<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 Encephalocele and can you explain it in depth? [/INST] Encephalocele is a neural tube defect characterized by sac-like protrusions of the brain and the membranes that cover it through openings in the skull. These defects are caused by failure of the neural tube to close completely during fetal development. Encephaloceles cause a groove down the middle of the skull, or between the forehead and nose, or on the back side of the skull. The severity of encephalocele varies, depending on its location.

Signs and symptoms
Encephaloceles are often accompanied by craniofacial abnormalities or other brain malformations. Symptoms may include neurologic problems, hydrocephalus (cerebrospinal fluid accumulated in the brain), spastic quadriplegia (paralysis of the limbs), microcephaly (an abnormally small head), ataxia (uncoordinated muscle movement), developmental delay, vision problems, mental and growth retardation, and seizures.

Causes
Since its earliest cited case in the 16th century, many generations of scientists have attempted to explain the cause. Little has been revealed in the centuries to follow. Although the exact cause is unknown, encephaloceles are caused by failure of the neural tube to close completely during fetal development. Both environmental and genetic factors have been seen to contribute to the cause of encephaloceles. Some studies have revealed a higher occurrence in female embryos, suggesting a genetic cause. Research has indicated that teratogens (substances known to cause birth defects), trypan blue (a stain used to color dead tissues or cells blue), and arsenic may damage the developing fetus and cause encephaloceles.Proper levels of folic acid have been shown to help prevent such defects when taken before pregnancy, and early in pregnancy.Occipital encephaloceles are frequently accompanied by hydrocephalus, as seen in 60-90% of patients.

Diagnosis
Usually encephaloceles are noticeable deformities and are diagnosed immediately after birth, but a small encephalocele in the nasal or forehead region can go undetected. Various physical and mental developmental delays can indicate the presence of encephaloceles.

Classifications
Encephaloceles of the face are generally classified as nasofrontal, nasoethmoidal, or naso-orbital, however, there can be some overlap in the type of encephalocele. They can also appear along any part of the cranial vault, as they result from abnormal closure of cranial bones; the most common location for encephaloceles is the occipital region.   If the bulging portion contains only cerebrospinal fluid and the overlying membrane, it may be called a meningocele. If brain tissue is present, it may be referred to as a meningoencephalocele. When the head size or occipitofrontal circumference is smaller than the herniating sac, then it is termed as giant encephalocele.Separation of the neural and surface ectoderm causes apoptosis in the midline. A disturbance in this separation process at the final closure due to the lack of apoptosis is considered to be a critical aspect of nasofrontal and nasoethmoidal encephalocele.

Prevention
It is recommended that women take a multivitamin with 400 micrograms of folic acid daily to reduce the likelihood of any type of neural tube defects before and during the first 28 days after conception.

Treatment
A series of steps involved in reconstructive surgery of a frontal encephalocele. The same child is in all the images.

Currently, the only effective treatment for encephaloceles is reparative surgery, generally performed during infancy. The extent to which it can be corrected depends on the location and size of the encephaloceles; however, large protrusions can be removed without causing major disability. Surgery repositions the bulging area back into the skull, removes the protrusions, and corrects the deformities, typically relieving pressure that can delay normal brain development. Occasionally, shunts are placed to drain excess cerebrospinal fluid from the brain.The goals of treatment include:

closure of open skin defects to prevent infection and desiccation of brain tissue
removal of nonfunctional extracranial cerebral tissue with water-tight closure of the dura
total craniofacial reconstruction with particular emphasis on avoiding the long-nose deformity (nasal elongation that results from depression of the cribiform plate and nasal placode). Without proper management, the long-nose deformity can be more obvious after repair.

Recovery
Recovery is difficult to predict prior to surgery, and depends on the type of brain tissue involved and location of the encephaloceles. If surgery is successful, and developmental delays have not occurred, a patient can develop normally. Where neurologic and developmental damage has occurred, the specialists will focus on minimizing both mental and physical disabilities.In general, when the bulging material consists of primarily cerebrospinal fluid, a complete recovery can occur. When a large amount of brain tissue is present in the encephaloceles, there is a higher chance of perioperative complication.

Epidemiology
Encephaloceles occur rarely, at a rate of one per 5,000 live births worldwide. Encephaloceles of the back of the head are more common in Europe and North America, while encephaloceles on the front of the head more frequently occur in Southeast Asia, Africa, Malaysia, and Russia. Ethnic, genetic, and environmental factors, as well as parental age, can all affect the likelihood of encephaloceles. The condition can occur in families with a family history of spina bifida.

Notable cases
The Facemakers: Operation Smile is a documentary co-produced by the Discovery Channel and BBC 1 in conjunction with century films aired on 21 June 2000. The Facemakers documents the remarkable changes that occurred in the lives of three children as a result of Operation Smiles visit to Davao City in the Philippines in 1999.  One child in particular, Abel Gastardo, had a condition too severe to be treated during the time of the mission </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 Nuchal fibroma and can you explain it in depth? [/INST] Nuchal-type fibroma is a rare benign proliferation involving the dermis and subcutaneous tissues, that is a collection of dense, hypocellular bundles of collagen with entrapped adipocytes and increased numbers of small nerves. It is no longer called a nuchal fibroma, but instead a "nuchal-type fibroma" since it develops in other anatomic sites. There is no known etiology. The World Health Organization, 2020, classified nuchal fibromas as a specific tumor form in the category of benign fibroblastic and myofibroblastic tumors.

Signs and symptoms
These lesions are generally asymptomatic, although patients give a long history of a solitary, superficial mass. The mass is usually in the neck (hence the name "nuchal-type"), but it can be seen in the extremities, lumbosacral area, buttocks, and face.
There is a strong association with diabetes mellitus and Gardner syndrome; in fact, it may be the initial manifestation of Gardner syndrome.

Pathology
The tumors are unencapsulated and poorly circumscribed, showing a firm, white cut surface. Most tumors are about 3.5 cm, but can be up to 8 cm.
By microscopic examination, there are haphazardly arranged thick collagen fibers, with a low cellularity and no pleomorphism. There are usually entrapped fat cells, skeletal muscle, and peripheral nerves. The may be perineural fibrosis. The elastic fibers may be altered, which is why an elastofibroma is considered in the differential diagnosis.

Immunohistochemistry
The tumor cells are strongly positive for vimentin, CD34, and sometimes with CD99. There is often (up to 2/3rds) a nuclear reaction with β-catenin.

Diagnosis
Differential diagnoses
The differential diagnosis includes elastofibroma, fibrolipoma, desmoid-type fibromatoses, and nuchal fibrocartilaginous pseudotumor.

Management
Simple excision is curative. However, in patients with Gardner syndrome, up to 45% will develop desmoid-type fibromatosis at other sites, and so this should be searched for and excluded. Patients can develop a recurrence, so follow-up is required.

Epidemiology
This is a rare tumor, presenting over a wide age range, but usually in the 3rd to 5th decades of life </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 Lichen myxedematosus and can you explain it in depth? [/INST]  </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 WDR45 and can you explain it in depth? [/INST]  </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 Fiddlers neck and can you explain it in depth? [/INST] Fiddlers neck is an occupational disease that affects violin and viola players.It is a cutaneous condition usually characterized by redness, thickening, and inflammation on the left side of the neck below the angle of the jaw where the instrument is held. Acne-like lesions and cysts may form at the site due to foreign body reactions, and infections may also occur due to poor hygiene. The primary causes of fiddlers neck are constant friction and local pressure. It is well known among professional orchestra musicians but is "not well recognized by dermatologists", and a red mark on the left side of the neck under the jaw "functions as an identifying sign" of a violinist or violist "in public without seeing the instrument".
Although the presence of fiddlers neck is sometimes used as an indicator of a violinists skill, or battle scars from constant practice, many violinists never develop fiddlers neck, due to differences in skin sensitivity, playing habits, and the materials used in the construction of the instrument. An accomplished professional player could practice hard their whole life and never develop fiddlers neck.

Signs and symptoms
Fiddlers neck usually involves highly localized lichenification, mild hyperpigmentation, and erythema where the chin rest or instrument body presses against the skin of the neck. Other signs and symptoms include scale buildup, cyst and scar formation, papules and pustules related to local infection, and focal edema. In Blum & Ritters study in West Germany (1990), they found that 27% of their population had only minor issues, 72% had a palpable mass at the site, and 23% reported pain and other signs of inflammation such as hyperthermia, pulsation, and cystic, pustular, or papular lesions. Size of masses were an average of 2 cm in diameter ranging up to 4 cm, some being associated with purulent drainage, continuous discharge, and crusting. Dystrophic calcinosis cutis has also been reported. Other serious sequelae include sialolithiasis of the submandibular gland and adenolymphoma of the parotid gland.The histopathology of fiddlers neck frequently shows hyperkeratosis and acanthosis, along with plugging of follicles. Histiocytic infiltration with granulomas to foreign body and follicular cysts are also common. Foreign body granulomas are thought to derive from abrasion of the wooden surface of the chin rest and its absorption into the superficial dermis. The location and complex mechanism of causation for fiddlers neck give rise to a wider spectrum of skin changes when compared to contact dermatitis from more common irritants. Fiddlers neck can be differentiated from rosacea and sarcoid reaction with granulomas.

