<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 Breech birth and explain in detail? [/INST] A breech birth is when a baby is born bottom first instead of head first, as is normal. Around 3–5% of pregnant women at term (37–40 weeks pregnant) have a breech baby. Due to their higher than average rate of possible complications for the baby, breech births are generally considered higher risk. Breech births also occur in many other mammals such as dogs and horses, see veterinary obstetrics.
Most babies in the breech position are delivered via caesarean section because it is seen as safer than being born vaginally. Doctors and midwives in the developing world often lack many of the skills required to safely assist women giving birth to a breech baby vaginally. Also, delivering all breech babies by caesarean section in developing countries is difficult to implement as there are not always resources available to provide this service. OB-GYNs do not recommend home births if a breech birth is expected, even when attended by a medical professional.

Cause
With regard to the fetal presentation during pregnancy, three periods have been distinguished.During the first period, which lasts until the 24th gestational week, the incidence of a longitudinal lie increases, with equal proportions of breech or cephalic presentations from this lie. This period is characterized by frequent changes of presentations. The fetuses in breech presentation during this period have the same probability for breech and cephalic presentation at delivery.
During the second period, lasting from the 25th to the 35th gestational week, the incidence of cephalic presentation increases, with a proportional decrease of breech presentation. The second period is characterized by a higher than random probability that the fetal presentation during this period will also be present at the time of delivery. The increase of this probability is gradual and identical for breech and cephalic presentations during this period.
In the third period, from the 36th gestational week onward, the incidence of cephalic and breech presentations remain stable, i.e. breech presentation around 3–4% and cephalic presentation approximately 95%. In the general population, incidence of breech presentation at preterm corresponds to the incidence of breech presentation when birth occurs.A breech presentation at delivery occurs when the fetus does not turn to a cephalic presentation. This failure to change presentation can result from endogenous and exogenous factors. Endogenous factors involve fetal inability to adequately move, whereas exogenous factors refer to insufficient intrauterine space available for fetal movements.The incidence of breech presentation is affected by both maternal and fetal diseases and medical conditions. When these factors are present, the probability of breech presentation is between 4% and 50%.

Rates in various medical conditions
Fetal entities:
First twin 17–30%
Second twin 28–39%
Stillborn 26%
Prader–Willi syndrome 50%, Werdnig–Hoffman syndrome 10%
Smith–Lemli–Opitz syndrome 40%
Fetal alcohol syndrome 40%
Potter anomaly 36%
Zellweger syndrome 27%
Myotonic dystrophy 21%, 13 trisomy syndrome 12%
18 trisomy syndrome 43%
21 trisomy syndrome 5%
de Lange syndrome 10%
Anencephalus 6–18%, Spina bifida 20–30%
Congenital hydrocephalus 24–37%
Osteogenesis imperfecta 33.3%
Amyoplasia 33.3%
Achondrogenesis 33.3%
Amelia 50%
Craniosynostosis 8%
Sacral agenesis 30.4%
Arthrogriposis multiplex congenita 33.3
Congenital dislocation of the hip 33.3%
Hereditary sensory neuropathy type III 25%
Centronuclear myopathy 16.7%
Multiple pituitary hormone deficiency 50%
Isolated pituitary hormone deficiency 20%
Ectopic posterior pituitary gland 33.3%
Congenital bilateral perisilvian syndrome 33.3
Symmetric fetal growth restriction 40%
Asymmetric fetal growth restriction 40%
Nonimmune hydrops fetalis 15%
Atresia ani 18.2%
Microcephalus 15.4%
Omphalocele 12.5%
Prematurity 40%
Placental and amniotic fluid entities:
Amniotic sheet perpendicular to the placenta 50%
Cornual–fundal implantation of the placenta 30%
Placenta previa 12.5%
Oligohydramnios 17%
Polyhydramnios 15.8%
Maternal entities:
Uterus arcuatus 22.6%
Uterus unicornuatus 33.3%
Uterus bicornuatus 34.8%
Uterus didelphys 30–41%
Uterus septus 45.8%
Leiomyoma uteri 9–20%
Spinal cord injury 10%
Carriers of Duchenne muscular dystrophy 17%
Combination of two medical entities:
First twin in uterus with two bodies 14.29%
Second twin in uterus with two bodies 18.52%.Also, women with previous Caesarean deliveries have a risk of breech presentation at term twice that of women with previous vaginal deliveries.The highest possible probability of breech presentation of 50% indicates that breech presentation is a consequence of random filling of the intrauterine space, with the same probability of breech and cephalic presentation in a longitudinally elongated uterus.

Types
Types of breech depend on how the babys legs are lying.
A frank breech (otherwise known as an extended breech) is where the babys legs are up next to its abdomen, with its knees straight and its feet next to its ears. This is the most common type of breech.
A complete breech (or flexed breech) is when the baby appears as though it is sitting crossed-legged with its legs bent at the hips and knees.
A footling breech is when one or both of the babys feet are born first instead of the pelvis. This is more common in babies born prematurely or before their due date.
A kneeling breech is when the baby is born knees first.In addition to the above, breech births in which the sacrum is the fetal denominator can be classified by the position of a fetus. Thus sacro-anterior, sacro-transverse and sacro-posterior positions all exist, but left sacro-anterior is the most common presentation. Sacro-anterior indicates an easier delivery compared to other forms.

Complications
Umbilical cord prolapse may occur, particularly in the complete, footling, or kneeling breech. This is caused by the lowermost parts of the baby not completely filling the space of the dilated cervix. When the waters break the amniotic sac, it is possible for the umbilical cord to drop down and become compressed. This complication severely diminishes oxygen flow to the baby, so the baby must be delivered immediately (usually by Caesarean section) so that he or she can breathe. If there is a delay in delivery, the brain can be damaged. Among full-term, head-down babies, cord prolapse is quite rare, occurring in 0.4 percent. Among frank breech babies the incidence is 0.5 percent, among complete breeches 5 percent, and among footling breeches 15 percent.Head entrapment is caused by the failure of the fetal head to negotiate the maternal midpelvis.  At full term, the fetal bitrochanteric diameter (the distance between the outer points of the hips) is about the same as the biparietal diameter (the transverse diameter of the skull)—simply put the size of the hips are the same as the size of the head. The relatively larger buttocks dilate the cervix as effectively as the head does in the typical head-down presentation. In contrast, the relative head size of a preterm baby is greater than the fetal buttocks. If the baby is preterm, it may be possible for the babys body to emerge while the cervix has not dilated enough for the head to emerge.
Because the umbilical cord—the babys oxygen supply—is significantly compressed while the head is in the pelvis during a breech birth, it is important that the delivery of the aftercoming fetal head not be delayed.  If the arm is extended alongside the head, delivery will not occur. If this occurs, the Løvset manoeuvre may be employed, or the arm may be manually brought to a position in front of the chest. The Løvset manoeuvre involves rotating the fetal body by holding the fetal pelvis.  Twisting the body such that an arm trails behind the shoulder, it will tend to cross down over the face to a position where it can be reached by the obstetricians finger, and brought to a position below the head. A similar rotation in the opposite direction is made to deliver the other arm. In order to present the smallest diameter (9.5 cm) to the pelvis, the babys head must be flexed (chin to chest). If the head is in a deflexed position, the risk of entrapment is increased.  Uterine contractions and maternal muscle tone encourage the head to flex.
Oxygen deprivation may occur from either cord prolapse or prolonged compression of the cord during birth, as in head entrapment. If oxygen deprivation is prolonged, it may cause permanent neurological damage (for instance, cerebral palsy) or death. It has been suggested that a fast vaginal delivery would mean the risk of stopping babys oxygen supply is reduced.  However, there is not enough research to show this and a quick delivery might cause more harm to the baby than a conservative approach to the birth.Injury to the brain and skull may occur due to the rapid passage of the babys head through the mothers pelvis. This causes rapid decompression of the babys head. In contrast, a baby going through labor in the head-down position usually experiences gradual molding (temporary reshaping of the skull) over the course of a few hours. This sudden compression and decompression in breech birth may cause no problems at all, but it can injure the brain. This injury is more likely in preterm babies. The fetal head may be controlled by a special two-handed grip call the Mauriceau–Smellie–Veit maneuver or the elective application of forceps. This will be of value in controlling the rate of delivery of the head and reduce decompression. Related to potential head trauma, researchers have identified a relationship between breech birth and autism.Squeezing the babys abdomen can damage internal organs. Positioning the baby incorrectly while using forceps to deliver the after coming head can damage the spine or spinal cord.  It is important for the birth attendant to be knowledgeable, skilled, and experienced with all variations of breech birth.

