<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Snakebite and can you explain it in depth? [/INST] A snakebite is an injury caused by the bite of a snake, especially a venomous snake. A common sign of a bite from a venomous snake is the presence of two puncture wounds from the animals fangs. Sometimes venom injection from the bite may occur. This may result in redness, swelling, and severe pain at the area, which may take up to an hour to appear. Vomiting, blurred vision, tingling of the limbs, and sweating may result. Most bites are on the hands, arms, or legs. Fear following a bite is common with symptoms of a racing heart and feeling faint. The venom may cause bleeding, kidney failure, a severe allergic reaction, tissue death around the bite, or breathing problems. Bites may result in the loss of a limb or other chronic problems or even death.The outcome depends on the type of snake, the area of the body bitten, the amount of snake venom injected, the general health of the person bitten and whether or not anti-venom serum has been administered by a doctor in a timely manner. Problems are often more severe in children than adults, due to their smaller size. Allergic reactions to snake venom can further complicate outcomes and can include anaphylaxis, requiring additional treatment and in some cases resulting in death.Snakes bite, both as a method of hunting, and as a means of protection. Risk factors for bites include working outside with ones hands such as in farming, forestry, and construction. Snakes commonly involved in envenomations include elapids (such as kraits, cobras and mambas), vipers, and sea snakes. The majority of snake species do not have venom and kill their prey by squeezing them. Venomous snakes can be found on every continent except Antarctica. Determining the type of snake that caused a bite is often not possible. The World Health Organization says snakebites are a "neglected public health issue in many tropical and subtropical countries", and in 2017, the WHO categorized snakebite envenomation as a Neglected Tropical Disease (Category A). The WHO also estimates that between 4.5 and 5.4 million people are bitten each year, and of those figures 40-50% develop some kind of clinical illness as a result. Furthermore, the death toll of such an injury could range between 80,000 and 130,000 people per year. The purpose was to encourage research, expand accessibility of antivenoms, and improve snakebite management in "developing countries".Prevention of snake bites can involve wearing protective footwear, avoiding areas where snakes live, and not handling snakes. Treatment partly depends on the type of snake. Washing the wound with soap and water and holding the limb still is recommended. Trying to suck out the venom, cutting the wound with a knife, or using a tourniquet is not recommended. Antivenom is effective at preventing death from bites; however, antivenoms frequently have side effects. The type of antivenom needed depends on the type of snake involved. When the type of snake is unknown, antivenom is often given based on the types known to be in the area. In some areas of the world, getting the right type of antivenom is difficult and this partly contributes to why they sometimes do not work. An additional issue is the cost of these medications. Antivenom has little effect on the area around the bite itself. Supporting the persons breathing is sometimes also required.The number of venomous snakebites that occur each year may be as high as five million. They result in about 2.5 million envenomations and 20,000 to 125,000 deaths. The frequency and severity of bites vary greatly among different parts of the world. They occur most commonly in Africa, Asia, and Latin America, with rural areas more greatly affected. Deaths are relatively rare in Australia, Europe and North America. For example, in the United States, about seven to eight thousand people per year are bitten by venomous snakes (about one in 40 thousand people) and about five people die (about one death per 65 million people).

Signs and symptoms
The most common first symptom of all snakebites is an overwhelming fear, which may contribute to other symptoms,  and may include nausea and vomiting, diarrhea, vertigo, fainting, tachycardia, and cold, clammy skin. Snake bites can have a variety of different signs and symptoms depending on their species.Dry snakebites and those inflicted by a non-venomous species may still cause severe injury. The bite may become infected from the snakes saliva. The fangs sometimes harbor pathogenic microbial organisms, including Clostridium tetani, and may require an updated tetanus immunization.Most snakebites, from either a venomous or a non-venomous snake, will have some type of local effect. Minor pain and redness occur in over 90 percent of cases, although this varies depending on the site. Bites by vipers and some cobras may be extremely painful, with the local tissue sometimes becoming tender and severely swollen within five minutes. This area may also bleed and blister, and may lead to tissue necrosis. Other common initial symptoms of pit viper and viper bites include lethargy, bleeding, weakness, nausea, and vomiting. Symptoms may become more life-threatening over time, developing into hypotension, tachypnea, severe tachycardia, severe internal bleeding, altered sensorium, kidney failure, and respiratory failure.Bites by some snakes, such as the kraits, coral snake, Mojave rattlesnake, and the speckled rattlesnake, may cause little or no pain, despite their serious and  potentially life-threatening venom. Some people report  experiencing a "rubbery", "minty", or "metallic" taste after being bitten by certain species of rattlesnake. Spitting cobras and rinkhalses can spit venom in a persons eyes. This results in immediate pain, ophthalmoparesis, and sometimes blindness.

