<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Problem gambling and explain in detail? [/INST] Problem gambling or ludomania is repetitive gambling behavior despite harm and negative consequences. Problem gambling may be diagnosed as a mental disorder according to DSM-5 if certain diagnostic criteria are met. Pathological gambling is a common disorder that is associated with both social and family costs.
The DSM-5 has re-classified the condition as an addictive disorder, with those affected exhibiting many similarities to those who have substance addictions.
The term gambling addiction has long been used in the recovery movement. Pathological gambling was long considered by the American Psychiatric Association to be an impulse-control disorder rather than an addiction. However, data suggest a closer relationship between pathological gambling and substance use disorders than exists between PG and obsessive-compulsive disorder, largely because the behaviors in problem gambling and most primary substance use disorders (i.e. those not resulting from a desire to "self-medicate" for another condition such as depression) seek to activate the brains reward mechanisms while the behaviors characterizing obsessive-compulsive disorder are prompted by overactive and misplaced signals from the brains fear mechanisms.Problem gambling is an addictive behavior with a high comorbidity with alcohol problems. A common tendency shared by people who have a gambling addiction is impulsivity.

Signs and symptoms
Research by governments in Australia led to a universal definition for that country which appears to be the only research-based definition not to use diagnostic criteria: "Problem gambling is characterized by many difficulties in limiting money and/or time spent on gambling which leads to adverse consequences for the gambler, others, or for the community." The University of Maryland Medical Center defines pathological gambling as "being unable to resist impulses to gamble, which can lead to severe personal or social consequences".Most other definitions of problem gambling can usually be simplified to any gambling that causes harm to the gambler or someone else in any way; however, these definitions are usually coupled with descriptions of the type of harm or the use of diagnostic criteria. The DSM-V has since reclassified pathological gambling as "gambling disorder" and has listed the disorder under substance-related and addictive disorders rather than impulse-control disorders. This is due to the symptomatology of the disorder resembling an addiction not dissimilar to that of a substance use disorder. In order to be diagnosed, an individual must have at least four of the following symptoms in a 12-month period:
Needs to gamble with increasing amounts of money in order to achieve the desired excitement
Is restless or irritable when attempting to cut down or stop gambling
Has made repeated unsuccessful efforts to control, cut back, or stop gambling
Is often preoccupied with gambling (e.g., having persistent thoughts of reliving past gambling experiences, handicapping or planning the next venture, thinking of ways to get money with which to gamble)
Often gambles when feeling distressed (e.g., helpless, guilty, anxious, depressed)
After losing money gambling, often returns another day to get even ("chasing" ones losses)
Lies to conceal the extent of involvement with gambling
Has jeopardized or lost a significant relationship, job, education, or career opportunity because of gambling
Relies on others to provide money to relieve desperate financial situations caused by gambling

Factors that lead to gambling addiction
Mayo Clinic specialists state that compulsive gambling may be result from biological, genetic, and environmental factors, such as:
mental health disorders (the presence of substance use disorders, personality disorders, emotional states)
age and sex (usually found in youth or middle-aged people, and more common to men than women)
impact on family or friends
personality traits
drugs with rare side-effects (for example, antipsychotic medications or dopamine agonists).Other studies add the following triggers to the mentioned above:
traumatic conditions
job-related stress
solitude
other addictionsIf not treated, problem gambling may cause very serious and lasting effects on an individuals life:
relationship related issues
problems with money, bankruptcy
legal problems, imprisonment
health problems
suicide, including suicidal thoughts and attempts

Suicide rates
A gambler who does not receive treatment for pathological gambling when in a desperation phase may contemplate suicide. Problem gambling is often associated with increased suicidal ideation and attempts compared to the general population.Early onset of problem gambling may increase lifetime risk of suicide. Both comorbid substance use and comorbid mental disorders increase the risk of suicide in people with problem gambling. A 2010 Australian hospital study found that 17% of suicidal patients admitted to the Alfred Hospitals emergency department were problem gamblers.

Mechanisms
Biology
According to the Illinois Institute for Addiction Recovery, evidence indicates that pathological gambling is an addiction similar to chemical addiction. It has been observed that some pathological gamblers have lower levels of norepinephrine than normal gamblers. According to a study conducted by Alec Roy, formerly at the National Institute on Alcohol Abuse and Alcoholism, norepinephrine is secreted under stress, arousal, or thrill, so pathological gamblers gamble to make up for their under-dosage.Studies have compared pathological gamblers to substance addicts, concluding that addicted gamblers display more physical symptoms during withdrawal.Deficiencies in serotonin might also contribute to compulsive behavior, including a gambling addiction. There are three important points discovered after these antidepressant studies:
Antidepressants can reduce pathological gambling in case when there is an effect on serotonergic reuptake inhibitors and 5-HT1/5-HT2 receptor antagonists.
Pathological gambling, as the part of obsessive-compulsive disorder, requires the higher doses of antidepressants as is usually required for depressive disorders.
In cases where participants do not have or have minimal symptoms of anxiety or depression, antidepressants still have those effect.A limited study was presented at a conference in Berlin, suggesting opioid release differs in problem gamblers from the general population, but in a very different way from people who have a substance use disorder.The findings in one review indicated the sensitization theory is responsible. Dopamine dysregulation syndrome has been observed in the aforementioned theory in people with regard to such activities as gambling.Some medical authors suggest that the biomedical model of problem gambling may be unhelpful because it focuses only on individuals. These authors point out that social factors may be a far more important determinant of gambling behavior than brain chemicals and they suggest that a social model may be more useful in understanding the issue. For example, an apparent increase in problem gambling in the UK may be better understood as a consequence of changes in legislation which came into force in 2007 and enabled casinos, bookmakers, and online betting sites to advertise on TV and radio for the first time and which eased restrictions on the opening of betting shops and online gambling sites.Pathological gambling is similar to many other impulse-control disorders such as kleptomania. According to evidence from both community- and clinic-based studies, individuals who are pathological gamblers are highly likely to exhibit other psychiatric problems concurrently, including substance use disorders, mood and anxiety disorders, or personality disorders.Pathological gambling shows several similarities with substance use disorders. There is a partial overlap in diagnostic criteria; pathological gamblers are also likely to have a substance use disorder. The "telescoping phenomenon" reflects the rapid development from initial to problematic behavior in women compared with men. This phenomenon was initially described for alcoholism, but it has also been applied to pathological gambling. Also biological data provide a support for a relationship between pathological gambling and substance use disorder. A comprehensive UK Gambling Commission study from 2018 has also hinted at the link between gambling addiction and a reduction in physical activity, poor diet and overall well-being. The study links problem gambling to a myriad of issues affecting relationships, and social stability.

Psychological
Several psychological mechanisms are thought to be implicated in the development and maintenance of problem gambling. First, reward processing seems to be less sensitive with problem gamblers. Second, some individuals use problem gambling as an escape from the problems in their lives (an example of negative reinforcement). Third, personality factors play a role, such as narcissism, risk-seeking, sensation-seeking, and impulsivity. Fourth, problem gamblers have a number of cognitive biases, including the illusion of control, unrealistic optimism, overconfidence and the gamblers fallacy (the incorrect belief that a series of random events tends to self-correct so that the absolute frequencies of each of various outcomes balance each other out). Fifth, problem gamblers represent a chronic state of a behavioral spin process, a gambling spin, as described by the criminal spin theory.Spains gambling watchdog has made an update to its 2019–2020 Responsible Gaming Program, classifying problem gambling as a mental disorder.

Diagnosis
The most common instrument used to screen for "probable pathological gambling" behavior is the South Oaks Gambling Screen (SOGS) developed by Lesieur and Blume (1987) at the South Oaks Hospital in New York City. In recent years the use of SOGS has declined due to a number of criticisms, including that it overestimates false positives (Battersby, Tolchard, Thomas & Esterman, 2002).
The DSM-IV diagnostic criteria presented as a checklist is an alternative to SOGS, it focuses on the psychological motivations underpinning problem gambling and was developed by the American Psychiatric Association. It consists of ten diagnostic criteria. One frequently used screening measure based upon the DSM-IV criteria is the National Opinion Research Center DSM Screen for Gambling Problems (NODS). The Canadian Problem Gambling Inventory (CPGI) and the Victorian Gambling Screen (VGS) are newer assessment measures. The Problem Gambling Severity Index, which focuses on the harms associated with problem gambling, is composed of nine items from the longer CPGI. The VGS is also harm based and includes 15 items. The VGS has proven validity and reliability in population studies as well as Adolescents and clinic gamblers.