Factors influencing safety
Birth attendants skill (and experience with breech birth) – The skill of the doctor or midwife and the number of breech births previously assisted is of crucial importance. Many of the dangers in vaginal birth for breech babies come from mistakes made by birth attendants. With the majority of breech babies being delivered by cesarean section there is more risk that birth attendants will lose their skills in delivering breech babies and therefore increase the risk of harm to the baby during a vaginal delivery.
Type of breech presentation – the frank breech has the most favorable outcomes in vaginal birth, with many studies suggesting no difference in outcome compared to head down babies. (Some studies, however, find that planned caesarean sections for all breech babies improve outcome. The difference may rest in part on the skill of the doctors who delivered babies in different studies.)  Complete breech presentation is the next most favorable position, but these babies sometimes shift and become footling breeches during labour.  Footling and kneeling breeches have a higher risk of cord prolapse and head entrapment.
Parity – Parity refers to the number of times a woman has given birth before.  If a woman has given birth vaginally, her pelvis has "proven" it is big enough to allow a baby of that babys size to pass through it. However, a head-down babys head often molds (shifts its shape to fit the maternal pelvis) and so may present a smaller diameter than the same-size baby born breech.
Fetal size in relation to maternal pelvic size – If the mothers pelvis is roomy and the baby is not large, this is favorable for vaginal breech delivery.  However, prenatal estimates of the size of the baby and the size of the pelvis are unreliable.
Hyperextension of the fetal head – this can be evaluated with ultrasound. Less than 5% of breech babies have their heads in the "star-gazing" position, face looking straight upwards and the back of the head resting against the back of the neck.  Caesarean delivery is absolutely necessary, because vaginal birth with the babys head in this position confers a high risk of spinal cord trauma and death.
Maturity of the baby – Premature babies appear to be at higher risk of complications if delivered vaginally than if delivered by caesarean section.
Progress of labor – A spontaneous, normally progressing, straightforward labor requiring no intervention is a favorable sign.
Second twins – If a first twin is born head down and the second twin is breech, the chances are good that the second twin can have a safe breech birth.

Management
As in labour with a baby in a normal head-down position, uterine contractions typically occur at regular intervals and gradually the cervix begins to thin and open. In the more common breech presentations, the babys bottom (rather than feet or knees) is what is first to descend through the maternal pelvis and emerge from the vagina.At the beginning of labour, the baby is generally in an oblique position, facing either the right or left side. The babys bottom is the same size in the term baby as the babys head.  Descent is thus as for the presenting fetal head and delay in descent is a cardinal sign of possible problems with the delivery of the head.
In order to begin the birth, descent of podalic pole along with compaction and internal rotation needs to occur.  This happens when the mothers pelvic floor muscles cause the baby to turn so that it can be born with one hip directly in front of the other.  At this point the baby is facing one of the mothers inner thighs.  Then, the shoulders follow the same path as the hips did.   At this time the baby usually turns to face the mothers back.   Next occurs external rotation, which is when the shoulders emerge as the babys head enters the maternal pelvis.  The combination of maternal muscle tone and uterine contractions cause the babys head to flex, chin to chest.   Then the  back of the babys head emerges and finally the face.
Due to the increased pressure during labour and birth, it is normal for the babys leading hip to be bruised and genitalia to be swollen. Babies who assumed the frank breech position in utero may continue to hold their legs in this position for some days after birth.

Cesarean or vaginal delivery
When a baby is born bottom first there is more risk that the birth will not be straight forward and that the baby could be harmed. For example, when the babys head passes through the mothers pelvis the umbilical cord can be compressed which prevents delivery of oxygenated blood to the baby. Due to this and other risks, babies in breech position are often born by a planned caesarean section in developed countries.Caesarean section reduces the risk of harm or death for the baby but does increase risk of harm to the mother compared with a vaginal delivery. It is best if the baby is in a head down position so that they can be born vaginally with less risk of harm to both mother and baby. The next section is looking at External cephalic version or ECV which is a method that can help the baby turn from a breech position to a head down position.
Vaginal birth of a breech baby has its risks but caesarean sections are not always available or possible, a mother might arrive in hospital at a late stage of her labour or may choose not to have a caesarean section. In these cases, it is important that the clinical skills needed to deliver breech babies are not lost so that mothers and babies are as safe as possible. Compared with developed countries, planned caesarean sections have not produced as good results in developing countries – it is suggested that this is due to more breech vaginal deliveries being performed by experienced, skilled practitioners in these settings.

Twin breech
In twin pregnancies, it is very common for one or both babies to be in the breech position. Most often twin babies do not have the chance to turn around because they are born prematurely. If both  babies are in the breech position and the mother has gone into labour early, a cesarean section may be the best option. About 30–40% of twin pregnancies result in only one baby being in the breech position. If this is the case, the babies can be born vaginally. After the first baby who is not in the breech position is delivered, the baby who is presented in the breech position may turn itself around, if this does not happen another procedure may performed called the breech extraction. The breech extraction is the procedure that involves the obstetrician grabbing the second twins feet and pulling him/her into the birth canal. This will help with delivering the second twin vaginally. However, if the second twin is larger than the first, complications with delivering the second twin vaginally may arise and a cesarean section should be performed. At times, the first twin (the twin closest to the birth canal) can be in the breech position with the second twin being in the cephalic position (vertical). When this occurs, risks of complications are higher than normal. In particular, a serious complication known as Locked twins </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 Eye injury and explain in detail? [/INST] Physical or chemical injuries of the eye can be a serious threat to vision if not treated appropriately and in a timely fashion. The most obvious presentation of ocular (eye) injuries is redness and pain of the affected eyes. This is not, however, universally true, as tiny metallic projectiles may cause neither symptom. Tiny metallic projectiles should be suspected when a patient reports metal on metal contact, such as with hammering a metal surface. Corneal foreign body is one of the most common preventable occupational hazard. Intraocular foreign bodies do not cause pain because of the lack of nerve endings in the vitreous humour and retina that can transmit pain sensations. As such, general or emergency department doctors should refer cases involving the posterior segment of the eye or intraocular foreign bodies to an ophthalmologist. Ideally, ointment would not be used when referring to an ophthalmologist, since it diminishes the ability to carry out a thorough eye examination.
Flicking sand, flying pieces of wood, metal, glass and stone are notorious for causing much of the eye trauma. Sporting balls such as cricket ball, lawn tennis ball, squash ball, shuttlecock, and other high speed flying objects can strike the eye. The eye is also susceptible to blunt trauma in a fistfight. Children’s games such as bow-and-arrows, bb guns and firecrackers can lead to eye trauma. Road traffic accidents (RTAs) with head and facial trauma may also have an eye injury - these are usually severe in nature with multiple lacerations, shards of glasses embedded in tissues, orbital fractures, severe hematoma and penetrating open-globe injuries with prolapse of eye contents.  Other causes of intraocular trauma may arise from workplace tools or even common household implements, including bottle-caps suddenly propelling at great force.About 5.3 million cases of foreign bodies in the eyes occurred in 2013.

Presentation
Complications
Multiple complications are known to occur following eye injury: corneal scarring, hyphema, iridodialysis, post-traumatic glaucoma, uveitis cataract, vitreous hemorrhage and retinal detachment. The complications risk is high with retinal tears, penetrating injuries and severe blunt trauma.

Diagnosis
The goal of investigation is the assessment of the severity of the ocular injury with an eye to implementing a management plan as soon as is required. The usual eye examination should be attempted, and may require a topical anesthetic in order to be tolerable.  Many topical agents cause burning upon instillation. Proxymetacaine has been found to have the best tolerance.Depending on the medical history and preliminary examination, the primary care physician should designate the eye injury as a true emergency, urgent or semi-urgent.

