<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Poland syndrome and explain in detail? [/INST] Poland syndrome is a birth defect characterized by an underdeveloped chest muscle and short webbed fingers on one side of the body. There may also be short ribs, less fat, and breast and nipple abnormalities on the same side of the body. Typically, the right side is involved. Those affected generally have normal movement and health.The cause of Poland syndrome is unknown. One theory is that it is due to disruption of blood flow during embryonic development. It is generally not inherited from a persons parents, and no genes that contribute to the disorder have been identified. Diagnosis of Poland syndrome is based on its symptoms. Often, those with the syndrome remain undiagnosed, and some may not realize they have it until puberty.Treatment of Poland syndrome depends on its severity and may include surgical correction. The syndrome affects about 1 in 20,000 newborns, and males are affected twice as often as females. It is named after English surgeon Sir Alfred Poland, who described the condition when he was a student in 1841.

Signs and symptoms
A list of the common side effects broken down by frequency.Very frequent

Abnormal gastrointestinal tract
Absent pectoral muscles
Brachydactyly (Short fingers)
Dextrocardia
Diaphragmatic hernia/defect
Humerus absent/abnormal
Liver/biliary tract anomalies
Maternal diabetes
Oligodactyly/missing fingers
Radius absent/abnormal
Rhizomelic micromelia (relatively shorter proximal segment of the limbs compared to the middle and the distal segments)
Sparsity or abnormality of axillary hair on affected side
Syndactyly of fingers (webbing)
Ulna absent/abnormal
Upper limb asymmetry
Abnormal rib
Simian crease on affected sideFrequent

Hypoplastic/absent nipples
Scapula anomalyOccasional

Agenesis/hypoplasia of kidneys
Encephalocele/exencephaly
Abnormal morphology of hypothalamic-hypophyseal axis
Abnormal function of hypothalamic-hypophyseal axis
Microcephaly
Preaxial polydactyly
Ureteric anomalies (reflux/duplex system)
Vertebral segmentation anomalyIt is usually considered a unilateral condition. Some have claimed that the term can be applied in bilateral presentation, but others recommend using alternate terminology in those cases.

Causes
The cause of Poland syndrome is unknown. However, an interruption of the embryonic blood supply to the arteries that lie under the collarbone (subclavian arteries) at about the 46th day of embryonic development is the prevailing theory.The subclavian arteries normally supply blood to embryonic tissues that give rise to the chest wall and hand. Variations in the site and extent of the disruption may explain the range of signs and symptoms that occur in Poland syndrome. Abnormality of an embryonic structure called the apical ectodermal ridge, which helps direct early limb development, may also be involved in this disorder.

Diagnosis
Poland syndrome is usually diagnosed at birth, based upon the physical characteristics. Imaging techniques such as a CT scan may reveal the extent to which the muscles are affected. The syndrome varies in severity and as such is often not reported until puberty, when lopsided growth becomes apparent.

Treatment
Technique
The complete or partial absence of the pectoralis muscle is the malformation that defines Poland syndrome. It can be treated by inserting a custom implant designed by CAD (computer aided design). A 3D reconstruction of the patients chest is done using an implant shaped from a medical scan and designed to be perfectly adapted to the anatomy. The implant is made of medical grade silicone rubber. The treatment is purely cosmetic and does not restore the patients imbalanced upper body strength.The Poland syndrome malformations are morphological, so correction by custom implant is the first-line treatment. This technique allows a wide variety of patients to be treated with good outcomes. Poland Syndrome can be associated with bones, subcutaneous and mammary atrophy: the first, as for pectus excavatum, is successfully corrected by a custom implant, while the others can require surgical intervention such as lipofilling or silicone breast implant, in a second operation.

Surgery
The surgery takes place under general anaesthesia and lasts less than 1 hour. The surgeon prepares the locus to the size of the implant after performing an 8-centimetre (3.1 in) axillary incision, then inserts the implant beneath the skin. The closure is made in two planes.The implant replaces the pectoralis major muscle, thus enabling the thorax to be symmetrical and, in women, the breast as well. If necessary, especially in the case of women, a second operation will complement the result by the implantation of a breast implant and / or lipofilling.Lipomodelling is progressively used in the correction of breast and chest wall deformities. In Poland syndrome, this technique appears to be a major advance that will probably revolutionize the treatment of severe cases. This is mainly due to its ability to achieve previously unachievable quality of reconstruction with minimal scarring.

Epidemiology
Poland syndrome affects males three times as often as females and affects the right side of the body twice as often as the left. The incidence is estimated to range from one in 7,000 to one in 100,000 live births.

History
It was named in 1962 by Patrick Clarkson, a New Zealand-born British plastic surgeon working at Guys Hospital and Queen Marys Hospital, London. He noticed that three of his patients had both a hand deformity and an underdeveloped breast on the same side. He discussed this with his colleague at Guys Hospital, Dr Philip Evans, who agreed that the syndrome was "not widely appreciated". Clarkson found a reference to a similar deformity published by Alfred Poland, an English surgeon, over a hundred years earlier in Guys Hospital reports, in 1841 </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Fucosidosis and explain in detail? [/INST] Fucosidosis is a rare lysosomal storage disorder in which the FUCA1 gene experiences mutations that severely reduce or stop the activity of the alpha-L-fucosidase enzyme.  The result is a buildup of complex sugars in parts of the body, which leads to death.
Fucosidosis is one of nine identified glycoprotein storage diseases. The gene encoding the alpha-fucosidase, FUCA 1, was found to be located to the short arm of chromosome 1p36 - p34, by Carrit and co-workers, in 1982.

Cause
Fucosidosis is an autosomal recessive disorder that affects many areas of the body. Mutations in the FUCA1 gene causes fucosidosis. The FUCA1 gene provides instructions for making an enzyme called alpha-L-fucosidase. The enzyme plays a role in the breakdown of complex sugars in the body. The disorder is characterized by lysosomal accumulation of a variety of glycoproteins, glycolipids, and oligosaccharides that contain fucose moieties. The deficiency of the enzyme alpha-L-fucosidase, which is used to metabolize complex compounds in the body (fucose-containing glycolipids and fucose-containing glycoproteins). With the lack of this enzyme activity, the result is incomplete breakdown of glycolipids and glycoproteins. These partially broken down compounds accumulate in various parts of the body and begin to cause malfunction in cells,  and can eventually cause cell death. Brain cells are especially sensitive to this buildup. Other results are progressive neurological deterioration, skin abnormalities, growth retardation, skeletal disease, and coarsening of facial features. Fucosidosis is the consequence of faulty degradation of both sphingolipids and polysaccharides. Major accumulation of the H-antigen (a member of the ABO blood group antigens), a glycolipid, is seen primarily in the liver of fucosidosis patients.

