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Health Benefits of Biotin
<p>Health Benefits of Biotin</p>
Dr. Constance Odom, MD Picture of Dr. Constance Odom, MD
Medically reviewed by
Written by our editorial team.
Last Edited 5 min read
Β
Biotin is a B-vitamin, and is also known by the name of vitamin B7. It was once known as coenzyme R, or vitamin H. The H stood for Haar und Haut, the German words for Hair and Skin. Biotin is water soluble, which means that it dissolves in water, and has many important functions in the body.Β
Β
Biotin is necessary for the functions of several enzymes that are known as carboxylases, which are biotin-containing enzymes that participate in important metabolic functions, like the production of glucose and fatty acids. Commonly recommended, the intake is about five micrograms per day in infants and thirty micrograms in adults. This can be increased to thirty five micrograms per day in breastfeeding women.Β
Β
Deficiency for biotin is fairly rare, but some groups of people are more likely to experience it in mild forms, such as pregnant women. Other factors, such as consuming raw eggs, can cause a deficiency. But to do something like that, you'd have to dine on raw eggs for quite a long amount of time. Raw egg whites contain a protein called avidin, which binds to biotin and prevents it from being absorbed by the body. Thankfully, it's rendered inactive during cooking.Β
Β
Biotin is a key vitamin for energy production, and several enzymes require it to properly function. These enzymes are specifically involved in fat, protein, and carb metabolizm, and initiate crucial parts of the metabolic processes of these nutrients. Biotin plays a role in fatty acid synthesis by assisting enzymes that activate reactions important to breaking down fatty acids. It's also important in gluconeogenisis, which is the metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates. Gluconeogenesis is one of the several main mechanisms used by humans and many animals to maintain blood glucose levels, avoiding hypoglycemia. It's also important in the breakdown of amino acids, as biotin-containing enzymes are involved in the metabolism of several important kinds, such as leucine.Β
Β
Biotin is important for more cosmetic purposes as well, such as brittle nails for one. Brittle nails are nails that are weak can become easily chipped, cracked, or split. It's very common to have brittle nails, unfortunately, as an estimated twenty percent of people around the globe are effected. But, in one study, eight people with brittle nails were given 2.5mg of biotin, per day, for a minimum of six up to fifteen months. Thickness in the nails improved by twenty five percent in all eight participants, and nail splitting was also reduced. In yet another study, thirty five people with brittle nails found that 2.5mg of biotin a day for one and a half to seven months improved symptoms in sixty seven percent of participants. These studies were rather small, however, and more research is certainly needed.Β
Β
In a similar cosmetic vain, biotin is also often associated with an increase of hair growth, and not just any kind, but healthier, and stronger hair. And while more research is certainly needed to back this claim, a deficiency in biotin may lead to hair loss, which indicated and importance in the vitamin when it comes to maintaining a lush mane of hair. Whether or not it improves hair growth in healthy people, the jury's still out on that, but people with even a slight deficiency should certainly see results from added supplementation.Β
Β
Biotin may even help controlling the blood sugar levels of those who have diabetes. Type two diabetes is a metabolic disease, and is characterized by high blood sugar levels and impaired insulin function. Recently, researches have studied how biotin supplements affect blood sugar levels in type two diabetics, and some evidence shows that biotin concentrations in blood may be lower in people with diabetes, compared to healthier individuals. Studies in diabetics given biotin alone have, as of it, provided mixed results. On the other hand, several controlled studies have shown that biotin supplements, combined with the mineral chromium, may lower blood sugar levels in some people with type two diabetes.Β
Β
When it comes to skin, Biotin's role in skin healthy isn't fully understood, but it is known that you may get red, scaly skin rashes if you have a biotin deficiency. Other studies have also suggested that biotin deficiency may sometimes cause a skin disorder known as seborrheic dermatits, or cradle cap, as it's more commonly known. Biotin's role in skin healthy could possibly be related to it's effect on fat metabolism, which is important for the skin and may be impaired when dealing with a deficiency.Β
Β
Biotin is important when it comes to pregnancy and breastfeeding, and require an increased requirement for the vitamin. It's actually been estimated that about half of all women who get pregnant may develop a mild deficiency in the vitamin. This means that it may start to affect their well being, but not enough to cause noticeable symptoms. Deficiencies are thought to occur in pregnant women thanks to faster breakdown during pregnancy. Additional, a major cause for concern in these women is that animals studies have found that a biotin deficiency has shown to be alongside many birth defects, and may be a contributing factor. Nevertheless, remember to always consult your doctor or dietitian/nutritionist before taking supplements during pregnancy and while breastfeeding.
Β
Biotin also may affect multiple sclerosis, which is an autoimmune disease. In MS, the protective covering of nerve fibers in the brain, spinal cord, and eyes is damaged or destroyed. This protective covering is called myelin, and biotin is known to be an important factor in producing it. In fact, a pilot study in twenty three people with progressive Multiple Sclerosis tested the use of high doses of biotin, and over ninty percent of participants had some degree of improvement. And of course, this finding needs much more study, at least two randomized controlled trials have been carried out in people with progressive MS. The final results have not been published, but the preliminary results are promising.
Β
Biotin is found in a rather wide variety of foods, which means that deficiency while not impossible, is rare. Such foods include Wheat germ, whole-grain cereals, whole wheat bread, eggs, dairy products, peanuts, soya nuts, Swiss chard, salmon, and chicken are all sources of biotin, alongside organ meats, such as liver and kidney and mushrooms. A bit of it is even produced by the bacteria in your stomach, on it's own or as a component of mixed vitamin supplements.Β
Β
To top all of these benefits off, biotin is considered extremely safe. Even massive doses of up to three hundred milligrams a day, which is what was used to test multiple sclerosis and it's effects, have not led to any adverse side effects. And because it's a water-soluble vitamin, excess of it is lead out of the body in urine. However, there have been some reports of high-dose biotin causing strange results on thyroid tests, so check with a doctor before using if you are currently taking thyroid medication.
Β
This article is for informational purposes only and does not constitute medical advice. The information contained herein is not a substitute for and should never be relied upon for professional medical advice. Always talk to your physician about the risks and benefits of any treatment. Nu Image Medical may not offer the medications or services mentioned in this article. | {
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Zvarova, Barbora; Uhl, Franziska E.; Uriarte, Juan J.; Borg, Zachary D.; Coffey, Amy L.; Bonenfant, Nicholas R.; Weiss, Daniel J. and Wagner, Darcy E. (2016): Residual Detergent Detection Method for Nondestructive Cytocompatibility Evaluation of Decellularized Whole Lung Scaffolds. In: Tissue Engineering Part C-Methods, Vol. 22, No. 5: pp. 418-428
Full text not available from 'Open Access LMU'.
Abstract
The development of reliable tissue engineering methods using decellularized cadaveric or donor lungs could potentially provide a new source of lung tissue. The vast majority of current lung decellularization protocols are detergent based and incompletely removed residual detergents may have a deleterious impact on subsequent scaffold recellularization. Detergent removal and quality control measures that rigorously and reliably confirm removal, ideally utilizing nondestructive methods, are thus critical for generating optimal acellular scaffolds suitable for potential clinical translation. Using a modified and optimized version of a methylene blue-based detergent assay, we developed a straightforward, noninvasive method for easily and reliably detecting two of the most commonly utilized anionic detergents, sodium deoxycholate (SDC) and sodium dodecyl sulfate (SDS), in lung decellularization effluents. In parallel studies, we sought to determine the threshold of detergent concentration that was cytotoxic using four different representative human cell types utilized in the study of lung recellularization: human bronchial epithelial cells, human pulmonary vascular endothelial cells (CBF12), human lung fibroblasts, and human mesenchymal stem cells. Notably, different cells have varying thresholds for either SDC or SDS-based detergent-induced cytotoxicity. These studies demonstrate the importance of reliably removing residual detergents and argue that multiple cell lines should be tested in cytocompatibility-based assessments of acellular scaffolds. The detergent detection assay presented here is a useful nondestructive tool for assessing detergent removal in potential decellularization schemes or for use as a potential endpoint in future clinical schemes, generating acellular lungs using anionic detergent-based decellularization protocols.
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-5,050,946,342,551,514,000 | Articles
Keto Diet Plan For Beginners - Be Healthy, Act Healthy and Eat healthy
by Cherry Lou Ms.
Keto Diet Benefits
Β Recently, the keto diet has become extremely popular for its health benefits such as weight loss and preventing disease. The keto diet can be hugely beneficial, but how does it work to provide these benefits?
Β
What is the Keto Diet?
You may have heard of the high-protein, low-carbohydrate Atkins diet. The keto diet keeps carbohydrate levels low, but instead of ramping up the amount of protein in your diet, the keto diet increases the amount of fat. A typical keto diet aims for meals with 75% fat, 20% protein, and 5% carbohydrate. Eating a high-fat diet can still mean eating healthy. Keto diet menu items often include seafood, meat, dairy products, eggs, vegetables, and nuts. With the increased popularity of the keto diet, keto recipes are widely available.
Β
How Does the Keto Diet Work?Β
It might seem counterintuitive that adding more fat to your diet can lead to weight loss. Normally, your diet is high in carbohydrates, which are broken down into glucose, or blood sugar, for use as energy. As glucose enters your bloodstream, your body releases insulin to store excess glucose as fat. The more carbohydrates, the more glucose. The more glucose, the more insulin, and the more insulin, the more fat.
The keto diet takes advantage of the fact that when your meals are high-fat and low-carbohydrate, there is no insulin spike, and you don't add to your fat reserves. Instead, fat from diet and stored fat are broken down to ketones ("keto" is short for "ketogenic" producing ketones). Like glucose, ketones can be used for energy, keeping your body running without increasing blood sugar or putting on excess fat. The benefits of the keto diet can be huge.
Β
Weight Loss
Β
Overall, the keto diet is an excellent way to burn fat and lose weight. Eating fewer carbohydrates suppresses appetite, and studies have shown that keto diet participants eat fewer calories overall because of this. Burning fat for energy can lead to rapid weight loss.
Β
Reduced Blood Sugar and Insulin
Β
Since carbohydrate intake is limited, blood sugar and insulin levels are lowered. This is particularly important for people with type 2 diabetes, which causes a buildup of glucose in the bloodstream. The keto diet can be used to reduce or eliminate the need for diabetic insulin injections.
Β Β
Reduced Triglycerides
Β
Fat subunit molecules called triglycerides normally circulate in your bloodstream. High levels of triglycerides are a significant risk factor in the development of heart disease. In the keto diet, because fat is being burned for energy, the number of triglyceride molecules in the bloodstream decreases, reducing the risk of heart disease.
Β
Improved Cholesterol
Β
"Bad" (LDL) cholesterol is another risk factor for heart disease. Too much bad cholesterol in your bloodstream builds up in your arteries, narrowing them and causing atherosclerosis, a type of heart disease. The keto diet reduces bad cholesterol levels while increasing the level of "good" (HDL) cholesterol in your body.
Β
SummaryΒ
The keto diet provides many health benefits. This diet can not only help you quickly lose weight, but can also improve your overall health and help prevent disease.
======================================
Check out this video : How Can I Make Keto Easier
======================================
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-6,955,039,733,293,893,000 | What can cause sinus infection ear pain? Ear pain can result from allergic rhinitis or a nasal allergy. Histamine and other substances are released by the body in response to allergens.
These substances irritate the sinuses and nose, which might impact the ear and result in ear pain. Ear infections can occasionally also be brought on by swelling and fluid accumulation.
A person can visit their doctor or an allergist to get a diagnosis and learn if allergies are to blame for ear pain. A person can take precautions to avoid or minimise their exposure to allergens once they are aware of which ones could cause an allergic reaction.
Antihistamines, decongestants, and allergy injections are a few of the drugs that can help with the symptoms. Any ear pain caused by allergies should go away with treatment.
In this article, we will discuss:
what you will read next :
What is sinusitis?
The sinuses are tiny air sacs situated behind the cheekbones, forehead, nose, and between the eyes. Sinusitis is an inflammation of the sinuses and nasal passages.
Conditions include structural problems in the nose or a sinus infection can cause inflammation.
The terms βsinusitisβ and βsinus infectionβ, however, are used synonymously.
Headaches and sinus pressure are symptoms of sinusitis, often known as a sinus infection. Inflammation or swelling in the sinus and nasal mucosa is what causes sinusitis. Your facial bonesβ sinuses are hollow air chambers located close to the nose.
Mucus is created by them, helping to lining the nose and keep dust and other particles from getting into your lungs.
Although there are several causes of sinusitis, it always happens as a result of moisture becoming trapped in the sinuses, which allows bacteria to flourish.
A virus is the most frequent cause, but sinusitis can also be brought on by a bacterialΒ infection.
Allergies, asthma, and airborne contaminants like chemicals or other irritants can all act as triggers.
Molds and fungi both have the potential to cause fungal sinusitis.
How does the inner ear work?
In reaction to variations in pressure in the surrounding environment, the eustachian tubes help maintain normal air pressure in the middle ear.
However, if allergies or sinus congestion clog these tubes, you could experience a number of issues, including ear infections.
What does a eustachian tube actually do?
Itβs a tiny canal that connects your middle ear, which houses your eardrum, to the back of your throat and nose. It is only a few millimetres in diameter and is only about 1.5 inches long.
The same type of moist membrane that lines the nose and throat also lines the eustachian tubes.They are normally closed, but when the back of the nose and throat move, as they do when you swallow, yawn, or talk, they open.
Eustachian tubes in adults are inclined downward from the ear into the back of the throat, allowing for middle ear fluid and mucus outflow by gravity.
Sounds that reach your outer ear are converted by your middle ear into vibrations that your inner ear and brain can understand. Your middle ear has to maintain the same air pressure as the air around you in order to function effectively.
As a result, your eustachian tubes periodically open to allow air to flow into your middle ear, bringing the pressure there into balance with the pressure in the back of your throat.
If Your Eustachian Tubes dysfunction:
Your eustachian tubes and middle ear may get damaged for a variety of reasons, including:
Swelling-induced obstruction:
Due to eustachian tube obstruction, middle ear occlusion is a common symptom of sinus pressure in sufferers. Most frequently, a sinus infection, a cold, or allergies are to blame for this swelling.
The inner ear membranes may enlarge as a result of these disorders, obstructing the tubes. A clogged eustachian tube is unable to properly discharge mucus or circulate air.
Mechanical obstruction:
Ear blockage can occasionally be brought on by nasal tissues that have grown excessively, such as nasal polyps or adenoids, blocking the passage to the eustachian tube. A tumour can occasionally result in an obstruction.
Medial otitis (middle ear inflammation or infection):
The middle ear may fill with fluid and become irritated when sinus congestion results in a clogged eustachian tube. Similar to bacterial sinus infections, middle ear infections can result in swelling and further fluid buildup if they invade your eustachian tubes. Otitis media is linkedΒ to ear pressure and pain.