Treatment
Most treatment for problem gambling involves counseling, step-based programs, self-help, peer-support, medication, or a combination of these. However, no one treatment is considered to be most efficacious and, in the United States, no medications have been approved for the treatment of pathological gambling by the U.S. Food and Drug Administration (FDA).
Gamblers Anonymous (GA) is a commonly used treatment for gambling problems. Modeled after Alcoholics Anonymous, GA is a twelve-step program that emphasizes a mutual-support approach. There are three in-patient treatment centers in North America. One form of counseling, cognitive behavioral therapy (CBT) has been shown to reduce symptoms and gambling-related urges. This type of therapy focuses on the identification of gambling-related thought processes, mood and cognitive distortions that increase ones vulnerability to out-of-control gambling. Additionally, CBT approaches frequently utilize skill-building techniques geared toward relapse prevention, assertiveness and gambling refusal, problem solving and reinforcement of gambling-inconsistent activities and interests.As to behavioral treatment, some recent research supports the use of both activity scheduling and desensitization in the treatment of gambling problems. In general, behavior analytic research in this area is growing There is evidence that the SSRI paroxetine is efficacious in the treatment of pathological gambling. Additionally, for patients with both pathological gambling and a comorbid bipolar spectrum condition, sustained-release lithium has shown efficacy in a preliminary trial. The opioid antagonist drug nalmefene has also been trialled quite successfully for the treatment of compulsive gambling. Group concepts based on CBT, such as the metacognitive training for problem gambling have also proven effective.

Step-based programs
12 Step-based programs such as Gamblers Anonymous are specific to gambling and generic to healing addiction, creating financial health, and improving mental wellness. Commercial alternatives that are designed for clinical intervention, using the best of health science and applied education practices, have been used as patient-centered tools for intervention since 2007. They include measured efficacy and resulting recovery metrics.

Motivational interviewing
Motivational interviewing is one of the treatments of compulsive gambling. The motivational interviewers basic goal is promoting readiness to change through thinking and resolving mixed feelings. Avoiding aggressive confrontation, argument, labeling, blaming, and direct persuasion, the interviewer supplies empathy and advice to compulsive gamblers who define their own goal. The focus is on promoting freedom of choice and encouraging confidence in the ability to change.

Peer support
A growing method of treatment is peer support. With the advancement of online gambling, many gamblers experiencing issues use various online peer-support groups to aid their recovery. This protects their anonymity while allowing them to attempt recovery on their own, often without having to disclose their issues to loved ones.

Self-help
Research into self-help for problem gamblers has shown benefits. A study by Wendy Slutske of the University of Missouri concluded one-third of pathological gamblers overcome it by natural recovery.

Anti-addiction drugs
Self-exclusion
Gambling self-exclusion (voluntary exclusion) programs are available in the US, the UK, Canada, Australia, South Africa, France, and other countries. They seem to help some (but not all) problem gamblers to gamble less often.Some experts maintain that casinos in general arrange for self-exclusion programs as a public relations measure without actually helping many of those with problem gambling issues. A campaign of this type merely "deflects attention away from problematic products and industries", according to Natasha Dow Schull, a cultural anthropologist at New York University and author of the book Addiction by Design.There is also a question as to the effectiveness of such programs, which can be difficult to enforce. In the province of Ontario, Canada, for example, the Self-Exclusion program operated by the governments Ontario Lottery and Gaming Corporation (OLG) is not effective, according to investigation conducted by the television series, revealed in late 2017. |"Gambling addicts ... said that while on the ... self-exclusion list, they entered OLG properties on a regular basis" in spite of the facial recognition technology in place at the casinos, according to the Canadian Broadcasting Corporation. As well, a CBC journalist who tested the system found that he was able to enter Ontario casinos and gamble on four distinct occasions, in spite of having been registered and photographed for the self-exclusion program. An OLG spokesman provided this response when questioned by the CBC: "We provide supports to self-excluders by training our staff, by providing disincentives, by providing facial recognition, by providing our security officers to look for players. No one element is going to be foolproof because it is not designed to be foolproof".

Impact (Australia)
According to the Productivity Commissions 2010 final report into gambling, the social cost of problem gambling is close to 4.7 billion dollars a year. Some of the harms resulting from problem gambling include depression, suicide, lower work productivity, job loss, relationship breakdown, crime and bankruptcy. A survey conducted in 2008 found that the most common motivation for fraud was problem gambling, with each incident averaging a loss of $1.1 million. According to Darren R. Christensen. Nicki A. Dowling, Alun C. Jackson and Shane A.Thomas a survey done from 1994 to 2008 in Tasmania gave results that gambling participation rates have risen rather than fallen over this period.

Prevalence
Europe
In Europe, the rate of problem gambling is typically 0.5 to 3 percent. The "British Gambling Prevalence Survey 2007", conducted by the United Kingdom Gambling Commission, found approximately 0.6 percent of the adult population had problem gambling issues—the same percentage as in 1999. The highest prevalence of problem gambling was found among those who participated in spread betting (14.7%), fixed odds betting terminals (11.2%), and betting exchanges (9.8%). In Norway, a December 2007 study showed the amount of current problem gamblers was 0.7 percent.With gambling addiction on the rise worldwide and across Europe in particular, those calling gambling a disease have been gaining grounds. The UK Gambling Commission announced a significant shift in their approach to gambling through their reclassification of gambling as a disease, and therefore, it should be addressed adequately by the NHS.
The World Health Organization has also classified gambling a disease. In its 72nd World Health Assembly held on Saturday, May 25, 2019, ‘gaming disorder’ was recognized as an official illness. The 194-member meet added excessive gaming to a classified list of diseases as it revised its International Statistical Classification of Diseases and Related Health Problems (ICD-11).

North America
In the United States, the percentage of pathological gamblers was 0.6 percent, and the percentage of problem gamblers was 2.3 percent in 2008. Studies commissioned by the National Gambling Impact Study Commission Act has shown the prevalence rate ranges from 0.1 percent to 0.6 percent. Nevada has the highest percentage of pathological gambling; a 2002 report estimated 2.2 to 3.6 percent of Nevada residents over the age of 18 could be called problem gamblers. Also, 2.7 to 4.3 percent could be called probable pathological gamblers.According to a 1997 meta-analysis by Harvard Medical Schools division on addictions, 1.1 percent of the adult population of the United States and Canada could be called pathological gamblers </s>


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


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


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Fibrocystic breast changes and explain in detail? [/INST] Fibrocystic breast changes is a condition of the breasts where there may be pain, breast cysts, and breast masses. The breasts may be described as "lumpy" or "doughy". Symptoms may worsen during certain parts of the menstrual cycle due to hormonal stimulation. These are normal breast changes, not associated with cancer.Risk factors include an early age at first menstrual period and either having children at a late age or not at all. It is not a disease but represents normal breast changes. Diagnosis involves ruling out breast cancer. Fibrocystic changes include fibroadenomas, fibrosis, and papillomas of the breast.Management may involve education about the condition, using a well fitting bra, and pain medication, if needed. Occasionally danazol or tamoxifen may be used for pain. It is estimated that up to 60% of women are affected. Most commonly between the ages of 30 and 50 years.

Signs and symptoms
The changes in fibrocystic breast disease are characterised by the appearance of fibrous tissue and a lumpy, cobblestone texture in the breasts. These lumps are smooth with well defined edges, and free-moving regarding adjacent structures. These lumps can sometimes be obscured by irregularities in the breast associated with the condition. Theyre often found in the upper, outer sections of the breast (nearest to the armpit), but can be found throughout the breast. Women with fibrocystic changes may experience a persistent or intermittent aching or breast tenderness related to periodic swelling. Breasts and nipples may also be tender or itchy.
Symptoms follow a periodic trend closely tied to the menstrual cycle. Symptoms tend to peak in the days to weeks before each period and decrease afterwards. At peak, breasts may feel full, heavy, swollen, and tender to the touch. No complications related to breastfeeding have been found.

Pathophysiology
The exact mechanism of the condition is not fully understood, though it is known to be tied to hormone level fluctuation, the condition usually subsides after menopause and is closely related to the menstrual cycle. Post-menopausal under hormone replacement therapy have also reported symptoms of fibrocystic breast changes indicating hormones may play a major role.
This condition is an accumulative process, partly caused by the normal hormonal variation during a womans monthly cycle. The most important of these hormones include: estrogen, progesterone and prolactin.
These hormones directly affect the breast tissue by causing cells to grow and multiply. Other hormones such as TSH, insulin, growth hormone and growth factors such as TGF-beta exert both direct and indirect effects by amplifying or regulating cell growth. Chronic hormonal fluctuations eventually produce small cysts and/or areas of dense or fibrotic tissue over the years. By the age of 30, multiple small cysts and breast pain may arise. Larger cysts usually do not occur until after the age of 35. Over time, presumably driven by aberrant growth signals, such lesions may accumulate epigenetic, genetic and karyotypic changes such as modified expression of hormone receptors and loss of heterozygosity.
Several variants of fibrocystic breast changes may be distinguished and may vary in cause and genetic predisposition. Adenosis involves an abnormal count and density of lobular units, while other lesions appear to mainly arise from ductal epithelial origins.
Theres evidence that iodine deficiency contributes to fibrocystic breast changes by enhancing breast tissue sensitivity to estrogen.

