<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 Common cold and explain in detail? [/INST] The common cold, also known simply as a cold, is a viral infectious disease of the upper respiratory tract that primarily affects the respiratory mucosa of the nose, throat, sinuses, and larynx. Signs and symptoms may appear less than two days after exposure to the virus. These may include coughing, sore throat, runny nose, sneezing, headache, and fever. People usually recover in seven to ten days, but some symptoms may last up to three weeks. Occasionally, those with other health problems may develop pneumonia.Well over 200 virus strains are implicated in causing the common cold, with rhinoviruses, coronaviruses, adenoviruses and enteroviruses being the most common. They spread through the air during close contact with infected people or indirectly through contact with objects in the environment, followed by transfer to the mouth or nose. Risk factors include going to child care facilities, not sleeping well, and psychological stress. The symptoms are mostly due to the bodys immune response to the infection rather than to tissue destruction by the viruses themselves. The symptoms of influenza are similar to those of a cold, although usually more severe and less likely to include a runny nose.There is no vaccine for the common cold. The primary methods of prevention are hand washing; not touching the eyes, nose or mouth with unwashed hands; and staying away from sick people. Some evidence supports the use of face masks. There is also no cure, but the symptoms can be treated. Zinc may reduce the duration and severity of symptoms if started shortly after the onset of symptoms. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen may help with pain. Antibiotics, however, should not be used, as all colds are caused by viruses, and there is no good evidence that cough medicines are effective.The common cold is the most frequent infectious disease in humans. Under normal circumstances, the average adult gets two to three colds a year, while the average child may get six to eight. Infections occur more commonly during the winter. These infections have existed throughout human history.

Signs and symptoms
The typical symptoms of a cold include cough, runny nose, sneezing, nasal congestion, and a sore throat, sometimes accompanied by muscle ache, fatigue, headache, and loss of appetite. A sore throat is present in about 40% of cases, a cough in about 50%, and muscle ache likewise in about 50%. In adults, a fever is generally not present but it is common in infants and young children. The cough is usually mild compared to that accompanying influenza. While a cough and a fever indicate a higher likelihood of influenza in adults, a great deal of similarity exists between these two conditions. A number of the viruses that cause the common cold may also result in asymptomatic infections.The color of the mucus or nasal secretion may vary from clear to yellow to green and does not indicate the class of agent causing the infection.

Progression
A cold usually begins with fatigue, a feeling of being chilled, sneezing, and a headache, followed in a couple of days by a runny nose and cough. Symptoms may begin within sixteen hours of exposure and typically peak two to four days after onset. They usually resolve in seven to ten days, but some can last for up to three weeks. The average duration of cough is eighteen days and in some cases people develop a post-viral cough which can linger after the infection is gone. In children, the cough lasts for more than ten days in 35–40% of cases and continues for more than 25 days in 10%.

Causes
Viruses
The common cold is an infection of the upper respiratory tract which can be caused by many different viruses. The most commonly implicated is a rhinovirus (30–80%), a type of picornavirus with 99 known serotypes. Other commonly implicated viruses include human coronaviruses (≈ 15%), influenza viruses (10–15%), adenoviruses (5%), human respiratory syncytial virus (RSV), enteroviruses other than rhinoviruses, human parainfluenza viruses, and human metapneumovirus. Frequently more than one virus is present. In total, more than 200 viral types are associated with colds.

Transmission
The common cold virus is typically transmitted via airborne droplets (aerosols), direct contact with infected nasal secretions, or fomites (contaminated objects). Which of these routes is of primary importance has not been determined. The viruses may survive for prolonged periods in the environment (over 18 hours for rhinoviruses) and can be picked up by peoples hands and subsequently carried to their eyes or nose where infection occurs. Transmission from animals is considered highly unlikely; an outbreak documented at a British scientific base on Adelaide Island after seventeen weeks of isolation was thought to have been caused by transmission from a contaminated object or an asymptomatic human carrier, rather than from the husky dogs which were also present at the base.Transmission is common in daycare and at school due to the proximity of many children with little immunity and frequently poor hygiene. These infections are then brought home to other members of the family. There is no evidence that recirculated air during commercial flight is a method of transmission. People sitting in close proximity appear to be at greater risk of infection.Rhinovirus-caused colds are most infectious during the first three days of symptoms; they are much less infectious afterwards.

Weather
A common misconception is that one can "catch a cold" simply through prolonged exposure to cold weather. Although it is now known that colds are viral infections, the prevalence of many such viruses are indeed seasonal, occurring more frequently during cold weather. The reason for the seasonality has not been conclusively determined. Possible explanations may include cold temperature-induced changes in the respiratory system, decreased immune response, and low humidity causing an increase in viral transmission rates, perhaps due to dry air allowing small viral droplets to disperse farther and stay in the air longer.The apparent seasonality may also be due to social factors, such as people spending more time indoors, near infected people, and specifically children at school. Although normal exposure to cold does not increase ones risk of infection, severe exposure leading to significant reduction of body temperature (hypothermia) may put one at a greater risk for the common cold; although controversial, the majority of evidence suggests that it may increase susceptibility to infection.

Other
Herd immunity, generated from previous exposure to cold viruses, plays an important role in limiting viral spread, as seen with younger populations that have greater rates of respiratory infections. Poor immune function is a risk factor for disease. Insufficient sleep and malnutrition have been associated with a greater risk of developing infection following rhinovirus exposure; this is believed to be due to their effects on immune function. Breast feeding decreases the risk of acute otitis media and lower respiratory tract infections among other diseases, and it is recommended that breast feeding be continued when an infant has a cold. In the developed world breast feeding may not be protective against the common cold in and of itself.

Pathophysiology
The symptoms of the common cold are believed to be primarily related to the immune response to the virus. The mechanism of this immune response is virus specific. For example, the rhinovirus is typically acquired by direct contact; it binds to humans via ICAM-1 receptors and the CDHR3 receptor through unknown mechanisms to trigger the release of inflammatory mediators. These inflammatory mediators then produce the symptoms. It does not generally cause damage to the nasal epithelium. The respiratory syncytial virus (RSV), on the other hand, is contracted by direct contact and airborne droplets. It then replicates in the nose and throat before frequently spreading to the lower respiratory tract. RSV does cause epithelium damage. Human parainfluenza virus typically results in inflammation of the nose, throat, and bronchi. In young children when it affects the trachea it may produce the symptoms of croup due to the small size of their airways.

Diagnosis
The distinction between viral upper respiratory tract infections is loosely based on the location of symptoms, with the common cold affecting primarily the nose (rhinitis), throat (pharyngitis), and lungs (bronchitis). There can be significant overlap, and more than one area can be affected. Self-diagnosis is frequent. Isolation of the viral agent involved is rarely performed, and it is generally not possible to identify the virus type through symptoms.

Prevention
The only useful ways to reduce the spread of cold viruses are physical measures such as using correct hand washing technique and face masks; in the healthcare environment, gowns and disposable gloves are also used. Isolation or quarantine is not used as the disease is so widespread and symptoms are non-specific. There is no vaccine to protect against the common cold. Vaccination has proven difficult as there are many viruses involved and they mutate rapidly. Creation of a broadly effective vaccine is, therefore, highly improbable.Regular hand washing appears to be effective in reducing the transmission of cold viruses, especially among children. Whether the addition of antivirals or antibacterials to normal hand washing provides greater benefit is unknown. Wearing face masks when around people who are infected may be beneficial; however, there is insufficient evidence for maintaining a greater social distance.It is unclear if zinc supplements affect the likelihood of contracting a cold. Routine vitamin C supplements do not reduce the risk or severity of the common cold, though they may reduce its duration. Gargling with water was found useful in one small trial.

Management
Treatments of the common cold primarily involve medications and other therapies for symptomatic relief. Getting plenty of rest, drinking fluids to maintain hydration, and gargling with warm salt water are reasonable conservative measures. Much of the benefit from symptomatic treatment is, however, attributed to the placebo effect. As of 2010, no medications or herbal remedies had been conclusively demonstrated to shorten the duration of infection.