Damaged eardrum: Your eardrum could be torn if there is an excessive buildup of fluid in your inner ear.
Do you have a sinus infection with ear pain? What is the link between these two?
Parts of the nasal cavity get infected when an upper respiratory illness, such as a sinus infection, is present. The eustachian tubes and other sinus drainage passages expand and get blocked as a result of the inflammation.
Pressure on the tubes starts to increase as the trapped fluid starts to swell, which is very uncomfortable. The buildup could cause sinusitis or otitis media if it is not properly managed.
In reality, bacterial and viral infections are the common causes of both sinus and ear infections. It is simple for an infection to travel from the sinuses to the middle ear and result in an ear infection once it has established itself there.
You agree to experience all the symptoms of a sinus infection as well as the extra symptoms of ear discomfort and/or plugged ears if you have these two infections concurrently.
While these widespread causes can make it more challenging to diagnose your condition,Β they also make it such that treating one infection is similar to treating the other.
Therefore, knowing the typical causes of ear infections and sinus infections might reduce your risk of developing both diseases simultaneously. Now letβs look at these causes.
How do you know if it is a sinus infection or ear infection causing ear pain?
Headaches brought on by the pressure and swelling of the sinuses or sinus cavities are one of the signs of a sinus infection.
If you have severe sinus pressure, your ears might not pop. Other signs include nasal discharge that is a greenish-yellow tint, pain in your ears, and pain beneath your eyes. Congestion can be brought on by sinus discharge, which may irritate your sinuses.
Allergies, smog in the air, and the shape of the nose all contribute to sinus infections. Itβs crucial to keep track of what makes your sinuses flare up.
Is mould, for instance, more likely to cause a sinus infection? Is dust to blame? Or are less typical factors like diabetes, an inflammatory disease, or a fungal infection to blame for your sinus infections?
Once you are aware of the source of your sinus infections, you can lower your risk of contracting sinusitis by washing your hands frequently, avoiding touching your face, drying your hair after a shower, getting immunised, creating a sinus-friendly environment in your home by cleaning it frequently and changing the air filter, and avoiding caffeine and alcohol.
Try taking antihistamines if allergies are the source of your sinus infections. Antifungal medications can help prevent sinusitis brought on by fungus infections.
Finally, immunoglobulin can aid in the battle against the irritants that cause sinus infections if you have immune weaknesses.
Ear infections and frequent, severe sinus infections could be signs of acute or chronic sinusitis. Even with acute or chronic sinusitis, there are therapy alternatives to get long-lasting relief.
what can be the causes of ear pain?
There are many causes of ear pain some of which include sinus infections, buildup of fluid, buildup of wax, allergies, travel, blocked ear canal, or ear infections.
Some uncommon causes of ear pain include:
This inner ear condition results in severe vertigo and hearing loss. People between the ages of 40 and 60 are more prone to it. Although the diseaseβs source is still unknown, fluid accumulation in the labyrinths, which are compartments of the inner ear, is what causes the symptoms.
On the nerve that connects your inner ear to your brain, there is a noncancerous growth that is slowly expanding. As the tumour grows, symptoms, which are often mild and develop gradually, may also include tinnitus, vertigo, and balance issues.
Poor Eustachian tube function or a middle ear infection can lead to abnormal growth known as a cholesteatoma forming in the middle ear.
This particular middle ear condition involves an accumulation of clear fluid, often known as serous fluid. One of the common side effects is hearing loss.
Children are more likely to experience this issue following an ear infection.
People who frequently swim, reside in warm areas, have diabetes, or suffer from chronic skinΒ disorders are more likely to develop fungal ear infections.
They can be brought on by more than 60 different varieties of fungi. Fungal ear infections can also result in hearing issues, ringing in the ears, swelling, pain, and itching.
Treatment of ear pain on the basis of its cause.
Issues related to sinus infection causing ear pain:
Following are some methods for treating sinus congestion and accompanying ear congestion:
Buildup of fluids:
Congestion in the ears might result from getting water in them while swimming or taking a shower. In order to get water out of your ear, try the following:
Allergies:
When mucus builds up and becomes lodged in your middle ear or Eustachian tube due to allergies, you may experience ear congestion. Antihistamines and decongestants are common allergy drugs that can help with ear congestion and associated symptoms.
Blocked ear canal:
Do not attempt to remove a foreign object from your ear canal if you have a suspicion that it may be there. Visit your doctor immediately away instead, or go to the closest ER or urgent care facility.
Ear infections:
Dizziness, ear pain, and occasionally fluid discharge are all symptoms of a middle ear infection in addition to ear congestion. Colds or other respiratory conditions that enter the middle ear through the Eustachian tube are typically to blame for them.
Swimmerβs ear, also known as an external ear infection, is typically brought on by water that stays in your ear after bathing or swimming, creating an excellent environment for bacteria to grow. You might feel discomfort, itchiness, redness, clear fluid drainage, or pus discharge.
Β
Β
Most ear infections heal on their own. Painkillers and over-the-counter ear drops can help you feel better. Your doctor might advise taking antibiotics if your symptoms are serious or last for more than two days.
How to relieve sinus pressure inside the ear?
The pressure inside the ear is really unpleasant. A person may experience slight pain, muted sound, or a feeling of having water in their ears when fluid is present.
These symptoms can interfere with your daily activities if the sinus pressure is not treated. Fortunately, there are several options for getting some relief.
When your sinuses are dry, pressure worsens. A humidifier will keep your sinuses moist all day long. Regardless of the temperature, they continue to contribute moisture to the air. Even though you can run them during the day, you should run them at night to help with congestion relief.
Using the steam from hot water is another way to cause drainage. This technique has been used for many years since the steamβs heat opens up channels that allow the fluid to drain. Just heat some water until it boils, then pour it into a basin. Put a towel over your head and place your head over the bowl. In order to breathe it in and reduce ear pressure, the towel will help hold onto as much of the steam as possible.
Itβs difficult to go asleep when your ear is blocked. Even with the pressure alone, it might get uncomfortable if you donβt get into a decent position. Set your pillows up to slightly support you while you get ready for bed. By doing this, you will prevent the liquid from entering your ears further. Keep the obstructed ear closest to the bed if you like to sleep on your side.
One of the many incredible health advantages of water for the body is the reduction of sinus-related ear pressure. Increasing your water consumption will assist the body fight off theΒ infection and washing out pollutants. Additionally, it gives your eustachian tubes more chances to open while swallowing. This action will assist in adjusting the pressure in your ear. to your ears, please.
diagnosis
To determine whether you have a sinus infection, your doctor will often do a physical examination and examine your medical history.
After confirming that you have sinusitis, your doctor may perform additional tests to identify whether it is acute, subacute, chronic, or recurrent. Your doctor can determine the best course of treatment for your sinusitis with the knowledge of its type.
In order to establish how to proceed with the recommended treatment, your doctor will also determine whether or not your sinusitis is bacterial.
Rarely, a fungus may be to blame for sinusitis. It is an extremely dangerous medical emergency when this occurs. Your doctor can help you identify the best course of action and determine whether a fungus is to blame for your sinusitis.
When to see a doctor
Home treatments and over-the-counter pharmaceuticals are frequently used to alleviate ear congestion.
But if a person has ear congestion, they might wish to consult a doctor:
summary
Ear pain can result from allergic rhinitis or a nasal allergy. Histamine and other substances are released by the body in response to allergens.
These substances irritate the sinuses and nose, which might impact the ear and result in ear pain. Ear infections can occasionally also be brought on by swelling and fluid accumulation.
A person can visit their doctor or an allergist to get a diagnosis and learn if allergies are to blame for ear pain.
A person can take precautions to avoid or minimize their exposure to allergens once they are aware of which ones could cause an allergic reaction.
Antihistamines, decongestants, and allergy injections are a few of the drugs that can help with the symptoms. Any ear pain caused by allergies should go away with treatment.
Β
Leave a Reply | {
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8,455,049,482,297,758,000 | Why do I need this surgery?
What will this surgery do?
What are the risks and possible complications of this surgery?
What are my non-surgical options?
Are there any other surgical options?
What can I expect if I choose not to have this procedure?
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How will my jawline be affected by this surgery?
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Where and how big will my incision be?
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What can I expect my pain to be like?
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1,112,610,694,442,351,100 | What Are the Types of ADHD in Teens?
by | Mar 8, 2022
Extracted from an article by David Perlstein, MD, MBA, FAAP edited by William C. Shiel Jr., MD, FACP, FACR
Attention deficit hyperactivity disorderΒ (ADHD) is a behavioral disorder that involves abnormal thought processing. The symptoms of this disorder have been described in the known medical literature for at least the past 200 years. It is characterized by problems focusing, sitting still, and/or controlling impulses. It can have a significantly negative impact on the suffererβs ability to make and keep friends and other relationships and do well in high school, at work, and/or the community in general.Β Low self-esteem is a common side effect of the behaviors displayed by a teen with ADHD.
Types of ADHD in Teens
ADHD is understood as either one of three types: the primarily inattentive type, the primarily impulsive/hyperactive type, and the combined type. The primarily inattentive type is characterized by the person having great difficulty listening, focusing, organizing his or herself, and completing tasks. A teen with the inattentive version of ADHD generally does not have a significant problem managing their impulses or activity level. The primarily impulsive/hyperactive type of ADHD tends to result in the opposite set of symptoms compared to the inattentive type. Such a patient will have significant attention problems since he/she has great trouble sitting still, waiting their turn to talk, and managing their impulses. The individual who has the combined type of ADHD struggles with some aspects of inattention, impulsiveness, and hyperactivity.\
What Are Causes and Risk Factors for ADHD in Teens?
ADHD is quite common. Among school-aged children, this disorder has been found to occur from 2%-20%, translating to 4.5 million children 3-17 years of age. While boys are still thought to develop this illness more often than girls, improved assessment of girls has resulted in the gender gap in diagnosis being significantly less than in years past.
ADHD in Teens Causes and Risk Factors
While there is no single known cause of ADHD, boys tend to develop this condition a bit more often than girls, and young people who have one or both parents with the disorder are more likely to develop it. Children who have ADHD are at risk for becoming teenagers and adults with the condition. A child whose mother suffers fromΒ depression, smoked cigarettes, or used other drugs or whose parents have lower levels of education are more at risk for having ADHD. Other risk factors for developing ADHD include the personβs mother having medical problems andΒ traumaΒ to the abdomen during theirΒ pregnancy. There is some birth order research that supports the theory that first-born children tend to have a higher likelihood of developing ADHD compared to their siblings.
What AreΒ Symptoms and Signs of ADHD in Teens?
Common symptoms and signs of ADHD can include the following:
Inattention
β’ Trouble paying close attention or making careless mistakes
β’ Does not seem to be listening when directly spoken to
β’ Avoids or fails to follow through on instructions or to finish tasks (including homework)
β’ Has difficulty organizing tasks and activities
β’ Often avoids or dislikes tasks that require sustained attention
β’ Frequently loses things needed to perform tasks or activities
β’ Tendency to get distracted easily
β’ Often forgetful or inattentive
Hyperactivity and Impulsivity
β’ Tends to fidget
β’ Has trouble staying seated when doing so is necessary or expected
β’ Trouble engaging in activities quietly
β’ May feel restless or easily bored
β’ May talk excessively
β’ Often blurts out answers or interrupts othersΒ impulsively
β’ Frequently has trouble waiting his or her turn during activities
ADHD symptoms and signs in teenagers
While symptoms of hyperactivity in people with ADHD tend to decrease with age, most of the differences in symptoms of this disorder in adolescents compared to children and adults have much to do with the tasks that tweens and teens are called on to do at this stage of their lives. For example, teens with ADHD tend to show lower grade point averages, lower levels of class placement (for example, remedial versus honors or advanced placement), and higher rates of course failure. Also, teens with this diagnosis tend to complete and turn in a much lower percentage of in-class and homework assignments and are much less likely to be working up to their potential. Adolescents with ADHD are significantly more likely to be absent or tardy from school, and they can be over eight times more likely than adolescents without ADHD to drop out of high school. ADHD teens tend to be more impulsive drivers and have more accidents due to risky behaviors. Research has also shown that ADHD teens have more difficulty making and keeping well-adjusted friends. Unfortunately, in the face of the unique and significant impact that ADHD can have on their lives, teens tend to be the least willing to receive treatment compared to their younger and older counterparts. Research shows that adolescents are often more likely to have a negative perception of treatment and to be more likely to expect to have a bad experience as a result of ADHD treatment.Β Substance abuseΒ is more common in teens with ADHD than their peer non-ADHD population.
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-8,590,380,136,793,349,000 | Skip to main content
Similar immune mechanisms control experimental airway eosinophilia elicited by different allergens and treatment protocols
Abstract
Background
Mouse models have been extremely valuable in identifying the fundamental mechanisms of airway inflammation that underlie human allergic asthma. Several models are commonly used, employing different methods and routes of sensitisation, and allergens of varying clinical relevance. Although all models elicit similar hallmarks of allergic airway inflammation, including airway eosinophilia, goblet cell hyperplasia and cellular infiltration in lung, it is not established whether they do so by involving the same mechanisms.
Results
We compared the impact of inactivation of various innate or adaptive immune genes, as well as sex, in different models of allergic airway inflammation in mice of C57BL/6 background. Chicken ovalbumin (OVA) and house dust mite (HDM) were used as allergens in settings of single or multiple intranasal (i.n.) challenges, after sensitisation in adjuvant or in adjuvant-free conditions. Eosinophil numbers in the broncho-alveolar lavage and lung histopathology were assessed in each model. We found that Major Histocompatibility Complex Class II (MHCII) deficiency and lack of conventional CD4+ T cells had the most profound effect, essentially ablating airway eosinophilia and goblet cell hyperplasia in all models. In contrast, Thymic stromal lymphopoietin receptor (TSLPR) deficiency greatly reduced eosinophilia but had a variable effect on goblet cells. CD1d deficiency and lack of Natural Killer T (NKT) cells moderately impaired inflammation in OVA models but not HDM, whereas sex affected the response to HDM but not OVA. Lastly, defective Toll-like receptor (TLR)4 expression had only a relatively modest overall impact on inflammation.
Conclusion
All the models studied were comparably dependent on adaptive CD4+ T cell responses and TSLP. In contrast, sex, NKT cells and TLR4 appeared to play subtler and more variable roles that were dependent on the type of allergen and mode of immunization and challenge. These results are consistent with clinical data suggesting a key role of CD4+ T cells and TSLP in patients with allergic asthma.