Diagnosis
This is an exclusion diagnosis, mostly done based on the clinical presentation after ruling out breast cancer. Nipple fluid aspiration can be used as a classification cyst type method (and to some extent improve breast cancer risk prediction) but its rarely used in practice. Biopsy or fine needle aspiration are rarely warranted.Fibrocystic breast disease is primarily diagnosed based on the symptoms, clinical breast exam and physical exam. During this examination, the doctor looks for unusual breast areas, both visually and manually. Also, the lymph nodes located in the axilla and lower neck are examined. A complete and accurate medical history is also helpful in the diagnosing process. If the patients medical history and physical exam findings are consistent with normal breast changes, no additional tests are needed; otherwise the patient will be asked to return a few weeks later for reassessment. Women may detect lumps in their breasts during self-examination, if this happens its strongly advised to visit a health professional right away.

Imaging
In order to establish whether the lump is a cyst or not, several imaging tests may be performed, these may include: mammography, X-rays, MRIs and ultrasound studies. Mammography is usually the first imaging test to be ordered when unusual breast changes are found during a clinical breast examination. A diagnostic mammography consists of X-ray series that provide clear and specific visualization areas in the breast.
Ultrasounds and MRIs are commonly performed in conjunction with mammographies as they produce clear images of the breast that clearly distinguish between solid masses and fluid-filled breast cysts. These can better evaluate dense breast tissue; specially in young patients, under 30 years.

Biopsy
Breast biopsy is a test used to confirm the suspected diagnosis, only after imaging tests have already been performed and revealed unusual looking areas. The procedure consists in removing a sample of breast tissue which is then studied by a pathologist under a microscope. The specialist analyzing the tissue sample will be able to conclude if the breast changes are benign or malignant.
There are four main types of procedures for breast biopsy that may be performed, these include: fine-needle, core-needle, stereotactic biopsy and surgical approach. A fine-needle aspiration biopsy is usually ordered when the doctor is almost certain that the lump is a cyst. This test is generally performed in conjunction with an ultrasound which is helpful in guiding the needle into a small or hard to find lump. The procedure consists in inserting a thin needle into the breast tissue while the lump is palpated and seen live under sonographic ultrasound waves.
The core-needle biopsy is normally performed under local anesthesia and in a physicians office. The needle used in this procedure is slightly larger than the one used in a fine-needle biopsy because the procedure is intended to remove a small cylinder of tissue that will be sent to the laboratory for further examination.
A newer type of breast biopsy technique is the stereotactic biopsy which relies on a three-dimensional X-ray to guide the needle of non-palpable mass. The biopsy is performed in a similar manner, by using a needle to remove tissue sample but locating the specific area of the breast is done by X-raying the breast in two different angles. Surgical biopsy is performed to remove the entire lump or a part of it. It may be painful and is done under local anesthesia.

Treatment
Most women with fibrocystic changes who are asymptomatic do not need treatment, only a closer follow-up may be advised. Theres no widely accepted treatment or prevention strategy for this condition. When the patient is symptomatic treatment may be necessary, same guidelines as treatment for cyclical breast pain are followed. Theres still controversy whether benign breast conditions improve or worsen with the use of oral contraceptives or hormone replacement therapy.Small-scale studies have indicated that fibrocystic breast changes may improve by making dietary changes (especially by reducing caffeine intake and related methylxanthines found in chocolate or tea) and usage of vitamin supplements. Tentative evidence has shown beneficial effects of iodine supplementation in women with fibrocystic breast changes.

Prognosis
There are usually no adverse side effects associated with this condition. In almost all cases it subsides after menopause. A possible complication arises through the fact that cancerous tumors may be more difficult to detect in women with fibrocystic changes.

Breast cancer risk
Breast cancer risk is elevated in a defined fraction of the lesions. Except for people with a strong family history of breast cancer, where the risk is two-fold, nonproliferative lesions have no increased risk. Proliferative lesions also have approximately a two-fold risk. In particular, atypical hyperplasia which is associated with an increased risk of developing breast cancer. Theres two types of atypical hyperplasia: lobular and ductal; the lobular type is associated a greater cancer risk of approximately 5-fold and especially high relative risk in premenopausal women. Atypical ductal hyperplasia is associated with 2.4-fold risk. In contrast, a New England Journal of Medicine article  states that for women with a strong familial history of breast cancer, the risk of future breast cancer is roughly doubled, independent of histological status </s>


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Breast engorgement and explain in detail? [/INST] Breast engorgement occurs in the mammary glands due to expansion and pressure exerted by the synthesis and storage of breast milk. It is also a main factor in altering the ability of the infant to latch-on. Engorgement changes the shape and curvature of the nipple region by making the breast inflexible, flat, hard, and swollen. The nipples on an engorged breast are flat or inverted. Sometimes it may lead to striae on nipples, mainly a preceding symptom of septation mastitis.Engorgement usually happens when the breasts switch from colostrum to mature milk (often referred to as when the milk "comes in"). However, engorgement can also happen later if lactating women miss several nursings and not enough milk is expressed from the breasts. It can be exacerbated by insufficient breastfeeding and/or blocked milk ducts.  When engorged the breasts may swell, throb, and cause mild to extreme pain.
Engorgement may lead to mastitis (inflammation of the breast) and untreated engorgement puts pressure on the milk ducts, often causing a plugged duct.  The woman will often feel a lump in one part of the breast, and the skin in that area may be red and/or warm.  If it continues unchecked, the plugged duct can become a breast infection, at which point she may have a fever or flu-like symptoms.

Signs and symptoms
Symptoms include the breasts being swollen and oedematous, and the skin appearing shiny and diffusely red. Usually the whole of both breasts are affected, and they are painful. The woman may have a fever that usually subsides in 24 hours </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Homocystinuria and explain in detail? [/INST] Homocystinuria or HCU is an inherited disorder of the metabolism of the amino acid methionine due to a deficiency of cystathionine beta synthase or methionine synthase. It is an inherited autosomal recessive trait, which means a child needs to inherit a copy of the defective gene from both parents to be affected. Symptoms of homocystinuria can also be caused by a deficiency of vitamins B6, B12, or folate.

Signs and symptoms
This defect leads to a multi-systemic disorder of the connective tissue, muscles, central nervous system (CNS), and cardiovascular system. Homocystinuria represents a group of hereditary metabolic disorders characterized by an accumulation of the amino acid homocysteine in the serum and an increased excretion of homocysteine in the urine. Infants appear to be normal and early symptoms, if any are present, are vague.Signs and symptoms of homocystinuria that may be seen include the following:

Cause
It is usually caused by the deficiency of the enzyme cystathionine beta synthase, mutations of other related enzymes such as methionine synthase, or the deficiency of folic acid, vitamin B12 and/or pyridoxine (vitamin B6).

Diagnosis
The term homocystinuria describes an increased excretion of the thiol amino acid homocysteine in urine (and incidentally, also an increased concentration in plasma). The source of this increase may be one of many metabolic factors, only one of which is CBS deficiency. Others include the re-methylation defects (cobalamin defects, methionine synthase deficiency, MTHFR) and vitamin deficiencies including riboflavin (vitamin B2), pyridoxal phosphate (vitamin B6), folate (vitamin B9), and cobalamin (vitamin B12). In light of this, a combined approach to laboratory diagnosis is required to reach a differential diagnosis.CBS deficiency may be diagnosed by routine metabolic biochemistry. Genetic testing may be used to screen for known SNPs (mutations). In the first instance, plasma or urine amino acid analysis will frequently show an elevation of methionine and the presence of homocysteine. Many neonatal screening programs include methionine as a metabolite. The disorder may be distinguished from the re-methylation defects (e.g., MTHFR, methionine synthase deficiency, or the cobalamin defects) in lieu of the elevated methionine concentration. Additionally, organic acid analysis or quantitative determination of methylmalonic acid should help to exclude cobalamin (vitamin B12) defects and vitamin B12 deficiency giving a differential diagnosis.The laboratory analysis of homocysteine itself is complicated because most homocysteine (possibly above 85%) is bound to other thiol amino acids and proteins in the form of disulphides (e.g., cysteine in cystine-homocysteine, homocysteine in homocysteine-homocysteine) via disulfide bonds. Since as an equilibrium process the proportion of free homocystene is variable a true value of total homocysteine (free + bound) is useful for confirming diagnosis and particularly for monitoring of treatment efficacy. To this end it is prudent to perform total homocyst(e)ine analysis in which all disulphide bonds are subject to reduction prior to analysis, traditionally by HPLC after derivatisation with a fluorescent agent, thus giving a true reflection of the quantity of homocysteine in a plasma sample.

