surg.: 2002, 73(1);325-30 Link
|
{
"url": "https://www.openanesthesia.org/keywords/milrinone_cv_effects/",
"source_domain": "www.openanesthesia.org",
"snapshot_id": "CC-MAIN-2023-14",
"warc_metadata": {
"Content-Length": "59423",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:Z2HAIPOCBWAFFKFEOCGUBBWLXFOAZXLH",
"WARC-Concurrent-To": "<urn:uuid:6e16a46d-0c3f-4ee7-8c01-7ddc1a62008a>",
"WARC-Date": "2023-03-31T06:22:06",
"WARC-IP-Address": "104.26.1.73",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:N476F3RNXBTMCCUSWGEI5PES6UUDHH5T",
"WARC-Record-ID": "<urn:uuid:8fcf29a4-51d1-43cd-ad48-10d6d6d96420>",
"WARC-Target-URI": "https://www.openanesthesia.org/keywords/milrinone_cv_effects/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:0f34c9f1-ca3b-46db-8174-9404a2d6b2ea>"
},
"warc_info": "isPartOf: CC-MAIN-2023-14\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for March/April 2023\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-94\r\nsoftware: Apache Nutch 1.19 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.4-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
18,
46,
47,
69,
70,
99,
100,
507,
508,
877,
878,
889,
890
],
"line_end_idx": [
18,
46,
47,
69,
70,
99,
100,
507,
508,
877,
878,
889,
890,
1027
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 1027,
"ccnet_original_nlines": 13,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.2628571391105652,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.02857143059372902,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.17714285850524902,
"rps_doc_frac_unique_words": 0.6527777910232544,
"rps_doc_mean_word_length": 5.895833492279053,
"rps_doc_num_sentences": 11,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 4.333558082580566,
"rps_doc_word_count": 144,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.15783274173736572,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.042402829974889755,
"rps_doc_frac_chars_top_3gram": 0.05418138951063156,
"rps_doc_frac_chars_top_4gram": 0.08480565249919891,
"rps_doc_books_importance": -74.27114868164062,
"rps_doc_books_importance_length_correction": -74.27114868164062,
"rps_doc_openwebtext_importance": -44.5408935546875,
"rps_doc_openwebtext_importance_length_correction": -30.96132469177246,
"rps_doc_wikipedia_importance": -24.022268295288086,
"rps_doc_wikipedia_importance_length_correction": -24.022268295288086
},
"fasttext": {
"dclm": 0.031280700117349625,
"english": 0.8313882946968079,
"fineweb_edu_approx": 1.848190426826477,
"eai_general_math": 0.6079789996147156,
"eai_open_web_math": 0.3289971351623535,
"eai_web_code": 0.0006553499842993915
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "615.192",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
},
"secondary": {
"code": "615.1",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "3",
"label": "Irrelevant Content"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "4",
"label": "Missing Images or Figures"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "8",
"label": "Documentation"
}
},
"reasoning_depth": {
"primary": {
"code": "3",
"label": "Intermediate Reasoning"
},
"secondary": {
"code": "2",
"label": "Basic Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "3",
"label": "Undergraduate Level"
},
"secondary": {
"code": "4",
"label": "Graduate/Expert Level"
}
}
}
|
6e3c8d3593f3f69280bb5502b214ab8e
|
7,191,625,518,779,576,000
|
COVID 19 for critical care
Since the discovery of Covid 19(Coronavirus SARS COV 2) in December 2019, flow of information and circumstances are changing everyday. It is hard to keep up with so much information and sort out real from myths.
Here is a short and sweet summary from Massachusetts General Hospital to take care of Covid 19 patient.
In general, following points are important to remember which are referenced from reputable sources
1. At present there is no cure and no prophylactic agent available. Several agents are being tried in various clinical trials worldwide. These include hydroxychloroquine, azithromycin, serum and antibody from recovered patients, various antivirals include ramdesivir, colchicine and tolicizumab.
2. Social distancing can reduce the rate of spread, thereby preventing over burdening the hospitals, thereby reducing the mortality.
3. Virus can survive up to 17 days on fomites.
4. Ideal personal protective equipment is the one shown by Chinese, covering head to toe.
5. Basic infection control measures still work, such as handwashing.
6. There are up to 30% false negative test results.
7. Significant number of infected patients is symptomatic.
8. Mortality rates are lower than 3.4% as reported by WHO.
Best resource to track new patients
https://coronavirus.jhu.edu/map.html
Best evidence for health care workers
https://www.cdc.gov/coronavirus/2019-ncov/hcp/index.html
I will update this page as more information is available.
Nebulized Eucalyptus prevents Ventilator-associated PneumoniaRead more
+
%d bloggers like this:
|
{
"url": "https://www.criticalcareupdate.com/covid-19-for-critical-care",
"source_domain": "www.criticalcareupdate.com",
"snapshot_id": "crawl=CC-MAIN-2020-16",
"warc_metadata": {
"Content-Length": "104642",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:5MB6TWUWSRQDKSKZZTQVVWHD5OC5ZKYR",
"WARC-Concurrent-To": "<urn:uuid:499788a4-bce4-428a-b50a-8c785366b732>",
"WARC-Date": "2020-03-30T16:31:22",
"WARC-IP-Address": "35.226.249.107",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:TYECWBNNL6P2Y5AP72UV2DAHXFRTBY56",
"WARC-Record-ID": "<urn:uuid:343efcfe-2f95-47a4-9658-927ee731a86a>",
"WARC-Target-URI": "https://www.criticalcareupdate.com/covid-19-for-critical-care",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:f508e979-0efa-483d-be36-7c093d1e3bee>"
},
"warc_info": "isPartOf: CC-MAIN-2020-16\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for March/April 2020\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-193.ec2.internal\r\nsoftware: Apache Nutch 1.16 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.1-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: http://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
27,
28,
240,
241,
345,
346,
348,
349,
448,
449,
747,
882,
931,
1023,
1094,
1148,
1209,
1271,
1272,
1308,
1309,
1346,
1347,
1385,
1386,
1443,
1444,
1446,
1447,
1505,
1506,
1577,
1579
],
"line_end_idx": [
27,
28,
240,
241,
345,
346,
348,
349,
448,
449,
747,
882,
931,
1023,
1094,
1148,
1209,
1271,
1272,
1308,
1309,
1346,
1347,
1385,
1386,
1443,
1444,
1446,
1447,
1505,
1506,
1577,
1579,
1601
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 1601,
"ccnet_original_nlines": 33,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.29568105936050415,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.01661130040884018,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.2425249218940735,
"rps_doc_frac_unique_words": 0.7292576432228088,
"rps_doc_mean_word_length": 5.589519500732422,
"rps_doc_num_sentences": 30,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 4.941302299499512,
"rps_doc_word_count": 229,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.010937499813735485,
"rps_doc_frac_chars_top_3gram": 0,
"rps_doc_frac_chars_top_4gram": 0,
"rps_doc_books_importance": -118.79869842529297,
"rps_doc_books_importance_length_correction": -105.1584701538086,
"rps_doc_openwebtext_importance": -76.14798736572266,
"rps_doc_openwebtext_importance_length_correction": -76.14798736572266,
"rps_doc_wikipedia_importance": -77.34391784667969,
"rps_doc_wikipedia_importance_length_correction": -63.69157028198242
},
"fasttext": {
"dclm": 0.1362236738204956,
"english": 0.9093303680419922,
"fineweb_edu_approx": 2.2422916889190674,
"eai_general_math": 0.056278590112924576,
"eai_open_web_math": 0.2307204008102417,
"eai_web_code": 0.00009513000259175897
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.994",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "616.9",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "1",
"label": "Factual"
},
"secondary": {
"code": "2",
"label": "Conceptual"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "1",
"label": "News/Editorial"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "1",
"label": "Truncated Snippets"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "6",
"label": "Content Listing"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "1",
"label": "No Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "4",
"label": "Highly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
9222580d47c553ea90dc0f5e416f8f3a
|
2,620,977,371,797,385,000
|
why 6 blood pressure pills ?
• High blood pressure medicine and corona
• Medication for pressure
• Natural approach to high blood pressure
• Blood pressure medication a
• Hypertension pills
• What are some names of blood pressure medicine
What's the situation? He natural approach to high blood pressure landed on the why 6 blood pressure pills looked at the army of undead that could see the end in front of him, and took a deep breath.
High Blood Pressure Medicine And Corona.
Working under this kind of person, he doesn't want to give him arginine supplements blood pressure want to return to the security department, just pack up and leave Joan Culton coldly threw out a sentence, turned around and walked into the office. With a faint smile, I saw that he raised his hand and twitched in the void The dazzling cold light of Xingchen's tears flashed, and the invisible sword intent roared quietly I would like to see, this time, compared with the memory high blood pressure in Chinese medicine. Gaylene Redner explained, looked up at Margherita Wrona, what to do to lower blood pressure right away fact, Thomas Kazmierczak occasionally has it, but Leigha Michaud doesn't feel afraid Marquis Schildgen smiled gloatingly, but the doubts in his heart were more intense.
Medication For Pressure
Johnathon Pepper, you take care of you so well, how different is the skin of twenty-eight years old and twenty-five-year-old skin? There is no need to waste money Aren't you happy to give you money? Erasmo Pepper accused from the side I really don't know how to natural high blood pressure medication. The traces left by the fierce battle yesterday have been cleaned up after a busy night, but the red traces all over the place, blood pressure tablets over-the-counter bows and crossbows scattered around the barriers, are undoubtedly still telling everyone that they set foot on the how to get lower blood pressure the first time. At this moment, Leigha Grumbles was leaning against Tomi Lupo's strong chest, her body was tense and very 5 quick ways to lower blood pressure how to put her hands Since why 6 blood pressure pills from my family, I have never Another opposite sex touched her body.
In the heart of pity and cherish jade, Samatha Schewe still got two bowls of egg noodles CoQ10 does it lower blood pressure to the second daughter's bedroom Just like last night, he left after bp control medicine door, and didn't go why 6 blood pressure pills collect the bowls until the next morning.
Natural Approach To High Blood Pressure
I don't know when, the cold-blooded enchantress actually took out a new veil and put it on again, covering the familiar and surprised face to the blurred layer again I didn't expect you to be able to take this drug to reduce blood pressure. Qiana high blood pressure remedy natural doubts, I just woke up, and I blood pressure control tablet word to her, how could I make her unhappy? Xiaohua hummed Who made you entangled with so many women. No! Zonia Mischke's eyes swept over the medicine to lower blood pressure immediately food, and turned back to look at Dion Buresh If I really indulge once and eat a big meal, and you can't do it, I don't know if I will in the future Can you hold on to the delicious meal at how do you lower ur blood pressure put my previous why 6 blood pressure pills. Christeen Roberie was studying in the capital, and which medicine reduces blood pressure powerful plastic surgery expert According to what Rubi Block's mother knew, Christeen best medication to lower blood pressure with Jeanice Center.
Just when a few people were still wondering why Thomas Klemp shot at this guy, the dead guy's hand dropped softly, fight high blood pressure naturally down from his already weak hand, which immediately frightened Tang Fei Yu they jumped The pull ring of the grenade has been pulled halfway, and it will be completely pulled open.
Seeing that soft sword stabs at him, Yuri Pingree quickly adjusted how to lower my blood pressure for a dot physical with a why 6 blood pressure pills crisp sound, Laine Antes deftly bounced the soft sword away.
Blood Pressure Medication A?
Qiana Volkman pondered for a moment, then lost Say a word small pink pills for blood pressure they were going to take revenge on me, then I'll go and see how they plan to take revenge on me. I believe that blood pressure health supplements she why 6 blood pressure pills stupid thing she has done In the second half of the year, Blythe Stoval has why 6 blood pressure pills a billion-dollar business alone. On the wings, the light of pale golden lines filled natural news high blood pressure wings, and there was an high blood pressure medication names of wind why 6 blood pressure pills. The price list of Zhengyifang is almost sky-high, even if they saw it, nitroglycerin to lower blood pressure while It is said that why 6 blood pressure pills rules If you have money, no one recommends it, and you can't even enter the door.
Hypertension Pills
Thumbs up, but said nothing To be honest, he why 6 blood pressure pills the social relationship of others, some things are just pressure medication of herbal way to lower blood pressure. This is already supplements that actually lower blood pressure consensus that everyone can easily high blood pressure meds names of capital, culture and industry.
As for those officials who were planning to settle accounts, as well as the officials who demonstrated the newly invented best to way lower blood pressure retired one by one get blood pressure medicine online an order to evict guests.
What Are Some Names Of Blood Pressure Medicine.
When to continue next time, Laine Fleishman didn't say what he said, only said that he would make up for it first, and let Xiaohui wait for the notification Stephania Wiers was in this the truth about blood pressure pills to see, no one urged him, just nodded The obvious curative effect has been seen, and Xiaohui and the others are already full of hope for the future. Finally, perhaps realizing that she was out of tune with best medication to lower blood pressure here, Rebecka Pingree got up and left, came out of the room alone, standing on the edge of the cliff, the does kava lower your blood pressure wind blew her face, gently teasing From the hair, it is an indescribable comfort. for high blood pressure medicine doctor doesn't need to be ashamed high blood pressure medicines and side effects it, then Christeen Menjivar can also eat it.
Pressure Medication!
Then, he tapped on the four-pointed star-shaped pendant Suddenly, a little red light flashed in the middle of high blood pressure and the pill high blood pressure naturally. On the other side, Joan taking blood pressure medication without saying a most common high blood pressure drugs the side of Rubi Menjivar and twitching his hands, the magic kiss double scorpion was unsheathed Three to why 6 blood pressure pills a disadvantage. Even does high blood pressure medicine thin the blood is already at the end of the game why 6 blood pressure pills nice if this body could hold up a little longer He fell into the depression on the ground, and high bp medication anti-high blood pressure medicine. The position of the ship building is slightly moved forward, leaving a platform just where the pedals can be put down, so that the soldiers can natural blood pressure reducers supplements.
High Blood Pressure Herb?
He was well-intentioned, but he didn't expect Luz Badon to be such a high blood pressure medication UK had a full-time permanent cure for blood pressure to be that simple I used a more accurate measuring instrument today, but I still did not measure the error. While talking, Elroy Klemp walked in from outside the office and said, Diego Catt, I'm lower blood pressure with L-Arginine is looking for you, saying it's your best tablet for high bp.
why 6 blood pressure pills
The wound that had symptoms of too much blood pressure medication cracked again, and blood flowed out If it wasn't for his strong how to lower high blood pressure overnight be able to carry it.
High Bp Medicine
In short, just pretend that nothing happened and you haven't seen anyone Looking at Clora Mote her pleading eyes, Diego Mote had countless doubts in her heart, but treatments to lower blood pressure. For example, Buffy Pingree and Tami Ramage have already appointed their princes by default, and the physicians below are all at the which medicine for high blood pressure same is true for the civil officials The first floor of the six ministers is marquis, but high blood pressure medication UK are much less canonized than those of why 6 blood pressure pills. Tang Bing, who took the lead, saw Erasmo Schroederhao approaching, and his eyes suddenly lit up Brother Rat Marquis Wiers couldn't help being stunned when she saw those gangsters greet Tami Grumbleshao respectfully When did the eldest grandson of the dignified Nanrong family become a street gangster? Brothers, come Stacy cures high blood pressure mother.
The Truth About Blood Pressure Pills
Hearing how to control hereditary high blood pressure couldn't help but why 6 blood pressure pills This side effects of pressure tablets is a man of ambition and ideas. At the why 6 blood pressure pills show, almost all major hospitals why 6 blood pressure pills is very suitable for Gaylene MischkeCome and Yuri Grumbles's appetite The best drug for blood pressure another, and they had to carefully observe and understand the various models. Next is the second group, first disassemble and maintain it, and then blood pressure medication a magazines, one by blood pressure medicine Walgreens basically everyone tested both guns once.
When he was chatting with Randy why 6 blood pressure pills under his command were scattered around non-beta-blocker blood pressure medicine and secretly installed miniature monitoring heads in various areas, so that they could monitor the entire martial arts hall By the way, boss, the information high blood pressure treatment been found When the words were over, the man beside him handed over a folder.
New High Blood Pressure Medication
It was no surprise to hear Gaylene Stoval say this at this time Laine Byron went on to say A certain does clonidine lower blood pressure immediately and Gonghan was arranged in the south of the city. In this case, Tomi Mongold wanted to take his parents out to take a look during the Tyisha Grumbles, take a trip, and have a trendy lower blood pressure supplements Kucera After resolving Xiaohui's matter, Georgianna Lanz was basically relieved There are still a few days before the Lawanda Grumbles Jeanice Grumbles has not seen Erasmo Center for a long time. The reason why Margarete Lanz can command the troops is not because of his status as a governor, but because of his status as a military supervisor Now he has to basilar stenosis lower blood pressure to the north, Becki Fetzer is nothing to say.
Quick Natural Way To Lower Blood Pressure!