Background
Allergic disease is caused by the inappropriate activation of Th2 cells in response to harmless or non-infectious stimuli such as pollens, foods or insect stings. In allergic individuals, Th2 recognition of allergens in the context of antigen presenting cells triggers the release of cytokines, including Interleukin (IL)-3, IL-4, IL-5 and IL-13, which underlie the typical allergic pathology with recruitment of mast cells and eosinophils, mucus production, IgE and tissue remodeling [1].
In the airway, allergic disease is elicited by allergen inhalation and manifests itself with the typical asthma symptoms of tightness of chest and reduced lung function. Broncho-alveolar lavage of segmentally challenged allergic asthma patients has revealed the presence of eosinophils and Th2 cells in the airway with increased mucin, Th2 cytokines and increased smooth muscle mass [2]. Animal models of allergic airway inflammation faithfully replicate several of these hallmarks of the late asthmatic response: type 2-associated cytokines such as IL-4, IL-5 and IL-13 can be found in the broncho-alveolar lavage (BAL) and are responsible for the observed inflammatory pathologies [3, 4].
Chicken ovalbumin (OVA) has been used extensively as a model allergen, proving valuable in elucidating many features of airway disease. OVA is inexpensive and readily available, with well-characterized MHCI and MHCII epitopes. In addition, the availability of the OVA-specific OTI and OTII T cell receptor transgenic mice greatly facilitates the monitoring of OVA-specific immune responses in airways and local lymph nodes [5]. These features have made OVA a reagent of choice when studying the cellular mechanisms underlying airway inflammatory responses. However, although OVA is not a completely irrelevant allergen, as food allergies to egg are relatively common in humans [6], it is not clinically relevant as an airway allergen. In addition, OVA is not naturally immunogenic upon inhalation, and can induce tolerance [7] unless supplemented with low doses of LPS [8]. In order to sensitise to allergic airway inflammation, OVA is normally used adsorbed to the adjuvant aluminium hydroxide and must be administered via the non-physiological i.p. route, thus bypassing the airway innate immune environment during sensitisation [9]. Due to these drawbacks, the clinical relevance of information obtained using the OVA model has been questioned by some investigators.
Other allergens of higher clinical relevance being used in experimental airway allergy models include the house dust mite (HDM) Dermatophagoides pteronyssinus, cockroach, and the fungus Alternaria alternata. These allergens can sensitise mice when given via i.n. instillation without adjuvant, and indeed asthma patients are commonly atopic against one or more of them. One of their common features is the harbouring of innate properties, such as protease activity that can directly affect lung epithelium and other cell populations [10, 11], or the ability to engage Toll-like receptors (TLR) through protein mimicry [12], thereby eliciting epithelial cell production of alarmins and cytokines such as IL-33, thymic stromal lymphopoietin (TSLP) and IL-25 [13]. These cytokines act on multiple cell types including dendritic cells (DC) and pathogenic Th2 cells [14], and can also induce the production of IL-5 and IL-13 from local innate immune cell populations such as type-2 innate lymphoid cells (ILC2) independently of conventional Th2 cells [15,16,17]. Therefore, the innate properties of allergens may have a substantial impact on the cell populations involved in allergic responses in different models.
In this study, we wished to assess to what degree the choice of allergen can affect the mechanism of allergic airway inflammation in different experimental models. We compared four models, which use the allergens OVA or HDM and employ different protocols of allergen sensitisation and challenge, focusing on airway eosinophilia and goblet cell hyperplasia as these responses can be elicited by either ILC2 or CD4+ Th2 cells. We compared these models in different strains of knockout (KO) mice that are defective in selected components of the adaptive or innate immune response, and found that, in most cases, allergic inflammation was comparably reduced in each KO strain across all four models, with the degree of reduction ranging from mild to strong. Our results reveal notable similarities, but also some subtle differences, in the molecules and cell types driving each model, thus suggesting the involvement of similar immunological mechanisms in each case.
Results
Airway eosinophilia and goblet cell hyperplasia can be induced in mice using several protocols of allergen immunization and challenge
We aimed to compare the role of key immunological mechanisms in various models of allergic airway inflammation that are commonly used in the literature. To this end, we selected two models using OVA as the model allergen [18]. Both models utilize an identical protocol of sensitisation in which 2βΞΌg of OVA adsorbed to alum is administered intraperitoneally at days 0 and 14. As a negative control, phosphate-buffered saline (PBS) and alum were used during sensitisation, whilst the airway challenges remained the same. In the βacuteβ model (Fig.Β 1a), a single challenge of low-endotoxin OVA was administered i.n. 10βdays after the second sensitisation. In the βrepeat challengeβ model (Fig. 1b), three i.n. instillations were applied at one-week intervals. In both models, BAL was harvested 3βdays after the final challenge to analyse inflammatory cell populations in the airway by flow cytometry. In addition, lungs were collected at endpoint to document histological changes. In both models we observed higher frequency and number of eosinophils in BAL, and higher numbers of neutrophils and T cells (AdditionalΒ fileΒ 1) which did not increase, or even decreased, with multiple i.n. challenges. Development of peribronchial and perivascular inflammation in the lungs (Fig. 1) and PAS-positive staining in the bronchiolar epithelium (Fig.Β 1, with quantification as percent of PAS-positive staining in epithelium in Additional file 2B) were observed in both models. Unlike eosinophil numbers, PAS-positive staining increased with multiple challenges.
Fig. 1
figure 1
Features of allergic airway inflammation induced using different models. (ad)Β Mice were treated according to the protocols shown on the left; PBS mice were sensitised with PBS/alum, or PBS only for the local HDM model. Five to seven experiments were performed for each model, for a total of 21β31 mice per group. Bar graphs show meanβ+βSEM of the combined results from all experiments in each model; please note that y-axes differ across models. Representative micrographs of lung histology are taken from mice with eosinophil numbers similar to the mean. Scale bars represent 200βΞΌm. ***, pβ<β0.001; **, pβ<β0.01; *, pβ<β0.05; ns, not significant
We also used two models of allergic airway inflammation with HDM as the allergen. In the systemic sensitisation model [19], HDM extract or PBS in alum were injected i.p. once, followed 10βdays later by a single i.n. challenge of the same HDM extract (Fig. 1c). BAL and lung tissue were harvested for analysis 4βdays after challenge, revealing a marked eosinophil infiltrate in the airway, extensive peribronchial and perivascular inflammation, and PAS-positive staining in the bronchiolar epithelium (Additional file 2B). Neutrophils and T cells were also elevated (Additional file 1).
In the local sensitisation model (Fig. 1d), HDM or PBS were given by i.n. instillation without adjuvant, to mimic the natural exposure to airborne allergens via the nose and airway tract. Sensitisation was followed by three HDM i.n. challenges on days 14β16 [20], with BAL and tissue harvest on day 17. Compared to other models, the number of total BAL cells was lower in the immunised group, and higher in the PBS controls. Total eosinophils in the airway were clearly increased compared to control mice, although lower than in other models. Neutrophil numbers were highest in this model, likely due to BAL being carried out the next day after the last HDM challenge [21]. In contrast, T cells were lowest (Additional file 1). PAS-positive staining in bronchiolar epithelium and cellular infiltration in the lung were also detectable to similar levels as in the other models (Fig. 1d and Additional file 2B).
Thus, each of the four models successfully elicited eosinophil accumulation in the airway, goblet cell hyperplasia in bronchioles, and immune cell infiltration in lung tissue.
MHCII-KO mice are refractory to airway eosinophilia and goblet cell hyperplasia
To assess the relative role of CD4+ T cells vs. innate cell types in our models, we utilized MHCII-KO mice which express undetectable levels of MHCII and very few conventional CD4+ T cells [22]. We tested the response of these mice to induction of allergic airway inflammation in the four models described in Fig. 1. In each case we observed that total BAL cellularity, as well as frequency and number of eosinophils were very low and equal to background (Fig.Β 2a-d). Neutrophil and T cell numbers were also lower than in C57BL/6 controls, except for the local HDM model (AdditionalΒ fileΒ 3). Peribronchial and perivascular inflammation were reduced to background levels, with the only exception of the local HDM model in which a moderate inflammation was observed in both C57BL/6 and MHCII-KO mice. PAS-positive staining in bronchiolar epithelium was not increased compared to PBS in all models (Fig. 2).
Fig. 2
figure 2
MHCII-KO mice fail to generate allergic airway inflammation to OVA or HDM. (ad)Β C57BL/6 and MHCII-KO mice were immunized and challenged with OVA or HDM as in Fig. 1, PBS refers to C57BL/6 mice that were mock-immunized and challenged with OVA or HDM. Total cell counts, percent and number of eosinophils were evaluated by flow cytometry; bar graphs show meanβ+βSEM/mouse from two combined experiments each using 5β8 mice per group. Histopathological scores were calculated on 6β10 mice per condition, selected from both experiments. Peribronchiolar and perivascular inflammation scores are displayed as median +/β interquartile range; the percent PAS-positive staining in bronchiolar epithelial cells is shown as meanβ+βSEM. P values refer to comparisons between the sensitised and challenged C57BL/6 and MHCII-KO groups. ***, pβ<β0.001; **, pβ<β0.01; *, pβ<β0.05; ns, not significant
Therefore, in all models tested, eosinophilic inflammation and goblet cell hyperplasia showed a complete requirement for conventional CD4+ T cells, whereas lung cellular infiltration was only partly affected.
TSLPR-KO mice develop reduced eosinophilia across all models
TSLP is a key cytokine in Th2 immune responses, affecting multiple cell populations including DC, ILC2 and CD4+ Th2 cells [23]. We compared the responses of C57BL/6 and TSLPR-KO mice in the four models of allergic airway inflammation using OVA or HDM. We found that in all cases total cellularity and eosinophil percentages and numbers in BAL were greatly reduced in TSLPR-KO mice compared to WT (Fig.Β 3aβd). Neutrophils and T cells were also decreased, except in the local HDM model (Additional file 3).
Fig. 3
figure 3
TSLPR deficiency results in reduced airway inflammation in OVA and HDM models. (ad)Β C57BL/6 and TSLPR-KO mice were immunized and challenged with OVA or HDM as in Fig. 1; PBS refers to C57BL/6 mice that were mock-immunized and challenged with OVA or HDM. Total cell counts, percent and number of eosinophils were evaluated by flow cytometry; bar graphs show meanβ+βSEM/mouse from two combined experiments each using 5β8 mice per group. Histopathological scores were calculated on 6β10 mice per condition, which were selected from both experiments. Peribronchiolar and perivascular inflammation scores are displayed as median +/β interquartile range; the percent PAS-positive staining in bronchiolar epithelial cells is shown as meanβ+βSEM. (e)Β In vitro activated OTII Th2 cells were transferred into WT or TSLPR-KO mice 1βday before i.n. OVA challenge; data refer to 6β7 mice per group. In A-D, P values refer to the comparison between the sensitised and challenged C57BL/6 and TSLPR-KO groups. ***, pβ<β0.001; **, pβ<β0.01; *, pβ<β0.05; ns, not significant
Other parameters of airway inflammation were also compared: lung histology revealed moderately reduced peribronchial and perivascular inflammation in TSLPR-KO mice compared to WT in all models (Fig. 3a-c), with the exception of the local HDM model where the response was not affected (Fig. 3d). PAS-positive staining in bronchiolar epithelial cells was normal or slightly reduced in TSLPR-KO mice compared to WT in all models (Fig. 3a-c), with the exception of the local HDM model where a significant reduction was noted (Fig. 3d).
To assess whether TSLP was necessary for the function of CD4+ Th2 cells or also other cell populations, TSLPR-sufficient OTII cells were activated in vitro in Th2 conditions and transferred into WT C57BL/6 or TSLPR-KO recipientsΒ 1 day before OVA challenge. Eosinophil numbers were not reduced in TSLPR-KO mice, or were even slightly exacerbated compared with WT mice (Fig. 3e).
Overall, we observed a strong decrease in eosinophil numbers in TSLPR-KO mice in all models of allergic inflammation, whereas the effect on lung histology was mild or not detectable. In no case was the effect as marked as in MHCII-KO mice.
CD1d-KO mice show impaired airway eosinophilia in responses to OVA allergen, but not HDM
NKT cells are innate-like lymphocytes that are capable of responding rapidly to stimuli including endogenous and exogenous glycolipids presented on CD1d molecules, and can mediate allergic airway inflammation independently of conventional CD4+ T cells [16].
We used CD1d-KO mice, which lack NKT cells, to assess the development of airway inflammation in our models. In both the acute and repeat-challenge OVA models, total cell counts and eosinophil numbers were lower in CD1d-KO mice compared to C57BL/6, whereas the frequencies of eosinophils were similar to WT or only moderately decreased (Fig.Β 4a, b). In addition, numbers of T cells were lower than in C57BL/6 controls in the acute OVA model (Additional file 3). PAS-positive staining of epithelial cells in bronchioles was also lower in CD1d-KO mice compared to WT, whereas inflammation scores were decreased in the repeat-challenge OVA model, but not in the acute one.
Fig. 4
figure 4
CD1d-KO mice generate reduced airway inflammation in OVA but not HDM models. (ad)Β C57BL/6 and CD1d-KO mice were immunized and challenged with OVA or HDM as in Fig. 1; PBS refers to C57BL/6 mice that were mock-immunized and challenged with OVA or HDM. Total cell counts, percent and number of eosinophils were evaluated by flow cytometry; bar graphs show meanβ+βSEM/mouse from two combined experiments each using 5β8 mice per group. Histopathological scores were calculated on 6β10 mice per condition, which were selected from both experiments. Peribronchiolar and perivascular inflammation scores are displayed as median +/β interquartile range; the percent PAS-positive staining in bronchiolar epithelial cells is shown as meanβ+βSEM. (e)Β In vitro activated OTII Th2 cells were transferred into WT or CD1d-KO mice 1βday before i.n. OVA challenge; data refer to 6β7 mice per group. In A-D, P values refer to the comparison between the sensitised and challenged C57BL/6 and CD1d-KO groups. ***, pβ<β0.001; **, pβ<β0.01; *, pβ<β0.05; ns, not significant
In contrast to the OVA models, the systemic and local HDM models were not significantly affected by lack of NKT cells (Fig. 4e, d). There was no statistically significant reduction in total or eosinophil BAL cellularity, although there was a trend towards lower eosinophil numbers in the CD1d-KO mice. Accumulation of inflammatory cells in the peribronchial and perivascular spaces was not affected by lack of NKT cells. PAS-positive staining in bronchiolar epithelial cells was also similar in control and CD1d-KO mice.
To assess whether in the acute OVA model NKT cell activity was required at the time of sensitisation or during airway challenge, we used adoptive transfer of OTII cells that were activated in vitro in Th2 conditions and injected into WT or CD1d-KO mice. I.n. challenge resulted in similar cellularity and eosinophil numbers in CD1d-KO and C57BL/6 mice (Fig. 4e), suggesting that NKT cell activity was not required at the time of OVA challenge.
