<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Food allergy and can you explain it in depth? [/INST] A food allergy is an abnormal immune response to food. The symptoms of the allergic reaction may range from mild to severe. They may include itchiness, swelling of the tongue, vomiting, diarrhea, hives, trouble breathing, or low blood pressure. This typically occurs within minutes to several hours of exposure. When the symptoms are severe, it is known as anaphylaxis. A food intolerance and food poisoning are separate conditions, not due to an immune response.Common foods involved include cows milk, peanuts, eggs, shellfish, fish, tree nuts, soy, wheat, sesame, rice, and fruit. The common allergies vary depending on the country. Risk factors include a family history of allergies, vitamin D deficiency, obesity, and high levels of cleanliness. Allergies occur when immunoglobulin E (IgE), part of the bodys immune system, binds to food molecules. A protein in the food is usually the problem. This triggers the release of inflammatory chemicals such as histamine. Diagnosis is usually based on a medical history, elimination diet, skin prick test, blood tests for food-specific IgE antibodies, or oral food challenge.Early exposure to potential allergens may be protective. Management primarily involves avoiding the food in question and having a plan if exposure occurs. This plan may include giving adrenaline (epinephrine) and wearing medical alert jewelry. The benefits of allergen immunotherapy for food allergies is unclear, thus is not recommended as of 2015. Some types of food allergies among children resolve with age, including that to milk, eggs, and soy; while others such as to nuts and shellfish typically do not.In the developed world, about 4% to 8% of people have at least one food allergy. They are more common in children than adults and appear to be increasing in frequency. Male children appear to be more commonly affected than females. Some allergies more commonly develop early in life, while others typically develop in later life. In developed countries, more people believe they have food allergies when they actually do not have them.

Signs and symptoms
Food allergy symptoms occur within minutes to hours after exposure and may include:
Rash
Hives
Itching of mouth, lips, tongue, throat, eyes, skin, or other areas
Swelling (angioedema) of lips, tongue, eyelids, or the whole face
Difficulty swallowing
Runny or congested nose
Hoarse voice
Wheezing and/or shortness of breath
Diarrhea, abdominal pain, and/or stomach cramps
Lightheadedness
Fainting
Nausea
VomitingIn some cases, however, onset of symptoms may be delayed for hours.Symptoms can vary. The amount of food needed to trigger a reaction also varies.Serious danger regarding allergies can begin when the respiratory tract or blood circulation is affected. The former can be indicated through wheezing and cyanosis. Poor blood circulation leads to a weak pulse, pale skin and fainting.A severe case of an allergic reaction, caused by symptoms affecting the respiratory tract and blood circulation, is called anaphylaxis.  When symptoms are related to a drop in blood pressure, the person is said to be in anaphylactic shock. Anaphylaxis occurs when IgE antibodies are involved, and areas of the body that are not in direct contact with the food become affected and show symptoms. Those with asthma or an allergy to peanuts, tree nuts, or seafood are at greater risk for anaphylaxis.

Causes
Although sensitivity levels vary by country, the most common food allergies are allergies to milk, eggs, peanuts, tree nuts, fish, shellfish, soy, and wheat. These are often referred to as "the big eight". Allergies to seeds—especially sesame—seem to be increasing in many countries. Sesame will join “the big eight” as a priority allergen in the United States by 2023. An example of an allergy more common to a particular region is that to rice in East Asia where it forms a large part of the diet.One of the most common food allergies is a sensitivity to peanuts, a member of the bean family. Peanut allergies may be severe, but children with peanut allergies sometimes outgrow them. Tree nuts, including almonds, brazil nuts, cashews, coconuts, hazelnuts, macadamia nuts, pecans, pistachios, pine nuts, and walnuts, are also common allergens. Affected individuals may be sensitive to one particular tree nut or to many different ones. Peanuts and seeds, including sesame seeds and poppy seeds, can be processed to extract oils, but trace amounts of protein may be present, and elicit an allergic reaction.Egg allergies affect about one in 50 children but are frequently outgrown by children when they reach age five.  Typically, the sensitivity is to proteins in the white, rather than the yolk.Milk from cows, goats, or sheep is another common food allergen, and many affected people are also unable to tolerate dairy products such as cheese. A small portion of children with a milk allergy, roughly 10%, have a reaction to beef because it contains small amounts of protein that are also present in cows milk.Seafood is one of the most common sources of food allergens; people may be allergic to proteins found in fish or to different proteins found in shellfish (crustaceans and mollusks).Other foods containing allergenic proteins include soy and wheat, and to a lesser frequency, fruits, vegetables, maize, spices, synthetic and natural colors, and chemical additives.Balsam of Peru, which is in various foods, is in the "top five" allergens most commonly causing patch test reactions in people referred to dermatology clinics.

Other than oral ingestion
Sensitization can occur through the gastrointestinal tract, respiratory tract and possibly the skin. Damage to the skin in conditions such as eczema has been proposed as a risk factor for sensitization.While the most obvious route for an allergic exposure is oral ingestion, some reactions are possible through external exposure. Peanut allergies are much more common in adults who had oozing and crusted skin rashes as infants. Airborne particles in a farm- or factory-scale peanut shelling or crushing environment, or from cooking, can produce respiratory effects in exposed allergic individuals. For seafood allergy, an industry review estimated that 28.5 million people worldwide were engaged in some aspect of the seafood industry: fishing, aquaculture, processing and industrial cooking. Exposure to fish allergenic proteins includes inhalation of wet aerosols from fresh fish handling, inhalation of dry aerosols from fishmeal processing, and dermal contact through skin breaks and cuts. Respiratory allergies are an occupational disease that develop in food service workers working with baked goods, known as "bakers asthma"). Previous studies detected 40 allergens from wheat; some cross-reacted with rye proteins and a few cross-reacted with grass pollens.Influenza vaccines are created by injecting a live virus into fertilized chicken eggs. The viruses are harvested, killed and purified, but a residual amount of egg white protein remains. There are options to receive recombinant flu vaccine grown on mammalian cell cultures instead of in eggs.

Atopy
Food allergies develop more easily in people with the atopic syndrome, a very common combination of diseases: allergic rhinitis and conjunctivitis, eczema, and asthma. The syndrome has a strong inherited component; a family history of allergic diseases can be indicative of the atopic syndrome.

Cross-reactivity
Some children who are allergic to cows milk protein also show a cross-sensitivity to soy-based products. Some infant formulas have their milk and soy proteins hydrolyzed, so when taken by infants, their immune systems do not recognize the allergen and they can safely consume the product. Hypoallergenic infant formulas can be based on proteins partially predigested to a less antigenic form. Other formulas, based on free amino acids, are the least antigenic and provide complete nutritional support in severe forms of milk allergy.Crustaceans (shrimp, crab, lobster, etc.) and molluscs (mussel, oyster, scallop, squid, octopus, snail, etc.) are different invertebrate classes, but the allergenic protein tropomyosin is present and responsible for cross-reactivity.People with latex allergy often also develop allergies to bananas, kiwifruit, avocados, and some other foods.

Pathophysiology
Conditions caused by food allergies are classified into three groups according to the mechanism of the allergic response:
IgE-mediated (classic) – the most common type, occurs shortly after eating and may involve anaphylaxis.
Non-IgE mediated – characterized by an immune response not involving immunoglobulin E; may occur some hours after eating, complicating diagnosis
IgE and/or non-IgE-mediated – a hybrid of the above two typesAllergic reactions are hyperactive responses of the immune system to generally innocuous substances. When immune cells encounter the allergenic protein, IgE antibodies are produced; this is similar to the immune systems reaction to foreign pathogens. The IgE antibodies identify the allergenic proteins as harmful and initiate the allergic reaction. The harmful proteins are those that do not break down due to the strong bonds of the protein. IgE antibodies bind to a receptor on the surface of the protein, creating a tag, just as a virus or parasite becomes tagged. Why some proteins do not denature and subsequently trigger allergic reactions and hypersensitivity while others do is not entirely clear.Hypersensitivities are categorized according to the parts of the immune system that are attacked and the amount of time it takes for the response to occur.  The four types of hypersensitivity reaction are:  type 1, immediate IgE-mediated; type 2, cytotoxic; type 3, immune complex-mediated; and type 4, delayed cell-mediated. The pathophysiology of allergic responses can be divided into two phases. The first is an acute response that occurs immediately after exposure to an allergen. This phase can either subside or progress into a "late-phase reaction" which can substantially prolong the symptoms of a response, and result in tissue damage.Many food allergies are caused by hypersensitivities to particular proteins in different foods.  Proteins have unique properties that allow them to become allergens, such as stabilizing forces in their tertiary and quaternary structures which prevent degradation during digestion. Many theoretically allergenic proteins cannot survive the destructive environment of the digestive tract, thus do not trigger hypersensitive reactions.