Classification
Based on the injury to the eyewall (outer fibrous coat of the eye consisting of cornea and sclera)

Closed globe injury: the eye globe is intact, but the seven rings of the eye have been classically described as affected by blunt trauma. Types include contusion and lamellar laceration
Open globe injury: there is a full thickness injury of the eye wall (cornea and sclera)It includes
A) Globe rupture: caused by blunt trauma and is an inside-out injury.
B) Globe laceration: a full-thickness wound caused by sharp objects. It includes
1)Penetrating trauma: the globe integrity is disrupted by a full-thickness entry wound and may be associated with prolapse of the internal contents of the eye. Such injuries are often referred to as a Globe fracture or a Globe rupture, although these can be incurred by blunt trauma as well.
2) Perforating trauma: the globe integrity is disrupted in two places due to an entrance and exit wound (through and through injury). This is a quite severe type of eye injury.
Other types include

Blowout fracture of the orbit is caused by blunt trauma, classically described for fist or ball injury, leading to fracture of the floor or medial wall of the orbit due to sudden increased pressure on the orbital contents.
Muscular Entrapment Fracture of the orbital bones can lead to muscular entrapment limiting gaze in one direction.

Emergency
An emergency must be treated within minutes. This includes chemical burns of both the conjunctiva and cornea.

Urgent
An urgent case must be treated within hours. This includes penetrating globe injuries; corneal abrasions or corneal foreign bodies; hyphema (must be referred); eyelid lacerations that are deep, involve the lid margin or involve the lacrimal canaliculi; radiant energy burns such as arc eye (welders burn) or snow blindness; or, rarely, traumatic optic neuropathy.

Semi-urgent
Semi-urgent cases must be managed within 1–2 days. They include orbital fractures and subconjunctival hemorrhages.

Management
Irrigation
The first line of management for chemical injuries is usually copious irrigation of the eye with an isotonic saline or sterile water. In the cases of chemical burns, one should not try to buffer the solution, but instead dilute it with copious flushing.

Patching
Depending on the type of ocular injury, either a pressure patch or shield patch should be applied </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 Alcoholic liver disease and explain in detail? [/INST] Alcoholic liver disease (ALD), also called alcohol-related liver disease (ARLD), is a term that encompasses the liver manifestations of alcohol overconsumption, including fatty liver, alcoholic hepatitis, and chronic hepatitis with liver fibrosis or cirrhosis.It is the major cause of liver disease in Western countries. Although steatosis (fatty liver disease) will develop in any individual who consumes a large quantity of alcoholic beverages over a long period of time, this process is transient and reversible. More than 90% of all heavy drinkers develop fatty liver whilst about 25% develop the more severe alcoholic hepatitis, and 15% liver cirrhosis.

Risk factors
Risk factors known as of 2010 are:

Quantity of alcohol taken: Consumption of 60–80 g per day (14 g is considered one standard drink in the US, i.e., 1.5 fl oz hard liquor, 5 fl oz wine, 12 fl oz beer; drinking a six-pack of 5% ABV beer daily would be 84 g and just over the upper limit) for 20 years or more in men, or 20 g/day for women significantly increases the risk of hepatitis and fibrosis by 6% to 41%.
Pattern of drinking: Drinking outside of meal times increases up to 3 times the risk of alcoholic liver disease.
Sex: Women are twice as susceptible to alcohol-related liver disease, and may develop alcoholic liver disease with shorter durations and doses of chronic consumption. The lesser amount of alcohol dehydrogenase secreted in the gut, higher proportion of body fat in women, and changes in alcohol absorption due to the menstrual cycle may explain this phenomenon.
Ethnicity: Higher rates of alcohol-related liver disease, unrelated to differences in amounts of alcohol consumed, are seen in African-American and Hispanic males compared to Caucasian males.
Hepatitis C infection: A concomitant hepatitis C infection significantly accelerates the process of liver injury.
Genetic factors: Genetic factors predispose both to alcoholism and to alcoholic liver disease. Both monozygotic twins are more likely to be alcoholics and to develop liver cirrhosis than both dizygotic twins. Polymorphisms in the enzymes involved in the metabolism of alcohol, such as ADH, ALDH, CYP4502E1, mitochondrial dysfunction, and cytokine polymorphism may partly explain this genetic component. However, no specific polymorphisms have currently been firmly linked to alcoholic liver disease.
Iron overload (hemochromatosis).
Diet: Malnutrition, particularly vitamin A and E deficiencies, can worsen alcohol-induced liver damage by preventing regeneration of hepatocytes. This is particularly a concern as alcoholics are usually malnourished because of a poor diet, anorexia, and encephalopathy.

Pathophysiology
The mechanism of ALD is not completely understood. 80% of alcohol passes through the liver to be detoxified. Chronic consumption of alcohol results in the secretion of pro-inflammatory cytokines (TNF-alpha, interleukin 6 and interleukin 8), oxidative stress, lipid peroxidation, and acetaldehyde toxicity. These factors cause inflammation, apoptosis and eventually fibrosis of liver cells. Why this occurs in only a few individuals is still unclear. Additionally, the liver has tremendous capacity to regenerate and even when 75% of hepatocytes are dead, it continues to function as normal.

Fatty change
Fatty change, or steatosis, is the accumulation of fatty acids in liver cells. These can be seen as fatty globules under the microscope. Alcoholism causes development of large fatty globules (macro-vesicular steatosis) throughout the liver and can begin to occur after a few days of heavy drinking. Alcohol is metabolized by alcohol dehydrogenase (ADH) into acetaldehyde, then further metabolized by aldehyde dehydrogenase (ALDH) into acetic acid, which is finally oxidized into carbon dioxide (CO2) and water (H2O). This process generates NADH, and increases the NADH/NAD+ ratio. A higher NADH concentration induces fatty acid synthesis while a decreased NAD level results in decreased fatty acid oxidation. Subsequently, the higher levels of fatty acids signal the liver cells to compound it to glycerol to form triglycerides. These triglycerides accumulate, resulting in fatty liver.

Alcoholic hepatitis
Alcoholic hepatitis is characterized by the inflammation of hepatocytes. Between 10% and 35% of heavy drinkers develop alcoholic hepatitis (NIAAA, 1993). While development of hepatitis is not directly related to the dose of alcohol, some people seem more prone to this reaction than others. This is called alcoholic steato-necrosis and the inflammation appears to predispose to liver fibrosis. Inflammatory cytokines (TNF-alpha, IL-6 and IL-8) are thought to be essential in the initiation and perpetuation of liver injury and cytotoxic hepatomegaly by inducing apoptosis and severe hepatotoxicity. One possible mechanism for the increased activity of TNF-α is the increased intestinal permeability due to liver disease. This facilitates the absorption of the gut-produced endotoxin into the portal circulation. The Kupffer cells of the liver then phagocytose endotoxin, stimulating the release of TNF-α. TNF-α then triggers apoptotic pathways through the activation of caspases, resulting in cell death.

Cirrhosis
Cirrhosis is a late stage of serious liver disease marked by inflammation (swelling), fibrosis (cellular hardening) and damaged membranes preventing detoxification of chemicals in the body, ending in scarring and necrosis (cell death). Between 10% to 20% of heavy drinkers will develop cirrhosis of the liver (NIAAA, 1993). Acetaldehyde may be responsible for alcohol-induced fibrosis by stimulating collagen deposition by hepatic stellate cells. The production of oxidants derived from NADPH oxi- dase and/or cytochrome P-450 2E1 and the formation of acetaldehyde-protein adducts damage the cell membrane.Symptoms include jaundice (yellowing), liver enlargement, and pain and tenderness from the structural changes in damaged liver architecture. Without total abstinence from alcohol use, cirrhosis will eventually lead to liver failure. Late complications of cirrhosis or liver failure include portal hypertension (high blood pressure in the portal vein due to the increased flow resistance through the damaged liver), coagulation disorders (due to impaired production of coagulation factors), ascites (heavy abdominal swelling due to buildup of fluids in the tissues) and other complications, including hepatic encephalopathy and the hepatorenal syndrome.
Cirrhosis can also result from other causes than hazardous alcohol use, such as viral hepatitis and heavy exposure to toxins other than alcohol. The late stages of cirrhosis may look similar medically, regardless of cause. This phenomenon is termed the "final common pathway" for the disease.
Fatty change and alcoholic hepatitis with abstinence can be reversible. The later stages of fibrosis and cirrhosis tend to be irreversible, but can usually be contained with abstinence for long periods of time.

Diagnosis
In the early stages, patients with ALD exhibit subtle and often no abnormal physical findings. It is usually not until development of advanced liver disease that stigmata of chronic liver disease become apparent. Early ALD is usually discovered during routine health examinations when liver enzyme levels are found to be elevated. These usually reflect alcoholic hepatic steatosis. Microvesicular and macrovesicular steatosis with inflammation are seen in liver biopsy specimens. These histologic features of ALD are indistinguishable from those of nonalcoholic fatty liver disease. Steatosis usually resolves after discontinuation of alcohol use. Continuation of alcohol use will result in a higher risk of progression of liver disease and cirrhosis. In patients with acute alcoholic hepatitis, clinical manifestations include fever, jaundice, hepatomegaly, and possible hepatic decompensation with hepatic encephalopathy, variceal bleeding, and ascites accumulation. Tender hepatomegaly may be present, but abdominal pain is unusual. Occasionally, the patient may be asymptomatic.