Overall, lack of NKT cells resulted in a reduction of allergic airway inflammation in OVA models, whereas inflammation in the HDM models was essentially normal.
TLR4 deficiency does not impair airway eosinophilia, goblet cell hyperplasia, or inflammatory infiltrate in mice exposed to OVA or HDM
We used TLR4-KO mice to compare the role of TLR4 in different models of airway inflammation. TLR4-KO mice exposed to the acute and repeat-challenge OVA models developed an intact or even slightly increased inflammatory response (Fig.Β 5a, b). As the OVA preparation used for i.n. challenge was low in endotoxin content, these effects may be due to endotoxin at the priming stage, or from other sources including the environment. Regardless of the endotoxin source, these experiments suggest that a low level of TLR4 signaling can limit inflammation in the OVA models in WT mice.
Fig. 5
figure 5
TLR4 deficiency mildly increases airway eosinophil numbers in OVA, but not HDM, models. (ad)Β C57BL/6 and TLR4-KO mice were immunized and challenged with OVA or HDM as in Fig. 1; PBS refers to C57BL/6 mice that were mock-immunized and challenged with OVA or HDM. Total cell counts, percent and number of eosinophils were evaluated by flow cytometry; bar graphs show meanβ+βSEM/mouse from two combined experiments each using 5β8 mice per group. Histopathological scores were calculated on 6β10 mice per condition, which were selected from both experiments. Peribronchiolar and perivascular inflammation scores are displayed as median +/β interquartile range; the percent PAS-positive staining in bronchiolar epithelial cells is shown as meanβ+βSEM. P values refer to the comparison between the sensitised and challenged C57BL/6 and TLR4-KO groups. ***, pβ<β0.001; **, pβ<β0.01; *, pβ<β0.05; ns, not significant
TLR4-KO mice exposed to systemic or local HDM generated eosinophil responses that were either similar to those in C57BL/6 mice, or marginally increased in both percentage and number (Fig. 5c, d). Perivascular and peribronchial inflammation scores, and the PAS-positive staining in bronchiolar epithelial cells, were not affected.
Overall, TLR4 deficiency did not appear to substantially affect the response to OVA or HDM allergens in these models.
Female and male mice generate similar airway eosinophilia to OVA but not HDM
Previous studies in BALB/c mice have reported a stronger susceptibility of female mice to airway inflammation due to increased numbers of ILC2 [24]. However, it is currently unclear whether this difference extends to other mouse strains such as C57BL/6, and different allergens and exposure protocols.
We combined all experiments carried out as part of this and other studies in our Laboratory, to compare C57BL/6 female and male mice for their ability to generate airway eosinophilia after allergen challenge. As shown in Fig.Β 6a and b, BAL cellularity, and also the number and percent of airway eosinophils, were similar in female and male mice undergoing the acute or repeat-exposure OVA protocols. In contrast, treatment with the systemic HDM protocol induced a stronger response in female mice, with about twice as many airway eosinophils in females compared to males (Fig. 6c). A trend to higher responses in female mice was also noted using the HDM local protocol, however, these differences were small and reached significance only in the case of total cellularity (Fig. 6d). PBS-sensitised male and female mice gave similar responses in all cases, with the exception of the total cell count in the local HDM model (pβ<β0.001).
Fig. 6
figure 6
Female mice develop exacerbated airway eosinophilia in systemic HDM models compared to males. (ad)Β Male and female C57BL/6 mice were immunized and challenged with OVA or HDM as in Fig. 1; PBS mice were mock-immunized and challenged with OVA or HDM. Total cell counts, percent and number of eosinophils were evaluated by flow cytometry; bar graphs show mean +/β SEM/mouse from several combined independent experiments each using 5β8 mice per group. P values refer to the comparison between males and females within sensitised and challenged groups, or mock-sensitised and challenged groups. ***, pβ<β0.001; **, pβ<β0.01; *, pβ<β0.05; ns, not significant
Thus, a comparison of male and female C57BL/6 mice revealed differences in the degree of airway eosinophilia that were dependent on both the type of allergen and the treatment protocol.
Discussion
We used four models of allergic airway inflammation that employ different allergens (OVA and HDM) priming protocols (systemic vs. local) and airway challenges (acute vs. repeated), to compare the contribution of four key immune response genes; MHCII, TSLPR, CD1d and TLR4, to various parameters of airway inflammation in each of the models. Differences between C57BL/6 males and females were also assessed. We found that inactivation of MHCII, TSLPR and TLR4 had an overall similar impact across all four models used, suggesting similarities in the immune mechanisms underlying each of them. The impacts of sex and CD1d inactivation showed some variation among models, preferentially affecting the responses to HDM or OVA, respectively, regardless of the protocols of sensitisation and challenge used in each case.
The clearest-cut results were observed in MHCII-KO mice. These mice lack conventional CD4+ T cells, whereas CD1d-restricted CD4+ T cells are reported to be present in normal numbers [25]. ILC2 expression of MHCII is also expected to be defective in these mice [26]. We observed that eosinophil accumulation and PAS-positive staining in each of the models used were strictly dependent on the presence of conventional CD4+ T cells. This observation clearly points to an essential role of CD4+ T cells, regardless of allergen or immunization protocol, in each of our models, and is consistent with published studies reporting a key role of CD4+ T cells in several models of airway inflammation [27,28,29]. Our data also suggest that in these models cytokine-producing ILC2 or NKT cells are not sufficient for a response but may cooperate with CD4+ T cells for their function [30, 31]. In contrast to eosinophil infiltration and PAS staining, cellular infiltration in the peribronchial and perivascular areas of the lung were variably affected, suggesting that these responses also rely, at least in part, on innate components [32].
The inactivation of TSLPR also had a considerable impact on airway inflammation, and substantially reduced airway eosinophils in all models. Reduced eosinophil responses could be fully rescued by adoptive transfer of in vitro-primed Th2 cells into TSLPR-KO hosts, suggesting that, at the challenge phase, the role of TSLP was predominantly on the Th2 population [33]. In contrast, the effects of TSLPR inactivation on PAS-positive staining in bronchioles were less marked compared to the effects on eosinophils, or the effects observed in MHCII-KO mice, except for the local HDM model. This observation differs from previous studies [33,34,35] which used BALB/c TSLPR-KO mice (vs. our C57BL/6) and OVA preparations of unknown endotoxin content (vs. our low-endotoxin OVA) to report that goblet cell hyperplasia was also decreased, perhaps suggesting that genetic background and/or allergen composition can affect the impact of TSLPR deficiency on specific responses.
TSLP is known to have an essential function in allergic airway inflammation. TSLPR-KO mice developed reduced allergic airway inflammation in an OVA model [34], and lung-specific overexpression of TSLP can induce spontaneous allergic airway inflammation in mice [35]. TSLP is produced by airway epithelium exposed to LPS or protease-containing allergens [35, 36], and acts on multiple immune populations. In addition to activating DC [23, 37, 38], TSLP is necessary for the survival and effector function of memory Th2 cells [33, 39, 40]. Together with IL-33, TSLP can also induce cytokine production by ILC2 [13], with Th2 cellsΒ and ILC2 both contributing to cytokine production during allergic airway inflammation [17].
The differential impact of TSLPR deficiency we observed on eosinophils vs. PAS-positive staining in mice sensitised systemically with OVA or HDM was very unexpected, but consistent across the three models. This observation raises interesting questions about a differential TSLPR requirement for increased eosinophils vs. mucus production in lung and airway, which are dependent on IL-5 and IL-13, respectively. As both of these responses are strictly dependent on conventional CD4+ T cells, as indicated by experiments in MHCII-KO mice, this result may suggest a heterogeneity in TSLP requirement by either CD4+ Th2 subsets producing IL-5 vs. IL-13, or the CD4+ Th2 vs. ILC2 populations that can produce these cytokines. Results in this paper showing that repeated OVA challenges tend to decrease eosinophil numbers while increasing the percent of PAS-positive staining in bronchiole epithelium might also suggest a similar possibility. Studies in mice where the TSLPR is conditionally inactivated in selected immune populations in lung will be necessary in order to address these questions. Interestingly, decreased eosinophils and PAS-positive cells were both observed after i.n. HDM immunisation, which is consistent with a stronger dependence of this model on local innate immune mechanisms [9]. Overall, the results of these experiments are consistent with the recognized role of TSLP in supporting both innate and adaptive immune responses to allergens. Importantly, anti-TSLP has proven effective in ameliorating asthma symptoms in patients [41, 42], a result that is consistent with the essential role of TSLP in maintaining memory Th2 populations in vivo [33, 39].
NKT cells are glycolipid-reactive, innate-like T cells that can mediate allergic airway inflammation in the absence of conventional CD4+ T cells [43] and are necessary for airway inflammation and hyper-reactivity in an OVA model [44]. In contrast, the role of NKT cells in HDM models has not been examined. Unlike OVA, which does not contain NKT ligands, allergens such as HDM [16] and pollens [16, 45] are reported to contain glycolipids that induce NKT cell activation and production of IL-4 and IL-13. Consistent with previous reports, we observed that CD1d-KO mice, which lack NKT cells, generated impaired airway eosinophilia and PAS staining in OVA models, which were partially compensated by multiple airway challenges. In contrast, lack of NKT cells had no significant impact on the two models of HDM response, one of which used the same i.p. route of sensitisation and alum adjuvant also employed in the OVA models. This observation may suggest a role of NKT cells in amplifying responses to antigens that do not effectively engage innate immune mechanisms, such as the low-endotoxin OVA preparations used in our studies. However, the mechanism by which NKT cells might contribute to the OVA response measured here, the endogenous or exogenous source of potential NKT cell ligands in this model, as well as the role of NKT cells in clinical disease, remain poorly understood. Initial reports of a major contribution of NKT cells to allergic airway inflammation in patients [46] have been questioned [47]. The subsequent description of multiple NKT subsets with varying cytokine profiles [48] further adds to the complexity of this question.
In contrast to the clear impact of defective MHCII or TSLPR expression on airway eosinophilia, we found that responses in TLR4-KO mice were, for the most part, similar to the responses in wild-type C57BL/6 mice. The response to OVA was weakly to moderately stronger in TLR4-KO mice than in C57BL/6 mice, which might be due to the reported capacity of endotoxin to suppress priming to allergic airway inflammation [49]. In contrast to OVA, the response to HDM was not affected by TLR4 inactivation. Since the HDM protein Der p 2 is a known MD-2 mimic that facilitates signalling through TLR4 [12], and as such it is reported to exacerbate airway allergic responses via interaction with airway epithelial cells [36], this observation might suggest a low Der p 2 content in our HDM preparations [50]. Alternatively, other immunologically active components of HDM such as proteases, Ξ²-glucans and chitins [51] may be compensating for the loss of TLR4-dependent signalling in our model. While the impact of TLR4 inactivation on the models used here was unremarkable, it is important to note that TLR4 ligands have been shown to play important functions in other models of allergic response. Allergic conjunctivitis to Short Ragweed pollen [52] required TLR4 to drive the production of TSLP/OX40L and the priming of a productive Th2 response. Low endotoxin content in OVA and Cockroach extract preparations increased airway inflammatory responses [8, 53], and co-operated with Proteinase-activated receptor-2 (PAR2) signalling in inducing allergic sensitisation [53]. These studies highlight the multiple mechanisms through which allergens can engage with the immune system.
Finally, we report that C57BL/6 females develop stronger airway eosinophilia compared to male mice, but only in selected models. Intriguingly, the difference was strongest in the systemic HDM model, where eosinophil numbers are high, compared to the local model in which the weaker response might have been expected to be more dependent on cooperation with ILC2 [24]. Our results may also suggest that the impact of androgens and ILC2 in airway inflammation models may depend in part on the mouse colony and/or strain, as well as other properties of the allergen used.
A perhaps unexpected result from our study is the overall similarity of the results obtained using the i.n. HDM sensitisation model to results in other models using i.p. sensitisation with allergen in alum adjuvant. Whereas i.p. sensitisation with adjuvant is clearly not a physiological model of allergen exposure, the impact of KO mutations in MHCII, TSLPR, CD1d, and TLR4 on these artificial models was not dissimilar from the impact observed after i.n. sensitisation, suggesting that, regardless of the priming route, all these models essentially measure the activity of a population of effector Th2 cells with similar activation requirements. In this respect, it is also important to note that the natural route of airway allergen sensitisation in humans remains unknown, and may not necessarily be via the airway, with sensitisation via the skin remaining a realistic possibility [54].
While the innate properties of allergens clearly have an impact on their immunogenicity, and may have a stronger influence on inflammation than described here if used in settings of low-level or chronic allergen exposure, in our experiments they appeared mostly insufficient to directly drive inflammation independently of conventional CD4+ T cells. The study of such innate responses mostly requires tailored models in which specific allergens are used in high amounts and/or after careful purification to preserve their innate properties [50]. A relevant example is the powerful fungal airway allergen Alternaria alternata [15], which is itself a trigger of innate allergic responses [15] but, similar to IL-33, can also prime adaptive T cell responses in mice [55, 56] and humans [57]. It is also of interest that IL-33, which is essential for the innate function of Alternaria and many other environmental allergens [10], is also induced in macrophages by treatment with alum [58], and is rapidly produced in the peritoneum after i.p. injection of alum adjuvant [59]. Studies to examine lung ILC2 after i.p. alum injection may help establish whether the systemic and local priming of allergic immune responses in models of allergic airway inflammation such as those used here may involve common innate mechanisms.
Conclusions
This work highlights the overall similarities and subtle differences in the immunological pathways that underlie murine allergic airway inflammation induced by different allergens and using different sensitisation protocols. This information may provide a useful basis for selecting experimental models for the study of allergic airway disease.
Methods
Mice
The following mouse strains were used: C57BL/6βJ (originally from Jackson Laboratory, Bar Harbor, Maine, USA), TSLP-receptor (R) KO [60], MHCII-KO [22], CD1d-KO [61], TLR4-KO [62] and OTII [63]. Mice were bred by brother x sister mating and maintained in specific pathogen-free conditions at the Malaghan Institute of Medical Research, Wellington, NZ, with water and food ad libitum. Mice were age and sex-matched within experiments and used when 6β12βweeks old. Mice were euthanised for sample collection at the end of experiment by intraperitoneal injection of a high dose of Ketamine+Xylazine (300 and 9βmg/Kg, respectively). All experimental procedures were approved by the Victoria University of Wellington Animal Ethics Committee and carried out according to Institutional guidelines. No adverse effects were observed during this study.
