<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 Repetitive strain injury and explain in detail? [/INST] A repetitive strain injury (RSI) is an injury to part of the musculoskeletal or nervous system caused by repetitive use, vibrations, compression or long periods in a fixed position.  Other common names include repetitive stress disorders, cumulative trauma disorders (CTDs), and overuse syndrome.

Signs and symptoms
Some examples of symptoms experienced by patients with RSI are aching, pulsing pain, tingling and extremity weakness, initially presenting with intermittent discomfort and then with a higher degree of frequency.

Definition
Repetitive strain injury (RSI) and associative trauma orders are umbrella terms used to refer to several discrete conditions that can be associated with repetitive tasks, forceful  exertions, vibrations,  mechanical compression, sustained or awkward positions, or repetitive eccentric contractions. The exact terminology is controversial, but the terms now used by the United States Department of Labor and the National Institute of Occupational Safety and Health (NIOSH) are musculoskeletal disorders (MSDs) and work-related muscular skeletal disorders (WMDs).Examples of conditions that may sometimes be attributed to such causes include tendinosis (or less often tendinitis), carpal tunnel syndrome, cubital tunnel syndrome, De Quervain syndrome, thoracic outlet syndrome, intersection syndrome, golfers elbow (medial epicondylitis), tennis elbow (lateral epicondylitis), trigger finger (so-called stenosing tenosynovitis), radial tunnel syndrome, ulnar tunnel syndrome, and focal dystonia.A general worldwide increase since the 1970s in RSIs of the arms, hands, neck, and shoulder has been attributed to the widespread use in the workplace of keyboard entry devices, such as typewriters and computers, which require long periods of repetitive motions in a fixed posture. Extreme temperatures have also been reported as risk factor for RSI.

Risk factors
Occupational risk factors
Workers in certain fields are at risk of repetitive strains. Most occupational injuries are musculoskeletal disorders, and many of these are caused by cumulative trauma rather than a single event.  Miners and poultry workers, for example, must make repeated motions which can cause tendon, muscular, and skeletal injuries. Jobs that involve repeated motion patterns or prolonged posture within a work cycle, or both, may be repetitive. Young athletes are predisposed to RSIs due to an underdeveloped musculoskeletal system.

Psychosocial factors
Factors such as personality differences to work-place organization problems.  Certain workers may negatively perceive their work organization due to excessive work rate, long work hours, limited job control, and low social support.  Previous studies shown elevated urinary catecholamines (stress-related chemicals) in workers with RSI.  Pain related to RSI may evolve into chronic pain syndrome particularly for workers who do not have supports from co-workers and supervisors.

Non-occupational factors
Age and gender are important risk factors for RSIs. The risk of RSI increases with age.   Women are more likely affected than men because of their smaller frame, lower muscle mass and strength, and due to endocrine influences. In addition, lifestyle choices such as smoking and alcohol consumption are recognizable risk factors for RSI. Recent scientific findings indicate that obesity and diabetes may predispose an individual to RSIs by creating a chronic low grade inflammatory response that prevents the body from effectively healing damaged tissues.

Diagnosis
RSIs are assessed using a number of objective clinical measures. These include effort-based tests such as grip and pinch strength, diagnostic tests such as Finkelsteins test for De Quervains tendinitis, Phalens contortion, Tinels percussion for carpal tunnel syndrome, and nerve conduction velocity tests that show nerve compression in the wrist. Various imaging techniques can also be used to show nerve compression such as x-ray for the wrist, and MRI for the thoracic outlet and cervico-brachial areas. Utilization of routine imaging  is useful in early detection and treatment of overuse injuries in at risk populations, which is important in preventing long term adverse effects.

Treatment
There are no quick fixes for RSI. Early diagnosis is critical to limiting damage. For Upper Limb Repetitive Strain Injury (RSI), Occupational Therapists create interventions that include education to facilitate ergonomics. This will minimize the possibility of an upper limb strain injury by learning the correct approach during facilitating functional task movements. The RICE treatment is used as the first treatment for many muscle strains, ligament sprains, or other bruises and injuries. RICE is used immediately after an injury happens and for the first 24 to 48 hours after the injury. These modalities can help reduce the swelling and pain. Commonly prescribed treatments for early-stage RSIs include analgesics, myofeedback, biofeedback, physical therapy, relaxation, and ultrasound therapy. Low-grade RSIs can sometimes resolve themselves if treatments begin shortly after the onset of symptoms. However, some RSIs may require more aggressive intervention including surgery and can persist for years.Although there are no "quick fixes" for RSI, there are effective approaches to its treatment and prevention. One is that of ergonomics, the changing of ones environment (especially workplace equipment) to minimize repetitive strain.
General exercise has been shown to decrease the risk of developing RSI.  Doctors sometimes recommend that those with RSI engage in specific strengthening exercises, for example to improve sitting posture, reduce excessive kyphosis, and potentially thoracic outlet syndrome. Modifications of posture and arm use are often recommended.

History
Although seemingly a modern phenomenon, RSIs have long been documented in the medical literature </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 Reactive airway disease and explain in detail? [/INST] Reactive airway disease (RAD) is an informal label that physicians apply to patients with symptoms similar to those of asthma. An exact definition of the condition does not exist. Individuals who are typically labeled as having RAD generally have a history of wheezing, coughing, dyspnea, and production of sputum that may or may not be caused by asthma. Symptoms may also include, but are not limited to, coughing, shortness of breath, excess mucus in the bronchial tube, swollen mucous membrane in the bronchial tube, and/or hypersensitive bronchial tubes. Physicians most commonly label patients with RAD when they are hesitant about formally diagnosing a patient with asthma, which is most prevalent in the pediatric setting. While some physicians may use RAD and asthma synonymously, there is controversy over this usage.
More generally, there is controversy over the use of RAD as a label in the healthcare setting, largely due to the ambiguous definition that the term has. Since RAD is not recognized as a real clinical diagnosis, its meaning is highly inconsistent and may cause confusion and misdiagnosis within the medical community. There are also concerns with overtreatment and undertreatment with RAD amongst physicians, since there is little formality with the label. Other problems that healthcare workers have with the use of the RAD label include its exclusion in the International Statistical Classification of Diseases and Related Health Problems, which can lead to billing issues in hospitals and other health care facilities, and the creation of a fabricated sense of security when using it has a diagnosis.RAD can be confused with reactive airways dysfunction syndrome, an asthma-like disorder that results from high exposure to vapors, fumes, and/or smoke. Unlike RAD, reactive airways dysfunction syndrome is recognized by multiple societies as a real clinical syndrome, including the American Thoracic Society and the American College of Chest Physicians.

Terminology
The term reactive airway disease originally began to appear in medical literature in the 1980s in reference to asthmatic patients with hyperactive airways, which is a common feature of asthma. This feature is characterized by increased bronchoconstriction reactions in response to stimuli that should not elicit so strong of response. These stimuli can include methacholine, histamine, and distilled water. However, while this was how the term initially was introduced, RAD soon began to be used interchangeably with the term asthma itself, which has led to the current controversy over its place in medical diagnoses.More commonly, RAD is now mostly used by physicians when they are hesitant to diagnose a patient with asthma. This is most prominent in pediatric settings for a variety of reasons. While infants tend to wheeze more often than adults, only one third of them eventually go on to actually have asthma. Asthma and viral bronchiolitis can also be nearly identical to each other when presented in very young children, since they both consist of wheezing, coughing, and nasal congestion. In addition, typical tests used to accurately diagnose children with asthma, such as the bronchial challenge test, are not considered to be accurate for children under the age of five. This can be due to failure of very young children to cooperate. Diagnosing a child with asthma also carries a certain negative connotation, causing hesitancy from some physicians to do so. All of these factors lead physicians to label young children with RAD instead of asthma, since the disease is often only suspected and unable to be confirmed with pediatric patients.Physicians will generally label an adult with RAD if they have no prior diagnosis or history of asthma while exhibiting symptoms of wheezing, production of sputum, and/or the use of an inhaler. Symptoms may also include, but are not limited to, coughing, shortness of breath, excess mucus in the bronchial tube, swollen mucous membrane in the bronchial tube, and/or hypersensitive bronchial tubes. In order to make a formal asthma diagnosis in adult patients, there is requirement to have documentation of either airway hyperreactivity or some sort of reversible airway obstruction. If none of these symptoms are present in an adult patients medical history or documentation, the physician may label the patient with RAD instead of asthma in order to still indicate there is an airway issue without formal diagnosis.

Reactive airways dysfunction syndrome
While the acronyms are similar, reactive airway disease (RAD) and reactive airways dysfunction syndrome (RADS) are not the same.Reactive airways dysfunction syndrome was first identified by Stuart M. Brooks and colleagues in 1985 as an asthma-like syndrome developing after a single exposure to high levels of an irritating vapor, fume, or smoke. It can manifest in adults with exposure to high levels of chlorine, ammonia, acetic acid, or sulphur dioxide, creating symptoms like asthma. These symptoms can vary from mild to fatal and can even create long-term airway damage, depending on the amount of exposure and the concentration of chlorine. Patients that have been diagnosed with RADS will likely have methacholine airway hyperreactivity, yet other tests that also measure pulmonary functions may appear normal. Some experts classify RADS as occupational asthma. Those with exposure to highly irritating substances should receive treatment to mitigate harmful effects. Treatment for RADS is similar to treatment for other disorders that result from acute inhalation. Preexisting allergies can be a risk factor for developing RADS.The main difference between RAD and RADS is that RADS can occur after just one exposure to the inhalants and without any prior sensitization. In addition, although the symptoms of RADS are very similar to those of asthma, they may be resolved. While some physicians argue that RADS is also not a real clinical syndrome, it is more commonly recognized in legitimate associations than RAD. These associations include the American Thoracic Society and the American College of Chest Physicians.