Causes
The proximal causes of fiddlers neck are friction and pressure, but both repetitive shearing stress and occlusion with consequent trapping of sweat give rise to progressive damage. This damage along with poor hygiene predisposes the area to local infection, and such infection can progress to scarring and other long-term effects. Hot weather is reported to exacerbate fiddlers neck, as are tiredness, playing emotional music, and playing in smaller groups where individual stress is higher. Type I hypersensitivity reactions may also be involved, particularly to rosewood and ebony in the chinrest and tailpiece, as well as to varnish of the instrument body when chinrests are not used and to rosin deposits on the instrument and on chin cloths. Nickel or other metal allergies are common causes if the chin rest has a metal clip that comes into constant contact with the skin. Rosin exposure in particular may lead to abietic acid dermatitis.

Diagnosis
Differential diagnoses
The differential diagnoses of fiddlers neck include branchial cleft cyst, disease of the salivary glands, tumors of the parotid gland, psoriasis, lichen planus, contact dermatitis, herpes simplex and similar infections, and insect bites and stings especially from fleas.

Treatment
Treatment for fiddlers neck is unnecessary if it is painless and shows minimal swelling, particularly since minor cases are taken as a mark of pride. But fiddlers neck may lead to worse disorders. The primary methods of treatment involve adjustments to playing of the instrument:
good hygiene for the affected area and for the instrument
use of a clean cotton cloth that is changed frequently
use of a comfortable pad to absorb sweat and reduce friction between the instrument and skin
use of a shoulder rest to reduce pressure below the jaw
a suitable chin rest, especially one carved or molded for the individual
covering or changing potentially allergenic materials on the instrument.
shifting the chin rest to the center of the body over the tailpiece
smoothing coarse surfaces to reduce abrasion
for males, growing a beard to avoid folliculitisSurgery is necessary for sialolithiasis, parotid tumors, and cysts </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 Dysphagia lusoria and can you explain it in depth? [/INST]  </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 Haemodialysis-associated amyloidosis and can you explain it in depth? [/INST] Amyloidosis is the accumulation on misfolded protein fibers in the body </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 Morphea and can you explain it in depth? [/INST] Morphea is a form of scleroderma that involves isolated patches of hardened skin on the face, hands, and feet, or anywhere else on the body, with no internal organ involvement.: 130

Signs and symptoms
Morphea most often presents as macules or plaques a few centimeters in diameter, but also may occur as bands or in guttate lesions or nodules.: 171 Morphea is a thickening and hardening of the skin and subcutaneous tissues from excessive collagen deposition.  Morphea includes specific conditions ranging from very small plaques only involving the skin to widespread disease causing functional and cosmetic deformities.  Morphea discriminates from systemic sclerosis by its supposed lack of internal organ involvement.  This classification scheme does not include the mixed form of morphea in which different morphologies of skin lesions are present in the same individual.  Up to 15% of morphea patients may fall into this previously unrecognized category.

Cause
Physicians and scientists do not know what causes morphea. Case reports and observational studies suggest there is a higher frequency of family history of autoimmune diseases in patients with morphea. Tests for autoantibodies associated with morphea have shown results in higher frequencies of anti-histone and anti-topoisomerase IIa antibodies. Case reports of morphea co-existing with other systemic autoimmune diseases such as primary biliary cirrhosis, vitiligo, and systemic lupus erythematosus lend support to morphea as an autoimmune disease.Borrelia burgdorferi infection may be relevant for the induction of a distinct autoimmune type of scleroderma; it may be called "Borrelia-associated early onset morphea" and is characterized by the combination of disease onset at younger age, infection with B. burgdorferi, and evident autoimmune phenomena as reflected by high-titer antinuclear antibodies.

Diagnosis
Classification
Morphea–lichen sclerosus et atrophicus overlap is characterized by both lesions of morphea and lichen sclerosus et atrophicus, most commonly seen in women.: 171
Generalized morphea is characterized by widespread indurated plaques and pigmentary changes, sometimes associated with muscle atrophy, but without visceral involvement.: 171
Morphea profunda involves deep subcutaneous tissue, including fascia, and there is a clinical overlap with eosinophilic fasciitis, eosinophilia-myalgia syndrome, and the Spanish toxic oil syndrome.: 171   Morphea profunda shows little response to corticosteroids and tends to run a more chronic debilitating course.: 171
Pansclerotic morphea is manifested by sclerosis of the dermis, panniculus, fascia, muscle, and at times, the bone, all causing disabling limitation of motion of joints.: 171
Linear scleroderma is a type of localised scleroderma which is an autoimmune disease characterized by a line of thickened skin which can affect the bones and muscles underneath it. It most often occurs in the arms, legs, or forehead, and may occur in more than one area.  It is also most likely to be on just one side of the body. Linear scleroderma generally first appears in young children.
Frontal linear scleroderma (also known as en coup de sabre or morphea en coup de sabre) is a type of linear scleroderma characterized by a linear band of atrophy and a furrow in the skin that occurs in the frontal or frontoparietal scalp.  Multiple lesions of en coup de sabre may coexist in a single patient, with one report suggesting that the lesions followed Blaschkos lines. It gets its name from the perceived similarity to a sabre wound.
Atrophoderma of Pasini and Pierini (also known as "Dyschromic and atrophic variation of scleroderma," "Morphea plana atrophica," "Sclérodermie atrophique demblée") is a disease characterized by large lesions with a sharp peripheral border dropping into a depression with no outpouching, which, on biopsy, elastin is normal, while collagen may be thickened. Atrophoderma of Pasini and Pierini affects less than 200,000 Americans and is classified as a rare disease by http://rarediseases.info.nih.gov.  The disease results in round or oval patches of hyper-pigmented skin. The darkened skin patches may sometimes have a bluish or purplish hue when they first appear and are often smooth to the touch and hairless.

Treatment
Throughout the years, many different treatments have been tried for morphea including topical, intra-lesional, and systemic corticosteroids.  Antimalarials such as hydroxychloroquine or chloroquine have been used.  Other immunomodulators such as methotrexate, topical tacrolimus, and penicillamine have been tried. Children and teenagers with active morphea (linear scleroderma, generalised morphea and mixed morphea: linear and circumscribed) may experience greater improvement of disease activity or damage with oral methotrexate plus prednisone than with placebo plus prednisone.  Some have tried prescription vitamin-D with success. Ultraviolet A (UVA) light, with or without psoralens have also been tried.  UVA-1, a more specific wavelength of UVA light, is able to penetrate the deeper portions of the skin and thus, thought to soften the plaques in morphea by acting in two fashions: by causing a systemic immunosuppression from UV light, or by inducing enzymes that naturally degrade the collagen matrix in the skin as part of natural sun-aging of the skin. [1] However, there is limited evidence that UVA‐1 (50 J/cm2), low‐dose UVA‐1 (20 J/cm2), and narrowband UVB differ from each other in effectiveness in treating children and adults with active morphea.

Epidemiology
Morphea is a form of scleroderma that is more common in women than men, in a ratio 3:1. Morphea occurs in childhood as well as in adult life </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 Nonvenereal endemic syphilis and can you explain it in depth? [/INST]  </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 Diabetes and can you explain it in depth? [/INST] Diabetes mellitus, commonly known as diabetes, is a group of metabolic disorders characterized by a high blood sugar level (hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased appetite. If left untreated, diabetes can cause many health complications. Acute complications can include diabetic ketoacidosis, hyperosmolar hyperglycemic state, or death. Serious long-term complications include cardiovascular disease, stroke, chronic kidney disease, foot ulcers, damage to the nerves, damage to the eyes and cognitive impairment.Diabetes is due to either the pancreas not producing enough insulin, or the cells of the body not responding properly to the insulin produced. Insulin is a hormone which is responsible for helping glucose from food get into cells to be used for energy. There are three main types of diabetes mellitus:
Type 1 diabetes results from failure of the pancreas to produce enough insulin due to loss of beta cells. This form was previously referred to as "insulin-dependent diabetes mellitus" or "juvenile diabetes". The loss of beta cells is caused by an autoimmune response. The cause of this autoimmune response is unknown. Although Type 1 diabetes usually appears during childhood or adolescence, it can also develop in adults.
Type 2 diabetes begins with insulin resistance, a condition in which cells fail to respond to insulin properly. As the disease progresses, a lack of insulin may also develop. This form was previously referred to as "non insulin-dependent diabetes mellitus" or "adult-onset diabetes". Type 2 diabetes is more common in older adults, but a significant increase in the prevalence of obesity among children has led to more cases of type 2 diabetes in younger people. The most common cause is a combination of excessive body weight and insufficient exercise.
Gestational diabetes is the third main form, and occurs when pregnant women without a previous history of diabetes develop high blood sugar levels. In women with gestational diabetes, blood sugar usually returns to normal soon after delivery. However, women who had gestational diabetes during pregnancy have a higher risk of developing type 2 diabetes later in life.Type 1 diabetes must be managed with insulin injections. Prevention and treatment of type 2 diabetes involves maintaining a healthy diet, regular physical exercise, a normal body weight, and avoiding use of tobacco. Type 2 diabetes may be treated with oral antidiabetic medications, with or without insulin. Control of blood pressure and maintaining proper foot and eye care are important for people with the disease. Insulin and some oral medications can cause low blood sugar (hypoglycemia). Weight loss surgery in those with obesity is sometimes an effective measure in those with type 2 diabetes. Gestational diabetes usually resolves after the birth of the baby.As of 2019, an estimated 463 million people had diabetes worldwide (8.8% of the adult population), with type 2 diabetes making up about 90% of the cases. Rates are similar in women and men. Trends suggest that rates will continue to rise. Diabetes at least doubles a persons risk of early death. In 2019, diabetes resulted in approximately 4.2 million deaths. It is the 7th leading cause of death globally. The global economic cost of diabetes-related health expenditure in 2017 was estimated at US$727 billion. In the United States, diabetes cost nearly US$327 billion in 2017. Average medical expenditures among people with diabetes are about 2.3 times higher.