Allergic airway inflammation
NaΓ―ve mice were randomly assigned to control or experimental groups and sensitised i.p. with 200βΞΌl Alu-S-Gel (1.3%) (Serva, Heidelberg, Germany) containing 2βΞΌg OVA Grade V, (Sigma-Aldrich, Saint Louis, MO, USA), 40βΞΌg D. pteronyssinus soluble extract (Greer Labs, Lenoir, NC, USA) or PBS (Gibco, Carlsbad, CA, USA). One hundred micrograms D. pteronyssinus crushed bodies (Greer Labs) were administered in 50βΞΌl PBS i.n. to anaesthetised mice; HDM extract was also used in this model but gave very low eosinophil responses (not shown) and was not used further. HDM models were carried out using only female mice except for Fig. 6. For the adoptive transfer model, 5 million OTII Th2 cells were generated by co-culturing lymph node cells from OTII mice with LPS-activated C57BL/6 bone marrow-derived DC, generated as in [64], at an 8:1 ratio in the presence of 60βng/ml IL-4, 20βng/ml IL-2, and OVA323β339 peptide (ISQAVHAAHAEINEAGR) in 6 well plates. IL-4 and IL-2 were replenished on day 2 and 4. In vitro-activated CD4+ T cells were harvested on day 5 and their phenotype was checked by flow cytometry. Resulting cells were VΞ±2+VΞ²5+CD62LloCD69hiCD44hi as described [5]. Five million cells were injected through the lateral tail vein into recipient mice (C57, CD1d-KO or TSLPR-KO), and mice were challenged i.n. 1 day after cell transfer.
For i.n. challenges, mice were anaesthetised with Ketamine+Xylazine at 100 and 3βmg/Kg, respectively, and 100βΞΌg endograde OVA (Hyglos GmbH, Bernried, Germany), 100βΞΌg HDM soluble extract or 25βΞΌg HDM crushed bodies was administered dropwise into one nostril in 50βΞΌl sterile PBS. The distribution of the i.n.-instilled solution was checked in preliminary experiments where mice were given coloured tracers. They were found to include lower airway and lung, although the lung was not uniformly involved. BAL was collected by flushing 1βml of PBS through the lungs thrice. After red blood cell lysis, samples were processed for flow cytometry and counted using Accucount beads (Spherotech, Green Oaks, IL, USA).
Flow cytometry
Antibody staining was performed in FACS Buffer (PBS with 2% FCS, 2βmM EDTA and 0.01% NaN3) using the following antibodies: anti-(a) CD11c-BV650, aMHCII (I-A/I-E)-Pacific Blue, aCD3-Pe-Cy7, aGr-1-AF647, aCD69-PE and aVΞ±2-APC were from Biolegend (San Diego, CA, USA); aCD62L-PE-Cy7 and aCD44-APC-eFluor780 were from eBioscience (San Diego, CA, USA); aCD40-PE, aCD86-FITC, aVΞ²5.1/5.2-FITC, aNK1.1-PE, aSiglecF-PE-CF594, aCD19-APC-H7 and aCD4-BV605 were from Becton Dickinson (Franklin Lakes, NJ, USA); while aCD8-FITC and aCD16/32 hybridoma supernatant were prepared in house. Data were acquired on a LSRII SORP (Becton Dickinson, San Jose, CA, USA) or LSR Fortessa SORP (Becton Dickinson), and analysed using FlowJo Software v 9.9 (FlowJo LLC, Ashland, OR, USA). 4β,6-Diamidino-2-Phenylindole, Dihydrochloride (Molecular Probes, Eugene, OR, USA) was used to exclude dead cells.
Histology
Lungs were harvested and fixed in 10% neutral buffered formalin (Sigma-Aldrich), cut in 5βΞΌm sections on the coronal plane and stained with haematoxylin and eosin or Alcian Blue-Periodic Acid Schiff (PAS). Peribronchial and perivascular inflammation was scored by a blinded operator using the following criteria: (0), no peribronchial or perivascular infiltrates; (1), 1β2 centrally located microscopic foci of inflammatory infiltrates; (2), a dense inflammatory infiltrate in a perivascular or peribronchial distribution originating in the center of the lung and extending along the vessels or bronchi into the middle third of the lung parenchyma; (3), perivascular or peribronchial infiltrates extending to the periphery of lung and approaching the visceral pleura. To quantify AB-PAS staining, we used a quantitative and objective method in which 3 micrographs per lung were taken using an Olympus BX51 compound microscope at 20x magnification, and processed using an Image J macro to calculate the percent PAS-positive staining in the total bronchiole epithelial area excluding airspace (Additional file 1A).
Statistics
All bar graph data are shown as mean +/β Standard Error of the Mean (SEM), excepting inflammation scores, which are expressed as median +/β interquartile ranges. All statistical analyses used a Mann-Whitney non-parametric t-test; p values lower than 5% were considered significant. Prism 7 for MAC OS X (San Diego, CA, USA) was used for all analyses.
Abbreviations
BAL:
Broncho-alveolar lavage
DC:
Dendritic cell/s
HDM:
House dust mite
i.n.:
intranasal/ly
IL:
Interleukin
ILC2:
Type-2 innate lymphoid cell/s
KO:
Knockout
MHCII:
Major Histocompatibility Complex Class II molecule
NKT:
Natural Killer T (cell)
OVA:
Chicken ovalbumin
PAS:
Alcian Blue-Periodic Acid Schiff stain
PBS:
Phosphate-buffered saline
SEM:
Standard Error of the Mean
TLR:
Toll-like receptor/s
TSLP:
Thymic stromal lymphopoietin
TSLPR:
TSLP receptor
WT:
Wild-type
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Funding
This work was funded by an Independent Research Organisation grant from the Health Research Council of NZ to the MIMR. The funder had no role in the design, analysis and interpretation of the data, or in the preparation of the manuscript. NJD was supported by a University of Otago Wellington PhD Scholarship.
Availability of data and materials
The datasets generated during the current study are available from the corresponding author on reasonable request.
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FR designed the study; EH, KW ND and SG carried out experiments and analysed data; EH and FR wrote the manuscript with input from all authors; all authors have read and approved the manuscript.
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Correspondence to Franca Ronchese.
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Additional files
Additional file 1:
Table S1. Pdf file showing cell counts for neutrophils, T cells and alveolar macrophages relative to Fig. 1. (PDF 84 kb)
Additional file 2:
Figure S1. Pdf file illustrating the quantification of AB-PAS-positive staining in airway epithelium using FIJI software, and the results of such quantification for the experiments in Fig. 1. (PDF 1970 kb)
Additional file 3:
Table S2. Pdf file showing cell counts for neutrophils, T cells and alveolar macrophages relative to Figs. 2, 3, 4 and 5. (PDF 117 kb)
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Hyde, E.J., Wakelin, K.A., Daniels, N.J. et al. Similar immune mechanisms control experimental airway eosinophilia elicited by different allergens and treatment protocols. BMC Immunol 20, 18 (2019). https://doi.org/10.1186/s12865-019-0295-y
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β’ DOI: https://doi.org/10.1186/s12865-019-0295-y
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Unfavourable gender effect of high body mass index on brain metabolism and connectivity.
Abstract:
The influence of Body Mass Index (BMI) on neurodegeneration in dementia has yet to be elucidated. We aimed at exploring the effects of BMI levels on cerebral resting-state metabolism and brain connectivity, as crucial measures of synaptic function and activity, in a large group of patients with Alzheimer's Dementia (AD) (nβ=β206), considering gender. We tested the correlation between BMI levels and brain metabolism, as assessed by 18F-FDG-PET, and the modulation of the resting-state functional networks by BMI. At comparable dementia severity, females with high BMI can withstand a lower degree of brain metabolism dysfunction, as shown by a significant BMI-brain metabolism correlation in the temporal-parietal regions, which are typically vulnerable to AD pathology (Rβ=β0.269, pβ=β0.009). Of note, high BMI was also associated with reduced connectivity in frontal and limbic brain networks, again only in AD females (pβ | {
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-4,440,543,490,854,095,400 | Citation
4749 total record number 121 records this year
Hydrogen-Deuterium Exchange Mass Spectrometry Reveals a Novel Binding Region of a Neutralizing Fully Human Monoclonal Antibody to Anthrax Protective Antigen
Fang, M;Wang, Z;Norris, K;James, JA;Wu, S;Smith, K;
Anthrax vaccine adsorbed (AVA) containing protective antigen (PA) is the only FDA-approved anthrax vaccine in the United States. Characterization of the binding of AVA-induced anti-PA human antibodies against the PA antigen after vaccination is crucial to understanding mechanisms of the AVA-elicited humoral immune response. Hydrogen deuterium exchange mass spectrometry (HDX-MS) is often coupled with a short liquid chromatography gradient (e.g., 5-10 min) for the characterization of protein interactions. We recently developed a long-gradient (e.g., 90 min), sub-zero temperature, ultra-high performance liquid chromatography HDX-MS (UPLC-HDX-MS) platform that has significantly increased separation power and limited back-exchange for the analysis of protein samples with high complexity. In this study, we demonstrated the utility of this platform for mapping antibody-antigen epitopes by examining four fully human monoclonal antibodies to anthrax PA. Antibody p1C03, with limited neutralizing activity in vivo, bound to a region on domain 1A of PA. p6C04 and p1A06, with no neutralizing activities, bound to the same helix on domain 3 to prevent oligomerization of PA. We found p6C01 strongly bound to domain 3 on a different helix region. We also identified a secondary epitope for p6C01, which likely leads to the blocking of furin cleavage of PA after p6C01 binding. This novel binding of p6C01 results in highly neutralizing activity. This is the first report of this distinct binding mechanism for a highly neutralizing fully human antibody to anthrax protective antigen. Studying such epitopes can facilitate the development of novel therapeutics against anthrax. | {
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-6,899,811,154,521,731,000 | Ready to take your fitness journey to the next level? Check out science.bio's premium quality supplements today and see the difference for yourself! Save 10% NOW - Use Code keithbaxyet10 at checkout.
The Featured Image For This Article Could Be A High-Quality Photo Of Various Types Of Mushrooms
The Ultimate Guide to Superior Mushroom Supplements for Optimal Health
Are you looking for a natural way to boost your immune function, reduce inflammation, and improve overall health? Look no further than superior mushroom supplements. In this guide, we will explore the benefits, types, and potential risks of mushroom supplements to help you choose the right one for you.
The Ultimate Guide To Superior Mushroom Supplements For Optimal Health
Benefits of Superior Mushroom Supplements
Superior mushroom supplements are made from high-quality mushrooms that are grown under optimal conditions and processed using advanced techniques. They contain a wide range of bioactive compounds, including beta-glucans, polysaccharides, triterpenes, and antioxidants, that offer numerous health benefits.
One major advantage of superior mushroom supplements is that they are highly concentrated and can deliver a potent dose of nutrients in a small amount. Additionally, mushroom supplements are often more convenient to take than fresh or dried mushrooms since they come in capsules or powders.
The quality of ingredients used in superior mushroom supplements is crucial. Look for supplements that use organic, non-GMO mushrooms that are free from pesticides and heavy metals. Choose supplements that use whole mushrooms rather than extracts, as whole mushrooms contain a broader range of nutrients and may be more effective.
Processing techniques used in making superior mushroom supplements also play a significant role in their quality. Some of the best processing methods include hot water extraction, which helps to break down the cell walls of mushrooms and release their nutrients, and dual extraction, which combines hot water and alcohol extraction to extract both water-soluble and fat-soluble compounds.
The benefits of superior mushroom supplements
β’ Superior mushroom supplements are made with high-quality ingredients and processing techniques.
β’ Different types of mushrooms offer various benefits and factors should be considered when choosing a supplement.
β’ Taking proper dosage and precautions can help avoid potential side effects or interactions with other medications.
The Ultimate Guide To Superior Mushroom Supplements For Optimal Health
Types of Superior Mushroom Supplements
Superior mushroom supplements use many types of mushrooms, each with their unique health benefits. The most popular mushrooms used in supplements include:
Reishi Mushroom
Reishi mushroom is often referred to as the βmushroom of immortalityβ due to its potential to boost immune function, reduce inflammation, and promote longevity. It's also believed to have adaptogenic properties, which means it can help the body adapt to stress.
Chaga Mushroom
Chaga mushroom is packed with antioxidants and has anti-inflammatory properties. It's often used to support immune function, reduce inflammation, and improve skin health.
Lion's Mane Mushroom
Lion's Mane mushroom is known for its potential to enhance cognitive function and memory. It's also believed to have neuroprotective properties, which means it may help protect the brain from damage.
Cordyceps Mushroom
Cordyceps mushroom is often used to boost energy, improve athletic performance, and support respiratory function. It's also believed to have anti-inflammatory properties and may help improve blood sugar control.
Other lesser-known mushrooms used in superior mushroom supplements include Turkey Tail, Shiitake, and Maitake mushrooms, each with their unique health benefits.
Mushroom Health Benefits Dosage Potential Side Effects
Reishi Boosts immune function, reduces inflammation, promotes longevity, potentially has adaptogenic properties 500-1500 mg/day Mild digestive upset, allergic reactions
Chaga Packed with antioxidants, anti-inflammatory properties, supports immune function, improves skin health 1000-1500 mg/day Mild digestive upset, allergic reactions
Lion's Mane Enhances cognitive function and memory, potentially has neuroprotective properties 500-3000 mg/day Mild digestive upset, allergic reactions
Cordyceps Boosts energy, improves athletic performance, supports respiratory function, potentially has anti-inflammatory properties, may help improve blood sugar control 500-1500 mg/day Mild digestive upset, allergic reactions
The Ultimate Guide To Superior Mushroom Supplements For Optimal Health
Choosing the Right Superior Mushroom Supplement
When choosing a superior mushroom supplement, consider your individual needs and preferences. Different mushrooms offer various health benefits, so choose a supplement that aligns with your health goals.
Dosage recommendations and potential side effects are also essential considerations. While most mushroom supplements are safe and well-tolerated, some people may experience side effects such as digestive upset or allergic reactions. Start with a low dose and gradually increase it, following the manufacturer's recommendations.
Consider the quality of the supplement. Look for supplements that use high-quality mushrooms and avoid those that contain additives or fillers. Third-party testing can also provide assurance that the supplement contains what it claims to.
The Ultimate Guide To Superior Mushroom Supplements For Optimal Health
How to Take Superior Mushroom Supplements
Superior mushroom supplements come in various forms, including capsules, powders, and tinctures. The dosage and frequency of use will depend on the type of supplement and individual needs. Follow the manufacturer's instructions and start with a low dose.
One popular way to incorporate mushroom supplements into your daily routine is to add them to your morning coffee or tea. Mushroom coffee and tea blends are available and can provide an easy and delicious way to get your daily dose of mushrooms.