Laboratory findings
In people with alcoholic hepatitis, the serum aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio is greater than 2:1. AST and ALT levels are almost always less than 500. The elevated AST to ALT ratio is due to deficiency of pyridoxal phosphate, which is required in the ALT enzyme synthetic pathway. Furthermore, alcohol metabolite–induced injury of hepatic mitochondria results in AST isoenzyme release. Other laboratory findings include red blood cell macrocytosis (mean corpuscular volume > 100) and elevations of serum gamma-glutamyl transferase (GGT), alkaline phosphatase, and bilirubin levels. Folate level is reduced in alcoholic patients due to decreased intestinal absorption, increased bone marrow requirement for folate in the presence of alcohol, and increased urinary loss. The magnitude of leukocytosis (white blood cell depletion) reflects severity of liver injury. Histologic features include Mallory bodies, giant mitochondria, hepatocyte necrosis, and neutrophil infiltration in the area around the veins. Mallory bodies, which are also present in other liver diseases, are condensations of cytokeratin components in the hepatocyte cytoplasm and do not contribute to liver injury. Up to 70% of patients with moderate to severe alcoholic hepatitis already have cirrhosis identifiable on biopsy examination at the time of diagnosis.

Treatment
Not drinking further alcohol is the most important part of treatment. People with chronic HCV infection should abstain from any alcohol intake, due to the risk for rapid acceleration of liver disease.

Medications
A 2006 Cochrane review did not find evidence sufficient for the use of androgenic anabolic steroids. Corticosteroids are sometimes used; however, this is recommended only when severe liver inflammation is present.Silymarin has been investigated as a possible treatment, with ambiguous results. One review claimed benefit for S-adenosyl methionine in disease models.The effects of anti-tumor necrosis factor medications such as infliximab and etanercept are unclear and possibly harmful. Evidence is unclear for pentoxifylline. Propylthiouracil may result in harm.Evidence does not support supplemental nutrition in liver disease.

Transplantation
Although in rare cases liver cirrhosis is reversible, the disease process remains mostly irreversible. Liver transplantation remains the only definitive therapy. Today, survival after liver transplantation is similar for people with ALD and non-ALD. The requirements for transplant listing are the same as those for other types of liver disease, except for a 6-month sobriety prerequisite along with psychiatric evaluation and rehabilitation assistance. Specific requirements vary among the transplant centers. Relapse to alcohol use after transplant listing results in delisting </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 Mycobacterium avium complex and explain in detail? [/INST] Mycobacterium avium complex is a group of mycobacteria comprising Mycobacterium intracellulare and Mycobacterium avium that are commonly grouped because they infect humans together; this group, in turn, is part of the group of nontuberculous mycobacteria.  These bacteria cause Mycobacterium avium-intracellulare infections or Mycobacterium avium complex infections in humans. These bacteria are common and are found in fresh and salt water, in household dust and in soil. MAC bacteria usually cause infection in those who are immunocompromised or those with severe lung disease.

Description
In the Runyon classification, both bacteria are nonchromogens.  They can be differentiated from M. tuberculosis and each other by commercially available DNA probes.: 245 They are characterized as Gram-positive, nonmotile, acid-fast, short to long rods.
Colony characteristics

Usually, colonies are smooth, rarely rough, and not pigmented colonies. Older colonies may become yellow.Physiology

Growth on Löwenstein-Jensen medium and Middlebrook 7H10 agar occurs at 37°C after seven or more days.
The complex can be (but is not often) resistant to isoniazid, ethambutol, rifampin, and streptomycin.Differential characteristics

M. intracellulare and M. avium form the M. avium complex (MAC).
Remarkable ITS heterogeneity is seen within different M. intracellulare isolates.

Type strains
M. intracellulare type strains include ATCC 13950, CCUG 28005, CIP 104243, DSM 43223, JCM 6384, and NCTC 13025.M. avium type strains include ATCC 25291, DSM 44156, and TMC 724.

Human health
MAC bacteria enter most peoples body when inhaled into the lungs or swallowed, but only cause infection in those who are immunocompromised or who have severe lung disease such as those with cystic fibrosis or chronic obstructive lung disease (COPD) </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 SARS and explain in detail? [/INST] Severe acute respiratory syndrome (SARS) is a viral respiratory disease of zoonotic origin caused by severe acute respiratory syndrome coronavirus (SARS-CoV or SARS-CoV-1), the first identified strain of the SARS coronavirus species severe acute respiratory syndrome–related coronavirus (SARSr-CoV). The first known cases occurred in November 2002, and the syndrome caused the 2002–2004 SARS outbreak. In the 2010s, Chinese scientists traced the virus through the intermediary of Asian palm civets to cave-dwelling horseshoe bats in Xiyang Yi Ethnic Township, Yunnan.SARS was a relatively rare disease; at the end of the epidemic in June 2003, the incidence was 8,469 cases with a case fatality rate (CFR) of 11%. No cases of SARS-CoV-1 have been reported worldwide since 2004.In December 2019, another strain of SARS-CoV was identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This new strain causes coronavirus disease 2019 (COVID-19), a disease which brought about the  COVID-19 pandemic.

Signs and symptoms
SARS produces flu-like symptoms which may include fever, muscle pain, lethargy, cough, sore throat, and other nonspecific symptoms. The only symptom common to all patients appears to be a fever above 38 °C (100 °F). SARS often leads to shortness of breath and pneumonia, which may be direct viral pneumonia or secondary bacterial pneumonia.The average incubation period for SARS is 4–6 days, although it is rarely as short as 1 day or as long as 14 days.

Transmission
The primary route of transmission for SARS-CoV is contact of the mucous membranes with respiratory droplets or fomites. While diarrhea is common in people with SARS, the fecal–oral route does not appear to be a common mode of transmission. The basic reproduction number of SARS-CoV, R0, ranges from 2 to 4 depending on different analyses. Control measures introduced in April 2003 reduced the R to 0.4.

Diagnosis
SARS-CoV may be suspected in a patient who has:
Any of the symptoms, including a fever of 38 °C (100 °F) or higher, and
Either a history of:
Contact (sexual or casual) with someone with a diagnosis of SARS within the last 10 days or
Travel to any of the regions identified by the World Health Organization (WHO) as areas with recent local transmission of SARS.
Clinical criteria of Sars-CoV diagnosisEarly illness: equal to or more than 2 of the following: chills, rigors, myalgia, diarrhea, sore throat (self-reported or observed)
Mild-to-moderate illness: temperature of >38 °C (100 °F) plus indications of lower respiratory tract infection (cough, dyspnea)
Severe illness: ≥1 of radiographic evidence, presence of ARDS, autopsy findings in late patients.For a case to be considered probable, a chest X-ray must be indicative for atypical pneumonia or acute respiratory distress syndrome.
The WHO has added the category of "laboratory confirmed SARS" which means patients who would otherwise be considered "probable" and have tested positive for SARS based on one of the approved tests (ELISA, immunofluorescence or PCR) but whose chest X-ray findings do not show SARS-CoV infection (e.g. ground glass opacities, patchy consolidations unilateral).The appearance of SARS-CoV in chest X-rays is not always uniform but generally appears as an abnormality with patchy infiltrates.