Symptomatic
Treatments that may help with symptoms include simple pain medication and medications for fevers such as ibuprofen and acetaminophen (paracetamol). It, however, is not clear if acetaminophen helps with symptoms. It is not known if over the counter cough medications are effective for treating an acute cough. Cough medicines are not recommended for use in children due to a lack of evidence supporting effectiveness and the potential for harm. In 2009, Canada restricted the use of over-the-counter cough and cold medication in children six years and under due to concerns regarding risks and unproven benefits. The misuse of dextromethorphan (an over-the-counter cough medicine) has led to its ban in a number of countries. Intranasal corticosteroids have not been found to be useful.In adults short term use of nasal decongestants may have a small benefit. Antihistamines may improve symptoms in the first day or two; however, there is no longer-term benefit and they have adverse effects such as drowsiness. Other decongestants such as pseudoephedrine appear effective in adults. Combined oral analgesics, antihistaminics and decongestants are generally effective for older children and adults. Ipratropium nasal spray may reduce the symptoms of a runny nose but has little effect on stuffiness. Ipratropium may also help with cough in adults. The safety and effectiveness of nasal decongestant use in children is unclear.Due to lack of studies, it is not known whether increased fluid intake improves symptoms or shortens respiratory illness. As of 2017 heated and humidified air, such as via RhinoTherm, is of unclear benefit. One study has found chest vapor rub to provide some relief of nocturnal cough, congestion, and sleep difficulty.Some advise to avoid physical exercise if there are symptoms such as fever, widespread muscle aches or fatigue. It is regarded as safe to perform moderate exercise if the symptoms are confined to the head, including runny nose, nasal congestion, sneezing, or a minor sore throat. There is a popular belief that having a hot drink can help with cold symptoms, but evidence to support this is very limited.

Antibiotics and antivirals
Antibiotics have no effect against viral infections, including the common cold. Due to their side effects, antibiotics cause overall harm but are still frequently prescribed. Some of the reasons that antibiotics are so commonly prescribed include peoples expectations for them, physicians desire to help, and the difficulty in excluding complications that may be amenable to antibiotics. There are no effective antiviral drugs for the common cold even though some preliminary research has shown benefits.

Zinc
Zinc supplements may shorten the duration of colds by up to 33% and reduce the severity of symptoms if supplementation begins within 24 hours of the onset of symptoms. Some zinc remedies directly applied to the inside of the nose have led to the loss of the sense of smell. A 2017 review did not recommend the use of zinc for the common cold for various reasons; whereas a 2017 and 2018 review both recommended the use of zinc, but also advocated further research on the topic.

Alternative medicine
While there are many alternative medicines and Chinese herbal medicines supposed to treat the common cold, there is insufficient scientific evidence to support their use. As of 2015, there is weak evidence to support nasal irrigation with saline. There is no firm evidence that Echinacea products or garlic provide any meaningful benefit in treating or preventing colds.

Vitamins C and D
Vitamin C supplementation does not affect the incidence of the common cold, but may reduce its duration. There is no conclusive evidence that vitamin D supplementation is efficacious in the prevention or treatment of respiratory tract infections.

Prognosis
The common cold is generally mild and self-limiting with most symptoms generally improving in a week. In children, half of cases go away in 10 days and 90% in 15 days. Severe complications, if they occur, are usually in the very old, the very young, or those who are immunosuppressed. Secondary bacterial infections may occur resulting in sinusitis, pharyngitis, or an ear infection. It is estimated that sinusitis occurs in 8% and ear infection in 30% of cases.

Epidemiology
The common cold is the most common human disease and affects people all over the globe. Adults typically have two to three infections annually, and children may have six to ten colds a year (and up to twelve colds a year for school children). Rates of symptomatic infections increase in the elderly due to declining immunity.Native Americans and Inuit are more likely to be infected with colds and develop complications such as otitis media than Caucasians. This may be explained as much by issues such as poverty and overcrowding as by ethnicity.

History
While the cause of the common cold was identified in the 1950s, the disease appears to have been with humanity since its early history. Its symptoms and treatment are described in the Egyptian Ebers papyrus, the oldest existing medical text, written before the 16th century BCE. The name "cold" came into use in the 16th century, due to the similarity between its symptoms and those of exposure to cold weather.In the United Kingdom, the Common Cold Unit (CCU) was set up by the Medical Research Council in 1946 and it was where the rhinovirus was discovered in 1956. In the 1970s, the CCU demonstrated that treatment with interferon during the incubation phase of rhinovirus infection protects somewhat against the disease, but no practical treatment could be developed. The unit was closed in 1989, two years after it completed research of zinc gluconate lozenges in the prevention and treatment of rhinovirus colds, the only successful treatment in the history of the unit.

Research directions
Antivirals have been tested for effectiveness in the common cold; as of 2009, none had been both found effective and licensed for use. There are ongoing trials of the anti-viral drug pleconaril which shows promise against picornaviruses as well as trials of BTA-798. The oral form of pleconaril had safety issues and an aerosol form is being studied. Double-stranded RNA activated caspase oligomerizer (DRACO), a broad-spectrum antiviral therapy, has shown preliminary effectiveness in treating rhinovirus, as well as other infectious viruses.The genomes of all known human rhinovirus strains have been sequenced.

Societal impact
The economic impact of the common cold is not well understood in much of the world. In the United States, the common cold leads to 75–100 million physician visits annually at a conservative cost estimate of $7.7 billion per year </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 Genital wart and explain in detail? [/INST] Genital warts are a sexually transmitted infection caused by certain types of human papillomavirus (HPV). They are generally pink in color and project out from the surface of the skin. Usually they cause few symptoms, but can occasionally be painful. Typically they appear one to eight months following exposure. Warts are the most easily recognized symptom of genital HPV infection.HPV types 6 and 11 are responsible for causing majority of genital warts whereas HPV types 16, 18, 31, 33, and 35 are also occasionally found. It is spread through direct skin-to-skin contact, usually during oral, genital, or anal sex with an infected partner. Diagnosis is generally based on symptoms and can be confirmed by biopsy. The types of HPV that cause cancer are not the same as those that cause warts.Some HPV vaccines can prevent genital warts as may condoms. Treatment options include creams such as podophyllin, imiquimod, and trichloroacetic acid. Cryotherapy or surgery may also be an option. After treatment warts often resolve within six months. Without treatment, in up to a third of cases they resolve on their own.About 1% of people in the United States have genital warts. Many people, however, are infected and do not have symptoms. Without vaccination nearly all sexually active people will get some type of HPV at one point in their lives. The disease has been known at least since the time of Hippocrates in 300 BC.

Signs and symptoms
They may be found anywhere in the anal or genital area, and are frequently found on external surfaces of the body, including the penile shaft, scrotum, or labia majora of the vagina. They can also occur on internal surfaces like the opening to the urethra, inside the vagina, on the cervix, or in the anus.They can be as small as 1-5mm in diameter, but can also grow or spread into large masses in the genital or anal area. In some cases they look like small stalks. They may be hard ("keratinized") or soft. Their color can be variable, and sometimes they may bleed.In most cases, there are no symptoms of HPV infection other than the warts themselves. Sometimes warts may cause itching, redness, or discomfort, especially when they occur around the anus. Although they are usually without other physical symptoms, an outbreak of genital warts may cause psychological distress, such as anxiety, in some people.

Causes
Transmission
HPV is most commonly transmitted through penetrative sex. While HPV can also be transmitted via non-penetrative sexual activity, it is less transmissible than via penetrative sex. There is conflicting evidence about the effect of condoms on transmission of low-risk HPV. Some studies have suggested that they are effective at reducing transmission. Other studies suggest that condoms are not effective at preventing transmission of the low-risk HPV variants that cause genital warts. The effect of condoms on HPV transmission may also be sex-dependent; there is some evidence that condoms are more effective at preventing infection of males than of females.The types of HPV that cause warts are highly transmissible. Roughly three out of four unaffected partners of patients with warts develop them within eight months.  Other studies of partner concordance suggest that the presence of visible warts may be an indicator of increased infectivity; HPV concordance rates are higher in couples where one partner has visible warts.

Latency and recurrence
Although 90% of HPV infections are cleared by the body within two years of infection, it is possible for infected cells to undergo a latency (quiet) period, with the first occurrence or a recurrence of symptoms happening months or years later. Latent HPV, even with no outward symptoms, is still transmissible to a sexual partner. If an individual has unprotected sex with an infected partner, there is a 70% chance that he or she will also become infected.In individuals with a history of previous HPV infection, the appearance of new warts may be either from a new exposure to HPV, or from a recurrence of the previous infection. As many as one-third of people with warts will experience a recurrence.