Controversy over use
There remains controversy over the use of RAD as an unofficial diagnosis. With its use not only being limited to clinical lexicon, but also transitioning to clinical literature now, more physicians are now increasingly disapproving its use in the healthcare setting.One of the largest problems with the using RAD as a diagnostic label lies in the ambiguity of its meaning, as RAD has no true clinical definition </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 Chronic traumatic encephalopathy and explain in detail? [/INST] Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repeated trauma to the head. The encephalopathy symptoms can include behavioral problems, mood problems, and problems with thinking. The disease often gets worse over time and can result in dementia. It is unclear if the risk of suicide is altered.Most documented cases have occurred in athletes involved in striking-based combat sports, such as boxing, kickboxing, mixed martial arts, and Muay Thai—hence its original name dementia pugilistica (Latin for "fistfighters dementia")—and contact sports such as American football, Australian rules football, professional wrestling, ice hockey, rugby, and association football (soccer), in semi-contact sports such as baseball and basketball, and military combat arms occupations. Other risk factors include being in the military, prior domestic violence, and repeated banging of the head. The exact amount of trauma required for the condition to occur is unknown, and as of 2022 definitive diagnosis can only occur at autopsy. The disease is classified as a tauopathy.There is no specific treatment for the disease. Rates of CTE have been found to be about 30% among those with a history of multiple head injuries; however, population rates are unclear. Research in brain damage as a result of repeated head injuries began in the 1920s, at which time the condition was known as dementia pugilistica or "fistfighters dementia", "boxers madness", or "punch drunk syndrome". It has been proposed that the rules of some sports be changed as a means of prevention.

Signs and symptoms
Symptoms of CTE, which occur in four stages, generally appear eight to ten years after an individual experiences repetitive mild traumatic brain injuries.First-stage symptoms are confusion, disorientation, dizziness, and headaches. Second-stage symptoms include memory loss, social instability, impulsive behavior, and poor judgment. Third and fourth stages include progressive dementia, movement disorders, hypomimia, speech impediments, sensory processing disorder, tremors, vertigo, deafness, depression and suicidality.Additional symptoms include dysarthria, dysphagia, cognitive disorders such as amnesia, and ocular abnormalities, such as ptosis. The condition manifests as dementia, or declining mental ability, problems with memory, dizzy spells or lack of balance to the point of not being able to walk under ones own power for a short time and/or Parkinsonism, or tremors and lack of coordination. It can also cause speech problems and an unsteady gait. Patients with CTE may be prone to inappropriate or explosive behavior and may display pathological jealousy or paranoia.

Cause
Most documented cases have occurred in athletes with mild repetitive head impacts (RHI) over an extended period of time. Evidence indicates that repetitive concussive and subconcussive blows to the head cause CTE. Specifically contact sports such as boxing, American football, Australian rules football, wrestling, mixed martial arts, ice hockey, rugby, and association football. In association football (soccer), whether this is just associated with prolific headers or other injuries is unclear as of 2017. Other potential risk factors include military personnel (repeated exposure to explosive charges or large caliber ordnance), domestic violence, and repeated banging of the head. The exact amount of trauma required for the condition to occur is unknown although it is believed that it may take years to develop.

Pathology
The neuropathological appearance of CTE is distinguished from other tauopathies, such as Alzheimers disease. The four clinical stages of observable CTE disability have been correlated with tau pathology in brain tissue, ranging in severity from focal perivascular epicenters of neurofibrillary tangles in the frontal neocortex to severe tauopathy affecting widespread brain regions.The primary physical manifestations of CTE include a reduction in brain weight, associated with atrophy of the frontal and temporal cortices and medial temporal lobe. The lateral ventricles and the third ventricle are often enlarged, with rare instances of dilation of the fourth ventricle. Other physical manifestations of CTE include anterior cavum septi pellucidi and posterior fenestrations, pallor of the substantia nigra and locus ceruleus, and atrophy of the olfactory bulbs, thalamus, mammillary bodies, brainstem and cerebellum. As CTE progresses, there may be marked atrophy of the hippocampus, entorhinal cortex, and amygdala.On a microscopic scale, a pathognomonic CTE lesion involves p-tau aggregates in neurons, with or without thorn-shaped astrocytes, at the depths of the cortical sulcus around a small blood vessel, deep in the parenchyma, and not restricted to the subpial and superficial region of the sulcus; the pathognomonic lesion must include p-tau in neurons to distinguish CTE from ARTAG. Supporting features of CTE are: superficial neurofibrillary tangles (NFTs); p–tau in CA2 and CA4 hippocampus; p-tau in: mammillary bodies, hypothalamic nuclei, amygdala, nucleus accumbens, thalamus, midbrain tegmentum, nucleus basalis of Meynert, raphe nuclei, substantia nigra and locus coeruleus; p-tau thorn-shaped astrocytes (TSA) in the subpial region; p-tau dot-like neurites. Purely astrocytic perivascular p-tau pathology represents ARTAG and does not meet the criteria for CTE. Beta-amyloid is not a feature of CTE, however a person with CTE may have comorbid pathologies such as Alzheimers disease.A small group of individuals with CTE have chronic traumatic encephalomyopathy (CTEM), which is characterized by symptoms of motor-neuron disease and which mimics amyotrophic lateral sclerosis (ALS). Progressive muscle weakness and balance and gait problems (problems with walking) seem to be early signs of CTEM.Exosome vesicles created by the brain are potential biomarkers of TBI, including CTE.Loss of neurons, scarring of brain tissue, collection of proteinaceous senile plaques, hydrocephalus, attenuation of the corpus callosum, diffuse axonal injury, neurofibrillary tangles, and damage to the cerebellum are implicated in the syndrome. Neurofibrillary tangles have been found in the brains of dementia pugilistica patients, but not in the same distribution as is usually found in people with Alzheimers. One group examined slices of brain from patients having had multiple mild traumatic brain injuries and found changes in the cells cytoskeletons, which they suggested might be due to damage to cerebral blood vessels.Increased exposure to concussions and subconcussive blows is regarded as the most important risk factor. This exposure can depend on the total number of fights, number of knockout losses, the duration of career, fight frequency, age of retirement, and boxing style.

Diagnosis
Diagnosis of CTE cannot be made in living individuals; a clear diagnosis is only possible during an autopsy. Though there are signs and symptoms some researchers associate with CTE, there is no definitive test to prove the existence in a living person. Signs are also very similar to that of other neurological conditions such as Alzheimers.The lack of distinct biomarkers is the reason CTE cannot typically be diagnosed while a person is alive. Concussions are non-structural injuries and do not result in brain bleeding, which is why most concussions cannot be seen on routine neuroimaging tests such as CT or MRI. Acute concussion symptoms (those that occur shortly after an injury) should not be confused with CTE. Differentiating between prolonged post-concussion syndrome (PCS, where symptoms begin shortly after a concussion and last for weeks, months, and sometimes even years) and CTE symptoms can be difficult. Research studies are examining whether neuroimaging can detect subtle changes in axonal integrity and structural lesions that can occur in CTE. Recently, more progress in in-vivo diagnostic techniques for CTE has been made, using DTI, fMRI, MRI, and MRS imaging; however, more research needs to be done before any such techniques can be validated.PET tracers that bind specifically to tau protein are desired to aid diagnosis of CTE in living individuals. One candidate is the tracer [18F]FDDNP, which is retained in the brain in individuals with a number of dementing disorders such as Alzheimers disease, Down syndrome, progressive supranuclear palsy, corticobasal degeneration, familial frontotemporal dementia, and Creutzfeldt–Jakob disease. In a small study of 5 retired NFL players with cognitive and mood symptoms, the PET scans revealed accumulation of the tracer in their brains. However, [18F]FDDNP binds to beta-amyloid and other proteins as well. Moreover, the sites in the brain where the tracer was retained were not consistent with the known neuropathology of CTE. A more promising candidate is the tracer [18F]-T807, which binds only to tau. It is being tested in several clinical trials.A putative biomarker for CTE is the presence in serum of autoantibodies against the brain. The autoantibodies were detected in football players who experienced a large number of head hits but no concussions, suggesting that even sub-concussive episodes may be damaging to the brain. The autoantibodies may enter the brain by means of a disrupted blood-brain barrier, and attack neuronal cells which are normally protected from an immune onslaught. Given the large numbers of neurons present in the brain (86 billion), and considering the poor penetration of antibodies across a normal blood-brain barrier, there is an extended period of time between the initial events (head hits) and the development of any signs or symptoms. Nevertheless, autoimmune changes in blood of players may constitute the earliest measurable event predicting CTE.According to 2017 study on brains of deceased gridiron football players, 99% of tested brains of NFL players, 88% of CFL players, 64% of semi-professional players, 91% of college football players, and 21% of high school football players had various stages of CTE. Players still alive are not able to be tested.