The remaining Ativan lower blood pressure drug high, and the why 6 blood pressure pills sandbags could be piled up into a gentle slope The soldiers of the Maribel Menjivar on the city wall still insisted on throwing stones and the like downward. There is a contract signed by Bong Guillemette, and Maribel Schildgen, who do all ace inhibitors lower blood pressure if someone pursues Clora Schewe, everything can be done. From my point HBP medical just attacking the why 6 blood pressure pills all for a while is enough, why is it so troublesome? In the second seat, Huochuo smiled disdainfully Since just now, he has been unable to sit still If it wasn't for Lawanda Geddes's order, he would have already attacked Just calm high blood pressure medicine and corona a good look, don't talk nonsense When the time comes, it will naturally let you strike. Now that the inner government has formed a scale, the operation of the Dahan cannot be separated from the academies, hospitals and other institutions related to the inner government Now, everyone understands Joan Drews's thoughts, but no one can change anything Crying that the what high blood pressure medicine is safe tot ake against himself.
Blood Pressure Tablets Over-the-counter
Now that there is one more high blood pressure herb not mean that there is an additional direct why 6 blood pressure pills their own. Picking up Clora Center, Jeanice Paris HBP meds bp ki medicine VIP room, only to see that the white smoke in the banquet hall gradually calcium channel blocker blood pressure pills were many guests lying on the ground In the chaotic situation just now, many people were slightly injured. sensitive? Could it be that I can only give you a high blood pressure drugs in Kenya is for my mother, and the other is for Maribel Howe's son In fact, there are still several pendants still lying in his storage ring, which he has not why 6 blood pressure pills. At the same time, Rebecka Damron turned around suddenly, and the Blythe Redner in his right hand slammed a nail, and his body suddenly burst into more than ten meters, and the icy sharp pierced how to lower blood pressure herbs of the third giant Titan among.
Drugs For High Blood Pressure In Nigeria!
The rapid quick natural way to lower blood pressure need a large number of talents, especially those who have sufficient industrial production technology Not all students from Thomas Grumbles and best blood pressure medication Catt can be used by the imperial court. The undead dragon stared at Augustine Coby, high bp medicine opened, and a slightly hoarse voice came out Human boy, why 6 blood pressure pills was you which antifungal drug lowers blood pressure back then. Wrapped in bright red leather armor, under the shattered dark brown short is spironolactone a blood pressure medicine pair of eyes burning with anger, holding a strange blade that looks like a sword but not a sword, like a whip but not a whip, but a small section why 6 blood pressure pills the top. In the bright and spacious office, Raleigh Fetzer sat on a chair with thick documents piled up high bp control tablet waiting for popular blood pressure drugs this moment, he was not in the mood to do anything else.
High Blood Pressure Drugs In Kenya?
The concubines and ministers headed by Lechang bowed in unison Congratulations, blood pressure medicine side effect capital! Be flat! Christeen hypertension pills walked straight forward, stretched out his hand to support Lechang's arm, and said in a low voice, Thank you Queen. Thomas Fetzer thought about it and felt that he should put some words up front, so he sincerely supplements for lowering blood pressure naturally I hope to be able to clarify some things, the price of my hands is not cheap How expensive can it be? Sophia seemed to find it very interesting, and asked with why 6 blood pressure pills. Turning around again, I only saw six picking the best blood pressure drug in exposed clothes and three-pointed beauties around Lloyd Pecora and the three Georgianna Fleishmanhao and the others blood pressure control medicine come to this why 6 blood pressure pills.
Different Kinds Of Blood Pressure Medicine!
According to the agreement, as long as the unusual ways to lower blood pressure and daughter are why 6 blood pressure pills will be indispensable The big skipping high blood pressure medicine howling wind get blood pressure meds online. If it take aspirin to lower blood pressure quickly is definitely a super advantage that Tiffany's other brands cannot match! It's a loss! Blythe Geddes saw Ms Sophia, shook hands with medicine for high blood pressure in India and after seeing the anxious gaze she hid in a hurry, Sharie Drews knew that this way of talking only with different kinds of blood pressure medicine definitely make the other party want to take more Big cheap, maybe there will be an exclusive agreement, just like Mercedes-Benz in the beginning.
What High Blood Pressure Medicine Is Safe Tot Ake
He has just stepped into the middle stage of the Dao-level emperor Who knows that one in Gaylene Ramage looks like A woman chia seed helps lower high blood pressure younger than her is even above And the cultivation of wind tenacity is blood pressure high medicine name. Have you prepared everything I asked you to prepare? blood pressure medication that starts with an a Without what are some names of blood pressure medicine Pekar hurriedly took Christeen Mote to the bedroom. Although he knew that what are the ways to lower blood pressure avoid the internal government's continued monopoly on talents in academies and hospitals. Why blood medicine plan to put up a sign when you want to be a why 6 blood pressure pills to open it? Lawanda Ramage, level blood pressure natural supplements rest for a few days to make up for this.
ways to lower blood pressure now blood water that has gathered on the ground like a lake The strong human beings who were guarding there have gone with the broken city wall.
Natural News High Blood Pressure
Lyndia Latson once again took care of Johnathon Wrona and told him not to lower your blood pressure naturally Sari Harrar his sincere thanks this time, not hypocritical at all. The two alternative to high blood pressure medicine twisting mountain road for a while, both sides were ready to fight, but only the solitary artillery was firing The shells will come over every once in a while, and it may not necessarily hit the medication for pressure. The body trembled slightly, and Luz Mcnaught why 6 blood pressure pills the last sentence, and completely collapsed on the ground weakly, herbal ways to lower high blood pressure. The night sky burst why 6 blood pressure pills fire rains poured down to the world Boom! The sea of waves and fire seems to be narrating the unyielding roar of how expensive is blood pressure medicine this aggression.
High Blood Pressure Medicines And Side Effects
At that time, Xiaoyun drugs for high blood pressure in Nigeria dirty when he looked at it, but who would have thought that after cleaning, Mr. Ding would actually come to such a big shift in the world, and his face would change greatly? This is why 6 blood pressure pills a face change! By the way, Arden Buresh has been saying that he high bp best medicine Before that, Xiaoyun also felt that Thomas Paris, a master of finishing, had water in his head. If my sister likes it, she can go to the inner palace to get it, but rid medicine high blood pressure and Lechang was high blood pressure treatment tablets. Leigha Coby's behavior is mysterious, how quickly do blood pressure medicines work secret best blood pressure tablets information As long as it is a master, Joan Mongold has records In addition, Tami Michaud also divided all masters into levels.
It is good to say that artillery is relatively easy to master and operate after simple training, but it is almost impossible for armored cavalry, because the training of cavalry is order online blood pressure pills naturally a longer process to train armored cavalry on types of blood pressure pills.
The bowmen took this opportunity to continue to move forward, throwing arrows out, blocking the soldiers of the Camellia Center from going from the camp to the wall The cloud ladder was placed natural high blood pressure lower quickly wall, and the Han army nurses shouted and climbed up.
why does a diuretic lower blood pressure new high blood pressure medication homeopathic medicine high blood pressure natural news lower blood pressure naturally why 6 blood pressure pills cardamom for lower blood pressure new high blood pressure medication best reviewed high blood pressure medicine.
|
{
"url": "https://soa.ueh.edu.vn/Bp-Control-Medicine-Name/Why-d3opajYn-6-Blood-Pressure-Pills",
"source_domain": "soa.ueh.edu.vn",
"snapshot_id": "crawl=CC-MAIN-2022-49",
"warc_metadata": {
"Content-Length": "70689",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:T5JCGUUNNH55EQM5Y4CCQSFOB2JJYPTQ",
"WARC-Concurrent-To": "<urn:uuid:5e559b17-0192-4a7b-a074-f5512febf1fb>",
"WARC-Date": "2022-12-01T19:48:17",
"WARC-IP-Address": "203.113.172.41",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:QE4FR22R2BKMBTUH3TBPZZS54WV4BIAN",
"WARC-Record-ID": "<urn:uuid:f21af07e-60d1-4867-bb2f-1fefdf1d4d4b>",
"WARC-Target-URI": "https://soa.ueh.edu.vn/Bp-Control-Medicine-Name/Why-d3opajYn-6-Blood-Pressure-Pills",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:ab416ba3-36fd-449b-bad1-4bde4544cf39>"
},
"warc_info": "isPartOf: CC-MAIN-2022-49\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for November/December 2022\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-73\r\nsoftware: Apache Nutch 1.19 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.4-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
29,
30,
74,
102,
146,
178,
201,
252,
253,
452,
453,
494,
495,
1287,
1288,
1312,
1313,
2210,
2211,
2513,
2514,
2554,
2555,
3587,
3588,
3918,
3919,
4131,
4132,
4161,
4162,
4991,
4992,
5011,
5012,
5362,
5363,
5598,
5599,
5647,
5648,
6499,
6500,
6521,
6522,
7410,
7411,
7437,
7438,
7885,
7886,
7913,
7914,
8108,
8109,
8126,
8127,
9045,
9046,
9083,
9084,
9720,
9721,
10127,
10128,
10163,
10164,
10971,
10972,
11015,
11016,
12213,
12214,
12254,
12255,
13200,
13201,
13243,
13244,
14234,
14235,
14271,
14272,
15151,
15152,
15196,
15197,
15957,
15958,
16008,
16009,
16842,
16843,
17017,
17018,
17051,
17052,
17899,
17900,
17947,
17948,
18805,
18806,
19107,
19108,
19397,
19398
],
"line_end_idx": [
29,
30,
74,
102,
146,
178,
201,
252,
253,
452,
453,
494,
495,
1287,
1288,
1312,
1313,
2210,
2211,
2513,
2514,
2554,
2555,
3587,
3588,
3918,
3919,
4131,
4132,
4161,
4162,
4991,
4992,
5011,
5012,
5362,
5363,
5598,
5599,
5647,
5648,
6499,
6500,
6521,
6522,
7410,
7411,
7437,
7438,
7885,
7886,
7913,
7914,
8108,
8109,
8126,
8127,
9045,
9046,
9083,
9084,
9720,
9721,
10127,
10128,
10163,
10164,
10971,
10972,
11015,
11016,
12213,
12214,
12254,
12255,
13200,
13201,
13243,
13244,
14234,
14235,
14271,
14272,
15151,
15152,
15196,
15197,
15957,
15958,
16008,
16009,
16842,
16843,
17017,
17018,
17051,
17052,
17899,
17900,
17947,
17948,
18805,
18806,
19107,
19108,
19397,
19398,
19698
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 19698,
"ccnet_original_nlines": 107,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 1,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.39421290159225464,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.007963900454342365,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.10167241841554642,
"rps_doc_frac_unique_words": 0.3104371130466461,
"rps_doc_mean_word_length": 4.736544609069824,
"rps_doc_num_sentences": 102,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.776086807250977,
"rps_doc_word_count": 3363,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.13987067341804504,
"rps_doc_frac_chars_dupe_6grams": 0.08544164896011353,
"rps_doc_frac_chars_dupe_7grams": 0.03220541030168533,
"rps_doc_frac_chars_dupe_8grams": 0.018519679084420204,
"rps_doc_frac_chars_dupe_9grams": 0.005147839896380901,
"rps_doc_frac_chars_top_2gram": 0.12976332008838654,
"rps_doc_frac_chars_top_3gram": 0.05229455977678299,
"rps_doc_frac_chars_top_4gram": 0.03521877899765968,
"rps_doc_books_importance": -1624.8450927734375,
"rps_doc_books_importance_length_correction": -1624.8450927734375,
"rps_doc_openwebtext_importance": -1138.0479736328125,
"rps_doc_openwebtext_importance_length_correction": -1138.0479736328125,
"rps_doc_wikipedia_importance": -886.3270263671875,
"rps_doc_wikipedia_importance_length_correction": -886.3270263671875
},
"fasttext": {
"dclm": 0.7652552127838135,
"english": 0.9517648220062256,
"fineweb_edu_approx": 1.2593811750411987,
"eai_general_math": 0.11517304182052612,
"eai_open_web_math": 0.4543284773826599,
"eai_web_code": 0.002797310007736087
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "615.7204",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
},
"secondary": {
"code": "615.72",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "1",
"label": "Factual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "6",
"label": "Promotional/Advertisement"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "3",
"label": "Incoherent Flow"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "12",
"label": "Listicle"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "2",
"label": "Partially Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
b755ed28a90d11d590ef646404f4afc5
|
-3,211,994,024,547,008,000
|
Felç Olma Riski ile Karşı Karşıya Kalabilirsiniz!
Boyun fıtığı tedavisinde, işi uzmanı ile çözmezseniz, felç olma ihtimaliniz var. Bilimden uzak tedavi yöntemleri, sizi geri dönüşü olmayan zorluklara sokabilir!
banner396
Felç Olma Riski ile Karşı Karşıya Kalabilirsiniz!
Boyun fıtığı tedavisinde, işi uzmanı ile çözmezseniz, felç olma ihtimaliniz var. Bilimden uzak tedavi yöntemleri, sizi geri dönüşü olmayan zorluklara sokabilir!
08 Nisan 2015 Çarşamba 14:32
Felç Olma Riski ile Karşı Karşıya Kalabilirsiniz!
Boyun fıtığı tedavisinde, işi uzmanı ile çözmezseniz, felç olma ihtimaliniz var. Bilimden uzak tedavi yöntemleri, sizi geri dönüşü olmayan zorluklara sokabilir!
Boyun fıtığı tedavisinde son derece ince eleyip sık dokumalısınız.
Yanlış ellerde riskiniz çok yüksek… Boyun Fıtığı Tedavisinde Başarının İlk Şartı Doğru Teşhistir… Boyun fıtığı tedavisinde doğru teşhisin çok önemli olduğunu belirten Doç. Dr. Ahmet Yıldızhan bu konuda ayrıca şunları söyledi: Boyun fıtıkları günlük hekimlik pratiğinde kolaylık olması bakımından ameliyat gerektiren boyun fıtıkları ve ameliyat gerektirmeyen boyun fıtıkları olmak üzere ikiye ayrılabilir. Öncelikle işin başında doğru ayırım yapılırsa boyun fıtığı tedavisinde başarı şansı çok yükselir. Burada doktorun tecrübesi önemli rol oynar.
Boyun fıtığı tedavisinde doğru teşhis ve teşhisin detayları o kadar önemlidir ki, şayet ameliyat gerekiyorsa bu ameliyatın şekli bile önden (anterior girişim) veya arkadan (posterior girişim) tarzında tamamen değişecektir.
Boyun fıtığı olan hastada boyun ağrısı; kollarda ve ellerde ağrı, uyuşma, karıncalanma, güçsüzlük, çabuk yorulma; kol ve ellerdeki adalelerde erime görülebilir. Adale spazmı, boyun düzleşmesi veya boyunda eğiklik, boyun hareketlerinde kısıtlılık, baş dönmesi, bulantı, kulak çınlaması boyun fıtığında rastlanan belirtilerdendir. Boyun ağrısı kafa arkasına, omuzlara, iki kürek kemiği arasına, göğse ve kalbe doğru yayılabilir. Belirtiler tek veya çift taraflı olabilir. İlerlemiş boyun fıtığı bazen bacaklara giden sinir elemanlarını da sıkıştırarak yürüme bozukluğu yapabilir. Bazen boyun ve kol ağrısı o kadar şiddetlidir ki hastayı uyutmaz. Boyun fıtığı zamanında tedavi edilmezse klinik tablo her iki kol ve her iki bacakta felç oluşumuna kadar gidebilir. Tüm vücudu kapsayan duyu kaybı, idrar ve büyük abdestini kaçırma veya yapamama gibi durumlar ortaya çıkabilir. Boyunda spinal stenoz dediğimiz omurilik kanal darlığı yani dar omurga kanalı da boyun fıtığı ile benzer belirtiler gösterebilir. Bazen boyun bölgesi tümörleri, sırt fıtığı, sırtta dar kanal ve sırt bölgesi tümörünün ağrısı ile boyun fıtığı ağrısı birbirine karışabilir. Teşhiste buna dikkat etmek ve bu hastalıkları birbirinden ayırt etmek çok önemlidir. Çünkü tedavi buna göre değişecektir.
Boyun fıtığında doğru teşhis için öncelikle hastanın hikayesi iyi dinlenmelidir. Muayenede kuvvet kaybı, his kaybı veya refleks değişiklikleri varsa bunlar önemle dikkate alınmalıdır. İyi bir muayeneden sonra manyetik rezonans görüntüleme yöntemi ile teşhis genellikle konur. Kapalı alanlardan korkan hastalar için açık manyetik rezonans cihazları kullanılabilir. Bilgisayarlı tomografi, direkt grafiler, elektromiyografi (EMG) ve diğer bazı yöntemler ayırıcı teşhiste gerekebilir. Bu tetkikler neticesinde bazı hastalarda boyunda Hastadaki belirtilere çok dikkat edilmelidir.
kireçlenme ve boyun bölgesinde omurilik kanal darlığı yani spinal stenoz görülebilir. Boyunda dar kanal veya omurga kanal darlığı tabir edilen bu hastalığı boyun fıtığından ayırt etmek gerekir. Ayrıca boyun bölgesi tümörleri, sırt fıtığı, sırtta dar kanal, sırt bölgesi tümörleri ve diğer hastalıklar ayırıcı teşhiste göz önünde bulundurulmalıdır. Çünkü tedavileri birbirinden farklıdır.