Children
Anal or genital warts may be transmitted during birth. The presence of wart-like lesions on the genitals of young children has been suggested as an indicator of sexual abuse. However, genital warts can sometimes result from autoinoculation by warts elsewhere on the body, such as from the hands.  It has also been reported from sharing of swimsuits, underwear, or bath towels, and from non-sexual touching during routine care such as diapering. Genital warts in children are less likely to be caused by HPV subtypes 6 and 11 than adults, and more likely to be caused by HPV types that cause warts elsewhere on the body ("cutaneous types"). Surveys of pediatricians who are child abuse specialists suggest that in children younger than 4 years old, there is no consensus on whether the appearance of new anal or genital warts, by itself, can be considered an indicator of sexual abuse.

Diagnosis
The diagnosis of genital warts is most often made visually, but may require confirmation by biopsy in some cases. Smaller warts may occasionally be confused with molluscum contagiosum.
Genital warts, histopathologically, characteristically rise above the skin surface due to enlargement of the dermal papillae, have parakeratosis and the characteristic nuclear changes typical of HPV infections (nuclear enlargement with perinuclear clearing).
DNA tests are available for diagnosis of high-risk HPV infections. Because genital warts are caused by low-risk HPV types, DNA tests cannot be used for diagnosis of genital warts or other low-risk HPV infections.Some practitioners use an acetic acid solution to identify smaller warts ("subclinical lesions"), but this practice is controversial. Because a diagnosis made with acetic acid will not meaningfully affect the course of the disease, and cannot be verified by a more specific test, a 2007 UK guideline advises against its use.

Prevention
Gardasil (sold by Merck & Co.) is a vaccine that protects against human papillomavirus types 6, 11, 16 and 18. Types 6 and 11 cause genital warts, while 16 and 18 cause cervical cancer.  The vaccine is preventive, not therapeutic, and must be given before exposure to the virus type to be effective, ideally before the beginning of sexual activity. The vaccine is approved by the US Food and Drug Administration for use in both males and females as early as 9 years of age.In the UK, Gardasil replaced Cervarix in September 2012 for reasons unrelated to safety. Cervarix had been used routinely in young females from its introduction in 2008, but was only effective against the high-risk HPV types 16 and 18, neither of which typically causes warts.

Management
There is no cure for HPV. Existing treatments are focused on the removal of visible warts, but these may also regress on their own without any therapy. There is no evidence to suggest that removing visible warts reduces transmission of the underlying HPV infection. As many as 80% of people with HPV will clear the infection within 18 months.A healthcare practitioner may offer one of several ways to treat warts, depending on their number, sizes, locations, or other factors. All treatments can potentially cause depigmentation, itching, pain, or scarring.Treatments can be classified as either physically ablative, or topical agents. Physically ablative therapies are considered more effective at initial wart removal, but like all therapies have significant recurrence rates.Many therapies, including folk remedies, have been suggested for treating genital warts, some of which have little evidence to suggest they are effective or safe. Those listed here are ones mentioned in national or international practice guidelines as having some basis in evidence for their use.

Physical ablation
Physically ablative methods are more likely to be effective on keratinized warts. They are also most appropriate for patients with fewer numbers of relatively smaller warts.
Simple excision, such as with scissors under local anesthesia, is highly effective.
Liquid nitrogen cryosurgery is usually performed in an office visit, at weekly intervals. It is effective, inexpensive, safe for pregnancy, and does not usually cause scarring.
Electrocauterization (sometimes called "loop electrical excision procedure" or LEEP) is a procedure with a long history of use and is considered effective.
Laser ablation has less evidence to suggest its use. It may be less effective than other ablative methods. It is extremely expensive, and often used as a last resort.
Formal surgical procedures, performed by a specialist under general anesthesia or spinal anesthesia may be necessary for larger or more extensive warts, intra-anal warts, or warts in children. It carries a greater risk of scarring than other methods.

Topical agents
A 0.15–0.5% podophyllotoxin (also called podofilox) solution in a gel or cream. It can be applied by the patient to the affected area and is not washed off. It is the purified and standardized active ingredient of podophyllin (see below). Podofilox is safer and more effective than podophyllin. Skin erosion and pain are more commonly reported than with imiquimod and sinecatechins. Its use is cycled (2 times per day for 3 days then 4–7 days off); one review states that it should only be used for four cycles.
Imiquimod is a topical immune response cream, applied to the affected area. It causes less local irritation than podofilox but may cause fungal infections (11% in package insert) and flu-like symptoms (less than 5% disclosed in package insert).
Sinecatechins is an ointment of catechins (55% epigallocatechin gallate) extracted from green tea and other components </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 Convex 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 Croup and explain in detail? [/INST] Croup, also known as laryngotracheobronchitis, is a type of respiratory infection that is usually caused by a virus. The infection leads to swelling inside the trachea, which interferes with normal breathing and produces the classic symptoms of "barking/brassy" cough, inspiratory stridor and a hoarse voice. Fever and runny nose may also be present. These symptoms may be mild, moderate, or severe. Often it starts or is worse at night and normally lasts one to two days.Croup can be caused by a number of viruses including parainfluenza and influenza virus. Rarely is it due to a bacterial infection. Croup is typically diagnosed based on signs and symptoms after potentially more severe causes, such as epiglottitis or an airway foreign body, have been ruled out. Further investigations, such as blood tests, X-rays and cultures, are usually not needed.Many cases of croup are preventable by immunization for influenza and diphtheria. Most cases of croup are mild and the child can be treated at home with supportive care. Croup is usually treated with a single dose of steroids by mouth. In more severe cases inhaled epinephrine may also be used. Hospitalization is required in one to five percent of cases.Croup is a relatively common condition that affects about 15% of children at some point. It most commonly occurs between six months and five years of age but may rarely be seen in children as old as fifteen. It is slightly more common in males than females. It occurs most often in autumn. Before vaccination, croup was frequently caused by diphtheria and was often fatal. This cause is now very rare in the Western world due to the success of the diphtheria vaccine.

Signs and symptoms
Croup is characterized by a "barking" cough, stridor, hoarseness, and difficult breathing which usually worsens at night. The "barking" cough is often described as resembling the call of a sea lion.  The stridor is worsened by agitation or crying, and if it can be heard at rest, it may indicate critical narrowing of the airways. As croup worsens, stridor may decrease considerably.Other symptoms include fever, coryza (symptoms typical of the common cold), and indrawing of the chest wall–known as Hoovers sign.  Drooling or a very sick appearance can indicate other medical conditions, such as epiglottitis or tracheitis.

Causes
Croup is usually deemed to be due to a viral infection. Others use the term more broadly, to include acute laryngotracheitis (laryngitis and tracheitis together), spasmodic croup, laryngeal diphtheria, bacterial tracheitis, laryngotracheobronchitis, and laryngotracheobronchopneumonitis. The first two conditions involve a viral infection and are generally milder with respect to symptomatology; the last four are due to bacterial infection and are usually of greater severity.

Viral
Viral croup or acute laryngotracheitis is most commonly caused by parainfluenza virus (a member of the paramyxovirus family), primarily types 1 and 2, in 75% of cases. Other viral causes include influenza A and B, measles, adenovirus and respiratory syncytial virus (RSV). Spasmodic croup is caused by the same group of viruses as acute laryngotracheitis, but lacks the usual signs of infection (such as fever, sore throat, and increased white blood cell count).  Treatment, and response to treatment, are also similar.

Bacteria and cocci
Croup caused by a bacterial infection is rare. Bacterial croup may be divided into laryngeal diphtheria, bacterial tracheitis, laryngotracheobronchitis, and laryngotracheobronchopneumonitis.  Laryngeal diphtheria is due to Corynebacterium diphtheriae while bacterial tracheitis, laryngotracheobronchitis, and laryngotracheobronchopneumonitis are usually due to a primary viral infection with secondary bacterial growth.  The most common cocci implicated are Staphylococcus aureus and Streptococcus pneumoniae, while the most common bacteria are Haemophilus influenzae, and Moraxella catarrhalis.

Pathophysiology
The viral infection that causes croup leads to swelling of the larynx, trachea, and large bronchi due to infiltration of white blood cells (especially histiocytes, lymphocytes, plasma cells, and neutrophils). Swelling produces airway obstruction which, when significant, leads to dramatically increased work of breathing and the characteristic turbulent, noisy airflow known as stridor.