Signs and symptoms
The classic symptoms of untreated diabetes are unintended weight loss, polyuria (increased urination), polydipsia (increased thirst), and polyphagia (increased hunger). Symptoms may develop rapidly (weeks or months) in type 1 diabetes, while they usually develop much more slowly and may be subtle or absent in type 2 diabetes.Several other signs and symptoms can mark the onset of diabetes although they are not specific to the disease. In addition to the known symptoms listed above, they include blurred vision, headache, fatigue, slow healing of cuts, and itchy skin. Prolonged high blood glucose can cause glucose absorption in the lens of the eye, which leads to changes in its shape, resulting in vision changes. Long-term vision loss can also be caused by diabetic retinopathy. A number of skin rashes that can occur in diabetes are collectively known as diabetic dermadromes.

Diabetic emergencies
People with diabetes (usually but not exclusively in type 1 diabetes) may also experience diabetic ketoacidosis (DKA), a metabolic disturbance characterized by nausea, vomiting and abdominal pain, the smell of acetone on the breath, deep breathing known as Kussmaul breathing, and in severe cases a decreased level of consciousness. DKA requires emergency treatment in hospital. A rarer but more dangerous condition is hyperosmolar hyperglycemic state (HHS), which is more common in type 2 diabetes and is mainly the result of dehydration caused by high blood sugars.Treatment-related low blood sugar (hypoglycemia) is common in people with type 1 and also type 2 diabetes depending on the medication being used. Most cases are mild and are not considered medical emergencies. Effects can range from feelings of unease, sweating, trembling, and increased appetite in mild cases to more serious effects such as confusion, changes in behavior such as aggressiveness, seizures, unconsciousness, and rarely permanent brain damage or death in severe cases. Rapid breathing, sweating, and cold, pale skin are characteristic of low blood sugar but not definitive. Mild to moderate cases are self-treated by eating or drinking something high in rapidly absorbed carbohydrates. Severe cases can lead to unconsciousness and must be treated with intravenous glucose or injections with glucagon.

Complications
All forms of diabetes increase the risk of long-term complications. These typically develop after many years (10–20) but may be the first symptom in those who have otherwise not received a diagnosis before that time.The major long-term complications relate to damage to blood vessels. Diabetes doubles the risk of cardiovascular disease and about 75% of deaths in people with diabetes are due to coronary artery disease. Other macrovascular diseases include stroke, and peripheral artery disease. These complications are also a strong risk factor for severe COVID-19 illness.The primary complications of diabetes due to damage in small blood vessels include damage to the eyes, kidneys, and nerves. Damage to the eyes, known as diabetic retinopathy, is caused by damage to the blood vessels in the retina of the eye, and can result in gradual vision loss and eventual blindness. Diabetes also increases the risk of having glaucoma, cataracts, and other eye problems. It is recommended that people with diabetes visit an eye doctor once a year. Damage to the kidneys, known as diabetic nephropathy, can lead to tissue scarring, urine protein loss, and eventually chronic kidney disease, sometimes requiring dialysis or kidney transplantation. Damage to the nerves of the body, known as diabetic neuropathy, is the most common complication of diabetes. The symptoms can include numbness, tingling, sudomotor dysfunction, pain, and altered pain sensation, which can lead to damage to the skin. Diabetes-related foot problems (such as diabetic foot ulcers) may occur, and can be difficult to treat, occasionally requiring amputation. Additionally, proximal diabetic neuropathy causes painful muscle atrophy and weakness.
There is a link between cognitive deficit and diabetes. Compared to those without diabetes, those with the disease have a 1.2 to 1.5-fold greater rate of decline in cognitive function. Having diabetes, especially when on insulin, increases the risk of falls in older people.

Causes
Diabetes mellitus is classified into six categories: type 1 diabetes, type 2 diabetes, hybrid forms of diabetes, hyperglycemia first detected during pregnancy, "unclassified diabetes", and "other specific types". "Hybrid forms of diabetes" include slowly evolving, immune-mediated diabetes of adults and ketosis-prone type 2 diabetes. "Hyperglycemia first detected during pregnancy" includes gestational diabetes mellitus and diabetes mellitus in pregnancy (type 1 or type 2 diabetes first diagnosed during pregnancy). The "other specific types" are a collection of a few dozen individual causes. Diabetes is a more variable disease than once thought and people may have combinations of forms.

Type 1
Type 1 diabetes is characterized by loss of the insulin-producing beta cells of the pancreatic islets, leading to insulin deficiency. This type can be further classified as immune-mediated or idiopathic. The majority of type 1 diabetes is of an immune-mediated nature, in which a T cell-mediated autoimmune attack leads to the loss of beta cells and thus insulin. It causes approximately 10% of diabetes mellitus cases in North America and Europe. Most affected people are otherwise healthy and of a healthy weight when onset occurs. Sensitivity and responsiveness to insulin are usually normal, especially in the early stages. Although it has been called "juvenile diabetes" due to the frequent onset in children, the majority of individuals living with type 1 diabetes are now adults."Brittle" diabetes, also known as unstable diabetes or labile diabetes, is a term that was traditionally used to describe the dramatic and recurrent swings in glucose levels, often occurring for no apparent reason in insulin-dependent diabetes. This term, however, has no biologic basis and should not be used. Still, type 1 diabetes can be accompanied by irregular and unpredictable high blood sugar levels, and the potential for diabetic ketoacidosis or serious low blood sugar levels. Other complications include an impaired counterregulatory response to low blood sugar, infection, gastroparesis (which leads to erratic absorption of dietary carbohydrates), and endocrinopathies (e.g., Addisons disease). These phenomena are believed to occur no more frequently than in 1% to 2% of persons with type 1 diabetes.

Type 1 diabetes is partly inherited, with multiple genes, including certain HLA genotypes, known to influence the risk of diabetes. In genetically susceptible people, the onset of diabetes can be triggered by one or more environmental factors, such as a viral infection or diet. Several viruses have been implicated, but to date there is no stringent evidence to support this hypothesis in humans. Among dietary factors, data suggest that gliadin (a protein present in gluten) may play a role in the development of type 1 diabetes, but the mechanism is not fully understood.Type 1 diabetes can occur at any age, and a significant proportion is diagnosed during adulthood. Latent autoimmune diabetes of adults (LADA) is the diagnostic term applied when type 1 diabetes develops in adults; it has a slower onset than the same condition in children. Given this difference, some use the unofficial term "type 1.5 diabetes" for this condition. Adults with LADA are frequently initially misdiagnosed as having type 2 diabetes, based on age rather than a cause.

Type 2
Type 2 diabetes is characterized by insulin resistance, which may be combined with relatively reduced insulin secretion. The defective responsiveness of body tissues to insulin is believed to involve the insulin receptor. However, the specific defects are not known. Diabetes mellitus cases due to a known defect are classified separately. Type 2 diabetes is the most common type of diabetes mellitus. Many people with type 2 diabetes have evidence of prediabetes (impaired fasting glucose and/or impaired glucose tolerance) before meeting the criteria for type 2 diabetes. The progression of prediabetes to overt type 2 diabetes can be slowed or reversed by lifestyle changes or medications that improve insulin sensitivity or reduce the livers glucose production.Type 2 diabetes is primarily due to lifestyle factors and genetics. A number of lifestyle factors are known to be important to the development of type 2 diabetes, including obesity (defined by a body mass index of greater than 30), lack of physical activity, poor diet, stress, and urbanization. Excess body fat is associated with 30% of cases in people of Chinese and Japanese descent, 60–80% of cases in those of European and African descent, and 100% of Pima Indians and Pacific Islanders. Even those who are not obese may have a high waist–hip ratio.Dietary factors such as sugar-sweetened drinks are associated with an increased risk. The type of fats in the diet is also important, with saturated fat and trans fats increasing the risk and polyunsaturated and monounsaturated fat decreasing the risk. Eating white rice excessively may increase the risk of diabetes, especially in Chinese and Japanese people. Lack of physical activity may increase the risk of diabetes in some people.Adverse childhood experiences, including abuse, neglect, and household difficulties, increase the likelihood of type 2 diabetes later in life by 32%, with neglect having the strongest effect.Antipsychotic medication side effects (specifically metabolic abnormalities, dyslipidemia and weight gain) and unhealthy lifestyles (including poor diet and decreased physical activity), are potential risk factors.