Treatment
No specific cure has been discovered for homocystinuria; however, many people are treated using high doses of vitamin B6 (also known as pyridoxine) </s>


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


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Muenke syndrome and explain in detail? [/INST] Muenke syndrome, also known as FGFR3-related craniosynostosis, is a human specific condition characterized by the premature closure of certain bones of the skull during development, which affects the shape of the head and face. First described by Maximilian Muenke, the syndrome occurs in about 1 in 30,000 newborns. This condition accounts for an estimated 8 percent of all cases of craniosynostosis.

Signs and symptoms
Many people with this disorder have a premature fusion of skull bones along the coronal suture. Not every case has had craniosynostosis however. Other parts of the skull may be malformed as well. This will usually cause an abnormally shaped head, wide-set eyes, low set ears and flattened cheekbones in these patients. About 5 percent of affected individuals have an enlarged head (macrocephaly). There may also be associated hearing loss in 10–33% of cases and it is important for affected individuals to have hearing tests to check on the possibility of a problem. They can lose about 33-100% of hearing.Most people with this condition have normal intellect, but developmental delay and learning disabilities are possible. The signs and symptoms of Muenke syndrome vary among affected people, and some findings overlap with those seen in other craniosynostosis syndromes. Between 6 percent and 7 percent of people with the gene mutation associated with Muenke syndrome do not have any of the characteristic features of the disorder.

Other Implications of Muenke Syndrome
Apart from craniosynostosis, it has been suggested that hearing loss, and learning difficulties are common in Muenke syndrome.  According to Ulster Medical Journal, most individuals with Muenke syndrome may have limb findings.  The most common ocular finding in Muenke syndrome is strabismus as studied by Dr. Agochukwu-Nwubah and her researching team.
Approximately 20% of people with Muenke Syndrome will also be affected by epilepsy.

Causes
Muenke syndrome is caused by a specific gene mutation in the FGFR3 gene. The mutation arises randomly; there is no full understanding for what causes this mutation.  This mutation causes the FGFR3 protein to be overly active; it interferes with normal bone growth, and allows skull bones to fuse prematurely. There is no connection between anything mother did (or did not do) to activate the syndrome. If neither of the parents have Muenke syndrome, chances of having another child with the syndrome are minimal.
This condition is inherited in an autosomal dominant pattern. This means if a parent has Muenke syndrome, every newborn has a 50% chance of inheriting the syndrome.

Genetics
Muenke syndrome is inherited in an autosomal dominant pattern. In some cases, an affected person inherits the mutation from one affected parent. If a patient is shown to have Muenke, they have a 50/50 chance of passing it on to their children. Not all cases of Muenke however is obvious. Other cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family.
A single mutation in the FGFR3 gene cause this syndrome. The FGFR3 gene provides instructions for making a protein that is involved in the development and maintenance of bone and brain tissue. This mutation causes the FGFR3 protein to be overly active, which interferes with normal bone growth and allows the bones of the skull to fuse before they should.As stated by researchers at the University of Washington, Muenke syndrome is inherited in an autosomal dominant manner with incomplete penetrance and variable expressivity.”  Prenatal diagnosis for pregnancies at increased risk is possible if the defining mutation has been identified in the family (Agochukwu et.al. 2006).  According to the article Craniosynostosis: Molecular Genetics, penetrance is higher in females (87%) than in males (76%).  Muenke syndrome is estimated to account for 25%-30% of all genetic causes of craniosynostosis according to the Journal of Anatomy.

Diagnosis
The diagnosis of Muenke syndrome is suspected bases on abnormal skull shape and a diagnosis of coronal craniosynostosis.  In 2006, Agochukwu and her colleagues concluded that “A distinct Muenke syndrome phenotype includes: uni or bilateral coronal synostosis, midface hypoplasia, broad toes, and brachydactyly.”  Due to phenotypic overlap and/or mild phenotypes, clinical differentiation of this syndrome may be difficult.  The suspected diagnosis is confirmed by a blood test to check for gene mutation.  To establish the extent of disease in an individual diagnosed with Muenke syndrome, various evaluations are recommended.

Treatment
The treatment of Muenke syndrome is focused on the correction of the abnormal skull shape and mirrors the treatment of coronal craniosynostosis.  The abnormal growth patterns continue throughout the growing years; therefore, intervention, accurate diagnosis, and a customized, expertly carried-out treatment plan should be a primary concern.  Although the timing of surgery can be highly individualized, surgical correction of the bicoronal craniosynostosis is most often done between 6 and 12 months of age.  Surgery is usually performed through a scalp incision that lies concealed within the hair of the head.  Your craniofacial surgeon will work in concert with a pediatric neurosurgeon in order to safely remove the bones of the skull.  Then, the craniofacial surgeon reshapes and repositions those bones to give a more normal skull shape.

References
Rannan-Eliya SV, Taylor IB, De Heer IM, Van Den Ouweland AM, Wall SA, Wilkie AO (August 2004). "Paternal origin of FGFR3 mutations in Muenke-type craniosynostosis". Hum. Genet. 115 (3): 200–7. doi:10.1007/s00439-004-1151-5. PMID 15241680. S2CID 24791706.
Agochukwu NB, Doherty ES, Muenke M (December 7, 2010). "Muenke Syndrome". Gene Reviews. PMID 20301588.
Hughes J, Nevin NC, Morrison PJ (2001). "Familial craniosynostosis due to Pro250Arg mutation in the fibroblast growth factor receptor 3 gene". Ulster Med J. 70 (70): 47–50. PMC 2449219 </s>


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Herpetic whitlow and explain in detail? [/INST] A herpetic whitlow is a lesion (whitlow) on a finger or thumb caused by the herpes simplex virus.  It is a painful infection that typically affects the fingers or thumbs.  Occasionally infection occurs on the toes or on the nail cuticle.  Herpes whitlow can be caused by infection by HSV-1 or HSV-2. HSV-1 whitlow is often contracted by health care workers that come in contact with the virus; it is most commonly contracted by dental workers and medical workers exposed to oral secretions. It is also often observed in thumb-sucking children with primary HSV-1 oral infection (autoinoculation) prior to seroconversion, and in adults aged 20 to 30 following contact with HSV-2-infected genitals.

Symptoms and signs
Symptoms of herpetic whitlow include swelling, reddening and tenderness of the skin of infected finger. This may be accompanied by fever and swollen lymph nodes. Small, clear vesicles initially form individually, then merge and become cloudy, unlike in bacterial whitlow when there is pus. Associated pain often seems largely relative to the physical symptoms. The herpes whitlow lesion usually heals in two to three weeks. It may reside in axillary sensory ganglia to cause recurrent herpetic lesions on that arm or digits. Blistering can occur in severe cases.

Causes
In children the primary source of infection is the orofacial area, and it is commonly inferred that the virus (in this case commonly HSV-1) is transferred by the cutting, chewing or sucking of fingernail or thumbnail.In adults, it is more common for the primary source to be the genital region, with a corresponding preponderance of HSV-2. It is also seen in adult health care workers such as dentists because of increased exposure to the herpes virus.Contact sports are also a potential source of infection with herpetic whitlows.

Treatment
Although it is a self-limited illness, oral or intravenous antiviral treatments, particularly acyclovir, have been used in the management of immunocompromised or severely infected patients. It is usually given when the condition fails to improve on its own. Topical acyclovir has not been shown to be effective in management of herpetic whitlow. Famciclovir has been demonstrated to effectively treat and prevent recurrent episodes.  Lancing or surgically debriding the lesion may make it worse by causing a superinfection or encephalitis.

Prognosis
Even though the disease is self-limiting, as with many herpes infections, the virus lies dormant in the peripheral nervous system. The disease recurs in about 20-50% of people. The most severe infection is usually the first one, with recurrences subsequently getting milder. The lesions the disease makes will either dry out, or burst, followed by healing </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Fibrochondrogenesis and explain in detail? [/INST] Fibrochondrogenesis is a rare autosomal recessive form of osteochondrodysplasia, causing abnormal fibrous development of cartilage and related tissues.It is a lethal rhizomelic (malformations which result in short, underdeveloped limbs) form of dwarfism, exhibiting both skeletal dysplasia (malformations of bone) and fibroblastic dysplasia (abnormal development of fibroblasts, specialized cells that make up fibrous connective tissue, which plays a role in the formation of cellular structure and promotes healing of damaged tissues) </s>


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Quadricuspid aortic valve and explain in detail? [/INST] A quadricuspid aortic valve (QAV) is a rare congenital heart defect characterized by the presence of four cusps, instead of the usual three found normally in the aortic valve. It is a defect that occurs during embryological development of the aortic trunk during gestation. There is an increased risk of developing post-natal aortic regurgitations and other heart-related diseases; therefore patients with the condition should be carefully monitored.

Signs and symptoms
Complications
The most common complications of QAV are aortic regurgitations. This is caused by the inadequate closing of the four cusps at the end of systole </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Neutrophil-specific granule deficiency and explain in detail? [/INST] Neutrophil-specific granule deficiency ( previously known as lactoferrin deficiency) is a rare congenital immunodeficiency characterized  by an increased risk for pyogenic infections due to defective production of specific granules and gelatinase granules in patient neutrophils.