Imaging
Although the diagnosis of CTE cannot be determined by imaging, the effects of head trauma may be seen with the use of structural imaging. Imaging techniques include the use of magnetic resonance imaging, nuclear magnetic resonance spectroscopy, CT scan, single-photon emission computed tomography, Diffusion MRI, and Positron emission tomography (PET). One specific use of imaging is the use of a PET scan is to evaluate for tau deposition, which has been conducted on retired NFL players.

Prevention
The use of helmets and mouth-guards has been put forward as a possible preventative measure; though neither has significant research to support its use, both have been shown to reduce direct head trauma. Although there is no significant research to support the use of helmets to reduce the risk of concussions, there is evidence to support that helmet use reduces impact forces. Mouth guards have been shown to decrease dental injuries, but again have not shown significant evidence to reduce concussions. Because repeated impacts are thought to increase the likelihood of CTE development, a growing area of practice is improved recognition and treatment for concussions and other head trauma; removal from sport participation during recovery from these traumatic injuries is essential. Proper return-to-play protocol after possible brain injuries is also important in decreasing the significance of future impacts.Efforts are being made to change the rules of contact sports to reduce the frequency and severity of blows to the head. Examples of these rule changes are the evolution of tackling technique rules in American football, such as the banning of helmet-first tackles, and the addition of rules to protect defenseless players. Likewise, another growing area of debate is better implementation of rules already in place to protect athletes.Because of the concern that boxing may cause CTE, there is a movement among medical professionals to ban the sport. Medical professionals have called for such a ban as early as the 1950s.

Management
No cure exists for CTE, and because it cannot be tested for until an autopsy is performed, people cannot know if they have it. Treatment is supportive as with other forms of dementia. Those with CTE-related symptoms may receive medication and non-medication related treatments.

Epidemiology
Rates of disease have been found to be about 30% among those with a history of multiple head injuries. Population rates, however, are unclear.Professional level athletes are the largest group with CTE, due to frequent concussions and sub-concussive impacts from play in contact sport. These contact-sports include American football, Australian rules football, ice hockey, Rugby football (Rugby union and Rugby league), boxing, kickboxing, mixed martial arts, association football, and wrestling. In association football, only prolific headers are known to have developed CTE.Cases of CTE were also recorded in baseball.According to a 2017 study on brains of deceased gridiron football players, 99% of tested brains of NFL players, 88% of CFL players, 64% of semi-professional players, 91% of college football players, and 21% of high school football players had various stages of CTE.Other individuals diagnosed with CTE were those involved in military service, had a previous history of chronic seizures, were domestically abused, or were involved in activities resulting in repetitive head collisions.

History
CTE was originally studied in boxers in the 1920s as "punch-drunk syndrome." Punch-drunk syndrome was first described in 1928 by a forensic pathologist, Dr. Harrison Stanford Martland, who was the chief medical examiner of Essex County in Newark, New Jersey, in a Journal of the American Medical Association article, in which he noted the tremors, slowed movement, confusion and speech problems typical of the condition. The term "punch-drunk" was replaced with "dementia pugilistica" in 1937 by J.A. Millsbaugh, as he felt the term was condescending to former boxers. The initial diagnosis of dementia pugilistica was derived from the Latin word for boxer pugil (akin to pugnus  fist, pugnāre  to fight).Other terms for the condition have included chronic boxers encephalopathy, traumatic boxers encephalopathy, boxers dementia, pugilistic dementia, chronic traumatic brain injury associated with boxing (CTBI-B), and punch-drunk syndrome.The seminal work on the disease came from British neurologist Macdonald Critchley, who in 1949 wrote a paper titled "Punch-drunk syndromes: the chronic traumatic encephalopathy of boxers". CTE was first recognized as affecting individuals who took considerable blows to the head, but was believed to be confined to boxers and not other athletes. As evidence pertaining to the clinical and neuropathological consequences of repeated mild head trauma grew, it became clear that this pattern of neurodegeneration was not restricted to boxers, and the term chronic traumatic encephalopathy became most widely used.In 1990, a patient nicknamed Wilma was diagnosed postmortem with dementia pugilistica; she was the first woman diagnosed with dementia pugilistica from domestic violence.In 2002, American football player Mike Webster died following unusual and unexplained behavior. In 2005 Nigerian-American neuropathologist Bennet Omalu, along with colleagues in the Department of Pathology at the University of Pittsburgh, published their findings in a paper titled "Chronic Traumatic Encephalopathy in a National Football League Player", followed by a paper on a second case in 2006 describing similar pathology.In June 2007 professional wrestler Chris Benoit murdered his wife and son before committing suicide days after appearing on television. His autopsy revealed he was in very advanced stages of CTE with his brain being said to resemble that of an 87-year-old with advanced Alzheimers.
In 2008, the Sports Legacy Institute joined with the Boston University School of Medicine (BUSM) to form the Center for the Study of Traumatic Encephalopathy (now the BU CTE Center). Brain Injury Research Institute (BIRI) also studies the impact of concussions.In 2014, Patrick Grange of Albuquerque was the first US soccer player with CTE at autopsy. He was well known for his heading and had died in 2012.On April 7, 2021, former National Football League player Phillip Adams was found to have shot and killed six people, before killing himself a day later. A subsequent autopsy revealed at that the time of the shooting, Adams had an "unusually severe" case of chronic traumatic encephalopathy.

Research
In 2005, forensic pathologist Bennet Omalu, along with colleagues in the Department of Pathology at the University of Pittsburgh, published a paper, "Chronic Traumatic Encephalopathy in a National Football League Player", in the journal Neurosurgery, based on analysis of the brain of deceased former NFL center Mike Webster. This was then followed by a paper on a second case in 2006 describing similar pathology, based on findings in the brain of former NFL player Terry Long.In 2008, the Center for the Study of Traumatic Encephalopathy at the BU School of Medicine (now the BU CTE Center) started the VA-BU-CLF Brain Bank at the Bedford Veterans Administration Hospital to analyze the effects of CTE and other neurodegenerative diseases on the brain and spinal cord of athletes, military veterans, and civilians. To date, the VA-BU-CLF Brain Bank is the largest CTE tissue repository in the world, with over 1000 brain donors.On 21 December 2009, the National Football League Players Association announced that it would collaborate with the BU CTE Center to support the centers study of repetitive brain trauma in athletes. Additionally, in 2010 the National Football League gave the BU CTE Center a $1 million gift with no strings attached. In 2008, twelve living athletes (active and retired), including hockey players Pat LaFontaine and Noah Welch as well as former NFL star Ted Johnson, committed to donate their brains to VA-BU-CLF Brain Bank after their deaths. In 2009, NFL Pro Bowlers Matt Birk, Lofa Tatupu, and Sean Morey pledged to donate their brains to the VA-BU-CLF Brain Bank.In 2010, 20 more NFL players and former players pledged to join the VA-BU-CLF Brain Donation Registry, including Chicago Bears linebacker Hunter Hillenmeyer, Hall of Famer Mike Haynes, Pro Bowlers Zach Thomas, Kyle Turley, and Conrad Dobler, Super Bowl Champion Don Hasselbeck and former pro players Lew Carpenter, and Todd Hendricks. In 2010, professional wrestlers Mick Foley, Booker T and Matt Morgan also agreed to donate their brains upon their deaths. Also in 2010, MLS player Taylor Twellman, who had to retire from the New England Revolution because of post-concussion symptoms, agreed to donate his brain upon his death. As of 2010, the VA-BU-CLF Brain Donation Registry consists of over 250 current and former athletes.In 2011, former North Queensland Cowboys player Shaun Valentine became the first Australian National Rugby League player to agree to donate his brain upon his death, in response to recent concerns about the effects of concussions on Rugby League players, who do not use helmets. Also in 2011, boxer Micky Ward, whose career inspired the film The Fighter, agreed to donate his brain upon his death. In 2018, NASCAR driver Dale Earnhardt Jr., who retired in 2017 citing multiple concussions, became the first auto racing competitor agreeing to donate his brain upon his death.In related research, the Center for the Study of Retired Athletes, which is part of the Department of Exercise and Sport Science at the University of North Carolina at Chapel Hill, is conducting research funded by National Football League Charities to "study former football players, a population with a high prevalence of exposure to prior Mild Traumatic Brain Injury (MTBI) and sub-concussive impacts, in order to investigate the association between increased football exposure and recurrent MTBI and neurodegenerative disorders such as cognitive impairment and Alzheimers disease (AD)".In February 2011, former NFL player Dave Duerson committed suicide via a gunshot to his chest, thus leaving his brain intact. Duerson left text messages to loved ones asking that his brain be donated to research for CTE. The family got in touch with representatives of the Boston University center studying the condition, said Robert Stern, the co-director of the research group. Stern said Duersons gift was the first time of which he was aware that such a request had been made by someone who had committed suicide that was potentially linked to CTE. Stern and his colleagues found high levels of the protein tau in Duersons brain. These elevated levels, which were abnormally clumped and pooled along the brain sulci, are indicative of CTE.In July 2010, NHL enforcer Bob Probert died of heart failure. Before his death, he asked his wife to donate his brain to CTE research because it was noticed that Probert experienced a mental decline in his 40s. In March 2011, researchers at Boston University concluded that Probert had CTE upon analysis of the brain tissue he donated </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Post-schizophrenic depression and explain in detail? [/INST] Post-schizophrenic depression is a "depressive episode arising in the aftermath of a schizophrenic illness where some low-level schizophrenic symptoms may still be present." Someone that has post-schizophrenic depression experiences both symptoms of depression and can also continue showing mild symptoms of schizophrenia. Unfortunately, depression is a common symptom found in patients with schizophrenia and can fly under the radar for years before others become aware of its presence in a patient. However, very little research has been done on the subject, meaning there are few answers to how it should be systematically diagnosed, treated, or what course the illness will take. Some scientists would entirely deny the existence of post-schizophrenic depression, insisting it is a phase in schizophrenia as a whole. As of late, post-schizophrenic depression has become officially recognized as a syndrome and is considered a sub-type of schizophrenia.