Gestational diabetes
Gestational diabetes resembles type 2 diabetes in several respects, involving a combination of relatively inadequate insulin secretion and responsiveness. It occurs in about 2–10% of all pregnancies and may improve or disappear after delivery. It is recommended that all pregnant women get tested starting around 24–28 weeks gestation. It is most often diagnosed in the second or third trimester because of the increase in insulin-antagonist hormone levels that occurs at this time. However, after pregnancy approximately 5–10% of women with gestational diabetes are found to have another form of diabetes, most commonly type 2. Gestational diabetes is fully treatable, but requires careful medical supervision throughout the pregnancy. Management may include dietary changes, blood glucose monitoring, and in some cases, insulin may be required.Though it may be transient, untreated gestational diabetes can damage the health of the fetus or mother. Risks to the baby include macrosomia (high birth weight), congenital heart and central nervous system abnormalities, and skeletal muscle malformations. Increased levels of insulin in a fetuss blood may inhibit fetal surfactant production and cause infant respiratory distress syndrome. A high blood bilirubin level may result from red blood cell destruction. In severe cases, perinatal death may occur, most commonly as a result of poor placental perfusion due to vascular impairment. Labor induction may be indicated with decreased placental function. A caesarean section may be performed if there is marked fetal distress or an increased risk of injury associated with macrosomia, such as shoulder dystocia.

Other types
Maturity onset diabetes of the young (MODY) is a rare autosomal dominant inherited form of diabetes, due to one of several single-gene mutations causing defects in insulin production. It is significantly less common than the three main types, constituting 1–2% of all cases. The name of this disease refers to early hypotheses as to its nature. Being due to a defective gene, this disease varies in age at presentation and in severity according to the specific gene defect; thus, there are at least 13 subtypes of MODY. People with MODY often can control it without using insulin.Some cases of diabetes are caused by the bodys tissue receptors not responding to insulin (even when insulin levels are normal, which is what separates it from type 2 diabetes); this form is very uncommon. Genetic mutations (autosomal or mitochondrial) can lead to defects in beta cell function. Abnormal insulin action may also have been genetically determined in some cases. Any disease that causes extensive damage to the pancreas may lead to diabetes (for example, chronic pancreatitis and cystic fibrosis). Diseases associated with excessive secretion of insulin-antagonistic hormones can cause diabetes (which is typically resolved once the hormone excess is removed). Many drugs impair insulin secretion and some toxins damage pancreatic beta cells, whereas others increase insulin resistance (especially glucocorticoids which can provoke "steroid diabetes"). The ICD-10 (1992) diagnostic entity, malnutrition-related diabetes mellitus (ICD-10 code E12), was deprecated by the World Health Organization (WHO) when the current taxonomy was introduced in 1999.
Yet another form of diabetes that people may develop is double diabetes. This is when a type 1 diabetic becomes insulin resistant, the hallmark for type 2 diabetes or has a family history for type 2 diabetes. It was first discovered in 1990 or 1991.
The following is a list of disorders that may increase the risk of diabetes:

Pathophysiology
Insulin is the principal hormone that regulates the uptake of glucose from the blood into most cells of the body, especially liver, adipose tissue and muscle, except smooth muscle, in which insulin acts via the IGF-1. Therefore, deficiency of insulin or the insensitivity of its receptors play a central role in all forms of diabetes mellitus.The body obtains glucose from three main sources: the intestinal absorption of food; the breakdown of glycogen (glycogenolysis), the storage form of glucose found in the liver; and gluconeogenesis, the generation of glucose from non-carbohydrate substrates in the body. Insulin plays a critical role in regulating glucose levels in the body. Insulin can inhibit the breakdown of glycogen or the process of gluconeogenesis, it can stimulate the transport of glucose into fat and muscle cells, and it can stimulate the storage of glucose in the form of glycogen.Insulin is released into the blood by beta cells (β-cells), found in the islets of Langerhans in the pancreas, in response to rising levels of blood glucose, typically after eating. Insulin is used by about two-thirds of the bodys cells to absorb glucose from the blood for use as fuel, for conversion to other needed molecules, or for storage. Lower glucose levels result in decreased insulin release from the beta cells and in the breakdown of glycogen to glucose. This process is mainly controlled by the hormone glucagon, which acts in the opposite manner to insulin.If the amount of insulin available is insufficient, or if cells respond poorly to the effects of insulin (insulin resistance), or if the insulin itself is defective, then glucose is not absorbed properly by the body cells that require it, and is not stored appropriately in the liver and muscles. The net effect is persistently high levels of blood glucose, poor protein synthesis, and other metabolic derangements, such as metabolic acidosis in cases of complete insulin deficiency.When glucose concentration in the blood remains high over time, the kidneys reach a threshold of reabsorption, and the body excretes glucose in the urine (glycosuria). This increases the osmotic pressure of the urine and inhibits reabsorption of water by the kidney, resulting in increased urine production (polyuria) and increased fluid loss. Lost blood volume is replaced osmotically from water in body cells and other body compartments, causing dehydration and increased thirst (polydipsia). In addition, intracellular glucose deficiency stimulates appetite leading to excessive food intake (polyphagia).

Diagnosis
Diabetes mellitus is diagnosed with a test for the glucose content in the blood, and is diagnosed by demonstrating any one of the following:
Fasting plasma glucose level ≥ 7.0 mmol/L (126 mg/dL). For this test, blood is taken after a period of fasting, i.e. in the morning before breakfast, after the patient had sufficient time to fast overnight.
Plasma glucose ≥ 11.1 mmol/L (200 mg/dL) two hours after a 75 gram oral glucose load as in a glucose tolerance test (OGTT)
Symptoms of high blood sugar and plasma glucose ≥ 11.1 mmol/L (200 mg/dL) either while fasting or not fasting
Glycated hemoglobin (HbA1C) ≥ 48 mmol/mol (≥ 6.5 DCCT %).A positive result, in the absence of unequivocal high blood sugar, should be confirmed by a repeat of any of the above methods on a different day. It is preferable to measure a fasting glucose level because of the ease of measurement and the considerable time commitment of formal glucose tolerance testing, which takes two hours to complete and offers no prognostic advantage over the fasting test. According to the current definition, two fasting glucose measurements above 7.0 mmol/L (126 mg/dL) is considered diagnostic for diabetes mellitus.
Per the WHO, people with fasting glucose levels from 6.1 to 6.9 mmol/L (110 to 125 mg/dL) are considered to have impaired fasting glucose. People with plasma glucose at or above 7.8 mmol/L (140 mg/dL), but not over 11.1 mmol/L (200 mg/dL), two hours after a 75 gram oral glucose load are considered to have impaired glucose tolerance. Of these two prediabetic states, the latter in particular is a major risk factor for progression to full-blown diabetes mellitus, as well as cardiovascular disease. The American Diabetes Association (ADA) since 2003 uses a slightly different range for impaired fasting glucose of 5.6 to 6.9 mmol/L (100 to 125 mg/dL).Glycated hemoglobin is better than fasting glucose for determining risks of cardiovascular disease and death from any cause.

Prevention
There is no known preventive measure for type 1 diabetes. Type 2 diabetes—which accounts for 85–90% of all cases worldwide—can often be prevented or delayed by maintaining a normal body weight, engaging in physical activity, and eating a healthy diet. Higher levels of physical activity (more than 90 minutes per day) reduce the risk of diabetes by 28%. Dietary changes known to be effective in helping to prevent diabetes include maintaining a diet rich in whole grains and fiber, and choosing good fats, such as the polyunsaturated fats found in nuts, vegetable oils, and fish. Limiting sugary beverages and eating less red meat and other sources of saturated fat can also help prevent diabetes. Tobacco smoking is also associated with an increased risk of diabetes and its complications, so smoking cessation can be an important preventive measure as well.The relationship between type 2 diabetes and the main modifiable risk factors (excess weight, unhealthy diet, physical inactivity and tobacco use) is similar in all regions of the world. There is growing evidence that the underlying determinants of diabetes are a reflection of the major forces driving social, economic and cultural change: globalization, urbanization, population aging, and the general health policy environment.

Management
Diabetes management concentrates on keeping blood sugar levels as close to normal, without causing low blood sugar. This can usually be accomplished with dietary changes, exercise, weight loss, and use of appropriate medications (insulin, oral medications).
Learning about the disease and actively participating in the treatment is important, since complications are far less common and less severe in people who have well-managed blood sugar levels. Per the American College of Physicians, the goal of treatment is an HbA1C level of 7-8%. Attention is also paid to other health problems that may accelerate the negative effects of diabetes. These include smoking, high blood pressure, metabolic syndrome obesity, and lack of regular exercise. Specialized footwear is widely used to reduce the risk of diabetic foot ulcers by relieving the pressure on the foot.The principles of managing diabetes may be similar across the general population with diabetes, however some considerations may need to be addressed when tailoring intervention, mainly in special populations.
Considering those with severe mental illness, the efficacy of type 2 diabetes self-management interventions is still poorly explored, with insufficient scientific evidence to show whether these interventions have similar results to those observed in general population.