Acute response
In the early stages of allergy, a type I hypersensitivity reaction against an allergen, encountered for the first time, causes a response in a type of immune cell called a TH2 lymphocyte, which belongs to a subset of T cells that produce a cytokine called interleukin-4 (IL-4).  These TH2 cells interact with other lymphocytes called B cells, whose role is the production of antibodies.  Coupled with signals provided by IL-4, this interaction stimulates the B cell to begin production of a large amount of a particular type of antibody known as IgE.  Secreted IgE circulates in the blood and binds to an IgE-specific receptor (a kind of Fc receptor called FcεRI) on the surface of other kinds of immune cells called mast cells and basophils, which are both involved in the acute inflammatory response.  The IgE-coated cells, at this stage, are sensitized to the allergen.If later exposure to the same allergen occurs, the allergen can bind to the IgE molecules held on the surface of the mast cells or basophils.  Cross-linking of the IgE and Fc receptors occurs when more than one IgE-receptor complex interacts with the same allergenic molecule and activates the sensitized cell.  Activated mast cells and basophils undergo a process called degranulation, during which they release histamine and other inflammatory chemical mediators (cytokines, interleukins, leukotrienes, and prostaglandins) from their granules into the surrounding tissue causing several systemic effects, such as vasodilation, mucous secretion, nerve stimulation, and smooth-muscle contraction. This results in rhinorrhea, itchiness, dyspnea, and anaphylaxis. Depending on the individual, the allergen, and the mode of introduction, the symptoms can be system-wide (classical anaphylaxis), or localized to particular body systems.

Late-phase response
After the chemical mediators of the acute response subside, late-phase responses can often occur due to the migration of other leukocytes such as neutrophils, lymphocytes, eosinophils, and macrophages to the initial site. The reaction is usually seen 2–24 hours after the original reaction. Cytokines from mast cells may also play a role in the persistence of long-term effects.

Diagnosis
Diagnosis is usually based on a medical history, elimination diet, skin prick test, blood tests for food-specific IgE antibodies, or oral food challenge.
For skin-prick tests, a tiny board with protruding needles is used.  The allergens are placed either on the board or directly on the skin.  The board is then placed on the skin, to puncture the skin and for the allergens to enter the body. If a hive appears, the person is considered positive for the allergy. This test only works for IgE antibodies.  Allergic reactions caused by other antibodies cannot be detected through skin-prick tests.Skin-prick testing is easy to do and results are available in minutes. Different allergists may use different devices for testing. Some use a "bifurcated needle", which looks like a fork with two prongs. Others use a "multitest", which may look like a small board with several pins sticking out of it. In these tests, a tiny amount of the suspected allergen is put onto the skin or into a testing device, and the device is placed on the skin to prick, or break through, the top layer of skin. This puts a small amount of the allergen under the skin. A hive will form at any spot where the person is allergic. This test generally yields a positive or negative result. It is good for quickly learning if a person is allergic to a particular food or not because it detects IgE. Skin tests cannot predict if a reaction would occur or what kind of reaction might occur if a person ingests that particular allergen. They can, however, confirm an allergy in light of a patients history of reactions to a particular food. Non-IgE-mediated allergies cannot be detected by this method.

Patch testing is used to determine if a specific substance causes allergic inflammation of the skin. It tests for delayed food reactions.
Blood testing is another way to test for allergies; however, it poses the same disadvantage and only detects IgE allergens and does not work for every possible allergen.  Radioallergosorbent testing (RAST) is used to detect IgE antibodies present to a certain allergen. The score taken from the RAST is compared to predictive values, taken from a specific type of RAST. If the score is higher than the predictive values, a great chance the allergy is present in the person exists. One advantage of this test is that it can test many allergens at one time.A CAP-RAST has greater specificity than RAST; it can show the amount of IgE present to each allergen. Researchers have been able to determine "predictive values" for certain foods, which can be compared to the RAST results. If a persons RAST score is higher than the predictive value for that food, over a 95% chance exists that patients will have an allergic reaction (limited to rash and anaphylaxis reactions) if they ingest that food. Currently, predictive values are available for milk, egg, peanut, fish, soy, and wheat. Blood tests allow for hundreds of allergens to be screened from a single sample, and cover food allergies as well as inhalants. However, non-IgE-mediated allergies cannot be detected by this method. Other widely promoted tests such as the antigen leukocyte cellular antibody test and the food allergy profile are considered unproven methods, the use of which is not advised.
Food challenges test for allergens other than those caused by IgE allergens. The allergen is given to the person in the form of a pill, so the person can ingest the allergen directly.  The person is watched for signs and symptoms. The problem with food challenges is that they must be performed in the hospital under careful watch, due to the possibility of anaphylaxis.Food challenges, especially double-blind, placebo-controlled food challenges, are the gold standard for diagnosis of food allergies, including most non-IgE-mediated reactions, but is rarely done. Blind food challenges involve packaging the suspected allergen into a capsule, giving it to the patient, and observing the patient for signs or symptoms of an allergic reaction.The recommended method for diagnosing food allergy is to be assessed by an allergist. The allergist will review the patients history and the symptoms or reactions that have been noted after food ingestion. If the allergist feels the symptoms or reactions are consistent with food allergy, he/she will perform allergy tests. Additional diagnostic tools for evaluation of eosinophilic or non-IgE mediated reactions include endoscopy, colonoscopy, and biopsy.

Differential diagnosis
Important differential diagnoses are:

Lactose intolerance generally develops later in life, but can present in young patients in severe cases. It is not an immune reaction and is due to an enzyme deficiency (lactase). It is more common in many non-Western people.
Celiac disease. While it is caused by a permanent intolerance to gluten (present in wheat, rye, barley and oats), is not an allergy nor simply an intolerance, but a chronic, multiple-organ autoimmune disorder primarily affecting the small intestine.
Irritable bowel syndrome
C1 Esterase inhibitor deficiency (hereditary angioedema), a rare disease, generally causes attacks of angioedema, but can present solely with abdominal pain and occasional diarrhea, and thus may be confused with allergy-triggered angioedema.

Prevention
Breastfeeding for more than four months may prevent atopic dermatitis, cows milk allergy, and wheezing in early childhood. Early exposure to potential allergens may be protective. Specifically, early exposure to eggs and peanuts reduces the risk of allergies to these. Guidelines suggest introducing peanuts as early as 4–6 months and include precautionary measures for high-risk infants. The former guidelines, advising delaying the introduction of peanuts, are now thought to have contributed to the increase in peanut allergy seen recently.To avoid an allergic reaction, a strict diet can be followed. It is difficult to determine the amount of allergenic food required to elicit a reaction, so complete avoidance should be attempted.  In some cases, hypersensitive reactions can be triggered by exposures to allergens through skin contact, inhalation, kissing, participation in sports, blood transfusions, cosmetics, and alcohol.

Inhalation exposure
Allergic reactions to airborne particles or vapors of known food allergens have been reported as an occupational consequence of people working in the food industry, but can also take place in home situations, restaurants, or confined spaces such as airplanes. According to two reviews, respiratory symptoms are common, but in some cases there has been progression to anaphylaxis. The most frequent reported cases of reactions by inhalation of allergenic foods were due to peanut, seafood, legumes, tree nut, and cows milk. Steam rising from cooking of lentils, green beans, chickpeas and fish has been well documented as triggering reactions, including anaphylactic reactions. One review mentioned case study examples of allergic responses to inhalation of other foods, including examples in which oral consumption of the food is tolerated.

