<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 Botulism and can you explain it in depth? [/INST] Botulism is a rare and potentially fatal illness caused by a toxin produced by the bacterium Clostridium botulinum. The disease begins with weakness, blurred vision, feeling tired, and trouble speaking. This may then be followed by weakness of the arms, chest muscles, and legs. Vomiting, swelling of the abdomen, and diarrhea may also occur. The disease does not usually affect consciousness or cause a fever.
Botulism can be spread in several ways. The bacterial spores which cause it are common in both soil and water. They produce the botulinum toxin when exposed to low oxygen levels and certain temperatures. Foodborne botulism happens when food containing the toxin is eaten. Infant botulism happens when the bacteria develops in the intestines and releases the toxin. This typically only occurs in children less than six months old, as protective mechanisms develop after that time. Wound botulism is found most often among those who inject street drugs. In this situation, spores enter a wound, and in the absence of oxygen, release the toxin. It is not passed directly between people. The diagnosis is confirmed by finding the toxin or bacteria in the person in question.
Prevention is primarily by proper food preparation. The bacteria, though not the spores, are destroyed by heating it to more than 85 °C (185 °F) for longer than 5 minutes. Honey can contain the organism, and for this reason, honey should not be fed to children under 12 months. Treatment is with an antitoxin. In those who lose their ability to breathe on their own, mechanical ventilation may be necessary for months. Antibiotics may be used for wound botulism. Death occurs in 5 to 10% of people. Botulism also affects many other animals. The word is from Latin botulus, meaning sausage.

Signs and symptoms
The muscle weakness of botulism characteristically starts in the muscles supplied by the cranial nerves—a group of twelve nerves that control eye movements, the facial muscles and the muscles controlling chewing and swallowing. Double vision, drooping of both eyelids, loss of facial expression and swallowing problems may therefore occur. In addition to affecting the voluntary muscles, it can also cause disruptions in the autonomic nervous system. This is experienced as a dry mouth and throat (due to decreased production of saliva), postural hypotension (decreased blood pressure on standing, with resultant lightheadedness and risk of blackouts), and eventually constipation (due to decreased forward movement of intestinal contents). Some of the toxins (B and E) also precipitate nausea, vomiting, and difficulty with talking. The weakness then spreads to the arms (starting in the shoulders and proceeding to the forearms) and legs (again from the thighs down to the feet).Severe botulism leads to reduced movement of the muscles of respiration, and hence problems with gas exchange. This may be experienced as dyspnea (difficulty breathing), but when severe can lead to respiratory failure, due to the buildup of unexhaled carbon dioxide and its resultant depressant effect on the brain. This may lead to respiratory compromise and death if untreated.Clinicians frequently think of the symptoms of botulism in terms of a classic triad: bulbar palsy and descending paralysis, lack of fever, and clear senses and mental status ("clear sensorium").

Infant botulism
Infant botulism (also referred to as floppy baby syndrome) was first recognized in 1976, and is the most common form of botulism in the United States. Infants are susceptible to infant botulism in the first year of life, with more than 90% of cases occurring in infants younger than six months. Infant botulism results from the ingestion of the C. botulinum spores, and subsequent colonization of the small intestine. The infant gut may be colonized when the composition of the intestinal microflora (normal flora) is insufficient to competitively inhibit the growth of C. botulinum and levels of bile acids (which normally inhibit clostridial growth) are lower than later in life.The growth of the spores releases botulinum toxin, which is then absorbed into the bloodstream and taken throughout the body, causing paralysis by blocking the release of acetylcholine at the neuromuscular junction. Typical symptoms of infant botulism include constipation, lethargy, weakness, difficulty feeding, and an altered cry, often progressing to a complete descending flaccid paralysis. Although constipation is usually the first symptom of infant botulism, it is commonly overlooked.Honey is a known dietary reservoir of C. botulinum spores and has been linked to infant botulism. For this reason, honey is not recommended for infants less than one year of age. Most cases of infant botulism, however, are thought to be caused by acquiring the spores from the natural environment. Clostridium botulinum is a ubiquitous soil-dwelling bacterium. Many infant botulism patients have been demonstrated to live near a construction site or an area of soil disturbance.Infant botulism has been reported in 49 of 50 US states (all save for Rhode Island), and cases have been recognized in 26 countries on five continents.

Complications
Infant botulism has no long-term side effects.
Botulism can result in death due to respiratory failure. However, in the past 50 years, the proportion of patients with botulism who die has fallen from about 50% to 7% due to improved supportive care. A patient with severe botulism may require mechanical ventilation (breathing support through a ventilator) as well as intensive medical and nursing care, sometimes for several months. The person may require rehabilitation therapy after leaving the hospital.

Cause
Clostridium botulinum is an anaerobic, Gram positive, spore-forming rod. Botulinum toxin is one of the most powerful known toxins: about one microgram is lethal to humans when inhaled. It acts by blocking nerve function (neuromuscular blockade) through inhibition of the excitatory neurotransmitter acetylcholines release from the presynaptic membrane of neuromuscular junctions in the somatic nervous system. This causes paralysis. Advanced botulism can cause respiratory failure by paralysing the muscles of the chest; this can progress to respiratory arrest. Furthermore, acetylcholine release from the presynaptic membranes of muscarinic nerve synapses is blocked. This can lead to a variety of autonomic signs and symptoms described above.
In all cases, illness is caused by the botulinum toxin produced by the bacterium C. botulinum in anaerobic conditions and not by the bacterium itself. The pattern of damage occurs because the toxin affects nerves that fire (depolarize) at a higher frequency first.Mechanisms of entry into the human body for botulinum toxin are described below.

Colonization of the gut
The most common form in Western countries is infant botulism. This occurs in infants who are colonized with the bacterium in the small intestine during the early stages of their lives. The bacterium then produces the toxin, which is absorbed into the bloodstream. The consumption of honey during the first year of life has been identified as a risk factor for infant botulism; it is a factor in a fifth of all cases. The adult form of infant botulism is termed adult intestinal toxemia, and is exceedingly rare.

Food
Toxin that is produced by the bacterium in containers of food that have been improperly preserved is the most common cause of food-borne botulism. Fish that has been pickled without the salinity or acidity of brine that contains acetic acid and high sodium levels, as well as smoked fish stored at too high a temperature, presents a risk, as does improperly canned food.
Food-borne botulism results from contaminated food in which C. botulinum spores have been allowed to germinate in low-oxygen conditions. This typically occurs in improperly prepared home-canned food substances and fermented dishes without adequate salt or acidity. Given that multiple people often consume food from the same source, it is common for more than a single person to be affected simultaneously. Symptoms usually appear 12–36 hours after eating, but can also appear within 6 hours to 10 days.

Wound
Wound botulism results from the contamination of a wound with the bacteria, which then secrete the toxin into the bloodstream. This has become more common in intravenous drug users since the 1990s, especially people using black tar heroin and those injecting heroin into the skin rather than the veins. Wound botulism accounts for 29% of cases.

Inhalation
Isolated cases of botulism have been described after inhalation by laboratory workers.

Injection
Symptoms of botulism may occur away from the injection site of botulinum toxin. This may include loss of strength, blurred vision, change of voice, or trouble breathing which can result in death. Onset can be hours to weeks after an injection. This generally only occurs with inappropriate strengths of botulinum toxin for cosmetic use or due to the larger doses used to treat movement disorders. Following a 2008 review the FDA added these concerns as a boxed warning.

Mechanism
The toxin is the protein botulinum toxin produced under anaerobic conditions (where there is no oxygen) by the bacterium Clostridium botulinum.
Clostridium botulinum is a large anaerobic Gram-positive bacillus that forms subterminal endospores.There are eight serological varieties of the bacterium denoted by the letters A to H. The toxin from all of these acts in the same way and produces similar symptoms: the motor nerve endings are prevented from releasing acetylcholine, causing flaccid paralysis and symptoms of blurred vision, ptosis, nausea, vomiting, diarrhea or constipation, cramps, and respiratory difficulty.
Botulinum toxin is broken into eight neurotoxins (labeled as types A, B, C [C1, C2], D, E, F, and G), which are antigenically and serologically distinct but structurally similar. Human botulism is caused mainly by types A, B, E, and (rarely) F. Types C and D cause toxicity only in other animals.In October 2013, scientists released news of the discovery of type H, the first new botulism neurotoxin found in forty years. However, further studies showed type H to be a chimeric toxin composed of parts of types F and A (FA).Some types produce a characteristic putrefactive smell and digest meat (types A and some of B and F); these are said to be proteolytic; type E and some types of B, C, D and F are nonproteolytic and can go undetected because there is no strong odor associated with them.When the bacteria are under stress, they develop spores, which are inert. Their natural habitats are in the soil, in the silt that comprises the bottom sediment of streams, lakes, and coastal waters and ocean, while some types are natural inhabitants of the intestinal tracts of mammals (e.g., horses, cattle, humans), and are present in their excreta. The spores can survive in their inert form for many years.Toxin is produced by the bacteria when environmental conditions are favourable for the spores to replicate and grow, but the gene that encodes for the toxin protein is actually carried by a virus or phage that infects the bacteria. Little is known about the natural factors that control phage infection and replication within the bacteria.The spores require warm temperatures, a protein source, an anaerobic environment, and moisture in order to become active and produce toxin. In the wild, decomposing vegetation and invertebrates combined with warm temperatures can provide ideal conditions for the botulism bacteria to activate and produce toxin that may affect feeding birds and other animals. Spores are not killed by boiling, but botulism is uncommon because special, rarely obtained conditions are necessary for botulinum toxin production from C. botulinum spores, including an anaerobic, low-salt, low-acid, low-sugar environment at ambient temperatures.Botulinum inhibits the release within the nervous system of acetylcholine, a neurotransmitter, responsible for communication between motor neurons and muscle cells. All forms of botulism lead to paralysis that typically starts with the muscles of the face and then spreads towards the limbs. In severe forms, botulism leads to paralysis of the breathing muscles and causes respiratory failure. In light of this life-threatening complication, all suspected cases of botulism are treated as medical emergencies, and public health officials are usually involved to identify the source and take steps to prevent further cases from occurring.Botulinum toxin A, C, and E cleave the SNAP-25, ultimately leading to paralysis.