Symptoms
Because the nature of acute schizophrenia is similar to depression, it is difficult to differentiate normal levels of depression in patients with schizophrenia from depressive levels in post-schizophrenic depression. "Prominent subjectively low mood, suggesting depression, and prominent blunting of affect, suggesting negative symptoms, are the two features which are most helpful in differentiating [schizophrenia and depression]." A number of researchers believe that depression is actually a symptom of schizophrenia that has been hidden by the psychosis. However, symptoms usually arise after the first psychotic episodes if they will arise at all. Officially, diagnosing post-schizophrenia depression in a patient requires for the patient to be experiencing a depressive episode of either short or long term following the overcoming of schizophrenia. The patient must still demonstrate some schizophrenic symptoms but those symptoms must no longer be the focus of the illness. Typically, the depressive symptoms are not severe enough to be classified as a severe depressive episode. Formally, diagnosis entails the patient having had schizophrenia within the past year, a number of schizophrenic symptoms, and depression being present for two weeks or more. Mild schizophrenic signs may be withdrawing socially, agitation or hostility, and irregular sleep such as in the case of insomnia and hypersomnia.

Causes
There is no clear cause to how certain patients with schizophrenia develop post-schizophrenic depression while others may surpass this stage. However, there are a few theories as to possible causes. Those with post-schizophrenic depression often experience social isolation due to their illness, which may increase depression levels. There is strong evidence of stigma-related isolation against those with mental illnesses in a variety of societies, especially those with schizophrenia as they are often viewed as dangerous and unpredictable. Because of this isolation and studies linking social isolation and depression, it is possible that patients under these stigmas eventually develop post-schizophrenic depression. Depression in patients with schizophrenia may also be caused by substance abuse, which is fairly common among those with schizophrenia, as depressants such as alcohol and cannabis can be relaxing. Furthermore, with what little information is currently known about post-schizophrenic depression, the onset may be caused by not giving patients with schizophrenia antipsychotic medications. After being taken off of antipsychotic medication, schizophrenic patients antidepressant medication had to be increased, while those under antipsychotic medication reported having fewer depressive symptoms, further giving reason to believe that a lack of antipsychotic medication in earlier stages of schizophrenia may lead to post-schizophrenic depression. However, some psychology professionals still push for the reduction of neuroleptic drugs, as there is a popular belief that post-schizophrenic depression is caused by neuroleptic treatment. Therapists are also believed to engage the depression in people with schizophrenia, having given too much psychotherapy after the patient had overcome their schizophrenic symptoms. Schizophrenia itself should not be overlooked as a key player in causing post-schizophrenic depression, though. A study done over a two-year time period shadowing patients with schizophrenia and monitoring their depression was unable to locate possible triggers such as the ones previously listed, so it is possible the nature of schizophrenia itself is the primary cause of post-schizophrenic depression.

Suicide
Those with post-schizophrenic depression are also commonly at risk for suicidal tendencies. There is a trend correlated between suicide and post-schizophrenic depression according to Mulholland and Coopers research in "The Symptoms of Depression in Schizophrenia and its Management." Furthermore, depression and schizophrenia have both been studied individually to try to determine if there is a correlation, and research has indicated that there is a very strong tendency for people with depression or schizophrenia to attempt suicide. Statistically, out of all patients with schizophrenia, "10%...commit suicide.  Depressed patients with schizophrenia are at a particularly high risk for suicide the first few months after diagnosis and after hospital discharge." Risk factors increasing the chance of suicide are, from highest to lowest, previous depressive orders, previous suicide attempts, drug abuse, and several other factors </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 Cryptorchidism and explain in detail? [/INST] Cryptorchidism is the absence of one or both testes from the scrotum. The word is from Greek κρυπτός (kryptos) hidden and ὄρχις (orchis) testicle. It is the most common birth defect of the male genital tract. About 3% of full-term and 30% of premature infant boys are born with at least one undescended testis.
However, about 80% of cryptorchid testes descend by the first year of life (the majority within three months), making the true incidence of cryptorchidism around 1% overall. Cryptorchidism may develop after infancy, sometimes as late as young adulthood, but that is exceptional.

Cryptorchidism is distinct from monorchism, the condition of having only one testicle. Though the condition may occur on one or both sides, it more commonly affects the right testis.A testis absent from the normal scrotal position may be:

Anywhere along the "path of descent" from high in the posterior (retroperitoneal) abdomen, just below the kidney, to the inguinal ring
In the inguinal canal
Ectopic, having "wandered" from the path of descent, usually outside the inguinal canal and sometimes even under the skin of the thigh, the perineum, the opposite scrotum, or the femoral canal
Undeveloped (hypoplastic) or severely abnormal (dysgenetic)
Missing (also see anorchia).About two-thirds of cases without other abnormalities are unilateral; most of the other third involve both testes. In 90% of cases, an undescended testis can be felt in the inguinal canal. In a small minority of cases, missing testes may be found in the abdomen or appear to be nonexistent (truly "hidden").
Undescended testes are associated with reduced fertility, increased risk of testicular germ-cell tumors, and psychological problems when fully-grown. Undescended testes are also more susceptible to testicular torsion (and subsequent infarction) and inguinal hernias. Without intervention, an undescended testicle will usually descend during the first year of life, but to reduce these risks, undescended testes can be brought into the scrotum in infancy by a surgical procedure called an orchiopexy.Although cryptorchidism nearly always refers to congenital absence or maldescent, a testis observed in the scrotum in early infancy can occasionally "reascend" (move back up) into the inguinal canal. A testis that can readily move or be moved between the scrotum and canal is referred to as retractile.
Cryptorchidism, hypospadias, testicular cancer, and poor semen quality make up the syndrome known as testicular dysgenesis syndrome.

Signs and symptoms
Infertility
Many men who were born with undescended testes have reduced fertility, even after orchiopexy in infancy. The reduction with unilateral cryptorchidism is subtle, with a reported infertility rate of about 10%, compared with about 6% reported by the same study for the general population of adult men.
The fertility reduction after orchiopexy for bilateral cryptorchidism is more marked, about 38%, or six times that of the general population. The basis for the universal recommendation for early surgery is research showing degeneration of spermatogenic tissue and reduced spermatogonia counts after the second year of life in undescended testes. The degree to which this is prevented or improved by early orchiopexy is still uncertain.

Cancer risk
One of the strongest arguments for early orchiopexy is reducing the risk of testicular cancer. About one in 500 men born with one or both testes undescended develops testicular cancer, roughly a four- to 40-fold increased risk. The peak incidence occurs in the third and fourth decades of life. The risk is higher for intra-abdominal testes and somewhat lower for inguinal testes, but even the normally descended testis of a man whose other testis was undescended has about a 20% higher cancer risk than those of other men.The most common type of testicular cancer occurring in undescended testes is seminoma. It is usually treatable if caught early, so urologists often recommend that boys who had orchiopexy as infants be taught testicular self-examination, to recognize testicular masses and seek early medical care for them. Cancer developing in an intra-abdominal testis would be unlikely to be recognized before considerable growth and spread, and one of the advantages of orchiopexy is that a mass developing in a scrotal testis is far easier to recognize than an intra-abdominal mass.
Orchidopexy was originally thought to result in easier detection of testicular cancer, but did not lower the risk of actually developing cancer.  However, recent data have shown a paradigm shift.  The New England Journal of Medicine published in 2007 that orchidopexy performed before puberty resulted in a significantly reduced risk of testicular cancer than if done after puberty.The risk of malignancy in the undescended testis is four to 10 times higher than that in the general population and is about one in 80 with a unilateral undescended testis and one in 40 to one in 50 for bilateral undescended testes. The peak age for this tumor is 15–45 years old. The most common tumor developing in an undescended testis is a seminoma (65%); in contrast, after orchiopexy, seminomas represent only 30% of testicular tumors.

Causes
In most full-term infant boys with cryptorchidism but no other genital abnormalities, a cause cannot be found, making this a common, sporadic, unexplained (idiopathic) birth defect. A combination of genetics, maternal health, and other environmental factors may disrupt the hormones and physical changes that influence the development of the testicles.