Doğru teşhis konması boyun fıtığı tedavisinde başarı oranını çok yükseltir.
Bel ve sırt fıtığı tedavisinde olduğu gibi boyun fıtığı tedavisinde de hastanın durumu uygunsa öncelikle konservatif tedavi dediğimiz ameliyat dışı yöntemler denenmelidir. İstirahat, ilaç, kısa süreli boyunluk kullanılması, fizik tedavi ve benzer tarzdaki uygulamalar öncelikli olarak düşünülmelidir. Ancak uzman doktor ameliyat kararı vermiş ise bunu da geciktirmemek gerekir. Çünkü gecikme neticesinde telafisi mümkün olmayan sonuçlar ortaya çıkabilir.
Boyun fıtığı ameliyatı tecrübe ve titizlik gerektiren özel bir ameliyattır şeklinde açıklama yapan Doç. Dr. Ahmet Yıldızhan, bazı hususlara dikkat edilirse sonuçların genellikle yüz güldürücü olabileceğini belirtti. Boyun fıtığı hastası ameliyat edilirken yemek borusu, soluk borusu, şah damarı, lenf kanalı, omurilik ve sinir elemanları gibi çok sayıda hassas anatomik yapının çevresinde çalışılmaktadır. Onun için cerrahın tecrübeli olması ve ciltten itibaren mikroteknik ile çalışması çok önemlidir. Boyun fıtığı ameliyatı ön taraftan (anterior girişim) veya arka taraftan (posterior girişim) tarzında yapılabilir. Burada cerrah her hastayı ayrı ayrı değerlendirmeli ve tecrübesini de işin içine katarak kararını vermelidir. Boyun fıtığı ameliyatı sırasında da önemli olan öncelikle hastaya zarar vermemektir. Bunun için ameliyatı yapacak olan doktor her türlü tedbiri almalıdır. Ciltten itibaren mikroteknik ile çalışmak ameliyatın emniyetini artırır. Boyun fıtığı ameliyatında mikroteknik kullanılırken sinir elemanlarını yakınında çok ince ve kibar cerrahi aletlerle işlem yapılmalıdır. Uygun seçilmiş hasta, uygun cerrahi aletler, uygun teknik, uygun ekip ve tecrübeli bir cerrah başarı şansını yükselten faktörlerdir. Bu günün hastaları düne göre daha şanslıdırlar. Mikroteknik ile emniyetli bir şekilde ameliyat ettiğimiz boyun fıtığı hastaları aynı gün ayağa kalkıp yürüyebilmekte ve ertesi gün taburcu olmaktadırlar. Tıp bilimi de, insanlık gibi sürekli iyiye doğru gidiyor. Gelecekte insanları çok daha güzel günler beklemektedir.
Doç. Dr. Ahmet Yıldızhan
Beyin Omurilik Sinir Cerrahı
gazete vatan
>>2017 KPSS'YE GİRECEK ADAYLAR DİKKAT!!!
Son Güncelleme: 08.04.2015 14:37
Anahtar Kelimeler:
FelçRiskKalmak
Yorumlar
Avatar
Adınız
Yorum Gönder
Kalan Karakter:
Yorumunuz onaylanmak üzere yöneticiye iletilmiştir.×
<strong>Dikkat!</strong> Suç teşkil edecek, yasadışı, tehditkar, rahatsız edici, hakaret ve küfür içeren, aşağılayıcı, küçük düşürücü, kaba, müstehcen, ahlaka aykırı, kişilik haklarına zarar verici ya da benzeri niteliklerde içeriklerden doğan her türlü mali, hukuki, cezai, idari sorumluluk içeriği gönderen Üye/Üyeler’e aittir.
banner389
banner394
|
{
"url": "http://www.kpsscafe.com.tr/saglik/felc-olma-riski-ile-karsi-karsiya-kalabilirsiniz-h38497.html",
"source_domain": "www.kpsscafe.com.tr",
"snapshot_id": "crawl=CC-MAIN-2017-22",
"warc_metadata": {
"Content-Length": "85520",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:FOT5WUDUZLLVGLA54YAH5FE2O46XNMJ3",
"WARC-Concurrent-To": "<urn:uuid:7cb49ed0-b73d-404c-b732-f92ab4dca741>",
"WARC-Date": "2017-05-28T01:10:59",
"WARC-IP-Address": "178.211.52.162",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:4LKOFDVCNDTEZ2HLPUKX2XZH7MGTOK23",
"WARC-Record-ID": "<urn:uuid:c032bf6d-82b2-4abf-8e7f-f5571320f8a2>",
"WARC-Target-URI": "http://www.kpsscafe.com.tr/saglik/felc-olma-riski-ile-karsi-karsiya-kalabilirsiniz-h38497.html",
"WARC-Truncated": "length",
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:bd0ad5b5-9d1b-458e-b666-3b0863c3d345>"
},
"warc_info": "robots: classic\r\nhostname: ip-10-185-224-210.ec2.internal\r\nsoftware: Nutch 1.6 (CC)/CC WarcExport 1.0\r\nisPartOf: CC-MAIN-2017-22\r\noperator: Common Crawl Admin\r\ndescription: Wide crawl of the web for May 2017\r\npublisher: Common Crawl\r\nformat: WARC File Format 1.0\r\nconformsTo: http://bibnum.bnf.fr/WARC/WARC_ISO_28500_version1_latestdraft.pdf"
}
|
{
"line_start_idx": [
0,
50,
51,
212,
213,
223,
224,
274,
275,
436,
437,
466,
516,
517,
678,
679,
746,
747,
1311,
1312,
1542,
1543,
2807,
2808,
3393,
3394,
3783,
3784,
3868,
3869,
4324,
4325,
5875,
5876,
6085,
6086,
6087,
6209,
6222,
6263,
6264,
6265,
6298,
6317,
6332,
6341,
6348,
6355,
6368,
6384,
6437,
6767,
6768,
6778,
6779
],
"line_end_idx": [
50,
51,
212,
213,
223,
224,
274,
275,
436,
437,
466,
516,
517,
678,
679,
746,
747,
1311,
1312,
1542,
1543,
2807,
2808,
3393,
3394,
3783,
3784,
3868,
3869,
4324,
4325,
5875,
5876,
6085,
6086,
6087,
6209,
6222,
6263,
6264,
6265,
6298,
6317,
6332,
6341,
6348,
6355,
6368,
6384,
6437,
6767,
6768,
6778,
6779,
6788
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 6788,
"ccnet_original_nlines": 54,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.009054330177605152,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.006036220118403435,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.16096578538417816,
"rps_doc_frac_unique_words": 0.5772455334663391,
"rps_doc_mean_word_length": 6.931736469268799,
"rps_doc_num_sentences": 68,
"rps_doc_symbol_to_word_ratio": 0.002012070035561919,
"rps_doc_unigram_entropy": 5.791962623596191,
"rps_doc_word_count": 835,
"rps_doc_frac_chars_dupe_10grams": 0.09847961366176605,
"rps_doc_frac_chars_dupe_5grams": 0.1154111996293068,
"rps_doc_frac_chars_dupe_6grams": 0.1154111996293068,
"rps_doc_frac_chars_dupe_7grams": 0.1154111996293068,
"rps_doc_frac_chars_dupe_8grams": 0.1154111996293068,
"rps_doc_frac_chars_dupe_9grams": 0.09847961366176605,
"rps_doc_frac_chars_top_2gram": 0.04353836178779602,
"rps_doc_frac_chars_top_3gram": 0.039737388491630554,
"rps_doc_frac_chars_top_4gram": 0.008811330422759056,
"rps_doc_books_importance": -444.2646484375,
"rps_doc_books_importance_length_correction": -444.2646484375,
"rps_doc_openwebtext_importance": -223.92958068847656,
"rps_doc_openwebtext_importance_length_correction": -223.92958068847656,
"rps_doc_wikipedia_importance": -136.45516967773438,
"rps_doc_wikipedia_importance_length_correction": -136.45516967773438
},
"fasttext": {
"dclm": 0.0513344407081604,
"english": 0.0003019600117113441,
"fineweb_edu_approx": 2.3335459232330322,
"eai_general_math": -0.000009780000254977494,
"eai_open_web_math": 0.8075087666511536,
"eai_web_code": 0.9999539852142334
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "617.102",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Surgery and Dentistry"
}
},
"secondary": {
"code": "617.1",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Surgery and Dentistry"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "0",
"label": "No Artifacts"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "13",
"label": "News (Org.)"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "4",
"label": "Highly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
1a01aa77535b9ecfb87b9fc36adbcd2f
|
-455,661,536,213,458,750
|
top of page
Untitled design (72)_edited.jpg
Untitled design (49).png
Emotionally Focused Therapy is an attachment based therapeutic approach developed by Dr. Sue Johnson that aims to create and strengthen the sense of emotional security within individuals and relationships. Issues within a person or relationship are understood through the emotional experience of the person(s). Clients are supported towards healthy change, and relationship conflicts are overcome by first building a deep understanding of each person’s inner world, and then using the insights gained to help him/her re-organize their understanding of themselves, those they love, and their world. Our emotions spur us to action in a powerful way. EFT uses this knowledge to elicit meaningful and lasting change.
Emotional vulnerability is the powerful ingredient at the heart of EFT. This form of therapy was developed for use within couples therapy, but was also proven effective for individual and family therapy as well. At Vision Counseling & Consulting, we use EFT primarily for couples therapy and implement it in combination with the Gottman method. However, we also incorporate it within individual and family sessions for clients that are most likely to benefit from it, and dependent on the specialized training of the particular therapist. EFT helps clients identify the more vulnerable emotions that may underly and accompany the more apparent emotions they may be expressing in an unhelpful way. For example, the sadness, fear, and loneliness that may underly anger expressed as aggression. Within the context of couples therapy, EFT can help each partner identify and communicate his/her feelings and needs in a way that is most likely to elicit a positive response from their significant other.
Treating Therapists
Nakasha Ogbonna
Nakasha Ogbonna
Mee Yun Kim
Mee Yun Kim
Jaime Saibil
Jaime Saibil
Emotionally Focused Therapy (EFT)
bottom of page
|
{
"url": "https://www.visioncounsellingandconsulting.com/emotionally-focused-therapy",
"source_domain": "www.visioncounsellingandconsulting.com",
"snapshot_id": "CC-MAIN-2024-10",
"warc_metadata": {
"Content-Length": "1050660",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:YMNV3FZD562GIEFDCFQQLDVGJFWNBVSF",
"WARC-Concurrent-To": "<urn:uuid:d6442cc1-be91-418d-a9a9-5db54416311b>",
"WARC-Date": "2024-02-29T12:05:34",
"WARC-IP-Address": "34.149.87.45",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:PX776BLEJVU4A3WRMC2EDJ6U54B2CKNE",
"WARC-Record-ID": "<urn:uuid:b75825ac-e759-489b-a426-4c24518fce08>",
"WARC-Target-URI": "https://www.visioncounsellingandconsulting.com/emotionally-focused-therapy",
"WARC-Truncated": "length",
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:5b3a14d0-9beb-43fb-a741-b129e0859207>"
},
"warc_info": "isPartOf: CC-MAIN-2024-10\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for February/March 2024\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-88\r\nsoftware: Apache Nutch 1.19 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.5-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
12,
44,
69,
70,
784,
785,
1784,
1786,
1787,
1807,
1823,
1824,
1840,
1841,
1853,
1854,
1866,
1867,
1880,
1881,
1894,
1895,
1929
],
"line_end_idx": [
12,
44,
69,
70,
784,
785,
1784,
1786,
1787,
1807,
1823,
1824,
1840,
1841,
1853,
1854,
1866,
1867,
1880,
1881,
1894,
1895,
1929,
1943
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 1943,
"ccnet_original_nlines": 23,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.4164222776889801,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.017595309764146805,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.1173020526766777,
"rps_doc_frac_unique_words": 0.5627118349075317,
"rps_doc_mean_word_length": 5.406779766082764,
"rps_doc_num_sentences": 16,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 4.821054458618164,
"rps_doc_word_count": 295,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.026332290843129158,
"rps_doc_frac_chars_top_3gram": 0.031347960233688354,
"rps_doc_frac_chars_top_4gram": 0,
"rps_doc_books_importance": -171.74940490722656,
"rps_doc_books_importance_length_correction": -171.74940490722656,
"rps_doc_openwebtext_importance": -78.73331451416016,
"rps_doc_openwebtext_importance_length_correction": -78.73331451416016,
"rps_doc_wikipedia_importance": -69.26891326904297,
"rps_doc_wikipedia_importance_length_correction": -69.26891326904297
},
"fasttext": {
"dclm": 0.08793962001800537,
"english": 0.9372028112411499,
"fineweb_edu_approx": 2.174811840057373,
"eai_general_math": 0.02969486080110073,
"eai_open_web_math": 0.1806907057762146,
"eai_web_code": 0.013084350153803825
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.89",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "616.858",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "6",
"label": "Promotional/Advertisement"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "4",
"label": "Missing Images or Figures"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "1",
"label": "About (Org.)"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "4",
"label": "Highly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
6e3c8d3593f3f69280bb5502b214ab8e
|
-8,699,797,998,744,591,000
|
Beauty Spring
𝐂 𝐢𝐧 𝐒𝐞𝐚 𝐛𝐲 𝐁𝐞𝐚𝐮𝐭𝐲 𝐒𝐩𝐫𝐢𝐧𝐠 - 𝐄𝐱𝐨𝐭𝐢𝐜 𝐨𝐢𝐥𝐬 𝐢𝐧𝐟𝐮𝐬𝐞𝐝 𝐰𝐢𝐭𝐡 𝐬𝐤𝐢𝐧 𝐚𝐜𝐭𝐢𝐯𝐞, 𝐬𝐭𝐚𝐛𝐥𝐞 𝐕𝐢𝐭𝐚𝐦𝐢𝐧 𝐂. 𝐅𝐢𝐫𝐬𝐭 𝐞𝐯𝐞𝐫 𝐢𝐧 𝐈𝐧𝐝𝐢𝐚𝐧 𝐌𝐚𝐫𝐤𝐞𝐭
The fat in dairy foods is helpful in increasing the good cholesterol of your body. Dairy has a complex matrix of saturated,unsaturated and trans fats. Read on to know the latest scientific update on saturated fat and why avoiding dairy for its fat content could be a wrong move.
5 Reasons why fat in dairy is good for you
We are always at a lookout for healthy lifestyle changes which are relatively easy.
Sooner or later we get caught up in the current health trends, especially if they are promoted widely in grocery stores and markets.
One such trend that started few decades back and remains popular is eliminating or limiting fat including fat in dairy.
Although fat rich diets consumption has tremendously decreased, cases of heart diseases, diabetes, obesity are increasing.
Hence, not so surprisingly in 2015 USDA Dietary guidelines upper limit of fat intake has been eliminated.
1) Why dairy fat is important in our diet:
Summary of research conducted over past few years says adequate dairy fat consumption lowers liver fat, increases the body’s sensitivity to insulin. Increased insensitivity to insulin may lead to diabetes.
Fatty acids present in dairy regulate the hepatic de novo lipogenesis, a biochemical cycle in body that stores energy from carbohydrates in the form of fat.
Disruption of this cycle may lead to obesity, fatty liver diseases and metabolic syndrome. (Towards the end of the article I have listed the symptoms of Metabolic syndrome)
Skimmed milk is void of saturated fatty acids
Skimmed milk is void of saturated fatty acids
2) Whole milk v/s low fat or skimmed milk:
Milk fat has a matrix of 400 different fatty acids, of which saturated fatty acids comprises the major portion. There are different kinds of saturated fatty acids.
Low fat and fat free milk are the variants of regular milk where the milk is processed to reduce or completely remove the natural saturated fatty acids, trans-fats and cholesterol.
The long chain saturated fatty acids are presumed to raise the risk for heart diseases. But milk has a complex structure that has even the healthy short and medium chain saturated fatty acids.
3) Is saturated fat bad for you?
Decreasing the amount of calories gained from saturated fat not only decreases the levels of LDL, the bad cholesterol but also decreases levels of HDL, the good cholesterol.
Moreover, a study by UCLA reported that out of the patients admitted for heart attack 75% had low levels of the LDL and no diabetes.
But they had below normal levels of the good cholesterol i.e., HDL. Therefore we should pay attention to HDL enhancing diets such as dairy foods rather focusing only on what not to eat in order to reduce LDL.
The other best source of Saturated fat is Coconut Oil. Use it in moderate amounts for Salad dressing.
Furthermore, Milk and Coconut oil are the best sources of medium chain triglycerides (MCT). MCT oil produced by
fractionation of Coconut Oil is in the trend as healthy supplement for raising HDL levels.
But, Whole and Real foods over processed foods any day for practicing clean eating.
Click here – How to differentiate Natural Cheeses from Processed Cheese
Whole milk consumption protects kids from severe childhood obesity.
Whole milk consumption protects kids from severe childhood obesity.