Diagnosis
Croup is typically diagnosed based on signs and symptoms. The first step is to exclude other obstructive conditions of the upper airway, especially epiglottitis, an airway foreign body, subglottic stenosis, angioedema, retropharyngeal abscess, and bacterial tracheitis.A frontal X-ray of the neck is not routinely performed, but if it is done, it may show a characteristic narrowing of the trachea, called the steeple sign, because of the subglottic stenosis, which resembles a steeple in shape.  The steeple sign is suggestive of the diagnosis, but is absent in half of cases.Other investigations (such as blood tests and viral culture) are discouraged, as they may cause unnecessary agitation and thus worsen the stress on the compromised airway. While viral cultures, obtained via nasopharyngeal aspiration, can be used to confirm the exact cause, these are usually restricted to research settings. Bacterial infection should be considered if a person does not improve with standard treatment, at which point further investigations may be indicated.

Severity
The most commonly used system for classifying the severity of croup is the Westley score. It is primarily used for research purposes rather than in clinical practice. It is the sum of points assigned for five factors: level of consciousness, cyanosis, stridor, air entry, and retractions. The points given for each factor is listed in the adjacent table, and the final score ranges from 0 to 17.
A total score of ≤ 2 indicates mild croup. The characteristic barking cough and hoarseness may be present, but there is no stridor at rest.
A total score of 3–5 is classified as moderate croup.  It presents with easily heard stridor, but with few other signs.
A total score of 6–11 is severe croup.  It also presents with obvious stridor, but also features marked chest wall indrawing.
A total score of ≥ 12 indicates impending respiratory failure.  The barking cough and stridor may no longer be prominent at this stage.85% of children presenting to the emergency department have mild disease; severe croup is rare (<1%).

Prevention
Croup is contagious during the first few days of the infection. Basic hygiene including hand washing can prevent transmission. There are no vaccines that have been developed to prevent croup, however, many cases of croup have been prevented by immunization for influenza and diphtheria. At one time, croup referred to a diphtherial disease, but with vaccination, diphtheria is now rare in the developed world.

Treatment
Most children with croup have mild symptoms and supportive care at home is effective. For children with moderate to severe croup, treatment with corticosteroids and nebulized epinephrine may be suggested. Steroids are given routinely, with epinephrine used in severe cases. Children with oxygen saturation less than 92% should receive oxygen, and those with severe croup may be hospitalized for observation. In very rare severe cases of croup that result in respiratory failure, emergency intubation and ventilation may be required. With treatment, less than 0.2% of children require endotracheal intubation. Since croup is usually a viral disease, antibiotics are not used unless secondary bacterial infection is suspected. The use of cough medicines, which usually contain dextromethorphan or guaifenesin, are also discouraged.

Supportive care
Supportive care for children with croup includes resting and keeping the child hydrated. Infections that are mild are suggested to be treated at home. Croup is contagious so washing hands is important. Children with croup should generally be kept as calm as possible. Over the counter medications for pain and fever may be helpful to keep the child comfortable. There is some evidence that cool or warm mist may be helpful, however, the effectiveness of this approach is not clear. If the child is showing signs is distress while breathing (inspiratory stridor, working hard to breath, blue (or blue-ish) coloured lips, or decrease in the level of alertness), immediate medical evaluation by a doctor is required.

Steroids
Corticosteroids, such as dexamethasone and budesonide, have been shown to improve outcomes in children with all severities of croup, however, the benefits may be delayed. Significant relief may be obtained as early as two hours after administration. While effective when given by injection, or by inhalation, giving the medication by mouth is preferred. A single dose is usually all that is required, and is generally considered to be quite safe. Dexamethasone at doses of  0.15, 0.3 and 0.6 mg/kg appear to be all equally effective.

Epinephrine
Moderate to severe croup (for example, in the case of severe stridor) may be improved temporarily with nebulized epinephrine. While epinephrine typically produces a reduction in croup severity within 10–30 minutes, the benefits are short-lived and last for only about 2 hours. If the condition remains improved for 2–4 hours after treatment and no other complications arise, the child is typically discharged from the hospital. Epinephrine treatment is associated with potential adverse effects (usually related to the dose of epinephrine) including tachycardia, arrhythmias, and hypertension.

Oxygen
More severe cases of croup may require treatment with oxygen. If oxygen is needed, "blow-by" administration (holding an oxygen source near the childs face) is recommended, as it causes less agitation than use of a mask.

Other
While other treatments for croup have been studied, none has sufficient evidence to support its use.  There is tentative evidence that breathing heliox (a mixture of helium and oxygen) to decrease the work of breathing is useful in those with severe disease, however, there is uncertainty in the effectiveness and the potential adverse effects and/or side effects are not well known.  In cases of possible secondary bacterial infection, the antibiotics vancomycin and cefotaxime are recommended. In severe cases associated with influenza A or B infections, the antiviral neuraminidase inhibitors may be administered.

Prognosis
Viral croup is usually a self-limiting disease, with half of cases resolving in a day and 80% of cases in two days. It can very rarely result in death from respiratory failure and/or cardiac arrest.  Symptoms usually improve within two days, but may last for up to seven days. Other uncommon complications include bacterial tracheitis, pneumonia, and pulmonary edema.

Epidemiology
Croup affects about 15% of children, and usually presents between the ages of 6 months and 5–6 years </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 Cryopyrin-associated periodic syndrome and explain in detail? [/INST] Cryopyrin-associated periodic syndrome (CAPS) is a group of rare, heterogeneous autoinflammatory disease characterized by interleukin 1β-mediated systemic inflammation and clinical symptoms involving skin, joints, central nervous system, and eyes. It encompasses a spectrum of three clinically overlapping autoinflammatory syndromes including familial cold autoinflammatory syndrome (FCAS, formerly termed familial cold-induced urticaria), the Muckle–Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease (NOMID, also called chronic infantile neurologic cutaneous and articular syndrome or CINCA) that were originally thought to be distinct entities, but in fact share a single genetic mutation and pathogenic pathway, and keratoendotheliitis fugax hereditaria in which the autoinflammatory symptoms affect only the anterior segment of the eye.

Signs and symptoms
The syndromes within CAPS overlap clinically, and patients may have features of more than one disorder. In a retrospective cohort of 136 CAPS patients with systemic involvement from 16 countries, the most prevalent clinical features were fever (84% of cases, often with concurrent constitutional symptoms such as fatigue, malaise, mood disorders or failure to thrive), skin rash (either urticarial or maculopapular rash; 97% of cases) especially after cold exposure, and musculoskeletal involvement (myalgia, arthralgia, and/or arthritis, or less commonly joint contracture, patellar overgrowth, bone deformity, bone erosion and/or osteolytic lesion; 86% of cases). Less common features included ophthalmological involvement (conjunctivitis and/or uveitis, or less commonly optic nerve atrophy, cataract, glaucoma or impaired vision; 71% of cases), neurosensory hearing loss (42% of cases), neurological involvement (morning headache, papilloedema, and/or meningitis, or less commonly seizure, hydrocephalus or mental retardation; 40% of cases), and AA amyloidosis (4% of cases).In keratoendotheliitis fugax hereditaria, systemic symptoms are not reported whereas the patients experience periodical transient inflammation of the corneal endothelium and stroma, leading to short term blurring of vision and, after repeated attacks, to central corneal stromal opacities in some patients.Age of onset is typically in infancy or early childhood. In 57% of cases, CAPS had a chronic phenotype with symptoms present almost daily, whereas the remaining 43% of patients experienced only acute episodes. Up to 56% of patients reported a family history of CAPS. Previous studies confirm these symptoms, although the exact reported rates vary.