Diagnosis
Diagnosis: A special urine test is available to check for any partially broken-down-sugars. If they are present, a skin or blood sample will be taken to test for below-normal amounts of alpha-fucosidase.- Fucosidosis is an autosomal recessive disorder, which means that both parents have to have the mutation and pass it on to the child. When both parents have the mutation, there is a 25% chance of each child having fucosidosis.

Type 1
Type 1 usually begins somewhere in the first three to 18 months of age and in considered the most severe of the three types </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Minamata disease and explain in detail? [/INST] Minamata disease is a neurological disease caused by severe mercury poisoning. Signs and symptoms include ataxia, numbness in the hands and feet, general muscle weakness, loss of peripheral vision, and damage to hearing and speech. In extreme cases, insanity, paralysis, coma, and death follow within weeks of the onset of symptoms. A congenital form of the disease can also affect fetuses in the womb and may cause cerebral palsy.
Minamata disease was first discovered in the city of Minamata, Kumamoto Prefecture, Japan, in 1956, hence its name. It was caused by the release of methylmercury in the industrial wastewater from a chemical factory owned by the Chisso Corporation, which continued from 1932 to 1968. It has also been suggested that some of the mercury sulfate in the wastewater was also metabolized to methylmercury by bacteria in the sediment. This highly toxic chemical bioaccumulated and biomagnified in shellfish and fish in Minamata Bay and the Shiranui Sea, which, when eaten by the local population, resulted in mercury poisoning. While cat, dog, pig, and human deaths continued for 36 years, Chisso and the Kumamoto prefectural government did little to prevent the epidemic. The animal effects were severe enough in cats that they came to be named as having "dancing cat fever".As of March 2001, 2,265 victims had been officially recognized as having Minamata disease and over 10,000 had received financial compensation from Chisso. By 2004, Chisso had paid US$86 million in compensation, and in the same year was ordered to clean up its contamination. On March 29, 2010, a settlement was reached to compensate as-yet uncertified victims.A second outbreak of Minamata disease occurred in Niigata Prefecture in 1965. The original Minamata disease and Niigata Minamata disease are considered two of the Four Big Pollution Diseases of Japan.

1908–1955
In 1908, the Chisso Corporation first opened a chemical factory in Minamata, Kumamoto Prefecture, located on the west coast of the southern island of Kyūshū. Initially producing fertilisers, the factory followed the nationwide expansion of Japans chemical industry, branching out into production of acetylene, acetaldehyde, acetic acid, vinyl chloride, and octanol, among others. The Minamata factory became the most advanced in all of Japan, both before and after World War II. The waste products resulting from the manufacture of these chemicals were released into Minamata Bay through the factory wastewater. These pollutants had an environmental impact. Fisheries were damaged in terms of reduced catches, and in response Chisso reached two separate compensation agreements with the fishery cooperative in 1926 and 1943.The rapid expansion of the Chisso factory spurred on the local economy, and as the company prospered so did Minamata. This fact, combined with the lack of other industry, meant that Chisso had great influence in the city. At one point, over half of the tax revenue of Minamata City authority came from Chisso and its employees, and the company and its subsidiaries were responsible for creating a quarter of all jobs in Minamata. The city was even dubbed Chissos "castle town," in reference to the capital cities of feudal lords who ruled Japan during the Edo period.The Chisso factory first started acetaldehyde production in 1932, with 210 tons that year. In 1951, production had jumped to 6,000 tons and eventually peaked at 45,245 tons in 1960. The factorys output historically amounted to between a quarter and a third of Japans total acetaldehyde production. The chemical reaction used to produce the acetaldehyde employed mercury sulfate as a catalyst. Starting in August 1951, the co-catalyst was changed from manganese dioxide to ferric sulfide. A side reaction of this catalytic cycle led to the production of a small amount (about 5% of the outflow) of the organic mercury compound methylmercury. As a result of the catalyst change, this highly toxic compound was released into Minamata Bay regularly between 1951 and 1968, when this production method was finally discontinued.

1956–1959
On 21 April 1956, a five-year-old girl was examined at Chissos factory hospital in Minamata. The physicians were puzzled by her symptoms: difficulty walking, difficulty speaking, and convulsions. Two days later, her younger sister also began to exhibit the same symptoms and she, too, was hospitalised. The girls mother informed doctors that her neighbours daughter was also experiencing similar problems. After a house-to-house investigation, eight further patients were discovered and hospitalised. On 1 May, the hospital director reported to the local public health office the discovery of an "epidemic of an unknown disease of the central nervous system", marking the official discovery of Minamata disease.To investigate the epidemic, the city government and various medical practitioners formed the Strange Disease Countermeasures Committee at the end of May 1956. Owing to the localised nature of the disease, it was suspected to be contagious and as a precaution patients were isolated and their homes disinfected. Although contagion was later disproved, this initial response contributed to the stigmatisation and discrimination experienced by Minamata survivors from the local community. During its investigations, the committee uncovered surprising anecdotal evidence of the strange behaviour of cats and other wildlife in the areas surrounding patients homes. From around 1950 onward, cats had been seen to have convulsions, go mad, and die. Locals called it the "cat dancing disease", owing to their erratic movement. Crows had fallen from the sky, seaweed no longer grew on the sea bed, and fish floated dead on the surface of the sea. As the extent of the outbreak was understood, the committee invited researchers from Kumamoto University (or Kumadai) to help in the research effort.The Kumamoto University Research Group was formed on 24 August 1956. Researchers from the School of Medicine began visiting Minamata regularly and admitted patients to the university hospital for detailed examinations. A more complete picture of the symptoms exhibited by patients was gradually uncovered. The disease developed without any prior warning, with patients complaining of a loss of sensation and numbness in their hands and feet. They became unable to grasp small objects or fasten buttons. They could not run or walk without stumbling, their voices changed in pitch, and many patients complained of difficulties seeing, hearing, and swallowing. In general, these symptoms worsened and were followed by severe convulsions, coma, and eventually death. By October 1956, forty patients had been discovered, fourteen of whom had died: an alarming case fatality rate of 35%.

Finding the cause
Researchers from Kumadai also began to focus on the cause of the strange disease. They found that the victims, often members of the same family, were clustered in fishing hamlets along the shore of Minamata Bay. The staple food of victims was invariably fish and shellfish from Minamata Bay. The cats in the local area, which tended to eat scraps from the family table, had died with symptoms similar to those now discovered in humans. This led the researchers to believe that the outbreak was caused by some kind of food poisoning, with contaminated fish and shellfish being the prime suspects.
On 4 November, the research group announced its initial findings: "Minamata disease is rather considered to be poisoning by a heavy metal, presumably it enters the human body mainly through fish and shellfish."