Treatment
The mainstay of treatment for food allergy is total avoidance of the foods identified as allergens.  An allergen can enter the body by consuming a portion of food containing the allergen, and can also be ingested by touching any surfaces that may have come into contact with the allergen, then touching the eyes or nose. For people who are extremely sensitive, avoidance includes avoiding touching or inhaling problematic food. Total avoidance is complicated because the declaration of the presence of trace amounts of allergens in foods is not mandatory (see regulation of labelling).
If the food is accidentally ingested and a systemic reaction (anaphylaxis) occurs, then epinephrine should be used. A second dose of epinephrine may be required for severe reactions.  The person should then be transported to the emergency room, where additional treatment can be given.  Other treatments include antihistamines and steroids.

Epinephrine
Epinephrine (adrenaline) is the first-line treatment for severe allergic reactions (anaphylaxis). If administered in a timely manner, epinephrine can reverse its effects. Epinephrine relieves airway swelling and obstruction, and improves blood circulation; blood vessels are tightened and heart rate is increased, improving circulation to body organs.  Epinephrine is available by prescription in an autoinjector.

Antihistamines
Antihistamines can alleviate some of the milder symptoms of an allergic reaction, but do not treat all symptoms of anaphylaxis.  Antihistamines block the action of histamine, which causes blood vessels to dilate and become leaky to plasma proteins. Histamine also causes itchiness by acting on sensory nerve terminals.  The most common antihistamine given for food allergies is diphenhydramine.

Steroids
Glucocorticoid steroids are used to calm down the immune system cells that are attacked by the chemicals released during an allergic reaction.  This treatment in the form of a nasal spray should not be used to treat anaphylaxis, for it only relieves symptoms in the area in which the steroid is in contact.  Another reason steroids should not be used is the delay in reducing inflammation.  Steroids can also be taken orally or through injection, by which every part of the body can be reached and treated, but a long time is usually needed for these to take effect.

Epidemiology
The most common food allergens account for about 90% of all allergic reactions; in adults they include crustacean shellfish, peanuts, tree nuts, fish, and egg. In children, they include milk, eggs, peanuts, and tree nuts. Six to 8% of children under the age of three have food allergies and nearly 4% of adults have food allergies.For reasons not entirely understood, the diagnosis of food allergies has apparently become more common in Western nations recently. One possible explanation for this is the "old friends" hypothesis which suggests that non disease causing organisms, such as helminths, could protect against allergy. Therefore, reduced exposure to these organisms, particularly in developed countries, could have contributed towards the increase.In the United States, food allergy affects as many as 5% of infants less than three years of age and 3% to 4% of adults. A similar prevalence is found in Canada.About 75% of children who have allergies to milk protein are able to tolerate baked-in milk products, i.e., muffins, cookies, cake, and hydrolyzed formulas.About 50% of children with allergies to milk, egg, soy, peanuts, tree nuts, and wheat will outgrow their allergy by the age of 6. Those who are still allergic by the age of 12 or so have less than an 8% chance of outgrowing the allergy.Peanut and tree nut allergies are less likely to be outgrown, although evidence shows that about 20% of those with peanut allergies and 9% of those with tree nut allergies will outgrow them.In Japan, allergy to buckwheat flour, used for soba noodles, is more common than peanuts, tree nuts or foods made from soy beans.

United States
In the United States, an estimated 12 million people have food allergies. Food allergy affects as many as 5% of infants less than three years of age and 3% to 4% of adults. The prevalence of food allergies is rising. Food allergies cause roughly 30,000 emergency room visits and 150 deaths per year.

Regulation
Whether rates of food allergy are increasing or not, food allergy awareness has definitely increased, with impacts on the quality of life for children, their parents and their caregivers. In the United States, the Food Allergen Labeling and Consumer Protection Act of 2004 causes people to be reminded of allergy problems every time they handle a food package, and restaurants have added allergen warnings to menus. The Culinary Institute of America, a premier school for chef training, has courses in allergen-free cooking and a separate teaching kitchen. School systems have protocols about what foods can be brought into the school. Despite all these precautions, people with serious allergies are aware that accidental exposure can easily occur at other peoples houses, at school or in restaurants.

Regulation of labelling
In response to the risk that certain foods pose to those with food allergies, some countries have responded by instituting labeling laws that require food products to clearly inform consumers if their products contain priority allergens or byproducts of major allergens among the ingredients intentionally added to foods.
The priority allergens vary by country.

There are no labeling laws mandating declaration of the presence of trace amounts in the final product as a consequence of cross-contamination, except in Brazil.

Ingredients intentionally added
In the United States, the Food Allergen Labeling and Consumer Protection Act of 2004 (FALCPA) requires companies to disclose on the label whether a packaged food product contains any of these eight major food allergens, added intentionally: cows milk, peanuts, eggs, shellfish, fish, tree nuts, soy and wheat. The eight-ingredient is list originated in 1999 from the World Health Organisation Codex Alimentarius Commission. To meet FALCPA labeling requirements, if an ingredient is derived from one of the required-label allergens, then it must either have its "food sourced name" in parentheses, for example, "Casein (milk)," or as an alternative, there must be a statement separate but adjacent to the ingredients list: "Contains milk" (and any other of the allergens with mandatory labeling). The European Union requires listing for those eight major allergens plus molluscs, celery, mustard, lupin, sesame and sulfites.In 2018, the US FDA issued a request for information for the consideration of labeling for sesame to help protect people who have sesame allergies. A decision was reached in November 2020 that food manufacturers voluntarily declare that when powdered sesame seeds are used as a previously unspecified spice or flavor, the label be changed to "spice (sesame)" or "flavor (sesame)."Congress and the President passed a law in April 2021, the "FASTER Act", stipulating that labeling be mandatory, to be effect January 1, 2023, making it the ninth required food ingredient label.FALCPA applies to packaged foods regulated by the FDA, which does not include poultry, most meats, certain egg products, and most alcoholic beverages. However, some meat, poultry, and egg processed products may contain allergenic ingredients. These products are regulated by the Food Safety and Inspection Service (FSIS), which requires that any ingredient be declared in the labeling only by its common or usual name. Neither the identification of the source of a specific ingredient in a parenthetical statement nor the use of statements to alert for the presence of specific ingredients, like "Contains: milk", are mandatory according to FSIS.  FALCPA also does not apply to food prepared in restaurants. The EU Food Information for Consumers Regulation 1169/2011 – requires food businesses to provide allergy information on food sold unpackaged, for example, in catering outlets, deli counters, bakeries and sandwich bars.In the United States, there is no federal mandate to address the presence of allergens in drug products. FALCPA does not apply to medicines nor to cosmetics.

Trace amounts as a result of cross-contamination
The value of allergen labeling other than for intentional ingredients is controversial. This concerns labeling for ingredients present unintentionally as a consequence of cross-contact or cross-contamination at any point along the food chain (during raw material transportation, storage or handling, due to shared equipment for processing and packaging, etc.). Experts in this field propose that if allergen labeling is to be useful to consumers, and healthcare professionals who advise and treat those consumers, ideally there should be agreement on which foods require labeling, threshold quantities below which labeling may be of no purpose, and validation of allergen detection methods to test and potentially recall foods that were deliberately or inadvertently contaminated.Labeling regulations have been modified to provide for mandatory labeling of ingredients plus voluntary labeling, termed precautionary allergen labeling (PAL), also known as "may contain" statements, for possible, inadvertent, trace amount, cross-contamination during production. PAL labeling can be confusing to consumers, especially as there can be many variations on the wording of the warning. PAL is optional in the United States. As of 2014, PAL is regulated only in Switzerland, Japan, Argentina, and South Africa. Argentina decided to prohibit precautionary allergen labeling since 2010 and instead puts the onus on the manufacturer to control the manufacturing process and label only those allergenic ingredients known to be in the products. South Africa does not permit the use of PAL, except when manufacturers demonstrate the potential presence of allergen due to cross-contamination through a documented risk assessment and despite adherence to Good Manufacturing Practice. In Australia and New Zealand there is a recommendation that PAL be replaced by guidance from VITAL 2.0 (Vital Incidental Trace Allergen Labeling). A review identified "the eliciting dose for an allergic reaction in 1% of the population" as ED01. This threshold reference dose for foods (such as cows milk, egg, peanut and other proteins) will provide food manufacturers with guidance for developing precautionary labeling and give consumers a better idea of what might be accidentally in a food product beyond "may contain." VITAL 2.0 was developed by the Allergen Bureau, a food industry sponsored, non-government organization. The European Union has initiated a process to create labeling regulations for unintentional contamination but is not expected to publish such before 2024.In Brazil, since April 2016, the declaration of the possibility of cross-contamination is mandatory when the product does not intentionally add any allergenic food or its derivatives, but the Good Manufacturing Practices and allergen control measures adopted are not sufficient to prevent the presence of accidental trace amounts. These allergens include wheat, rye, barley, oats and their hybrids, crustaceans, eggs, fish, peanuts, soybean, milk of all species of mammalians, almonds, hazelnuts, cashew nuts, Brazil nuts, macadamia nuts, walnuts, pecan nuts, pistachios, pine nuts, and chestnuts.