Diagnosis
For botulism in babies, diagnosis should be made on signs and symptoms. Confirmation of the diagnosis is made by testing of a stool or enema specimen with the mouse bioassay.
In people whose history and physical examination suggest botulism, these clues are often not enough to allow a diagnosis. Other diseases such as Guillain–Barré syndrome, stroke, and myasthenia gravis can appear similar to botulism, and special tests may be needed to exclude these other conditions. These tests may include a brain scan, cerebrospinal fluid examination, nerve conduction test (electromyography, or EMG), and an edrophonium chloride (Tensilon) test for myasthenia gravis. A definite diagnosis can be made if botulinum toxin is identified in the food, stomach or intestinal contents, vomit or feces. The toxin is occasionally found in the blood in peracute cases. Botulinum toxin can be detected by a variety of techniques, including enzyme-linked immunosorbent assays (ELISAs), electrochemiluminescent (ECL) tests and mouse inoculation or feeding trials. The toxins can be typed with neutralization tests in mice. In toxicoinfectious botulism, the organism can be cultured from tissues. On egg yolk medium, toxin-producing colonies usually display surface iridescence that extends beyond the colony.

Prevention
Although the vegetative form of the bacteria is destroyed by boiling, the spore itself is not killed by the temperatures reached with normal sea-level-pressure boiling, leaving it free to grow and again produce the toxin when conditions are right.A recommended prevention measure for infant botulism is to avoid giving honey to infants less than 12 months of age, as botulinum spores are often present. In older children and adults the normal intestinal bacteria suppress development of C. botulinum.While commercially canned goods are required to undergo a "botulinum cook" in a pressure cooker at 121 °C (250 °F) for 3 minutes, and thus rarely cause botulism, there have been notable exceptions. Two were the 1978 Alaskan salmon outbreak and the 2007 Castleberrys Food Company outbreak. Foodborne botulism is the rarest form though, accounting for only around 15% of cases (US) and has more frequently been from home-canned foods with low acid content, such as carrot juice, asparagus, green beans, beets, and corn. However, outbreaks of botulism have resulted from more unusual sources. In July 2002, fourteen Alaskans ate muktuk (whale meat) from a beached whale, and eight of them developed symptoms of botulism, two of them requiring mechanical ventilation.Other, much rarer sources of infection (about every decade in the US) include garlic or herbs stored covered in oil without acidification, chili peppers, improperly handled baked potatoes wrapped in aluminum foil, tomatoes, and home-canned or fermented fish.
When canning or preserving food at home, attention should be paid to hygiene, pressure, temperature, refrigeration and storage. When making home preserves, only acidic fruit such as apples, pears, stone fruits and berries should be used. Tropical fruit and tomatoes are low in acidity and must have some acidity added before they are canned.Low-acid foods have pH values higher than 4.6. They include red meats, seafood, poultry, milk, and all fresh vegetables except for most tomatoes. Most mixtures of low-acid and acid foods also have pH values above 4.6 unless their recipes include enough lemon juice, citric acid, or vinegar to make them acidic. Acid foods have a pH of 4.6 or lower. They include fruits, pickles, sauerkraut, jams, jellies, marmalades, and fruit butters.Although tomatoes usually are considered an acid food, some are now known to have pH values slightly above 4.6. Figs also have pH values slightly above 4.6. Therefore, if they are to be canned as acid foods, these products must be acidified to a pH of 4.6 or lower with lemon juice or citric acid. Properly acidified tomatoes and figs are acid foods and can be safely processed in a boiling-water canner.Oils infused with fresh garlic or herbs should be acidified and refrigerated. Potatoes which have been baked while wrapped in aluminum foil should be kept hot until served or refrigerated. Because the botulism toxin is destroyed by high temperatures, home-canned foods are best boiled for 10 minutes before eating. Metal cans containing food in which bacteria are growing may bulge outwards due to gas production from bacterial growth or the food inside may be foamy or have a bad odor; such cans with any of these signs should be discarded.Any container of food which has been heat-treated and then assumed to be airtight which shows signs of not being so, e.g., metal cans with pinprick holes from rust or mechanical damage, should be discarded. Contamination of a canned food solely with C. botulinum may not cause any visual defects to the container, such as bulging. Only assurance of sufficient thermal processing during production, and absence of a route for subsequent contamination, should be used as indicators of food safety.
The addition of nitrites and nitrates to processed meats such as ham, bacon, and sausages reduces growth and toxin production of C. botulinum.

Vaccine
Vaccines are under development, but they have disadvantages, and in some cases there are concerns that they may revert to dangerous native activity. As of 2017 work to develop a better vaccine was being carried out, but the US FDA had not approved any vaccine against botulism.

Treatment
Botulism is generally treated with botulism antitoxin and supportive care.Supportive care for botulism includes monitoring of respiratory function. Respiratory failure due to paralysis may require mechanical ventilation for 2 to 8 weeks, plus intensive medical and nursing care. After this time, paralysis generally improves as new neuromuscular connections are formed.In some abdominal cases, physicians may try to remove contaminated food still in the digestive tract by inducing vomiting or using enemas. Wounds should be treated, usually surgically, to remove the source of the toxin-producing bacteria.

Antitoxin
Botulinum antitoxin consists of antibodies that neutralize botulinum toxin in the circulatory system by passive immunization. This prevents additional toxin from binding to the neuromuscular junction, but does not reverse any already inflicted paralysis.In adults, a trivalent antitoxin containing antibodies raised against botulinum toxin types A, B, and E is used most commonly; however, a heptavalent botulism antitoxin has also been developed and was approved by the U.S. FDA in 2013. In infants, horse-derived antitoxin is sometimes avoided for fear of infants developing serum sickness or lasting hypersensitivity to horse-derived proteins. To avoid this, a human-derived antitoxin has been developed and approved by the U.S. FDA in 2003 for the treatment of infant botulism. This human-derived antitoxin has been shown to be both safe and effective for the treatment of infant botulism. However, the danger of equine-derived antitoxin to infants has not been clearly established, and one study showed the equine-derived antitoxin to be both safe and effective for the treatment of infant botulism.Trivalent (A,B,E) botulinum antitoxin is derived from equine sources utilizing whole antibodies (Fab and Fc portions). In the United States, this antitoxin is available from the local health department via the CDC. The second antitoxin, heptavalent (A,B,C,D,E,F,G) botulinum antitoxin, is derived from "despeciated" equine IgG antibodies which have had the Fc portion cleaved off leaving the F(ab)2 portions. This less immunogenic antitoxin is effective against all known strains of botulism where not contraindicated.

Prognosis
The paralysis caused by botulism can persist for 2 to 8 weeks, during which supportive care and ventilation may be necessary to keep the person alive. Botulism can be fatal in 5% to 10% of people who are affected. However, if left untreated, botulism is fatal in 40% to 50% of cases.Infant botulism typically has no long-term side effects but can be complicated by treatment-associated adverse events. The case fatality rate is less than 2% for hospitalized babies.

Epidemiology
Globally, botulism is fairly rare, with approximately 1,000 identified cases yearly.

United States
In the United States an average of 145 cases are reported each year. Of these, roughly 65% are infant botulism, 20% are wound botulism, and 15% are foodborne. Infant botulism is predominantly sporadic and not associated with epidemics, but great geographic variability exists. From 1974 to 1996, for example, 47% of all infant botulism cases reported in the U.S. occurred in California.Between 1990 and 2000, the Centers for Disease Control and Prevention reported 263 individual foodborne cases from 160 botulism events in the United States with a case-fatality rate of 4%. Thirty-nine percent (103 cases and 58 events) occurred in Alaska, all of which were attributable to traditional Alaska aboriginal foods. In the lower 49 states, home-canned food was implicated in 70 events (~69%) with canned asparagus being the most frequent cause. Two restaurant-associated outbreaks affected 25 people. The median number of cases per year was 23 (range 17–43), the median number of events per year was 14 (range 9–24). The highest incidence rates occurred in Alaska, Idaho, Washington, and Oregon. All other states had an incidence rate of 1 case per ten million people or less.The number of cases of food borne and infant botulism has changed little in recent years, but wound botulism has increased because of the use of black tar heroin, especially in California.All data regarding botulism antitoxin releases and laboratory confirmation of cases in the US are recorded annually by the Centers for Disease Control and Prevention and published on their website.
On 2 July 1971, the U.S. Food and Drug Administration (FDA) released a public warning after learning that a New York man had died and his wife had become seriously ill due to botulism after eating a can of Bon Vivant vichyssoise soup.
Between 31 March and 6 April 1977, 59 individuals developed type B botulism. All who fell ill had eaten at the same Mexican restaurant in Pontiac, Michigan, and had consumed a hot sauce made with improperly home-canned jalapeño peppers, either by adding it to their food, or by eating nachos that had been prepared with the hot sauce. The full clinical spectrum (mild symptomatology with neurologic findings through life-threatening ventilatory paralysis) of type B botulism was documented.
In April 1994, the largest outbreak of botulism in the United States since 1978 occurred in El Paso, Texas. Thirty people were affected; 4 required mechanical ventilation. All ate food from a Greek restaurant. The attack rate among people who ate a potato-based dip was 86% (19/22) compared with 6% (11/176) among people who did not eat the dip (relative risk [RR] = 13.8; 95% confidence interval [CI], 7.6–25.1). The attack rate among people who ate an eggplant-based dip was 67% (6/9) compared with 13% (24/189) among people who did not (RR = 5.2; 95% CI, 2.9–9.5). Botulism toxin type A was detected in patients and in both dips. Toxin formation resulted from holding aluminum foil-wrapped baked potatoes at room temperature, apparently for several days, before they were used in the dips. Food handlers should be informed of the potential hazards caused by holding foil-wrapped potatoes at ambient temperatures after cooking.
In 2002, fourteen Alaskans ate muktuk (whale blubber) from a beached whale, resulting in eight of them developing botulism, with two of the affected requiring mechanical ventilation.
Beginning in late June 2007, 8 people contracted botulism poisoning by eating canned food products produced by Castleberrys Food Company in its Augusta, Georgia plant. It was later identified that the Castleberrys plant had serious production problems on a specific line of retorts that had under-processed the cans of food. These issues included broken cooking alarms, leaking water valves and inaccurate temperature devices, all the result of poor management of the company. All of the victims were hospitalized and placed on mechanical ventilation. The Castleberrys Food Company outbreak was the first instance of botulism in commercial canned foods in the United States in over 30 years.
One person died, 21 cases were confirmed, and 10 more were suspected in Lancaster, Ohio when a botulism outbreak occurred after a church potluck in April 2015. The suspected source was a salad made from home-canned potatoes.
A botulism outbreak occurred in Northern California in May 2017 after 10 people consumed nacho cheese dip served at a gas station in Sacramento County. One man died as a result of the outbreak.