Severely premature infants can be born before descent of testes.  Low birth weight is also a known factor.
A contributing role of environmental chemicals called endocrine disruptors that interfere with normal fetal hormone balance has been proposed.  The Mayo Clinic lists "parents exposure to some pesticides" as a known risk factor.
Risk factors may include exposure to regular alcohol consumption during pregnancy (five or more drinks per week, associated with a three-fold increase in cryptorchidism when compared to nondrinking mothers.  Cigarette smoking is also a known risk factor.
Family history of undescended testicles or other problems of genital development
Cryptorchidism occurs at a much higher rate in a large number of congenital malformation syndromes. Among the more common are Down syndrome, Prader–Willi syndrome, and Noonan syndrome.
In vitro fertilization, use of cosmetics by the mother, and pre-eclampsia have also been recognized as risk factors for development of cryptorchidism.In 2008, a study was published that investigated the possible relationship between cryptorchidism and prenatal exposure to a chemical called phthalate (DEHP), which is used in the manufacture of plastics. The researchers found a significant association between higher levels of DEHP metabolites in pregnant mothers and several sex-related changes, including incomplete descent of the testes in their sons.  According to the lead author of the study, a national survey found that 25% of U.S. women had phthalate levels similar to the levels that were found to be associated with sexual abnormalities.A 2010 study  examined the prevalence of congenital cryptorchidism among offspring whose mothers had taken mild analgesics, primarily over-the-counter pain medications including ibuprofen (e.g. Advil) and paracetamol (acetaminophen). Combining the results from a survey of pregnant women prior to their due date in correlation with the health of their children and an ex vivo rat model, the study found  that pregnant women who had been exposed to mild analgesics had a higher prevalence of baby boys born with congenital cryptorchidism.New insight into the testicular descent mechanism has been hypothesized by the concept of a male programming window derived from animal studies. According to this concept, testicular descent status is "set" during the period from eight to 14 weeks of gestation in humans. Undescended testis is a result of disruption in androgen levels only during this programming window.

Mechanism
Normal development
The testes begin as an immigration of primordial germ cells into testicular cords along the gonadal ridge in the abdomen of the early embryo. The interaction of several male genes organizes this developing gonad into a testis rather than an ovary by the second month of gestation. During the third to fifth months, the cells in the testes differentiate into testosterone-producing Leydig cells, and anti-Müllerian hormone-producing Sertoli cells. The germ cells in this environment become fetal spermatogonia. Male external genitalia develops during the third and fourth months of gestation and the fetus continues to grow, develop, and differentiate.
The testes remain high in the abdomen until the seventh month of gestation when they move from the abdomen through the inguinal canals into the two sides of the scrotum. Movement has been proposed to occur in two phases, under the control of somewhat different factors. The first phase, movement across the abdomen to the entrance of the inguinal canal, appears controlled (or at least greatly influenced) by anti-Müllerian hormone (AMH). The second phase, in which the testes move through the inguinal canal into the scrotum, is dependent on androgens (most importantly testosterone). In rodents, androgens induce the genitofemoral nerve to release calcitonin gene-related peptide, which produces rhythmic contractions of the gubernaculum, a ligament which connects the testis to the scrotum, but a similar mechanism has not been demonstrated in humans. Maldevelopment of the gubernaculum or deficiency or insensitivity to either AMH or androgen can, therefore, prevent the testes from descending into the scrotum. Some evidence suggests an additional paracrine hormone, referred to as descendin, may be secreted by the testes.
In many infants with inguinal testes, further descent of the testes into the scrotum occurs in the first six months of life. This is attributed to the postnatal surge of gonadotropins and testosterone that normally occurs between the first and fourth months of life.
Spermatogenesis continues after birth. In the third to fifth months of life, some of the fetal spermatogonia residing along the basement membrane become type A spermatogonia. More gradually, other fetal spermatogonia become type B spermatogonia and primary spermatocytes by the fifth year after birth. Spermatogenesis arrests at this stage until puberty.
Most normal-appearing undescended testes are also normal by microscopic examination, but reduced spermatogonia can be found. The tissue in undescended testes becomes more markedly abnormal ("degenerates") in microscopic appearance between two and four years after birth. Some evidence indicates early orchiopexy reduces this degeneration.

Pathophysiology
At least one contributing mechanism for reduced spermatogenesis in cryptorchid testes is temperature. The temperature of testes in the scrotum is at least a few degrees cooler than in the abdomen. Animal experiments in the middle of the 20th century suggested that raising the temperature could damage fertility. Some circumstantial evidence suggests tight underwear and other practices that raise the testicular temperature for prolonged periods can be associated with lower sperm counts. Nevertheless, research in recent decades suggests that the issue of fertility is more complex than a simple matter of temperature. Subtle or transient hormone deficiencies or other factors that lead to a lack of descent also may impair the development of spermatogenic tissue.
The inhibition of spermatogenesis by ordinary intra-abdominal temperature is so potent that continual suspension of normal testes tightly against the inguinal ring at the top of the scrotum by means of special "suspensory briefs" has been researched as a method of male contraception, and was referred to as "artificial cryptorchidism" by one report.
An additional factor contributing to infertility is the high rate of anomalies of the epididymis in boys with cryptorchidism (over 90% in some studies). Even after orchiopexy, these may also affect sperm maturation and motility at an older age.

Diagnosis
The most common diagnostic dilemma in otherwise normal boys is distinguishing a retractile testis from a testis that will not descend spontaneously into the scrotum. Retractile testes are more common than truly undescended testes and do not need to be operated on. In normal males, as the cremaster muscle relaxes or contracts, the testis moves lower or higher ("retracts") in the scrotum. This cremasteric reflex is much more active in infant boys than older men. A retractile testis high in the scrotum can be difficult to distinguish from a position in the lower inguinal canal. Though various maneuvers are used to do so, such as using a cross-legged position, soaping the examiners fingers, or examining in a warm bath, the benefit of surgery in these cases can be a matter of clinical judgment.
In the minority of cases with bilaterally nonpalpable testes, further testing to locate the testes, assess their function, and exclude additional problems is often useful. Scrotal ultrasound or magnetic resonance imaging performed and interpreted by a radiologist can often locate the testes while confirming absence of a uterus. At ultrasound, the undescended testis usually appears small, less echogenic than the contralateral normal testis and usually located in the inguinal region.  With color Doppler ultrasonography, the vascularity of the undescended testis is poor.A karyotype can confirm or exclude forms of dysgenetic primary hypogonadism, such as Klinefelter syndrome or mixed gonadal dysgenesis. Hormone levels (especially gonadotropins and AMH) can help confirm that hormonally functional testes are worth attempting to rescue, as can stimulation with a few injections of human chorionic gonadotropin to elicit a rise of the testosterone level. Occasionally, these tests reveal an unsuspected and more complicated intersex condition.
In the even smaller minority of cryptorchid infants who have other obvious birth defects of the genitalia, further testing is crucial and has a high likelihood of detecting an intersex condition or other anatomic anomalies. Ambiguity can indicate either impaired androgen synthesis or reduced sensitivity. The presence of a uterus by pelvic ultrasound suggests either persistent Müllerian duct syndrome (AMH deficiency or insensitivity) or a severely virilized genetic female with congenital adrenal hyperplasia. An unambiguous micropenis, especially accompanied by hypoglycemia or jaundice, suggests congenital hypopituitarism.

Treatment
The primary management of cryptorchidism is watchful waiting, due to the high likelihood of self-resolution. Where this fails, orchiopexy is effective if inguinal testes have not descended after 4–6 months.  Surgery is often performed by a pediatric urologist or pediatric surgeon, but in many communities still by a general urologist or surgeon.
When the undescended testis is in the inguinal canal, hormonal therapy is sometimes attempted and very occasionally successful. The most commonly used hormone therapy is human chorionic gonadotropin (hCG). A series of hCG injections (10 injections over five weeks is common) is given and the status of the testis/testes is reassessed at the end. Although many trials have been published, the reported success rates range widely, from roughly 5% to 50%, probably reflecting the varying criteria for distinguishing retractile testes from low inguinal testes. Hormone treatment does have the occasional incidental benefits of allowing confirmation of Leydig cell responsiveness (proven by a rise of the testosterone by the end of the injections) or inducing additional growth of a small penis (via the testosterone rise). Some surgeons have reported facilitation of surgery, perhaps by enhancing the size, vascularity, or healing of the tissue. A newer hormonal intervention used in Europe is the use of GnRH analogs such as nafarelin or buserelin; the success rates and putative mechanism of action are similar to hCG, but some surgeons have combined the two treatments and reported higher descent rates. Limited evidence suggests that germ cell count is slightly better after hormone treatment; whether this translates into better sperm counts and fertility rates at maturity has not been established. The cost of either type of hormone treatment is less than that of surgery and the chance of complications at appropriate doses is minimal. Nevertheless, despite the potential advantages of a trial of hormonal therapy, many surgeons do not consider the success rates high enough to be worth the trouble, since the surgery itself is usually simple and uncomplicated.
In cases where the testes are identified preoperatively in the inguinal canal, orchiopexy is often performed as an outpatient and has a very low complication rate. An incision is made over the inguinal canal. The testis with accompanying cord structure and blood supply is exposed, partially separated from the surrounding tissues ("mobilized"), and brought into the scrotum. It is sutured to the scrotal tissue or enclosed in a "subdartos pouch". The associated passage back into the inguinal canal, an inguinal hernia, is closed to prevent reascent.
In patients with intra-abdominal maldescended testis, laparoscopy is useful to see for oneself the pelvic structures, position of the testis and decide upon surgery (single or staged procedure ).
Surgery becomes more complicated if the blood supply is not ample and elastic enough to be stretched into the scrotum. In these cases, the supply may be divided, some vessels sacrificed with expectation of adequate collateral circulation. In the worst case, the testis must be "autotransplanted" into the scrotum, with all connecting blood vessels cut and reconnected (anastomosed).
When the testis is in the abdomen, the first stage of surgery is exploration to locate it, assess its viability, and determine the safest way to maintain or establish the blood supply. Multistage surgeries, or autotransplantation and anastomosis, are more often necessary in these situations. Just as often, intra-abdominal exploration discovers that the testis is nonexistent ("vanished"), or dysplastic and not salvageable.
The principal major complication of all types of orchiopexy is a loss of the blood supply to the testis, resulting in loss of the testis due to ischemic atrophy or fibrosis.