Genetically modified food
Although there is a scientific consensus that available food derived from GM crops poses no greater risk to human health than conventional food, and a 2016 U.S. National Academy of Sciences report concluded that there is no relationship between consumption of GM foods and the increase in prevalence of food allergies, there are concerns that genetically modified foods, also described as foods sourced from genetically modified organisms (GMO), could be responsible for allergic reactions, and that the widespread acceptance of GMO foods may be responsible for what is a real or perceived increase in the percentage of people with allergies.One concern is that genetic engineering could make an allergy-provoking food more allergic, meaning that smaller portions would suffice to set off a reaction. Of the food currently in widespread GMO use, only soybeans are identified as a common allergen. However, for the soybean proteins known to trigger allergic reactions, there is more variation from strain to strain than between those and the GMO varieties. Another concern is that genes transferred from one species to another could introduce an allergen in a food not thought of as particularly allergenic. Research on an attempt to enhance the quality of soybean protein by adding genes from Brazil nuts was terminated when human volunteers known to have tree nut allergy reacted to the modified soybeans.Prior to a new GMO food receiving government approval, certain criteria need to be met. These include: Is the donor species known to be allergenic? Does the amino acid sequence of the transferred proteins resemble the sequence of known allergenic proteins? Are the transferred proteins resistant to digestion - a trait shared by many allergenic proteins? Genes approved for animal use can be restricted from human consumption due to potential for allergic reactions. In 1998 Starlink brand corn restricted to animals was detected in the human food supply, leading to first a voluntary and then a FDA mandated recall. There are requirements in some countries and recommendations in others that all foods containing GMO ingredients be so labeled, and that there be a post-launch monitoring system to report adverse effects (much there exists in some countries for drug and dietary supplement reporting).

Restaurants
In the US, the FDA Food Code states that the person in charge in restaurants should have knowledge about major food allergens, cross-contacts, and symptoms of food allergy
reactions. Restaurant staff, including wait staff and kitchen staff, may not be adequately informed about allergenic ingredients, or the risk of cross-contact when kitchen utensils used to prepare food may have been in previous contact with an allergenic food. The problem may be compounded when customers have a hard time describing their food allergies or when wait staff have a hard time understanding those with food allergies when taking an order.

Diagnosing issues
There exists both over-reporting and under-reporting of the prevalence of food allergies. Self-diagnosed perceptions of food allergy are greater than the rates of true food allergy because people confuse non-allergic intolerance with allergy, and also attribute non-allergy symptoms to an allergic response. Conversely, healthcare professionals treating allergic reactions on an out-patient or even hospitalized basis may not report all cases. Recent increases in reported cases may reflect a real change in incidence or an increased awareness on the part of healthcare professionals.

Social impact
Food fear has a significant impact on quality of life. For children with allergies, their quality of life is also affected by the actions of their peers. An increased occurrence of bullying has been observed, which can include threats or deliberate acts of forcing allergic children to contact foods that they must avoid or intentional contamination of allergen-free food.

Portrayal in media
Media portrayals of food allergy in television and film are not accurate, often used for comedic effect or underplaying the potential severity of an allergic reaction. These tropes missinform the public and also contribute to how entertainment media will continue to wrongly portray food allergies in the future. Types of tropes: 1) characters have food allergies, providing a weakness that can be used to sabotage them. In the movie Parasite a housekeeper is displaced by taking advantage of her peach allergy. In the animated film Peter Rabbit, the farm owner is attacked by being pelted with blackberries, causing an anaphylactic reaction requiring emergency treatment with epinephrine. After many public protests, Sony Pictures and the Peter Rabbit director apologized for making light of food allergies. 2) Food allergy is used for comedic effect, such as in the movies Hitch and in television, Kelsos egg allergy in That 70s Show 3) Food allergies may be incorporated into characters who are also portrayed as annoying, weak and oversensitive, which can be taken as implying that their allergies are either not real or not potentially severe. In season 1, episode 16 of The Big Bang Theory Howard Wolowitz deliberately consumes a peanut-containing food bar (and has a serious reaction) just to delay Leonard from returning to his apartment where a surprise birthday party is being arranged. 4) Any of these portrayals may underplay the potential severity of food allergy, some showing that Benadryl treatment is sufficient. Viewing of humorous portrayals of food allergies has been shown to have a negative effect on related health policy support due to low perceived seriousness.

Research
A number of desensitization techniques are being studied. Areas of research include anti-IgE antibody (omalizumab), specific oral tolerance induction (SOTI, also known as OIT for oral immunotherapy), and sublingual immunotherapy (SLIT). The benefits of allergen immunotherapy for food allergies is unclear, thus is not recommended as of 2015.There is research on the effects of increasing intake of polyunsaturated fatty acids (PUFAs) during pregnancy, lactation, via infant formula and in early childhood on the subsequent risk of developing food allergies during infancy and childhood. From two reviews, maternal intake of omega-3, long-chain fatty acids during pregnancy appeared to reduce the risks of medically diagnosed IgE-mediated allergy, eczema and food allergy per parental reporting in the first 12 months of life, but the effects were not all sustained past 12 months. The reviews characterized the literatures evidence as inconsistent and limited. Results when breastfeeding mothers were consuming a diet high in PUFAs were inconclusive. For infants, supplementing their diet with oils high in PUFAs did not affect the risks of food allergies, eczema or asthma either as infants or into childhood.There is research on probiotics, prebiotics and the combination of the two (synbiotics) as a means of treating or preventing infant and child allergies. From reviews, there appears to be a treatment benefit for eczema, but not asthma, wheezing or rhinoconjunctivitis. The evidence was not consistent for preventing food allergies and this approach cannot yet be recommended.The Food Standards Agency, in the United Kingdom, are in charge of funding research into food allergies and intolerance. Since their founding in 1994 they have funded over 45 studies. In 2005 Europe created EuroPrevall, a multi-country project dedicated to research involving allergies.

See also
List of allergens (food and non-food)

References
NotesNester, Eugene W.; Anderson, Denise G.; Roberts Jr, C. Evans; Nester, Martha T. (2009). "Immunologic Disorders". Microbiology: A Human Perspective (6th ed.). New York: McGraw-Hill. pp </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Endoscopic foreign body retrieval and can you explain it in depth? [/INST] Endoscopic foreign body retrieval refers to the removal of ingested objects from the esophagus, stomach and duodenum by endoscopic techniques.  It does not involve surgery, but rather encompasses a variety of techniques employed through the gastroscope for grasping foreign bodies, manipulating them, and removing them while protecting the esophagus and trachea.  It is of particular importance with children, people with mental illness, and prison inmates as these groups have a high rate of foreign body ingestion.
Commonly swallowed objects include coins, buttons, batteries, and small bones (such as fish bones), but can include more complex objects, such as eyeglasses, spoons, and toothbrushes (see image).

Indications and contraindications
Some patients at risk for foreign body ingestion may not be able to give an accurate medical history of ingestion, either due to age or mental illness </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Labial fusion and can you explain it in depth? [/INST] Labial fusion is a medical condition of the female genital anatomy where the labia minora become fused together. It is generally a pediatric condition.

Presentation
Labial fusion is rarely present at birth, but rather acquired later in infancy, since it is caused by insufficient estrogen exposure and newborns have been exposed to maternal estrogen in utero. It typically presents in infants at least 3 months old. Most presentations are asymptomatic and are discovered by a parent or during routine medical examination. In other cases, patients may present with associated symptoms of dysuria, urinary frequency, refusal to urinate, or post-void dribbling. Some patients present with vaginal discharge due to pooling of urine in the vulval vestibule or vagina.