Symptoms and signs
Atypical infections are the key clinical manifestation of SGD. Within the first few years of life, patients will experience repeated pyogenic infections by species such as Staphylococcus aureus, Pseudomonas aeruginosa or other Enterobacteriaceae, and Candida albicans. Cutaneous ulcers or abscesses and pneumonia and chronic lung disease are common. Patients may also develop sepsis, mastoiditis, otitis media, and lymphadenopathy. Infants may present with vomiting, diarrhea, and failure to thrive.Diagnosis can be made based upon CEBPE gene mutation or a pathognomonic finding of a blood smear showing lack of specific granules </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Hyperthyroidism and explain in detail? [/INST] Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism.  It is noted that thyrotoxicosis is related to hyper-kinetic movement disorders including chorea and myoclonus. Some, however, use the terms interchangeably. Signs and symptoms vary between people and may include irritability, muscle weakness, sleeping problems, a fast heartbeat, heat intolerance, diarrhea, enlargement of the thyroid, hand tremor, and weight loss. Symptoms are typically less severe in the elderly and during pregnancy. An uncommon complication is thyroid storm in which an event such as an infection results in worsening symptoms such as confusion and a high temperature and often results in death. The opposite is hypothyroidism, when the thyroid gland does not make enough thyroid hormone.Graves disease is the cause of about 50% to 80% of the cases of hyperthyroidism in the United States. Other causes include multinodular goiter, toxic adenoma, inflammation of the thyroid, eating too much iodine, and too much synthetic thyroid hormone. A less common cause is a pituitary adenoma. The diagnosis may be suspected based on signs and symptoms and then confirmed with blood tests. Typically blood tests show a low thyroid stimulating hormone (TSH) and raised T3 or T4. Radioiodine uptake by the thyroid, thyroid scan, and TSI antibodies may help determine the cause.Treatment depends partly on the cause and severity of disease. There are three main treatment options: radioiodine therapy, medications, and thyroid surgery. Radioiodine therapy involves taking iodine-131 by mouth which is then concentrated in and destroys the thyroid over weeks to months. The resulting hypothyroidism is treated with synthetic thyroid hormone. Medications such as beta blockers may control the symptoms, and anti-thyroid medications such as methimazole may temporarily help people while other treatments are having an effect. Surgery to remove the thyroid is another option. This may be used in those with very large thyroids or when cancer is a concern. In the United States hyperthyroidism affects about 1.2% of the population. It occurs between two and ten times more often in women. Onset is commonly between 20 and 50 years of age. Overall the disease is more common in those over the age of 60 years.

Signs and symptoms
Hyperthyroidism may be asymptomatic or present with significant symptoms. Some of the symptoms of hyperthyroidism include nervousness, irritability, increased perspiration, heart racing, hand tremors, anxiety, trouble sleeping, thinning of the skin, fine brittle hair, and muscular weakness—especially in the upper arms and thighs. More frequent bowel movements may occur, and diarrhea is common. Weight loss, sometimes significant, may occur despite a good appetite (though 10% of people with a hyperactive thyroid experience weight gain), vomiting may occur, and, for women, menstrual flow may lighten and menstrual periods may occur less often, or with longer cycles than usual.Thyroid hormone is critical to normal function of cells. In excess, it both overstimulates metabolism and disrupts the normal functioning of sympathetic nervous system, causing "speeding up" of various body systems and symptoms resembling an overdose of epinephrine (adrenaline). These include fast heartbeat and symptoms of palpitations, nervous system tremor such as of the hands and anxiety symptoms, digestive system hypermotility, unintended weight loss, and, in lipid panel blood tests, a lower and sometimes unusually low serum cholesterol.Major clinical signs of hyperthyroidism include weight loss (often accompanied by an increased appetite), anxiety, heat intolerance, hair loss (especially of the outer third of the eyebrows), muscle aches, weakness, fatigue, hyperactivity, irritability, high blood sugar, excessive urination, excessive thirst, delirium, tremor, pretibial myxedema (in Graves disease), emotional lability, and sweating.  Panic attacks, inability to concentrate, and memory problems may also occur. Psychosis and paranoia, common during thyroid storm, are rare with milder hyperthyroidism. Many persons will experience complete remission of symptoms 1 to 2 months after a euthyroid state is obtained, with a marked reduction in anxiety, sense of exhaustion, irritability, and depression. Some individuals may have an increased rate of anxiety or persistence of affective and cognitive symptoms for several months to up to 10 years after a euthyroid state is established. In addition, those with hyperthyroidism may present with a variety of physical symptoms such as palpitations and abnormal heart rhythms (the notable ones being atrial fibrillation), shortness of breath (dyspnea), loss of libido, amenorrhea, nausea, vomiting, diarrhea, gynecomastia and feminization. Long term untreated hyperthyroidism can lead to osteoporosis. These classical symptoms may not be present often in the elderly.Neurological manifestations can include tremors, chorea, myopathy, and in some susceptible individuals (in particular of Asian descent) periodic paralysis. An association between thyroid disease and myasthenia gravis has been recognized. Thyroid disease, in this condition, is autoimmune in nature and approximately 5% of people with myasthenia gravis also have hyperthyroidism. Myasthenia gravis rarely improves after thyroid treatment and the relationship between the two entities is not well understood.In Graves disease, ophthalmopathy may cause the eyes to look enlarged because the eye muscles swell and push the eye forward. Sometimes, one or both eyes may bulge. Some have swelling of the front of the neck from an enlarged thyroid gland (a goiter).Minor ocular (eye) signs, which may be present in any type of hyperthyroidism, are eyelid retraction ("stare"), extraocular muscle weakness, and lid-lag. In hyperthyroid stare (Dalrymple sign) the eyelids are retracted upward more than normal (the normal position is at the superior corneoscleral limbus, where the "white" of the eye begins at the upper border of the iris). Extraocular muscle weakness may present with double vision. In lid-lag (von Graefes sign), when the person tracks an object downward with their eyes, the eyelid fails to follow the downward moving iris, and the same type of upper globe exposure which is seen with lid retraction occurs, temporarily. These signs disappear with treatment of the hyperthyroidism.Neither of these ocular signs should be confused with exophthalmos (protrusion of the eyeball), which occurs specifically and uniquely in hyperthyroidism caused by Graves disease (note that not all exophthalmos is caused by Graves disease, but when present with hyperthyroidism is diagnostic of Graves disease). This forward protrusion of the eyes is due to immune-mediated inflammation in the retro-orbital (eye socket) fat. Exophthalmos, when present, may exacerbate hyperthyroid lid-lag and stare.

Thyroid storm
Thyroid storm is a severe form of thyrotoxicosis characterized by rapid and often irregular heart beat, high temperature, vomiting, diarrhea, and mental agitation. Symptoms may not be typical in the young, old, or pregnant. It usually occurs due to untreated hyperthyroidism and can be provoked by infections. It is a medical emergency and requires hospital care to control the symptoms rapidly. Even with treatment, death occurs in 20% to 50% of cases.

Hypothyroidism
Hyperthyroidism due to certain types of thyroiditis can eventually lead to hypothyroidism (a lack of thyroid hormone), as the thyroid gland is damaged. Also, radioiodine treatment of Graves disease often eventually leads to hypothyroidism. Such hypothyroidism may be diagnosed with thyroid hormone testing and treated by oral thyroid hormone supplementation.

Causes
There are several causes of hyperthyroidism. Most often, the entire gland is overproducing thyroid hormone. Less commonly, a single nodule is responsible for the excess hormone secretion, called a "hot" nodule. Thyroiditis (inflammation of the thyroid) can also cause hyperthyroidism. Functional thyroid tissue producing an excess of thyroid hormone occurs in a number of clinical conditions.
The major causes in humans are:

Graves disease. An autoimmune disease (usually, the most common cause with 50–80% worldwide, although this varies substantially with location- i.e., 47% in Switzerland (Horst et al., 1987) to 90% in the USA (Hamburger et al. 1981)). Thought to be due to varying levels of iodine in the diet. It is eight times more common in females than males and often occurs in young females, around 20 – 40 years of age.
Toxic thyroid adenoma (the most common cause in Switzerland, 53%, thought to be atypical due to a low level of dietary iodine in this country)
Toxic multinodular goiterHigh blood levels of thyroid hormones (most accurately termed hyperthyroxinemia) can occur for a number of other reasons:

Inflammation of the thyroid is called thyroiditis. There are several different kinds of thyroiditis including Hashimotos thyroiditis (Hypothyroidism immune-mediated), and subacute thyroiditis (de Quervains). These may be initially associated with secretion of excess thyroid hormone but usually progress to gland dysfunction and, thus, to hormone deficiency and hypothyroidism.
Oral consumption of excess thyroid hormone tablets is possible (surreptitious use of thyroid hormone), as is the rare event of eating ground beef or pork contaminated with thyroid tissue, and thus thyroid hormones (termed hamburger thyrotoxicosis or alimentary thyrotoxicosis). Pharmacy compounding errors may also be a cause.
Amiodarone, an antiarrhythmic drug, is structurally similar to thyroxine and may cause either under-or overactivity of the thyroid.
Postpartum thyroiditis (PPT) occurs in about 7% of women during the year after they give birth. PPT typically has several phases, the first of which is hyperthyroidism. This form of hyperthyroidism usually corrects itself within weeks or months without the need for treatment.
A struma ovarii is a rare form of monodermal teratoma that contains mostly thyroid tissue, which leads to hyperthyroidism.
Excess iodine consumption notably from algae such as kelp.Thyrotoxicosis can also occur after taking too much thyroid hormone in the form of supplements, such as levothyroxine (a phenomenon known as exogenous thyrotoxicosis, alimentary thyrotoxicosis, or occult factitial thyrotoxicosis).Hypersecretion of thyroid stimulating hormone (TSH), which in turn is almost always caused by a pituitary adenoma, accounts for much less than 1 percent of hyperthyroidism cases.