Some Australian elapids and most viper envenomations will cause coagulopathy, sometimes so severe that a person may bleed spontaneously from the mouth, nose, and even old, seemingly healed wounds. Internal organs may bleed, including the brain and intestines, and ecchymosis (bruising) of the skin is often seen.The venom of elapids, including sea snakes, kraits, cobras, king cobra, mambas, and many Australian species, contains toxins which attack the nervous system, causing neurotoxicity. The person may present with strange disturbances to their vision, including blurriness. Paresthesia throughout the body, as well as difficulty in speaking and breathing, may be reported. Nervous system problems will cause a huge array of symptoms, and those provided here are not exhaustive. If not treated immediately they may die from respiratory failure.Venom emitted from some types of cobras, almost all vipers and some sea snakes causes necrosis of muscle tissue. Muscle tissue will begin to die throughout the body, a condition known as rhabdomyolysis.  Rhabdomyolysis can result in damage to the kidneys as a result of myoglobin accumulation in the renal tubules. This, coupled with hypotension, can lead to acute kidney injury, and, if left untreated, eventually death.Snakebite is also known to cause depression and post-traumatic stress disorder in a high proportion of people who survive.

Cause
In the developing world most snakebites occur in those who work outside such as farmers, hunters, and fishermen. They often happen when a person steps on the snake or approaches it too closely. In the United States and Europe snakebites most commonly occur in those who keep them as pets.The type of snake that most often delivers serious bites depends on the region of the world. In Africa, it is mambas, Egyptian cobras, puff adders, and carpet vipers. In the Middle East, it is carpet vipers and elapids. In Latin America, it is snakes of the Bothrops and Crotalus types, the latter including rattlesnakes. In North America, rattlesnakes are the primary concern, and up to 95% of all snakebite-related deaths in the United States are attributed to the western and eastern diamondback rattlesnakes. In South Asia, it was previously believed that Indian cobras, common kraits, Russells viper, and carpet vipers were the most dangerous; other snakes, however, may also cause significant problems in this area of the world.

Pathophysiology
Since envenomation is completely voluntary, all venomous snakes are capable of biting without injecting venom into a person. Snakes may deliver such a "dry bite" rather than waste their venom on a creature too large for them to eat, a behaviour called venom metering. However, the percentage of dry bites varies among species: 80 percent of bites inflicted by sea snakes, which are normally timid, do not result in envenomation, whereas only 25 percent of pit viper bites are dry. Furthermore, some snake genera, such as rattlesnakes, significantly increase the amount of venom injected in defensive bites compared to predatory strikes.Some dry bites may also be the result of imprecise timing on the snakes part, as venom may be prematurely released before the fangs have penetrated the person. Even without venom, some snakes, particularly large constrictors such as those belonging to the Boidae and Pythonidae families, can deliver damaging bites; large specimens often cause severe lacerations, or the snake itself pulls away, causing the flesh to be torn by the needle-sharp recurved teeth embedded in the person. While not as life-threatening as a bite from a venomous species, the bite can be at least temporarily debilitating and could lead to dangerous infections if improperly dealt with.While most snakes must open their mouths before biting, African and Middle Eastern snakes belonging to the family Atractaspididae are able to fold their fangs to the side of their head without opening their mouth and jab a person.