Identification of mercury
As soon as the investigation identified a heavy metal as the causal substance, the wastewater from the Chisso factory was immediately suspected as the origin. The companys own tests revealed that its wastewater contained many heavy metals in concentrations sufficiently high to bring about serious environmental degradation, including lead, mercury, manganese, arsenic, thallium, and copper, plus the chalcogen selenium. Identifying which particular poison was responsible for the disease proved to be extremely difficult and time-consuming. During 1957 and 1958, many different theories were proposed by different researchers. At first, manganese was thought to be the causal substance due to the high concentrations found in fish and the organs of the deceased. Thallium, selenium, and a multiple contaminant theory were also proposed, but in March 1958, visiting British neurologist Douglas McAlpine suggested that Minamata symptoms resembled those of organic mercury poisoning, so the focus of the investigation centered on mercury.
In February 1959, the mercury distribution in Minamata Bay was investigated. The results shocked the researchers involved. Large quantities of mercury were detected in fish, shellfish, and sludge from the bay. The highest concentrations centred around the Chisso factory wastewater canal in Hyakken Harbour and decreased going out to sea, clearly identifying the plant as the source of contamination. Pollution was so heavy at the mouth of the wastewater canal, a figure of 2 kg of mercury per ton of sediment was measured: a level that would be economically viable to mine. Indeed, Chisso did later set up a subsidiary to reclaim and sell the mercury recovered from the sludge.Hair samples were taken from the individuals with the disease and also from the Minamata population in general. In patients, the maximum mercury level recorded was 705 parts per million (ppm), indicating very heavy exposure and in nonsymptomatic Minamata residents, the level was 191 ppm. This compared to an average level of 4 ppm for people living outside the Minamata area.On 12 November 1959, the Ministry of Health and Welfares Minamata Food Poisoning Subcommittee published its results:

Minamata disease is a poisoning disease that affects mainly the central nervous system and is caused by the consumption of large quantities of fish and shellfish living in Minamata Bay and its surroundings, the major causative agent being some sort of organic mercury compound.

1959
During the Kumadai investigation, the causal substance had been identified as a heavy metal and it was widely presumed that the Chisso factory was the source of the contamination. Chisso was coming under closer scrutiny and to deflect criticism, the wastewater output route was changed. Chisso knew of the environmental damage caused by its wastewater and was well aware that it was the prime suspect in the Minamata disease investigation. Despite this, from September 1958, instead of discharging its waste into Hyakken Harbour (the focus of investigation and source of original contamination), it discharged wastewater directly into Minamata River. The immediate effect was the death of fish at the mouth of the river, and from that point on, new Minamata disease victims began to appear in other fishing villages up and down the coast of the Shiranui Sea, as the pollution spread over an even greater area.Chisso failed to co-operate with the Kumadai research team. It withheld information on its industrial processes, leaving researchers to speculate what products the factory was producing and by what methods. The Chisso factorys hospital director, Hajime Hosokawa, established a laboratory in the research division of the facility to carry out his own experiments into Minamata disease in July 1959. Food to which factory wastewater had been added was fed to healthy cats. Seventy-eight days into the experiment, cat 400 exhibited symptoms of Minamata disease and pathological examinations confirmed a diagnosis of organic mercury poisoning. Chisso did not reveal these significant results to the investigators and ordered Hosokawa to stop his research.In an attempt to undermine Kumadai researchers organic mercury theory, Chisso and other parties with a vested interest that the factory remain open (including the Ministry of International Trade and Industry and the Japan Chemical Industry Association) funded research into alternative causes of the disease, other than its own waste.

Compensation of fishermen and patients, 1959
Polluting wastewater had damaged the fisheries around Minamata ever since the opening of the Chisso factory in 1908. The Minamata Fishing Cooperative had managed to win small payments of "sympathy money" from the company in 1926 and again in 1943, but after the outbreak of Minamata disease, the fishing situation was becoming critical. Fishing catches had declined by 91% between 1953 and 1957. The Kumamoto prefectural government issued a partial ban on the sale of fish caught in the heavily polluted Minamata Bay – but not an all-out ban, which would have legally obliged it to compensate the fishermen. The fishing cooperative protested against Chisso and angrily forced their way into the factory on 6 August and 12 August, demanding compensation. A committee was set up by Minamata Mayor Todomu Nakamura to mediate between the two sides, but this committee was stacked heavily in the companys favour. On 29 August, the fishing cooperative agreed to the mediation committees proposal, stating: "In order to end the anxiety of the citizens, we swallow our tears and accept". Chisso paid the cooperative ¥20 million (US$183,477 — about US$1.7 million in 2021 value) and set up a ¥15 million ($137,608 — about 1.25 million today) fund to promote the recovery of fishing.

Since the change of route of wastewater output in 1958, pollution had spread up and down the Shiranui Sea, damaging fisheries there as well. Emboldened by the success of the small Minamata cooperative, the Kumamoto Prefectural Alliance of Fishing Cooperatives also decided to seek compensation from Chisso. On 17 October, 1,500 fishermen from the alliance descended on the factory to demand negotiations. When this produced no results, the alliance members took their campaign to Tokyo, securing an official visit to Minamata by members of the Japanese Diet. During the visit on 2 November, alliance members forced their way into the factory and rioted, causing many injuries and ¥10 million ($100,000) worth of damage. The violence was covered widely in the media, bringing the nations attention to the Minamata issue for the first time since the outbreak began. Another mediation committee was set up, and an agreement was hammered out and signed on 17 December. Some ¥25 million of "sympathy money" was paid to the alliance and a ¥65 million fishing recovery fund was established.
In 1959, the people with  Minamata disease were in a much weaker position than the fishermen. The recently formed Minamata Disease Patients Families Mutual Aid Society was much more divided than the fishing cooperatives. Patients families were the victims of discrimination and ostracism from the local community. Local people felt that the company (and their city that depended upon it) was facing economic ruin. To some patients, this ostracism by the community represented a greater fear than the disease itself. After beginning a sit-in at the Chisso factory gates in November 1959, the patients asked Kumamoto Prefecture Governor Hirosaku Teramoto to include the patients request for compensation with the mediation that was ongoing with the prefectural fishing alliance. Chisso agreed and after a few weeks further negotiation, another "sympathy money" agreement was signed. Patients who were certified by a Ministry of Health and Welfare committee would be compensated: adult patients received ¥100,000 ($917) per year; children ¥30,000 ($275) per year, and families of dead patients would receive a one-off ¥320,000 ($2935) payment.

Wastewater treatment
On 21 October 1959, Chisso was ordered by the Ministry of International Trade and Industry to switch back its wastewater drainage from the Minamata River to Hyakken Harbour and to speed up the installation of wastewater treatment systems at the factory. Chisso installed a Cyclator purification system on 19 December 1959, and opened it with a special ceremony. Chissos president Kiichi Yoshioka drank a glass of water supposedly treated through the Cyclator to demonstrate that it was safe. In fact, the wastewater from the factory, which the company knew still contained mercury and led to Minamata disease when fed to cats, was not being treated through the Cyclator at the time. Testimony at a later Niigata Minamata disease trial proved that Chisso knew the Cyclator to be completely ineffective: "The purification tank was installed as a social solution and did nothing to remove organic mercury."The deception was successful and almost all parties involved in Minamata disease were duped into believing that the factorys wastewater had been made safe from December 1959 onward. This widespread assumption meant that doctors were not expecting new patients to appear, resulting in numerous problems in the years to follow as the pollution continued. In most peoples minds, the issue of Minamata disease had been resolved.