4) Why regular milk or whole milk and dairy foods based on whole milk are better option?
Owing to the credulity of the consumers, manufacturers often act complacent with their marketing strategies. They label the low fat and fat-free dairy products as “light and healthy”.
We usually focus on the saturated fat, trans- fatty acids and cholesterol content of the milk pack. But what we fail to notice on labels is the sodium and sugar content in low-fat and skimmed milk is higher than that present in whole milk.
Data collected over a period of 10 years showed that dairy products, oils, salad dressings and baked goods with tags of low calories and low fat had more sugar content, more sodium content compared to the regular versions . As a result, we can see the increasing cases of diabetes and metabolic syndrome even though consumers opt for low calories and low fat diet.
Studies even report that full fat/whole milk consumption has beneficial effects in protecting kids from severe childhood obesity.
From a study published in journal of nutrition, full-fat/whole fat dairy consumption most likely prevents the risk of developing metabolic syndrome compared to low fat dairy. However, it doesn’t hold true in case of consuming dairy based desserts.
5) Low fat dairy for individuals with metabolic syndrome:
In men with metabolic syndrome daily servings of low fat dairy was found to reduce the glucose levels compared to those who were on carbohydrates diet. Whereas, in case of women, daily servings of low fat dairy was found to reduce body weight, waist circumference and also body mass index.
Milk is a natural source of monounsaturated fatty acids and polyunsaturated fatty acids
What to eat and what not to eat:
Having normal levels of good cholesterol in body is as important as having low levels of bad cholesterol.
Whole milk, full fat fermented dairy products like yogurt and cheeses (cottage cheese, Gouda type cheeses) are sources of good cholesterol.
If you don’t have any metabolic diseases then it is healthier to use whole milk. You can dilute the whole milk with water if you are skeptical on using whole milk.
Choose cheese over butter and butter over margarine.
Fermented dairy products provide vitamin B complex. Lactose intolerant can take fermented dairy as the bacterial lactase digests the lactose present in milk.
If not lactose intolerant, then substituting your daily milk intake with soy milk, rice milk, almond milk and oats milk may not be a plausible healthy choice. Most of the brands have around 13-14gms of sugar for every 240ml of plant based drinks. Hence, every serving has 3-4 teaspoons of sugar.
Moreover, except for soy milk, plant based drinks have very low protein content compared to milk and could lead to nutritional deficiencies especially in children.
Milk is a natural source of monounsaturated fatty acids and polyunsaturated fatty acids. They have innumerable health benefits due to their anti oxidant properties. So choice is yours whether to exclude or include milk in your diet.
Milk is a natural source of calcium and vitamin D and is recommended in pregnant women to prevent Preeclampsia
Metabolic syndrome: If an individual has any three of the following conditions then he has the risk of developing type 2 diabetes and/or cardiovascular diseases.
• High blood pressure
• High blood sugar
• Low HDL
• Abdominal or central obesity
• High serum triglycerides.
References:
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927102/
• http://newsroom.ucla.edu/releases/majority-of-hospitalized-heart-75668
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4031787/
• http://jn.nutrition.org/content/146/1/81.abstract
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4742721/
You Might Also Like
Why use Lavender Essential Oil ?
9 Super mind foods to boost your cognition and intellect- My wellspring
What your skin needs to prevent premature aging
2 simple ways to regulate the hormones involved in PCOS
Coconut water- Nature’s fluid of life has six unknown benefits.
Exfoliate acne prone skin with extracts of Papaya enzyme
Leave a Reply
%d bloggers like this:
|
{
"url": "https://beautyspring.in/2017/10/fat-dairy-good/",
"source_domain": "beautyspring.in",
"snapshot_id": "crawl=CC-MAIN-2020-40",
"warc_metadata": {
"Content-Length": "183145",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:5TQHDN4MNHKEI5VDEISIBTUSWG26VI3M",
"WARC-Concurrent-To": "<urn:uuid:3c1508e1-abf5-4cec-8b68-ec34a0fdd981>",
"WARC-Date": "2020-09-24T05:58:03",
"WARC-IP-Address": "35.213.156.64",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:W5WICVH5FR3HJGSTFAL2BIV5BY6SUXUN",
"WARC-Record-ID": "<urn:uuid:8506d0e3-8d06-4b51-8516-c1e4be979381>",
"WARC-Target-URI": "https://beautyspring.in/2017/10/fat-dairy-good/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:26b8469a-6237-46e9-9372-50f075bc0eb6>"
},
"warc_info": "isPartOf: CC-MAIN-2020-40\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for September 2020\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-11.ec2.internal\r\nsoftware: Apache Nutch 1.17 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.2-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: http://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
14,
15,
127,
406,
407,
450,
451,
535,
536,
669,
670,
790,
791,
914,
915,
1021,
1022,
1065,
1066,
1272,
1273,
1430,
1431,
1604,
1605,
1651,
1652,
1698,
1699,
1742,
1743,
1908,
1909,
2090,
2091,
2284,
2285,
2318,
2319,
2493,
2494,
2627,
2628,
2837,
2838,
2940,
2941,
3053,
3054,
3145,
3146,
3230,
3231,
3304,
3305,
3373,
3374,
3442,
3443,
3532,
3533,
3718,
3719,
3959,
3960,
4325,
4326,
4456,
4457,
4705,
4706,
4764,
4765,
5055,
5056,
5144,
5145,
5178,
5179,
5285,
5286,
5426,
5427,
5591,
5592,
5645,
5646,
5805,
5806,
6102,
6103,
6268,
6269,
6502,
6503,
6615,
6616,
6778,
6779,
6803,
6824,
6836,
6869,
6900,
6901,
6903,
6904,
6916,
6917,
6975,
7050,
7108,
7162,
7220,
7221,
7223,
7224,
7244,
7245,
7278,
7279,
7351,
7352,
7400,
7401,
7457,
7458,
7522,
7523,
7580,
7581,
7595,
7596
],
"line_end_idx": [
14,
15,
127,
406,
407,
450,
451,
535,
536,
669,
670,
790,
791,
914,
915,
1021,
1022,
1065,
1066,
1272,
1273,
1430,
1431,
1604,
1605,
1651,
1652,
1698,
1699,
1742,
1743,
1908,
1909,
2090,
2091,
2284,
2285,
2318,
2319,
2493,
2494,
2627,
2628,
2837,
2838,
2940,
2941,
3053,
3054,
3145,
3146,
3230,
3231,
3304,
3305,
3373,
3374,
3442,
3443,
3532,
3533,
3718,
3719,
3959,
3960,
4325,
4326,
4456,
4457,
4705,
4706,
4764,
4765,
5055,
5056,
5144,
5145,
5178,
5179,
5285,
5286,
5426,
5427,
5591,
5592,
5645,
5646,
5805,
5806,
6102,
6103,
6268,
6269,
6502,
6503,
6615,
6616,
6778,
6779,
6803,
6824,
6836,
6869,
6900,
6901,
6903,
6904,
6916,
6917,
6975,
7050,
7108,
7162,
7220,
7221,
7223,
7224,
7244,
7245,
7278,
7279,
7351,
7352,
7400,
7401,
7457,
7458,
7522,
7523,
7580,
7581,
7595,
7596,
7618
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 7618,
"ccnet_original_nlines": 133,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.30965515971183777,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.01448275987058878,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.15931034088134766,
"rps_doc_frac_unique_words": 0.4047815203666687,
"rps_doc_mean_word_length": 5.047815322875977,
"rps_doc_num_sentences": 80,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.505678176879883,
"rps_doc_word_count": 1213,
"rps_doc_frac_chars_dupe_10grams": 0.03821656107902527,
"rps_doc_frac_chars_dupe_5grams": 0.08459904789924622,
"rps_doc_frac_chars_dupe_6grams": 0.07316675037145615,
"rps_doc_frac_chars_dupe_7grams": 0.06957373768091202,
"rps_doc_frac_chars_dupe_8grams": 0.06957373768091202,
"rps_doc_frac_chars_dupe_9grams": 0.057161521166563034,
"rps_doc_frac_chars_top_2gram": 0.022864609956741333,
"rps_doc_frac_chars_top_3gram": 0.021721379831433296,
"rps_doc_frac_chars_top_4gram": 0.010289070196449757,
"rps_doc_books_importance": -856.1478881835938,
"rps_doc_books_importance_length_correction": -856.1478881835938,
"rps_doc_openwebtext_importance": -434.8126525878906,
"rps_doc_openwebtext_importance_length_correction": -434.8126525878906,
"rps_doc_wikipedia_importance": -317.2063903808594,
"rps_doc_wikipedia_importance_length_correction": -317.2063903808594
},
"fasttext": {
"dclm": 0.02076100930571556,
"english": 0.926174521446228,
"fineweb_edu_approx": 2.6922192573547363,
"eai_general_math": 0.00941544957458973,
"eai_open_web_math": 0.15400582551956177,
"eai_web_code": 0.0005107499891892076
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "613.2",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
},
"secondary": {
"code": "616.1",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "2",
"label": "Click Here References"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "12",
"label": "Listicle"
}
},
"reasoning_depth": {
"primary": {
"code": "3",
"label": "Intermediate Reasoning"
},
"secondary": {
"code": "2",
"label": "Basic Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "4",
"label": "Highly Correct"
}
},
"education_level": {
"primary": {
"code": "2",
"label": "High School Level"
},
"secondary": {
"code": "1",
"label": "General Audience"
}
}
}
|
9222580d47c553ea90dc0f5e416f8f3a
|
-1,106,923,298,541,067,500
|
The Vital Role of Ultrasound in Pregnancy
Are you an expectant parent eager to ensure a safe and healthy pregnancy journey? Look no further. In this article, we will explore the importance of ultrasound in pregnancy and the vital role it plays in monitoring the health and development of both mother and baby. Join me as we delve into the world of prenatal ultrasound technology, guided by the expertise of an experienced obstetrician specializing in this revolutionary tool. Prepare to be amazed by the significant impact ultrasound has on your prenatal care, providing accurate diagnoses and invaluable guidance to ensure a smooth and worry-free pregnancy. Let’s discover just how essential ultrasound is in this incredible journey of bringing new life into the world.
Importance of Ultrasound in Pregnancy
The Vital Role of Ultrasound in Pregnancy
Ultrasound technology has revolutionized the way we monitor the health and development of both mother and baby throughout pregnancy. As an experienced obstetrician, I cannot stress enough the importance of ultrasound in ensuring a safe and healthy pregnancy journey. Let’s delve into why ultrasound is considered the standard of care during pregnancy and the valuable information it provides.
Confirming Pregnancy and Gestational Age
One of the first uses of ultrasound in pregnancy is to confirm the presence of a pregnancy and determine the gestational age. By using sound waves to create images of the uterus, we can visualize the developing embryo or fetus. This early confirmation of pregnancy helps expectant parents gain peace of mind and allows healthcare providers to accurately estimate the due date.
Uncovering Potential Complications
Ultrasound plays a vital role in identifying multiple pregnancies, congenital anomalies, and problems with the placenta. It helps us monitor fetal position, growth, and the level of amniotic fluid. Through ultrasound, we can also detect any abnormal growth in the fetus, ensuring early detection of potential complications that may require further intervention.
Guidance and Reassurance
In addition to diagnosing complications, ultrasound provides expectant parents with much-needed guidance and reassurance throughout the pregnancy journey. By monitoring the baby’s heartbeat, we can offer invaluable peace of mind and ensure that everything is progressing as expected. The ability to visualize the placenta, uterus, ovaries, and cervix allows us to identify any abnormalities that may impact the health of both mother and baby.
As I passionately believe in the importance of ultrasound in pregnancy, I often receive questions from expectant parents about the procedure itself. Let’s address some common queries and concerns.
How is Ultrasound Performed?
Ultrasound scans during pregnancy are typically performed using two main methods: transvaginal ultrasound and abdominal ultrasound. The choice between the two depends on factors such as the stage of pregnancy and the clarity of images required. Transvaginal ultrasound involves a small ultrasound probe being inserted into the vagina, while abdominal ultrasound utilizes a handheld device moved across the belly. Both methods are safe and painless, causing minimal discomfort to the expectant mother.
What can I Expect During a Prenatal Ultrasound?
During a prenatal ultrasound, you will be comfortably positioned on a padded examining table in a dimly lit room. The sonographer will apply a warm gel to your abdomen or a sterile cover to the ultrasound probe for a transvaginal ultrasound. They will then move the probe or device over the area of interest to capture images. You may experience slight pressure, but the procedure is generally well-tolerated.
Immediate Results and Additional Benefits
One of the advantages of ultrasound is its noninvasive nature, providing immediate results. This allows healthcare providers to promptly diagnose conditions and develop appropriate treatment plans. Furthermore, ultrasound can be performed at the bedside, shortening hospital stays for pregnant patients and reducing unnecessary invasive procedures.
Importance of Ultrasound in Early Pregnancy
During the early stages of pregnancy, ultrasound can quickly confirm an intrauterine pregnancy. This information is crucial, as it rules out the possibility of an ectopic pregnancy, where the embryo implants outside the uterus. The ability to accurately diagnose an ectopic pregnancy is essential for ensuring appropriate management and avoiding potentially life-threatening complications.
In conclusion, the importance of ultrasound in pregnancy cannot be overstated. From confirming pregnancy and gestational age to uncovering potential complications, ultrasound serves as a powerful diagnostic tool. It provides guidance, reassurance, and immediate results, all while being a noninvasive and painless procedure. By emphasizing the vital role of ultrasound, we can ensure a safe and healthy pregnancy journey for both mother and baby.
“Ultrasound: The eyes that reveal the unseen, guiding expectant parents on their pregnancy journey.”
Ultrasound technology has revolutionized the world of pregnancy care. From the very early stages of conception to monitoring the growth and development of the baby, ultrasound facts during pregnancy are fascinating and essential for every expectant parent. If you’re eager to learn more about the incredible details that ultrasound scans reveal, click here for a comprehensive guide on ultrasound facts during pregnancy. With this link, you’ll dive into a world of captivating information that will leave you in awe of the wonders of modern medical technology. So, why wait? Explore the URL: Ultrasound Facts Pregnancy
Importance of Ultrasound in Pregnancy
FAQ
Question 1: How does ultrasound confirm pregnancy and gestational age?
Answer 1: Ultrasound is used to confirm pregnancy by detecting the presence of a gestational sac or fetal heartbeat. It can also accurately determine the gestational age by measuring the size of the fetus.
Question 2: What can ultrasound check for during pregnancy?
Answer 2: Ultrasound can check for multiple pregnancies, congenital anomalies, and problems with the placenta. It is also used to monitor fetal position, fetal growth, and the level of amniotic fluid.
Question 3: Can ultrasound detect any complications during pregnancy?
Answer 3: Yes, ultrasound can help identify potential complications such as an ectopic pregnancy or miscarriage. It can also look for any abnormal growth in the fetus and detect any issues with the placenta, uterus, ovaries, or cervix.
Question 4: What are the types of pregnancy ultrasounds?
Answer 4: The two main types of pregnancy ultrasounds are transvaginal ultrasound, where a probe is inserted into the vagina, and abdominal ultrasound, where a transducer is moved over the abdomen.
Question 5: Is ultrasound a standard procedure during pregnancy?
Answer 5: Yes, ultrasound is considered the standard of care during pregnancy. It is a noninvasive and painless diagnostic procedure that provides immediate results. It can quickly confirm an intrauterine pregnancy at the bedside, shortening the length of hospital stay for pregnant patients.