Complications
Labial fusion can lead to urinary tract infection, vulvar vestibulitis and inflammation caused by chronic urine exposure. In severe cases, labial adhesions can cause complete obstruction of the urethra, leading to anuria and urinary retention.

Pathophysiology
The primary contributing factor to labial fusion is low estrogen levels. A vulva with low estrogen exposure, such as that of a preadolescent, has delicate epithelial lining and is therefore vulnerable to irritation </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Gastric erosion and can you explain it in depth? [/INST] Gastric erosion occurs when the mucous membrane lining the stomach becomes inflamed. Specifically, the term "erosion," in this context means damage that is limited to the mucosa (which consists of three distinct layers: The epithelium (in the case of a healthy stomach, this is non-ciliated simple columnar epithelium), basement membrane, and lamina propria). An erosion is different from an ulcer </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Gestational trophoblastic disease and can you explain it in depth? [/INST] Gestational trophoblastic disease (GTD) is a term used for a group of pregnancy-related tumours. These tumours are rare, and they appear when cells in the womb start to proliferate uncontrollably. The cells that form gestational trophoblastic tumours are called trophoblasts and come from tissue that grows to form the placenta during pregnancy.
There are several different types of GTD. A hydatidiform mole also known as a molar pregnancy, is the most common and is usually benign. Sometimes it may develop into an invasive mole, or, more rarely into a choriocarcinoma. A choriocarcinoma is likely to spread quickly, but is very sensitive to chemotherapy, and has a very good prognosis. Trophoblasts are of particular interest to cell biologists because, like cancer, they can invade tissue (the uterus), but unlike cancer, they usually  "know" when to stop.GTD can simulate pregnancy, because the uterus may contain fetal tissue, albeit abnormal. This tissue may grow at the same rate as a normal pregnancy, and produces chorionic gonadotropin, a hormone which is measured to monitor fetal well-being.While GTD overwhelmingly affects women of child-bearing age, it may rarely occur in postmenopausal women.

Types
GTD is the common name for five closely related tumours (one benign tumour, and four malignant tumours):
The benign tumour
Hydatidiform moleHere, first a fertilised egg implants into the uterus, but some cells around the fetus (the chorionic villi) do not develop properly. The pregnancy is not viable, and the normal pregnancy process turns into a benign tumour. There are two subtypes of hydatidiform mole: complete hydatidiform mole, and partial hydatidiform mole.

The four malignant tumours
Invasive mole
Choriocarcinoma
Placental site trophoblastic tumour
Epithelioid trophoblastic tumourAll five closely related tumours develop in the placenta. All five tumours arise from trophoblast cells that form the outer layer of the blastocyst in the early development of the fetus. In a normal pregnancy, trophoblasts aid the implantation of the fertilised egg into the uterine wall. But in GTD, they develop into tumour cells.

Cause
Two main risk factors increase the likelihood for the development of GTD: 1) The woman being under 20 years of age, or over 35 years of age, and 2) previous GTD.
Although molar pregnancies affect women of all ages, women under 16 and over 45 years of age have an increased risk of developing a molar pregnancy. Being from Asia/of Asian ethnicity is an important risk factor.Hydatidiform moles are abnormal conceptions with excessive placental development. Conception takes place, but placental tissue grows very fast, rather than supporting the growth of a fetus.Complete hydatidiform moles have no fetal tissue and no maternal DNA, as a result of a maternal ovum with no functional DNA. Most commonly, a single spermatozoon duplicates and fertilises an empty ovum. Less commonly, two separate spermatozoa fertilise an empty ovum (dispermic fertilisation).
Partial hydatidiform moles have a fetus or fetal cells. They are triploid in origin, containing one set of maternal haploid genes and two sets of paternal haploid genes. They almost always occur following dispermic fertilisation of a normal ovum. Malignant forms of GTD are very rare. About 50% of malignant forms of GTD develop from a hydatidiform mole.

Diagnosis
Cases of GTD can be diagnosed through routine tests given during pregnancy, such as blood tests and ultrasound, or through tests done after miscarriage or abortion. Vaginal bleeding, enlarged uterus, pelvic pain or discomfort, and vomiting too much (hyperemesis) are the most common symptoms of GTD. But GTD also leads to elevated serum hCG (human chorionic gonadotropin hormone). Since pregnancy is by far the most common cause of elevated serum hCG, clinicians generally first suspect a pregnancy with a complication. However, in GTD, the beta subunit of hCG (beta hCG) is also always elevated. Therefore, if GTD is clinically suspected, serum beta hCG is also measured.The initial clinical diagnosis of GTD should be confirmed histologically, which can be done after the evacuation of pregnancy (see Treatment below) in women with hydatidiform mole. However, malignant GTD is highly vascular. If malignant GTD is suspected clinically, biopsy is contraindicated, because biopsy may cause life-threatening haemorrhage.
Women with persistent abnormal vaginal bleeding after any pregnancy, and women developing acute respiratory or neurological symptoms after any pregnancy, should also undergo hCG testing, because these may be signs of a hitherto undiagnosed GTD.
There might be some signs and symptoms of hyperthyroidism as well as an increase in the levels of thyroid hormones in some patients. The proposed mechanism is attaching hCG to TSH receptors and acting like TSH weakly.

Differential diagnosis
These are not GTD, and they are not tumoursExaggerated placental site
Placental site noduleBoth are composed of intermediate trophoblast, but their morphological features and clinical presentation can differ significantly.
Exaggerated placental site is a benign, non cancerous lesion with an increased number of implantation site intermediate trophoblastic cells that infiltrate the endometrium and the underlying myometrium. An exaggerated placental site may occur with normal pregnancy, or after an abortion. No specific treatment or follow up is necessary.
Placental site nodules are lesions of chorionic type intermediate trophoblast, usually small. 40 to 50% of placental site nodules are found in the cervix. They almost always are incidental findings after a surgical procedure. No specific treatment or follow up is necessary.

Treatment
Treatment is always necessary.The treatment for hydatidiform mole consists of the evacuation of pregnancy. Evacuation will lead to the relief of symptoms, and also prevent later complications. Suction curettage is the preferred method of evacuation. Hysterectomy is an alternative if no further pregnancies are wished for by the female patient. Hydatidiform mole also has successfully been treated with systemic (intravenous) methotrexate.The treatment for invasive mole or choriocarcinoma generally is the same. Both are usually treated with chemotherapy. Methotrexate and dactinomycin are among the chemotherapy drugs used in GTD. In women with low risk gestational trophoblastic neoplasia, a review has found that Actinomycin D is probably more effective as a treatment and more likely to achieve a cure in the first instance than methotrexate. Only a few women with GTD have poor prognosis metastatic gestational trophoblastic disease. Their treatment usually includes chemotherapy. Radiotherapy can also be given to places where the cancer has spread, e.g. the brain.Women who undergo chemotherapy are advised not to conceive for one year after completion of treatment. These women also are likely to have an earlier menopause. It has been estimated by the Royal College of Obstetricians and Gynaecologists that the age at menopause for women who receive single agent chemotherapy is advanced by one year, and by three years for women who receive multi agent chemotherapy.

Follow up
Follow up is necessary in all women with gestational trophoblastic disease, because of the possibility of persistent disease, or because of the risk of developing malignant uterine invasion or malignant metastatic disease even after treatment in some women with certain risk factors.The use of a reliable contraception method is very important during the entire follow up period, as patients are strongly advised against pregnancy at that time. If a reliable contraception method is not used during the follow-up, it could be initially unclear to clinicians as to whether a rising hCG level is caused by the patient becoming pregnant again, or by the continued presence of GTD.
In women who have a malignant form of GTD, hCG concentrations stay the same (plateau) or they rise. Persistent elevation of serum hCG levels after a non molar pregnancy (i.e., normal pregnancy [term pregnancy], or preterm pregnancy, or ectopic pregnancy [pregnancy taking place in the wrong place, usually in the fallopian tube], or abortion) always indicate persistent GTD (very frequently due to choriocarcinoma or placental site trophoblastic tumour), but this is not common, because treatment mostly is successful.
In rare cases, a previous GTD may be reactivated after a subsequent pregnancy, even after several years. Therefore, the hCG tests should be performed also after any subsequent pregnancy in all women who had had a previous GTD (6 and 10 weeks after the end of any subsequent pregnancy).