1959–1969
The years between the first set of "sympathy money" agreements in 1959 and the start of the first legal action to be taken against Chisso in 1969 are often called the "ten years of silence". In fact, much activity on the part of the patients and fishermen took place during this period, but nothing had a significant impact on the actions of the company or the coverage of Minamata in the Japanese media.

Continued pollution
Despite the almost universal assumption to the contrary, the wastewater treatment facilities installed in December 1959 had no effect on the level of organic mercury being released into the Shiranui Sea. The pollution and the disease it caused continued to spread. The Kumamoto and Kagoshima prefectural governments conducted a joint survey in late 1960 and early 1961 into the level of mercury in the hair of people living around the Shiranui Sea. The results confirmed that organic mercury had spread all around the inland sea and that people were still being poisoned by contaminated fish. Hundreds of people were discovered to have levels greater than 50 ppm of mercury in their hair, the level at which people are likely to experience nerve damage. The highest result recorded was that of a woman from Goshonoura island who had 920 ppm in her sample.
The prefectural governments did not publish the results and did nothing in response to these surveys. The participants who had donated hair samples were not informed of their result, even when they requested it. A follow-up study ten years later discovered that many had died from "unknown causes".

Congenital Minamata disease
Local doctors and medical officials had noticed for a long time an abnormally high frequency of cerebral palsy and other infantile disorders in the Minamata area. In 1961, a number of medical professionals, including Masazumi Harada (later to be honored by the United Nations for his body of work on Minamata disease), set about re-examining children diagnosed with cerebral palsy. The symptoms of the children closely mirrored those of adult Minamata disease patients, but many of their mothers did not exhibit symptoms. The fact that these children had been born after the initial outbreak and had never been fed contaminated fish also led their mothers to believe they were not victims. At the time the medical establishment believed the placenta would protect the foetus from toxins in the bloodstream, which is indeed the case with most chemicals. What was not known at the time was that exactly the opposite is the case with methylmercury: the placenta removes it from the mothers bloodstream and concentrates the chemical in the foetus.
After several years of study and the autopsies of two children, the doctors announced that these children had an as-yet unrecognised congenital form of Minamata disease. The certification committee convened on 29 November 1962 and agreed that the two dead children and the sixteen children still alive should be certified as patients, and therefore liable for "sympathy" payments from Chisso, in line with the 1959 agreement.

Outbreak of Niigata Minamata disease
Minamata disease broke out again in 1965, this time along the banks of the Agano River in Niigata Prefecture. The polluting factory (owned by Showa Denko) employed a chemical process using a mercury catalyst very similar to that used by Chisso in Minamata. As in Minamata, from the autumn of 1964 to the spring of 1965, cats living along the banks of the Agano River had been seen to go mad and die. Before long, patients appeared with identical symptoms to patients living on the Shiranui Sea, and the outbreak was made public on 12 June 1965. Researchers from the Kumamoto University Research Group and Hajime Hosokawa (who had retired from Chisso in 1962) used their experience from Minamata and applied it to the Niigata outbreak. In September 1966, a report was issued proving Showa Denkos pollution to be the cause of this second Minamata disease outbreak.
Unlike the patients in Minamata, the victims of Showa Denkos pollution lived a considerable distance from the factory and had no particular link to the company. As a result, the local community was much more supportive of patients groups and a lawsuit was filed against Showa Denko in March 1968, only three years after discovery.
The events in Niigata catalysed a change in response to the original Minamata incident. The scientific research carried out in Niigata forced a re-examination of that done in Minamata and the decision of Niigata patients to sue the polluting company allowed the same response to be considered in Minamata. Masazumi Harada has said that, "It may sound strange, but if this second Minamata disease had not broken out, the medical and social progress achieved by now in Kumamoto... would have been impossible."Around this time, two other pollution-related diseases were also grabbing headlines in Japan. People with Yokkaichi asthma and itai-itai disease were forming citizens groups and filed lawsuits against the polluting companies in September 1967 and March 1968, respectively. As a group, these diseases came to be known as the four big pollution diseases of Japan.Slowly but surely, the mood in Minamata and Japan as a whole was shifting. Minamata patients found the public gradually becoming more receptive and sympathetic as the decade wore on. This culminated in 1968 with the establishment in Minamata of the Citizens Council for Minamata Disease Countermeasures, which was to become the chief citizens support group to the Minamata patients. A founding member of the citizens council was Michiko Ishimure, a local housewife and poet who later that year published Pure Land, Poisoned Sea: Our Minamata disease, a book of poetic essays that received national acclaim.

1969–1973
Official government recognition
Finally on 26 September 1968 – twelve years after the discovery of the disease (and four months after Chisso had stopped production of acetaldehyde using its mercury catalyst) – the Japanese government issued an official conclusion as to the cause of Minamata disease:

Minamata disease is a disease of the central nervous system, a poisoning caused by long-term consumption, in large amounts, of fish and shellfish from Minamata Bay. The causative agent is methylmercury. Methylmercury produced in the acetaldehyde acetic acid facility of Shin Nihon Chissos Minamata factory was discharged in factory wastewater... Minamata disease patients last appeared in 1960, and the outbreak has ended. This is presumed to be because consumption of fish and shellfish from Minamata Bay was banned in the fall of 1957, and the fact that the factory had waste-treatment facilities in place from January 1960.
The conclusion contained many factual errors: eating fish and shellfish from other areas of the Shiranui Sea, not just Minamata Bay, could cause the disease; eating small amounts, as well as large amounts of contaminated fish over a long time also produced symptoms; the outbreak had not, in fact, ended in 1960 nor had mercury-removing wastewater facilities been installed in January 1960. Nevertheless, the government announcement brought a feeling of relief to a great many victims and their families. Many felt vindicated in their long struggle to force Chisso to accept responsibility for causing the disease and expressed thanks that their plight had been recognised by their social superiors. The struggle now focused on to what extent the victims should be compensated.

Struggle for a new agreement
In light of the government announcement, the patients of the Mutual Aid Society decided to ask for a new compensation agreement with Chisso and submitted the demand on 6 October. Chisso replied that it was unable to judge what would be fair compensation and asked the Japanese government to set up a binding arbitration committee to decide. This proposal split the members of the patients society, many of whom were extremely wary of entrusting their fate to a third party, as they had done in 1959 with unfortunate results. At a meeting on the 5 April 1969, the opposing views within the society could not be reconciled and the organisation split into the pro-arbitration group and the litigation group (who decided to sue the company). That summer, Chisso sent gifts to the families who opted for arbitration rather than litigation.