Pathogenesis
Cryopyrin-associated periodic syndromes are associated with a gain-of-function missense mutation in exon 3 of NLRP3, the gene encoding cryopyrin, a major component of the interleukin 1 inflammasome. In keratoendotheliitis fugax hereditaria, the mutation occurs in exon 1. Intracellular formation of the interleukin 1 inflammasome leads to the activation of the potent pro-inflammatory cytokines interleukin 1β and interleukin-18 through a cascade involving caspase 1. The IL-1 inflammasome may also be released from activated macrophages, amplifying the cytokine production cascade. The mutation in NLRP3 leads to aberrant formation of this inflammasome and subsequent unregulated production of interleukin 1β.Up to 170 heterogenous mutations in NLRP3 have been identified </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 Cushings syndrome and explain in detail? [/INST] Cushings syndrome is a collection of signs and symptoms due to prolonged exposure to glucocorticoids such as cortisol. Signs and symptoms may include high blood pressure, abdominal obesity but with thin arms and legs, reddish stretch marks, a round red face, a fat lump between the shoulders, weak muscles, weak bones, acne, and fragile skin that heals poorly. Women may have more hair and irregular menstruation. Occasionally there may be changes in mood, headaches, and a chronic feeling of tiredness.Cushings syndrome is caused by either excessive cortisol-like medication, such as prednisone, or a tumor that either produces or results in the production of excessive cortisol by the adrenal glands. Cases due to a pituitary adenoma are known as Cushings disease, which is the second most common cause of Cushings syndrome after medication. A number of other tumors, often referred to as ectopic due to their placement outside the pituitary, may also cause Cushings. Some of these are associated with inherited disorders such as multiple endocrine neoplasia type 1 and Carney complex. Diagnosis requires a number of steps. The first step is to check the medications a person takes. The second step is to measure levels of cortisol in the urine, saliva or in the blood after taking dexamethasone. If this test is abnormal, the cortisol may be measured late at night. If the cortisol remains high, a blood test for ACTH may be done.Most cases can be treated and cured. If due to medications, these can often be slowly decreased if still required or slowly stopped. If caused by a tumor, it may be treated by a combination of surgery, chemotherapy, and/or radiation. If the pituitary was affected, other medications may be required to replace its lost function. With treatment, life expectancy is usually normal. Some, in whom surgery is unable to remove the entire tumor, have an increased risk of death.About two to three people per million are affected each year. It most commonly affects people who are 20 to 50 years of age. Women are affected three times more often than men. A mild degree of overproduction of cortisol without obvious symptoms, however, is more common. Cushings syndrome was first described by American neurosurgeon Harvey Cushing in 1932. Cushings syndrome may also occur in other animals including cats, dogs, and horses.

Signs and symptoms
Symptoms include rapid weight gain, particularly of the trunk and face with sparing of the limbs (central obesity). Common signs include the growth of fat pads along the collarbone, on the back of the neck ("buffalo hump" or lipodystrophy), and on the face ("moon face"). Other symptoms include excess sweating, dilation of capillaries, thinning of the skin (which causes easy bruising and dryness, particularly the hands) and mucous membranes, purple or red striae (the weight gain in Cushings syndrome stretches the skin, which is thin and weakened, causing it to hemorrhage) on the trunk, buttocks, arms, legs, or breasts, proximal muscle weakness (hips, shoulders), and hirsutism (facial male-pattern hair growth), baldness and/or extremely dry and brittle hair. In rare cases, Cushings can cause hypocalcemia. The excess cortisol may also affect other endocrine systems and cause, for example, insomnia, inhibited aromatase, reduced libido, impotence in men, and amenorrhoea, oligomenorrhea and infertility in women due to elevations in androgens. Studies have also shown that the resultant amenorrhea is due to hypercortisolism, which feeds back onto the hypothalamus resulting in decreased levels of GnRH release.Many of the features of Cushings are those seen in metabolic syndrome, including insulin resistance, hypertension, obesity, and elevated blood levels of triglycerides.Cognitive conditions, including memory and attention dysfunctions, as well as depression, are commonly associated with elevated cortisol, and may be early indicators of exogenous or endogenous Cushings. Depression and anxiety disorders are also common.Other striking and distressing skin changes that may appear in Cushings syndrome include facial acne, susceptibility to superficial fungus (dermatophyte and malassezia) infections, and the characteristic purplish, atrophic striae on the abdomen.: 500 Other signs include increased urination (and accompanying increased thirst), persistent high blood pressure (due to cortisols enhancement of epinephrines vasoconstrictive effect) and insulin resistance (especially common with ACTH production outside the pituitary), leading to high blood sugar and insulin resistance which can lead to diabetes mellitus.  Insulin resistance is accompanied by skin changes such as acanthosis nigricans in the axilla and around the neck, as well as skin tags in the axilla. Untreated Cushings syndrome can lead to heart disease and increased mortality. Cortisol can also exhibit mineralocorticoid activity in high concentrations, worsening the hypertension and leading to hypokalemia (common in ectopic ACTH secretion) and hypernatremia (increased Na+ ions concentration in plasma). Furthermore, excessive cortisol may lead to gastrointestinal disturbances, opportunistic infections, and impaired wound healing related to cortisols suppression of the immune and inflammatory responses. Osteoporosis is also an issue in Cushings syndrome since osteoblast activity is inhibited. Additionally, Cushings syndrome may cause sore and aching joints, particularly in the hip, shoulders, and lower back.Brain changes such as cerebral atrophy may occur. This atrophy is associated with areas of high glucocorticoid receptor concentrations such as the hippocampus and correlates highly with psychopathological personality changes.
Rapid weight gain
Moodiness, irritability, or depression
Muscle and bone weakness
Memory and attention dysfunction
Osteoporosis
Diabetes mellitus
Hypertension
Immune suppression
Sleep disturbances
Menstrual disorders such as amenorrhea in women
Infertility in women
Impotence in men
Hirsutism
Baldness
Hypercholesterolemia

Hyperpigmentation
Cushings syndrome due to excess ACTH may also result in hyperpigmentation. This is due to melanocyte-stimulating hormone production as a byproduct of ACTH synthesis from pro-opiomelanocortin (POMC). Alternatively, it is proposed that the high levels of ACTH, β-lipotropin, and γ-lipotropin, which contain weak MSH function, can act on the melanocortin 1 receptor. A variant of Cushings disease can be caused by ectopic, i.e. extra pituitary, ACTH production from, for example, a small-cell lung cancer.When Cushings syndrome is caused by an increase of cortisol at the level of the adrenal glands (via an adenoma or hyperplasia), negative feedback ultimately reduces ACTH production in the pituitary. In these cases, ACTH levels remain low and no hyperpigmentation develops.

Causes
Cushings syndrome may result from any cause of increased glucocorticoid levels, whether due to medication or internal processes. Some sources however do not consider the glucocorticoid medication-induced condition as "Cushings syndrome" proper, instead using the term "Cushingoid" to describe the medications side effects which mimic the endogenous condition.Cushings disease is a specific type of Cushings syndrome caused by a pituitary tumor leading to excessive production of ACTH (adrenocorticotropic hormone). Excessive ACTH stimulates the adrenal cortex to produce high levels of cortisol, producing the disease state. While all Cushings disease gives Cushings syndrome, not all Cushings syndrome is due to Cushings disease. Several possible causes of Cushings syndrome are known.

Exogenous
The most common cause of Cushings syndrome is the use of prescribed glucocorticoids to treat other diseases (iatrogenic Cushings syndrome). Glucocorticoids are used in treatment of a variety of disorders, including asthma and rheumatoid arthritis, and also used for immunosuppression after organ transplants. Administration of synthetic ACTH is also possible, but ACTH is less often prescribed due to cost and lesser utility. Rarely, Cushings syndrome can also be due to the use of medroxyprogesterone acetate. In exogenous Cushings, the adrenal glands may often gradually atrophy due to lack of stimulation by ACTH, the production of which is suppressed by glucocorticoid medication. Abruptly stopping the medication can thus result in acute and potentially life-threatening adrenal insufficiency and the dose must hence be slowly and carefully tapered off to allow internal cortisol production to pick up. In some cases, patients never recover sufficient levels of internal production and must continue taking glucocorticoids at physiological doses for life.Cushings syndrome in childhood is especially rare and usually results from use of glucocorticoid medication.

Endogenous
Endogenous Cushings syndrome results from some derangement of the bodys own system of cortisol secretion. Normally, ACTH is released from the pituitary gland when necessary to stimulate the release of cortisol from the adrenal glands.
In pituitary Cushings, a benign pituitary adenoma secretes ACTH. This is also known as Cushings disease and is responsible for 70% of endogenous Cushings syndrome.
In adrenal Cushings, excess cortisol is produced by adrenal gland tumors, hyperplastic adrenal glands, or adrenal glands with nodular adrenal hyperplasia.
Tumors outside the normal pituitary-adrenal system can produce ACTH (occasionally with CRH) that affects the adrenal glands. This etiology is called ectopic or paraneoplastic Cushings disease and is seen in diseases such as small cell lung cancer.
Finally, rare cases of CRH-secreting tumors (without ACTH secretion) have been reported, which stimulates pituitary ACTH production.

Pseudo-Cushings syndrome
Elevated levels of total cortisol can also be due to estrogen found in oral contraceptive pills that contain a mixture of estrogen and progesterone, leading to pseudo-Cushings syndrome. Estrogen can cause an increase of cortisol-binding globulin and thereby cause the total cortisol level to be elevated. However, the total free cortisol, which is the active hormone in the body, as measured by a 24-hour urine collection for urinary free cortisol, is normal.