Prognosis
Women with a hydatidiform mole have an excellent prognosis. Women with a malignant form of GTD usually have a very good prognosis.Choriocarcinoma, for example, is an uncommon, yet almost always curable cancer. Although choriocarcinoma is a highly malignant tumour and a life-threatening disease, it is very sensitive to chemotherapy. Virtually all women with non-metastatic disease are cured and retain their fertility; the prognosis is also very good for those with metastatic (spreading) cancer, in the early stages, but fertility may be lost. Hysterectomy (surgical removal of the uterus) can also be offered to patients > 40 years of age or those for whom sterilisation is not an obstacle. Only a few women with GTD have a poor prognosis, e.g. some forms of stage IV GTN. The FIGO staging system is used. The risk can be estimated by scoring systems such as the Modified WHO Prognostic Scoring System, wherein scores between 1 and 4 from various parameters are summed together:
In this scoring system, women with a score of 7 or greater are considered at high risk.
It is very important for malignant forms of GTD to be discovered in time. In Western countries, women with molar pregnancies are followed carefully; for instance, in the UK, all women who have had a molar pregnancy are registered at the National Trophoblastic Screening Centre. There are efforts in this direction in the developing countries too, and there have been improvements in these countries in the early detection of choriocarcinoma, thereby significantly reducing the mortality rate also in  developing countries.

Becoming pregnant again
Most women with GTD can become pregnant again and can have children again. The risk of a further molar pregnancy is low. More than 98% of women who become pregnant following a molar pregnancy will not have a further hydatidiform mole or be at increased risk of complications.
In the past, it was seen as important not to get pregnant straight away after a GTD. Specialists recommended a waiting period of six months after the hCG levels become normal. Recently, this standpoint has been questioned. New medical data suggest that a significantly shorter waiting period after the hCG levels become normal is reasonable for approximately 97% of the patients with hydatidiform mole.

Risk of a repeat GTD
The risk of a repeat GTD is approximately 1 in 100, compared with approximately 1 in 1000 risk in the general population. Especially women whose hCG levels remain significantly elevated are at risk of developing a repeat GTD.

Persistent trophoblastic disease
The term «persistent trophoblastic disease» (PTD) is used when after treatment of a molar pregnancy, some molar tissue is left behind and again starts growing into a tumour. Although PTD can spread within the body like a malignant cancer, the overall cure rate is nearly 100%.In the vast majority of patients, treatment of PTD consist of chemotherapy. Only about 10% of patients with PTD can be treated successfully with a second curettage.

GTD coexisting with a normal fetus, also called "twin pregnancy"
In some very rare cases, a GTD can coexist with a normal fetus. This is called a "twin pregnancy". These cases should be managed only by experienced clinics, after extensive consultation with the patient. Because successful term delivery might be possible, the pregnancy should be allowed to proceed if the mother wishes, following appropriate counselling. The probability of achieving a healthy baby is approximately 40%, but there is a risk of complications, e.g. pulmonary embolism and pre-eclampsia </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Giardiasis and can you explain it in depth? [/INST] Giardiasis is a parasitic disease caused by Giardia duodenalis (also known as G. lamblia and G. intestinalis). Infected individuals who experience symptoms (about 10% have no symptoms) may have diarrhea, abdominal pain, and weight loss. Less common symptoms include vomiting and blood in the stool. Symptoms usually begin 1 to 3 weeks after exposure and, without treatment, may last two to six weeks or longer.Giardiasis usually spreads when Giardia duodenalis cysts within feces contaminate food or water that is later consumed orally. The disease can also spread between people and through other animals. Cysts may survive for nearly three months in cold water. Giardiasis is diagnosed via stool tests.Prevention may be improved through proper hygiene practices. Asymptomatic cases often do not need treatment. When symptoms are present, treatment is typically provided with either tinidazole or metronidazole. Infection may cause a person to become lactose intolerant, so it is recommended to temporarily avoid lactose following an infection. Resistance to treatment may occur in some patients.Giardiasis occurs worldwide. It is one of the most common parasitic human diseases. Infection rates are as high as 7% in the developed world and 30% in the developing world. In 2013, there were approximately 280 million people worldwide with symptomatic cases of giardiasis. The World Health Organization classifies giardiasis as a neglected disease. It is popularly known as beaver fever in North America.

Signs and symptoms
Symptoms vary from none to severe diarrhea with poor absorption of nutrients. The cause of this wide range in severity of symptoms is not fully known but the intestinal flora of the infected host may play a role. Diarrhea is less likely to occur in people from developing countries.Symptoms typically develop 9–15 days after exposure, but may occur as early as one day. The most common and prominent symptom is chronic diarrhea, which can occur for weeks or months if untreated. Diarrhea is often greasy and foul-smelling, with a tendency to float. This characteristic diarrhea is often accompanied by a number of other symptoms, including gas, abdominal cramps, and nausea or vomiting. Some people also experience symptoms outside of the gastrointestinal tract, such as itchy skin, hives, and swelling of the eyes and joints, although these are less common. Fever occurs in only about 15% of people, in spite of the nickname "beaver fever".Prolonged disease is often characterized by diarrhea, along with malabsorption of nutrients in the intestine. This malabsorption results in fatty stools, substantial weight loss, and fatigue. Additionally, those with giardiasis often have difficulty absorbing lactose, vitamin A, folate, and vitamin B12. In children, prolonged giardiasis can cause failure to thrive and may impair mental development. Symptomatic infections are well recognized as causing lactose intolerance, which, while usually temporary, may become permanent.

Cause
Giardiasis is caused by the protozoan Giardia duodenalis. The infection occurs in many animals, including beavers, other rodents, cows, and sheep. Animals are believed to play a role in keeping infections present in an environment.G. duodenalis has been sub-classified into eight genetic assemblages (designated A–H). Genotyping of G. duodenalis isolated from various hosts has shown that assemblages A and B infect the largest range of host species, and appear to be the main and possibly only G. duodenalis assemblages that infect humans.

Risk factors
According to the United States Centers for Disease Control and Prevention (CDC), people at greatest risk of infection are:

People in childcare settings
People who are in close contact with someone who has the disease
Travelers within areas that have poor sanitation
People who have contact with feces during sexual activity
Backpackers or campers who drink untreated water from springs, lakes, or rivers
Swimmers who swallow water from swimming pools, hot tubs, interactive fountains, or untreated recreational water from springs, lakes, or rivers
People who get their household water from a shallow well
People with weakened immune systems
People who have contact with infected animals or animal environments contaminated with fecesFactors that increase infection risk for people from developed countries include changing diapers, consuming raw food, owning a dog, and travelling in the developing world. However, 75% of infections in the United Kingdom are acquired in the UK, not through travel elsewhere. In the United States, giardiasis occurs more often in summer, which is believed to be due to a greater amount of time spent on outdoor activities and traveling in the wilderness.

Transmission
Giardiasis is transmitted via the fecal-oral route with the ingestion of cysts. Primary routes are personal contact and contaminated water and food. The cysts can stay infectious for up to three months in cold water.Many people with Giardia infections have no or few symptoms. They may, however, still spread the disease.