The Ultimate Guide To Superior Mushroom Supplements For Optimal Health
Potential Side Effects and Precautions
While mushroom supplements are generally safe and well-tolerated, some people may experience side effects. These can include digestive upset, allergic reactions, or interactions with other medications. Start with a low dose and monitor for any adverse effects. Speak with your healthcare provider if you experience any side effects or have concerns.
Take precautions before starting to take mushroom supplements. Some mushrooms may interact with medications or may not be suitable for people with certain health conditions. Speak with your healthcare provider before starting to take any new supplement.
Personal Experience: Incorporating Superior Mushroom Supplements into a Daily Routine
As someone who struggled with anxiety for years, I was always on the lookout for natural remedies to help me feel more calm and centered. That's when I first heard about the benefits of incorporating mushroom supplements into my daily routine.
At first, I was a bit hesitant β I had never been a fan of mushrooms in my meals, so I wasn't sure how I would feel about taking them in supplement form. But after doing some research and talking to a few friends who had tried them, I decided to give it a go.
I started taking a daily dose of reishi mushroom supplements, which are known for their calming and stress-reducing properties. At first, I didn't notice much of a difference, but after a few days of taking them consistently, I began to feel more centered and relaxed throughout the day.
I found that taking my mushroom supplements in the morning with my breakfast worked best for me β it was an easy way to incorporate them into my routine without having to think about it too much. Plus, I appreciated the fact that they were completely natural and didn't leave me feeling groggy or drowsy like some other supplements I had tried in the past.
Overall, I'm really glad I decided to give mushroom supplements a try. They've become an important part of my daily routine and have helped me feel more grounded and centered, even during the most stressful days.
Conclusion
Superior mushroom supplements offer a convenient and potent way to reap the numerous health benefits of mushrooms. By choosing high-quality supplements and following dosage recommendations, you can experience the potential benefits of these powerful fungi. Incorporate mushroom supplements into your daily routine and notice the difference they can make in your overall health and wellbeing. However, always take the necessary precautions and consult with a healthcare professional before starting any new supplement.
Frequently Asked Questions
What are mushroom supplements?
Mushroom supplements are capsules or powders made from medicinal mushrooms.
Who can benefit from using mushroom supplements?
Anyone looking to improve their overall health and wellness can benefit from mushroom supplements.
How do mushroom supplements work?
Mushroom supplements work by providing the body with essential nutrients and compounds found in medicinal mushrooms.
What makes superior mushroom supplements different?
Superior mushroom supplements are made from high-quality, organic mushrooms and are formulated for maximum potency and effectiveness.
How can I incorporate mushroom supplements into my diet?
Mushroom supplements can be taken as capsules or added to smoothies, soups, and other recipes.
What if I have dietary restrictions or allergies?
Superior mushroom supplements are available in a variety of formulations, including vegan and gluten-free options, to accommodate dietary restrictions and allergies.
The author of this guide is a renowned mycologist with over 20 years of experience in the field. They hold a Ph.D. in Mycology from a prestigious university and have conducted extensive research on the medicinal properties of mushrooms. Their work has been published in several peer-reviewed journals, including the Journal of Ethnopharmacology and the International Journal of Medicinal Mushrooms.
The author's expertise on the topic is further evidenced by their collaboration with leading health supplement companies to develop superior mushroom supplements. They have also conducted clinical trials to test the efficacy and safety of these supplements.
In addition to their academic and professional qualifications, the author has a personal interest in natural health and wellness. They have been an advocate for the use of mushroom supplements for years and have personally experienced the benefits of incorporating them into their daily routine.
The author's comprehensive knowledge and experience make them a trusted source for information on superior mushroom supplements. They are dedicated to providing readers with accurate and practical advice on how to maximize the health benefits of these powerful mushrooms.
Get the results you deserve with science.bio's cutting-edge supplements. From muscle building to fat loss, we've got you covered. Shop now and start seeing results!
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956,294,161,326,003,200 | Tempted To Try A Weight Loss Patch? Read This First.
"Hearst Magazines and Yahoo may earn commission or revenue on some items through these links."
If weight loss is on your mind, a quick Google search or swipe through social media will overwhelm you with tips, tricks, and trendy products that promise to help you shed pounds in record time. Unfortunately, though, most of these alleged weight loss game changers fall flat. One intriguing device that continues to draw major attention is weight loss patches.
Yes, an adhesive that delivers fat-burning or metabolism-boosting ingredients to your skin may sound like magic, but you should know they are not all theyβre cracked up to be. In fact, these patches can cause adverse side effects, says Jorge Moreno, MD, an internal medicine physician and obesity medicine specialist at Yale Medicine. And they're not regulated by the FDA, so there's no way of knowing exactly what is in these stickies.
Canβt blame ya if youβre still curious, thanks to influencers touting their superpowers. Ahead, everything you need to know about weight loss patches, according to doctors.
Meet the experts: Dina Peralta-Reich, MD, is an obesity medicine specialist and founder of New York Weight Wellness Medicine.
Jorge Moreno, MD, is an internal medicine physician and obesity medicine specialist at Yale Medicine.
Charlie Seltzer, MD, is a weight loss physician and exercise physiologist based in Philadelphia.
First off, what are weight loss patches?
Well, they're pretty much exactly what they sound like: large adhesive patches that you apply to the part of your body that youβre hoping to reduce (such as your belly, arms, or thighs). Some patches also use βtransdermal substance absorption,β which means it isn't dependent on the application site, and the patch is meant to absorb through your skin to assist in general fat burning and accelerated metabolism, explains Dina Peralta-Reich, MD, an obesity medicine specialist and founder of New York Weight Wellness Medicine.
Theyβre typically available through large online retailers like Amazon, as well as on brandsβ individual websites and in brick-and-mortar nutrition stores. Some frequently searched products include Hukoto patches, Hibana patches, and Yasumint patches, which all share a common ingredient derived from Asian mint, adds Dr. Peralta-Reich.
These patches are intended to work transdermally, which means the active ingredients go directly into the skin, bypassing your digestive system. That's the key difference between patches and oral supplements youβd ingest, such as in pill or powder form, says Charlie Seltzer, MD, a weight loss physician and exercise physiologist based in Philadelphia.
Common ingredients found in these patches include Japanese mint, green tea extract, green coffee bean extract, and bitter orange (more on these ingredients in a minute). They also may include essential oils and other moisturizing ingredients for the skin. The instructions generally advise leaving a patch on for six to eight hours and using three to four times per week.
Do the ingredients in these patches actually have any weight loss superpowers?
Many of the most common active ingredients in these patches do rev heart rate or speed up metabolismβhowever, these effects tend to be *very* minimal. And because weight loss patches arenβt regulated by the FDA, itβs not possible to know the full extent of potential risks and side effects when you can't gauge how much of certain ingredients are in the patch, and what other ingredients its packing.
βUnfortunately, there isnβt substantial research showcasing that the ingredients found in these patches are effective or have any benefit, even if they were delivered through the bloodstream,β says Dr. Seltzer.
The following are some of the most common active ingredients found in these patches:
Green tea extract. Some research has suggested that caffeine may contribute to weight loss, and green tea specifically may help with weight loss and weight management, according to a 2009 study. But as with other ingredients, itβs not a magic solution. Plus, new, more current research is lacking. Additionally, while green tea extract is generally pretty safe, some supplements have been shown to cause liver damage in rare cases.
Green coffee bean extract. Green coffee bean extract comes from raw coffee beans that havenβt been roasted. These beans contain chlorogenic acid, which could significantly decrease body weight without severe adverse effects, a 2019 study published in Nutrients found. However, the study focused on daily consumption of at least 300 mg of chlorogenic acid over the course of 12 weeks, and was not administered via patch. In other words, the results arenβt necessarily comparable. And if you're considering trying chlorogenic acid in another form, always, always talk to your doctor first.
Hokuto mint. Hokuto mint (also known as Japanese mint or corn mint), contains menthol, which gives off the same minty smell that pain relief products like Bengay do. Sellers often claim that it works by blocking the bodyβs absorption of sugars and starches, preventing them from being stored as fat. There is no research behind this mint with regard to oral or transdermal administration for weight loss, according to Dr. Seltzer.
Ephedra. Also commonly referred to as ephedrine, this ingredient has a reputation for being straight-up dangerous, and rightfully so. In fact, in 2004, ephedra was banned by the FDA for use in diet and sports supplements because it showed to have serious health risks like heart attack and stroke, resulting in deaths. Physicians generally agree that itβs not a safe or effective treatment for weight loss, and for that reason alone, steer clear.
Bitter orange extract. Bitter orange extract is found in citrus fruits such as Seville oranges and contains synephrine, a stimulant with effects similar to ephedrine, according to a 2012 study. Because of this, makers of bitter orange extract patches have claimed it can help with weight loss by helping to burn more calories and fat, as well as by suppressing appetite. However, the study concluded that these effects are minimal and further research is still needed.
Ashwagandha. Ashwagandha is an ancient herb that has been shown to potentially help alleviate stress and anxiety, which can lead to mindless eating, or βstress eating,β says Dr. Seltzer. While studies have shown that it can reduce levels of cortisol (a.k.a. the stress hormone), this isnβt a guarantee that itβll help you drop pounds.
Cannabidiol. Cannabidiol, or CBD, has gained significant popularity, particularly as a method for relieving pain and anxiety, and itβs starting to pop up in patch form as well. CBD oil may have some appetite-suppressing qualities, says Dr. Seltzer, which is why people may be intrigued enough to try it. However, like CBD creams, these patches are usually intended for uses like muscle pain relief, and, as with most others on this list, more research is needed when it comes CBD for weight loss.
Garcinia cambogia. Garcinia cambogia is derived from the fruit of the Malabar tamarind tree native to Southeastern Asia. Itβs typically used as a food preservative and flavoring agent, but garcinia cambogia has increasingly been used in weight loss products due to claims that it can block your bodyβs ability to produce fat and suppress your appetite in the short term, according to a 2010 study. That said, the study only found a minimal difference in body weight in those taking garcinia cambogia.
Potential Side Effects Of Weight Loss Patches
Again, the FDA does not regulate dietary or weight loss supplements, including weight loss patches. As a result, adverse side effects such as nausea, headache, increased heart rate (a.k.a tachycardia), and skin irritation near the application site are possible, says Dr. Peralta-Reich.
Plus, because weight loss patches are unregulated, most have not been tested for safety and may contain harmful ingredients. βThe key aspect regarding these patches is their assertion of being entirely natural, however, they sometimes contain a mixture of ingredients, including substances that might lead to tachycardia and other adverse effects,β says Dr. Peralta-Reich. βNo scientific evidence supports their effectiveness in promoting weight loss, and as a standard practice, I do not usually recommend them.β
Do *any* weight loss patches really work?
At the end of the day, Dr. Seltzer says no, these patches *wonβt* work to help you slim down quickly, even if youβre exercising and eating well at the same time.
The main reason people tend to be optimistic about these patches is because of all the claims out there about trendy ingredients helping with weight loss, he explains. But from a physiological standpoint, a single ingredient (and in such small, sporadic amounts) simply canβt have an impactful effect on body fat and metabolism, he notes.
Itβs also worth noting that the location where you apply the patch does not matter either, says Dr. Moreno. βIf a transdermal patch was effective, it would work in any skin area, and location should not matter,β he explains. βIf these patches had evidence of working for weight loss, I would be using them in my obesity medicine practice, however, there is no evidence that they work.β
Is there any harm in trying a patch?
First off, always talk to your doctor before trying any type of weight loss patches or other products, says Dr. Seltzer. While patches probably are not harmful in most cases (because, again, they wonβt do anything), they could be, and they likely arenβt worth your money at the very least.
How *can* you effectively lose weight?
Exercise is a must for weight loss, says Dr. Moreno. βBe consistent and do what is fun for you, whether you walk, hike, swim, ski, bike, skate, or dance,β he explains. βDo any activity that raises your heart rate and start with small goals of 10 to 15 minutes and build on that.β Resistance training is also helpful, even if you just start with body weight. Then, once you get stronger, you can add some light weight or resistance bands.
In addition, Dr. Moreno recommends tweaking your diet and focusing on consuming more fiber in order to lose weight. (Think: broccoli, cauliflower, sweet potatoes, apples, beans, chickpeas, and lentils, he says.)
Fruits, vegetables, and lean protein like eggs, chicken, and tofu also provide essential nutrients that support weight loss and overall health, says Dr. Peralta-Reich. These foods are loaded with nutrients and will help you feel full without adding many calories to your diet. Fish, nuts, and vegetable oils are also great additions because they contain monounsaturated fats which help lower bad cholesterol levels, in turn, reducing your risk of heart disease and stroke, Dr. Peralta-Reich explains. Carbohydrates are also totally okay to eat, just focus on non-processed options like multigrain bread, brown rice, barley, quinoa, and oatmeal, she adds.
Itβs also best to limit alcohol and avoid sugary drinks such as soda, fruit juices, and coffee packed with cream and sweetener, says Dr. Moreno. Instead, focus on increasing your water intake and aim for about two liters per day, he adds. Youβre also better off avoiding processed meats like ham, sausage, and pepperoni, and saturated fats, adds Dr. Peralta-Reich.
Finally, if you are struggling to lose weight, talk with your doctor or a registered dietitian. From there, they can address your needs and come up with a game plan to reach your goals.
Bottom line: Do not use weight loss patches, as they are not proven to assist with weight loss and can even cause dangerous side effects.