Diagnosis
Measuring the level of thyroid-stimulating hormone (TSH), produced by the pituitary gland (which in turn is also regulated by the hypothalamuss TSH Releasing Hormone) in the blood is typically the initial test for suspected hyperthyroidism. A low TSH level typically indicates that the pituitary gland is being inhibited or "instructed" by the brain to cut back on stimulating the thyroid gland, having sensed increased levels of T4 and/or T3 in the blood. In rare circumstances, a low TSH indicates primary failure of the pituitary, or temporary inhibition of the pituitary due to another illness (euthyroid sick syndrome) and so checking the T4 and T3 is still clinically useful.Measuring specific antibodies, such as anti-TSH-receptor antibodies in Graves disease, or anti-thyroid peroxidase in Hashimotos thyroiditis—a common cause of hypothyroidism—may also contribute to the diagnosis. The diagnosis of hyperthyroidism is confirmed by blood tests that show a decreased thyroid-stimulating hormone (TSH) level and elevated T4 and T3 levels. TSH is a hormone made by the pituitary gland in the brain that tells the thyroid gland how much hormone to make. When there is too much thyroid hormone, the TSH will be low. A radioactive iodine uptake test and thyroid scan together characterizes or enables radiologists and doctors to determine the cause of hyperthyroidism. The uptake test uses radioactive iodine injected or taken orally on an empty stomach to measure the amount of iodine absorbed by the thyroid gland. Persons with hyperthyroidism absorb much more iodine than healthy persons which includes radioactive iodine which is easy to measure.  A thyroid scan producing images is typically conducted in connection with the uptake test to allow visual examination of the over-functioning gland.Thyroid scintigraphy is a useful test to characterize (distinguish between causes of) hyperthyroidism, and this entity from thyroiditis. This test procedure typically involves two tests performed in connection with each other: an iodine uptake test and a scan (imaging) with a gamma camera. The uptake test involves administering a dose of radioactive iodine (radioiodine), traditionally iodine-131 (131I), and more recently iodine-123 (123I). Iodine-123 may be the preferred radionuclide in some clinics due to its more favorable radiation dosimetry (i.e. less radiation dose to the person per unit administered radioactivity) and a gamma photon energy more amenable to imaging with the gamma camera. For the imaging scan, I-123 is considered an almost ideal isotope of iodine for imaging thyroid tissue and thyroid cancer metastasis.Typical administration involves a pill or liquid containing sodium iodide (NaI) taken orally, which contains a small amount of iodine-131, amounting to perhaps less than a grain of salt. A 2-hour fast of no food prior to and for 1 hour after ingesting the pill is required. This low dose of radioiodine is typically tolerated by individuals otherwise allergic to iodine (such as those unable to tolerate contrast mediums containing larger doses of iodine such as used in CT scan, intravenous pyelogram (IVP), and similar imaging diagnostic procedures). Excess radioiodine that does not get absorbed into the thyroid gland is eliminated by the body in urine. Some people with hyperthyroidism may experience a slight allergic reaction to the diagnostic radioiodine and may be given an antihistamine.The person returns 24 hours later to have the level of radioiodine "uptake" (absorbed by the thyroid gland) measured by a device with a metal bar placed against the neck, which measures the radioactivity emitting from the thyroid. This test takes about 4 minutes while the uptake % (i.e., percentage) is accumulated (calculated) by the machine software. A scan is also performed, wherein images (typically a center, left and right angle) are taken of the contrasted thyroid gland with a gamma camera; a radiologist will read and prepare a report indicating the uptake % and comments after examining the images. People with hyperthyroid will typically "take up" higher than normal levels of radioiodine. Normal ranges for RAI uptake are from 10 to 30%.
In addition to testing the TSH levels, many doctors test for T3, Free T3, T4, and/or Free T4 for more detailed results. Free T4 is unbound to any protein in the blood. Adult limits for these hormones are: TSH (units): 0.45 – 4.50 uIU/mL; T4 Free/Direct (nanograms): 0.82 – 1.77 ng/dl; and T3 (nanograms): 71 – 180 ng/dl. Persons with hyperthyroidism can easily exhibit levels many times these upper limits for T4 and/or T3. See a complete table of normal range limits for thyroid function at the thyroid gland article.
In hyperthyroidism CK-MB (Creatine kinase) is usually elevated.

Subclinical
In overt primary hyperthyroidism, TSH levels are low and T4 and T3 levels are high. Subclinical hyperthyroidism is a milder form of hyperthyroidism characterized by low or undetectable serum TSH level, but with a normal serum free thyroxine level. Although the evidence for doing so is not definitive, treatment of elderly persons having subclinical hyperthyroidism could reduce the number of cases of atrial fibrillation. There is also an increased risk of bone fractures (by 42%) in people with subclinical hyperthyroidism; there is insufficient evidence to say whether treatment with antithyroid medications would reduce that risk.A 2022 meta-analysis found subclinical hyperthyroidism to be associated with cardiovascular death.

Screening
In those without symptoms who are not pregnant there is little evidence for or against screening.

Treatment
Antithyroid drugs
Thyrostatics (antithyroid drugs) are drugs that inhibit the production of thyroid hormones, such as carbimazole (used in the UK) and methimazole (used in the US, Germany and Russia), and propylthiouracil. Thyrostatics are believed to work by inhibiting the iodination of thyroglobulin by thyroperoxidase and, thus, the formation of tetraiodothyronine (T4). Propylthiouracil also works outside the thyroid gland, preventing the conversion of (mostly inactive) T4 to the active form T3. Because thyroid tissue usually contains a substantial reserve of thyroid hormone, thyrostatics can take weeks to become effective and the dose often needs to be carefully titrated over a period of months, with regular doctor visits and blood tests to monitor results.A very high dose is often needed early in treatment, but, if too high a dose is used persistently, people can develop symptoms of hypothyroidism. This titrating of the dose is difficult to do accurately, and so sometimes a "block and replace" attitude is taken. In block and replace treatments thyrostatics are taken in sufficient quantities to completely block thyroid hormones, and the person treated as though they have complete hypothyroidism.

Beta-blockers
Many of the common symptoms of hyperthyroidism such as palpitations, trembling, and anxiety are mediated by increases in beta-adrenergic receptors on cell surfaces. Beta blockers, typically used to treat high blood pressure, are a class of drugs that offset this effect, reducing rapid pulse associated with the sensation of palpitations, and decreasing tremor and anxiety. Thus, a person with hyperthyroidism can often obtain immediate temporary relief until the hyperthyroidism can be characterized with the Radioiodine test noted above and more permanent treatment take place. Note that these drugs do not treat hyperthyroidism or any of its long-term effects if left untreated, but, rather, they treat or reduce only symptoms of the condition.Some minimal effect on thyroid hormone production however also comes with propranolol—which has two roles in the treatment of hyperthyroidism, determined by the different isomers of propranolol. L-propranolol causes beta-blockade, thus treating the symptoms associated with hyperthyroidism such as tremor, palpitations, anxiety, and heat intolerance. D-propranolol inhibits thyroxine deiodinase, thereby blocking the conversion of T4 to T3, providing some though minimal therapeutic effect. Other beta-blockers are used to treat only the symptoms associated with hyperthyroidism. Propranolol in the UK, and metoprolol in the US, are most frequently used to augment treatment for people with hyperthyroid .

Diet
People with autoimmune hyperthyroidism (such as in Graves disease) should not eat foods high in iodine, such as edible seaweed and kelps.From a public health perspective, the general introduction of iodized salt in the United States in 1924 resulted in lower disease, goiters, as well as improving the lives of children whose mothers would not have eaten enough iodine during pregnancy which would have lowered the IQs of their children.