Pathophysiology
The hypothalamus is in the brain and the pituitary gland sits just below it. The paraventricular nucleus (PVN) of the hypothalamus releases corticotropin-releasing hormone (CRH), which stimulates the pituitary gland to release adrenocorticotropin (ACTH).  ACTH travels via the blood to the adrenal gland, where it stimulates the release of cortisol. Cortisol is secreted by the cortex of the adrenal gland from a region called the zona fasciculata in response to ACTH. Elevated levels of cortisol exert negative feedback on CRH in the hypothalamus, which decreases the amount of ACTH released from the anterior pituitary gland.Strictly, Cushings syndrome refers to excess cortisol of any etiology (as syndrome means a group of symptoms). One of the causes of Cushings syndrome is a cortisol-secreting adenoma in the cortex of the adrenal gland (primary hypercortisolism/hypercorticism). The adenoma causes cortisol levels in the blood to be very high, and negative feedback on the pituitary from the high cortisol levels causes ACTH levels to be very low.Cushings disease refers only to hypercortisolism secondary to excess production of ACTH from a corticotroph pituitary adenoma (secondary hypercortisolism/hypercorticism) or due to excess production of hypothalamus CRH (Corticotropin releasing hormone) (tertiary hypercortisolism/hypercorticism). This causes the blood ACTH levels to be elevated along with cortisol from the adrenal gland. The ACTH levels remain high because the tumor is unresponsive to negative feedback from high cortisol levels.When Cushings syndrome is due to extra ACTH it is known as ectopic Cushing syndrome. This may be seen in a paraneoplastic syndrome.
When Cushings syndrome is suspected, either a dexamethasone suppression test (administration of dexamethasone and frequent determination of cortisol and ACTH level), or a 24-hour urinary measurement for cortisol offers equal detection rates. Dexamethasone is a glucocorticoid and simulates the effects of cortisol, including negative feedback on the pituitary gland. When dexamethasone is administered and a blood sample is tested, cortisol levels >50 nmol/L (1.81 μg/dL) would be indicative of Cushings syndrome because an ectopic source of cortisol or ACTH (such as adrenal adenoma) exists which is not inhibited by the dexamethasone. A novel approach, recently cleared by the US FDA, is sampling cortisol in saliva over 24 hours, which may be equally sensitive, as late-night levels of salivary cortisol are high in cushingoid patients. Other pituitary hormone levels may need to be ascertained.  Performing a physical examination to determine any visual field defect may be necessary if a pituitary lesion is suspected, which may compress the optic chiasm, causing typical bitemporal hemianopia.When any of these tests is positive, CT scanning of the adrenal gland and MRI of the pituitary gland are performed to detect the presence of any adrenal or pituitary adenomas or incidentalomas (the incidental discovery of harmless lesions). Scintigraphy of the adrenal gland with iodocholesterol scan is occasionally necessary. Occasionally, determining the ACTH levels in various veins in the body by venous catheterization, working towards the pituitary (petrosal sinus sampling) is necessary. In many cases, the tumors causing Cushings disease are less than 2 mm in size and difficult to detect using MRI or CT imaging. In one study of 261 patients with confirmed pituitary Cushings disease, only 48% of pituitary lesions were identified using MRI prior to surgery.Plasma CRH levels are inadequate at diagnosis (with the possible exception of tumors secreting CRH) because of peripheral dilution and binding to CRHBP.

Diagnosis
Cushings syndrome can be ascertained via a variety of test which include the following:
24-hour urine free cortisol
Dexamethasone suppression test
Saliva cortisol level

Treatment
Most cases of Cushingoid symptoms are caused by corticosteroid medications, such as those used for asthma, arthritis, eczema and other inflammatory conditions.  Consequently, most patients are effectively treated by carefully tapering off (and eventually stopping) the medication that causes the symptoms.If an adrenal adenoma is identified, it may be removed by surgery. An ACTH-secreting corticotrophic pituitary adenoma should be removed after diagnosis. Regardless of the adenomas location, most patients require steroid replacement postoperatively at least in the interim, as long-term suppression of pituitary ACTH and normal adrenal tissue does not recover immediately. Clearly, if both adrenals are removed, replacement with hydrocortisone or prednisolone is imperative.In those patients not suited for or unwilling to undergo surgery, several drugs have been found to inhibit cortisol synthesis (e.g. ketoconazole, metyrapone) but they are of limited efficacy. Mifepristone is a powerful glucocorticoid type II receptor antagonist and, since it does not interfere with normal cortisol homeostasis type I receptor transmission, may be especially useful for treating the cognitive effects of Cushings syndrome. However, the medication faces considerable controversy due to its use as an abortifacient. In February 2012, the FDA approved mifepristone to control high blood sugar levels (hyperglycemia) in adult patients who are not candidates for surgery, or who did not respond to prior surgery, with the warning that mifepristone should never be used by pregnant women- although pregnancy is extremely rare during the course of Cushings Syndrome  In March 2020, Isturisa (osilodrostat) oral tablets a 11-beta-hydroxylase enzyme inhibitor was approved by FDA for treating those patients who cannot undergo pituitary surgery or for patients who underwent surgery but continue to have the disease.Removal of the adrenals in the absence of a known tumor is occasionally performed to eliminate the production of excess cortisol </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 Cyanide poisoning and explain in detail? [/INST] Cyanide poisoning is poisoning that results from exposure to any of a number of forms of cyanide. Early symptoms include headache, dizziness, fast heart rate, shortness of breath, and vomiting. This phase may then be followed by seizures, slow heart rate, low blood pressure, loss of consciousness, and cardiac arrest. Onset of symptoms usually occurs within a few minutes. Some survivors have long-term neurological problems.Toxic cyanide-containing compounds include hydrogen cyanide gas and a number of cyanide salts. Poisoning is relatively common following breathing in smoke from a house fire. Other potential routes of exposure include workplaces involved in metal polishing, certain insecticides, the medication sodium nitroprusside, and certain seeds such as those of apples and apricots. Liquid forms of cyanide can be absorbed through the skin. Cyanide ions interfere with cellular respiration, resulting in the bodys tissues being unable to use oxygen.Diagnosis is often difficult. It may be suspected in a person following a house fire who has a decreased level of consciousness, low blood pressure, or high lactic acid. Blood levels of cyanide can be measured but take time. Levels of 0.5–1 mg/L are mild, 1–2 mg/L are moderate, 2–3 mg/L are severe, and greater than 3 mg/L generally result in death.If exposure is suspected, the person should be removed from the source of exposure and decontaminated. Treatment involves supportive care and giving the person 100% oxygen. Hydroxocobalamin (vitamin B12a) appears to be useful as an antidote and is generally first-line. Sodium thiosulphate may also be given. Historically cyanide has been used for mass suicide and by the Nazis for genocide.

Signs and symptoms
Acute exposure
If hydrogen cyanide is inhaled it can cause a coma with seizures, apnea, and cardiac arrest, with death following in a matter of seconds.  At lower doses, loss of consciousness may be preceded by general weakness, dizziness, headaches, vertigo, confusion, and perceived difficulty in breathing. At the first stages of unconsciousness, breathing is often sufficient or even rapid, although the state of the person progresses towards a deep coma, sometimes accompanied by pulmonary edema, and finally cardiac arrest. A cherry red skin color that darkens may be present as the result of increased venous hemoglobin oxygen saturation. Despite the similar name, cyanide does not directly cause cyanosis. A fatal dose for humans can be as low as 1.5 mg/kg body weight.  Other sources claim a lethal dose is 1–3 mg per kg body weight for vertebrates.

Chronic exposure
Exposure to lower levels of cyanide over a long period (e.g., after use of improperly processed cassava roots, which are a primary food source in tropical Africa) results in increased blood cyanide levels, which can result in weakness and a variety of symptoms, including permanent paralysis, nervous lesions, hypothyroidism, and miscarriages. Other effects include mild liver and kidney damage.