Prevention
There is no vaccine for SARS, although immunologist Anthony Fauci mentioned that the CDC developed one and placed it in the US national stockpile.  That vaccine, however, is a prototype and not field-ready as of March 2020. Clinical isolation and quarantine remain the most effective means to prevent the spread of SARS. Other preventive measures include:

Hand-washing with soap and water, or use of alcohol-based hand sanitizer
Disinfection of surfaces of fomites to remove viruses
Avoiding contact with bodily fluids
Washing the personal items of someone with SARS in hot, soapy water (eating utensils, dishes, bedding, etc.)
Avoiding travel to affected areas
Wearing masks and gloves
Keeping people with symptoms home from school
Simple hygiene measures
Isolating oneself as much as possible to minimize the chances of transmission of the virusMany public health interventions were made to try to control the spread of the disease, which is mainly spread through respiratory droplets in the air, either inhaled or deposited on surfaces and subsequently transferred to a bodys mucous membranes. These interventions included earlier detection of the disease; isolation of people who are infected; droplet and contact precautions; and the use of personal protective equipment (PPE), including masks and isolation gowns. A 2017 meta-analysis found that for medical professionals wearing N-95 masks could reduce the chances of getting sick up to 80% compared to no mask. A screening process was also put in place at airports to monitor air travel to and from affected countries.SARS-CoV is most infectious in severely ill patients, which usually occurs during the second week of illness. This delayed infectious period meant that quarantine was highly effective; people who were isolated before day five of their illness rarely transmitted the disease to others.As of 2017, the CDC was still working to make federal and local rapid-response guidelines and recommendations in the event of a reappearance of the virus.It has been found that those with a Vitamin D deficiency were at a 19.61-fold higher risk of having a critical result from Covid-19 disease versus those with an adequate amount of vitamin D. Patients with low vitamin D levels had worse symptoms, were more likely to be hospitalized, and had a greater risk of death. It is believed the reason vitamin D supplementation helps with the prevention of Covid-19 is due to the fact that vitamin D combats cytokine storms that are brought on because of Covid-19. Vitamin D supplementation is only effective in preventing Covid-19 but has been shown to have no effect after Covid-19 is contracted.

Treatment
As SARS is a viral disease, antibiotics do not have direct effect but may be used against bacterial secondary infection. Treatment of SARS is mainly supportive with antipyretics, supplemental oxygen and mechanical ventilation as needed. While ribavirin is commonly used to treat SARS, there seems to have little to no effect on SARS-CoV, and no impact on patients outcomes. There is currently no proven antiviral therapy. Tested substances, include ribavirin, lopinavir, ritonavir, type I interferon, that have thus far shown no conclusive contribution to the diseases course. Administration of corticosteroids, is recommended by the British Thoracic Society/British Infection Society/Health Protection Agency in patients with severe disease and O2 saturation of <90%.People with SARS-CoV must be isolated, preferably in negative-pressure rooms, with complete barrier nursing precautions taken for any necessary contact with these patients, to limit the chances of medical personnel becoming infected. In certain cases, natural ventilation by opening doors and windows is documented to help decreasing indoor concentration of virus particles.Some of the more serious damage caused by SARS may be due to the bodys own immune system reacting in what is known as cytokine storm.

Vaccine
Vaccines can help immune system to create enough antibodies and also it can help to decrease a risk of side effects like arm pain, fever, headache etc. According to research papers published in 2005 and 2006, the identification and development of novel vaccines and medicines to treat SARS was a priority for governments and public health agencies around the world. In early 2004, an early clinical trial on volunteers was planned. A major researchers 2016 request, however, demonstrated that no field-ready SARS vaccine had been completed because likely market-driven priorities had ended funding.

Prognosis
Several consequent reports from China on some recovered SARS patients showed severe long-time sequelae. The most typical diseases include, among other things, pulmonary fibrosis, osteoporosis, and femoral necrosis, which have led in some cases to the complete loss of working ability or even self-care ability of people who have recovered from SARS. As a result of quarantine procedures, some of the post-SARS patients have been diagnosed with post-traumatic stress disorder (PTSD) and major depressive disorder.

Epidemiology
SARS was a relatively rare disease; at the end of the epidemic in June 2003, the incidence was 8,422 cases with a case fatality rate (CFR) of 11%.The case fatality rate (CFR) ranges from 0% to 50% depending on the age group of the patient. Patients under 24 were least likely to die (less than 1%); those 65 and older were most likely to die (over 55%).As with MERS and COVID-19, SARS resulted in significantly more deaths of males than females.

Outbreak in South China
The SARS epidemic began in the Guangdong province of China in November 2002. The earliest case developed symptoms on 16 November 2002. The index patient, a farmer from Shunde, Foshan, Guangdong, was treated in the First Peoples Hospital of Foshan. The patient died soon after, and no definite diagnosis was made on his cause of death. Despite taking some action to control it, Chinese government officials did not inform the World Health Organization of the outbreak until February 2003. This lack of openness caused delays in efforts to control the epidemic, resulting in criticism of the Peoples Republic of China from the international community. China officially apologized for early slowness in dealing with the SARS epidemic.The viral outbreak was subsequently genetically traced to a colony of cave-dwelling horseshoe bats in Xiyang Yi Ethnic Township, Yunnan.The outbreak first came to the attention of the international medical community on 27 November 2002, when Canadas Global Public Health Intelligence Network (GPHIN), an electronic warning system that is part of the World Health Organizations Global Outbreak Alert and Response Network (GOARN), picked up reports of a "flu outbreak" in China through Internet media monitoring and analysis and sent them to the WHO. While GPHINs capability had recently been upgraded to enable Arabic, Chinese, English, French, Russian, and Spanish translation, the system was limited to English or French in presenting this information. Thus, while the first reports of an unusual outbreak were in Chinese, an English report was not generated until 21 January 2003. The first super-spreader was admitted to the Sun Yat-sen Memorial Hospital in Guangzhou on 31 January, which soon spread the disease to nearby hospitals.In early April 2003, after a prominent physician, Jiang Yanyong, pushed to report the danger to China, there appeared to be a change in official policy when SARS began to receive a much greater prominence in the official media. Some have directly attributed this to the death of an American teacher, James Earl Salisbury, in Hong Kong. It was around this same time that Jiang Yanyong made accusations regarding the undercounting of cases in Beijing military hospitals. After intense pressure, Chinese officials allowed international officials to investigate the situation there. This revealed problems plaguing the aging mainland Chinese healthcare system, including increasing decentralization, red tape, and inadequate communication.Many healthcare workers in the affected nations risked their lives and died by treating patients, and trying to contain the infection before ways to prevent infection were known.

Spread to other regions
The epidemic reached the public spotlight in February 2003, when an American businessman traveling from China, Johnny Chen, became affected by pneumonia-like symptoms while on a flight to Singapore. The plane stopped in Hanoi, Vietnam, where the patient died in Hanoi French Hospital. Several of the medical staff who treated him soon developed the same disease despite basic hospital procedures. Italian doctor Carlo Urbani identified the threat and communicated it to WHO and the Vietnamese government; he later died from the disease.The severity of the symptoms and the infection among hospital staff alarmed global health authorities, who were fearful of another emergent pneumonia epidemic. On 12 March 2003, the WHO issued a global alert, followed by a health alert by the United States Centers for Disease Control and Prevention (CDC). Local transmission of SARS took place in Toronto, Ottawa, San Francisco, Ulaanbaatar, Manila, Singapore, Taiwan, Hanoi and Hong Kong whereas within China it spread to Guangdong, Jilin, Hebei, Hubei, Shaanxi, Jiangsu, Shanxi, Tianjin, and Inner Mongolia.

Hong Kong
The disease spread in Hong Kong from Liu Jianlun, a Guangdong doctor who was treating patients at Sun Yat-Sen Memorial Hospital. He arrived in February and stayed on the ninth floor of the Metropole Hotel in Kowloon, infecting 16 of the hotel visitors. Those visitors traveled to Canada, Singapore, Taiwan, and Vietnam, spreading SARS to those locations.Another larger cluster of cases in Hong Kong centred on the Amoy Gardens housing estate. Its spread is suspected to have been facilitated by defects in its bathroom drainage system that allowed sewer gases including virus particles to vent into the room. Bathroom fans exhausted the gases and wind carried the contagion to adjacent downwind complexes. Concerned citizens in Hong Kong worried that information was not reaching people quickly enough and created a website called sosick.org, which eventually forced the Hong Kong government to provide information related to SARS in a timely manner. The first cohort of affected people were discharged from hospital on 29 March 2003.

Canada
The first case of SARS in Toronto was identified on 23 February 2003. Beginning with an elderly woman, Kwan Sui-Chu, who had returned from a trip to Hong Kong and died on 5 March, the virus eventually infected 257 individuals in the province of Ontario. The trajectory of this outbreak is typically divided into two phases, the first centring around her son Tse Chi Kwai, who infected other patients at the Scarborough Grace Hospital and died on 13 March. The second major wave of cases was clustered around accidental exposure among patients, visitors, and staff within the North York General Hospital. The WHO officially removed Toronto from its list of infected areas by the end of June 2003.The official response by the Ontario provincial government and Canadian federal government has been widely criticized in the years following the outbreak. Brian Schwartz, vice-chair of Ontarios SARS Scientific Advisory Committee, described public health officials preparedness and emergency response at the time of the outbreak as "very, very basic and minimal at best". Critics of the response often cite poorly outlined and enforced protocol for protecting healthcare workers and identifying infected patients as a major contributing factor to the continued spread of the virus. The atmosphere of fear and uncertainty surrounding the outbreak resulted in staffing issues in area hospitals when healthcare workers elected to resign rather than risk exposure to SARS.