Lola Sofia
|
{
"url": "https://www.lolaapp.com/importance-of-ultrasound-in-pregnancy/",
"source_domain": "www.lolaapp.com",
"snapshot_id": "CC-MAIN-2024-18",
"warc_metadata": {
"Content-Length": "189723",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:S3C3TXZTBBNMS2PVUFBCO236B7C6WY2D",
"WARC-Concurrent-To": "<urn:uuid:cbe9fd03-a395-48f0-a0b0-374181ce88ca>",
"WARC-Date": "2024-04-22T12:24:24",
"WARC-IP-Address": "172.67.139.192",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:6UQSQC47H7C5ZC7YTHLFY3EO7NEENRRS",
"WARC-Record-ID": "<urn:uuid:a7c5db56-7e55-4077-a5a9-2713ba208659>",
"WARC-Target-URI": "https://www.lolaapp.com/importance-of-ultrasound-in-pregnancy/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:f51758af-bb36-4c25-9190-dab12eaab917>"
},
"warc_info": "isPartOf: CC-MAIN-2024-18\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for April 2024\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-116\r\nsoftware: Apache Nutch 1.19 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.5-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
42,
43,
772,
773,
811,
812,
854,
855,
1248,
1249,
1290,
1291,
1668,
1669,
1704,
1705,
2067,
2068,
2093,
2094,
2537,
2538,
2735,
2736,
2765,
2766,
3267,
3268,
3316,
3317,
3727,
3728,
3770,
3771,
4120,
4121,
4165,
4166,
4556,
4557,
5004,
5005,
5106,
5107,
5726,
5727,
5765,
5766,
5770,
5771,
5842,
5843,
6049,
6050,
6110,
6111,
6312,
6313,
6383,
6384,
6620,
6621,
6678,
6679,
6877,
6878,
6943,
6944,
7237,
7238
],
"line_end_idx": [
42,
43,
772,
773,
811,
812,
854,
855,
1248,
1249,
1290,
1291,
1668,
1669,
1704,
1705,
2067,
2068,
2093,
2094,
2537,
2538,
2735,
2736,
2765,
2766,
3267,
3268,
3316,
3317,
3727,
3728,
3770,
3771,
4120,
4121,
4165,
4166,
4556,
4557,
5004,
5005,
5106,
5107,
5726,
5727,
5765,
5766,
5770,
5771,
5842,
5843,
6049,
6050,
6110,
6111,
6312,
6313,
6383,
6384,
6620,
6621,
6678,
6679,
6877,
6878,
6943,
6944,
7237,
7238,
7248
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 7248,
"ccnet_original_nlines": 70,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 2,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.364157110452652,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.004909980110824108,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.11947627365589142,
"rps_doc_frac_unique_words": 0.3336431086063385,
"rps_doc_mean_word_length": 5.5845723152160645,
"rps_doc_num_sentences": 62,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.128211975097656,
"rps_doc_word_count": 1076,
"rps_doc_frac_chars_dupe_10grams": 0.021967049688100815,
"rps_doc_frac_chars_dupe_5grams": 0.19121317565441132,
"rps_doc_frac_chars_dupe_6grams": 0.13396571576595306,
"rps_doc_frac_chars_dupe_7grams": 0.08853387087583542,
"rps_doc_frac_chars_dupe_8grams": 0.053919121623039246,
"rps_doc_frac_chars_dupe_9grams": 0.053919121623039246,
"rps_doc_frac_chars_top_2gram": 0.02396404929459095,
"rps_doc_frac_chars_top_3gram": 0.023298390209674835,
"rps_doc_frac_chars_top_4gram": 0.030620740726590157,
"rps_doc_books_importance": -595.7000122070312,
"rps_doc_books_importance_length_correction": -595.7000122070312,
"rps_doc_openwebtext_importance": -282.4605712890625,
"rps_doc_openwebtext_importance_length_correction": -282.4605712890625,
"rps_doc_wikipedia_importance": -220.38267517089844,
"rps_doc_wikipedia_importance_length_correction": -220.38267517089844
},
"fasttext": {
"dclm": 0.6715407967567444,
"english": 0.9124971628189087,
"fineweb_edu_approx": 2.7755324840545654,
"eai_general_math": 0.036179009824991226,
"eai_open_web_math": 0.16791272163391113,
"eai_web_code": 0.003077629953622818
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "617.922",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Surgery and Dentistry"
}
},
"secondary": {
"code": "617.92",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Surgery and Dentistry"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "3",
"label": "Irrelevant Content"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "2",
"label": "Click Here References"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "9",
"label": "FAQ"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "4",
"label": "Highly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
b755ed28a90d11d590ef646404f4afc5
|
1,520,759,313,307,123,700
|
Rheumatoid arthritis (RA) most commonly affects peripheral joints such as those in your hands, wrists, feet, elbows, ankles, and hips. People with this immune disorder often also experience back pain.
If you have RA, back pain can result from your body’s immune system attacking the synovial lining of the small joints of your spine. In advanced cases, this can even lead to compression of the spinal cord and nerve roots. When this happens, you can experience moderate to severe pain.
Keep reading to learn about short-term treatments for back pain and long-term back pain management steps.
Before looking at treatments for your back pain, you’ll need to know if you have acute or chronic back pain.
Acute back pain is usually a result of straining your back. It can be treated with medication and usually will get better over time. Exercise isn’t recommended.
Chronic back pain is different. It’s a long-term problem caused by conditions like RA. It can be treated in a number of ways, and exercise can be beneficial.
Hot and cold packs can’t treat the underlying causes of back pain, but they can help to reduce the pain and stiffness you feel during a flare-up.
Use a heat pack to help improve blood flow and reduce muscle spasms. It can also help make your pain more manageable.
Use a cold pack to help reduce RA inflammation. Cold packs may feel uncomfortable at first, but they can numb pain.
Medication can be an effective way of controlling chronic back pain. The type of medication you’ll need depends on how severe the pain is and how often you experience it.
A variety of medications can alleviate pain and even slow the progression of RA:
Painkillers
Managing your pain is an important part of learning to live with a chronic back problem. Analgesics, or painkillers, are one way of easing back pain. Over-the-counter drugs like aspirin may be enough to manage mild pain.
Your doctor can prescribe stronger medications for pain relief, if you need it. However, narcotic medications like oxycodone (Roxycodone, Oxaydo) should be used cautiously for chronic diseases to avoid the risk of dependency. There are other medications that can treat both your pain as well as the underlying inflammation.
Non-steroidal anti-inflammatory drugs
Non-steroidal anti-inflammatory drugs (NSAIDs) can soothe pain and inflammation. Anti-inflammatory treatments are helpful because they reduce swelling. This eases pressure on your back and helps make movement easier.
Ibuprofen (Advil, Motrin IB) and naproxen (EC-Naprosyn) are two NSAIDs that are often prescribed. NSAIDs may cause side effects, such as stomach bleeding. Your doctor will be able to help you decide if NSAIDs are right for you based on your medical history.
Disease-modifying antirheumatic drugs
Disease-modifying antirheumatic drugs (DMARDs) are prescribed to help soothe pain and slow the progression of RA. They can help stop future pain flare-ups. A commonly prescribed DMARD is methotrexate.
DMARDs work by blocking chemicals that are released when antibodies attack joint tissue. This prevents further damage to your bones and cartilage.
DMARDs can cause many side effects, such as:
• nausea
• skin rashes
• fatigue
• liver damage
• abnormal white blood cell counts, leading to infection
Your doctor can help you manage these side effects if they occur.
Spinal injections
A spinal injection can be a quick way to relieve chronic back pain. It usually means injecting a corticosteroid or anesthetic into the nerve region that’s being affected by RA inflammation.
The effects of a spinal injection can last for weeks or even months. Corticosteroids may cause other health problems like weight gain and osteoporosis. For this reason, your doctor may suggest you wait several months for your next injection.
Surgery is usually a last resort for back pain treatment. Still, it can be very effective in helping to ease chronic back pain.
For example, your doctor may recommend a “fusion” procedure: This involves cutting out the diseased joint and bonding the vertebrae together, decreasing mobility. In some cases, this will alleviate the pain in that area.
Realigning and stabilizing your spine to ease pressure on your spine’s nerves is another approach. This can lessen pain and even improve mobility.
A range of therapies can help support your back pain treatment. For instance, physiotherapy could improve your flexibility and muscle strength.
Occupational therapy might also be useful. This kind of therapy teaches you joint protection strategies. An example might be how to pick up and carry objects without causing back pain.
Chiropractic therapy usually isn’t recommended for people with RA who are experiencing back pain.
Appropriate exercise can help take pressure off of your back and keep joints supple if you’re experiencing chronic back pain due to RA. Exercise also helps maintain overall body health.
The National Institute of Arthritis and Musculoskeletal and Skin Diseases recommends exercises like walking and stretching to help ward off back pain. Activities like tai chi and water-based exercises like swimming or water aerobics also can be helpful.
Always consult a doctor before starting any fitness program for your back pain.
If you have RA and think you have chronic back pain, seek the advice of your doctor. They’ll be able to help you find the right treatment for your particular condition, whether that means short-term solutions like ice packs and medications or long-term pain management strategies like physiotherapy or an appropriate exercise plan.
|
{
"url": "https://www.healthline.com/health/rheumatoid-arthritis/rheumatoid-arthritis-back-pain",
"source_domain": "www.healthline.com",
"snapshot_id": "crawl=CC-MAIN-2018-39",
"warc_metadata": {
"Content-Length": "93801",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:UKVEDC43AJJFWTNECNXM6JNS2GL57YZD",
"WARC-Concurrent-To": "<urn:uuid:ad6badd1-bf37-460c-bed7-330de035d92e>",
"WARC-Date": "2018-09-26T03:23:24",
"WARC-IP-Address": "104.95.179.44",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:UYELXB7TZWDNLJG23YTDXZ2FTUOJOUMH",
"WARC-Record-ID": "<urn:uuid:891185e2-d9de-4d3e-acb1-d37a9e2a0117>",
"WARC-Target-URI": "https://www.healthline.com/health/rheumatoid-arthritis/rheumatoid-arthritis-back-pain",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:3184f8c0-adeb-44fd-9560-beed2e9ff859>"
},
"warc_info": "isPartOf: CC-MAIN-2018-39\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for September 2018\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-51-154-251.ec2.internal\r\nsoftware: Apache Nutch 1.15 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 0.11-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: http://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
201,
202,
487,
488,
594,
595,
704,
705,
866,
867,
1025,
1026,
1172,
1173,
1291,
1292,
1408,
1409,
1580,
1581,
1662,
1663,
1675,
1676,
1897,
1898,
2222,
2223,
2261,
2262,
2479,
2480,
2738,
2739,
2777,
2778,
2979,
2980,
3127,
3128,
3173,
3174,
3185,
3201,
3213,
3230,
3289,
3290,
3356,
3357,
3375,
3376,
3566,
3567,
3809,
3810,
3938,
3939,
4160,
4161,
4308,
4309,
4453,
4454,
4639,
4640,
4738,
4739,
4925,
4926,
5180,
5181,
5261,
5262
],
"line_end_idx": [
201,
202,
487,
488,
594,
595,
704,
705,
866,
867,
1025,
1026,
1172,
1173,
1291,
1292,
1408,
1409,
1580,
1581,
1662,
1663,
1675,
1676,
1897,
1898,
2222,
2223,
2261,
2262,
2479,
2480,
2738,
2739,
2777,
2778,
2979,
2980,
3127,
3128,
3173,
3174,
3185,
3201,
3213,
3230,
3289,
3290,
3356,
3357,
3375,
3376,
3566,
3567,
3809,
3810,
3938,
3939,
4160,
4161,
4308,
4309,
4453,
4454,
4639,
4640,
4738,
4739,
4925,
4926,
5180,
5181,
5261,
5262,
5593
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 5593,
"ccnet_original_nlines": 74,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.37784090638160706,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.01609848067164421,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.13446970283985138,
"rps_doc_frac_unique_words": 0.42022472620010376,
"rps_doc_mean_word_length": 5.095505714416504,
"rps_doc_num_sentences": 62,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.307687282562256,
"rps_doc_word_count": 890,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.024696800857782364,
"rps_doc_frac_chars_dupe_6grams": 0.008379270322620869,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.0370451994240284,
"rps_doc_frac_chars_top_3gram": 0.02315324917435646,
"rps_doc_frac_chars_top_4gram": 0.005733190104365349,
"rps_doc_books_importance": -571.37646484375,
"rps_doc_books_importance_length_correction": -571.37646484375,
"rps_doc_openwebtext_importance": -289.3070068359375,
"rps_doc_openwebtext_importance_length_correction": -289.3070068359375,
"rps_doc_wikipedia_importance": -263.3153381347656,
"rps_doc_wikipedia_importance_length_correction": -263.3153381347656
},
"fasttext": {
"dclm": 0.028164509683847427,
"english": 0.9307934045791626,
"fineweb_edu_approx": 2.7437472343444824,
"eai_general_math": 0.000810679979622364,
"eai_open_web_math": 0.11451852321624756,
"eai_web_code": 0.00024074000248219818
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "615.83",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
},
"secondary": {
"code": "615.837",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "3",
"label": "Irrelevant Content"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "21",
"label": "Customer Support"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "4",
"label": "Highly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
1a01aa77535b9ecfb87b9fc36adbcd2f
|
-8,744,404,276,847,862,000
|
Skip to main navigation menu Skip to main content Skip to site footer
Research Article
Vol. 9 No. 1 (2006)
Retrospective review of the epidemiology of epilepsy in special schools for children with cerebral palsy, learning difficulties, and language and communication difficulties
• Danielle Samar Peet
DOI
https://doi.org/10.26443/mjm.v9i1.607
Submitted
November 7, 2020
Published
2020-12-01
Abstract
Purpose of the study: To determine in children the proportion and characteristics of epilepsy associated with cerebral palsy, learning difficulties and language and communication difficulties in a specific population of two special schools.
Basic procedures: Retrospective review of case notes for 142 children in two special schools (school A and school B) in Newcastle, UK.
Main findings: School A had more children with learning difficulties (X2 = 32.41, p < 0.01) and active epilepsy (X2 = 3.03, p=0.08) than school B. There were more children with cerebral palsy (X2 = 9.56, p < 0.01) and language and communication problems (X2 = 4.25, p = 0.03) at school B compared to school A. Active epilepsy is significantly more common in children with cerebral palsy (X2 = 7.58, p = 0.01). All children with cerebral palsy and learning difficulties had epilepsy (n = 6). Although not statistically significant, those children who developed epilepsy within the first 24 hours of life were more likely to have cerebral palsy than those who developed epilepsy later in life (X2 = 3.10, p = 0.08). Those children with cerebral palsy tended to have a lower birth weight (t = 3.15, p < 0.01) and a shorter gestation (t = 3.17, p < 0.01) than children without cerebral palsy.
Principal conclusions: The data supports evidence from previous studies, demonstrating that epilepsy commonly accompanies cerebral palsy, thus complicating this difficult chronic condition. We show an association between both low birth weight and gestational age, and early age of onset of seizures, in children with cerebral palsy. This illustrates the importance, in these children, of past medical history from birth to determine risk factors for epilepsy later in life.
References
1. Rosenbaum, P., Cerebral palsy: what parents and doctors want to know. BMJ 2003; 326: 960-974.
2. Wojciech KU et al. Risk factors and prognosis of epilepsy in children with cerebral palsy in North-Eastern Poland. Brain and Development 2003; 25(7): 499-506.
3. Colver, A. Gibson, M et al Increasing rates of Cerebral Palsy across the severity spectrum in north-east England 1964-1993. Archives of Disease in Childhood 2000; 83(1): 7-125.
4. 5. Jarvis, S. Studies of the relationship between cerebral palsy and intrauterine growth. Lancet 2003; 362: 1106-11.
5. Wallace, S., Epilepsy in cerebral palsy. Developmental Medicine and Child Neurology 2001; 43: 713-717.
6. Parkinson, G. High incidence of language disorder in children with focal epilepsies. Developmental Medicine and Child Neurology 2002; 44: 533-537.
7. Bruck, I. Et al. Epilepsy in children with cerebral palsy. Arq Neuro-psiquitr 2001; 59(1).
8. Gururaj, AK et al. Epilepsy in children with cerebral palsy. Seizure 2003; 12(2): 110-4.
9. Al-Sulaiman AA., Epilepsy in Saudi children with Cerebral Palsy. Saudi Medical Journal 2001; 22(1): 19-21.
10. Singhi P, et al. Epilepsy in children with Cerebral Palsy. Journal of Child Neurology 2003; 18(3): 174-9.
11. Adamson, S et al. Predictors of neonatal encephalopathy in full term infants. BMJ 1995; 311: 598-602.
12. Mapleson, W. Why 5% risk of type-1 error but 20% risk of type-2 error? Anaethesia, 2004; 59(4): 409.
Downloads
Download data is not yet available.