Causes
Cyanide poisoning can result from the ingestion of cyanide salts; imbibing pure liquid prussic acid; skin absorption of prussic acid; intravenous infusion of nitroprusside for hypertensive crisis; or the inhalation of hydrogen cyanide gas. The last typically occurs through one of three mechanisms:

The gas is directly released from canisters (e.g. as part of a pesticide, insecticide, or Zyklon B).
It is generated on site by reacting potassium cyanide or sodium cyanide with sulfuric acid (e.g. in a modern American gas chamber).
Fumes arise during a building fire or any similar scenario involving the burning of polyurethane, vinyl or other polymer products that required nitriles in their production.As potential contributing factors, cyanide is present in:

Tobacco smoke.
Many seeds or kernels such as those of almonds, apricots, apples, oranges, and flaxseed.
Foods including cassava (also known as tapioca, yuca or manioc) and bamboo shoots.As a potential harm-reduction factor, Vitamin B12, in the form of hydroxocobalamin (also spelled hydroxycobalamin), might reduce the negative effects of chronic exposure; whereas, a deficiency might worsen negative health effects following exposure to cyanide.

Mechanism
Cyanide is a potent cytochrome c oxidase (COX, a.k.a Complex IV) inhibitor. As such, cyanide poisoning is a form of histotoxic hypoxia, because it interferes with oxidative phosphorylation.: 1475 Specifically, cyanide binds to the heme a3-CuB binuclear center of COX (and thus is a non-competitive inhibitor of it). This prevents electrons passing through COX from being transferred to O2, which not only blocks the mitochondrial electron transport chain but also interferes with the pumping of a proton out of the mitochondrial matrix which would otherwise occur at this stage. Therefore, cyanide interferes not only with aerobic respiration but also with the ATP synthesis pathway it facilitates, owing to the close relationship between those two processes.: 705 One antidote for cyanide poisoning, nitrite (i.e. via amyl nitrite), works by converting ferrohemoglobin to ferrihemoglobin, which can then compete with COX for free cyanide (as the cyanide will bind to the iron in its heme groups instead). Ferrihemoglobin cannot carry oxygen, but the amount of ferrihemoglobin that can be formed without impairing oxygen transport is much greater than the amount of COX in the body.: 1475 Cyanide is a broad-spectrum poison because the reaction it inhibits is essential to aerobic metabolism; COX is found in many forms of life. However, susceptibility to cyanide is far from uniform across affected species; for instance, plants have an alternative electron transfer pathway available that passes electrons directly from ubiquinone to O2, which confers cyanide resistance by bypassing COX.: 704

Diagnosis
Lactate is produced by anaerobic glycolysis when oxygen concentration becomes too low for the normal aerobic respiration pathway. Cyanide poisoning inhibits aerobic respiration and therefore increases anaerobic glycolysis which causes a rise of lactate in the plasma. A lactate concentration above 10 mmol per liter is an indicator of cyanide poisoning, as defined by the presence of a blood cyanide concentration above 40 µmol per liter. Lactate levels greater than 6 mmol/L after reported or strongly suspected pure cyanide poisoning, such as cyanide-containing smoke exposure, suggests significant cyanide exposure.Methods of detection include colorimetric assays such as the Prussian blue test, the pyridine-barbiturate assay, also known as the "Conway diffusion method" and the taurine fluorescence-HPLC but like all colorimetric assays these are prone to false positives. Lipid peroxidation resulting in "TBARS," an artifact of heart attack produces dialdehydes that cross-react with the pyridine-barbiturate assay.  Meanwhile, the taurine-fluorescence-HPLC assay used for cyanide detection is identical to the assay used to detect glutathione in spinal fluid.
Cyanide and thiocyanate assays have been run with mass spectrometry (LC/MS/MS), which are considered specific tests. Since cyanide has a short half-life, the main metabolite, thiocyanate is typically measured to determine exposure. Other methods of detection include the identification of plasma lactate.

Treatment
Decontamination
Decontamination of people exposed to hydrogen cyanide gas only requires removal of the outer clothing and the washing of their hair. Those exposed to liquids or powders generally require full decontamination.

Antidote
The International Programme on Chemical Safety issued a survey (IPCS/CEC Evaluation of Antidotes Series) that lists the following antidotal agents and their effects: oxygen, sodium thiosulfate, amyl nitrite, sodium nitrite, 4-dimethylaminophenol, hydroxocobalamin, and dicobalt edetate (Kelocyanor), as well as several others. Other commonly-recommended antidotes are solutions A and B (a solution of ferrous sulfate in aqueous citric acid, and aqueous sodium carbonate, respectively) and amyl nitrite.
The United States standard cyanide antidote kit first uses a small inhaled dose of amyl nitrite, followed by intravenous sodium nitrite, followed by intravenous sodium thiosulfate. Hydroxocobalamin was approved for use in the US in late 2006 and is available in Cyanokit antidote kits. Sulfanegen TEA, which could be delivered to the body through an intra-muscular (IM) injection, detoxifies cyanide and converts the cyanide into thiocyanate, a less toxic substance. Alternative methods of treating cyanide intoxication are used in other countries.
The Irish Health and Safety Executive (HSE) has recommended against the use of solutions A and B because of their limited shelf life, potential to cause iron poisoning, and limited applicability (effective only in cases of cyanide ingestion, whereas the main modes of poisoning are inhalation and skin contact). The HSE has also questioned the usefulness of amyl nitrite due to storage/availability problems, risk of abuse, and lack of evidence of significant benefits. It also states that the availability of kelocyanor at the workplace may mislead doctors into treating a patient for cyanide poisoning when this is an erroneous diagnosis. The HSE no longer recommends a particular cyanide antidote.

History
Fires
The República Cromañón nightclub fire broke out in Buenos Aires, Argentina on 30 December 2004, killing 194 people and leaving at least 1,492 injured. Most of the victims died from inhaling poisonous gases, and carbon monoxide. After the fire, the technical institution INTI found that the level of toxicity due to the materials and volume of the building was 225 ppm of cyanide in the air. A lethal dose for rats is between 150 ppm and 220 ppm, meaning the air in the building was highly toxic.
On 5 December 2009, a fire in the night club Lame Horse (Khromaya Loshad) in the Russian city of Perm took the lives of 156 people. Fatalities consisted of 111 people at the site and 45 later in hospitals. One of the main causes of death was poisoning from cyanide and other toxic gases released by the burning of plastic and polyurethane foam used in the construction of club interiors. Taking into account the number of deaths, this was the largest fire in post-Soviet Russia.On 27 January 2013, a fire at the Kiss nightclub in the city of Santa Maria, in the south of Brazil, caused the poisoning of hundreds of young people by cyanide released by the combustion of soundproofing foam made with polyurethane. By March 2013, 245 fatalities were confirmed.

Gas chambers
In early 1942, Zyklon B, which contains hydrogen cyanide, emerged as the preferred killing tool of Nazi Germany for use in extermination camps during the Holocaust. The chemical was used to murder roughly one million people in gas chambers installed in extermination camps at Auschwitz-Birkenau, Majdanek, and elsewhere. Most of the people who were murdered were Jews, and by far the majority of these murders took place at Auschwitz. Zyklon B was supplied to concentration camps at Mauthausen, Dachau, and Buchenwald by the distributor Heli, and to Auschwitz and Majdanek by Testa. Camps also occasionally bought Zyklon B directly from the manufacturers. Of the 729 tonnes of Zyklon B sold in Germany in 1942–44, 56 tonnes (about eight percent of domestic sales) were sold to concentration camps. Auschwitz received 23.8 tonnes, of which six tonnes were used for fumigation. The remainder was used in the gas chambers or lost to spoilage (the product had a stated shelf life of only three months). Testa conducted fumigations for the Wehrmacht and supplied them with Zyklon B. They also offered courses to the SS in the safe handling and use of the material for fumigation purposes. In April 1941, the German agriculture and interior ministries designated the SS as an authorized applier of the chemical, and thus they were able to use it without any further training or governmental oversight.Hydrogen cyanide gas has been used for judicial execution in some states of the United States, where cyanide was generated by reaction between potassium cyanide (or sodium cyanide) dropped into a compartment containing sulfuric acid, directly below the chair in the gas chamber.

Suicide
Cyanide salts are sometimes used as fast-acting suicide devices. Cyanide reacts at a higher level with high stomach acidity.