Identification of virus
In late February 2003, Italian doctor Carlo Urbani was called into The French Hospital of Hanoi to look at Johnny Chen, an American businessman who had fallen ill with what doctors thought was a bad case of influenza. Urbani realized that Chens ailment was probably a new and highly contagious disease. He immediately notified the WHO. He also persuaded the Vietnamese Health Ministry to begin isolating patients and screening travelers, thus slowing the early pace of the epidemic. He subsequently contracted the disease himself, and died in March 2003.The CDC and Canadas National Microbiology Laboratory identified the SARS genome in April 2003. Scientists at Erasmus University in Rotterdam, the Netherlands demonstrated that the SARS coronavirus fulfilled Kochs postulates thereby suggesting it as the causative agent. In the experiments, macaques infected with the virus developed the same symptoms as human SARS patients.

Origin and animal vectors
In late May 2003, a study was conducted using samples of wild animals sold as food in the local market in Guangdong, China. The study found that "SARS-like" coronaviruses could be isolated from masked palm civets (Paguma sp.). Genomic sequencing determined that these animal viruses were very similar to human SARS viruses, however they were phylogenetically distinct, and so the study concluded that it was unclear whether they were the natural reservoir in the wild. Still, more than 10,000 masked palm civets were killed in Guangdong Province since they were a "potential infectious source." The virus was also later found in raccoon dogs (Nyctereuteus sp.), ferret badgers (Melogale spp.), and domestic cats.In 2005, two studies identified a number of SARS-like coronaviruses in Chinese bats. Phylogenetic analysis of these viruses indicated a high probability that SARS coronavirus originated in bats and spread to humans either directly or through animals held in Chinese markets. The bats did not show any visible signs of disease, but are the likely natural reservoirs of SARS-like coronaviruses. In late 2006, scientists from the Chinese Centre for Disease Control and Prevention of Hong Kong University and the Guangzhou Centre for Disease Control and Prevention established a genetic link between the SARS coronavirus appearing in civets and in the second, 2004 human outbreak, bearing out claims that the disease had jumped across species.It took 14 years to find the original bat population likely responsible for the SARS pandemic. In December 2017, "after years of searching across China, where the disease first emerged, researchers reported ... that they had found a remote cave in Xiyang Yi Ethnic Township, Yunnan province, which is home to horseshoe bats that carry a strain of a particular virus known as a coronavirus </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 CREST syndrome and explain in detail? [/INST] CREST syndrome, also known as the limited cutaneous form of systemic sclerosis (lcSSc), is a multisystem connective tissue disorder. The acronym "CREST" refers to the five main features:  calcinosis, Raynauds phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia.CREST syndrome is associated with detectable antibodies against centromeres (a component of the cell nucleus), and usually spares the kidneys (a feature more common in the related condition systemic scleroderma). If the lungs are involved, it is usually in the form of pulmonary arterial hypertension.

Signs and symptoms
Calcinosis
CREST causes thickening and tightening of the skin with deposition of calcific nodules ("calcinosis").

Raynauds phenomenon
Raynauds phenomenon is frequently the first manifestation of CREST/lcSSc, preceding other symptoms by years. Stress and cold temperature induce an exaggerated vasoconstriction of the small arteries, arterioles, and thermoregulatory vessels of the skin of the digits. Clinically this manifests as a white-blue-red transition in skin color.  Underlying this transition is pallor and cyanosis of the digits, followed by a reactive hyperemia as they rewarm. When extreme and frequent, this phenomenon can lead to digital ulcerations, gangrene, or amputation.
Ulceration can predispose to chronic infections of the involved site.

Esophageal dysmotility
Presents as a sensation of food getting stuck (dysphagia) in the mid- or lower esophagus, atypical chest pain, or cough. People often state they must drink liquids to swallow solid food.  This motility problem results from atrophy of the gastrointestinal tract wall smooth muscle.  This change may occur with or without pathologic evidence of significant tissue fibrosis.

Sclerodactyly
Though it is the most easily recognizable manifestation, it is not prominent in all patients. Thickening generally only involves the skin of the fingers distal to the metacarpophalangeal joints in CREST.  Early in the course of the disease, the skin may appear edematous and inflamed </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 Chikungunya and explain in detail? [/INST] Chikungunya is an infection caused by the Chikungunya virus (CHIKV). Symptoms include fever and joint pains. These typically occur two to twelve days after exposure. Other symptoms may include headache, muscle pain, joint swelling, and a rash. Symptoms usually improve within a week; however, occasionally the joint pain may last for months or years. The risk of death is around 1 in 1,000. The very young, old, and those with other health problems are at risk of more severe disease.The virus is spread between people by two types of mosquitos: Aedes albopictus and Aedes aegypti. They mainly bite during the day. The virus may circulate within a number of animals including birds and rodents. Diagnosis is by either testing the blood for the viruss RNA or antibodies to the virus. The symptoms can be mistaken for those of dengue fever and Zika fever. It is believed most people become immune after a single infection.The best means of prevention is overall mosquito control and the avoidance of bites in areas where the disease is common. This may be partly achieved by decreasing mosquito access to water and with the use of insect repellent and mosquito nets. There is no vaccine and no specific treatment as of 2016. Recommendations include rest, fluids, and medications to help with fever and joint pain.While the disease typically occurs in Africa and Asia, outbreaks have been reported in Europe and the Americas since the 2000s. In 2014 more than a million suspected cases occurred. In 2014 it was occurring in Florida in the continental United States but as of 2016 there were no further locally acquired cases. The disease was first identified in 1952 in Tanzania. The term is from the Kimakonde language and means "to become contorted".

Signs and symptoms
Around 85% of people infected with Chikungunya virus experience symptoms, typically beginning with a sudden high fever above 39 °C (102 °F). The fever is soon followed by severe muscle and joint pain. Pain usually affects multiple joints in the arms and legs, and is symmetric – i.e. if one elbow is affected, the other is as well. People with Chikungunya also frequently experience headache, back pain, nausea, and fatigue. Around half of those affected develop a rash, with reddening and sometimes small bumps on the palms, foot soles, torso, and face. For some, the rash remains constrained to a small part of the body; for others, the rash can be extensive, covering more than 90% of the skin. Some people experience gastrointestinal issues, with abdominal pain and vomiting. Others experience eye problems, namely sensitivity to light, conjunctivitis, and pain behind the eye. This first set of symptoms – called the "acute phase" of Chikungunya – lasts around a week, after which most symptoms resolve on their own.Many people continue to have symptoms after the "acute phase" resolves, termed the "post-acute phase" for symptoms lasting three weeks to three months, and the "chronic stage" for symptoms lasting longer than three months. In both cases, the lasting symptoms tend to be joint pains: arthritis, tenosynovitis, and/or bursitis. If the affected person had pre-existing joint issues, these tend to worsen. Overuse of a joint can result in painful swelling, stiffness, nerve damage, and neuropathic pain. Typically the joint pain improves with time; however, the chronic stage can last anywhere from a few months to several years.Joint pain is reported in 87–98% of cases, and nearly always occurs in more than one joint, though joint swelling is uncommon. Typically the affected joints are located in both arms and legs. Joints are more likely to be affected if they have previously been damaged by disorders such as arthritis. Pain most commonly occurs in peripheral joints, such as the wrists, ankles, and joints of the hands and feet as well as some of the larger joints, typically the shoulders, elbows and knees. Pain may also occur in the muscles or ligaments. In more than half of cases, normal activity is limited by significant fatigue and pain. Infrequently, inflammation of the eyes may occur in the form of iridocyclitis, or uveitis, and retinal lesions may occur. Temporary damage to the liver may occur.People with Chikungunya occasionally develop neurologic disorders, most frequently swelling or degeneration of the brain, inflammation or degneration of the myelin sheaths around neurons, Guillain–Barré syndrome, acute disseminated encephalomyelitis, hypotonia (in newborns), and issues with visual processing. In particularly rare cases, people may develop behavioral changes, seizures, irritation of the cerebellum or meninges, oculomotor nerve palsy, or paralysis of the eye muscles.Newborns are susceptible to particularly severe effects of Chikungunya infection. Signs of infection typically begin with fever, rash, and swelling at the extremities. Around half of newborns have a mild case of the disease that resolves on its own; the other half have severe disease with inflammation of the brain and seizures. In severe cases, affected newborns may also have issues with bleeding and bloodflow, and problems with heart function.In addition to newborns, the elderly, and those with diabetes, heart disease, liver and kidney diseases, and human immunodeficiency virus infection tend to have more severe cases of Chikungunya. Around 1 to 5 in 1,000 people with symptomatic Chikungunya die of the disease.