United Kingdom
The largest recorded outbreak of foodborne botulism in the United Kingdom occurred in June 1989. A total of 27 patients were affected; one patient died. Twenty-five of the patients had eaten one brand of hazelnut yogurt in the week before the onset of symptoms. Control measures included the cessation of all yogurt production by the implicated producer, the withdrawal of the firms yogurts from sale, the recall of cans of the hazelnut conserve, and advice to the general public to avoid the consumption of all hazelnut yogurts.

China
From 1958 to 1983 there were 986 outbreaks of botulism in China involving 4,377 people with 548 deaths.

Qapqal disease
After the Chinese Communist Revolution in 1949, a mysterious plague (named Qapqal disease) was noticed to be affecting several Sibe villages in Qapqal Xibe Autonomous County. It was endemic with distinctive epidemic patterns, yet the underlying cause remained unknown for a long period of time. It caused a number of deaths and forced some people to leave the place.In 1958, a team of experts were sent to the area by the Ministry of Health to investigate the cases. The epidemic survey conducted proved that the disease was primarily type A botulism, with several cases of type B. The team also discovered that, the source of the botulinum was local fermented grain and beans, as well as a raw meat food called mi song hu hu. They promoted the improvement of fermentation techniques among local residents, and thus eliminated the disease.

Canada
From 1985 to 2015 there were outbreaks causing 91 confirmed cases of foodborne botulism in Canada, 85% of which were in Inuit communities, especially Nunavik, as well as  First Nations of the coast of British Columbia, following consumption of traditionally prepared marine mammal and fish products.

Ukraine
In 2017, there were 70 cases of botulism with 8 deaths in Ukraine. The previous year there were 115 cases with 12 deaths. Most cases were the result of dried fish, a common local drinking snack.

Vietnam
In 2020, several cases of botulism were reported in Vietnam. All of them were related to a product containing contaminated vegetarian pâté. Some patients were put on life support.

Other susceptible species
Botulism can occur in many vertebrates and invertebrates. Botulism has been reported in such species as rats, mice, chicken, frogs, toads, goldfish, aplysia, squid, crayfish, drosophila and leeches.Death from botulism is common in waterfowl; an estimated 10,000 to 100,000 birds die of botulism annually. The disease is commonly called "limberneck". In some large outbreaks, a million or more birds may die. Ducks appear to be affected most often. An enzootic form of duck botulism in the Western USA and Canada is known as "western duck sickness". Botulism also affects commercially raised poultry. In chickens, the mortality rate varies from a few birds to 40% of the flock.
Botulism seems to be relatively uncommon in domestic mammals; however, in some parts of the world, epidemics with up to 65% mortality are seen in cattle. The prognosis is poor in large animals that are recumbent.
In cattle, the symptoms may include drooling, restlessness, uncoordination, urine retention, dysphagia, and sternal recumbency. Laterally recumbent animals are usually very close to death. In sheep, the symptoms may include drooling, a serous nasal discharge, stiffness, and incoordination. Abdominal respiration may be observed and the tail may switch on the side. As the disease progresses, the limbs may become paralyzed and death may occur.
Phosphorus-deficient cattle, especially in southern Africa, are inclined to ingest bones and carrion containing clostridial toxins and consequently develop lame sickness or lamsiekte.
The clinical signs in horses are similar to cattle. The muscle paralysis is progressive; it usually begins at the hindquarters and gradually moves to the front limbs, neck, and head. Death generally occurs 24 to 72 hours after initial symptoms and results from respiratory paralysis. Some foals are found dead without other clinical signs.
Clostridium botulinum type C toxin has been incriminated as the cause of grass sickness, a condition in horses which occurs in rainy and hot summers in Northern Europe. The main symptom is pharynx paralysis.Domestic dogs may develop systemic toxemia after consuming C. botulinum type C exotoxin or spores within bird carcasses or other infected meat but are generally resistant to the more severe effects of Clostridium botulinum type C. Symptoms include flaccid muscle paralysis, which can lead to death due to cardiac and respiratory arrest.Pigs are relatively resistant to botulism. Reported symptoms include anorexia, refusal to drink, vomiting, pupillary dilation, and muscle paralysis.In poultry and wild birds, flaccid paralysis is usually seen in the legs, wings, neck and eyelids </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 Colonoscopy and can you explain it in depth? [/INST] Colonoscopy () or coloscopy () is the endoscopic examination of the large bowel and the distal part of the small bowel with a CCD camera or a fiber optic camera on a flexible tube passed through the anus. It can provide a visual diagnosis (e.g., ulceration, polyps) and grants the opportunity for biopsy or removal of suspected colorectal cancer lesions.
Colonoscopy can remove polyps smaller than one millimeter. Once polyps are removed, they can be studied with the aid of a microscope to determine if they are precancerous or not. It can take up to 15 years for a polyp to turn cancerous.Colonoscopy is similar to sigmoidoscopy—the difference being related to which parts of the colon each can examine. A colonoscopy allows an examination of the entire colon (1,200–1,500 mm in length). A sigmoidoscopy allows an examination of the distal portion (about 600 mm) of the colon, which may be sufficient because benefits to cancer survival of colonoscopy have been limited to the detection of lesions in the distal portion of the colon.A sigmoidoscopy is often used as a screening procedure for a full colonoscopy, often done in conjunction with a fecal occult blood test (FOBT). About 5% of these screened patients are referred to colonoscopy.Virtual colonoscopy, which uses 2D and 3D imagery reconstructed from computed tomography (CT) scans or from nuclear magnetic resonance (MR) scans, is also possible, as a totally non-invasive medical test. Virtual colonoscopy does not allow therapeutic maneuvers such as polyp and tumour removal or biopsy, nor visualization of lesions smaller than five millimeters; if a growth or polyp is detected using CT colonography, it would require removal during a standard colonoscopy. Surgeons have used the term pouchoscopy to refer to a colonoscopy of the ileo-anal pouch.

Medical uses
Conditions that call for colonoscopies include gastrointestinal hemorrhage, unexplained changes in bowel habit and suspicion of malignancy. Colonoscopies are often used to diagnose colon polyp and colon cancer, but are also frequently used to diagnose inflammatory bowel disease. In older patients (sometimes even younger ones) an unexplained drop in hematocrit (one sign of anemia) is an indication that calls for a colonoscopy, usually along with an esophagogastroduodenoscopy (EGD), even if no obvious blood has been seen in the stool (feces).Fecal occult blood is a quick test which can be done to test for microscopic traces of blood in the stool. A positive test is almost always an indication to do a colonoscopy. In most cases the positive result is just due to hemorrhoids; however, it can also be due to diverticulosis, inflammatory bowel disease (Crohns disease, ulcerative colitis), colon cancer, or polyps. Colonic polypectomy has become a routine part of colonoscopy, allowing quick and simple removal of polyps during the procedure, without invasive surgery.

Colon cancer screening
Colonoscopy is one of the colorectal cancer screening tests available to people in the US who are 45 years of age and older. The other screening tests include flexible sigmoidoscopy, double-contrast barium enema, computed tomographic (CT) colongraphy (virtual colonoscopy), guaiac-based fecal occult blood test (gFOBT), fecal immunochemical test (FIT), and multitarget stool DNA screening test (Cologuard).Subsequent rescreenings are then scheduled based on the initial results found, with a five- or ten-year recall being common for colonoscopies that produce normal results. People with a family history of colon cancer are often first screened during their teenage years.
Among people who have had an initial colonoscopy that found no polyps, the risk of developing colorectal cancer within five years is extremely low. Therefore, there is no need for those people to have another colonoscopy sooner than five years after the first screening.Some medical societies in the US recommend a screening colonoscopy every 10 years beginning at age 50 for adults without increased risk for colorectal cancer. Research shows that the risk of cancer is low for 10 years if a high-quality colonoscopy does not detect cancer, so tests for this purpose are indicated every ten years.Colonoscopy screening prevents approximately two-thirds of deaths due to colorectal cancers on the left side of the colon, and is not associated with a significant reduction in deaths from right-sided disease.Colonoscopy reduces cancer rates by detecting some colon polyps and cancers on the left side of the colon early enough that they may be treated, and a smaller number on the right side; many of these left-sided growths would have been detected by a sigmoidoscopy procedure.Since polyps often take 10 to 15 years to transform into cancer in someone at average risk of colorectal cancer, guidelines recommend 10 years after a normal screening colonoscopy before the next colonoscopy. (This interval does not apply to people at high risk of colorectal cancer, or to those who experience symptoms of colorectal cancer.)Although widely touted in the US as the "gold standard" of colon cancer screening, colonoscopy has never been studied as a screening tool. Most of the potential benefits of colonoscopy have been extrapolated from randomized trials of the sigmoidoscopy. The CONFIRM trial, a randomized trial on colonoscopy vs. FIT is currently ongoing.

Recommendations
The American Cancer Society recommends, beginning at age 45, both men and women follow one of these testing schedules for screening to find colon polyps and/or cancer:
Flexible sigmoidoscopy every 5 years, or
Colonoscopy every 10 years, or
Double-contrast barium enema every 5 years, or
CT colonography (virtual colonoscopy) every 5 years
Yearly guaiac-based fecal occult blood test (gFOBT)
Yearly fecal immunochemical test (FIT)
Stool DNA test (sDNA) every 3 years

Medicare coverage
In the United States, Medicare insurance covers the following colorectal-cancer screening tests:
Colonoscopy: average risk — every 10 years beginning at age 50, high risk — every 2 years with no age restriction
Flexible sigmoidoscopy — every 4 years beginning at age 50
Double-contrast barium enema: average risk  — every 4 years beginning at age 50, high risk — every 2 years
(CT) colongraphy: not covered by Medicare
gFOBT: average risk — every year beginning at age 50
FIT: average risk — every year beginning at age 50
Cologuard: average risk — every 3 years beginning at age 50

Risks
About 1 in 200 people who undergo a colonoscopy experience a serious complication. Perforation of the colon occurs in about 1 in 2000 procedures, bleeding in 2.6 per 1000, and death in 3 per 100,000, with an overall risk of serious complications of 0.35%.In some low-risk populations screening by colonoscopy in the absence of symptoms does not outweigh the risks of the procedure. For example, the odds of developing colorectal cancer between the ages of 20 and 40 in the absence of specific risk factors are about 1 in 1,250 (0.08%).The rate of complications varies with the practitioner and institution performing the procedure, and other variables.