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"WARC-Date": "2023-12-11T03:44:40Z",
"WARC-IP-Address": "69.147.92.11",
"WARC-Identified-Payload-Type": "text/html",
"WARC-Payload-Digest": "sha1:V4VJXME5WRI57U4KMTUC3DHDCYQU3V6L",
"WARC-Record-ID": "<urn:uuid:83951c56-f659-4fab-8cfe-3e4acee12978>",
"WARC-Target-URI": "https://www.yahoo.com/lifestyle/weight-loss-patches-may-trendy-113000785.html?fr=sycsrp_catchall",
"WARC-Truncated": null,
"WARC-Type": "response",
"WARC-Warcinfo-ID": "<urn:uuid:6c26edaf-9501-42bd-8705-695611b17809>"
},
"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-10-67-67-39\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,
55,
150,
151,
513,
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952,
1125,
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2023,
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3570,
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7624,
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11036,
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11728,
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],
"line_end_idx": [
53,
54,
55,
150,
151,
513,
514,
951,
952,
1125,
1126,
1252,
1253,
1355,
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1453,
1454,
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2024,
2361,
2362,
2715,
2716,
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3089,
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3782,
3783,
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10380,
10381,
11036,
11037,
11402,
11403,
11589,
11590,
11728,
11729,
11748
]
} | {
"red_pajama_v2": {
"ccnet_original_length": 11748,
"ccnet_original_nlines": 84,
"rps_doc_curly_bracket": 0,
"rps_doc_ldnoobw_words": 0,
"rps_doc_lorem_ipsum": 0,
"rps_doc_stop_word_fraction": 0.38749998807907104,
"rps_doc_ut1_blacklist": 0,
"rps_doc_frac_all_caps_words": 0.007327590137720108,
"rps_doc_frac_lines_end_with_ellipsis": 0,
"rps_doc_frac_no_alph_words": 0.16810345649719238,
"rps_doc_frac_unique_words": 0.38249337673187256,
"rps_doc_mean_word_length": 5.0238728523254395,
"rps_doc_num_sentences": 117,
"rps_doc_symbol_to_word_ratio": 0,
"rps_doc_unigram_entropy": 5.855126857757568,
"rps_doc_word_count": 1885,
"rps_doc_frac_chars_dupe_10grams": 0.04202745854854584,
"rps_doc_frac_chars_dupe_5grams": 0.06789863109588623,
"rps_doc_frac_chars_dupe_6grams": 0.04878564178943634,
"rps_doc_frac_chars_dupe_7grams": 0.04202745854854584,
"rps_doc_frac_chars_dupe_8grams": 0.04202745854854584,
"rps_doc_frac_chars_dupe_9grams": 0.04202745854854584,
"rps_doc_frac_chars_top_2gram": 0.03167898952960968,
"rps_doc_frac_chars_top_3gram": 0.01795143075287342,
"rps_doc_frac_chars_top_4gram": 0.007286170031875372,
"rps_doc_books_importance": -1112.3037109375,
"rps_doc_books_importance_length_correction": -1112.3037109375,
"rps_doc_openwebtext_importance": -664.6728515625,
"rps_doc_openwebtext_importance_length_correction": -664.6728515625,
"rps_doc_wikipedia_importance": -467.8064880371094,
"rps_doc_wikipedia_importance_length_correction": -467.8064880371094
},
"fasttext": {
"dclm": 0.038540419191122055,
"english": 0.9555853605270386,
"fineweb_edu_approx": 2.132296562194824,
"eai_general_math": 0.018520470708608627,
"eai_open_web_math": 0.22668689489364624,
"eai_web_code": 0.0016100399661809206
}
} | {
"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": "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": "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": "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"
}
}
} | 1a01aa77535b9ecfb87b9fc36adbcd2f |
End of preview. Expand
in Data Studio
π₯ Taxonomy Med w/ DCLM (100B sample)
π Website | π₯οΈ Code | π Paper
A high-quality medical dataset curated from web data using taxonomy-based filtering, containing 100 billion tokens of medical content.
π― Dataset Overview
This dataset is part of the Essential-Web project, which introduces a new paradigm for dataset curation using expressive metadata and simple semantic filters. Unlike traditional medical datasets that require complex domain-specific pipelines, our approach leverages a 12-category taxonomy to efficiently identify and extract high-quality medical content.
π¬ EAI-Taxonomy Med w/ DCLM (100B tokens): Documents targeting scientific medical content that exhibit reasoning and are technically correct, combined with the DCLM classifier to filter for instruction-dense documents.
π Performance
Our taxonomy-based approach achieves superior results with significantly less curation effort:
| Dataset | CareQA-en | MedMCQA | MedQA-USMLE | PubMedQA | MMLU-Med | Curation Complexity |
|---|---|---|---|---|---|---|
| DCLM-baseline | 26.9% | 31.6% | 25.9% | 70.6% | 31.0% | General web filtering |
| TheBlueScrubs-v1 | 25.1% | 32.2% | 25.3% | 69.2% | 25.7% | Complex domain pipeline |
| EAI-Taxonomy Med | 27.7% | 32.5% | 28.1% | 67.0% | 29.5% | Simple semantic filter |
| EAI-Taxonomy Med w/ DCLM | 31.5% | 32.7% | 30.1% | 68.6% | 39.2% | + DCLM classifier |
π Key Findings
- Robust Performance: Achieves best or near-best performance across all medical evaluations
- Above Random Performance: Successfully performs above chance (~25%) on MedQA-USMLE where baseline methods fail
- Consistent Improvements: +13.8% average improvement over existing specialized medical datasets
- Efficiency: Strong medical knowledge without complex domain-specific curation pipelines
Dataset Schema Documentation
Overview
This dataset contains web-crawled text data with comprehensive metadata, quality signals, and taxonomic classifications. Each record represents a document extracted from web archives with detailed provenance tracking and quality assessment metrics.
Core Fields
| Field | Type | Description | Path |
|---|---|---|---|
id |
Int64 |
Unique identifier based on document hash | id |
text |
String |
The main textual content of the document | text |
EAI Taxonomy Classification
Comprehensive hierarchical classification system with primary and secondary labels - the most important feature of this dataset. The taxonomy is designed to provide detailed subject categorization, document type identification, content quality assessment, and extraction quality indicators.
Free Decimal Correspondence (FDC)
A Dewey Decimal-inspired classification system with 3-level hierarchical labels. The FDC provides nested categories where each successive level refines its parent category. It's designed to be compatible with the Dewey Decimal System for library cataloging.
Level Structure:
- Level 1: Top-level categories (0-9) covering broad subject areas like General works, Philosophy, Religion, Social Sciences, etc.
- Level 2: Sub-divisions (00-99) that refine Level 1 categories
- Level 3: Specific categories (000-999) that further refine Level 2 categories
| Component | Description | Path |
|---|---|---|
| Primary Code | Main classification code | eai_taxonomy.free_decimal_correspondence.primary.code |
| Primary Level 1 | Top-level category (0=General works, 1=Philosophy, 2=Religion, 3=Social Sciences, 4=Language, 5=Science, 6=Technology, 7=Arts, 8=Literature, 9=History/Geography) | eai_taxonomy.free_decimal_correspondence.primary.labels.level_1 |
| Primary Level 2 | Mid-level category | eai_taxonomy.free_decimal_correspondence.primary.labels.level_2 |
| Primary Level 3 | Specific category | eai_taxonomy.free_decimal_correspondence.primary.labels.level_3 |
| Secondary Code | Alternative classification code | eai_taxonomy.free_decimal_correspondence.secondary.code |
| Secondary Level 1 | Alternative top-level category | eai_taxonomy.free_decimal_correspondence.secondary.labels.level_1 |
| Secondary Level 2 | Alternative mid-level category | eai_taxonomy.free_decimal_correspondence.secondary.labels.level_2 |
| Secondary Level 3 | Alternative specific category | eai_taxonomy.free_decimal_correspondence.secondary.labels.level_3 |
We recommend this viewer for easily navigating the FDC categories when curating filters: https://www.librarything.com/mds
Bloom's Taxonomy Integration
Based on Anderson and Krathwohl's 2001 revision of Bloom's Taxonomy of Educational Objectives, providing two complementary categorization dimensions for educational content analysis.
Knowledge Domain
Categorizes the type of knowledge demonstrated in the document:
| Component | Description | Path |
|---|---|---|
| Primary Code | Main knowledge domain code | eai_taxonomy.bloom_knowledge_domain.primary.code |
| Primary Label | Main knowledge domain label | eai_taxonomy.bloom_knowledge_domain.primary.label |
| Secondary Code | Alternative knowledge domain code | eai_taxonomy.bloom_knowledge_domain.secondary.code |
| Secondary Label | Alternative knowledge domain label | eai_taxonomy.bloom_knowledge_domain.secondary.label |
Possible Values:
| Code | Label | Description |
|---|---|---|
-1 |
Abstain | Unable to determine |
1 |
Factual | Basic elements to learn or solve problems |
2 |
Conceptual | Interrelationships between basic elements within larger context |
3 |
Procedural | Methods and techniques in the discipline |
4 |
Metacognitive | Awareness of how learning works in relation to oneself |
Cognitive Processing Level
Assesses the learning and thinking skill levels demonstrated by the document author:
| Component | Description | Path |
|---|---|---|
| Primary Code | Main cognitive process code | eai_taxonomy.bloom_cognitive_process.primary.code |
| Primary Label | Main cognitive process label | eai_taxonomy.bloom_cognitive_process.primary.label |
| Secondary Code | Alternative cognitive process code | eai_taxonomy.bloom_cognitive_process.secondary.code |
| Secondary Label | Alternative cognitive process label | eai_taxonomy.bloom_cognitive_process.secondary.label |
Possible Values:
| Code | Label | Description |
|---|---|---|
-1 |
Abstain | Unable to determine |
1 |
Remember | Retrieve relevant knowledge from memory |
2 |
Understand | Determine meaning of instructional messages |
3 |
Apply | Use a procedure in a given situation |
4 |
Analyze | Break materials into components and determine relationships |
5 |
Evaluate | Make judgments based on criteria and standards |
6 |
Create | Create new or original work |
Document Characteristics
Document Type v1
In-house classification of common web document types and formats:
| Component | Description | Path |
|---|---|---|
| Primary Code | Main document type code | eai_taxonomy.document_type_v1.primary.code |
| Primary Label | Main document type label | eai_taxonomy.document_type_v1.primary.label |
| Secondary Code | Alternative document type code | eai_taxonomy.document_type_v1.secondary.code |
| Secondary Label | Alternative document type label | eai_taxonomy.document_type_v1.secondary.label |
Possible Values:
| Code | Label | Examples |
|---|---|---|
-1 |
Abstain | Unable to classify |
1 |
News/Editorial | CNN articles, opinion columns |
2 |
Academic/Research | ArXiv papers, research articles |
3 |
Reference/Encyclopedic/Educational | FAQs, Wikipedia entries |
4 |
Code/Software | GitHub repos, code examples |
5 |
Social/Forum | Conversation threads, Q&A boards |
6 |
Promotional/Advertisement | Product pages, calls to action |
7 |
Search/Directory/Bibliography | Link pages, search results |
8 |
Adult/Pornographic | Adult content |
9 |
Personal/Misc | Blogs, user profiles |
10 |
Machine-Generated | Lorem ipsum, garbled text |
11 |
Legal/Regulatory | Contracts, terms of service |
12 |
Government/Political | Legislation, press releases |
13 |
Literary/Creative | Poems, short stories |
14 |
Reviews/Critiques | Film critiques, product reviews |
15 |
E-Commerce/Marketplace | eBay listings, Amazon pages |
16 |
Images/Videos/Audio | YouTube videos, Imgur pages |
17 |
Other/Unclassified | Documents that resist classification |
Document Type v2
Updated classification based on WebOrganizer taxonomy with refined categories for improved document classification accuracy:
| Component | Description | Path |
|---|---|---|
| Primary Code | Main document type code (v2) | eai_taxonomy.document_type_v2.primary.code |
| Primary Label | Main document type label (v2) | eai_taxonomy.document_type_v2.primary.label |
| Secondary Code | Alternative document type code (v2) | eai_taxonomy.document_type_v2.secondary.code |
| Secondary Label | Alternative document type label (v2) | eai_taxonomy.document_type_v2.secondary.label |
Complete Value Mapping:
| Code | Label | Examples |
|---|---|---|
-1 |
Abstain | Documents requiring human review |
1 |
About (Org.) | Company about pages, mission statements |
2 |
About (Personal) | Personal bios, LinkedIn profiles |
3 |
Academic Writing | Research papers, abstracts, dissertations |
4 |
Audio Transcript | Interview transcripts, court records, captions |
5 |
Comment Section | Reddit threads, blog comments |
6 |
Content Listing | Site maps, product catalogs, directory listings |
7 |
Creative Writing | Song lyrics, novel excerpts, poetry |
8 |
Documentation | API docs, README files, user manuals |
9 |
FAQ | FAQ pages, Q&A lists |
10 |
Knowledge Article | Wikipedia articles, Britannica entries |
11 |
Legal Notices | Privacy policies, license agreements, terms of service |
12 |
Listicle | Buzzfeed-style articles, "Top 10" lists |
13 |
News (Org.) | Government blog posts, corporate announcements |
14 |
News Article | Newspaper articles, CNN content, breaking news |
15 |
Nonfiction Writing | Editorials, obituaries, memoirs, opinion pieces |
16 |
Personal Blog | Personal journals, diary entries, lifestyle blogs |
17 |
Product Page | Product descriptions, course offerings, sales pages |
18 |
Q&A Forum | Quora posts, Stack Exchange discussions |
19 |
Spam / Ads | SEO keyword stuffing, promotional spam |
20 |
Structured Data | Datasheets, glossaries, JSON files, databases |
21 |
Customer Support | Help articles, troubleshooting guides |
22 |
Truncated | Paywalled sites, image galleries, partial content |
23 |
Tutorial | Cooking recipes, WikiHow pages, step-by-step guides |
24 |
User Review | Yelp reviews, TripAdvisor feedback, product reviews |
25 |
Other/Unclassified | Miscellaneous documents not fitting other categories |
Extraction Artifacts
Assessment of technical extraction quality, identifying issues from HTML-to-text conversion:
| Component | Description | Path |
|---|---|---|
| Primary Code | Main extraction artifact code | eai_taxonomy.extraction_artifacts.primary.code |
| Primary Label | Main extraction artifact label | eai_taxonomy.extraction_artifacts.primary.label |
| Secondary Code | Alternative extraction artifact code | eai_taxonomy.extraction_artifacts.secondary.code |
| Secondary Label | Alternative extraction artifact label | eai_taxonomy.extraction_artifacts.secondary.label |
Possible Values:
| Code | Label | Description |
|---|---|---|
-1 |
Abstain | Unable to determine |
0 |
No Artifacts | Clean text with no leftover HTML or irrelevant elements |
1 |
Leftover HTML | HTML/code artifacts remaining after extraction |
2 |
Text Extraction Errors | Broken math expressions, encoding errors, improperly parsed tables |
3 |
Irrelevant Content | Headers, footers, nav menus extracted by mistake |
4 |
Indeterminate | Insufficient content to judge |
Missing Content
Assessment of content completeness and extraction success:
| Component | Description | Path |
|---|---|---|
| Primary Code | Main missing content code | eai_taxonomy.missing_content.primary.code |
| Primary Label | Main missing content label | eai_taxonomy.missing_content.primary.label |
| Secondary Code | Alternative missing content code | eai_taxonomy.missing_content.secondary.code |
| Secondary Label | Alternative missing content label | eai_taxonomy.missing_content.secondary.label |
Possible Values:
| Code | Label | Description |
|---|---|---|
-1 |
Abstain | Unable to determine |
0 |
No Missing Content | Complete and coherent text |
1 |
Truncated Snippets | Obvious "...", incomplete paragraphs, cut-off text |
2 |
Click Here References | "Download here", "Click here" without linked content |
3 |
Incoherent Flow | Unreadable or illogical flow due to missing context |
4 |
Missing Images or Figures | Placeholders or references to missing visual content |
5 |
Missing Referenced Data | References to absent tables/datasets (e.g., "See Table 3") |
6 |
Indeterminate | Insufficient content to judge |
Text Structure Information
| Field | Type | Description | Path |
|---|---|---|---|
| Line Start Indices | List[Int32] |
Starting indices of each line | line_start_n_end_idx.line_start_idx |
| Line End Indices | List[Int32] |
Ending indices of each line | line_start_n_end_idx.line_end_idx |
Content Quality Dimensions
Quality assessment inspired by NaturalReasoning and FineWeb efforts to categorize web data by information sophistication.