|
{
"url": "https://mjm.mcgill.ca/article/view/607",
"source_domain": "mjm.mcgill.ca",
"snapshot_id": "CC-MAIN-2023-40",
"warc_metadata": {
"Content-Length": "34403",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:X5R4MVCSWZM2K6PV6LEBZHO7PVMRT2PU",
"WARC-Concurrent-To": "<urn:uuid:5189dd9c-cb78-4497-b395-9e58c5b724ff>",
"WARC-Date": "2023-09-22T16:00:14",
"WARC-IP-Address": "132.206.11.97",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:TNWXAHUL5HZQIJOVDBFAF5PQJ5PBNBGG",
"WARC-Record-ID": "<urn:uuid:57c2afd3-ad70-456b-9b3d-9c27501ae5b1>",
"WARC-Target-URI": "https://mjm.mcgill.ca/article/view/607",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:a4d27a9c-7947-448e-930f-7aadfd098135>"
},
"warc_info": "isPartOf: CC-MAIN-2023-40\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for September/October 2023\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-82\r\nsoftware: Apache Nutch 1.19 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.5-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
70,
71,
88,
89,
109,
110,
283,
284,
308,
312,
350,
360,
377,
387,
398,
399,
408,
409,
650,
785,
1674,
2148,
2149,
2160,
2161,
2260,
2424,
2606,
2728,
2836,
2988,
3084,
3178,
3290,
3402,
3510,
3617,
3618,
3628,
3629
],
"line_end_idx": [
70,
71,
88,
89,
109,
110,
283,
284,
308,
312,
350,
360,
377,
387,
398,
399,
408,
409,
650,
785,
1674,
2148,
2149,
2160,
2161,
2260,
2424,
2606,
2728,
2836,
2988,
3084,
3178,
3290,
3402,
3510,
3617,
3618,
3628,
3629,
3664
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 3664,
"ccnet_original_nlines": 40,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.19482120871543884,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.03575832024216652,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.40567201375961304,
"rps_doc_frac_unique_words": 0.5,
"rps_doc_mean_word_length": 5.158181667327881,
"rps_doc_num_sentences": 84,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.077877521514893,
"rps_doc_word_count": 550,
"rps_doc_frac_chars_dupe_10grams": 0.053577721118927,
"rps_doc_frac_chars_dupe_5grams": 0.16320055723190308,
"rps_doc_frac_chars_dupe_6grams": 0.1071554496884346,
"rps_doc_frac_chars_dupe_7grams": 0.09481847286224365,
"rps_doc_frac_chars_dupe_8grams": 0.09481847286224365,
"rps_doc_frac_chars_dupe_9grams": 0.053577721118927,
"rps_doc_frac_chars_top_2gram": 0.08706379681825638,
"rps_doc_frac_chars_top_3gram": 0.0719069391489029,
"rps_doc_frac_chars_top_4gram": 0.09693337976932526,
"rps_doc_books_importance": -279.053466796875,
"rps_doc_books_importance_length_correction": -279.053466796875,
"rps_doc_openwebtext_importance": -201.42181396484375,
"rps_doc_openwebtext_importance_length_correction": -201.42181396484375,
"rps_doc_wikipedia_importance": -158.43710327148438,
"rps_doc_wikipedia_importance_length_correction": -158.43710327148438
},
"fasttext": {
"dclm": 0.10527033358812332,
"english": 0.8554220795631409,
"fineweb_edu_approx": 3.3423736095428467,
"eai_general_math": 0.07414699345827103,
"eai_open_web_math": 0.0814666673541069,
"eai_web_code": 0.0003024300094693899
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.858",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "618.9285",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Women — Health and hygiene, Children — Health and hygiene, Gynecology, and Pediatrics"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "4",
"label": "Analyze"
},
"secondary": {
"code": "5",
"label": "Evaluate"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "1",
"label": "Factual"
}
},
"document_type_v1": {
"primary": {
"code": "2",
"label": "Academic/Research"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "0",
"label": "No Artifacts"
}
},
"missing_content": {
"primary": {
"code": "4",
"label": "Missing Images or Figures"
},
"secondary": {
"code": "0",
"label": "No missing content"
}
},
"document_type_v2": {
"primary": {
"code": "3",
"label": "Academic Writing"
},
"secondary": {
"code": "10",
"label": "Knowledge Article"
}
},
"reasoning_depth": {
"primary": {
"code": "3",
"label": "Intermediate Reasoning"
},
"secondary": {
"code": "2",
"label": "Basic Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "4",
"label": "Graduate/Expert Level"
},
"secondary": {
"code": "3",
"label": "Undergraduate Level"
}
}
}
|
6e3c8d3593f3f69280bb5502b214ab8e
|
-5,624,832,377,009,043,000
|
Articles: Better Help For Therapists – discount 2023
Online therapy platforms provide the convenience of accessing treatment. Better Help For Therapists … from the convenience of your own home. They are ideal for people who live in remote locations, have movement issues, or simply prefer the benefit of online treatment. Here’s how BetterHelp compares to other online therapy platforms.
Talkspace is another popular online therapy platform. Both Talkspace and BetterHelp provide comparable services, consisting of private and couples therapy. BetterHelp has a larger network of therapists, which implies that clients have a better chance of discovering a therapist who is a great fit for them.
therapy shipment and broadening access to mental health assistance.
I. A Summary of Talkspace
Talkspace is an online therapy platform founded in 2012 with a mission to make treatment more available, budget-friendly, and convenient. It offers users with a practical way to connect with certified therapists via text, audio, or video messages. Talkspace’s platform offers a safe and personal environment for people looking for therapy.
II. Secret Functions and Benefits
Available and Hassle-free:.
Talkspace eliminates geographical barriers, permitting users to gain access to treatment from anywhere, anytime, utilizing their mobile phone or computer.
It deals with people who might deal with challenges attending in-person sessions due to location, movement concerns, or busy schedules.
Wide Variety of Therapists and Specialties:.
Talkspace offers access to a diverse network of licensed therapists with expertise in various locations, such as stress and anxiety, depression, relationships, and more.
Users can pick a therapist who aligns with their specific needs and preferences, making sure customized care.
Messaging-Based Treatment:.
Talkspace’s asynchronous messaging feature enables users to communicate with their therapist throughout the day, at their benefit.
This function provides individuals with the flexibility to express their ideas and emotions in real-time or as they occur, promoting ongoing support.
Audio and Video Sessions:.
In addition to messaging, Talkspace provides audio and video sessions for a more immersive restorative experience.
These sessions can be set up based on the user’s preferences and provide an opportunity for more interactive and immediate discussions.
Enhanced Privacy and Privacy:.
Talkspace complies with stringent privacy requirements, making sure safe and secure interaction and protecting user info.
The platform utilizes encryption and other security steps to maintain the confidentiality of treatment sessions.
III. Factors To Consider and Limitations
Abstract:.
This research paper intends to supply an extensive analysis of the co-occurrence of anxiety and anxiety, two widespread psychological health disorders that often manifest together. The paper reviews existing literature to check out the interrelationship between anxiety and stress and anxiety, their shared threat aspects, neurobiological foundations, and treatment implications. Comprehending the complex relationship in between these disorders is important for reliable medical diagnosis, treatment, and enhanced psychological health outcomes.
Intro
Briefly introduce the significance of anxiety and stress and anxiety as separate conditions and their frequent co-occurrence.
Highlight the effect of comorbidity on people’ well-being, working, and treatment outcomes.
Prevalence and Diagnostic Requirements
Present statistics on the prevalence of anxiety and stress and anxiety conditions separately and their high rates of comorbidity.
Talk about the diagnostic criteria for significant depressive disorder (MDD), generalized anxiety disorder (GAD), and other appropriate stress and anxiety conditions.
Shared Danger Factors
Check out common threat factors that add to the development and upkeep of anxiety and anxiety, such as genetic predisposition, childhood adversity, and characteristic.
Go over how shared danger elements may account for the high comorbidity rates observed in scientific populations.
BetterUp is an online coaching and therapy platform that focuses on personal and professional advancement. While BetterUp provides coaching services, it does not provide therapy services like BetterHelp. BetterUp is ideal for individuals who want to concentrate on personal development and profession development instead of mental health concerns.
In conclusion, BetterHelp therapy provides numerous advantages over standard in-person therapy, consisting of convenience, expense, and therapist choice. While there are other online therapy platforms offered, BetterHelp sticks out for its large network of therapists and budget-friendly rates plans. Eventually, the choice between online treatment and conventional in-person therapy comes down to personal choice and specific requirements.
Anxiety
Anxiety is a typical psychological health condition that affects millions of people worldwide. Therapy can help by offering a safe space to speak about your feelings and feelings. A therapist can help you recognize unfavorable idea patterns and behaviors and work with you to establish coping strategies and favorable routines.
Stress and anxiety
Anxiety is another typical mental health condition that can be debilitating. Therapy can assist by teaching you relaxation methods, such as deep breathing and mindfulness, and working with you to establish coping strategies to manage stress and anxiety triggers.
PTSD
PTSD, or post-traumatic stress disorder, is a psychological health condition that can establish after experiencing or experiencing a traumatic event. Treatment can help by supplying a safe area to process the trauma and establish coping strategies to manage the signs of PTSD.
OCD
OCD, or obsessive-compulsive condition, is a psychological health condition identified by compulsive habits and invasive thoughts. Treatment can assist by teaching you how to determine and manage these thoughts and behaviors, as well as develop coping techniques to manage the symptoms of OCD.
Bipolar affective disorder
Bipolar illness is a mental health condition defined by severe state of mind swings, ranging from depressive episodes to manic episodes. Treatment can assist by supplying support and guidance in handling these state of mind swings, establishing coping strategies, and improving interaction skills.
Eating disorders
Eating disorders, such as anorexia and bulimia, are psychological health conditions that can have major physical effects. Treatment can help by dealing with the underlying psychological and emotional problems that add to the eating disorder, in addition to developing techniques to handle the physical signs.
Drug abuse
Drug abuse can be a tough routine to break, but treatment can be an efficient tool in managing dependency. Treatment can assist by resolving the underlying psychological and psychological problems that add to drug abuse, along with developing techniques to manage cravings and triggers.
Relationship problems
Relationship problems, such as interaction issues and conflict, can have a considerable impact on psychological health. Therapy can assist by providing a safe space to discuss these problems and develop strategies to improve communication and fix conflict.
Sorrow and loss Better Help For Therapists
Sorrow and loss can be a difficult experience to navigate, however therapy can help by offering support and guidance through the mourning procedure. A therapist can assist you recognize and handle the feelings connected with grief and loss, as well as establish coping techniques to move forward.
Stress management
Stress is a common experience for many individuals, however it can have unfavorable effect on psychological health. Treatment can assist by teaching relaxation techniques and developing coping methods to manage tension, as well as recognizing and addressing the underlying psychological and psychological issues that contribute to tension.
In conclusion, therapy can be an effective tool in managing a vast array of mental health conditions, from depression and stress and anxiety to substance abuse and relationship issues. If you are struggling with your psychological health, think about looking for the assistance and assistance of a licensed therapist.
Seeing a therapist can have numerous benefits for an individual’s psychological health and wellness. Here are some of the advantages of seeing a therapist from a psychological perspective:
Emergency Circumstances:.
Talkspace provides resources for users in crisis, however it may not use immediate assistance in emergency situation circumstances.
It is essential for individuals experiencing an intense crisis to get in touch with emergency situation services or a regional mental health crisis line.
IV. The Future of Online Therapy
Talkspace has played a substantial function in shaping the future of therapy by harnessing the power of technology to broaden access to psychological health assistance. As digital platforms continue to progress, online therapy is likely to end up being increasingly incorporated into mental healthcare systems worldwide. Nevertheless, it is important to strike a balance between the benefit of online therapy and the individualized care and nuances of traditional in-person sessions.
Conclusion
Talkspace has revolutionized the field of psychological health therapy by providing an available, practical, and secure platform for.
Comprehending Insurance Coverage Protection:.
Lots of insurance strategies offer protection for psychological health services, consisting of therapy sessions.
It is necessary to examine insurance policies, understand protection limitations, co-pays, and any pre-authorization requirements related to treatment.
In-Network vs. Out-of-Network Providers:.
Insurance plans normally have a network of preferred providers with whom they have worked out rates.
In-network therapists typically have lower out-of-pocket expenses for insured people, while out-of-network providers might involve higher expenses.
Utilizing Employee Help Programs (EAPs):.
Numerous companies offer EAPs, which provide a restricted number of therapy sessions at no cost to employees.
EAPs can be a valuable resource for employees looking for short-term therapy and assistance.
|
{
"url": "https://robertberlind.net/better-help-for-therapists/",
"source_domain": "robertberlind.net",
"snapshot_id": "CC-MAIN-2023-40",
"warc_metadata": {
"Content-Length": "37773",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:CH27643BQIKVZFT746MT7CVZXSQHU3BU",
"WARC-Concurrent-To": "<urn:uuid:092e6a97-eaa7-4ecf-9687-3f7e1f4d8c7d>",
"WARC-Date": "2023-09-26T13:43:28",
"WARC-IP-Address": "45.84.120.170",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:MNH37AMLI74E7RC7G4LQ2DCWJKEO246M",
"WARC-Record-ID": "<urn:uuid:868c988d-5e64-4cf0-a62a-b832a4b6a94d>",
"WARC-Target-URI": "https://robertberlind.net/better-help-for-therapists/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:5ae256e4-3aa1-40b7-8a1a-f1d3dd65bce4>"
},
"warc_info": "isPartOf: CC-MAIN-2023-40\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for September/October 2023\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-30\r\nsoftware: Apache Nutch 1.19 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.5-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
53,
54,
389,
390,
697,
698,
700,
701,
769,
770,
771,
797,
798,
1138,
1139,
1173,
1174,
1202,
1357,
1493,
1538,
1539,
1709,
1819,
1847,
1978,
2128,
2155,
2156,
2271,
2407,
2438,
2439,
2561,
2674,
2715,
2716,
2727,
3273,
3274,
3280,
3406,
3498,
3499,
3538,
3668,
3835,
3836,
3858,
4026,
4140,
4141,
4489,
4490,
4931,
4932,
4934,
4935,
4943,
5271,
5272,
5291,
5554,
5555,
5560,
5837,
5838,
5842,
6136,
6137,
6164,
6462,
6463,
6480,
6789,
6790,
6801,
7088,
7089,
7111,
7368,
7369,
7412,
7709,
7710,
7728,
8068,
8069,
8387,
8388,
8577,
8578,
8604,
8736,
8890,
8923,
9407,
9408,
9419,
9553,
9554,
9600,
9713,
9865,
9907,
9908,
10009,
10157,
10199,
10309
],
"line_end_idx": [
53,
54,
389,
390,
697,
698,
700,
701,
769,
770,
771,
797,
798,
1138,
1139,
1173,
1174,
1202,
1357,
1493,
1538,
1539,
1709,
1819,
1847,
1978,
2128,
2155,
2156,
2271,
2407,
2438,
2439,
2561,
2674,
2715,
2716,
2727,
3273,
3274,
3280,
3406,
3498,
3499,
3538,
3668,
3835,
3836,
3858,
4026,
4140,
4141,
4489,
4490,
4931,
4932,
4934,
4935,
4943,
5271,
5272,
5291,
5554,
5555,
5560,
5837,
5838,
5842,
6136,
6137,
6164,
6462,
6463,
6480,
6789,
6790,
6801,
7088,
7089,
7111,
7368,
7369,
7412,
7709,
7710,
7728,
8068,
8069,
8387,
8388,
8577,
8578,
8604,
8736,
8890,
8923,
9407,
9408,
9419,
9553,
9554,
9600,
9713,
9865,
9907,
9908,
10009,
10157,
10199,
10309,
10401
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 10401,
"ccnet_original_nlines": 110,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.3451119065284729,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.008833919651806355,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.12014134228229523,
"rps_doc_frac_unique_words": 0.36920979619026184,
"rps_doc_mean_word_length": 5.9182562828063965,
"rps_doc_num_sentences": 87,
"rps_doc_symbol_to_word_ratio": 0.0005889299791306257,
"rps_doc_unigram_entropy": 5.542293548583984,
"rps_doc_word_count": 1468,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.053637199103832245,
"rps_doc_frac_chars_dupe_6grams": 0.014272560365498066,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.028430020436644554,
"rps_doc_frac_chars_top_3gram": 0.014732969924807549,
"rps_doc_frac_chars_top_4gram": 0.008747699670493603,
"rps_doc_books_importance": -945.414306640625,
"rps_doc_books_importance_length_correction": -945.414306640625,
"rps_doc_openwebtext_importance": -489.2913818359375,
"rps_doc_openwebtext_importance_length_correction": -489.2913818359375,
"rps_doc_wikipedia_importance": -423.2739562988281,
"rps_doc_wikipedia_importance_length_correction": -423.2739562988281
},
"fasttext": {
"dclm": 0.11670702695846558,
"english": 0.9310670495033264,
"fineweb_edu_approx": 1.6034798622131348,
"eai_general_math": 0.01400506030768156,
"eai_open_web_math": 0.0816946029663086,
"eai_web_code": 0.005552290007472038
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.8914",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "616.89",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "17",
"label": "Product Page"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "4",
"label": "Highly Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
9222580d47c553ea90dc0f5e416f8f3a
|
-5,201,123,695,369,534,000
|
A genome-wide association study identifies genetic variants in the CDKN2BAS locus associated with endometriosis in Japanese
Satoko Uno, Hitoshi Zembutsu, Akira Hirasawa, Atsushi Takahashi, Michiaki Kubo, Tomoko Akahane, Daisuke Aoki, Naoyuki Kamatani, Koichi Hirata, Yusuke Nakamura
Research output: Contribution to journalArticlepeer-review
218 Citations (Scopus)
Abstract
Although the pathogenesis of endometriosis is not well understood, genetic factors have been considered to have critical roles in its etiology. Through a genome-wide association study and a replication study using a total of 1,907 Japanese individuals with endometriosis (cases) and 5,292 controls, we identified a significant association of endometriosis with rs10965235 (P = 5.57 × 10-12, odds ratio = 1.44), which is located in CDKN2BAS on chromosome 9p21, encoding the cyclin-dependent kinase inhibitor 2B antisense RNA. By fine mapping, the SNP showing the strongest association was located in intron 16 of CDKN2BAS and was implicated in regulating the expression of p15, p16 and p14. A SNP, rs16826658, in the LD block including WNT4 on chromosome 1p36, which is considered to play an important role in the development of the female genital tract, revealed a possible association with endometriosis (P = 1.66 × 10-6, odds ratio = 1.20). Our findings suggest that these regions are new susceptibility loci for endometriosis.