Perforation
The most serious complication generally is gastrointestinal perforation, which is life-threatening and in most cases requires immediate major surgery for repair. Fewer than 20% of cases may be successfully managed with a conservative (non-surgical) approach.A 2003 analysis of the relative risks of sigmoidoscopy and colonoscopy brought into attention that the risk of perforation after colonoscopy is approximately double that after sigmoidoscopy (consistent with the fact that colonoscopy examines a longer section of the colon), a difference that appeared to be decreasing.

Bleeding
Bleeding complications may be treated immediately during the procedure by cauterization using the instrument. Delayed bleeding may also occur at the site of polyp removal up to a week after the procedure, and a repeat procedure can then be performed to treat the bleeding site. Even more rarely, splenic rupture can occur after colonoscopy because of adhesions between the colon and the spleen.

Anaesthesia
As with any procedure involving anaesthesia, other complications would include cardiopulmonary complications such as a temporary drop in blood pressure and oxygen saturation usually the result of overmedication, and are easily reversed. Anesthesia can also increase the risk of developing blood clots and lead to pulmonary embolism or deep venous thrombosis. (DVT)  In rare cases, more serious cardiopulmonary events such as a heart attack, stroke, or even death may occur; these are extremely rare except in critically ill patients with multiple risk factors. In rare cases, coma associated with anesthesia may occur.

Bowel preparation
Dehydration caused by the laxatives that are usually administered during the bowel preparation for colonoscopy also may occur. Therefore, patients must drink large amounts of fluids during the day of colonoscopy preparation to prevent dehydration. Loss of electrolytes or dehydration is a potential risk that can even prove deadly. In rare cases, severe dehydration can lead to kidney damage or dysfunction under the form of phosphate nephropathy.

Other
Virtual colonoscopies carry risks that are associated with radiation exposure.Colonoscopy preparation and colonoscopy procedure can cause inflammation of the bowels and diarrhea or bowel obstruction.During colonoscopies where a polyp is removed (a polypectomy), the risk of complications has been higher, although still low at about 2.3 percent.  One of the most serious complications that may arise after colonoscopy is the postpolypectomy syndrome. This syndrome occurs due to potential burns to the bowel wall when the polyp is removed, and may cause fever and abdominal pain. It is a rare complication, treated with intravenous fluids and antibiotics.
Bowel infections are a potential colonoscopy risk, although rare. The colon is not a sterile environment; many bacteria that normally live in the colon ensure the well-functioning of the bowel, and the risk of infections is minimal. Infections can occur during biopsies when too much tissue is removed and bacteria protrude in areas they do not belong to, or in cases when the lining of the colon is perforated and the bacteria get into the abdominal cavity.  Infection may also be transmitted between patients if the colonoscope is not cleaned and sterilized properly between tests.
Minor colonoscopy risks may include nausea, vomiting or allergies to the sedatives that are used. If medication is given intravenously, the vein may become irritated. Most localized irritations to the vein leave a tender lump lasting a number of days but going away eventually. The incidence of these complications is less than 1%.
On rare occasions, intracolonic explosion may occur. A meticulous bowel preparation is the key to prevent this complication.Signs of complications include severe abdominal pain, fevers and chills, or rectal bleeding (more than half a cup or 100ml).

Procedure
Preparation
The colon must be free of solid matter for the test to be performed properly. For one to three days, the patient is required to follow a low fiber or clear-liquid-only diet. Examples of clear fluids are apple juice, chicken and/or beef broth or bouillon, lemon-lime soda, lemonade, sports drink, and water. It is important that the patient remains hydrated. Sports drinks contain electrolytes which are depleted during the purging of the bowel. Drinks containing fiber such as prune and orange juice  should not be consumed, nor should liquids dyed red, purple, orange, or sometimes brown; however, cola is allowed. In most cases, tea or coffee taken without milk are allowed.The day before the colonoscopy, the patient is either given a laxative preparation (such as bisacodyl, phospho soda, sodium picosulfate, or sodium phosphate and/or magnesium citrate) and large quantities of fluid, or whole bowel irrigation is performed using a solution of polyethylene glycol and electrolytes. The procedure may involve both a pill-form laxative and a bowel irrigation preparation with the polyethylene glycol powder dissolved into any clear liquid, such as a sports drink that contains electrolytes.

A typical procedure regimen then would be as follows: in the morning of the day before the procedure, a 238 g bottle of polyethylene glycol powder should be poured into 1.9 litres (64 oz.) of the chosen clear liquid, which then should be mixed and refrigerated.  Two bisacodyl 5 mg tablets are taken 3 pm; at 5 pm, the patient starts drinking the mixture (approx. 8 oz. (0.5 litres) each 15-30 min. until finished); at 8 pm, take two bisacodyl 5 mg tablets; continue drinking/hydrating into the evening until bedtime with clear permitted fluids. The procedure may be scheduled early in the day so the patient need not go without food and only limited fluids until later.The goal of the preparation is to clear the colon of solid matter, and the patient may be advised to spend the day at home with ready access to toilet facilities.  The patient may also want to have at hand moist towelettes or a bidet for cleaning the anus.  A soothing salve such as petroleum jelly applied after cleaning the anus will reduce discomfort.
The patient may be asked not to take aspirin or similar products such as salicylate, ibuprofen, etc. for up to ten days before the procedure to avoid the risk of bleeding if a polypectomy is performed during the procedure. A blood test may be performed before the procedure.

Investigation
During the procedure the patient is often given sedation intravenously, employing agents such as fentanyl or midazolam. Although meperidine (Demerol) may be used as an alternative to fentanyl, the concern of seizures has relegated this agent to second choice for sedation behind the combination of fentanyl and midazolam. The average person will receive a combination of these two drugs, usually between 25 and 100 µg IV fentanyl and 1–4 mg IV midazolam. Sedation practices vary between practitioners and nations; in some clinics in Norway, sedation is rarely administered.Some endoscopists are experimenting with, or routinely use, alternative or additional methods such as nitrous oxide and propofol, which have advantages and disadvantages relating to recovery time (particularly the duration of amnesia after the procedure is complete), patient experience, and the degree of supervision needed for safe administration. This sedation is called "twilight anesthesia". For some patients it is not fully effective, so they are indeed awake for the procedure and can watch the inside of their colon on the color monitor. Substituting propofol for midazolam, which gives the patient quicker recovery, is gaining wider use, but requires closer monitoring of respiration.
A meta-analysis found that playing music improves tolerability to patients of the procedure.The first step is usually a digital rectal examination, to examine the tone of the sphincter and to determine if preparation has been adequate. The endoscope is then passed through the anus up the rectum, the colon (sigmoid, descending, transverse and ascending colon, the cecum), and ultimately the terminal ileum. The endoscope has a movable tip and multiple channels for instrumentation, air, suction and light. The bowel is occasionally insufflated with air to maximize visibility (a procedure that gives the patient the false sensation of needing to take a bowel movement). Biopsies are frequently taken for histology. Additionally in a procedure known as chromoendoscopy, a contrast-dye (such as indigo carmine) may be sprayed through the endoscope onto the bowel wall to help visualise any abnormalities in the mucosal morphology. A Cochrane review updated in 2016 found strong evidence that chromoscopy enhances the detection of cancerous tumours in the colon and rectum.In most experienced hands, the endoscope is advanced to the junction of where the colon and small bowel join up (cecum) in under 10 minutes in 95% of cases. Due to tight turns and redundancy in areas of the colon that are not "fixed", loops may form in which advancement of the endoscope creates a "bowing" effect that causes the tip to actually retract. These loops often result in discomfort due to stretching of the colon and its associated mesentery. Manoeuvres to "reduce" or remove the loop include pulling the endoscope backwards while twisting it. Alternatively, body position changes and abdominal support from external hand pressure can often "straighten" the endoscope to allow the scope to move forward. In a minority of patients, looping is often cited as a cause for an incomplete examination. Usage of alternative instruments leading to completion of the examination has been investigated, including use of pediatric colonoscope, push enteroscope and upper GI endoscope variants.For screening purposes, a closer visual inspection is then often performed upon withdrawal of the endoscope over the course of 20 to 25 minutes. Lawsuits over missed cancerous lesions have recently prompted some institutions to better document withdrawal time as rapid withdrawal times may be a source of potential medical legal liability. This is often a real concern in clinical settings where high caseloads could provide financial incentive to complete colonoscopies as quickly as possible.
Suspicious lesions may be cauterized, treated with laser light or cut with an electric wire for purposes of biopsy or complete removal polypectomy. Medication can be injected, e.g. to control bleeding lesions. The procedure typically takes 20–30 minutes, depending on the indication and findings; with multiple polypectomies or biopsies, procedure times may be longer. As mentioned above, anatomic considerations may also affect procedure times.
After the procedure, some recovery time is usually allowed to let the sedative wear off. Outpatient recovery time can take an estimated 30–60 minutes. Most facilities require that patients have a person with them to help them home afterwards (depending on the sedation method used).
One common after-effect from the procedure is a bout of flatulence and minor wind pain caused by air insufflation into the colon during the procedure.
An advantage of colonoscopy over X-ray imaging or other less invasive tests is the ability to perform therapeutic interventions during the test. A polyp is a growth of excess of tissue that can develop into cancer. If a polyp is found, for example, it can be removed by one of several techniques. A snare device can be placed around a polyp for removal. Even if the polyp is flat on the surface it can often be removed. For example, the following shows a polyp removed in stages:

Pain management
The pain associated with the procedure is not caused by the insertion of the scope but rather by the inflation of the colon in order to do the inspection. The scope itself is essentially a long, flexible tube about a centimeter in diameter — that is, as big around as the little finger, which is less than the diameter of an average stool.
The colon is wrinkled and corrugated, somewhat like an accordion or a clothes-dryer exhaust tube, which gives it the large surface area needed for water absorption. In order to inspect this surface thoroughly, the physician blows it up like a balloon, using air from a compressor or carbon dioxide from a gas bottle (CO2 is absorbed into the bloodstream through the mucosal lining of the colon much faster than air and then exhaled through the lungs which is associated with less post procedural pain), in order to get the creases out. The stomach, intestines, and colon have a so-called "second brain" wrapped around them, which autonomously runs the chemical factory of digestion. It uses complex hormone signals and nerve signals to communicate with the brain and the rest of the body. Normally a colons job is to digest food and regulate the intestinal flora. The harmful bacteria in rancid food, for example, creates gas.
The colon has distension sensors that can tell when there is unexpected gas pushing the colon walls out—thus the "second brain" tells the person that he or she is having intestinal difficulties by way of the sensation of nausea. Doctors typically recommend either total anesthesia or a partial twilight sedative to either preclude or to lessen the patients awareness of pain or discomfort, or just the unusual sensations of the procedure. Once the colon has been inflated, the doctor inspects it with the scope as it is slowly pulled backward. If any polyps are found they are then cut out for later biopsy.
Some doctors prefer to work with totally anesthetized patients inasmuch as the lack of any perceived pain or discomfort allows for a leisurely examination. Twilight sedation is, however, inherently safer than general anesthesia; it also allows the patients to follow simple commands and even to watch the procedure on a closed-circuit monitor. Tens of millions of adults annually need to have colonoscopies, and yet many dont because of concerns about the procedure.Colonoscopy can be carried out without any sedation and without problems with pain, which is practised in several institutions in many countries with the patients agreement. This allows the patient to shift the body position to help the doctor carry out the procedure and significantly reduces recovery time and side-effects. There is some discomfort when the colon is distended with air, but this is not usually particularly painful, and it passes relatively quickly. Unsedated patients can be released from the hospital on their own without any feelings of nausea, able to continue with normal activities, and without the need for an escort as recommended after sedation.

Ultrasound
Duodenography and colonography are performed like a standard abdominal examination using B-mode and color flow Doppler ultrasonography using a low frequency transducer — for example a 2.5 MHz — and a high frequency transducer, for example a 7.5 MHz probe. Detailed examination of duodenal walls and folds, colonic walls and haustra was performed using a 7.5 MHz probe. Deeply located abdominal structures were examined using 2.5 MHz probe. All ultrasound examinations are performed after overnight fasting (for at least 16 hours) using standard scanning procedure. Subjects are examined with and without water contrast. Water contrast imaging is performed by having adult subjects take at least one liter of water prior to examination. Patients are examined in the supine, left posterior oblique, and left lateral decubitus positions using the intercostal and subcostal approaches. The liver, gall bladder, spleen, pancreas, duodenum, colon, and kidneys are routinely evaluated in all patients.
With patient lying supine, the examination of the duodenum with high frequency ultrasound duodenography is performed with 7.5 MHz probe placed in the right upper abdomen, and central epigastric successively; for high frequency ultrasound colonography, the ascending colon, is examined with starting point usually midway of an imaginary line running from the iliac crest to the umbilicus and proceeding cephalid through the right mid abdomen; for the descending colon, the examination begins from the left upper abdomen proceeding caudally and traversing the left mid abdomen and left lower abdomen, terminating at the sigmoid colon in the lower pelvic region. Color flow Doppler sonography is used to examine the localization of lesions in relation to vessels. All measurements of diameter and wall thickness are performed with built-in software. Measurements are taken between peristaltic waves.

Economics
Researchers have found that older patients with three or more significant health problems, like dementia or heart failure, had high rates of repeat colonoscopies without medical indications. These patients are less likely to live long enough to develop colon cancer. Gordon states, "At about $1,000 per procedure, theres clearly an economic incentive".The Hemoccult II FOBT (combined with follow-up colonoscopy if indicated by the test) is over 5 times as cost effective as other screening strategies, but is only about 85% as sensitive. Because of this relatively low sensitivity, US guidelines advocate the over 5 times more expensive procedures instead, because even the relatively small increase in lives saved and 5-fold cost increase is seen as worth choosing, given US living standards.

History
In the 1960s, Dr. Niwa and Dr. Yamagata at Tokyo University developed the device. After 1968, Dr. William Wolff and Dr. Hiromi Shinya pioneered the development of the colonoscope. Their invention, in 1969 in Japan, was an advance over the barium enema and the flexible sigmoidoscope because it allowed for the visualization and removal of polyps from the entire large intestine. Wolff and Shinya advocated for their invention and published much of the early evidence needed to overcome skepticism about the devices safety and efficacy.
Colonoscopy with CCD invention and market is led by Fuji film, Olympus and Hoya in Japan. In 1982, Dr. Lawrence Kaplan of Aspen Medical Group in St. Paul, MN reported a series of 100 consecutive colonoscopies and upper endoscopies performed in a free-standing clinic miles from the nearest hospital, demonstrating the safety and cost effectiveness of these outpatient procedures. (Personal communication to the Joint Commission on Ambulatory Care, May 1983)

Etymology
The terms colonoscopy or coloscopy are derived from the ancient Greek noun κόλον, same as English colon, and the verb σκοπεῖν, look (in)to, examine. The term colonoscopy is however ill-constructed, as this form supposes that the first part of the compound consists of a possible root κολων- or κολον-, with the connecting vowel -o, instead of the root κόλ- of κόλον. A compound such as κολωνοειδής, like a hill, (with the additional -on-) is derived from the ancient Greek word κολώνη or κολωνός, hill. Similarly, colonoscopy (with the additional -on-) can literally be translated as examination of the hill, instead of the examination of the colon.
In English, multiple words exist that are derived from κόλον, such as colectomy, colocentesis, colopathy, and colostomy among many others, that actually lack the incorrect additional -on-. A few compound words such as colonopathy have doublets with -on- inserted.

See also
References
Further reading
Gupta S, Lieberman D, Anderson JC, Burke CA, Dominitz JA, Kaltenbach T,  et al. (March 2020). "Recommendations for Follow-Up After Colonoscopy and Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colorectal Cancer". Gastroenterology. 158 (4): 1131–1153.e5. doi:10.1053/j.gastro.2019.10.026. PMC 7672705. PMID 32044092.
Gupta S, Lieberman D, Anderson JC, Burke CA, Dominitz JA, Kaltenbach T,  et al </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 Bronchopulmonary dysplasia and can you explain it in depth? [/INST] Bronchopulmonary dysplasia (BPD; part of the spectrum of chronic lung disease of infancy) is a chronic lung disease in which premature infants, usually those who were treated with supplemental oxygen, require long-term oxygen. The alveoli that are present tend to not be mature enough to function normally. It is more common in infants with low birth weight (LBW) and those who receive prolonged mechanical ventilation to treat respiratory distress syndrome (RDS). It results in significant morbidity and mortality.  The definition of BPD has continued to evolve primarily due to changes in the population, such as more survivors at earlier gestational ages, and improved neonatal management including surfactant, antenatal glucocorticoid therapy, and less aggressive mechanical ventilation.Currently the description of BPD includes the grading of its severity into mild, moderate and severe. This correlates with the infants maturity, growth and overall severity of illness. The new system offers a better description of underlying pulmonary disease and its severity.

Presentation
Complications
Feeding problems are common in infants with bronchopulmonary dysplasia, often due to prolonged intubation. Such infants often display oral-tactile hypersensitivity (also known as oral aversion).
Physical findings:
hypoxemia;
hypercapnia;
crackles, wheezing, & decreased breath sounds;
increased bronchial secretions;
hyperinflation;
frequent lower respiratory infections;
delayed growth & development;
cor pulmonale;
CXR shows with hyperinflation, low diaphragm, atelectasis, cystic changes.

Cause
Prolonged high oxygen delivery in premature infants causes necrotizing bronchiolitis and alveolar septal injury, with inflammation and scarring. This results in hypoxemia. Today, with the advent of surfactant therapy and high frequency ventilation and oxygen supplementation, infants with BPD experience much milder injury without necrotizing bronchiolitis or alveolar septal fibrosis. Instead, there are usually uniformly dilated acini with thin alveolar septa and little or no interstitial fibrosis. It develops most commonly in the first 4 weeks after birth.

Diagnosis
Earlier criteria
The classic diagnosis of BPD may be assigned at 28 days of life if the following criteria are met:
Positive pressure ventilation during the first 2 weeks of life for a minimum of 3 days.
Clinical signs of abnormal respiratory function.
Requirements for supplemental oxygen for longer than 28 days of age to maintain PaO2 above 50 mm Hg.
Chest radiograph with diffuse abnormal findings characteristic of BPD.

Newer criteria
The 2006 National Institute of Health (US) criteria for BPD (for neonates treated with more than 21% oxygen for at least 28 days) is as follows:,
MildBreathing room air at 36 weeks post-menstrual age or discharge (whichever comes first) for babies born before 32 weeks, or
breathing room air by 56 days postnatal age, or discharge (whichever comes first) for babies born after 32 weeks gestation.ModerateNeed for <30% oxygen at 36 weeks postmenstrual age, or discharge (whichever comes first) for babies born before 32 weeks, or
need for <30% oxygen to 56 days postnatal age, or discharge (whichever comes first) for babies born after 32 weeks gestation.SevereNeed for >30% oxygen, with or without positive pressure ventilation or continuous positive pressure at 36 weeks postmenstrual age, or discharge (whichever comes first) for babies born before 32 weeks, or
need for >30% oxygen with or without positive pressure ventilation or continuous positive pressure at 56 days postnatal age, or discharge (whichever comes first) for babies born after 32 weeks gestation.

Management
Infants with bronchopulmonary dysplasia are often treated with diuretics that decrease fluid in the alveoli where gas exchange occurs and bronchodilators that relax the airway muscles to facilitate breathing. Viral immunization is important for these children who have a higher risk of infections in the respiratory tract.