An arbitration committee was duly set up by the Ministry of Health and Welfare on 25 April, but it took almost a year to draw up a draft compensation plan. A newspaper leak in March 1970 revealed that the committee would ask Chisso to pay only ¥2 million ($5,600) for dead patients and ¥140,000 to ¥200,000 ($390 to $560) per year to surviving patients. The arbitration group were dismayed by the sums on offer. They petitioned the committee, together with patients and supporters of the litigation group, for a fairer deal. The arbitration committee announced their compensation plan on 25 May in a disorderly session at the Ministry of Health and Welfare in Tokyo. Thirteen protesters were arrested.
Instead of accepting the agreement as they had promised, the arbitration group asked for increases. The committee was forced to revise its plan and the patients waited inside the ministry building for two days while they did so. The final agreement was signed on 27 May. Payments for deaths ranged from ¥1.7 million to ¥4 million ($4,700 to $11,100), one-time payments from ¥1 million to ¥4.2 million ($2,760 to $11,660) and annual payments between ¥170,000 and ¥380,000 ($470 to $1,100) for surviving patients. On the day of the signing, the Minamata Citizens Council held a protest outside the Chisso factory gates. One of the Chisso trade unions held an eight-hour strike in protest at the poor treatment of the arbitration group by their own company.The litigation group, representing 41 certified patients (17 already deceased) in 28 families, submitted their suit against Chisso in the Kumamoto District Court on 14 June 1969. The leader of the group, Eizō Watanabe (a former leader of the Mutual Aid Society), declared, "Today, and from this day forth, we are fighting against the power of the state." Those who decided to sue the company came under fierce pressure to drop their lawsuits. One woman was visited personally by a Chisso executive and harassed by her neighbours. She was blackballed by the community, her familys fishing boat used without permission, their fishing nets were cut, and human faeces were thrown at her in the street.The litigation group and their lawyers were helped substantially by an informal national network of citizens groups that had sprung up around the country in 1969. The Associations to Indict those Responsible for Minamata Disease were instrumental in raising awareness and funds for the lawsuit. The Kumamoto branch, in particular, was especially helpful to the case. In September 1969, they set up a Trial Research Group, which included law professors, medical researchers (including Harada), sociologists and even Michiko Ishimure to provide useful material to the lawyers to improve their legal arguments. Their report, Corporate Responsibility for Minamata Disease: Chissos Illegal Acts, published in August 1970, formed the basis of the ultimately successful lawsuit.The trial lasted almost four years. The litigation groups lawyers sought to prove Chissos corporate negligence. Three main legal points had to be overcome to win the case. First, the lawyers had to show that methylmercury caused Minamata disease and that the companys factory was the source of pollution. The extensive research by Kumadai and the governments conclusion meant that this point was proved quite easily. Second, they needed to show that Chisso could and should have anticipated the effect of its wastewater and taken steps to prevent the tragedy (i.e., was the company negligent in its duty of care). Third, it had to disprove that the "sympathy money" agreement of 1959, which forbade the patients from claiming any further compensation, was a legally binding contract.
The trial heard from patients and their families, but the most important testimony came from Chisso executives and employees. The most dramatic testimony came from Hosokawa, who spoke on 4 July 1970 from his hospital bed where he was dying of cancer. Hosokawa explained his experiments with cats, including the infamous "cat 400", which developed Minamata disease after being fed factory wastewater. He also spoke of his opposition to the 1958 change in wastewater output route to Minamata River. Hosokawas testimony was backed up by a colleague who also told how Chisso officials had ordered them to halt their cat experiments in the autumn of 1959. Hosokawa died three months after giving his testimony. Former factory manager Eiichi Nishida admitted that the company put profits ahead of safety, resulting in dangerous working conditions and a lack of care with mercury. Former Chisso President Kiichi Yoshioka admitted that the company promoted a theory of dumped World War II explosives, though it knew it to be unfounded.
The verdict handed down on 20 March 1973 represented a complete victory for the patients of the litigation group:

The defendants factory was a leading chemical plant with the most advanced technology and ... should have assured the safety of its wastewater. The defendant could have prevented the occurrence of Minamata disease or at least have kept it at a minimum. We cannot find that the defendant took any of the precautionary measures called for in this situation whatsoever. The presumption that the defendant had been negligent from beginning to end in discharging wastewater from its acetaldehyde plant is amply supported. The defendant cannot escape liability for negligence.
The "sympathy money" agreement was found to be invalid and Chisso was ordered to make one-time payments of ¥18 million ($66,000) for each deceased patient and from ¥16 million to ¥18 million ($59,000 to $66,000) for each surviving patient. The total compensation of ¥937 million ($3.4 million) was the largest sum ever awarded by a Japanese court.

Uncertified patients fight to be recognised
While the struggles of the arbitration and litigation groups against Chisso were continuing, a new group of individuals with Minamata disease emerged. To qualify for compensation under the 1959 agreement, patients had to be officially recognised by various ad hoc certification committees according to their symptoms. However, in an effort to limit the liability and financial burden on the company, these committees were sticking to a rigid interpretation of Minamata disease. They required that patients must exhibit all symptoms of Hunter-Russell syndrome – the standard diagnosis of organic mercury poisoning at the time, which originated from an industrial accident in the United Kingdom in 1940. The committee certified only patients exhibiting explicit symptoms of the British syndrome, rather than basing their diagnosis on the disease in Japan. This resulted in many applicants being rejected by the committee, leaving them confused and frustrated.

Legacies
Epidemiology
As of March 2001, 2,265 victims had been officially certified and over 10,000 people had received financial compensation from Chisso, although they were not recognised as official victims. The issue of quantifying the impact of Minamata disease is complicated, as a full epidemiological study has never been conducted and patients were recognised only if they voluntarily applied to a certification council to seek financial compensation. Many individuals with Minamata disease faced discrimination and ostracism from the local community if they came out into the open about their symptoms. Some people feared the disease to be contagious, and many local people were fiercely loyal to Chisso, depending on the company for their livelihoods. In this atmosphere, those affected were reluctant to come forward and seek certification. Despite these factors, over 17,000 people have applied to the council for certification. Also, in recognising an applicant as having Minamata disease, the certification council qualified that patient to receive financial compensation from Chisso. For that reason, the council has always been under immense pressure to reject claimants and minimise the financial burden placed on Chisso. Rather than being a council of medical recognition, the decisions of the council were always affected by the economic and political factors surrounding Minamata and the Chisso corporation. Furthermore, compensation of the victims led to continued strife in the community, including unfounded accusations that some of the people who sought compensation did not actually have the disease. More properly, the impact should be called a criminal poisoning, not a clinical disease. These forms of obfuscation are commonly experienced by environmental victims in many countries.In 1978, the National Institute for Minamata Disease was established in Minamata. It consists of four departments: The Department of Basic Medical Science, The Department of Clinical Medicine, The Department of Epidemiology and The Department of International Affairs and Environmental Sciences. In 1986, The Institute became a WHO Collaborating Centre for Studies on the Health Effects of Mercury Compounds. The Institute seeks to improve medical treatment of Minamata disease patients and conducts research on mercury compounds and their impact on organisms as well as potential detoxification mechanisms. In April, 2008 the Institute invented a method for absorbing gaseous mercury in order to prevent air pollution and enable recycling of the metal.