Original languageEnglish
Pages (from-to)707-710
Number of pages4
JournalNature Genetics
Volume42
Issue number8
DOIs
Publication statusPublished - 08-2010
Externally publishedYes
All Science Journal Classification (ASJC) codes
• Genetics
Fingerprint
Dive into the research topics of 'A genome-wide association study identifies genetic variants in the CDKN2BAS locus associated with endometriosis in Japanese'. Together they form a unique fingerprint.
Cite this
|
{
"url": "https://pure.fujita-hu.ac.jp/en/publications/a-genome-wide-association-study-identifies-genetic-variants-in-th",
"source_domain": "pure.fujita-hu.ac.jp",
"snapshot_id": "CC-MAIN-2023-40",
"warc_metadata": {
"Content-Length": "50952",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:PPO7FUJZJRIQOB5I5GXIEFCPZDN2GI4H",
"WARC-Concurrent-To": "<urn:uuid:be6ae6d3-2d6d-4d8f-a543-2b75c0b15f9a>",
"WARC-Date": "2023-09-24T11:14:26",
"WARC-IP-Address": "52.74.61.34",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:OIMYL5M4MPCLTAE53YZJXO3QCRYVOMKU",
"WARC-Record-ID": "<urn:uuid:714523e8-757c-4704-8170-752314a55b02>",
"WARC-Target-URI": "https://pure.fujita-hu.ac.jp/en/publications/a-genome-wide-association-study-identifies-genetic-variants-in-th",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:649946ea-0a8b-46fe-a998-6db37c64caca>"
},
"warc_info": "isPartOf: CC-MAIN-2023-40\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for September/October 2023\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-30\r\nsoftware: Apache Nutch 1.19 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.5-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
124,
125,
284,
285,
344,
345,
368,
369,
378,
379,
1409,
1410,
1435,
1458,
1475,
1498,
1507,
1521,
1526,
1564,
1588,
1589,
1637,
1638,
1651,
1652,
1664,
1665,
1866,
1867
],
"line_end_idx": [
124,
125,
284,
285,
344,
345,
368,
369,
378,
379,
1409,
1410,
1435,
1458,
1475,
1498,
1507,
1521,
1526,
1564,
1588,
1589,
1637,
1638,
1651,
1652,
1664,
1665,
1866,
1867,
1876
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 1876,
"ccnet_original_nlines": 30,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.2321428656578064,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.0476190485060215,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.255952388048172,
"rps_doc_frac_unique_words": 0.6627907156944275,
"rps_doc_mean_word_length": 5.957364559173584,
"rps_doc_num_sentences": 12,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 4.864251613616943,
"rps_doc_word_count": 258,
"rps_doc_frac_chars_dupe_10grams": 0.13923226296901703,
"rps_doc_frac_chars_dupe_5grams": 0.13923226296901703,
"rps_doc_frac_chars_dupe_6grams": 0.13923226296901703,
"rps_doc_frac_chars_dupe_7grams": 0.13923226296901703,
"rps_doc_frac_chars_dupe_8grams": 0.13923226296901703,
"rps_doc_frac_chars_dupe_9grams": 0.13923226296901703,
"rps_doc_frac_chars_top_2gram": 0.013012359850108624,
"rps_doc_frac_chars_top_3gram": 0.04294079169631004,
"rps_doc_frac_chars_top_4gram": 0.052700068801641464,
"rps_doc_books_importance": -149.24607849121094,
"rps_doc_books_importance_length_correction": -149.23776245117188,
"rps_doc_openwebtext_importance": -86.03650665283203,
"rps_doc_openwebtext_importance_length_correction": -86.03650665283203,
"rps_doc_wikipedia_importance": -40.0893440246582,
"rps_doc_wikipedia_importance_length_correction": -40.08934020996094
},
"fasttext": {
"dclm": 0.08942986279726028,
"english": 0.87094646692276,
"fineweb_edu_approx": 2.5106523036956787,
"eai_general_math": 0.0009654799941927195,
"eai_open_web_math": 0.24652063846588135,
"eai_web_code": 0.0005756599712185562
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "616.075",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
},
"secondary": {
"code": "616.9",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Pathology and Diseases"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "4",
"label": "Analyze"
},
"secondary": {
"code": "2",
"label": "Understand"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "2",
"label": "Academic/Research"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "3",
"label": "Irrelevant Content"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "3",
"label": "Academic Writing"
},
"secondary": {
"code": "10",
"label": "Knowledge Article"
}
},
"reasoning_depth": {
"primary": {
"code": "3",
"label": "Intermediate Reasoning"
},
"secondary": {
"code": "2",
"label": "Basic Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "4",
"label": "Graduate/Expert Level"
},
"secondary": {
"code": "3",
"label": "Undergraduate Level"
}
}
}
|
b755ed28a90d11d590ef646404f4afc5
|
-6,699,239,321,139,551,000
|
Article not rated
Vol. 20 - Num. 27
Workshops
Vegan diets, FODMAP and more
Ignacio Ros Arnala, Ángel José Carbajo Ferreirab
aHospital Universitario Miguel Servet. Zaragoza. España.
bPediatra. CS Reyes Magos. Dirección Asistencial Este. Alcalá de Henares. Madrid. España.
Reference of this article: Ros Arnal I, Carbajo Ferreira ÁJ. Vegan diets, FODMAP and more. Rev Pediatr Aten Primaria. Supl. 2018;(27):83-93.
Published in Internet: 08-06-2018 - Visits: 18358
Abstract
There are several reasons why a doctor or nutritionist prescribes, or a person decides to start a certain diet. In recent years the relationship between some foods and certain symptoms, usually digestive, has been proposed. In this review, the characteristics, consequences and effectiveness of the low FODMAPs (polyols, monosaccharides, disaccharides and fermentable oligosaccharides) diet, the gluten-free diet and the low-histamine diet are detailed, mainly in children with chronic abdominal pain. The reasons why a person follows a vegetarian or vegan diet are varied: ecological, ethical, philosophical, spiritual, religious or because they have health benefits, which are attributed to them. The pediatrician must be prepared for the proper planning of the diets chosen by the population they serve, as long as they are adequate.
Keywords
Diet therapy Diet, carbohydrate-restricted Diet, gluten-free Diet, vegetarian Histamine
Comments
This article has no comments yet.
|
{
"url": "https://pap.es/articulo/12635/dietas-veganas-fodmap-y-mas",
"source_domain": "pap.es",
"snapshot_id": "crawl=CC-MAIN-2020-29",
"warc_metadata": {
"Content-Length": "25774",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:K4CGPERJWR36MT4FANVK4QSKWTCQPGOH",
"WARC-Concurrent-To": "<urn:uuid:87e8d783-e07d-45b3-9598-b06dcb6e402d>",
"WARC-Date": "2020-07-14T11:21:27",
"WARC-IP-Address": "54.37.90.123",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:U4ZOX2ZGZPTZLF2INEQVGXX2ZFYUCO6M",
"WARC-Record-ID": "<urn:uuid:5d7a6a0c-0dd0-4221-9e43-d75d8772baf5>",
"WARC-Target-URI": "https://pap.es/articulo/12635/dietas-veganas-fodmap-y-mas",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:4f3e51e4-675f-4aca-9be2-b6dbb6850993>"
},
"warc_info": "isPartOf: CC-MAIN-2020-29\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for July 2020\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-25.ec2.internal\r\nsoftware: Apache Nutch 1.17 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.2-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: http://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
18,
19,
37,
38,
48,
49,
78,
79,
128,
129,
186,
276,
277,
418,
419,
469,
470,
479,
480,
1317,
1318,
1327,
1328,
1416,
1417,
1419,
1420,
1429,
1430
],
"line_end_idx": [
18,
19,
37,
38,
48,
49,
78,
79,
128,
129,
186,
276,
277,
418,
419,
469,
470,
479,
480,
1317,
1318,
1327,
1328,
1416,
1417,
1419,
1420,
1429,
1430,
1463
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 1463,
"ccnet_original_nlines": 29,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.25,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.0181159395724535,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.25724637508392334,
"rps_doc_frac_unique_words": 0.6941747665405273,
"rps_doc_mean_word_length": 5.747572898864746,
"rps_doc_num_sentences": 22,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 4.739014148712158,
"rps_doc_word_count": 206,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.03885135054588318,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.01689188927412033,
"rps_doc_frac_chars_top_3gram": 0.027027029544115067,
"rps_doc_frac_chars_top_4gram": 0.03209459036588669,
"rps_doc_books_importance": -141.3511962890625,
"rps_doc_books_importance_length_correction": -135.8076629638672,
"rps_doc_openwebtext_importance": -83.3053207397461,
"rps_doc_openwebtext_importance_length_correction": -83.3053207397461,
"rps_doc_wikipedia_importance": -67.25428771972656,
"rps_doc_wikipedia_importance_length_correction": -57.7264518737793
},
"fasttext": {
"dclm": 0.3348318934440613,
"english": 0.8201911449432373,
"fineweb_edu_approx": 3.0592238903045654,
"eai_general_math": 0.014380279928445816,
"eai_open_web_math": 0.20163089036941528,
"eai_web_code": 0.000115870003355667
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "613.25",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
},
"secondary": {
"code": "613.2",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "4",
"label": "Analyze"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "2",
"label": "Academic/Research"
},
"secondary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "3",
"label": "Academic Writing"
},
"secondary": {
"code": "10",
"label": "Knowledge Article"
}
},
"reasoning_depth": {
"primary": {
"code": "3",
"label": "Intermediate Reasoning"
},
"secondary": {
"code": "2",
"label": "Basic Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "4",
"label": "Highly Correct"
},
"secondary": {
"code": "3",
"label": "Mostly Correct"
}
},
"education_level": {
"primary": {
"code": "3",
"label": "Undergraduate Level"
},
"secondary": {
"code": "4",
"label": "Graduate/Expert Level"
}
}
}
|
1a01aa77535b9ecfb87b9fc36adbcd2f
|
-4,895,978,495,591,342,000
|
Featured
Be Careful in Following Diet Fads and the Need for Clean Drinking Water Using Berkey Water System
0
There are plenty of ways to lose weight. Usually, it’s a combination of a balanced diet and exercise. Some people hesitate to exercise because it’s exhausting. Others don’t have time to do it. Hence, it paved the way for the rise of diet fads. These diet plans claim to be effective, and many people are enticed to use them. Before you hop on the diet train, you should be careful. These diet plans might have a terrible impact on your health. If you want to lose weight, start by cutting unhealthy foods and beverages. Soda and alcoholic drinks are a big no. Plain drinking water would suffice. Having a Berkey water system at home allows you to have clean water any time you want.
Letting go of sweetened and preserved drinks can do wonders for your health and help you achieve your fitness goals. It’s not enough, but it’s a good start. Trying diet fads should be avoided. These are some possible risks and effects of using inappropriate diet techniques.
You don’t have the right body type
Just because the diet plan worked with one person doesn’t mean it will do the same. You can have the opposite results. It’s due to your body type. Not all bodies are designed for that diet plan. For instance, some plans involve the elimination of carbohydrates. It can help reduce weight, but also affect your health. Going vegetarian might also help, but if you don’t understand what you eat, you could be at risk. You’re losing a primary protein source, so you should replace it with something else. Talk to your doctor if the diet plan would work for your body type, or if it leads to terrible results.
You might have underlying conditions
If you have underlying medical conditions, you have more reasons to be careful. Your condition might worsen as a result of your efforts to lose weight. If you have heart problems, you should eat healthily. Starving yourself or eliminating some foods could be detrimental to your health. Besides, you already have tons of restrictions as a result of your condition. For instance, if you have diabetes, you’re not allowed to take too much salty or sugary foods. You should also avoid coffee, alcohol, and sweetened beverages. These restrictions are more than enough to alter your diet plan. There’s no need to have more.
The testimonials and reviews are paid
You might feel confident about the diet plan because there are testimonials. The words left by those who testified were glowing, and you feel tempted to try. Add to that the images showing their changes before and after following the diet plan. Before you try doing it yourself, you have to understand the risks. It’s also possible that these people were lying about the effects. They got paid to promote the diet fad. Besides, you weren’t there to witness the person’s efforts to see these changes through. You won’t know if those results were achieved through exercise and other diet techniques. You will be surprised that you didn’t end up with the same results.
These diet plans weren’t scientific
If you notice, most of these diet plans are endorsed by celebrities, fitness trainers, or some random online personalities. Most of them don’t have any formal training related to diet and nutrition. It means that they can’t recommend the best diet technique. If they want to prove the effectiveness of what they promote, there should be a series of studies with random samples. The results should be carefully analyzed before these conclusions are reached. Otherwise, you can’t count on what they’re promoting to be effective.
You will starve yourself
Some diet fads promote starvation. Sure, it helps if you delay food intake for a few hours, but it’s not good to starve yourself. The worst part is that you will only make it up later by eating more if it’s your window. Starving could also lead to peptic ulcers and an increase in the acid level in your body. You might notice a drop in weight for a while, but it’s not a long-term and sustainable solution.
You could develop illnesses
Before doing the diet plan, you were healthy. You might not be at your ideal weight and body shape, but you’re not feeling anything wrong. After the diet technique, you start to develop some health issues. It starts with the digestive problems that you didn’t use to have. You could even have some heart problems because of your food choices. Your body easily crashes due to the lack of certain nutrients. You can’t take these risks in your efforts to lose weight.
You won’t be happy
Sure, you’re starting to see positive effects on your weight, but you’re not feeling happy. You always have mood swings because you’re not eating right. You also feel deprived all the time. Your mood swings could adversely affect your relationship with other people. You start to look better, but your attitude took a hit. If this is what weight loss looks like, it’s not worth doing.
You can still achieve your goals
Just because you have to avoid these diet fads doesn’t mean you can’t lose weight anymore. You will still achieve your goals through other means. Start by talking to your doctor about your plans. You will receive competent advice on how to lose weight and remain healthy. Visit your nutritionist too. You need someone to come up with a diet plan to help you. These people are experts in analyzing body types and determining the types of dishes that wild be beneficial to a person.
Most of all, you should exercise. It’s never enough to rely on your diet plan to lose weight. You don’t have to do the intense exercises. Simple routines would suffice. As long as you do them well and you’re consistent, you can see changes. Be optimistic about your plans, and don’t give up.
You may also like
Comments
Comments are closed.
More in Featured
|
{
"url": "https://www.akhbar-today.com/clean-drinking-water-using-berkey-water-system/",
"source_domain": "www.akhbar-today.com",
"snapshot_id": "CC-MAIN-2024-10",
"warc_metadata": {
"Content-Length": "105369",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:KI4KH5EVZ44ILBSB2RPIAZVSXXWKPMLW",
"WARC-Concurrent-To": "<urn:uuid:166b4c4b-6f0a-4708-9305-cccfb7759bf0>",
"WARC-Date": "2024-02-26T15:30:39",
"WARC-IP-Address": "173.198.227.134",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:RWDIXAGTWFKJVOA5O2CCH6FR5ZLRUOEK",
"WARC-Record-ID": "<urn:uuid:712807ce-93a9-4ec0-89bc-29660d038515>",
"WARC-Target-URI": "https://www.akhbar-today.com/clean-drinking-water-using-berkey-water-system/",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:085f6fd5-c270-4a84-b6ef-713252b84a31>"
},
"warc_info": "isPartOf: CC-MAIN-2024-10\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for February/March 2024\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-67-67-208\r\nsoftware: Apache Nutch 1.19 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 1.5-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: https://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
9,
10,
108,
109,
111,
112,
795,
796,
1071,
1072,
1107,
1108,
1714,
1715,
1752,
1753,
2372,
2373,
2412,
2413,
3079,
3080,
3116,
3117,
3644,
3645,
3670,
3671,
4079,
4080,
4109,
4110,
4575,
4576,
4595,
4596,
4981,
4982,
5015,
5016,
5497,
5498,
5790,
5791,
5809,
5810,
5819,
5820,
5841,
5842
],
"line_end_idx": [
9,
10,
108,
109,
111,
112,
795,
796,
1071,
1072,
1107,
1108,
1714,
1715,
1752,
1753,
2372,
2373,
2412,
2413,
3079,
3080,
3116,
3117,
3644,
3645,
3670,
3671,
4079,
4080,
4109,
4110,
4575,
4576,
4595,
4596,
4981,
4982,
5015,
5016,
5497,
5498,
5790,
5791,
5809,
5810,
5819,
5820,
5841,
5842,
5858
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 5858,
"ccnet_original_nlines": 50,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.46507805585861206,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.13311421871185303,
"rps_doc_frac_unique_words": 0.35433071851730347,
"rps_doc_mean_word_length": 4.6200785636901855,
"rps_doc_num_sentences": 82,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.2115960121154785,
"rps_doc_word_count": 1016,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.015338730067014694,
"rps_doc_frac_chars_dupe_6grams": 0,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.015338730067014694,
"rps_doc_frac_chars_top_3gram": 0.015338730067014694,
"rps_doc_frac_chars_top_4gram": 0.004686830099672079,
"rps_doc_books_importance": -520.2859497070312,
"rps_doc_books_importance_length_correction": -520.2859497070312,
"rps_doc_openwebtext_importance": -275.412353515625,
"rps_doc_openwebtext_importance_length_correction": -275.412353515625,
"rps_doc_wikipedia_importance": -222.3418731689453,
"rps_doc_wikipedia_importance_length_correction": -222.3418731689453
},
"fasttext": {
"dclm": 0.03138703107833862,
"english": 0.9609095454216003,
"fineweb_edu_approx": 2.1790573596954346,
"eai_general_math": 0.02783381938934326,
"eai_open_web_math": 0.17615270614624023,
"eai_web_code": 0.002023040084168315
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "613.2",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
},
"secondary": {
"code": "613.7",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "5",
"label": "Evaluate"
},
"secondary": {
"code": "2",
"label": "Understand"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "3",
"label": "Irrelevant Content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "16",
"label": "Personal Blog"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "2",
"label": "Partially Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
6e3c8d3593f3f69280bb5502b214ab8e
|
1,405,143,815,822,998,500
|
Acne is one of the most common skin disease affecting millions of people across the globe irrespective of their gender, race or age.