Pathophysiology
The life cycle of Giardia consists of a cyst form and a trophozoite form. The cyst form is infectious and once it has found a host, transforms into the trophozoite form. This trophozoite attaches to the intestinal wall and replicates within the gut.  As trophozoites continue along the gastrointestinal tract, they convert back to their cyst form which is then excreted with feces. Ingestion of only a few of these cysts is needed to generate infection in another host.Infection with Giardia results in decreased expression of brush border enzymes, morphological changes to the microvillus, increased intestinal permeability, and programmed cell death of small intestinal epithelial cells. Both trophozoites and cysts are contained within the gastrointestinal tract and do not invade beyond it.The attachment of trophozoites causes villous flattening and inhibition of enzymes that break down disaccharide sugars in the intestines. Ultimately, the community of microorganisms that lives in the intestine may overgrow and may be the cause of further symptoms, though this idea has not been fully investigated. The alteration of the villi leads to an inability of nutrient and water absorption from the intestine, resulting in diarrhea, one of the predominant symptoms. In the case of asymptomatic giardiasis, there can be malabsorption with or without histological changes to the small intestine. The degree to which malabsorption occurs in symptomatic and asymptomatic cases is highly varied.The species Giardia intestinalis uses enzymes that break down proteins to attack the villi of the brush border and appears to increase crypt cell proliferation and crypt length of crypt cells existing on the sides of the villi. On an immunological level, activated host T lymphocytes attack endothelial cells that have been injured in order to remove the cell. This occurs after the disruption of proteins that connect brush border endothelial cells to one another. The result is increased intestinal permeability.There appears to be a further increase in programmed enterocyte cell death by Giardia intestinalis, which further damages the intestinal barrier and increases permeability. There is significant upregulation of the programmed cell death cascade by the parasite, and, furthermore, substantial downregulation of the anti-apoptotic protein Bcl-2 and upregulation of the proapoptotic protein Bax. These connections suggest a role of caspase-dependent apoptosis in the pathogenesis of giardiasis.Giardia protects its own growth by reducing the formation of the gas nitric oxide by consuming all local arginine, which is the amino acid necessary to make nitric oxide. Arginine starvation is known to be a cause of programmed cell death, and local removal is a strong apoptotic agent.

Host defense
Host defense against Giardia consists of natural barriers, production of nitric oxide, and activation of the innate and adaptive immune systems.

Natural barriers
Natural barriers defend against parasite entering the hosts body. Natural barriers consist of mucus layers, bile salt, proteases, and lipases. Additionally, peristalsis and the renewal of enterocytes provide further protection against parasites.

Nitric oxide production
Nitric oxide does not kill the parasite, but it inhibits the growth of trophozoites as well as excystation and encystation.

Innate immune system
Lectin pathway of complement
The lectin pathway of complement is activated by mannose-binding lectin (MBL) which binds to N-acetylglucosamine. N-acetylglucosamine is a ligand for MBL and is present on the surface of Giardia.

The classical pathway of complement
The classical pathway of complement is activated by antibodies specific against Giardia.

Adaptive immune system
Antibodies
Antibodies inhibit parasite replication and also induce parasite death via the classical pathway of complement.Infection with Giardia typically results in a strong antibody response against the parasite. While IgG is made in significant amounts, IgA is believed to be more important in parasite control. IgA is the most abundant isotype in intestinal secretions, and it is also the dominant isotype in mothers milk. Antibodies in mothers milk protect children against giardiasis (passive immunization).

T cells
The major aspect of adaptive immune responses is the T cell response. Giardia is an extracellular pathogen. Therefore CD4+ helper T cells are primarily responsible for this protective effect.One role of helper T cells is to promote antibody production and isotype switching. Other roles include cytokine production (Il-4,IL-9) to help recruit other effector cells of the immune response.

Diagnosis
According to the CDC, detection of antigens on the surface of organisms in stool specimens is the current test of choice for diagnosis of giardiasis and provides increased sensitivity over more common microscopy techniques.
A trichrome stain of preserved stool is another method used to detect Giardia.
Microscopic examination of the stool can be performed for diagnosis.  This method is not preferred, however, due to inconsistent shedding of trophozoites and cysts in infected hosts.  Multiple samples over a period of time, typically one week, must be examined.
The Entero-Test uses a gelatin capsule with an attached thread. One end is attached to the inner aspect of the hosts cheek, and the capsule is swallowed. Later, the thread is withdrawn and shaken in saline to release trophozoites which can be detected with a microscope. The sensitivity of this test is low, however, and is not routinely used for diagnosis.
Immunologic enzyme-linked immunosorbent assay (ELISA) testing may be used for diagnosis. These tests are capable of a 90% detection rate or more.Although hydrogen breath tests indicate poorer rates of carbohydrate absorption in those asymptomatically infected, such tests are not diagnostic of infection.  Serological tests are not helpful in diagnosis.

Prevention
The CDC recommends hand-washing and avoiding potentially contaminated food and untreated water.Boiling water contaminated with Giardia effectively kills infectious cysts. Chemical disinfectants or filters may be used. Iodine-based disinfectants are preferred over chlorination as the latter is ineffective at destroying cysts.Although the evidence linking the drinking of water in the North American wilderness and giardiasis has been questioned, a number of studies raise concern. Most if not all CDC verified backcountry giardiasis outbreaks have been attributed to water. Surveillance data (for 2013 and 2014) reports six outbreaks (96 cases) of waterborne giardiasis contracted from rivers, streams or springs and less than 1% of reported giardiasis cases are associated with outbreaks.Person-to-person transmission accounts for the majority of Giardia infections, and is usually associated with poor hygiene and sanitation. Giardia is often found on the surface of the ground, in the soil, in undercooked foods, and in water, and on hands that have not been properly cleaned after handling infected feces.  Water-borne transmission is associated with the ingestion of contaminated water. In the U.S., outbreaks typically occur in small water systems using inadequately treated surface water. Venereal transmission happens through fecal-oral contamination. Additionally, diaper changing and inadequate handwashing are risk factors for transmission from infected children. Lastly, food-borne epidemics of Giardia have developed through the contamination of food by infected food-handlers.

Vaccine
There are no vaccines for humans yet, however there are several vaccine candidates in development. They are targeting: recombinant proteins, DNA vaccine, variant-specific surface proteins (VSP), cyst wall proteins (CWP), giadins and enzymes.At present, one commercially available vaccine exists – GiardiaVax, made from G. lamblia whole trophozoite lysate. It is a vaccine for veterinary use only in dogs and cats. GiardiaVax should promote production of specific antibodies.

Treatment
Treatment is not always necessary as the infection usually resolves on its own. However, if the illness is acute or symptoms persist and medications are needed to treat it, a nitroimidazole medication is used such as metronidazole, tinidazole, secnidazole or ornidazole.The World Health Organization and Infectious Disease Society of America recommend metronidazole as first line therapy. The US CDC lists metronidazole, tinidazole, and nitazoxanide as effective first-line therapies; of these three, only nitazoxanide and tinidazole are approved for the treatment of giardiasis by the US FDA. A meta-analysis done by the Cochrane Collaboration found that compared to the standard of metronidazole, albendazole had equivalent efficacy while having fewer side effects, such as gastrointestinal or neurologic issues. Other meta-analyses have reached similar conclusions. Both medications need a five to 10 day long course; albendazole is taken once a day, while metronidazole needs to be taken three times a day. The evidence for comparing metronidazole to other alternatives such as mebendazole, tinidazole or nitazoxanide was felt to be of very low quality. While tinidazole has side effects and efficacy similar to those of metronidazole, it is administered with a single dose.Resistance has been seen clinically to both nitroimidazoles and albendazole, but not nitazoxanide, though nitazoxanide resistance has been induced in research laboratories. The exact mechanism of resistance to all of these medications is not well understood. In the case of nitroimidazole-resistant strains of Giardia, other drugs are available which have showed efficacy in treatment including quinacrine, nitazoxanide, bacitracin zinc, furazolidone and paromomycin. Mepacrine may also be used for refractory cases.Probiotics, when given in combination with the standard treatment, has been shown to assist with clearance of Giardia.During pregnancy, paromomycin is the preferred treatment drug because of its poor intestinal absorption, resulting in less exposure to the fetus. Alternatively, metronidazole can be used after the first trimester as there has been wide experience in its use for trichomonas in pregnancy.

Prognosis
In people with a properly functioning immune system, infection may resolve without medication. A small portion, however, develop a chronic infection. People with an impaired immune system are at higher risk of chronic infection. Medication is an effective cure for nearly all people although there is growing drug-resistance.Children with chronic giardiasis are at risk for failure to thrive as well as more long-lasting sequelae such as growth stunting. Up to half of infected people develop a temporary lactose intolerance leading symptoms that may mimic a chronic infection. Some people experience post-infectious irritable bowel syndrome after the infection has cleared. Giardiasis has also been implicated in the development of food allergies. This is thought to be due to its effect on intestinal permeability.