Cause
Virology
Chikungunya virus (CHIKV), is a member of the genus Alphavirus, and family Togaviridae. It was first isolated in 1953 in Tanzania and is an RNA virus with a positive-sense single-stranded genome of about 11.6kb. It is a member of the Semliki Forest virus complex and is closely related to Ross River virus, Onyongnyong virus, and Semliki Forest virus. Because it is transmitted by arthropods, namely mosquitoes, it can also be referred to as an arbovirus (arthropod-borne virus). In the United States, it is classified as a category B priority pathogen, and work requires biosafety level III precautions.

Transmission
Chikungunya is generally transmitted from mosquitoes to humans. Less common modes of transmission include vertical transmission, which is transmission from mother to child during pregnancy or at birth. Transmission via infected blood products and through organ donation is also theoretically possible during times of outbreak, though no cases have yet been documented. The incubation period ranges from one to twelve days, and is most typically three to seven.Chikungunya is related to mosquitoes, their environments, and human behavior. The adaptation of mosquitoes to the changing climate of North Africa around 5,000 years ago made them seek out environments where humans stored water. Human habitation and the mosquitoes environments were then very closely connected. During periods of epidemics humans are the reservoir of the virus. Because high amounts of virus are present in the blood in the beginning of acute infection, the virus can be spread from a viremic human to a mosquito, and back to a human. During other times, monkeys, birds and other vertebrates have served as reservoirs. Three genotypes of this virus have been described, each with a distinct genotype and antigenic character: West African, East/Central/South African, and Asian genotypes. The Asian lineage originated in 1952 and has subsequently split into two lineages – India (Indian Ocean Lineage) and South East Asian clades. This virus was first reported in the Americas in 2014. Phylogenetic investigations have shown that there are two strains in Brazil – the Asian and East/Central/South African types – and that the Asian strain arrived in the Caribbean (most likely from Oceania) in about March 2013. The rate of molecular evolution was estimated to have a mean rate of 5 × 10−4 substitutions per site per year (95% higher probability density 2.9–7.9 × 10−4).Chikungunya is spread through bites from Aedes mosquitoes, and the species A. aegypti was identified as the most common vector, though the virus has recently been associated with many other species, including A. albopictus. Research by the Pasteur Institute in Paris has suggested Chikungunya virus strains in the 2005-2006 Reunion Island outbreak incurred a mutation that facilitated transmission by the Asian tiger mosquito (A. albopictus). Other species potentially able to transmit Chikungunya virus include Ae. furcifer-taylori, Ae. africanus, and Ae. luteocephalus.

Mechanism
Chikungunya virus is passed to humans when a bite from an infected mosquito breaks the skin and introduces the virus into the body.  The pathogenesis of chikungunya infection in humans is still poorly understood, despite recent outbreaks. It appears that in vitro, Chikungunya virus is able to replicate in human epithelial and endothelial cells, primary fibroblasts, and monocyte-derived macrophages. Viral replication is highly cytopathic, but susceptible to type-I and -II interferon. In vivo, in studies using living cells, chikungunya virus appears to replicate in fibroblasts, skeletal muscle progenitor cells, and myofibers.The type-1 interferon response seems to play an important role in the hosts response to chikungunya infection. Upon infection with chikungunya, the hosts fibroblasts produce type-1 alpha and beta interferon (IFN-α and IFN-β). In mouse studies, deficiencies in INF-1 in mice exposed to the virus cause increased morbidity and mortality. The chikungunya-specific upstream components of the type-1 interferon pathway involved in the hosts response to chikungunya infection are still unknown. Nonetheless, mouse studies suggest that IPS-1 is an important factor, and that IRF3 and IRF7 are important in an age-dependent manner. Mouse studies also suggest that chikungunya evades host defenses and counters the type-I interferon response by producing NS2, a nonstructural protein that degrades RBP1 and turns off the host cells ability to transcribe DNA. NS2 interferes with the JAK-STAT signaling pathway and prevents STAT from becoming phosphorylated.In the acute phase of chikungunya, the virus is typically present in the areas where symptoms present, specifically skeletal muscles, and joints. In the chronic phase, it is suggested that viral persistence (the inability of the body to entirely rid itself of the virus), lack of clearance of the antigen, or both, contribute to joint pain. The inflammation response during both the acute and chronic phase of the disease results in part from interactions between the virus and monocytes and macrophages. Chikungunya virus disease in humans is associated with elevated serum levels of specific cytokines and chemokines. High levels of specific cytokines have been linked to more severe acute disease: interleukin-6 (IL-6), IL-1β, RANTES, monocyte chemoattractant protein 1 (MCP-1), monokine induced by gamma interferon (MIG), and interferon gamma-induced protein 10 (IP-10). Cytokines may also contribute to chronic Chikungunya virus disease, as persistent joint pain has been associated with elevated levels of IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF). In those with chronic symptoms, a mild elevation of C-reactive protein (CRP) has been observed, suggesting ongoing chronic inflammation. However, there is little evidence linking chronic Chikungunya virus disease and the development of autoimmunity.

Viral replication
The virus consists of four nonstructural proteins and three structural proteins. The structural proteins are the capsid and two envelope glycoproteins: E1 and E2, which form heterodimeric spikes on the viron surface. E2 binds to cellular receptors in order to enter the host cell through receptor-mediated endocytosis. E1 contains a fusion peptide which, when exposed to the acidity of the endosome in eukaryotic cells, dissociates from E2 and initiates membrane fusion that allows the release of nucleocapsids into the host cytoplasm, promoting infection. The mature virion contains 240 heterodimeric spikes of E2/E1, which after release, bud on the surface of the infected cell, where they are released by exocytosis to infect other cells.

Diagnosis
Chikungunya is diagnosed on the basis of clinical, epidemiological, and laboratory criteria. Clinically, acute onset of high fever and severe joint pain would lead to suspicion of chikungunya. Epidemiological criteria consist of whether the individual has traveled to or spent time in an area in which chikungunya is present within the last twelve days (i.e.) the potential incubation period). Laboratory criteria include a decreased lymphocyte count consistent with viremia. However a definitive laboratory diagnosis can be accomplished through viral isolation, RT-PCR, or serological diagnosis.The differential diagnosis may include other mosquito-borne diseases, such as dengue or malaria, or other infections such as influenza. Chronic recurrent polyarthralgia occurs in at least 20% of chikungunya patients one year after infection, whereas such symptoms are uncommon in dengue.Virus isolation provides the most definitive diagnosis, but takes one to two weeks for completion and must be carried out in biosafety level III laboratories. The technique involves exposing specific cell lines to samples from whole blood and identifying Chikungunya virus-specific responses. RT-PCR using nested primer pairs is used to amplify several chikungunya-specific genes from whole blood, generating thousands to millions of copies of the genes in order to identify them. RT-PCR can also be used to quantify the viral load in the blood. Using RT-PCR, diagnostic results can be available in one to two days. Serological diagnosis requires a larger amount of blood than the other methods, and uses an ELISA assay to measure chikungunya-specific IgM levels in the blood serum. One advantage offered by serological diagnosis is that serum IgM is detectable from 5 days to months after the onset of symptoms, but drawbacks are that results may require two to three days, and false positives can occur with infection due to other related viruses, such as onyongnyong virus and Semliki Forest virus.Presently, there is no specific way to test for chronic signs and symptoms associated with Chikungunya fever although nonspecific laboratory findings such as C reactive protein and elevated cytokines can correlate with disease activity.