Surgery
Surgery (thyroidectomy to remove the whole thyroid or a part of it) is not extensively used because most common forms of hyperthyroidism are quite effectively treated by the radioactive iodine method, and because there is a risk of also removing the parathyroid glands, and of cutting the recurrent laryngeal nerve, making swallowing difficult, and even simply generalized staphylococcal infection as with any major surgery. Some people with Graves may opt for surgical intervention. This includes those that cannot tolerate medicines for one reason or another, people that are allergic to iodine, or people that refuse radioiodine.If people have toxic nodules treatments typically include either removal or injection of the nodule with alcohol.

Radioiodine
In iodine-131 (radioiodine) radioisotope therapy, which was first pioneered by Dr. Saul Hertz, radioactive iodine-131 is given orally (either by pill or liquid) on a one-time basis, to severely restrict, or altogether destroy the function of a hyperactive thyroid gland. This isotope of radioactive iodine used for ablative treatment is more potent than diagnostic radioiodine (usually iodine-123 or a very low amount of iodine-131), which has a biological half-life from 8–13 hours. Iodine-131, which also emits beta particles that are far more damaging to tissues at short range, has a half-life of approximately 8 days.  People not responding sufficiently to the first dose are sometimes given an additional radioiodine treatment, at a larger dose. Iodine-131 in this treatment is picked up by the active cells in the thyroid and destroys them, rendering the thyroid gland mostly or completely inactive.Since iodine is picked up more readily (though not exclusively) by thyroid cells, and (more important) is picked up even more readily by over-active thyroid cells, the destruction is local, and there are no widespread side effects with this therapy. Radioiodine ablation has been used for over 50 years, and the only major reasons for not using it are pregnancy and breastfeeding (breast tissue also picks up and concentrates iodine). Once the thyroid function is reduced, replacement hormone therapy (levothyroxine) taken orally each day replaces the thyroid hormone that is normally produced by the body.There is extensive experience, over many years, of the use of radioiodine in the treatment of thyroid overactivity and this experience does not indicate any increased risk of thyroid cancer following treatment. However, a study from 2007 has reported an increased number of cancer cases after radioiodine treatment for hyperthyroidism.The principal advantage of radioiodine treatment for hyperthyroidism is that it tends to have a much higher success rate than medications. Depending on the dose of radioiodine chosen, and the disease under treatment (Graves vs. toxic goiter, vs. hot nodule etc.), the success rate in achieving definitive resolution of the hyperthyroidism may vary from 75 to 100%. A major expected side-effect of radioiodine in people with Graves disease is the development of lifelong hypothyroidism, requiring daily treatment with thyroid hormone. On occasion, some people may require more than one radioactive treatment, depending on the type of disease present, the size of the thyroid, and the initial dose administered.People with Graves disease manifesting moderate or severe Graves ophthalmopathy are cautioned against radioactive iodine-131 treatment, since it has been shown to exacerbate existing thyroid eye disease. People with mild or no ophthalmic symptoms can mitigate their risk with a concurrent six-week course of prednisone. The mechanisms proposed for this side effect involve a TSH receptor common to both thyrocytes and retro-orbital tissue.As radioactive iodine treatment results in the destruction of thyroid tissue, there is often a transient period of several days to weeks when the symptoms of hyperthyroidism may actually worsen following radioactive iodine therapy. In general, this happens as a result of thyroid hormones being released into the blood following the radioactive iodine-mediated destruction of thyroid cells that contain thyroid hormone. In some people, treatment with medications such as beta blockers (propranolol, atenolol, etc.) may be useful during this period of time. Most people do not experience any difficulty after the radioactive iodine treatment, usually given as a small pill. On occasion, neck tenderness or a sore throat may become apparent after a few days, if moderate inflammation in the thyroid develops and produces discomfort in the neck or throat area. This is usually transient, and not associated with a fever, etc.It is recommended that breastfeeding be stopped at least six weeks before radioactive iodine treatment and that it not be resumed, although it can be done in future pregnancies. It also shouldnt be done during pregnancy, and pregnancy should be put off until at least 6–12 months after treatment.A common outcome following radioiodine is a swing from hyperthyroidism to the easily treatable hypothyroidism, which occurs in 78% of those treated for Graves thyrotoxicosis and in 40% of those with toxic multinodular goiter or solitary toxic adenoma. Use of higher doses of radioiodine reduces the number of cases of treatment failure, with penalty for higher response to treatment consisting mostly of higher rates of eventual hypothyroidism which requires hormone treatment for life.There is increased sensitivity to radioiodine therapy in thyroids appearing on ultrasound scans as more uniform (hypoechogenic), due to densely packed large cells, with 81% later becoming hypothyroid, compared to just 37% in those with more normal scan appearances (normoechogenic).

Thyroid storm
Thyroid storm presents with extreme symptoms of hyperthyroidism.  It is treated aggressively with resuscitation measures along with a combination of the above modalities including: an intravenous beta blockers such as propranolol, followed by a thioamide such as methimazole, an iodinated radiocontrast agent or an iodine solution if the radiocontrast agent is not available, and an intravenous steroid such as hydrocortisone.

Alternative medicine
In countries such as China, herbs used alone or with antithyroid medications are used to treat hyperthyroidism. Very low quality evidence suggests that traditional Chinese herbal medications may be beneficial when taken along with routine hyperthyroid medications, however, there is no reliable evidence to determine the effectiveness of Chinese herbal medications for treating hyperthyroidism.

Epidemiology
In the United States hyperthyroidism affects about 1.2% of the population. About half of these cases have obvious symptoms while the other half do not. It occurs between two and ten times more often in women. The disease is more common in those over the age of 60 years.Subclinical hyperthyroidism modestly increases the risk of cognitive impairment and dementia.

History
Caleb Hillier Parry first made the association between the goiter and protrusion of the eyes in 1786, however, did not publish his findings until 1825. In 1835, Irish doctor Robert James Graves discovered a link between the protrusion of the eyes and goiter, giving his name to the autoimmune disease now known as Graves Disease.

Pregnancy
Recognizing and evaluating hyperthyroidism in pregnancy is a diagnostic challenge. Thyroid hormones are naturally elevated during pregnancy. Thyroid function generally normalizes in by the second trimester without treatment. Hyperthyroidism must also be distinguished from gestational transient thyrotoxicosis; as it can increase the risk of complications for mother and child. Such risks include pregnancy-related hypertension, pregnancy loss, low-birth weight, still birth and behavioral disorders later in the childs life. Nonetheless, high maternal FT4 levels during pregnancy have been associated with impaired brain developmental outcomes of the offspring and this was independent of for example hCG levels.

Other animals
Cats
Hyperthyroidism is one of the most common endocrine conditions affecting older domesticated housecats. In the United States, up to 10% of cats over ten years old have hyperthyroidism. The disease has become significantly more common since the first reports of feline hyperthyroidism in the 1970s. The most common cause of hyperthyroidism in cats is the presence of benign tumors called adenomas. 98% of cases are caused by the presence of an adenoma, but the reason these cats develop such tumors continues to be studied.
The most common presenting symptoms are: rapid weight loss, tachycardia (rapid heart rate), vomiting, diarrhea, increased consumption of fluids (polydipsia), increased appetite (polyphagia), and increased urine production (polyuria). Other symptoms include hyperactivity, possible aggression, an unkempt appearance, and large, thick claws. Heart murmurs and a gallop rhythm can develop due to secondary hypertrophic cardiomyopathy.  About 70% of affected cats also have enlarged thyroid glands (goiter). 10% of cats exhibit "apathetic hyperthyroidism", which is characterized by anorexia and lethargy.The same three treatments used with humans are also options in treating feline hyperthyroidism (surgery, radioiodine treatment, and anti-thyroid drugs). There is also a special low iodine diet available that will control the symptoms providing no other food is fed; Hills y/d formula, when given exclusively, decreases T4 production by limiting the amount of iodine needed for thyroid hormone production. It is the only available commercial diet that focuses on managing feline hyperthyroidism. Medical and dietary management using methimazole and Hills y/d cat food will give hyperthyroid cats an average of 2 years before dying due to secondary conditions such as heart and kidney failure. Drugs used to help manage the symptoms of hyperthyroidism are methimazole and carbimazole. Drug therapy is the least expensive option, even though the drug must be administered daily for the remainder of the cats life. Carbimazole is only available as a once daily tablet. Methimazole is available as an oral solution, a tablet, and compounded as a topical gel that is applied using a finger cot to the hairless skin inside a cats ear. Many cat owners find this gel a good option for cats that dont like being given pills.
Radioiodine treatment, however, is not available in all areas, as this treatment requires nuclear radiological expertise and facilities that not only board the cat, but are specially equipped to manage the cats urine, sweat, saliva, and stool, which are radioactive for several days after the treatment, usually for a total of 3 weeks (the cat spends the first week in total isolation and the next two weeks in close confinement). In the United States, the guidelines for radiation levels vary from state to state; some states such as Massachusetts allow hospitalization for as little as two days before the animal is sent home with care instructions.