Environmental protection
The movement for redress by Minamata victims and activists and the national outrage their movement elicited played a central role in the rise of environmental protection in Japan. The 1970 session of the Japanese Diet became remembered as the "Pollution Diet", as the Japanese government took action under rising pressure from the Minamata disease movement as well as other major environmental catastrophes such as Yokkaichi asthma and itai-itai disease. Fourteen new environmental laws were passed in a single session, giving Japan what at the time were the most stringent environmental protection laws in the world. These new laws included a Water Pollution Act and nationwide regulations of toxic discharges. The "polluter pays" principle was introduced. A national Environmental Agency, which later developed into the Ministry of Environment, was founded in 1971. National governmental expenditures on environmental issues almost doubled between 1970 and 1975 and tripled at the local government level.

Democratizing effects
According to historian Timothy S. George, the environmental protests that surrounded the disease appeared to aid in the democratization of Japan. When the first cases were reported and subsequently suppressed, the rights of the victims were not recognised, and they were given no compensation. Instead, the affected were ostracised from their community due to ignorance about the disease, as people were afraid that it was contagious.
The people directly impacted by the pollution of Minamata Bay were not originally allowed to participate in actions that would affect their future. Disease victims, fishing families, and company employees were excluded from the debate. Progress occurred when Minamata victims were finally allowed to come to a meeting to discuss the issue. As a result, postwar Japan took a small step toward democracy.
Through the evolution of public sentiments, the victims and environmental protesters were able to acquire standing and proceed more effectively in their cause. The involvement of the press also aided the process of democratization because it caused more people to become aware of the facts of Minamata disease and the pollution that caused it. However, although the environmental protests did result in Japan becoming more democratized, it did not completely rid Japan of the system that first suppressed the fishermen and individuals with Minamata disease.

Popular culture
Toshiko Akiyoshi, touched by the plight of the fishing village, wrote a jazz suite, "Minamata", that was to be the central piece of the Toshiko Akiyoshi-Lew Tabackin Big Bands 1976 album on RCA, Insights. The piece was constructed in three parts, to musically reflect the tragedy – "Peaceful Village", "Prosperity & Consequence", and "Epilogue". Akiyoshi used Japanese vocalists to sing the Japanese lyrics of a tone poem that were part of the composition. The album won many awards in jazz circles, including Downbeats best album award, largely on the strength of this piece, which brought some further attention to the tragedy. Insights (Toshiko Akiyoshi – Lew Tabackin Big Band)
The song "Kepone Factory" on Dead Kennedys In God We Trust, Inc. makes reference to the disaster in its chorus.
The song "The Disease of the Dancing Cats" by the band Bush on the album The Science of Things is in reference to the disaster.

Visual documentation
Photographic documentation of Minamata started in the early 1960s. One photographer who arrived in 1960 was Shisei Kuwabara, straight from university and photo school, who had his photographs published in Weekly Asahi as early as May 1960. The first exhibition of his photographs of Minamata was held in the Fuji Photo Salon in Tokyo in 1962, and the first of his book-length anthologies, Minamata Disease, was published in Japan in 1965. He has returned to Minamata many times since.A dramatic photographic essay by W. Eugene Smith brought world attention to Minamata disease. He and his Japanese wife lived in Minamata from 1971 to 1973. The most famous and striking photo of the essay, Tomoko and Mother in the Bath (1972), shows Ryoko Kamimura holding her severely deformed daughter, Tomoko, in a Japanese bath chamber. Tomoko was poisoned by methylmercury while still in the womb. The photo was very widely published. It was posed by Smith with the co-operation of Ryoko and Tomoko to dramatically illustrate the consequences of the disease. It has subsequently been withdrawn from circulation at the request of Tomokos family, so does not appear in recent anthologies of Smiths works. Smith and his wife were extremely dedicated to the cause of the people with  Minamata disease, closely documenting their struggle for recognition and right to compensation. Smith was himself attacked and seriously injured by Chisso employees in an incident in Goi, Ichihara city, near Tokyo on January 7, 1972, in an attempt to stop the photographer from further revealing the issue to the world. The 54-year-old Smith survived the attack, but his sight in one eye deteriorated and his health never fully recovered before his death in 1978. Johnny Depp plays W. Eugene Smith in Minamata (2020) a drama based on the book written by Smiths wife.
Japanese photographer Takeshi Ishikawa, who assisted Smith in Minamata, has since exhibited his own photographs documenting the disease. His photographs cover the years 1971 to the present, with Minamata victims as his subjects.The prominent Japanese documentary filmmaker Noriaki Tsuchimoto made a series of films, starting with Minamata: The Victims and Their World (1971) and including The Shiranui Sea (1975), documenting the incident and siding with the victims in their struggle against Chisso and the government.
Kikujiro Fukushima, a well-known Japanese photographer and journalist, published a series of photographs in 1980 concerning pollution in Japan, including Minamata disease. Some negatives of these photos are available on the website, and Kyodo News Images holds the rights to them.

Today
Minamata disease remains an important issue in contemporary Japanese society. Lawsuits against Chisso and the prefectural and national governments are still continuing and many regard the government responses to date as inadequate. The companys "historical overview" in its current website makes no mention of their role in the mass contamination of Minamata and the dreadful aftermath. Their 2004 Annual Report, however, reports an equivalent of about US$50 million (5,820 million yen) in "Minamata Disease Compensation Liabilities". From 2000 to 2003, the company also reported total compensation liabilities of over US$170 million. Their 2000 accounts also show that the Japanese and Kumamoto prefectural governments waived an enormous US$560 million in related liabilities. Their FY2004 and FY2005 reports refer to Minamata disease as "mad hatters disease", a term coined from the mercury poisoning experienced by hat-makers of the last few centuries (cf. Erethism).A memorial service was held at the Minamata Disease Municipal Museum on 1 May 2006 to mark 50 years since the official discovery of the disease. Despite bad weather, the service was attended by over 600 people, including Chisso chairman Shunkichi Goto and Environment Minister Yuriko Koike.On Monday, March 29, 2010, a group of 2,123 uncertified victims reached a settlement with the government of Japan, the Kumamoto Prefectural government, and Chisso Corporation to receive individual lump-sum payments of 2.1 million yen and monthly medical allowances.Most congenital patients are now in their forties and fifties and their health is deteriorating. Their parents, who are often their only source of care, are into their seventies or eighties or already deceased. Often, these patients find themselves tied to their own homes and the care of their family, effectively isolated from the local community. Some welfare facilities for patients do exist. One notable example is Hot House, a vocational training centre for congenital patients as well as other disabled people in the Minamata area. Hot House members are also involved in raising awareness of Minamata disease, often attending conferences and seminars as well as making regular visits to elementary schools throughout Kumamoto Prefecture.