Lifestyle
People with diabetes can benefit from education about the disease and treatment, dietary changes, and exercise, with the goal of keeping both short-term and long-term blood glucose levels within acceptable bounds. In addition, given the associated higher risks of cardiovascular disease, lifestyle modifications are recommended to control blood pressure.Weight loss can prevent progression from prediabetes to diabetes type 2, decrease the risk of cardiovascular disease, or result in a partial remission in people with diabetes. No single dietary pattern is best for all people with diabetes. Healthy dietary patterns, such as the Mediterranean diet, low-carbohydrate diet, or DASH diet, are often recommended, although evidence does not support one over the others. According to the ADA, "reducing overall carbohydrate intake for individuals with diabetes has demonstrated the most evidence for improving glycemia", and for individuals with type 2 diabetes who cannot meet the glycemic targets or where reducing anti-glycemic medications is a priority, low or very-low carbohydrate diets are a viable approach. For overweight people with type 2 diabetes, any diet that achieves weight loss is effective.

Medications
Glucose control
Most medications used to treat diabetes act by lowering blood sugar levels through different mechanisms. There is broad consensus that when people with diabetes maintain tight glucose control – keeping the glucose levels in their blood within normal ranges – they experience fewer complications, such as kidney problems or eye problems. There is however debate as to whether this is appropriate and cost effective for people later in life in whom the risk of hypoglycemia may be more significant.There are a number of different classes of anti-diabetic medications. Type 1 diabetes requires treatment with insulin, ideally using a "basal bolus" regimen that most closely matches normal insulin release: long-acting insulin for the basal rate and short-acting insulin with meals. Type 2 diabetes is generally treated with medication that is taken by mouth (e.g. metformin) although some eventually require injectable treatment with insulin or GLP-1 agonists.Metformin is generally recommended as a first-line treatment for type 2 diabetes, as there is good evidence that it decreases mortality. It works by decreasing the livers production of glucose. Several other groups of drugs, mostly given by mouth, may also decrease blood sugar in type 2 diabetes. These include agents that increase insulin release (sulfonylureas), agents that decrease absorption of sugar from the intestines (acarbose), agents that inhibit the enzyme dipeptidyl peptidase-4 (DPP-4) that inactivates incretins such as GLP-1 and GIP (sitagliptin), agents that make the body more sensitive to insulin (thiazolidinedione) and agents that increase the excretion of glucose in the urine (SGLT2 inhibitors). When insulin is used in type 2 diabetes, a long-acting formulation is usually added initially, while continuing oral medications. Doses of insulin are then increased until glucose targets are reached.

Blood pressure lowering
Cardiovascular disease is a serious complication associated with diabetes, and many international guidelines recommend blood pressure treatment targets that are lower than 140/90 mmHg for people with diabetes. However, there is only limited evidence regarding what the lower targets should be. A 2016 systematic review found potential harm to treating to targets lower than 140 mmHg, and a subsequent systematic review in 2019 found no evidence of additional benefit from blood pressure lowering to between 130 – 140mmHg, although there was an increased risk of adverse events.2015 American Diabetes Association recommendations are that people with diabetes and albuminuria should receive an inhibitor of the renin-angiotensin system to reduce the risks of progression to end-stage renal disease, cardiovascular events, and death. There is some evidence that angiotensin converting enzyme inhibitors (ACEIs) are superior to other inhibitors of the renin-angiotensin system such as angiotensin receptor blockers (ARBs), or aliskiren in preventing cardiovascular disease. Although a more recent review found similar effects of ACEIs and ARBs on major cardiovascular and renal outcomes. There is no evidence that combining ACEIs and ARBs provides additional benefits.

Aspirin
The use of aspirin to prevent cardiovascular disease in diabetes is controversial. Aspirin is recommended by some in people at high risk of cardiovascular disease, however routine use of aspirin has not been found to improve outcomes in uncomplicated diabetes. 2015 American Diabetes Association recommendations for aspirin use (based on expert consensus or clinical experience) are that low-dose aspirin use is reasonable in adults with diabetes who are at intermediate risk of cardiovascular disease (10-year cardiovascular disease risk, 5–10%). National guidelines for England and Wales by the National Institute for Health and Care Excellence (NICE) recommend against the use of aspirin in people with type 1 or type 2 diabetes who do not have confirmed cardiovascular disease.

Surgery
Weight loss surgery in those with obesity and type 2 diabetes is often an effective measure. Many are able to maintain normal blood sugar levels with little or no medications following surgery and long-term mortality is decreased. There is, however, a short-term mortality risk of less than 1% from the surgery. The body mass index cutoffs for when surgery is appropriate are not yet clear. It is recommended that this option be considered in those who are unable to get both their weight and blood sugar under control.A pancreas transplant is occasionally considered for people with type 1 diabetes who have severe complications of their disease, including end stage kidney disease requiring kidney transplantation.

Self-management and support
In countries using a general practitioner system, such as the United Kingdom, care may take place mainly outside hospitals, with hospital-based specialist care used only in case of complications, difficult blood sugar control, or research projects. In other circumstances, general practitioners and specialists share care in a team approach. Home telehealth support can be an effective management technique.The use of technology to deliver educational programs for adults with type 2 diabetes includes computer-based self-management interventions to collect for tailored responses to facilitate self-management. There is no adequate evidence to support effects on cholesterol, blood pressure, behavioral change (such as physical activity levels and dietary), depression, weight and health-related quality of life, nor in other biological, cognitive or emotional outcomes.

Epidemiology
In 2017, 425 million people had diabetes worldwide, up from an estimated 382 million people in 2013 and from 108 million in 1980. Accounting for the shifting age structure of the global population, the prevalence of diabetes is 8.8% among adults, nearly double the rate of 4.7% in 1980. Type 2 makes up about 90% of the cases. Some data indicate rates are roughly equal in women and men, but male excess in diabetes has been found in many populations with higher type 2 incidence, possibly due to sex-related differences in insulin sensitivity, consequences of obesity and regional body fat deposition, and other contributing factors such as high blood pressure, tobacco smoking, and alcohol intake.The WHO estimates that diabetes resulted in 1.5 million deaths in 2012, making it the 8th leading cause of death. However another 2.2 million deaths worldwide were attributable to high blood glucose and the increased risks of cardiovascular disease and other associated complications (e.g. kidney failure), which often lead to premature death and are often listed as the underlying cause on death certificates rather than diabetes. For example, in 2017, the International Diabetes Federation (IDF) estimated that diabetes resulted in 4.0 million deaths worldwide, using modeling to estimate the total number of deaths that could be directly or indirectly attributed to diabetes.Diabetes occurs throughout the world but is more common (especially type 2) in more developed countries. The greatest increase in rates has however been seen in low- and middle-income countries, where more than 80% of diabetic deaths occur. The fastest prevalence increase is expected to occur in Asia and Africa, where most people with diabetes will probably live in 2030. The increase in rates in developing countries follows the trend of urbanization and lifestyle changes, including increasingly sedentary lifestyles, less physically demanding work and the global nutrition transition, marked by increased intake of foods that are high energy-dense but nutrient-poor (often high in sugar and saturated fats, sometimes referred to as the "Western-style" diet). The global number of diabetes cases might increase by 48% between 2017 and 2045.

History
Diabetes was one of the first diseases described, with an Egyptian manuscript from c. 1500 BCE mentioning "too great emptying of the urine." The Ebers papyrus includes a recommendation for a drink to take in such cases. The first described cases are believed to have been type 1 diabetes. Indian physicians around the same time identified the disease and classified it as madhumeha or "honey urine", noting the urine would attract ants.The term "diabetes" or "to pass through" was first used in 230 BCE by the Greek Apollonius of Memphis. The disease was considered rare during the time of the Roman empire, with Galen commenting he had only seen two cases during his career. This is possibly due to the diet and lifestyle of the ancients, or because the clinical symptoms were observed during the advanced stage of the disease. Galen named the disease "diarrhea of the urine" (diarrhea urinosa).The earliest surviving work with a detailed reference to diabetes is that of Aretaeus of Cappadocia (2nd or early 3rd century CE). He described the symptoms and the course of the disease, which he attributed to the moisture and coldness, reflecting the beliefs of the "Pneumatic School". He hypothesized a correlation between diabetes and other diseases, and he discussed differential diagnosis from the snakebite, which also provokes excessive thirst. His work remained unknown in the West until 1552, when the first Latin edition was published in Venice.Two types of diabetes were identified as separate conditions for the first time by the Indian physicians Sushruta and Charaka in 400–500 CE with one type being associated with youth and another type with being overweight. Effective treatment was not developed until the early part of the 20th century when Canadians Frederick Banting and Charles Herbert Best isolated and purified insulin in 1921 and 1922. This was followed by the development of the long-acting insulin NPH in the 1940s.

Etymology
The word diabetes ( or ) comes from Latin diabētēs, which in turn comes from Ancient Greek διαβήτης (diabētēs), which literally means "a passer through; a siphon". Ancient Greek physician Aretaeus of Cappadocia (fl. 1st century CE) used that word, with the intended meaning "excessive discharge of urine", as the name for the disease. Ultimately, the word comes from Greek διαβαίνειν (diabainein), meaning "to pass through", which is composed of δια- (dia-), meaning "through" and βαίνειν (bainein), meaning "to go". The word "diabetes" is first recorded in English, in the form diabete, in a medical text written around 1425.
The word mellitus ( or ) comes from the classical Latin word mellītus, meaning "mellite" (i.e. sweetened with honey; honey-sweet). The Latin word comes from mell-, which comes from mel, meaning "honey"; sweetness; pleasant thing, and the suffix -ītus, whose meaning is the same as that of the English suffix "-ite". It was Thomas Willis who in 1675 added "mellitus" to the word "diabetes" as a designation for the disease, when he noticed the urine of a person with diabetes had a sweet taste (glycosuria). This sweet taste had been noticed in urine by the ancient Greeks, Chinese, Egyptians, Indians, and Persians.