On 26 January 1904, company promoter and swindler Whitaker Wright committed suicide by ingesting cyanide in a court anteroom immediately after being convicted of fraud.
In February 1937, the Uruguayan short story writer Horacio Quiroga committed suicide by drinking cyanide in a hospital at Buenos Aires.
In 1937, polymer chemist Wallace Carothers committed suicide by cyanide.
In the 1943 Operation Gunnerside to destroy the Vemork Heavy Water Plant in World War II (an attempt to stop or slow German atomic bomb progress), the commandos were given cyanide tablets (cyanide enclosed in rubber) kept in the mouth and were instructed to bite into them in case of German capture. The tablets ensured death within three minutes.
Cyanide, in the form of pure liquid prussic acid (a historical name for hydrogen cyanide), was the favored suicide agent of Nazi Germany. Erwin Rommel (1944), Adolf Hitlers wife, Eva Braun (1945), and Nazi leaders Heinrich Himmler (1945), possibly Martin Bormann (1945), and Hermann Göring (1946) all committed suicide by ingesting it.
It is speculated that, in 1954, Alan Turing used an apple that had been injected with a solution of cyanide to commit suicide after being convicted of having a homosexual relationship, which was illegal at the time in the United Kingdom, and forced to undergo hormonal castration to avoid prison. An inquest determined that Turings death from cyanide poisoning was a suicide, although this has been disputed.
Members of the Sri Lankan LTTE (Liberation Tigers of Tamil Eelam, whose insurgency lasted from 1983 to 2009), used to wear cyanide vials around their necks with the intention of committing suicide if captured by the government forces.
On 22 June 1977, Moscow, Aleksandr Dmitrievich Ogorodnik, a Soviet diplomat accused of spying on behalf of the Colombian Intelligence Agency and the US Central Intelligence Agency, was arrested. During the interrogations, Ogorodnik offered to write a full confession and asked for his pen. Inside the pen cap was a cleverly hidden cyanide pill, which when bitten on, caused Ogorodnik to die before he hit the floor, according to the Soviets.
On 18 November 1978, Jonestown. A total of 909 individuals died in Jonestown, many from apparent cyanide poisoning, in an event termed "revolutionary suicide" by Jones and some members on an audio tape of the event and in prior discussions. The poisonings in Jonestown followed the murder of five others by Temple members at Port Kaituma, including United States Congressman Leo Ryan, an act that Jones ordered. Four other Temple members committed murder-suicide in Georgetown at Jones command.
On 6 June 1985, serial killer Leonard Lake died in custody after having ingested cyanide pills he had sewn into his clothes.
On 28 June 2012, Wall Street trader Michael Marin ingested a cyanide pill seconds after a guilty verdict was read in his arson trial in Phoenix, AZ; he died minutes after.
On 22 June 2015, John B. McLemore, a horologist and the central figure of the podcast S-Town, died after ingesting cyanide.
On 29 November 2017, Slobodan Praljak died from drinking potassium cyanide, after being convicted of war crimes by the International Criminal Tribunal for the former Yugoslavia.

Mining and industrial
In 1993, an illegal spill resulted in the death of seven people in Avellaneda, Argentina. In their memory, the National Environmental Conscious Day (Día Nacional de la Conciencia Ambiental) was established.
In 2000, a spill at Baia Mare, Romania, resulted in the worst environmental disaster in Europe since Chernobyl.
In 2000, Allen Elias, CEO of Evergreen Resources was convicted of knowing endangerment for his role in the cyanide poisoning of employee Scott Dominguez. This was one of the first successful criminal prosecutions of a corporate executive by the Environmental Protection Agency.

Murder
John Tawell, a murderer who in 1845 became the first person to be arrested as the result of telecommunications technology.
Grigori Rasputin (1916; attempted, later killed by gunshot)
The Goebbels children (1945)
Stepan Bandera (1959)
Jonestown, Guyana, was the site of a large mass murder–suicide, in which over 900 members of the Peoples Temple drank potassium cyanide–laced Flavor Aid in 1978.
Chicago Tylenol murders (1982)
Timothy Marc OBryan (1966–1974) died on October 31, 1974 by ingesting potassium cyanide placed into a giant Pixy Stix. His father, Ronald Clark OBryan, was  convicted of Tims murder plus four counts of attempted murder. OBryan put potassium cyanide into five giant Pixy Stix that he gave to his son and daughter along with three other children. Only Timothy ate the poisoned candy and died.
Bruce Nickell (5 June 1986) Murdered by his wife who poisoned a bottle of Excedrin.
Richard Kuklinski (1935–2006)
Janet Overton (1942–1988) Her husband, Richard Overton was convicted of poisoning her, but Janets symptoms did not match those of classic cyanide poisoning, the timeline was inconsistent with cyanide poisoning, and the amount found was just a trace. The diagnostic method used was prone to false positives. Richard Overton died in prison in 2009.
Urooj Khan (1966–2012), won the lottery and was found dead a few days later. A blood diagnostic reported a lethal level of cyanide in his blood, but the body did not display any classic symptoms of cyanide poisoning, and no link to cyanide could be found in Uroojs social circle.  The diagnostic method used was the Conway diffusion method, prone to false positives with artifacts of heart attack and kidney failure.
Autumn Marie Klein (20 April 2013), a prominent 41-year-old neuroscientist and physician, died from cyanide poisoning. Kleins husband, Robert J. Ferrante, also a prominent neuroscientist who used cyanide in his research, was convicted of murder and sentenced to life in prison for her death. Robert Ferrante is appealing his conviction.
Mirna Salihin died in hospital on 6 January 2016, after drinking a Vietnamese iced coffee at a cafe in a shopping mall in Jakarta. Police reports claim that cyanide poisoning was the most likely cause of her death.
Jolly Thomas of Kozhikode, Kerala, India, was arrested in 2019 for the murder of 6 family members. Murders took place over 14-year period and each victim ate a meal prepared by the killer. The murders were allegedly motivated by wanting control of the family finances and property.
Mei Xiang Li of Brooklyn, NY, collapsed and died in April 2017, with cyanide later reported to be in her blood. However, Mei never exhibited symptoms of cyanide poisoning and no link to cyanide could be found in her life.

Warfare or terrorism
In 1988, between 3,200 and 5,000 people died in the Halabja massacre owing to unknown chemical nerve agents. Hydrogen cyanide gas was strongly suspected.
In 1995, a device was discovered in a restroom in the Kayabacho Tokyo subway station, consisting of bags of sodium cyanide and sulfuric acid with a remote controlled motor to rupture them in what was believed to be an attempt by the Aum Shinrikyo cult to produce toxic amounts of hydrogen cyanide gas.
In 2003, Al Qaeda reportedly planned to release cyanide gas into the New York City Subway system. The attack was supposedly aborted because there would not be enough casualties.

Research
Cobinamide is the final compound in the biosynthesis of cobalamin. It has greater affinity for the cyanide than cobalamin itself, which suggests that it could be a better option for emergency treatment.

See also
Anaerobic glycolysis
Lactic acidosis
List of poisonings
Konzo

References
Explanatory notes
Citations
Sources
Longerich, Peter (2010). Holocaust: The Nazi Persecution and Murder of the Jews. Oxford; New York: Oxford University Press. ISBN 978-0-19-280436-5.
Hayes, Peter (2004) </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 Cycloplegia and explain in detail? [/INST] Cycloplegia is paralysis of the ciliary muscle of the eye, resulting in a loss of accommodation.  Because of the paralysis of the ciliary muscle, the curvature of the lens can no longer be adjusted to focus on nearby objects. This results in similar problems as those caused by presbyopia, in which the lens has lost elasticity and can also no longer focus on close-by objects. Cycloplegia with accompanying mydriasis (dilation of pupil) is usually due to topical application of muscarinic antagonists such as atropine and cyclopentolate.
Belladonna alkaloids are used for testing the error of refraction and examination of eye.

Management
Cycloplegic drugs are generally muscarinic receptor blockers. These include atropine, cyclopentolate, homatropine, scopolamine and tropicamide. They are indicated for use in cycloplegic refraction (to paralyze the ciliary muscle in order to determine the true refractive error of the eye) and the treatment of uveitis. All cycloplegics are also mydriatic (pupil dilating) agents and are used as such during eye examination to better visualize the retina.
When cycloplegic drugs are used as a mydriatic to dilate the pupil, the pupil in the normal eye regains its function when the drugs are metabolized or carried away.  Some cycloplegic drugs can cause dilation of the pupil for several days.  The ones specifically used by ophthalmologists or optometrists wear off in hours, but when the patient leaves the office strong sunglasses are provided for comfort.

See also
References
External links
Kels, Barry D.; Grzybowski, Andrzej; Grant-Kels, Jane M. (March 2015). "Human ocular anatomy". Clinics in Dermatology. 33 (2): 140–146 </s>