Corticosteroid treatment
There is evidence that steroids (systemic corticosteroid treatment) given to babies less than 7 days old can prevent bronchopulmonary dysplasia. This treatment increases the risk of neurodevelopmental sequelae (cerebral palsy) and gastrointestinal perforation.For babies 7 days old and older, "late systemic postnatal corticosteroid treatment" may reduce the risk of death and of bronchopulmonary dysplasia. There is some evidence that this treatment does not increase the risk of cerebral palsy, however, long-term studies considering the neurodevelopmental outcomes is needed to further understand the risk of this treatment option. Late systemic postnatal corticosteroid treatment is therefore only recommended for babies 7 days old or older who cannot be taken off of a ventilator </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 Brucellosis and can you explain it in depth? [/INST] Brucellosis is a highly contagious zoonosis caused by ingestion of unpasteurized milk or undercooked meat from infected animals, or close contact with their secretions. It is also known as undulant fever, Malta fever, and Mediterranean fever.The bacteria causing this disease, Brucella, are small, Gram-negative, nonmotile, nonspore-forming, rod-shaped (coccobacilli) bacteria. They function as facultative intracellular parasites, causing chronic disease, which usually persists for life. Four species infect humans: B. abortus, B. canis, B. melitensis, and B. suis. B. abortus is less virulent than B. melitensis and is primarily a disease of cattle. B. canis affects dogs. B. melitensis is the most virulent and invasive species; it usually infects goats and occasionally sheep. B. suis is of intermediate virulence and chiefly infects pigs. Symptoms include profuse sweating and joint and muscle pain. Brucellosis has been recognized in animals and humans since the early 20th century.

Signs and symptoms
The symptoms are like those associated with many other febrile diseases, but with emphasis on muscular pain and night sweats. The duration of the disease can vary from a few weeks to many months or even years.
In the first stage of the disease, bacteremia occurs and leads to the classic triad of undulant fevers, sweating (often with characteristic foul, moldy smell sometimes likened to wet hay), and migratory arthralgia and myalgia (joint and muscle pain). Blood tests characteristically reveal a low number of white blood cells and red blood cells, show some elevation of liver enzymes such as aspartate aminotransferase and alanine aminotransferase, and demonstrate positive Bengal rose and Huddleston reactions. Gastrointestinal symptoms occur in 70% of cases and include nausea, vomiting, decreased appetite, unintentional weight loss, abdominal pain, constipation, diarrhea, an enlarged liver, liver inflammation, liver abscess, and an enlarged spleen.This complex is, at least in Portugal, Israel, Syria, and Jordan, known as Malta fever. During episodes of Malta fever, melitococcemia (presence of brucellae in the blood) can usually be demonstrated by means of blood culture in tryptose medium or Albini medium. If untreated, the disease can give origin to focalizations or become chronic. The focalizations of brucellosis occur usually in bones and joints, and osteomyelitis or spondylodiscitis of the lumbar spine accompanied by sacroiliitis is very characteristic of this disease. Orchitis is also common in men.
The consequences of Brucella infection are highly variable and may include arthritis, spondylitis, thrombocytopenia, meningitis, uveitis, optic neuritis, endocarditis, and various neurological disorders collectively known as neurobrucellosis.

Cause
Brucellosis in humans is usually associated with consumption of unpasteurized milk and soft cheeses made from the milk of infected animals—primarily goats, infected with B. melitensis and with occupational exposure of laboratory workers, veterinarians, and slaughterhouse workers. Some vaccines used in livestock, most notably B. abortus strain 19, also cause disease in humans if accidentally injected. Brucellosis induces inconstant fevers, miscarriage, sweating, weakness, anemia, headaches, depression, and muscular and bodily pain. The other strains,  B. suis and B. canis, cause infection in pigs and dogs, respectively.Overall findings support that brucellosis poses an occupational risk to goat farmers with specific areas of concern including weak awareness of disease transmission to humans and lack of knowledge on specific safe farm practices such as quarantine practices.

Diagnosis
The diagnosis of brucellosis relies on:
Demonstration of the agent: blood cultures in tryptose broth, bone marrow cultures: The growth of brucellae is extremely slow (they can take up to two months to grow) and the culture poses a risk to laboratory personnel due to high infectivity of brucellae.
Demonstration of antibodies against the agent either with the classic Huddleson, Wright, and/or Bengal Rose reactions, either with ELISA or the 2-mercaptoethanol assay for IgM antibodies associated with chronic disease
Histologic evidence of granulomatous hepatitis on hepatic biopsy
Radiologic alterations in infected vertebrae: the Pedro Pons sign (preferential erosion of the anterosuperior corner of lumbar vertebrae) and marked osteophytosis are suspicious of brucellic spondylitis.Definite diagnosis of brucellosis requires the isolation of the organism from the blood, body fluids, or tissues, but serological methods may be the only tests available in many settings. Positive blood culture yield ranges between 40 and 70% and is less commonly positive for B. abortus than B. melitensis or  B. suis. Identification of specific antibodies against bacterial lipopolysaccharide and other antigens can be detected by the standard agglutination test (SAT), rose Bengal, 2-mercaptoethanol (2-ME), antihuman globulin (Coombs) and indirect enzyme-linked immunosorbent assay (ELISA). SAT is the most commonly used serology in endemic areas. An agglutination titre greater than 1:160 is considered significant in nonendemic areas and greater than 1:320 in endemic areas.Due to the similarity of the O polysaccharide of Brucella to that of various other Gram-negative bacteria (e.g. Francisella tularensis, Escherichia coli, Salmonella urbana, Yersinia enterocolitica, Vibrio cholerae, and Stenotrophomonas maltophilia), the appearance of cross-reactions of class M immunoglobulins may occur. The inability to diagnose B. canis by SAT due to lack of cross-reaction is another drawback. False-negative SAT may be caused by the presence of blocking antibodies (the prozone phenomenon) in the α2-globulin (IgA) and in the α-globulin (IgG) fractions.Dipstick assays are new and promising, based on the binding of Brucella IgM antibodies, and are simple, accurate, and rapid. ELISA typically uses cytoplasmic proteins as antigens. It measures IgM, IgG, and IgA with  better sensitivity and specificity than the SAT in most recent comparative studies. The commercial Brucellacapt test, a single-step immunocapture assay for the detection of total anti-Brucella antibodies, is an increasingly used adjunctive test when resources permit. PCR is fast and should be specific. Many varieties of PCR have been developed (e.g. nested PCR, realtime PCR, and PCR-ELISA) and found to have superior specificity and sensitivity in detecting both primary infection and relapse after treatment. Unfortunately, these are not standardized for routine use, and some centres have reported persistent PCR positivity after clinically successful treatment, fuelling the controversy about the existence of prolonged chronic brucellosis.Other laboratory findings include normal peripheral white cell count, and occasional leucopenia with relative lymphocytosis. The serum biochemical profiles are commonly normal.

Prevention
Surveillance using serological tests, as well as tests on milk such as the milk ring test, can be used for screening and play an important role in campaigns to eliminate the disease. Also, individual animal testing both for trade and for disease-control purposes is practiced. In endemic areas, vaccination is often used to reduce the incidence of infection. An animal vaccine is available that uses modified live bacteria. The World Organisation for Animal Health Manual of Diagnostic Test and Vaccines for Terrestrial Animals provides detailed guidance on the production of vaccines. As the disease is closer to being eliminated, a test and eradication program is required to eliminate it.The main way of preventing brucellosis is by using fastidious hygiene in producing raw milk products, or by pasteurizing all milk that is to be ingested by human beings, either in its unaltered form or as a derivative, such as cheese.

Treatment
Antibiotics such as tetracyclines, rifampicin, and the aminoglycosides streptomycin and gentamicin are effective against Brucella bacteria. However, the use of more than one antibiotic is needed for several weeks, because the bacteria incubate within cells.The gold standard treatment for adults is daily intramuscular injections of streptomycin 1 g for 14 days and oral doxycycline 100 mg twice daily for 45 days (concurrently). Gentamicin 5 mg/kg by intramuscular injection once daily for 7 days is an acceptable substitute when streptomycin is not available or contraindicated. Another widely used regimen is doxycycline plus rifampicin twice daily for at least 6 weeks. This regimen has the advantage of oral administration. A triple therapy of doxycycline, with rifampicin and co-trimoxazole, has been used successfully to treat neurobrucellosis. Doxycycline plus streptomycin regimen (for 2 to 3 weeks) is more effective than doxycycline plus rifampicin regimen (for 6 weeks).Doxycycline is able to cross the blood–brain barrier, but requires the addition of two other drugs to prevent relapse. Ciprofloxacin and co-trimoxazole therapy is associated with an unacceptably high rate of relapse. In brucellic endocarditis, surgery is required for an optimal outcome. Even with optimal antibrucellic therapy, relapses still occur in 5 to 10% of patients with Malta fever.

Prognosis
The mortality of the disease in 1909, as recorded in the British Army and Navy stationed in Malta, was 2%. The most frequent cause of death was endocarditis. Recent advances in antibiotics and surgery have been successful in preventing death due to endocarditis. Prevention of human brucellosis can be achieved by eradication of the disease in animals by vaccination and other veterinary control methods such as testing herds/flocks and slaughtering animals when infection is present. Currently, no effective vaccine is available for humans. Boiling milk before consumption, or before using it to produce other dairy products, is protective against transmission via ingestion. Changing traditional food habits of eating raw meat, liver, or bone marrow is necessary, but difficult to implement. Patients who have had brucellosis should probably be excluded indefinitely from donating blood or organs. Exposure of diagnostic laboratory personnel to Brucella organisms remains a problem in both endemic settings and when brucellosis is unknowingly imported by a patient. After appropriate risk assessment, staff with significant exposure should be offered postexposure prophylaxis and followed up serologically for 6 months.

Epidemiology
Argentina
According to a study published in 2002, an estimated 10–13% of farm animals are infected with Brucella species. Annual losses from the disease were calculated at around $60 million. Since 1932, government agencies have undertaken efforts to contain the disease. Currently, all cattle of ages 3–8 months must receive the Brucella abortus strain 19 vaccine.

Australia
Australia is free of cattle brucellosis, although it occurred in the past. Brucellosis of sheep or goats has never been reported. Brucellosis of pigs does occur. Feral pigs are the typical source of human infections.

Canada
On 19 September 1985, the Canadian government declared its cattle population brucellosis-free. Brucellosis ring testing of milk and cream, and testing of cattle to be slaughtered ended on 1 April 1999. Monitoring continues through testing at auction markets, through standard disease-reporting procedures, and through  testing of cattle being qualified for export to countries other than the United States.