Other animals
Cryptorchidism is seen in all domestic animals, most commonly in stallions, boars, and canines. The prevalence of this condition can vary depending on species and breed. Evidence of this condition is more likely in companion animals and swine than ruminants. The cause of this condition can vary from a combination of genetics, environment, and epigenetics.

Dogs
Cryptorchidism is common in male dogs, occurring at a rate  up to 10%.  This condition is one of the most common congenital defects in purebred dogs (11%), with 14% reported in Siberian Huskies. Although the genetics are not fully understood, it is thought to be a recessive, and probably polygenetic, trait.  Some have speculated that it is a sex-limited autosomal recessive trait; however, it is unlikely to be simple recessive. Dog testes usually descend by 10 days of age and it is considered to be cryptorchidism if they do not descend by the age of eight weeks.  Cryptorchidism can be either bilateral (causing sterility) or unilateral, and inguinal or abdominal (or both).  Because it is an inherited trait, affected dogs should not be bred and should be castrated.  The parents should be considered carriers of the defect and a breeder should thoughtfully consider whether to breed the carrier parent or not.  Littermates may be normal, carriers, or cryptorchid.  Castration of the undescended teste(s) should be considered for cryptorchid dogs due to the high rate of testicular cancer, especially Sertoli cell tumors </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 Cytomegalovirus and explain in detail? [/INST] Cytomegalovirus (CMV) (from cyto- cell via Greek κύτος kútos- container + μέγας mégas big, megalo- + -virus via Latin vīrus poison) is a genus of viruses in the order Herpesvirales, in the family Herpesviridae, in the subfamily Betaherpesvirinae. Humans and other primates serve as natural hosts. The 11 species in this genus include human betaherpesvirus 5 (HCMV, human cytomegalovirus, HHV-5), which is the species that infects humans. Diseases associated with HHV-5 include mononucleosis and pneumonia. In the medical literature, most mentions of CMV without further specification refer implicitly to human CMV. Human CMV is the most studied of all cytomegaloviruses.MX2/MXB was identified as a restriction factor for herpesviruses, which acts at a very early stage of the replication cycle and MX2/MXB restriction of herpesvirus requires GTPase activity.

Taxonomy
Within the Herpesviridae, CMV belongs to the Betaherpesvirinae subfamily, which also includes the genera Muromegalovirus and Roseolovirus (human herpesvirus 6 and human betaherpesvirus 7). It is also related to other herpesviruses within the Alphaherpesvirinae subfamily, which includes herpes simplex viruses 1 and 2 and varicella-zoster virus, and the Gammaherpesvirinae subfamily, which includes Epstein–Barr virus and Kaposis sarcoma-associated herpesvirus.Several species of Cytomegalovirus have been identified and classified for different mammals. The most studied is Human cytomegalovirus (HCMV), which is also known as Human betaherpesvirus 5 (HHV-5). Other primate CMV species include Chimpanzee cytomegalovirus (CCMV) that infects chimpanzees and orangutans, and Simian cytomegalovirus (SCCMV) and Rhesus cytomegalovirus (RhCMV) that infect macaques; CCMV is known as both Panine beta herpesvirus 2 (PaHV-2) and Pongine betaherpesvirus 4 (PoHV-4). SCCMV is called cercopithecine betaherpesvirus 5 (CeHV-5) and RhCMV, Cercopithecine betaherpesvirus 8 (CeHV-8). A further two viruses found in the night monkey are tentatively placed in the genus Cytomegalovirus, and are called Herpesvirus aotus 1 and Herpesvirus aotus 3. Rodents also have viruses previously called cytomegaloviruses that are now reclassified under the genus Muromegalovirus; this genus contains Mouse cytomegalovirus (MCMV) is also known as Murid betaherpesvirus 1 (MuHV-1) and the closely related Murid betaherpesvirus 2 (MuHV-2) that is found in rats.

Species
The genus consists of these 11 species:
Aotine betaherpesvirus 1
Cebine betaherpesvirus 1
Cercopithecine betaherpesvirus 5
Human betaherpesvirus 5
Macacine betaherpesvirus 3
Macacine betaherpesvirus 8
Mandrilline betaherpesvirus 1
Panine betaherpesvirus 2
Papiine betaherpesvirus 3
Papiine betaherpesvirus 4
Saimiriine betaherpesvirus 4

Structure
Viruses in Cytomegalovirus are enveloped, with icosahedral, spherical to pleomorphic, and round geometries, and T=16 symmetry. The diameter is around 150–200 nm. Genomes are linear and nonsegmented, around 200 kb in length.

Genome
Herpesviruses have some of the largest genomes among human viruses, often encoding hundreds of proteins. For instance, the double‑stranded DNA (dsDNA) genome of wild-type HCMV strains has a size of around 235 kb and encodes at least 208 proteins. It is thus longer than all other human herpesviruses and one of the longest genomes of all human viruses in general. It has the characteristic herpesvirus class E genome architecture, consisting of two unique regions (unique long UL and unique short US), both flanked by a pair of inverted repeats (terminal/internal repeat long TRL/IRL and internal/terminal repeat short IRS/TRS). Both sets of repeats share a region of a few hundred bps, the so-called "a sequence"; the other regions of the repeats are sometimes referred to as "b sequence" and "c sequence".

Life cycle
Viral replication is nuclear and lysogenic </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 Steatocystoma simplex 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 Generalized eruptive histiocytoma 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 Proximal femoral focal deficiency and explain in detail? [/INST] Proximal femoral focal deficiency (PFFD), also known as Congenital Femoral Deficiency (CFD),   is a rare, non-hereditary birth defect that affects the pelvis, particularly the hip bone, and the proximal femur.  The disorder may affect one side or both, with the hip being deformed and the leg shortened.
It is commonly linked with the absence or shortening of a leg bone (fibular hemimelia) and the absence of a kneecap.  Other linked birth defects include the dislocation or instability of the joint between the femur and the kneecap, a shortened tibia or fibula, and foot deformities.

Causes
The cause of PFFD is uncertain.  Two hypotheses have been advanced.  The theory of sclerotome subtraction posits injury to neural crest cells that are the precursors to sensory nerves at the level of L4 and L5. Histologic studies of a fetus with unilateral PFFD have prompted an alternative hypothesis that PFFD is caused by a defect in maturation of chondrocytes (cartilage cells) at the growth plate.  In either hypothesis, the agent causing the injury is usually not known. Thalidomide is known to cause PFFD when the mother is exposed to it in the fifth or sixth week of pregnancy, and it is speculated that exposure to other toxins during pregnancy may also be a cause.  Other etiologies that have been suggested, but not proven, include anoxia, ischemia, radiation, infection, hormones, and mechanical force. PFFD occurs sporadically, and does not appear to be hereditary.

Diagnosis
Classifications
There are typically four classes (or types) of PFFD, ranging from class A to class D, as detailed by Aitken.Types of PFFD
Type A — The femur bone is slightly shorter on the proximal end (near the hip), and the femoral head (the ball of the thigh bone that goes into the hip socket) may not be solid enough to be seen on X-rays at birth, but later hardens (ossifies). This deformity is sometimes called congenital short femur, because the child’s anatomy from hip to knee is contiguous and similar to their peers except for the one shortened bone. In some cases, children with type A deformities will also have an externally rotated femur, which could lead to bowing of the legs (genu varum).
Type B — The femur bone is shorter on the proximal end (near the hip) and the defect affects both the femoral head (the ball) and the femoral shaft (the long part of the bone). This defect is more severe than type A deformities because it will not heal spontaneously and, at skeletal maturity, the proximal femur (lower part near the knee) will not connect with the femoral head.
Type C — The entire top half of the femur bone is absent, including the trochanters (the part of the bone in which muscles are attached to the upper thigh), and the femoral head </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 Cystic eyeball 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 Lupoid sycosis 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 Aneurysm of sinus of Valsalva and explain in detail? [/INST] Aneurysm of the aortic sinus, also known as the sinus of Valsalva, is a rare abnormality of the aorta, the largest artery in the body.  The aorta normally has three small pouches that sit directly above the aortic valve (the sinuses of Valsalva), and an aneurysm of one of these sinuses is a thin-walled swelling.  Aneurysms may affect the right (65–85%), non-coronary (10–30%), or rarely the left (< 5%) coronary sinus. These aneurysms may not cause any symptoms but if large can cause shortness of breath, palpitations or blackouts. Aortic sinus aneurysms can burst or rupture into adjacent cardiac chambers, which can lead to heart failure if untreated.
Aortic sinus aneurysms may occur in isolation, or may been seen in association with other diseases of the aorta including Marfan syndrome, Loeys-Dietz syndrome, and bicuspid aortic valve.  They can be diagnosed using an echocardiogram or cardiac magnetic resonance imaging (MRI) scan.  Treatment includes blood pressure control but surgical repair may be needed, especially if the aneurysm ruptures.