See also
Heavy metal poisoning
Minamata Convention on Mercury
Ontario Minamata disease
Mercury in fish

References
Further reading
"Minamata Disease: The History and Measures", The Ministry of the Environment, (2002), retrieved 17 January 2007
"Minamata Disease Archives" by the National Institute for Minamata Disease, retrieved 29 October 2006
Harada, Masazumi. (1972). Minamata Disease. Kumamoto Nichinichi Shinbun Centre & Information Center/Iwanami Shoten Publishers. ISBN 4-87755-171-9 C3036
George, S. Timothy. (2001). Minamata: Pollution and the Struggle for Democracy in Postwar Japan. Harvard University Press. ISBN 0-674-00785-9
Ui, Jun. (1992). Industrial Pollution in Japan. United Nations University Press. ISBN 92-808-0548-7. Chapter 4, section IV
Smith, W. E. and Smith, A. M. (1975). Minamata. Chatto & Windus, Ltd. (London), ISBN 0-7011-2131-9
Eto, K., Marumoto, M. and Takeya, M. (2010) "The pathology of methylmercury poisoning (Minamata disease)", retrieved 7 December 2013
Oiwa, Keibo. (2001). Rowing the Eternal Sea: The Story of a Minamata Fisherman. Rowman & Littlefield Publishers. ISBN 0-7425-0021-7
Steingraber, Sandra. (2001). Having Faith: An Ecologist Journey to Motherhood </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Post-dural-puncture headache and explain in detail? [/INST] Post-dural-puncture headache (PDPH) is a complication of puncture of the dura mater (one of the membranes around the brain and spinal cord). The headache is severe and described as "searing and spreading like hot metal", involving the back and front of the head and spreading to the neck and shoulders, sometimes involving neck stiffness. It is exacerbated by movement and sitting or standing and is relieved to some degree by lying down. Nausea, vomiting, pain in arms and legs, hearing loss, tinnitus, vertigo, dizziness and paraesthesia of the scalp are also common.PDPH is a common side effect of lumbar puncture and spinal anesthesia. Leakage of cerebrospinal fluid causes reduced fluid levels in the brain and spinal cord. Onset occurs within two days in 66% of cases and three days in 90%. It occurs so rarely immediately after puncture that other possible causes should be investigated when it does.Using a pencil point needle rather than a cutting spinal needle decreases the risk. The size of the pencil point needle does not appear to make a difference. PDPH is estimated to occur in between 0.1% and 36% people following dural puncture.

Signs and symptoms
PDPH typically occurs hours to days after puncture and presents with symptoms such as headache (which is mostly bi-frontal or occipital) and nausea that typically worsen when the patient assumes an upright posture. The headache usually occurs 24–48 hours after puncture but may occur as many as 12 days after. It usually resolves within a few days but has been rarely documented to take much longer.

Pathophysiology
PDPH is thought to result from a loss of cerebrospinal fluid into the epidural space. A decreased hydrostatic pressure in the subarachnoid space then leads to traction to the meninges with associated symptoms.

Diagnosis
Differential diagnosis
Although in very rare cases the headache may present immediately after a puncture, this is almost always due to another cause such as increased intracranial pressure and requires immediate attention.

Prevention
Using a pencil point rather than a cutting spinal needle decreases the risk. The size of the pencil point needle does not appear to make a difference, while smaller cutting needles have a low risk compared to larger ones. Modern, atraumatic needles such as the Sprotte or Whitacre spinal needle leave a smaller perforation and reduce the risk for PDPH. However, the evidence that atraumatic needles reduce the risk of post-dural puncture headache (PDPH) without increasing adverse events such as paraesthesia or backache is moderate-quality and further research should be done.Morphine, cosyntropin, and aminophylline appear effective in reducing post dural puncture headaches. Evidence does not support the use of bed rest or intravenous fluids to prevent PDPH.

Treatment
Some people require no other treatment than pain medications and bed rest. A 2015 review found tentative evidence to support the use of caffeine. Vigorous hydration is routinely encouraged in postpartum patients as a noninvasive, low-risk therapy.Pharmacological treatments as; gabapentin, pregabalin,  neostigmine/atropine,  methylxanthines, and triptans </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Sea-blue histiocytosis and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Hyperoxaluria and explain in detail? [/INST] Hyperoxaluria is an excessive urinary excretion of oxalate. Individuals with hyperoxaluria often have calcium oxalate kidney stones.  It is sometimes called Birds disease, after Golding Bird, who first described the condition.

Causes
Hyperoxaluria can be primary (as a result of a genetic defect) or secondary to another disease process.
Type I primary hyperoxaluria (PH1) is associated mutations in the gene encoding AGXT, a key enzyme involved in oxalate metabolism. PH1 is an example of a protein mistargeting disease, wherein AGXT shows a trafficking defect. Instead of being trafficked to peroxisomes, it is targeted to mitochondria, where it is metabolically deficient despite being catalytically active </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Aspartylglucosaminuria and explain in detail? [/INST] Aspartylglucosaminuria (AGU) is an inherited disease that is characterized by a decline in mental functioning, accompanied by an increase in skin, bone and joint issues.
The disease is caused by a defect in an enzyme known as aspartylglucosaminidase. This enzyme plays a significant role in our bodies because it aids in breaking down certain sugars (for example, oligosaccharides) that are attached to specific proteins (for example, glycoproteins). Aspartylglucosaminuria itself is characterized as a lysosomal disease because it does deal with inadequate activity in an enzymes function. Aspartylglucosaminidase functions to break down glycoproteins. These proteins are most abundant in the tissues of the body and in the surfaces of major organs, such as the liver, spleen, thyroid and nerves. When glycoproteins are not broken down, aspartylglucosaminidase backs up in the lysosomes along with other substances. This backup causes progressive damage to the tissues and organs.

Signs and symptoms
At birth, there is no sign that a child will develop symptoms of aspartylglucosaminuria. Typically, signs and symptoms become apparent between two and four years of age and become progressively worse as the individual ages. The following signs and symptoms  may appear:

Individuals are more prone to respiratory infections
Development of scoliosis
Seizures or difficulty with movement
Skin and joints may become loose
Facial features change progressively; this may include:thickening of the skin
features becoming more prominent
large head
broad lower jaw
short, broad nose
rounded cheeksProgression of developmental and mental disabilities, including:progressive loss of speech
decrease in mental functioning
before school age, concentration lowers
development continues, but becomes slower than usualAn intellectual peak occurs in the mid-teens and allows a plateau for the disease. Once an individual hits the age of 25-30 the decrease begins again, including:learned skills become lost which result in severe learning disabilities
motor skills deteriorate
individuals become less mobile and more dependent(Children are physically uncoordinated, but remain able to play sports and do everyday activities until they reach adulthood.)