China
An outbreak infecting humans took place in Lanzhou in 2020 after the Lanzhou Biopharmaceutical Plant, which was involved in vaccine production, accidentally pumped out the bacteria into the atmosphere in exhaust air due to use of expired disinfectant. The outbreak affected over 6,000 people.

Europe
Malta
Until the early 20th century, the disease was endemic in Malta to the point of it being referred to as "Maltese fever". Since 2005, due to a strict regimen of certification of milk animals and widespread use of pasteurization, the illness has been eradicated from Malta.

Republic of Ireland
Ireland was declared free of brucellosis on 1 July 2009. The disease had troubled the countrys farmers and veterinarians for several decades. The Irish government submitted an application to the European Commission, which verified that Ireland had been liberated. Brendan Smith, Irelands then Minister for Agriculture, Food and the Marine, said the elimination of brucellosis was "a landmark in the history of disease eradication in Ireland". Irelands Department of Agriculture, Food and the Marine intends to reduce its brucellosis eradication programme now that eradication has been confirmed.

UK
Mainland Britain has been free of brucellosis since 1979, although there have been episodic re-introductions since. The last outbreak of brucellosis in Great Britain was in cattle in Cornwall in 2004. Northern Ireland was declared officially brucellosis-free in 2015.

New Zealand
Brucellosis in New Zealand is limited to sheep (B. ovis). The country is free of all other species of Brucella.

United States
Dairy herds in the U.S. are tested at least once a year to be certified brucellosis-free with the Brucella milk ring test. Cows confirmed to be infected are often killed. In the United States, veterinarians are required to vaccinate all young stock, to further reduce the chance of zoonotic transmission. This vaccination is usually referred to as a "calfhood" vaccination. Most cattle receive a tattoo in one of their ears, serving as proof of their vaccination status. This tattoo also includes the last digit of the year they were born.The first state–federal cooperative efforts towards eradication of brucellosis caused by B. abortus in the U.S. began in 1934.Brucellosis was originally imported to North America with non-native domestic cattle (Bos taurus), which transmitted the disease to wild bison (Bison bison) and elk (Cervus canadensis). No records exist of brucellosis in ungulates native to America until the early 19th century.

History
Brucellosis first came to the attention of British medical officers in the 1850s in Malta during the Crimean War, and was referred to as Malta Fever. Jeffery Allen Marston (1831–1911) described his own case of the disease in 1861. The causal relationship between organism and disease was first established in 1887 by David Bruce. Bruce considered the agent spherical and classified it as a coccus.
In 1897, Danish veterinarian Bernhard Bang isolated a bacillus as the agent of heightened spontaneous abortion in cows, and the name "Bangs disease" was assigned to this condition. Bang considered the organism rod-shaped and classified it as a bacillus. So at the time, no one knew that this bacillus had anything to do with the causative agent in Malta fever.Maltese scientist and archaeologist Themistocles Zammit identified unpasteurized goat milk as the major etiologic factor of undulant fever in June 1905.In the late 1910s, American bacteriologist Alice C. Evans was studying the Bang bacillus and gradually realized that it was virtually indistinguishable from the Bruce coccus. The short-rod versus oblong-round morphologic borderline explained the leveling of the erstwhile bacillus/coccus distinction (that is, these "two" pathogens were not a coccus versus a bacillus but rather were one coccobacillus). The Bang bacillus was already known to be enzootic in American dairy cattle, which showed itself in the regularity with which herds experienced contagious abortion. Having made the discovery that the bacteria were certainly nearly identical and perhaps totally so, Evans then wondered why Malta fever was not widely diagnosed or reported in the United States. She began to wonder whether many cases of vaguely defined febrile illnesses were in fact caused by the drinking of raw (unpasteurized) milk. During the 1920s, this hypothesis was vindicated. Such illnesses ranged from undiagnosed and untreated gastrointestinal upset to misdiagnosed febrile and painful versions, some even fatal. This advance in bacteriological science sparked extensive changes in the American dairy industry to improve food safety. The changes included making pasteurization standard and greatly tightening the standards of cleanliness in milkhouses on dairy farms. The expense prompted delay and skepticism in the industry, but the new hygiene rules eventually became the norm. Although these measures have sometimes struck people as overdone in the decades since,  being unhygienic at milking time or in the milkhouse, or drinking raw milk, are not a safe alternative.In the decades after Evanss work, this genus, which received the name Brucella in honor of Bruce, was found to contain several species with varying virulence. The name "brucellosis" gradually replaced the 19th-century names Mediterranean fever and Malta fever.Neurobrucellosis, a neurological involvement in brucellosis, was first described in 1879. In the late 19th century, its symptoms were described in more detail by M. Louis Hughes, a Surgeon-Captain of the Royal Army Medical Corps stationed in Malta who isolated brucella organisms from a patient with meningo-encephalitis. In 1989, neurologists in Saudi Arabia made significant contributions to the medical literature involving neurobrucellosis.These obsolete names have previously been applied to brucellosis:

Biological warfare
Brucella species were weaponized by several advanced countries by the mid-20th century. In 1954, B. suis became the first agent weaponized by the United States at its Pine Bluff Arsenal near Pine Bluff, Arkansas. Brucella species survive well in aerosols and resist drying. Brucella and all other remaining biological weapons in the U.S. arsenal were destroyed in 1971–72 when the American offensive biological warfare  program was discontinued by order of President Richard Nixon.The experimental American bacteriological warfare program focused on three agents of the Brucella group:
Porcine brucellosis (agent US)
Bovine brucellosis (agent AA)
Caprine brucellosis (agent AM)Agent US was in advanced development by the end of World War II. When the United States Air Force (USAF) wanted a biological warfare capability, the Chemical Corps offered Agent US in the M114 bomblet, based on the four-pound bursting bomblet developed for spreading anthrax during World War II. Though the capability was developed, operational testing indicated the weapon was less than desirable, and the USAF designed it as an interim capability until it could eventually be replaced by a more effective biological weapon.The main drawback of using the M114 with Agent US was that it acted mainly as an incapacitating agent, whereas the USAF administration wanted weapons that were deadly. The stability of M114 in storage was too low to allow for storing it at forward air bases, and the logistical requirements to neutralize a target were far higher than was originally planned. Ultimately, this would have required too much logistical support to be practical in the field.Agents US and AA had a median infective dose of 500 organisms/person, and for Agent AM it was 300 organisms/person. The incubation time was believed to be about 2 weeks, with a duration of infection of several months. The lethality estimate was, based on epidemiological information, 1 to 2
per cent. Agent AM was believed to be a somewhat more virulent disease, with a fatality rate of 3 per cent being expected.

Other animals
Species infecting domestic livestock are B. abortus (cattle, bison, and elk), B. canis (dogs), B. melitensis (goats and sheep), B. ovis (sheep), and B. suis (caribou and pigs). Brucella species have also been isolated from several marine mammal species (cetaceans and pinnipeds).

Cattle
B. abortus is the principal cause of brucellosis in cattle. The bacteria are shed from an infected animal at or around the time of calving or abortion. Once exposed, the likelihood of an animal becoming infected is variable, depending on age, pregnancy status, and other intrinsic factors of the animal, as well as the number of bacteria to which the animal was exposed. The most common clinical signs of cattle infected with B. abortus are high incidences of abortions, arthritic joints, and retained placenta.The two main causes for spontaneous abortion in animals are erythritol, which can promote infections in the fetus and placenta, and the lack of anti-Brucella activity in the amniotic fluid. Males can also harbor the bacteria in their reproductive tracts, namely seminal vesicles, ampullae, testicles, and epididymes.

Dogs
The causative agent of brucellosis in dogs, B. canis, is transmitted to other dogs through breeding and contact with aborted fetuses. Brucellosis can occur in humans who come in contact with infected aborted tissue or semen. The bacteria in dogs normally infect the genitals and lymphatic system, but can also spread to the eyes, kidneys, and intervertebral discs. Brucellosis in the intervertebral disc is one possible cause of discospondylitis. Symptoms of brucellosis in dogs include abortion in female dogs and  scrotal inflammation and orchitis in males. Fever is uncommon. Infection of the eye can cause uveitis, and infection of the intervertebral disc can cause pain or weakness. Blood testing of the dogs prior to breeding can prevent the spread of this disease. It is treated with antibiotics, as with humans, but it is difficult to cure.

Aquatic wildlife
Brucellosis in cetaceans is caused by the bacterium B. ceti. First discovered in the aborted fetus of a bottlenose dolphin, the structure of B. ceti is similar to Brucella in land animals. B. ceti is commonly detected in two suborders of cetaceans, the Mysticeti and Odontoceti. The Mysticeti include four families of baleen whales, filter-feeders, and the Odontoceti include two families of toothed cetaceans ranging from dolphins to sperm whales. B. ceti is believed to transfer from animal to animal through sexual intercourse, maternal feeding, aborted fetuses, placental issues, from mother to fetus, or through fish reservoirs. Brucellosis is a reproductive disease, so has an extreme negative impact on the population dynamics of a species. This becomes a greater issue when the already low population numbers of cetaceans are taken into consideration. B. ceti has been identified in four  of the 14 cetacean families, but the antibodies have been detected in seven of the families. This indicates that B. ceti is common amongst cetacean families and populations. Only a small percentage of exposed individuals become ill or die. However, particular species apparently are more likely to become infected by B. ceti. The harbor porpoise, striped dolphin, white-sided dolphin, bottlenose dolphin, and common dolphin have the highest frequency of infection amongst ondontocetes. In the mysticetes families, the northern minke whale is by far the most infected species. Dolphins and porpoises are more likely to be infected than cetaceans such as whales. With regard to sex and age biases, the infections do not seem influenced by the age or sex of an individual. Although fatal to cetaceans, B. ceti has a low infection rate for humans.