Society and culture
The 1989 "St. Vincent Declaration" was the result of international efforts to improve the care accorded to those with diabetes. Doing so is important not only in terms of quality of life and life expectancy but also economically – expenses due to diabetes have been shown to be a major drain on health – and productivity-related resources for healthcare systems and governments.
Several countries established more and less successful national diabetes programmes to improve treatment of the disease.People with diabetes who have neuropathic symptoms such as numbness or tingling in feet or hands are twice as likely to be unemployed as those without the symptoms.In 2010, diabetes-related emergency room (ER) visit rates in the United States were higher among people from the lowest income communities (526 per 10,000 population) than from the highest income communities (236 per 10,000 population). Approximately 9.4% of diabetes-related ER visits were for the uninsured.

Naming
The term "type 1 diabetes" has replaced several former terms, including childhood-onset diabetes, juvenile diabetes, and insulin-dependent diabetes mellitus. Likewise, the term "type 2 diabetes" has replaced several former terms, including adult-onset diabetes, obesity-related diabetes, and noninsulin-dependent diabetes mellitus. Beyond these two types, there is no agreed-upon standard nomenclature.Diabetes mellitus is also occasionally known as "sugar diabetes" to differentiate it from diabetes insipidus.

Other animals
In animals, diabetes is most commonly encountered in dogs and cats. Middle-aged animals are most commonly affected. Female dogs are twice as likely to be affected as males, while according to some sources, male cats are more prone than females. In both species, all breeds may be affected, but some small dog breeds are particularly likely to develop diabetes, such as Miniature Poodles.Feline diabetes is strikingly similar to human type 2 diabetes. The Burmese, Russian Blue, Abyssinian, and Norwegian Forest cat breeds are at higher risk than other breeds. Overweight cats are also at higher risk.The symptoms may relate to fluid loss and polyuria, but the course may also be insidious. Diabetic animals are more prone to infections. The long-term complications recognized in humans are much rarer in animals. The principles of treatment (weight loss, oral antidiabetics, subcutaneous insulin) and management of emergencies (e.g </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 Coagulation factor VII and can you explain it in depth? [/INST] Coagulation factor VII (EC 3.4.21.21, formerly known as proconvertin) is one of the proteins that causes blood to clot in the coagulation cascade, and in humans is coded for by the gene F7.  It is an enzyme of the serine protease class. Once bound to tissue factor released from damaged tissues, it is converted to factor VIIa (or blood-coagulation factor VIIa, activated blood coagulation factor VII), which in turn activates factor IX and factor X.
Using genetic recombination a recombinant factor VIIa (eptacog alfa) (trade names include NovoSeven) has been approved by the FDA for the control of bleeding in hemophilia. It is sometimes used unlicensed in severe uncontrollable bleeding, although there have been safety concerns. A biosimilar form of recombinant activated factor VII (AryoSeven) is also available, but does not play any considerable role in the market.
In April 2020, the US FDA approved a new rFVIIa product, eptacog beta (SEVENFACT), the first bypassing agent (BPA) approved in more than 2 decades. As an rFVIIa product, eptacog beta works in a complex with tissue factor to activate factor X to Xa, thereby bypassing FVIII and FIX. The activation of Factor X to Xa initiates the coagulation cascade’s common pathway, leading to clot formation at the site of hemorrhage. Activated FVII binds to endothelial protein C receptor (EPCR), which enhances hemostasis.14 One study showed that eptacog beta binds to EPCR with 25% to 30% more affinity than eptacog alfa, displacing protein C from EPCR binding sites and downregulating activated protein C generation, contributing to its hemostatic effect.

Physiology
The main role of factor VII (FVII) is to initiate the process of coagulation in conjunction with tissue factor (TF/factor III). Tissue factor is found on the outside of blood vessels - normally not exposed to the bloodstream. Upon vessel injury, tissue factor is exposed to the blood and circulating factor VII. Once bound to TF, FVII is activated to FVIIa by different proteases, among which are thrombin (factor IIa), factor Xa, IXa, XIIa, and the FVIIa-TF complex itself </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 Auditory processing disorder and can you explain it in depth? [/INST] Auditory processing disorder (APD), rarely known as King-Kopetzky syndrome or auditory disability with normal hearing (ADN), is a neurodevelopmental disorder affecting the way the brain processes auditory information. Individuals with APD usually have normal structure and function of the outer, middle, and inner ear (peripheral hearing). However, they cannot process the information they hear in the same way as others do, which leads to difficulties in recognizing and interpreting sounds, especially the sounds composing speech. It is thought that these difficulties arise from dysfunction in the central nervous system. It is highly prevalent in individuals with other neurodevelopmental disorders, such as Attention Deficit Hyperactivity Disorder, Autism Spectrum Disorders, Dyslexia, and Sensory Processing Disorder.
The American Academy of Audiology notes that APD is diagnosed by difficulties in one or more auditory processes known to reflect the function of the central auditory nervous system. It can affect both children and adults. Although the actual prevalence is currently unknown, it has been estimated to be 2–7% in children in US and UK populations. APD can continue into adulthood. Cooper and Gates (1991) estimated the prevalence of adult APD to be 10 to 20%. It has been reported that males are twice as likely to be affected by the disorder as females, and that prevalence is higher in the elderly and increases with age.Neurodevelopmental forms of APD are differentiable from aphasia in that aphasia is by definition caused by acquired brain injury, but acquired epileptic aphasia has been viewed as a form of APD.

Signs and symptoms
Many people experience problems with learning and day-to-day tasks with difficulties over time. Adults with this disorder can experience the signs and symptoms below:
talk louder than necessary
talk softer than necessary
have trouble remembering a list or sequence
often need words or sentences repeated
have poor ability to memorize information learned by listening
interpret words too literally
need assistance hearing clearly in noisy environments
rely on accommodation and modification strategies
find or request a quiet work space away from others
request written material when attending oral presentations
ask for directions to be given one step at a time

Relation to attention deficit hyperactivity disorder
It has been discovered that APD and ADHD present overlapping symptoms. Below is a ranked order of behavioral symptoms that are most frequently observed in each disorder. Professionals evaluated the overlap of symptoms between the two disorders. The order below is of symptoms that are almost always observed. This chart shows that although the symptoms listed are different, it is easy to get confused between many of them.
There is a co-occurrence between ADHD and APD. A systematic review published in 2018 detailed one study that showed 10% of children with APD have confirmed or suspected ADHD. It also stated that it is sometimes difficult to distinguish the two, since characteristics and symptoms between APD and ADHD tend to overlap. The systematic review mentioned here described this overlap between APD and other behavioral disorders and whether or not it was easy to distinguish those children that solely had auditory processing disorder.

Relation to specific language impairment and developmental dyslexia
There has been considerable debate over the relationship between APD and Specific language impairment (SLI).
SLI is diagnosed when a child has difficulties with understanding or producing spoken language for no obvious cause. The problems cannot be explained in terms of peripheral hearing loss. The child is typically late in starting to talk, and may have problems in producing speech sounds clearly, and in producing or understanding complex sentences. Some theoretical accounts of SLI regard it as the result of auditory processing problems. However, this view of SLI is not universally accepted, and others regard the main difficulties in SLI as stemming from problems with higher-level aspects of language processing. Where a child has both auditory and language problems, it can be difficult to sort out the causality at play.Similarly with developmental dyslexia, researchers continue to explore the hypothesis that reading problems emerge as a downstream consequence of difficulties in rapid auditory processing. Again, cause and effect can be hard to unravel. This is one reason why some experts have recommended using non-verbal auditory tests to diagnose APD. Specifically regarding neurological factors, dyslexia has been linked to polymicrogyria which causes cell migrational problems. Children that have polymicrogyri almost always present with deficits on APD testing. It has also been suggested that APD may be related to cluttering, a fluency disorder marked by word and phrase repetitions.
It has been found that a higher than expected proportion of individuals diagnosed with SLI and dyslexia on the basis of language and reading tests also perform poorly on tests in which auditory processing skills are tested. APD can be assessed using tests that involve identifying, repeating or discriminating speech, and a child may do poorly because of primary language problems. In a study comparing children with a diagnosis of dyslexia and those with a diagnosis of APD, they found the two groups could not be distinguished. Analogous results were observed in studies comparing children diagnosed with SLI or APD, the two groups presenting with similar diagnostic criteria. As such, the diagnosis a child receives may depend on which specialist they consult: the same child who might be diagnosed with APD by an audiologist may instead be diagnosed with SLI by a speech-language therapist or with dyslexia by a psychologist.

Causes
Acquired
Acquired APD can be caused by any damage to or dysfunction of the central auditory nervous system and can cause auditory processing problems. For an overview of neurological aspects of APD, see T. D. Griffiths 2002 article "Central Auditory Pathologies".