Prevention
Because no approved vaccine exists, the most effective means of prevention are protection against contact with the disease-carrying mosquitoes and controlling mosquito populations by limiting their habitat. Mosquito control focuses on eliminating the standing water where mosquitos lay eggs and develop as larva; if elimination of the standing water is not possible, insecticides or biological control agents can be added. Methods of protection against contact with mosquitos include using insect repellents with substances such as DEET, icaridin, PMD (p-menthane-3,8-diol, a substance derived from the lemon eucalyptus tree), or ethyl butylacetylaminopropionate (IR3535). However, increasing insecticide resistance presents a challenge to chemical control methods.Wearing bite-proof long sleeves and trousers also offers protection, and garments can be treated with pyrethroids, a class of insecticides that often has repellent properties. Vaporized pyrethroids (for example in mosquito coils) are also insect repellents. As infected mosquitoes often feed and rest inside homes, securing screens on windows and doors will help to keep mosquitoes out of the house. In the case of the day-active A. aegypti and A. albopictus, however, this will have only a limited effect, since many contacts between the mosquitoes and humans occur outdoors.

Vaccine
As of 2021, no approved vaccines are available. A phase-II vaccine trial used a live, attenuated virus, to develop viral resistance in 98% of those tested after 28 days and 85% still showed resistance after one year. However, 8% of people reported transient joint pain, and attenuation was found to be due to only two mutations in the E2 glycoprotein. Alternative vaccine strategies have been developed, and show efficacy in mouse models. In August 2014 researchers at the National Institute of Allergy and Infectious Diseases in the USA were testing an experimental vaccine which uses virus-like particles (VLPs) instead of attenuated virus.  All the 25 people participated in this phase 1 trial developed strong immune responses. As of 2015, a phase 2 trial was planned, using 400 adults aged 18 to 60 and to take place at 6 locations in the Caribbean. Even with a vaccine, mosquito population control and bite prevention will be necessary to control chikungunya disease. In 2021, two vaccine manufacturers, one in France, the other in the United States, reported successful completion of Phase II clinical trials.

Treatment
Currently, no specific treatment for chikungunya is available. Supportive care is recommended, and symptomatic treatment of fever and joint swelling includes the use of nonsteroidal anti-inflammatory drugs such as naproxen, non-aspirin analgesics such as paracetamol (acetaminophen) and fluids. Aspirin is not recommended due to the increased risk of bleeding. Despite anti-inflammatory effects, corticosteroids are not recommended during the acute phase of disease, as they may cause immunosuppression and worsen infection.Passive immunotherapy has potential benefit in treatment of chikungunya. Studies in animals using passive immunotherapy have been effective, and clinical studies using passive immunotherapy in those particularly vulnerable to severe infection are currently in progress. Passive immunotherapy involves administration of anti-CHIKV hyperimmune human intravenous antibodies (immunoglobulins) to those exposed to a high risk of chikungunya infection. No antiviral treatment for Chikungunya virus is currently available, though testing has shown several medications to be effective in vitro.

Chronic arthritis
In those who have more than two weeks of arthritis, ribavirin may be useful. The effect of chloroquine is not clear. It does not appear to help acute disease, but tentative evidence indicates it might help those with chronic arthritis. Steroids do not appear to be an effective treatment. NSAIDs and simple analgesics can be used to provide partial symptom relief in most cases. Methotrexate, a drug used in the treatment of rheumatoid arthritis, has been shown to have benefit in treating inflammatory polyarthritis resulting from chikungunya, though the drug mechanism for improving viral arthritis is unclear.

Prognosis
The mortality rate of chikungunya is slightly less than 1 in 1000. Those over the age of 65, neonates, and those with underlying chronic medical problems are most likely to have severe complications. Neonates are vulnerable as it is possible to vertically transmit chikungunya from mother to infant during delivery, which results in high rates of morbidity, as infants lack fully developed immune systems. The likelihood of prolonged symptoms or chronic joint pain is increased with increased age and prior rheumatological disease.

Epidemiology
Historically, chikungunya has been present mostly in the developing world. The disease causes an estimated 3 million infections each year. Epidemics in the Indian Ocean, Pacific Islands, and in the Americas, continue to change the distribution of the disease.
In Africa, chikungunya is spread by a sylvatic cycle in which the virus largely cycles between other non-human primates, small mammals, and mosquitos between human outbreaks. During outbreaks, due to the high concentration of virus in the blood of those in the acute phase of infection, the virus can circulate from humans to mosquitoes and back to humans. The transmission of the pathogen between humans and mosquitoes that exist in urban environments was established on multiple occasions from strains occurring on the eastern half of Africa in non-human primate hosts. This emergence and spread beyond Africa may have started as early as the 18th century. Currently, available data does not indicate whether the introduction of chikungunya into Asia occurred in the 19th century or more recently, but this epidemic Asian strain causes outbreaks in India and continues to circulate in Southeast Asia. In Africa, outbreaks were typically tied to heavy rainfall causing increased mosquito population. In recent outbreaks in urban centers, the virus has spread by circulating between humans and mosquitoes.Global rates of chikungunya infection are variable, depending on outbreaks. When chikungunya was first identified in 1952, it had a low-level circulation in West Africa, with infection rates linked to rainfall. Beginning in the 1960s, periodic outbreaks were documented in Asia and Africa. However, since 2005, following several decades of relative inactivity, chikungunya has re-emerged and caused large outbreaks in Africa, Asia, and the Americas. In India, for instance, chikungunya re-appeared following 32 years of absence of viral activity. Outbreaks have occurred in Europe, the Caribbean, and South America, areas in which chikungunya was not previously transmitted. Local transmission has also occurred in the United States and Australia, countries in which the virus was previously unknown. In 2005, an outbreak on the island of Réunion was the largest then documented, with an estimated 266,000 cases on an island with a population of approximately 770,000. In a 2006 outbreak, India reported 1.25 million suspected cases. Chikungunya was recently introduced to the Americas, and from 2013 to 2014 in the Americas, 1,118,763 suspected cases and 24,682 confirmed cases were reported by the PAHO.An analysis of the genetic code of Chikungunya virus suggests that the increased severity of the 2005–present outbreak may be due to a change in the genetic sequence which altered the E1 segment of the virus viral coat protein, a variant called E1-A226V. This mutation potentially allows the virus to multiply more easily in mosquito cells. The change allows the virus to use the Asian tiger mosquito (an invasive species) as a vector in addition to the more strictly tropical main vector, Aedes aegypti. Enhanced transmission of Chikungunya virus by A. albopictus could mean an increased risk for outbreaks in other areas where the Asian tiger mosquito is present. A albopictus is an invasive species which has spread through Europe, the Americas, the Caribbean, Africa and the Middle East.After the detection of zika virus in Brazil in April 2015, the first ever in the Western Hemisphere, it is now thought some chikungunya and dengue cases could in fact be zika virus cases or coinfections.

History
The word chikungunya is believed to have been derived from a description in the Makonde language, meaning "that which bends up", of the contorted posture of people affected with the severe joint pain and arthritic symptoms associated with this disease. The disease was first described by Marion Robinson and W.H.R. Lumsden in 1955, following an outbreak in 1952 on the Makonde Plateau, along the border between Mozambique and Tanganyika (the mainland part of modern-day Tanzania).According to the initial 1955 report about the epidemiology of the disease, the term chikungunya is derived from the Makonde root verb kungunyala, meaning to dry up or become contorted. In concurrent research, Robinson glossed the Makonde term more specifically as "that which bends up". Subsequent authors apparently overlooked the references to the Makonde language and assumed the term to have been derived from Swahili, the lingua franca of the region. The erroneous attribution to Swahili has been repeated in numerous print sources. Many erroneous spellings of the name of the disease are also in common use.
Since its discovery in Tanganyika, Africa, in 1952, Chikungunya virus outbreaks have occurred occasionally in Africa, South Asia, and Southeast Asia, but recent outbreaks have spread the disease over a wider range.The first recorded outbreak of this disease may have been in 1779. This is in agreement with the molecular genetics evidence that suggests it evolved around the year 1700.

Research
Chikungunya is one of more than a dozen agents researched as a potential biological weapon.This disease is part of the group of neglected tropical diseases.

See also
Coalition for Epidemic Preparedness Innovations
Epidemiology of chikungunya

References
Works cited
Burt FJ, Chen W, Miner JJ, Lenschow DJ, Merits A, Schnettler E, Kohl A, Rudd PA, Taylor A, Herrero LJ, Zaid A, Ng LF, Mahalingam S (April 2017). "Chikungunya virus: an update on the biology and pathogenesis of this emerging pathogen". Lancet Infect Dis. 17 (4): e107–e117. doi:10.1016/S1473-3099(16)30385-1. PMID 28159534.
Vairo F, Haider N, Kock R, Ntoumi F, Ippolito G, Zumla A (December 2019) </s>