Epidemiology
In some developing countries Giardia is present in 30% of the population. In the United States it is estimated that it is present in 3–7% of the population.The number of reported cases in the United States in 2018 was 15,584. All states that classify giardiasis as a notifiable disease had cases of giardiasis. The states of Illinois, Kentucky, Mississippi, North Carolina, Oklahoma, Tennessee, Texas, and Vermont did not notify the Center for Disease Control regarding cases in 2018. The states with the highest number of cases in 2018 were California, New York, Florida, and Wisconsin. There are seasonal trends associated with giardiasis </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Gingivitis and can you explain it in depth? [/INST] Gingivitis is a non-destructive disease that causes inflammation of the gums. The most common form of gingivitis, and the most common form of periodontal disease overall, is in response to bacterial biofilms (also called plaque) that is attached to tooth surfaces, termed plaque-induced gingivitis. Most forms of gingivitis are plaque-induced.While some cases of gingivitis never progress to periodontitis, periodontitis is always preceded by gingivitis.Gingivitis is reversible with good oral hygiene; however, without treatment, gingivitis can progress to periodontitis, in which the inflammation of the gums results in tissue destruction and bone resorption around the teeth.  Periodontitis can ultimately lead to tooth loss.

Signs and symptoms
The symptoms of gingivitis are somewhat non-specific and manifest in the gum tissue as the classic signs of inflammation:

Swollen gums
Bright red or purple gums
Gums that are tender or painful to the touch
Bleeding gums or bleeding after brushing and/or flossing
Bad breath (halitosis)Additionally, the stippling that normally exists in the gum tissue of some individuals will often disappear and the gums may appear shiny when the gum tissue becomes swollen and stretched over the inflamed underlying connective tissue. The accumulation may also emit an unpleasant odor. When the gingiva are swollen, the epithelial lining of the gingival crevice becomes ulcerated and the gums will bleed more easily with even gentle brushing, and especially when flossing.

Complications
Recurrence of gingivitis
Periodontitis
Infection or abscess of the gingiva or the jaw bones
Trench mouth (bacterial infection and ulceration of the gums)
Swollen lymph nodes
Associated with premature birth and low birth weight

Alzheimers and dementia
A new study from 2018 found evidence that gingivitis bacteria may be linked to Alzheimers disease. Scientists agree that more research is needed to prove a cause and effect link. "Studies have also found that the bacteria P. gingivalis – which are responsible for many forms of gum disease – can migrate from the mouth to the brain in mice. And on entry to the brain, P. gingivalis can reproduce all of the characteristic features of Alzheimer’s disease."

Cause
The cause of plaque-induced gingivitis is bacterial plaque, which acts to initiate the bodys host response.  This, in turn, can lead to destruction of the gingival tissues, which may progress to destruction of the periodontal attachment apparatus.  The plaque accumulates in the small gaps between teeth, in the gingival grooves and in areas known as plaque traps: locations that serve to accumulate and maintain plaque.  Examples of plaque traps include bulky and overhanging restorative margins, clasps of removable partial dentures and calculus (tartar) that forms on teeth. Although these accumulations may be tiny, the bacteria in them produce chemicals, such as degradative enzymes, and toxins, such as lipopolysaccharide (LPS, otherwise known as endotoxin) or lipoteichoic acid (LTA), that promote an inflammatory response in the gum tissue.  This inflammation can cause an enlargement of the gingiva and subsequent formation. Early plaque in health consists of a relatively simple bacterial community dominated by Gram-positive cocci and rods. As plaque matures and gingivitis develops, the communities become increasingly complex with higher proportions of Gram-negative rods, fusiforms, filaments, spirilla and spirochetes. Later experimental gingivitis studies, using culture, provided more information regarding the specific bacterial species present in plaque. Taxa associated with gingivitis included Fusobacterium nucleatum subspecies polymorphum, Lachnospiraceae [G-2] species HOT100, Lautropia species HOTA94, and Prevotella oulorum (a species of Prevotella bacterium), whilst Rothia dentocariosa was associated with periodontal health. Further study of these taxa is warranted and may lead to new therapeutic approaches to prevent periodontal disease.

Risk factors
Risk factors associated with gingivitis include the following:

age
osteoporosis
low dental care utilization
poor oral hygiene
overly aggressive oral hygiene such as brushing with stiff bristles
mouth breathing during sleep
Orthodontic braces
medications and conditions that dry the mouth
cigarette smoking
genetic factors
stress
mental health issues such as depression
pre-existing conditions such as diabetes

Diagnosis
Gingivitis is a category of periodontal disease in which there is no loss of bone but inflammation and bleeding are present.
Each tooth is divided into four gingival units (mesial, distal, buccal, and lingual) and given a score from 0–3 based on the gingival index. The four scores are then averaged to give each tooth a single score.
The diagnosis of the periodontal disease gingivitis is done by a dentist.  The diagnosis is based on clinical assessment data acquired during a comprehensive periodontal exam.  Either a registered dental hygienist or a dentist may perform the comprehensive periodontal exam but the data interpretation and diagnosis are done by the dentist.  The comprehensive periodontal exam consists of a visual exam, a series of radiographs, probing of the gingiva, determining the extent of current or past damage to the periodontium and a comprehensive review of the medical and dental histories.
Current research shows that activity levels of the following enzymes in saliva samples are associated with periodontal destruction: aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), and acid phosphatase (ACP). Therefore, these enzyme biomarkers may be used to aid in the diagnosis and treatment of gingivitis and periodontitis.
A dental hygienist or dentist will check for the symptoms of gingivitis, and may also examine the amount of plaque in the oral cavity. A dental hygienist or dentist will also look for signs of periodontitis using X-rays or periodontal probing as well as other methods.
If gingivitis is not responsive to treatment, referral to a periodontist (a specialist in diseases of the gingiva and bone around teeth and dental implants) for further treatment may be necessary.

Classification
1999 Classification
As defined by the 1999 World Workshop in Clinical Periodontics, there are two primary categories of gingival diseases, each with numerous subgroups:
Dental plaque-induced gingival diseases.
Gingivitis associated with plaque only
Gingival diseases modified by systemic factors
Gingival diseases modified by medications
Gingival diseases modified by malnutrition
Non-plaque-induced gingival lesions
Gingival diseases of specific bacterial origin
Gingival diseases of viral origin
Gingival diseases of fungal origin
Gingival diseases of genetic origin
Gingival manifestations of systemic conditions
Traumatic lesions
Foreign body reactions
Not otherwise specified

2017 Classification
As defined by the 2017 World Workshop, periodontal health, gingival diseases/ conditions have been categorised into the following:
Periodontal health and gingival health
Clinical gingival health on an intact periodontium
Clinical gingival health on a reduced periodontium
Stable periodontitis patient
Non-periodontitis patient
Gingivitis – dental biofilm-induced
Associated with dental biofilm alone
Mediated by systemic or local risk factors
Drug-influenced gingival enlargement
Gingival diseases – non-dental biofilm induced
Genetic/ developmental disorders
Specific infections
Inflammatory and immune conditions
Reactive processes
Neoplasms
Endocrine, nutritional & metabolic diseases
Traumatic lesions
Gingival pigmentation

Prevention
Gingivitis can be prevented through regular oral hygiene that includes daily brushing and flossing. Hydrogen peroxide, saline, alcohol or chlorhexidine mouth washes may also be employed. In a 2004 clinical study, the beneficial effect of hydrogen peroxide on gingivitis has been highlighted. The use of oscillation type brushes might reduce the risk of gingivitis compared to manual brushing.Rigorous plaque control programs along with periodontal scaling and curettage also have proved to be helpful, although according to the American Dental Association, periodontal scaling and root planing are considered as a treatment for periodontal disease, not as a preventive treatment for periodontal disease. In a 1997 review of effectiveness data, the U.S. Food and Drug Administration (FDA) found clear evidence showing that toothpaste containing triclosan was effective in preventing gingivitis. In 2017 the FDA banned triclosan in many consumer products but allowed it to remain in toothpaste because of its effectiveness against gingivitis.  In 2019, Colgate, under pressure from health advocates, removed triclosan from the last toothpaste on the market containing it, Colgate Total.

Treatment
The focus of treatment is to remove plaque </s>