Genetics
Some studies have indicated an increased prevalence of a family history of hearing impairment in these patients. The pattern of results is suggestive that auditory processing disorder may be related to conditions of autosomal dominant inheritance. The ability to listen to and comprehend multiple messages at the same time is a trait that is heavily influenced by our genes, say federal researchers. These "short circuits in the wiring" sometimes run in families or result from a difficult birth, just like any learning disability. Auditory processing disorder can be associated with conditions affected by genetic traits, such as various developmental disorders. Inheritance of auditory processing disorder refers to whether the condition is inherited from your parents or "runs" in families.  Central auditory processing disorder may be hereditary neurological traits from the mother or the father.

Developmental
In the majority of cases of developmental APD, the cause is unknown. An exception is acquired epileptic aphasia or Landau-Kleffner syndrome, where a childs development regresses, with language comprehension severely affected. The child is often thought to be deaf, but normal peripheral hearing is found. In other cases, suspected or known causes of APD in children include delay in myelin maturation, ectopic (misplaced) cells in the auditory cortical areas, or genetic predisposition. In a family with autosomal dominant epilepsy, seizures which affected the left temporal lobe seemed to cause problems with auditory processing. In another extended family with a high rate of APD, genetic analysis showed a haplotype in chromosome 12 that fully co-segregated with language impairment.Hearing begins in utero, but the central auditory system continues to develop for at least the first decade. There is considerable interest in the idea that disruption to hearing during a sensitive period may have long-term consequences for auditory development. One study showed thalamocortical connectivity in vitro was associated with a time sensitive developmental window and required a specific cell adhesion molecule (lcam5) for proper brain plasticity to occur. This points to connectivity between the thalamus and cortex shortly after being able to hear (in vitro) as at least one critical period for auditory processing. Another study showed that rats reared in a single tone environment during critical periods of development had permanently impaired auditory processing. Bad auditory experiences, such as temporary deafness by cochlear removal in rats leads to neuron shrinkage. In a study looking at attention in APD patients, children with one ear blocked developed a strong right-ear advantage but were not able to modulate that advantage during directed-attention tasks.In the 1980s and 1990s, there was considerable interest in the role of chronic Otitis media (middle ear disease or glue ear) in causing APD and related language and literacy problems. Otitis media with effusion is a very common childhood disease that causes a fluctuating conductive hearing loss, and there was concern this may disrupt auditory development if it occurred during a sensitive period. Consistent with this, in a sample of young children with chronic ear infections recruited from a hospital otolargyngology department, increased rates of auditory difficulties were found later in childhood. However, this kind of study will have sampling bias because children with otitis media will be more likely to be referred to hospital departments if they are experiencing developmental difficulties. Compared with hospital studies, epidemiological studies, which assesses a whole population for otitis media and then evaluate outcomes, have found much weaker evidence for long-term impacts of otitis media on language outcomes.

Somatic
It seems that somatic anxiety (that is, physical symptoms of anxiety such as butterflies in the stomach or cotton mouth) and situations of stress may be determinants of speech-hearing disability.

Diagnosis
Questionnaires can be used for the identification of persons with possible auditory processing disorders, as these address common problems of listening. They can help in the decision for pursuing clinical evaluation. One of the most common listening problems is speech recognition in the presence of background noise. According to the respondents who participated in a study by Neijenhuis, de Wit, and Luinge (2017), the following symptoms are characteristic in children with listening difficulties, and they are typically problematic with adolescents and adults. They include:
Difficulty hearing in noise
Auditory attention problems
Better understanding in one on one situations
Difficulties in noise localization
Difficulties in remembering oral informationAccording to the New Zealand Guidelines on Auditory Processing Disorders (2017) a checklist of key symptoms of APD or comorbidities that can be used to identify individuals who should be referred for audiological and APD assessment includes, among others:

Difficulty following spoken directions unless they are brief and simple
Difficulty attending to and remembering spoken information
Slowness in processing spoken information
Difficulty understanding in the presence of other sounds
Overwhelmed by complex or "busy" auditory environments e.g. classrooms, shopping malls
Poor listening skills
Insensitivity to tone of voice or other nuances of speech
Acquired brain injury
History of frequent or persistent middle ear disease (otitis media, glue ear).
Difficulty with language, reading or spelling
Suspicion or diagnosis of dyslexia
Suspicion or diagnosis of language disorder or delayFinally, the New Zealand guidelines state that behavioral checklists and questionnaires should only be used to provide guidance for referrals, for information gathering (for example, prior to assessment or as outcome measures for interventions), and as measures to describe the functional impact of auditory processing disorder.  They are not designed for the purpose of diagnosing auditory processing disorders. The New Zealand guidelines indicate that a number of questionnaires have been developed to identify children who might benefit from evaluation of their problems in listening.  Examples of available questionnaires include the Fishers Auditory Problems Checklist, the Childrens Auditory Performance Scale, the Screening Instrument for Targeting Educational Risk, and the Auditory Processing Domains Questionnaire among others. All of the previous questionnaires were designed for children and none are useful for adolescents and adults.The University of Cincinnati Auditory Processing Inventory (UCAPI) was designed for use with adolescents and adults seeking  testing for evaluation of problems with listening and/or to be used following diagnosis of an auditory processing disorder to determine the subjects status.  Following a model described by Zoppo et al. (2015) a 34-item questionnaire was developed that investigates auditory processing abilities in each of the six common areas of complaint in APD (listening and concentration, understanding speech, following spoken instructions, attention, and other.)  The final questionnaire was standardized on normally-achieving young adults ranging from 18 to 27 years of age.  Validation data was acquired from subjects with language-learning or auditory processing disorders who were either self-reported or confirmed by diagnostic testing.  A UCAPI  total score is calculated by combining the totals from the six listening conditions and provides an overall value to categorize listening abilities. Additionally, analysis of the scores from the six listening conditions provides an auditory profile for the subject. Each listening condition can then be utilized by the professional in making recommendation for diagnosing problem of learning through listening and treatment decisions.  The UCAPI provides information on listening problems in various populations that can aid examiners in making recommendations for assessment and management.APD has been defined anatomically in terms of the integrity of the auditory areas of the nervous system. However, children with symptoms of APD typically have no evidence of neurological disease and the diagnosis is made on the basis of performance on behavioral auditory tests. Auditory processing is "what we do with what we hear", and in APD there is a mismatch between peripheral hearing ability (which is typically normal) and ability to interpret or discriminate sounds. Thus in those with no signs of neurological impairment, APD is diagnosed on the basis of auditory tests. There is, however, no consensus as to which tests should be used for diagnosis, as evidenced by the succession of task force reports that have appeared in recent years. The first of these occurred in 1996. This was followed by a conference organized by the American Academy of Audiology.Experts attempting to define diagnostic criteria have to grapple with the problem that a child may do poorly on an auditory test for reasons other than poor auditory perception: for instance, failure could be due to inattention, difficulty in coping with task demands, or limited language ability. In an attempt to rule out at least some of these factors, the American Academy of Audiology conference explicitly advocated that for APD to be diagnosed, the child must have a modality-specific problem, i.e. affecting auditory but not visual processing. However, a committee of the American Speech-Language-Hearing Association subsequently rejected modality-specificity as a defining characteristic of auditory processing disorders.

Definitions
in 2005 The American Speech-Language-Hearing Association (ASHA) published "Central Auditory Processing Disorders" as an update to the 1996 "Central Auditory Processing: Current Status of Research and Implications for Clinical Practice". The American Academy of Audiology has released more current practice guidelines related to the disorder. ASHA formally defines APA as "a difficulty in the efficiency and effectiveness by which the central nervous system (CNS) utilizes auditory information."In 2018, the British Society of Audiology published a position statement and practice guidance on auditory processing disorder (APD) updated its definition of APD. According to the Society, APD refers to the inability to process speech and on-speech sounds.Auditory processing disorder can be developmental or acquired. It may result from ear infections, head injuries or neurodevelopmental delays that affect processing of auditory information. This can include problems with: "...sound localization and lateralization (see also binaural fusion); auditory discrimination; auditory pattern recognition; temporal aspects of audition, including temporal integration, temporal discrimination (e.g., temporal gap detection), temporal ordering, and temporal masking; auditory performance in competing acoustic signals (including dichotic listening); and auditory performance with degraded acoustic signals".The Committee of UK Medical Professionals Steering the UK Auditory Processing Disorder Research Program have developed the following working definition of auditory processing disorder: "APD results from impaired neural function and is characterized by poor recognition, discrimination, separation, grouping, localization, or ordering of speech sounds. It does not solely result from a deficit in general attention, language or other cognitive processes."