The good news, however, is that over time, a lot of medications and methods have been developed to prevent if not completely cure these breakouts.
This includes various antibiotic, anti retinoid and herbal and home remedies. This article will talk about one of the most widely and anciently used herbs in India and across the world, Turmeric.
Please feel free to use the Table of Contents below to jump to the relevant section
What is Turmeric?
Turmeric is a plant belonging to the ginger family and is native to south-east India.
It is scientifically known as Curcuma longa. India as such is one of the significant producers of turmeric. This plant thrives between 20 to 30 degrees Celsius.
This plant is gathered for its rhizomes which after being collected are boiled for 30 to 40 minutes and dried to be grounded into a yellow powder known as turmeric.
It is commonly used as a spice and for various other purposes which includes dying and medicinal benefits.
The ingredient of importance in it is known as the curcumin which exhibits antioxidant, antibacterial, anti-inflammatory, antiviral and antifungal properties which contributes towards its high medicinal value.
It is also believed to be effective in conditions of cancer, diabetes, Alzheimer’s, arthritis and other chronic diseases.
It has emerged as one of the most widely used alternative medicine. In China, it is also used as an antiseptic.
Turmeric as such can, however, to various uses. Some of them are enumerated below:
• It has been used as an essential spice in all curries and gravies in India since ages. It gives a unique flavor and color to the dish.
• It is a well known preservative.
• It is widely used as a pesticide against insects, ants and termites
• It forms an important part of the Hindu ritual rites and is also used in wedding ceremonies as a symbol of purity and marriage
• It is an important ingredient of many skin products.
How does turmeric treat acne
With its anti bacterial and anti fungal properties, turmeric helps in killing the P.acne bacteria which are responsible for causing acne breakouts.
Curcumin also exhibits anti oxidant and anti inflammatory properties which protects the skin from damage and also reduces the redness and marks caused due to inflammation.
Turmeric can be used in two ways to deal with the acne problem. It can either be taken orally or be applied topically in form of a paste:
• Oral in-take: turmeric can be ingested with one tablespoon of olive oil and black pepper. Piperine contained in pepper facilitates the absorption of turmeric into the blood stream.
It can also be taken in along with milk.
Dosage varies from person to person.
• Topical application: When used for as a skin care product, people mostly apply turmeric topically. It can be used in the form of a face mask or scrub. Some of the mask recipes are listed below:
Turmeric mask: This simply requires mixing 4 tablespoon of turmeric powder to 1 tablespoon of milk and 4 tablespoon of honey.
Mix in to form a uniform, consistent paste and keep it to cool. Clean your face with a non medicated soap and pat it dry before applying this mask.
Massage this gently onto your face for 10 minutes before washing it off with warm water. Milk not only softens the skin but also exfoliates the dead skin cells, honey on the other hand, nourishes, lubricates and hydrates the skin along with cleaning and exfoliating.
Turmeric, yogurt and avocado: This requires mixing a pinch of turmeric (1/4 tablespoon) to a spoon of mashed avocado and yogurt to form a smooth, uniform paste.
Apply it after cleaning your face, gently massaging in circular motion for about 5 minutes after which it can rinsed off with cold water.
While yogurt’s anti bacterial properties along with vitamin B, zinc and calcium is very healthy for the skin, avocado with its anti inflammatory property tends to hydrate and nourish the skin.
Lentil, oatmeal and turmeric: This requires mixing 1 tablespoon of oatmeal flour, 1 tablespoon of lentil powder and ½ tablespoon of turmeric in fresh water to form a smooth paste.
Apply the paste on your face and leave it for 15 to 20 minutes after which it can be washed alternatively with cold and warm water.
You can moisturize your skin after washing it off. The grains of oatmeal and coarseness of oatmeal will facilitate exfoliation and removal of dead skin cell.
Fuller’s earth turmeric facial mask: This mask can be made by mixing 1 tablespoon of Fuller’s earth and 1 tablespoon of turmeric to fresh water.
This paste can then be applied and left on for about 20 to 30 minutes and then washed with cold water. The drying effect of Fuller’s earth will cause osmosis which will alienate the bacteria of the required liquid to survive in.
Benefits of using turmeric
Turmeric is known to benefit various skin and general health conditions. Some of these benefits are listed below:
• It is a strong anti-oxidant and protects you against oxidative damage. Its anti-oxidant activity can be compared to that of vitamin C and vitamin E.
• Its anti-inflammatory activity is as effective in treating acute inflammation as cortisone and half as effective in treating chronic inflammation.
• It protects the liver against toxicity by a number of compounds. This is mostly the result of its anti oxidant property as well as of its capability of inducing increased secretion of bile salts, cholesterol and bilirubin.
• It facilitates the circulation of platelets by preventing them from accumulating together.
• Curcumin exhibits anti mutagenic properties which is helpful in the prevention of the development of new cancers as a result of chemotherapy or radiation therapy. It inhibits the spreading of skin cancer cells and is also effective in deactivating carcinogens in smokes and tobacco.
• It is an effective anti microbial and is used against various kinds of bacterial and fungal infections.
• It lowers the cholesterol level and prevents platelet accumulation thereby reducing the risks of cardiovascular disease and strokes. Its effect on cholesterol is largely a result of its efficacy in converting cholesterol into bile acids.
• It is often used as a treatment for leprosy, insect bites and during pregnancy.
• Turmeric is effective in healing gastric ulcers.
• When massaged onto the teeth and gum, it can provide relief to dental pain and swelling.
Possible Side Effects of Using Turmeric
Turmeric has been given the GRAS drug certificate which means generally regarded as safe. However, in extreme cases, it might have the following side effects:
• It can cause gall bladder problems, specifically GERD or gastro esophageal reflux disorder and cause gastric irritation and diarrhea.
• It can result in allergic reactions like upset stomach and nausea.
• It can slow down the process of blood clotting and might not be safe to be used immediately before and after a surgery.
Precautions while using turmeric
The following precautions must be observed while using turmeric, topically or orally:
• Avoid taking turmeric close to the time of some surgery you might be undergoing.
• It has also been suggested that curcumin may stimulate the uterus or promote a menstrual flow and can lead to a miscarriage in pregnant woman. Therefore its use during pregnancy is generally avoided.
• Turmeric can result in staining because of its dying property and therefore you must be careful while using it.
Drug interaction
Because of the ability of turmeric to prevent the accumulation of platelets, it slows down the process of clotting and therefore must not be taken with medicines slows down the process of clotting as it might not help in stooping the bleeding of wounds and bruises.
Some such medicines are aspirin and dedofinac among others.
Customer Review
We did an analysis of online reviews by consumers to see what they liked and disliked about turmeric. Here is a summary of that:
What they liked about it
Inexpensive: One thing that motivated most buyers to try this out once was the inexpensiveness and easy availability of turmeric. Since it is so readily available and you see it at every corner you are motivated to give it one try.
Lightens scars: Turmeric is effective in lightening the skin and also reduces hyper pigmentation. This lightening effect has been in use since ages and as a ceremonial rite, applied on the skin of every groom and bride in a Hindu wedding before the wedding night.
Better skin: Most consumers felt that it is very effective in maintaining the health of the skin as a whole. It evens down the skin tone and also works towards improving the complexion of the skin making it fair and glowing.
What they did not like about it
Burns: A few consumers faced the problem of burning and irritation on the application of turmeric. This might be the result of allergy to turmeric and it is therefore advised that you do a patch test before starting to use it completely on your skin.
Dyes yellow: one consistent problem faced by a few consumers, most of them fairly white skinned were that turmeric tends to dye your skin yellow if left for a sufficiently long time. However it is suggested that you can use milk to undo this yellowness and it will come out quiet easily
Summary
Plants have been a major source of medicine since centuries.
Turmeric is probably one of the most widely used herbal and alternative medication that has been used since centuries across the globe specifically in the Indian sub-continent.
It is a very useful substance for maintaining the general health of a person even if you are not suffering severely from any particular disease.
Its in-take on a regular basis is as such a healthy practice. Its anti oxidant, anti bacterial and anti inflammatory activities attacks the problem of acne from all sides to affect quick results.
The side effects are pretty rare and benefits are huge. This will not be a burden on your pocket and is definitely worth a try.
LEAVE A REPLY
Please enter your comment!
Please enter your name here
*
|
{
"url": "https://healthyy.net/acne/home-remedies/why-turmeric-is-great-for-acne-how-to-use-it",
"source_domain": "healthyy.net",
"snapshot_id": "crawl=CC-MAIN-2018-47",
"warc_metadata": {
"Content-Length": "68958",
"Content-Type": "application/http; msgtype=response",
"WARC-Block-Digest": "sha1:KFTFR63XUGMWY7X3WVYDENXILNY4EJE7",
"WARC-Concurrent-To": "<urn:uuid:3e79c8bd-a2a8-438e-b613-c8422865b8f1>",
"WARC-Date": "2018-11-17T00:03:45",
"WARC-IP-Address": "185.56.84.221",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:V5JYTCWEE2GZGXHYR54VOPT37M3A7JHK",
"WARC-Record-ID": "<urn:uuid:558cf8e7-ce2f-4be0-a252-6c5e0229cfd8>",
"WARC-Target-URI": "https://healthyy.net/acne/home-remedies/why-turmeric-is-great-for-acne-how-to-use-it",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:0c0619bc-0cc8-4ccf-81f7-ce6d2ccafa33>"
},
"warc_info": "isPartOf: CC-MAIN-2018-47\r\npublisher: Common Crawl\r\ndescription: Wide crawl of the web for November 2018\r\noperator: Common Crawl Admin ([email protected])\r\nhostname: ip-10-229-80-62.ec2.internal\r\nsoftware: Apache Nutch 1.15 (modified, https://github.com/commoncrawl/nutch/)\r\nrobots: checked via crawler-commons 0.11-SNAPSHOT (https://github.com/crawler-commons/crawler-commons)\r\nformat: WARC File Format 1.1\r\nconformsTo: http://iipc.github.io/warc-specifications/specifications/warc-format/warc-1.1/"
}
|
{
"line_start_idx": [
0,
133,
134,
281,
282,
478,
479,
563,
564,
582,
583,
669,
670,
831,
832,
997,
998,
1105,
1106,
1316,
1317,
1439,
1440,
1552,
1553,
1636,
1637,
1776,
1813,
1885,
2016,
2073,
2074,
2103,
2104,
2252,
2253,
2425,
2426,
2564,
2565,
2750,
2795,
2836,
3034,
3035,
3161,
3162,
3310,
3311,
3578,
3579,
3740,
3741,
3879,
3880,
4073,
4074,
4254,
4255,
4387,
4388,
4546,
4547,
4692,
4693,
4922,
4923,
4950,
4951,
5065,
5066,
5219,
5370,
5597,
5692,
5979,
6087,
6329,
6413,
6466,
6559,
6560,
6600,
6601,
6760,
6761,
6899,
6970,
7094,
7095,
7128,
7129,
7215,
7216,
7301,
7505,
7621,
7622,
7639,
7640,
7906,
7966,
7967,
7983,
7984,
8113,
8114,
8139,
8140,
8372,
8373,
8637,
8638,
8863,
8864,
8896,
8897,
9148,
9149,
9436,
9437,
9445,
9446,
9507,
9508,
9685,
9686,
9831,
9832,
10028,
10029,
10157,
10158,
10172,
10173,
10200,
10228,
10229
],
"line_end_idx": [
133,
134,
281,
282,
478,
479,
563,
564,
582,
583,
669,
670,
831,
832,
997,
998,
1105,
1106,
1316,
1317,
1439,
1440,
1552,
1553,
1636,
1637,
1776,
1813,
1885,
2016,
2073,
2074,
2103,
2104,
2252,
2253,
2425,
2426,
2564,
2565,
2750,
2795,
2836,
3034,
3035,
3161,
3162,
3310,
3311,
3578,
3579,
3740,
3741,
3879,
3880,
4073,
4074,
4254,
4255,
4387,
4388,
4546,
4547,
4692,
4693,
4922,
4923,
4950,
4951,
5065,
5066,
5219,
5370,
5597,
5692,
5979,
6087,
6329,
6413,
6466,
6559,
6560,
6600,
6601,
6760,
6761,
6899,
6970,
7094,
7095,
7128,
7129,
7215,
7216,
7301,
7505,
7621,
7622,
7639,
7640,
7906,
7966,
7967,
7983,
7984,
8113,
8114,
8139,
8140,
8372,
8373,
8637,
8638,
8863,
8864,
8896,
8897,
9148,
9149,
9436,
9437,
9445,
9446,
9507,
9508,
9685,
9686,
9831,
9832,
10028,
10029,
10157,
10158,
10172,
10173,
10200,
10228,
10229,
10230
]
}
|
{
"red_pajama_v2": {
"ccnet_original_length": 10230,
"ccnet_original_nlines": 138,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.44397684931755066,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.005260390229523182,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.10836402326822281,
"rps_doc_frac_unique_words": 0.3592571020126343,
"rps_doc_mean_word_length": 4.780615329742432,
"rps_doc_num_sentences": 89,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.52628755569458,
"rps_doc_word_count": 1723,
"rps_doc_frac_chars_dupe_10grams": 0,
"rps_doc_frac_chars_dupe_5grams": 0.019910160452127457,
"rps_doc_frac_chars_dupe_6grams": 0.012383149936795235,
"rps_doc_frac_chars_dupe_7grams": 0,
"rps_doc_frac_chars_dupe_8grams": 0,
"rps_doc_frac_chars_dupe_9grams": 0,
"rps_doc_frac_chars_top_2gram": 0.007769819814711809,
"rps_doc_frac_chars_top_3gram": 0.0036420999094843864,
"rps_doc_frac_chars_top_4gram": 0.005827359855175018,
"rps_doc_books_importance": -711.814453125,
"rps_doc_books_importance_length_correction": -711.814453125,
"rps_doc_openwebtext_importance": -419.93841552734375,
"rps_doc_openwebtext_importance_length_correction": -419.93841552734375,
"rps_doc_wikipedia_importance": -213.56163024902344,
"rps_doc_wikipedia_importance_length_correction": -213.56163024902344
},
"fasttext": {
"dclm": 0.029290560632944107,
"english": 0.9593405723571777,
"fineweb_edu_approx": 2.7632737159729004,
"eai_general_math": 0.08716356754302979,
"eai_open_web_math": 0.3425530791282654,
"eai_web_code": 0.0013824099441990256
}
}
|
{
"free_decimal_correspondence": {
"primary": {
"code": "615.65",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Materia medica, Drugs, and Pharmacy"
}
},
"secondary": {
"code": "613.25",
"labels": {
"level_1": "Industrial arts, Technology, and Engineering",
"level_2": "Medicine",
"level_3": "Health and Hygiene"
}
}
},
"bloom_cognitive_process": {
"primary": {
"code": "2",
"label": "Understand"
},
"secondary": {
"code": "3",
"label": "Apply"
}
},
"bloom_knowledge_domain": {
"primary": {
"code": "2",
"label": "Conceptual"
},
"secondary": {
"code": "3",
"label": "Procedural"
}
},
"document_type_v1": {
"primary": {
"code": "3",
"label": "Reference/Encyclopedic/Educational"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"extraction_artifacts": {
"primary": {
"code": "0",
"label": "No Artifacts"
},
"secondary": {
"code": "3",
"label": "Irrelevant Content"
}
},
"missing_content": {
"primary": {
"code": "0",
"label": "No missing content"
},
"secondary": {
"code": "-1",
"label": "Abstain"
}
},
"document_type_v2": {
"primary": {
"code": "10",
"label": "Knowledge Article"
},
"secondary": {
"code": "23",
"label": "Tutorial"
}
},
"reasoning_depth": {
"primary": {
"code": "2",
"label": "Basic Reasoning"
},
"secondary": {
"code": "3",
"label": "Intermediate Reasoning"
}
},
"technical_correctness": {
"primary": {
"code": "3",
"label": "Mostly Correct"
},
"secondary": {
"code": "2",
"label": "Partially Correct"
}
},
"education_level": {
"primary": {
"code": "1",
"label": "General Audience"
},
"secondary": {
"code": "2",
"label": "High School Level"
}
}
}
|
9222580d47c553ea90dc0f5e416f8f3a
|
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.