During the first year of life inguinal and umbilical hernias are common.
Less severe symptoms include:enlargement of the spleen and liver
diarrheaPeople with aspartylglucosaminuria may have lower than average height, because they tend to go through puberty earlier.
Epilepsy may develop in adulthood.
Finnish studies have shown that life expectancy is shorter than average.

Genetics
Aspartylglucosaminuria is an autosomal recessive genetic condition that is inherited from both parents. The AGU patient is born with two copies of the mutated AGA gene. One copy comes from the mother’s egg and the other copy comes from the father’s sperm. In order to develop aspartylglucosaminuria, the individual must inherit changes in both of his AGU genes (autonomic recessive inheritance). When a person receives one changed form of the gene AGU from one of the parents, the individual is then classified as a carrier.

Diagnosis
In order to be diagnosed with AGU an individual takes a urine test, which will show indication of an increased amount of aspartylglucosamin being secreted. The confirmation of the diagnosis of aspartylglucosaminuria requires a blood test. This helps show if the enzyme aspartylglucosaminidase is present or partially absent. A skin simple will also show the amount of aspartylglucosaminidase present.

Pre-natal diagnosis
When families have a child who has already been diagnosed with AGU, they have the option to observe the enzymes activity that codes for AGU in future pregnancy, to help determine if the next child will also have a positive diagnosis for aspartylglucosaminuria.

Treatment
No treatment is available to cure or slow down the progression of aspartylglucosaminuria. Bone marrow transplants have been conducted in hope that the bone marrow will produce the missing enzyme. The results of the tests thus far have shown to be inconclusive.

Preventions/interventions to signs and symptoms
Since ear infections and respiratory infections are common for children diagnosed with aspartylglucosaminuria, it is best to have regular checkups for both the ears and the respiratory tract.Extreme sensitivity to the sun’s rays may develop; the best way to protect an individual diagnosed with aspartylglucosaminuria is to have them wear sunglasses, hats or caps to protect their eyes.Epilepsy and insomnia can both be treated with medication.It will be beneficial to children who are diagnosed with AGU to receive an education from a school with special teaching.

Habilitation
The process of habilitation for individuals diagnosed with AGU needs to be established in their early stages of life </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Persistent left superior vena cava and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Cogan syndrome and explain in detail? [/INST] Cogan syndrome (also Cogans syndrome) is a rare disorder characterized by recurrent inflammation of the front of the eye (the cornea) and often fever, fatigue, and weight loss, episodes of vertigo (dizziness), tinnitus (ringing in the ears) and hearing loss. It can lead to deafness or blindness if untreated. The classic form of the disease was first described by D. G. Cogan in 1945.

Signs and symptoms
Cogan syndrome is a rare, rheumatic disease characterized by inflammation of the ears and eyes. Cogan syndrome can lead to vision difficulty, hearing loss and dizziness. The condition may also be associated with blood-vessel inflammation (called vasculitis) in other areas of the body that can cause major organ damage in 15% of those affected or, in a small number of cases, even death. It most commonly occurs in a persons 20s or 30s. The cause is not known. However, one theory is that it is an autoimmune disorder in which the bodys immune system mistakenly attacks tissue in the eye and ear.

Causes
It is currently thought that Cogan syndrome is an autoimmune disease. The inflammation in the eye and ear are due to the patients own immune system producing antibodies that attack the inner ear and eye tissue. Autoantibodies can be demonstrated in the blood of some patients, and these antibodies have been shown to attack inner ear tissue in laboratory studies. Infection with the bacteria Chlamydia pneumoniae has been demonstrated in some patients prior to the development of Cogan syndrome, leading some researchers to hypothesize that the autoimmune disease may be initiated by the infection. C. pneumoniae is a common cause of mild pneumonia, and the vast majority of patients who are infected with the bacteria do not develop Cogan syndrome.

Diagnosis
While the white blood cell count, erythrocyte sedimentation rate, and C-reactive protein tests may be abnormal and there may be abnormally high levels of platelets in the blood or too few red blood cells in the blood, none of these findings is a reliable indicator of the disease. A slit-lamp examination is essential. Recent work has suggested that high-resolution MRI and antibodies to inner ear antigens may be helpful. Cogan syndrome can occur in children, and is particularly difficult
to recognize in that situation.

Treatment
For more severe disease, oral corticosteroids may be necessary to reduce the inflammatory response. When large amounts of steroids are required or if the disease is severe and is not responding to steroid therapy, other immunosuppressive medications often are recommended. These immunosuppressive drugs include methotrexate, cyclophosphamide, cyclosporine or azathioprine. In some cases, combinations of these medicines are prescribed. Occasionally, if the disease has damaged blood vessels in the ear, cochlear implantation may be used to restore some sense of hearing.Cinnarizine is mainly used to treat nausea and vomiting associated with motion sickness, vertigo, Ménières disease, or Cogan syndrome. Studies have shown it to produce significant improvement in hearing loss in some patients.

History
In 1945, the ophthalmologist David Glendenning Cogan (1908–1993) first described the "nonsyphilitic interstitial keratitis and vestibuloauditory symptoms" that would later bear his name. In 1963, the atypical form of Cogan syndrome, also known as "Logan Syndrome" was first described.

References
Further reading
Haynes BF, Kaiser-Kupfer MI, Mason P, Fauci AS (November 1980). "Cogan syndrome: studies in thirteen patients, long-term follow-up, and a review of the literature". Medicine. 59 (6): 426–41. doi:10.1097/00005792-198011000-00003. PMID 6969345.
Gluth MB, Baratz KH, Matteson EL, Driscoll CL (April 2006). "Cogan syndrome: a retrospective review of 60 patients throughout a half century". Mayo Clinic Proceedings. 81 (4): 483–8. doi:10.4065/81.4.483. PMID 16610568.
Norton EW, Cogan DG (May 1959). "Syndrome of nonsyphilitic interstitial keratitis and vestibuloauditory symptoms; a long-term follow-up". Archives of Ophthalmology. 61 (5): 695–7. doi:10.1001/archopht.1959.00940090697004. PMID 13636563.
Bicknell JM, Holland JV (March 1978). "Neurologic manifestations of Cogan syndrome". Neurology. 28 (3): 278–81. doi:10.1212/wnl.28.3.278. PMID 305011. S2CID 22367876.
Casselman JW, Majoor MH, Albers FW (January 1994). "MR of the inner ear in patients with Cogan syndrome". American Journal of Neuroradiology. 15 (1): 131–8. PMC 8332073. PMID 8141044.
Allen NB, Cox CC, Cobo M,  et al. (March 1990) </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Fracture blister and explain in detail? [/INST] Fracture blisters occur on skin overlying a fractured bone, and fractures complicated by the development of overlying blisters remain a clinical dilemma in orthopedics.: 43 Fracture blisters are tense vesicles or bullae that arise on markedly swollen skin directly overlying a fracture. Fracture blisters pop up in trauma patients occasionally. A fracture blister typically occurs near fractures where the skin has little subcutaneous tissue between it and bone </s>