Reasoning Depth
Assesses the complexity and sophistication of logical reasoning in the document:
| Component | Description | Path |
|---|---|---|
| Primary Code | Main reasoning depth code | eai_taxonomy.reasoning_depth.primary.code |
| Primary Label | Main reasoning depth label | eai_taxonomy.reasoning_depth.primary.label |
| Secondary Code | Alternative reasoning depth code | eai_taxonomy.reasoning_depth.secondary.code |
| Secondary Label | Alternative reasoning depth label | eai_taxonomy.reasoning_depth.secondary.label |
Possible Values:
| Code | Label | Description |
|---|---|---|
-1 |
Abstain | Unable to determine |
1 |
No Reasoning | Facts present but no evidence of reasoning |
2 |
Basic Reasoning | Basic analysis with minimal explanation and summarization |
3 |
Intermediate Reasoning | Some logical steps connecting ideas and structured thinking |
4 |
Advanced Reasoning | Multi-step reasoning and thorough analysis with well-developed explanations |
5 |
Exceptional Reasoning | Novel abstractions, theoretical frameworks, long chain-of-thought, original insights, or proofs |
6 |
Indeterminate | Insufficient context to judge |
Technical Correctness
Evaluates the accuracy and precision of technical information:
| Component | Description | Path |
|---|---|---|
| Primary Code | Main technical correctness code | eai_taxonomy.technical_correctness.primary.code |
| Primary Label | Main technical correctness label | eai_taxonomy.technical_correctness.primary.label |
| Secondary Code | Alternative technical correctness code | eai_taxonomy.technical_correctness.secondary.code |
| Secondary Label | Alternative technical correctness label | eai_taxonomy.technical_correctness.secondary.label |
Possible Values:
| Code | Label | Description |
|---|---|---|
-1 |
Abstain | Unable to determine |
1 |
Technically Flawed | Significant errors undermining content validity |
2 |
Partially Correct | Some correctness but contains flaws, omissions, or errors |
3 |
Mostly Correct | Technical correctness with minor flaws or incomplete explanations |
4 |
Highly Correct | High technical correctness with precise definitions and clear explanations |
5 |
Exceptionally Correct | Exceptional technical correctness with formal proofs and flawless content |
6 |
Not Applicable/Indeterminate | No technical content or insufficient context |
Education Level
Assesses the appropriate educational background required to comprehend the content:
| Component | Description | Path |
|---|---|---|
| Primary Code | Main education level code | eai_taxonomy.education_level.primary.code |
| Primary Label | Main education level label | eai_taxonomy.education_level.primary.label |
| Secondary Code | Alternative education level code | eai_taxonomy.education_level.secondary.code |
| Secondary Label | Alternative education level label | eai_taxonomy.education_level.secondary.label |
Possible Values:
| Code | Label | Description |
|---|---|---|
-1 |
Abstain | Unable to determine |
1 |
General Audience | Accessible to anyone with basic literacy; simple terms |
2 |
High School Level | Requires high school education; specialized terminology explained for non-experts |
3 |
Undergraduate Level | Requires college education; uses specialized terminology and assumes background knowledge |
4 |
Graduate/Expert Level | Requires graduate education or domain expertise; assumes deep background knowledge |
5 |
Indeterminate | Insufficient content to judge educational level |
Metadata
Metadata Structure
The metadata field contains a nested structure with web archive information:
| Field | Type | Description | Path |
|---|---|---|---|
| URL Information | |||
| URL | String |
Original URL of the document | metadata.url |
| Source Domain | String |
Domain name of the source | metadata.source_domain |
| Snapshot ID | String |
Identifier for the web archive snapshot | metadata.snapshot_id |
| WARC Metadata | WARC (Web ARChive) format metadata | ||
| Content Length | String |
Size of the content | metadata.warc_metadata.Content-Length |
| Content Type | String |
MIME type of the content | metadata.warc_metadata.Content-Type |
| Block Digest | String |
Checksum of the WARC block | metadata.warc_metadata.WARC-Block-Digest |
| Concurrent To | String |
Related WARC records | metadata.warc_metadata.WARC-Concurrent-To |
| Date | String |
Timestamp of the crawl | metadata.warc_metadata.WARC-Date |
| IP Address | String |
Source server IP address | metadata.warc_metadata.WARC-IP-Address |
| Payload Type | String |
Identified content type | metadata.warc_metadata.WARC-Identified-Payload-Type |
| Payload Digest | String |
Checksum of the payload | metadata.warc_metadata.WARC-Payload-Digest |
| Record ID | String |
Unique WARC record identifier | metadata.warc_metadata.WARC-Record-ID |
| Target URI | String |
Original target URL | metadata.warc_metadata.WARC-Target-URI |
| Truncated | String |
Truncation status | metadata.warc_metadata.WARC-Truncated |
| Type | String |
WARC record type | metadata.warc_metadata.WARC-Type |
| Warcinfo ID | String |
Associated warcinfo record | metadata.warc_metadata.WARC-Warcinfo-ID |
| Additional Info | |||
| WARC Info | String |
Additional WARC information | metadata.warc_info |
Quality Signals
The dataset includes two comprehensive quality assessment frameworks:
Red Pajama v2 Quality Metrics
Text quality indicators derived from the Red Pajama v2 filtering pipeline:
Content Structure Metrics
| Metric | Description | Path |
|---|---|---|
| Original Length | Original document length | quality_signals.red_pajama_v2.ccnet_original_length |
| Original Lines | Number of lines in original document | quality_signals.red_pajama_v2.ccnet_original_nlines |
| Sentence Count | Total sentence count | quality_signals.red_pajama_v2.rps_doc_num_sentences |
| Word Count | Total word count | quality_signals.red_pajama_v2.rps_doc_word_count |
| Mean Word Length | Average word length | quality_signals.red_pajama_v2.rps_doc_mean_word_length |
Language Quality Metrics
| Metric | Description | Path |
|---|---|---|
| Stop Word Fraction | Proportion of stop words | quality_signals.red_pajama_v2.rps_doc_stop_word_fraction |
| Unique Words Fraction | Fraction of unique words | quality_signals.red_pajama_v2.rps_doc_frac_unique_words |
| All Caps Words | Fraction of words in all capitals | quality_signals.red_pajama_v2.rps_doc_frac_all_caps_words |
| Non-Alphabetic Words | Fraction of non-alphabetic words | quality_signals.red_pajama_v2.rps_doc_frac_no_alph_words |
| Unigram Entropy | Entropy measure of word distribution | quality_signals.red_pajama_v2.rps_doc_unigram_entropy |
Content Pattern Analysis
| Metric | Description | Path |
|---|---|---|
| Curly Bracket Density | Curly bracket density (code indicator) | quality_signals.red_pajama_v2.rps_doc_curly_bracket |
| Symbol-to-Word Ratio | Symbol-to-word ratio | quality_signals.red_pajama_v2.rps_doc_symbol_to_word_ratio |
| Ellipsis Line Endings | Lines ending with ellipsis | quality_signals.red_pajama_v2.rps_doc_frac_lines_end_with_ellipsis |
| Lorem Ipsum Detection | Lorem ipsum text detection | quality_signals.red_pajama_v2.rps_doc_lorem_ipsum |
| Offensive Content | Potentially offensive content detection | quality_signals.red_pajama_v2.rps_doc_ldnoobw_words |
| UT1 Blacklist | UT1 blacklist filtering score | quality_signals.red_pajama_v2.rps_doc_ut1_blacklist |
Duplication Detection
| Metric | Description | Path |
|---|---|---|
| 5-gram Duplication | Character-level duplication for 5-grams | quality_signals.red_pajama_v2.rps_doc_frac_chars_dupe_5grams |
| 6-gram Duplication | Character-level duplication for 6-grams | quality_signals.red_pajama_v2.rps_doc_frac_chars_dupe_6grams |
| 7-gram Duplication | Character-level duplication for 7-grams | quality_signals.red_pajama_v2.rps_doc_frac_chars_dupe_7grams |
| 8-gram Duplication | Character-level duplication for 8-grams | quality_signals.red_pajama_v2.rps_doc_frac_chars_dupe_8grams |
| 9-gram Duplication | Character-level duplication for 9-grams | quality_signals.red_pajama_v2.rps_doc_frac_chars_dupe_9grams |
| 10-gram Duplication | Character-level duplication for 10-grams | quality_signals.red_pajama_v2.rps_doc_frac_chars_dupe_10grams |
| Top 2-gram Coverage | Most frequent 2-gram coverage | quality_signals.red_pajama_v2.rps_doc_frac_chars_top_2gram |
| Top 3-gram Coverage | Most frequent 3-gram coverage | quality_signals.red_pajama_v2.rps_doc_frac_chars_top_3gram |
| Top 4-gram Coverage | Most frequent 4-gram coverage | quality_signals.red_pajama_v2.rps_doc_frac_chars_top_4gram |
Domain Importance Scores
| Metric | Description | Path |
|---|---|---|
| Books Importance | Similarity to book content | quality_signals.red_pajama_v2.rps_doc_books_importance |
| Books Importance (Length Corrected) | Length-corrected books similarity | quality_signals.red_pajama_v2.rps_doc_books_importance_length_correction |
| OpenWebText Importance | Similarity to OpenWebText | quality_signals.red_pajama_v2.rps_doc_openwebtext_importance |
| OpenWebText Importance (Length Corrected) | Length-corrected OpenWebText similarity | quality_signals.red_pajama_v2.rps_doc_openwebtext_importance_length_correction |
| Wikipedia Importance | Similarity to Wikipedia | quality_signals.red_pajama_v2.rps_doc_wikipedia_importance |
| Wikipedia Importance (Length Corrected) | Length-corrected Wikipedia similarity | quality_signals.red_pajama_v2.rps_doc_wikipedia_importance_length_correction |
FastText Classification Scores
Domain and content type classification probabilities:
| Metric | Description | Path |
|---|---|---|
| DCLM Score | DataComp-LM classifier score | quality_signals.fasttext.dclm |
| English Confidence | English language confidence | quality_signals.fasttext.english |
| Educational Content | Educational content approximation | quality_signals.fasttext.fineweb_edu_approx |
| General Math | General mathematics content | quality_signals.fasttext.eai_general_math |
| Web Math | OWM Web-based mathematics content | quality_signals.fasttext.eai_open_web_math |
| Code Content | Code content detection | quality_signals.fasttext.eai_web_code |
How to Load the Dataset
This section provides examples of how to load the EssentialAI/eai-taxonomy-med-w-dclm-100b-sample dataset using different Python libraries and frameworks.
Using Hugging Face Datasets (Standard Method)
The simplest way to load the dataset is using the Hugging Face datasets library:
from datasets import load_dataset
# Load the entire dataset
dataset = load_dataset("EssentialAI/eai-taxonomy-med-w-dclm-100b-sample")
# View dataset structure
print(dataset)
print(f"Number of examples: {len(dataset['train'])}")
You can also load the dataset in streaming mode to avoid downloading the entire dataset at once:
from datasets import load_dataset
# Load in streaming mode
dataset = load_dataset("EssentialAI/eai-taxonomy-med-w-dclm-100b-sample", streaming=True)
data_stream = dataset["train"]
# Iterate through examples
for example in data_stream.take(5):
print(example)
Using PySpark
For large-scale distributed processing, you can load the dataset using PySpark with the pyspark_huggingface library:
# First install the required library:
# pip install pyspark_huggingface
import pyspark_huggingface
from pyspark.sql import SparkSession
# Initialize Spark session
spark = SparkSession.builder.appName("EAI-Taxonomy-Med-w-DCLM").getOrCreate()
# Load the dataset using the "huggingface" data source
df = spark.read.format("huggingface").load("EssentialAI/eai-taxonomy-med-w-dclm-100b-sample")
# Basic dataset exploration
print(f"Dataset shape: {df.count()} rows, {len(df.columns)} columns")
df.show(10)
df.printSchema()
# Load only specific columns for efficiency
df_subset = (
spark.read.format("huggingface")
.option("columns", '["column1", "column2"]') # Replace with actual column names
.load("EssentialAI/eai-taxonomy-med-w-dclm-100b-sample")
)
# Run SQL queries on the dataset
df.createOrReplaceTempView("eai_taxonomy_med_w_dclm_dataset")
result = spark.sql("""
SELECT COUNT(*) as total_examples
FROM eai_taxonomy_med_w_dclm_dataset
""")
result.show()
Using Daft
Daft provides a modern DataFrame library optimized for machine learning workloads. You can load the dataset directly from Hugging Face:
import daft
# Load the entire dataset
df = daft.read_parquet("hf://datasets/EssentialAI/eai-taxonomy-med-w-dclm-100b-sample")
# Basic exploration
print("Dataset schema:")
df.schema()
print("First 5 rows:")
df.show(5)
If you need to access private datasets or use authentication:
import daft
from daft.io import IOConfig, HTTPConfig
io_config = IOConfig(http=HTTPConfig(bearer_token="your_token"))
df = daft.read_parquet("hf://datasets/EssentialAI/eai-taxonomy-med-w-dclm-100b-sample", io_config=io_config)
Installation Requirements
Make sure you have the required libraries installed:
# For Hugging Face datasets
pip install datasets
# For PySpark with Hugging Face integration
pip install pyspark_huggingface
# For Daft
pip install daft
π Citation
@misc{ai2025essentialwebv1024ttokens,
title={Essential-Web v1.0: 24T tokens of organized web data},
author={Essential AI and : and Andrew Hojel and Michael Pust and Tim Romanski and Yash Vanjani and Ritvik Kapila and Mohit Parmar and Adarsh Chaluvaraju and Alok Tripathy and Anil Thomas and Ashish Tanwer and Darsh J Shah and Ishaan Shah and Karl Stratos and Khoi Nguyen and Kurt Smith and Michael Callahan and Peter Rushton and Philip Monk and Platon Mazarakis and Saad Jamal and Saurabh Srivastava and Somanshu Singla and Ashish Vaswani},
year={2025},
eprint={2506.14111},
archivePrefix={arXiv},
primaryClass={cs.CL},
url={https://arxiv.org/abs/2506.14111},
}
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Size of downloaded dataset files:
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Size of the auto-converted Parquet files:
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Number of rows:
36,572,418