Terrestrial wildlife
The disease in its various strains can infect multiple wildlife species, including elk (Cervus canadensis), bison (Bison bison), African buffalo (Syncerus caffer), European wild boar (Sus scrofa), caribou (Rangifer tarandus), moose (Alces alces), and marine mammals (see section on aquatic wildlife above). While some regions use vaccines to prevent the spread of brucellosis between infected and uninfected wildlife populations, no suitable brucellosis vaccine for terrestrial wildlife has been developed. This gap in medicinal knowledge creates more pressure for management practices that reduce spread of the disease.Wild bison and elk in the greater Yellowstone area are the last remaining reservoir of B. abortus in the US. The recent transmission of brucellosis from elk back to cattle in Idaho and Wyoming illustrates how the area, as the last remaining reservoir in the United States, may adversely affect the livestock industry. Eliminating brucellosis from this area is a challenge, as many viewpoints exist on how to manage diseased wildlife. However, the Wyoming Game and Fish Department has recently begun to protect scavengers (particularly coyotes and red fox) on elk feedgrounds, because they act as sustainable, no-cost, biological control agents by removing infected elk fetuses quickly.The National Elk Refuge in Jackson, Wyoming asserts that the intensity of the winter feeding program affects the spread of brucellosis more than the population size of elk and bison. Since concentrating animals around food plots accelerates spread of the disease, management strategies to reduce herd density and increase dispersion could limit its spread.

Effects on hunters
Hunters may be at additional risk for exposure to brucellosis due to increased contact with susceptible wildlife, including predators that may have fed on infected prey. Hunting dogs can also be at risk of infection. Exposure can occur through contact with open wounds or by directly inhaling the bacteria while cleaning game </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 Burning mouth syndrome and can you explain it in depth? [/INST] Burning mouth syndrome (BMS) is a burning, tingling or scalding sensation in the mouth, lasting for at least four to six months, with no underlying known dental or medical cause. No related signs of disease are found in the mouth.  People with burning mouth syndrome may also have a subjective xerostomia (dry mouth sensation where no cause can be found such as reduced salivary flow), paraesthesia (altered sensation such as tingling in the mouth), or an altered sense of taste or smell.A burning sensation in the mouth can be a symptom of another disease when local or systemic factors are found to be implicated; this is not considered to be burning mouth syndrome,  which is a syndrome of medically unexplained symptoms.  The International Association for the Study of Pain defines burning mouth syndrome as "a distinctive nosological entity characterized by unremitting oral burning or similar pain in the absence of detectable mucosal changes" and "burning pain in the tongue or other oral mucous membranes", and the International Headache Society defines it as "an intra-oral burning sensation for which no medical or dental cause can be found". To ensure the correct diagnosis of burning mouth syndrome, Research Diagnostic Criteria (RDC/BMS) have been developed.Insufficient evidence leaves it unclear if effective treatments exist.

Signs and symptoms
By definition, BMS has no signs. Sometimes affected persons will attribute the symptoms to sores in the mouth, but these are in fact normal anatomic structures (e.g. lingual papillae, varices). Symptoms of BMS are variable, but the typical clinical picture is given below, considered according to the Socrates pain assessment method (see table). If clinical signs are visible, then another explanation for the burning sensation may be present. Erythema (redness) and edema (swelling) of papillae on the tip of the tongue may be a sign that the tongue is being habitually pressed against the teeth. The number and size of filiform papillae may be reduced. If the tongue is very red and smooth, then there is likely a local or systemic cause (e.g. eythematous candidiasis, anemia).

Causes
Theories
In about 50% of cases of burning mouth sensation  no identifiable cause is apparent; these cases are termed (primary) BMS. Several theories of what causes BMS have been proposed, and these are supported by varying degrees of evidence, but none is proven.
As most people with BMS are postmenopausal women, one theory of the cause of BMS is of estrogen or progesterone deficit, but a strong statistical correlation has not been demonstrated. Another theory is that BMS is related to autoimmunity, as abnormal antinuclear antibody and rheumatoid factor can be found in the serum of more than 50% of persons with BMS, but these levels may also be seen in elderly people who do not have any of the symptoms of this condition. Whilst salivary flow rates are normal and there are no clinical signs of a dry mouth to explain a complaint of dry mouth, levels of salivary proteins and phosphate may be elevated and salivary pH or buffering capacity may be reduced.Depression and anxiety are strongly associated with BMS. It is not known if depression is a cause or result of BMS, as depression may develop in any setting of constant unrelieved irritation, pain, and sleep disturbance. It is estimated that about 20% of BMS cases involve psychogenic factors, and some consider BMS a psychosomatic illness, caused by cancerophobia, concern about sexually transmitted infections, or hypochondriasis.Chronic low-grade trauma due to parafunctional habits (e.g. rubbing the tongue against the teeth or pressing it against the palate), may be involved. BMS is more common in persons with Parkinsons disease, so it has been suggested that it is a disorder of reduced pain threshold and increased sensitivity. Often people with BMS have unusually raised taste sensitivity, termed hypergeusia ("super tasters"). Dysgeusia (usually a bitter or metallic taste) is present in about 60% of people with BMS, a factor which led to the concept of a defect in sensory peripheral neural mechanisms. Changes in the oral environment, such as changes in the composition of saliva, may induce neuropathy or interruption of nerve transduction. The onset of BMS is often spontaneous, although it may be gradual. There is sometimes a correlation with a major life event or stressful period in life. In women, the onset of BMS is most likely three to twelve years following menopause.

Other causes of an oral burning sensation
Several local and systemic factors can give a burning sensation in the mouth without any clinical signs, and therefore may be misdiagnosed as BMS. Some sources state that where there is an identifiable cause for a burning sensation, this can be termed "secondary BMS" to distinguish it from primary BMS. However, the accepted definitions of BMS hold that there are no identifiable causes for BMS, and where there are identifiable causes, the term BMS should not be used.Some causes of a burning mouth sensation may be accompanied by clinical signs in the mouth or elsewhere on the body. For example, burning mouth pain may be a symptom of allergic contact stomatitis. This is a contact sensitivity (type IV hypersensitivity reaction) in the oral tissues to common substances such as sodium lauryl sulfate, cinnamaldehyde or dental materials. However, allergic contact stomatitis is accompanied by visible lesions and gives positive response with patch testing. Acute (short term) exposure to the allergen (the substance triggering the allergic response) causes non-specific inflammation and possibly mucosal ulceration. Chronic (long term) exposure to the allergen may appear as chronic inflammatory, lichenoid (lesions resembling oral lichen planus), or plasma cell gingivitis, which may be accompanied by glossitis and cheilitis. Apart from BMS itself, a full list of causes of an oral burning sensation is given below:

Deficiency of iron, folic acid or various B vitamins (glossitis e.g. due to anemia), or zinc
Neuropathy, e.g. following damage to the chorda tympani nerve.
Hypothyroidism.
Medications ("scalded mouth syndrome", unrelated to BMS) - protease inhibitors and angiotensin-converting-enzyme inhibitors (e.g. captopril).
Type 2 diabetes
True xerostomia, caused by hyposalivation e.g. Sjögrens syndrome
Parafunctional activity, e.g. nocturnal bruxism or a tongue thrusting habit.
Restriction of the tongue by poorly constructed dentures.
Geographic tongue.
Oral candidiasis.
Herpetic infection (herpes simplex virus).
Fissured tongue.
Lichen planus.
Allergies and contact sensitivities to foods, metals, and other substances (see table).
Hiatal hernia.
Human immunodeficiency virus.
Multiple myeloma

Diagnosis
BMS is a diagnosis of exclusion, i.e. all other explanations for the symptoms are ruled out before the diagnosis is made. There are no clinically useful investigations that would help to support a diagnosis of BMS (by definition all tests would have normal results), but blood tests and / or urinalysis may be useful to rule out anemia, deficiency states, hypothyroidism and diabetes. Investigation of a dry mouth symptom may involve sialometry, which objectively determines if there is any reduction of the salivary flow rate (hyposalivation). Oral candidiasis can be tested for with use of a swabs, smears, an oral rinse or saliva samples.  It has been suggested that allergy testing (e.g., patch test) is inappropriate in the absence of a clear history and clinical signs in people with a burning sensation in the mouth. The diagnosis of a people with a burning symptom may also involve psychologic screening e.g. depression questionnaires.The second edition of the International Classification of Headache Disorders lists diagnostic criteria for "Glossodynia and Sore Mouth":

A. Pain in the mouth present daily and persisting for most of the day,
B. Oral mucosa is of normal appearance,
C. Local and systemic diseases have been excluded.

Classification
A burning sensation in the mouth may be primary (i.e. burning mouth syndrome) or secondary to systemic or local factors. Other sources refer to a "secondary BMS" with a similar definition, i.e. a burning sensation which is caused by local or systemic factors, or "where oral burning is explained by a clinical abnormality". However this contradicts the accepted definition of BMS which specifies that no cause can be identified. "Secondary BMS" could therefore be considered a misnomer. BMS is an example of dysesthesia, or a distortion of sensation.Some consider BMS to be a variant of atypical facial pain. More recently, BMS has been described as one of the 4 recognizable symptom complexes of chronic facial pain, along with atypical facial pain, temporomandibular joint dysfunction and atypical odontalgia. BMS has been subdivided into three general types, with type two being the most common and type three being the least common. Types one and two have unremitting symptoms, whereas type three may show remitting symptoms.
Type 1 - Symptoms not present upon waking, and then increase throughout the day
Type 2 - Symptoms upon waking and through the day
Type 3 - No regular pattern of symptomsSometimes those terms specific to the tongue (e.g. glossodynia) are reserved for when the burning sensation is located only on the tongue.

Treatment
If a cause can be identified for a burning sensation in the mouth, then treatment of this underlying factor is recommended. If symptom persist despite treatment a diagnosis of BMS is confirmed. BMS has been traditionally treated by reassurance and with antidepressants, anxiolytics or anticonvulsants. A 2016 Cochrane review of treatment for burning mouth syndrome concluded that strong evidence of an effective treatment was not available, however,  a systematic review in 2018 found that the use of antidepressants and alpha-lipoic acids gave promising results.Other treatments which have been used include atypical antipsychotics, histamine receptor antagonists, and dopamine agonists. Supplementation with vitamin complexes and cognitive behavioral therapy may be helpful in the management of burning mouth syndrome.

Prognosis
BMS is benign (importantly, it is not a symptom of oral cancer), but as a cause of chronic pain which is poorly controlled, it can detriment quality of life, and may become a fixation which cannot be ignored, thus interfering with work and other daily activities. Two thirds of people with BMS have a spontaneous partial recovery six to seven years after the initial onset, but in others the condition is permanent. Recovery is often preceded by a change in the character of the symptom from constant to intermittent </s>