Types of testing
The SCAN-C for children and SCAN-A for adolescents and adults are the most common tools for screening and diagnosing APD in the USA.   Both tests are standardized on a large number of subjects and include validation data on subjects with auditory processing disorders.   The SCAN test batteries include screening tests: norm-based criterion-referenced scores; diagnostic tests: scaled scores, percentile ranks and ear advantage scores for all tests except the Gap Detection test.  The four tests include four subsets on which the subject scores are derived include: discrimination of monaurally presented single words against background noise (speech in noise), acoustically degraded single words (filtered words), dichotically presented single words and sentences.
Random Gap Detection Test (RGDT) is also a standardized test. It assesses an individuals gap detection threshold of tones and white noise. The exam includes stimuli at four different frequencies (500, 1000, 2000, and 4000 Hz) and white noise clicks of 50 ms duration. It is a useful test because it provides an index of auditory temporal resolution. In children, an overall gap detection threshold greater than 20 ms means they have failed and may have an auditory processing disorder based on abnormal perception of sound in the time domain.
Gaps in Noise Test (GIN) also measures temporal resolution by testing the patients gap detection threshold in white noise.
Pitch Patterns Sequence Test (PPT) and Duration Patterns Sequence Test (DPT) measure auditory pattern identification. The PPS has s series of three tones presented at either of two pitches (high or low). Meanwhile, the DPS has a series of three tones that vary in duration rather than pitch (long or short). Patients are then asked to describe the pattern of pitches presented.
Masking Level Difference (MLD) at 500 Hz measures overlapping temporal processing, binaural processing, and low-redundancy by measuring the difference in threshold of an auditory stimulus when a masking noise is presented in and out of phase.
The Staggered Spondaic Word Test (SSW) is one of the oldest tests for APD developed by Jack Katz. Although it has fallen into some disuse by audiologists as it is complicated to score, it is one of the quickest and most sensitive tests to determine APD.

Modality-specificity and controversies
The issue of modality-specificity has led to considerable debate among experts in this field.  Cacace and McFarland have argued that APD should be defined as a modality-specific perceptual dysfunction that is not due to peripheral hearing loss. They criticise more inclusive conceptualizations of APD as lacking diagnostic specificity. A requirement for modality-specificity could potentially avoid including children whose poor auditory performance is due to general factors such as poor attention or memory. Others, however, have argued that a modality-specific approach is too narrow, and that it would miss children who had genuine perceptual problems affecting both visual and auditory processing. It is also impractical, as audiologists do not have access to standardized tests that are visual analogs of auditory tests. The debate over this issue remains unresolved between modality-specific researchers such as Cacace, and associations such as the American Speech-Language-Hearing Association (among others). It is clear, however, that a modality-specific approach will diagnose fewer children with APD than a modality-general one, and that the latter approach runs a risk of including children who fail auditory tests for reasons other than poor auditory processing. Although modality-specific testing has been advocated for well over a decade, the visual analog of APD testing has met with sustained resistance from the fields of optometry and ophthalmology.Another controversy concerns the fact that most traditional tests of APD use verbal materials. The British Society of Audiology has embraced Moores (2006) recommendation that tests for APD should assess processing of non-speech sounds. The concern is that if verbal materials are used to test for APD, then children may fail because of limited language ability. An analogy may be drawn with trying to listen to sounds in a foreign language. It is much harder to distinguish between sounds or to remember a sequence of words in a language you do not know well: the problem is not an auditory one, but rather due to lack of expertise in the language.In recent years there have been additional criticisms of some popular tests for diagnosis of APD. Tests that use tape-recorded American English have been shown to over-identify APD in speakers of other forms of English. Performance on a battery of non-verbal auditory tests devised by the Medical Research Councils Institute of Hearing Research was found to be heavily influenced by non-sensory task demands, and indices of APD had low reliability when this was controlled for. This research undermines the validity of APD as a distinct entity in its own right and suggests that the use of the term "disorder" itself is unwarranted. In a recent review of such diagnostic issues, it was recommended that children with suspected auditory processing impairments receive a holistic psychometric assessment including general intellectual ability, auditory memory, and attention, phonological processing, language, and literacy. The authors state that "a clearer understanding of the relative contributions of perceptual and non-sensory, unimodal and supramodal factors to performance on psychoacoustic tests may well be the key to unravelling the clinical presentation of these individuals."Depending on how it is defined, APD may share common symptoms with ADD/ADHD, specific language impairment, and autism spectrum disorders. A review showed substantial evidence for atypical processing of auditory information in children with autism. Dawes and Bishop noted how specialists in audiology and speech-language pathology often adopted different approaches to child assessment, and they concluded their review as follows: "We regard it as crucial that these different professional groups work together in carrying out assessment, treatment and management of children and undertaking cross-disciplinary research."  In practice, this seems rare.To ensure that APD is correctly diagnosed, the examiners must differentiate APD from other disorders with similar symptoms. Factors that should be taken into account during the diagnosis are: attention, auditory neuropathy, fatigue, hearing and sensitivity, intellectual and developmental age, medications, motivation, motor skills, native language and language experience, response strategies and decision-making style, and visual acuity.It should also be noted that children under the age of seven cannot be evaluated correctly because their language and auditory processes are still developing. In addition, the presence of APD cannot be evaluated when a childs primary language is not English.

Characteristics
The American Speech-Language-Hearing Association state that children with (central) auditory processing disorder often:

have trouble paying attention to and remembering information presented orally, and may cope better with visually acquired information
have problems carrying out multi-step directions given orally; need to hear only one direction at a time
have poor listening skills
need more time to process information
have difficulty learning a new language
have difficulty understanding jokes, sarcasm, and learning songs or nursery rhymes
have language difficulties (e.g., they confuse syllable sequences and have problems developing vocabulary and understanding language)
have difficulty with reading, comprehension, spelling, and vocabularyAPD can manifest as problems determining the direction of sounds, difficulty perceiving differences between speech sounds and the sequencing of these sounds into meaningful words, confusing similar sounds such as "hat" with "bat", "there" with "where", etc.  Fewer words may be perceived than were actually said, as there can be problems detecting the gaps between words, creating the sense that someone is speaking unfamiliar or nonsense words. In addition, it is common for APD to cause speech errors involving the distortion and substitution of consonant sounds. Those with APD may have problems relating what has been said with its meaning, despite obvious recognition that a word has been said, as well as repetition of the word.  Background noise, such as the sound of a radio, television or a noisy bar can make it difficult to impossible to understand speech, since spoken words may sound distorted either into irrelevant words or words that dont exist, depending on the severity of the auditory processing disorder. Using a telephone can be problematic for someone with auditory processing disorder, in comparison with someone with normal auditory processing, due to low quality audio, poor signal, intermittent sounds and the chopping of words. Many who have auditory processing disorder subconsciously develop visual coping strategies, such as lip reading, reading body language, and eye contact, to compensate for their auditory deficit, and these coping strategies are not available when using a telephone.As noted above, the status of APD as a distinct disorder has been queried, especially by speech-language pathologists and psychologists, who note the overlap between clinical profiles of children diagnosed with APD and those with other forms of specific learning disability. Many audiologists, however, would dispute that APD is just an alternative label for dyslexia, SLI, or ADHD, noting that although it often co-occurs with these conditions, it can be found in isolation.

Subcategories
Based on sensitized measures of auditory dysfunction and on psychological assessment, patients can be subdivided into seven subcategories:
middle ear dysfunction
mild cochlear pathology
central/medial olivocochlear efferent system (MOCS) auditory dysfunction
purely psychological problems
multiple auditory pathologies
combined auditory dysfunction and psychological problems
unknownDifferent subgroups may represent different pathogenic and aetiological factors. Thus, subcategorization provides further understanding of the basis of auditory processing disorder, and hence may guide the rehabilitative management of these patients. This was suggested  by Professor Dafydd Stephens and F Zhao at the Welsh Hearing Institute, Cardiff University.

Treatment
Treatment of APD typically focuses on three primary areas: changing learning environment, developing higher-order skills to compensate for the disorder, and remediation of the auditory deficit itself. However, there is a lack of well-conducted evaluations of intervention using randomized controlled trial methodology. Most evidence for effectiveness adopts weaker standards of evidence, such as showing that performance improves after training. This does not control for possible influences of practice, maturation, or placebo effects. Recent research has shown that practice with basic auditory processing tasks (i.e. auditory training) may improve performance on auditory processing measures and phonemic awareness measures.  Changes after auditory training have also been recorded at the physiological level. Many of these tasks are incorporated into computer-based auditory training programs such as Earobics and Fast ForWord, an adaptive software available at home and in clinics worldwide,  but overall, evidence for effectiveness of these computerised interventions in improving language and literacy is not impressive. One small-scale uncontrolled study reported successful outcomes for children with APD using auditory training software.Treating additional issues related to APD can result in success. For example, treatment for phonological disorders (difficulty in speech) can result in success in terms of both the phonological disorder as well as APD. In one study, speech therapy improved auditory evoked potentials (a measure of brain activity in the auditory portions of the brain).While there is evidence that language training is effective for improving APD, there is no current research supporting the following APD treatments:

Auditory Integration Training typically involves a child attending two 30-minute sessions per day for ten days.
Lindamood-Bell Learning Processes (particularly, the Visualizing and Verbalizing program)
Physical activities that require frequent crossing of the midline (e.g., occupational therapy)
Sound Field Amplification
Neuro-Sensory Educational Therapy
NeurofeedbackHowever, use of an individual FM transmitter/receiver system by teachers and students has been shown to produce significant improvements with children over time.

History
Samuel J. Kopetzky first described the condition in 1948. P. F. King, first discussed the etiological factors behind it in 1954. Helmer Rudolph Myklebusts 1954 study, "Auditory Disorders in Children". suggested auditory processing disorder was separate from language learning difficulties </s>