Symptoms and signs
If unruptured, sinus of Valsalva aneurysm (commonly abbreviated SVA or SOVA) is usually asymptomatic and typically goes undetected until symptoms appear or medical imaging is performed for other reasons. If symptoms do occur, the most common are shortness of breath, palpitations, myocardial ischemia, and syncope. Even less common, but more serious, presentations are embolic stroke and myocardial infarction due to blockage of a coronary artery by the aneurysm.A ruptured aneurysm typically leads to an aortocardiac shunt and progressively worsening heart failure.An aneurysm of the aortic sinus may rupture due to infective endocarditis involving the aortic wall and tertiary-stage syphilis.The manifestations appear depending on the site where the sinus has ruptured. For example, if the sinus ruptures in a low pressure area like the right atrium or right ventricle then a continuous type of murmur is heard. The murmur is located in the left parasternal region mainly confined to the lower sternum. It is also accompanied by a superficial thrill. A ruptured Sinus of Valsalva abscess represents a surgical emergency.

Causes
This type of aneurysm is typically congenital and may be associated with heart defects </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 Syringomyelia and explain in detail? [/INST] Syringomyelia is a generic term referring to a disorder in which a cyst or cavity forms within the spinal cord. Often, syringomyelia is used as a generic term before an etiology is determined. This cyst, called a syrinx, can expand and elongate over time, destroying the spinal cord. The damage may result in loss of feeling, paralysis, weakness, and stiffness in the back, shoulders, and extremities. Syringomyelia may also cause a loss of the ability to feel extremes of hot or cold, especially in the hands. It may also lead to a cape-like bilateral loss of pain and temperature sensation along the upper chest and arms. The combination of symptoms varies from one patient to another depending on the location of the syrinx within the spinal cord, as well as its extent.
Syringomyelia has a prevalence estimated at 8.4 cases per 100,000 people, with symptoms usually beginning in young adulthood. Signs of the disorder tend to develop slowly, although sudden onset may occur with coughing, straining, or myelopathy.

Signs and symptoms
Syringomyelia causes a wide variety of neuropathic symptoms, due to damage to the spinal cord. Patients may experience severe chronic pain, abnormal sensations and loss of sensation, particularly in the hands. Some patients experience paralysis or paresis, temporarily or permanently. A syrinx may also cause disruptions in the parasympathetic and sympathetic nervous systems, leading to abnormal body temperature or sweating, bowel control issues, or other problems. If the syrinx is higher up in the spinal cord or affecting the brainstem, as in syringobulbia, vocal cord paralysis, ipsilateral tongue wasting, trigeminal nerve sensory loss, and other signs may be present. Rarely, bladder stones can occur at the onset of weakness in the lower extremities.
Classically, syringomyelia spares the dorsal column/medial lemniscus of the spinal cord, leaving pressure, vibration, touch and proprioception intact in the upper extremities. Neuropathic arthropathy, also known as a Charcot joint, can occur, particularly in the shoulders, in patients with syringomyelia. The loss of sensory fibers to the joint is theorized to lead to degeneration of the joint over time.

Cause
Generally, there are two forms of syringomyelia: congenital and acquired. Syringomyelia is generally a chronic disorder that occurs over time, resulting in muscular atrophy. Acquired Syringomyelia can be caused by a serious physical trauma to the body such as in a road traffic accident. Syringomyelia can also be classified into communicating and noncommunicating forms. Communicating typically occurs due to lesions on the foramen magnum and noncommunicating occurring due to other spinal cord diseases.

Congenital
The first major form relates to an abnormality of the brain called an Arnold–Chiari malformation or Chiari malformation. This is the most common cause of syringomyelia, where the anatomic abnormality, which may be due to a small posterior fossa, causes the lower part of the cerebellum to protrude from its normal location in the back of the head into the cervical or neck portion of the spinal canal. A syrinx may then develop in the cervical region of the spinal cord. Here, symptoms usually begin between the ages of 25 and 40 and may worsen with straining, called a valsalva maneuver, or any activity that causes cerebrospinal fluid pressure to fluctuate suddenly. Some patients, however, may have long periods of stability. Some patients with this form of the disorder also have hydrocephalus, in which cerebrospinal fluid accumulates in the skull, or a condition called arachnoiditis, in which a covering of the spinal cord—the arachnoid membrane—is inflamed.  Some cases of syringomyelia are familial, although this is rare.

Acquired
The second major form of syringomyelia occurs as a complication of trauma, meningitis, hemorrhage, a tumor, or arachnoiditis. Here, the syrinx or cyst develops in a segment of the spinal cord damaged by one of these conditions. The syrinx then starts to expand. This is sometimes referred to as noncommunicating syringomyelia. Symptoms may appear months or even years after the initial injury, starting with pain, weakness, and sensory impairment originating at the site of trauma.The primary symptom of post-traumatic syringomyelia (often referred to using the abbreviation of PTS) is pain, which may spread upward from the site of injury. Symptoms, such as pain, numbness, weakness, and disruption in temperature sensation, may be limited to one side of the body. Syringomyelia can also adversely affect sweating, sexual function, and, later, bladder and bowel control. A typical cause of PTS would be a car accident or similar trauma involving a whiplash injury.What can make PTS difficult to diagnose is the fact that symptoms can often first appear long after the actual cause of the syrinx occurred (e.g., a car accident occurring and then the patient first experiencing PTS symptoms such as pain, loss of sensation, and reduced ability on the skin to feel varying degrees of hot and cold a number of months after the car accident).

Pathogenesis
The pathogenesis of syringomyelia is debated. The cerebrospinal fluid also serves to cushion the brain. Excess cerebrospinal fluid in the central canal of the spinal cord is called hydromyelia. This term refers to increased cerebrospinal fluid that is contained within the ependyma of the central canal.  When fluid dissects into the surrounding white matter forming a cystic cavity or syrinx, the term syringomyelia is applied.  As these conditions coexist in the majority of cases, the term syringohydromyelia is applied. The terms are used interchangeably.It has been observed that obstruction of the cerebrospinal fluid spaces in the subarachnoid space can result in syrinx formation, and alleviation of the obstruction may improve symptoms.  A number of pathological conditions can cause an obstruction of the normal cerebrospinal fluid spaces. These include Chiari malformation, spinal arachnoiditis, scoliosis, spinal vertebrae misalignment, spinal tumors, spina bifida, and others.  The reasons that blockage of the cerebrospinal fluid space within the subarachnoid space can result in syrinx formation are not fully understood although a small posterior fossa is one known cause.  It is unclear if syrinx fluid originates from bulk movement of cerebrospinal fluid into the spinal cord, from bulk transmural movement of blood fluids through the spinal vasculature into the syrinx, or from a combination of both. Recent work suggests that central nervous system compliance is the underlying problem for the central nervous system, and also that hydrocephalus and syringomyelia have related causes.

Diagnosis
Physicians now use magnetic resonance imaging (MRI) to diagnose syringomyelia. The MRI radiographer takes images of body anatomy, such as the brain and spinal cord, in vivid detail. This test will show the syrinx in the spine or any other conditions, such as the presence of a tumor. MRI is safe, painless, and informative and has greatly improved the diagnosis of syringomyelia.The physician may order additional tests to help confirm the diagnosis. One of these is called electromyography (EMG), which show possible lower motor neuron damage.Note this test isnt used diagnostically for injuries to the spine but to nerves and muscles.This would be part of a patients rehab routine. In addition, computed axial tomography (CT) scans of a patients head may reveal the presence of tumors and other abnormalities such as hydrocephalus.Like MRI and CT scans, another test, called a myelogram, uses radiographs and requires a contrast medium to be injected into the subarachnoid space. Since the introduction of MRI, this test is rarely necessary to diagnose syringomyelia.The possible causes are trauma, tumors, and congenital defects. It is most usually observed in the part of the spinal cord corresponding to the neck area. Symptoms are due to spinal cord damage and include pain, decreased sensation of touch, weakness, and loss of muscle tissue. The diagnosis is confirmed with a spinal CT, myelogram or MRI of the spinal cord. The cavity may be reduced by surgical decompression.Furthermore, evidence also suggests that impact injuries to the thorax area highly correlate with the occurrence of a cervical-located syrinx.