Dogs
Hyperthyroidism is much less common in dogs compared to cats. Hyperthyroidism may be caused by a thyroid tumor. This may be a thyroid carcinoma. About 90% of carcinomas are very aggressive; they invade the surrounding tissues and metastasize (spread) to other tissues, particularly the lungs </s>


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Mitochondrial disease and explain in detail? [/INST] Mitochondrial disease is a group of disorders caused by mitochondrial dysfunction. Mitochondria are the organelles that generate energy for the cell and are found in every cell of the human body except red blood cells. They convert the energy of food molecules into the ATP that powers most cell functions.
Mitochondrial diseases take on unique characteristics both because of the way the diseases are often inherited and because mitochondria are so critical to cell function. A subclass of these diseases that have neuromuscular symptoms are known as mitochondrial myopathies.

Types
Examples of mitochondrial diseases include:

Mitochondrial myopathy
Diabetes mellitus and deafness (DAD)
this combination at an early age can be due to mitochondrial disease
Diabetes mellitus and deafness can be found together for other reasons
Lebers hereditary optic neuropathy (LHON)
visual loss beginning in young adulthood
eye disorder characterized by progressive loss of central vision due to degeneration of the optic nerves and retina
affects 1 in 50,000 people in Finland
Leigh syndrome, subacute necrotizing encephalomyelopathyafter normal development the disease usually begins late in the first year of life, although onset may occur in adulthood
a rapid decline in function occurs and is marked by seizures, altered states of consciousness, dementia, ventilatory failure
Neuropathy, ataxia, retinitis pigmentosa, and ptosis (NARP)
progressive symptoms as described in the acronym
dementia
Myoneurogenic gastrointestinal encephalopathy (MNGIE)
gastrointestinal pseudo-obstruction
neuropathy
MERRF syndrome
progressive myoclonic epilepsy
"Ragged Red Fibers" are clumps of diseased mitochondria that accumulate in the subsarcolemmal region of the muscle fiber and appear when muscle is stained with modified Gömöri trichrome stain
short stature
hearing loss
lactic acidosis
exercise intolerance
MELAS syndrome
Mitochondrial DNA depletion syndromeConditions such as Friedreichs ataxia can affect the mitochondria but are not associated with mitochondrial proteins.

Presentation
Associated conditions
Acquired conditions in which mitochondrial dysfunction has been involved are:

diabetes
Huntingtons disease
cancer
Alzheimers disease,
Parkinsons disease
bipolar disorder, schizophrenia, aging and senescence, anxiety disorders
cardiovascular disease
sarcopenia
chronic fatigue syndromeThe body, and each mutation, is modulated by other genome variants; the mutation that in one individual may cause liver disease might in another person cause a brain disorder. The severity of the specific defect may also be great or small. Some defects include exercise intolerance. Defects often affect the operation of the mitochondria and multiple tissues more severely, leading to multi-system diseases.It has also been reported that drug tolerant cancer cells have an increased number and size of mitochondria, which suggested an increase in mitochondrial biogenesis. Interestingly, a recent study in Nature Nanotechnology has reported that cancer cells can hijack the mitochondria from immune cells via physical tunneling nanotubes.As a rule, mitochondrial diseases are worse when the defective mitochondria are present in the muscles, cerebrum, or nerves, because these cells use more energy than most other cells in the body.
Although mitochondrial diseases vary greatly in presentation from person to person, several major clinical categories of these conditions have been defined, based on the most common phenotypic features, symptoms, and signs associated with the particular mutations that tend to cause them.An outstanding question and area of research is whether ATP depletion or reactive oxygen species are in fact responsible for the observed phenotypic consequences.Cerebellar atrophy or hypoplasia has sometimes been reported to be associated.

Causes
Mitochondrial disorders may be caused by mutations (acquired or inherited), in mitochondrial DNA (mtDNA), or in nuclear genes that code for mitochondrial components. They may also be the result of acquired mitochondrial dysfunction due to adverse effects of drugs, infections, or other environmental causes. Oxalate may enter cells where it is known to cause mitochondrial dysfunction.

Nuclear DNA has two copies per cell (except for sperm and egg cells), one copy being inherited from the father and the other from the mother. Mitochondrial DNA, however, is inherited from the mother only (with some exceptions) and each mitochondrion typically contains between 2 and 10 mtDNA copies. During cell division the mitochondria segregate randomly between the two new cells. Those mitochondria make more copies, normally reaching 500 mitochondria per cell. As mtDNA is copied when mitochondria proliferate, they can accumulate random mutations, a phenomenon called heteroplasmy. If only a few of the mtDNA copies inherited from the mother are defective, mitochondrial division may cause most of the defective copies to end up in just one of the new mitochondria (for more detailed inheritance patterns, see human mitochondrial genetics). Mitochondrial disease may become clinically apparent once the number of affected mitochondria reaches a certain level; this phenomenon is called "threshold expression".
Mitochondria possess many of the same DNA repair pathways as nuclei do—but not all of them; therefore, mutations occur more frequently in mitochondrial DNA than in nuclear DNA (see Mutation rate). This means that mitochondrial DNA disorders may occur spontaneously and relatively often. Defects in enzymes that control mitochondrial DNA replication (all of which are encoded for by genes in the nuclear DNA) may also cause mitochondrial DNA mutations.
Most mitochondrial function and biogenesis is controlled by nuclear DNA. Human mitochondrial DNA encodes 13 proteins of the respiratory chain, while most of the estimated 1,500 proteins and components targeted to mitochondria are nuclear-encoded. Defects in nuclear-encoded mitochondrial genes are associated with hundreds of clinical disease phenotypes including anemia, dementia, hypertension, lymphoma, retinopathy, seizures, and neurodevelopmental disorders.A study by Yale University researchers (published in the February 12, 2004, issue of the New England Journal of Medicine) explored the role of mitochondria in insulin resistance among the offspring of patients with type 2 diabetes.
Other studies have shown that the mechanism may involve the interruption of the mitochondrial signaling process in body cells (intramyocellular lipids). A study conducted at the Pennington Biomedical Research Center in Baton Rouge, Louisiana showed that this, in turn, partially disables the genes that produce mitochondria.

Mechanisms
The effective overall energy unit for the available body energy is referred to as the daily glycogen generation capacity, and is used to compare the mitochondrial output of affected or chronically glycogen-depleted individuals to healthy individuals. This value is slow to change in a given individual, as it takes between 18 and 24 months to complete a full cycle.The glycogen generation capacity is entirely dependent on, and determined by, the operating levels of the mitochondria in all of the cells of the human body; however, the relation between the energy generated by the mitochondria and the glycogen capacity is very loose and is mediated by many biochemical pathways. The energy output of full healthy mitochondrial function can be predicted exactly by a complicated theoretical argument, but this argument is not straightforward, as most energy is consumed by the brain and is not easily measurable.

Diagnosis
Mitochondrial diseases are usually detected by analysing muscle samples, where the presence of these organelles is higher. The most common tests for the detection of these diseases are:

Southern blot to detect big deletions or duplications
Polymerase chain reaction and specific mutation testing
Sequencing

Treatments
Although research is ongoing, treatment options are currently limited; vitamins are frequently prescribed, though the evidence for their effectiveness is limited.Pyruvate has been proposed in 2007 as a treatment option. N-acetyl cysteine reverses many models of mitochondrial dysfunction. In the case of mood disorders, specifically bipolar disorder, it is hypothesized that N-acetyl-cysteine (NAC), acetyl-L-carnitine (ALCAR), S-adenosylmethionine (SAMe), coenzyme Q10 (CoQ10), alpha-lipoic acid (ALA), creatine monohydrate (CM), and melatonin could be potential treatment options.

Gene therapy prior to conception
Mitochondrial replacement therapy (MRT), where the nuclear DNA is transferred to another healthy egg cell leaving the defective mitochondrial DNA behind, is an IVF treatment procedure. Using a similar pronuclear transfer technique, researchers at Newcastle University led by Douglass Turnbull successfully transplanted healthy DNA in human eggs from women with mitochondrial disease into the eggs of women donors who were unaffected. In such cases, ethical questions have been raised regarding biological motherhood, since the child receives genes and gene regulatory molecules from two different women. Using genetic engineering in attempts to produce babies free of mitochondrial disease is controversial in some circles and raises important ethical issues. A male baby was born in Mexico in 2016 from a mother with Leigh syndrome using MRT.In September 2012 a public consultation was launched in the UK to explore the ethical issues involved. Human genetic engineering was used on a small scale to allow infertile women with genetic defects in their mitochondria to have children.
In June 2013, the United Kingdom government agreed to develop legislation that would legalize the three-person IVF procedure as a treatment to fix or eliminate mitochondrial diseases that are passed on from mother to child </s>


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


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