Treatment
Surgery
Treating syringomyelia sometimes requires surgery. Surgery involving the spinal cord carries certain risks, and as with any medical treatment, the potential benefits have to be weighed against the possible complications. On the other hand, delaying treatment can increase the risk of permanent damage. Evaluation of the condition is necessary because syringomyelia can remain stationary for long periods of time, and in some cases progress rapidly.The main goal of surgical intervention is to correct the condition which led to the formation of the syrinx. Draining the syrinx can also help, by preventing it from becoming worse, but the symptoms the syrinx has already caused may not go away.In cases involving an Arnold–Chiari malformation, the main goal of surgery is to provide more space for the cerebellum at the base of the skull and upper cervical spine, without entering the brain or spinal cord. This often causes the syrinx to shrink or disappear over time, as the normal flow of cerebrospinal fluid is restored. If syringomyelia is caused by a tumor, removing the tumor – if possible – is the treatment of choice.Most patients’ symptoms stabilize or have a modest improvement following surgery. Syringomyelia can come back, however, requiring additional surgeries which may be less effective.In some cases, including both communicating and non-communicating forms of the condition, a syrinx may require ongoing drainage. This is done with a shunt, which uses tubes and valves to let cerebrospinal fluid (CSF) drain from the syrinx into another cavity within the body (usually the abdomen). This type of shunt, called a ventriculoperitoneal shunt, is particularly useful in cases involving hydrocephalus. By continually draining the syrinx, a shunt can arrest the progression of symptoms and relieve pain, headache, and tightness.Many factors affect the decision to use a shunt. There are risks of injury to the spinal cord, infection, drainage becoming blocked, and bleeding, and they do not always achieve the intended results. Draining the fluid more quickly does not produce better outcomes, but for some syrinxes, a shunt is the only drainage option.In the case of trauma-related syringomyelia, the surgeon operates at the level of the initial injury. The syrinx collapses at surgery, but a tube or shunt is usually necessary to prevent it from returning.

Non-surgical interventions
Surgery is not always recommended for syringomyelia patients. While there is no medication which can cure the condition, for many patients, the main treatment is analgesia to manage the symptoms. Physicians specializing in pain management can develop a medication and treatment plan to ameliorate pain. Medications to combat any neuropathic pain symptoms such as shooting and stabbing pains (e.g. gabapentin or pregabalin) would be first-line choices. Opiates are usually prescribed for pain for management of this condition. Conversely, facet joint injections are not indicated for the treatment of syringomyelia.Radiation is rare, but may be used if a tumor is involved. In these cases, it can halt the extension of a cavity and may help to alleviate pain.Treatment is usually reserved for cases which are causing symptoms. Treatment may not provide enough benefits to be recommended for elderly patients, or when symptoms are stable instead of worsening </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 Acneiform eruption 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 Complement 4 deficiency 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 Carrions disease and explain in detail? [/INST] Carrions disease is an infectious disease produced by Bartonella bacilliformis infection.
It is named after Daniel Alcides Carrión.

Signs and symptoms
The clinical symptoms of bartonellosis are pleomorphic and some patients from endemic areas may be asymptomatic. The two classical clinical presentations are the acute phase and the chronic phase, corresponding to the two different host cell types invaded by the bacterium (red blood cells and endothelial cells). An individual can be affected by either or both phases.

Acute phase
It is also called the hematic phase. The most common findings are fever (usually sustained, but with temperature no greater than 102 °F (39 °C)), pale appearance, malaise, painless liver enlargement, jaundice, enlarged lymph nodes, and enlarged spleen. This phase is characterized by severe hemolytic anemia and transient immunosuppression. The case fatality ratios of untreated patients exceeded 40% but reach around 90% when opportunistic infection with Salmonella spp. occurs. In a recent study, the attack rate was 13.8% (123 cases) and the case-fatality rate was 0.7%.Other symptoms include a headache, muscle aches, and general abdominal pain. Some studies have suggested a link between Carrions disease and heart murmurs due to the diseases impact on the circulatory system. In children, symptoms of anorexia, nausea, and vomiting have been investigated as possible symptoms of the disease.Most of the mortality of Carrions disease occurs during the acute phase. Studies vary in their estimates of mortality. In one study, mortality has been estimated as low as just 1% in studies of hospitalized patients, to as high as 88% in untreated, unhospitalized patients. In developed countries, where the disease rarely occurs, it is recommended to seek the advice of a specialist in infectious disease when diagnosed. Mortality is often thought to be due to subsequent infections due to the weakened immune symptoms and opportunistic pathogen invasion, or consequences of malnutrition due to weight loss in children. In a study focusing on pediatric and gestational effects of the disease,  mortality rates for pregnant women with the acute phase were estimated at 40% and rates of spontaneous abortion in another 40%.

Chronic phase
It is also called the eruptive phase or tissue phase, in which the patients develop a cutaneous rash produced by a proliferation of endothelial cells and is known as "Peruvian warts" or "verruga peruana". Depending on the size and characteristics of the lesions, there are three types: miliary (1–4 mm), nodular or subdermic, and mular (>5mm). Miliary lesions are the most common </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 Polyneuropathy and explain in detail? [/INST] Polyneuropathy (poly- + neuro- + -pathy) is damage or disease affecting peripheral nerves (peripheral neuropathy) in roughly the same areas on both sides of the body, featuring weakness, numbness, and burning pain. It usually begins in the hands and feet and may progress to the arms and legs and sometimes to other parts of the body where it may affect the autonomic nervous system. It may be acute or chronic. A number of different disorders may cause polyneuropathy, including diabetes and some types of Guillain–Barré syndrome.

Classification
Polyneuropathies may be classified in different ways, such as by cause, by presentation, or by classes of polyneuropathy, in terms of which part of the nerve cell is affected mainly: the axon, the myelin sheath, or the cell body.

Distal axonopathy, is the result of interrupted function of the peripheral nerves. It is the most common response of neurons to metabolic or toxic disturbances, and may be caused by metabolic diseases such as diabetes, kidney failure, connective tissue disease, deficiency syndromes such as malnutrition and alcoholism, or the effects of toxins or drugs such as chemotherapy. They may be divided according to the type of axon affected (large-fiber, small-fiber, or both), the most distal portions of axons are usually the first to degenerate, and axonal atrophy advances slowly toward the nerves cell body.  However, if the cause is removed, then regeneration is possible, although the prognosis depends on the duration and severity of the original stimulus. People with distal axonopathies usually present with sensorimotor disturbances such as amyotrophic lateral sclerosis
Myelinopathy, is due to a loss of myelin or of the Schwann cells. This demyelination slows down or completely blocks the conduction of action potentials through the axon of the nerve cell (neurapraxia). The most common cause is acute inflammatory demyelinating polyneuropathy AIDP, the most common form of Guillain–Barré syndrome (although other causes include chronic inflammatory demyelinating polyneuropathy )
Neuronopathy is the result of issues in the peripheral nervous system (PNS) neurons. They may be caused by motor neurone diseases, sensory neuronopathies, toxins, or autonomic dysfunction. Neurotoxins such as chemotherapy agents may cause neuronopathies.

Signs and symptoms
Among the signs/symptoms of polyneuropathy, which can be divided (into sensory and hereditary) and are consistent with the following:
Sensory polyneuropathy – ataxia, numbness, muscle wasting and paraesthesiae.
Hereditary polyneuropathy – scoliosis and hammer toes

Causes
The causes of polyneuropathy can be divided into hereditary and acquired and are therefore as follows:
Inherited -are hereditary motor neuropathies, Charcot–Marie–Tooth disease, and hereditary neuropathy with liability to pressure palsy
Acquired -are diabetes mellitus, vascular neuropathy, alcohol use disorder, and vitamin B12 deficiency

Pathophysiology
In regard to the pathophysiology of polyneuropathy, of course, the former depends on which polyneuropathy. For instance in the case of chronic inflammatory demyelinating polyneuropathy, one finds that it is an autoimmune disease. Here, T cells involvement has been demonstrated, while in terms of demyelination, antibodies alone are not capable.

Diagnosis
The diagnosis of polyneuropathies begins with a history and physical examination to ascertain the pattern of the disease process (such as-arms, legs, distal, proximal) if they fluctuate, and what deficits and pain are involved. If pain is a factor, determining where and how long the pain has been present is important, one also needs to know what disorders are present within the family and what diseases the person may have. Although diseases often are suggested by the physical examination and history alone, tests that may be employed include: electrodiagnostic testing, serum protein electrophoresis, nerve conduction studies, urinalysis, serum creatine kinase (CK) and antibody testing (nerve biopsy is sometimes done).Other tests may be used, especially tests for specific disorders associated with polyneuropathies, quality measures have been developed to diagnose patients with distal symmetrical polyneuropathy (DSP).

Differential diagnosis
In terms of the differential diagnosis for polyneuropathy one must look at the following:

Treatment
In the treatment of polyneuropathies one must ascertain and manage the cause, among management activities are: weight decrease, use of a walking aid, and occupational therapist assistance. Additionally, BP control in those with diabetes is helpful, while intravenous immunoglobulin is used for multifocal motor neuropathy.According to Lopate, et al., methylprednisolone is a viable treatment for chronic inflammatory demyelinative polyneuropathy (which can also be treated with intravenous immunoglobulin). The authors also indicate that prednisone has greater adverse effects in such treatment, as opposed to intermittent (high-doses) of the aforementioned medication.According to Wu, et al., in critical illness polyneuropathy supportive and preventive therapy are important for the affected individual, as well as, avoiding (or limiting) corticosteroids.

See also
References
Further reading
Dimachkie, Mazen M.; Barohn, Richard J. (7 April 2013). "Chronic Inflammatory Demyelinating Polyneuropathy". Current Treatment Options in Neurology. 15 (3): 350–366. doi:10.1007/s11940-013-0229-6. ISSN 1092-8480. PMC 3987657. PMID 23564314.
Katirji, Bashar; Kaminski, Henry J.; Ruff, Robert L. (2013-10-11) </s>