Snake venom
It has been suggested that snakes evolved the mechanisms necessary for venom formation and delivery sometime during the Miocene epoch. During the mid-Tertiary, most snakes were large ambush predators belonging to the superfamily Henophidia, which use constriction to kill their prey. As open grasslands replaced forested areas in parts of the world, some snake families evolved to become smaller and thus more agile. However, subduing and killing prey became more difficult for the smaller snakes, leading to the evolution of snake venom. Other research on Toxicofera, a hypothetical clade thought to be ancestral to most living reptiles, suggests an earlier time frame for the evolution of snake venom, possibly to the order of tens of millions of years, during the Late Cretaceous.Snake venom is produced in modified parotid glands normally responsible for secreting saliva. It is stored in structures called alveoli behind the animals eyes, and ejected voluntarily through its hollow tubular fangs.
Venom in many snakes, such as pit vipers, affects virtually every organ system in the human body and can be a combination of many toxins, including cytotoxins, hemotoxins, neurotoxins, and myotoxins, allowing for an enormous variety of symptoms. Snake venom may cause cytotoxicity as various enzymes including hyaluronidases, collagenases, proteinases and phospholipases lead to breakdown (dermonecrosis) and injury of local tissue and inflammation which leads to pain, edema and blister formation. Metalloproteinases further lead to breakdown of the extracellular matrix (releasing inflammatory mediators) and cause microvascular damage, leading to hemorrhage, skeletal muscle damage (necrosis), blistering and further dermonecrosis. The metalloproteinase release of the inflammatory mediators leads to pain, swelling and white blood cell (leukocyte) infiltration. The lymphatic system may be damaged by the various enzymes contained in the venom leading to edema; or the lymphatic system may also allow the venom to be carried systemically. Snake venom may cause muscle damage or myotoxicity via the enzyme phospholipase A2 which disrupts the plasma membrane of muscle cells. This damage to muscle cells may cause rhabdomyolysis, respiratory muscle compromise, or both. Other enzymes such as bradykinin potentiating peptides, natriuretic peptides, vascular endothelial growth factors, proteases can also cause hypotension or low blood pressure. Toxins in snake venom can also cause kidney damage (nephrotoxicity) via the same inflammatory cytokines. The toxins cause direct damage to the glomeruli in the kidneys as well as causing protein deposits in Bowmans capsule. Or the kidneys may be indirectly damaged by envenomation due to shock, clearance of toxic substances such as immune complexes, blood degradation products or products of muscle breakdown (rhabdomyolysis).In venom-induced consumption coagulopathy, toxins in snake venom promote hemorrhage via activation, consumption and subsequent depletion of clotting factors in the blood. These clotting factors normally work as part of the coagulation cascade in the blood to form blood clots and prevent hemorrhage. Toxins in snake venom (especially the venom of new world pit vipers (the family crotalina))  may also cause low platelets (thrombocytopenia) or altered platelet function also leading to bleeding.Snake venom is known to cause neuromuscular paralysis, usually as a flaccid paralysis that is descending; starting at the facial muscles, causing ptosis or drooping eyelids and dysarthria or poor articulation of speech, and descending to the respiratory muscles causing respiratory compromise. The neurotoxins can either bind to and block membrane receptors at the post-synaptic neurons or they can be taken up into the pre-synaptic neuron cells and impair neurotransmitter release. Venom toxins that are taken up intra-cellularly, into the cells of the pre-synaptic neurons are much more difficult to reverse using anti-venom as they are inaccessible to the anti-venom when they are intracellular.The strength of venom differs markedly between species and even more so between families, as measured by median lethal dose (LD50) in mice. Subcutaneous LD50 varies by over 140-fold within elapids and by more than 100-fold in vipers. The amount of venom produced also differs among species, with the Gaboon viper able to potentially deliver from 450 to 600 milligrams of venom in a single bite, the most of any snake. Opisthoglyphous colubrids have venom ranging from life-threatening (in the case of the boomslang) to barely noticeable (as in Tantilla).

Prevention
Snakes are most likely to bite when they feel threatened, are startled, are provoked, or when they have been cornered. Snakes are likely to approach residential areas when attracted by prey, such as rodents. Regular pest control can reduce the threat of snakes considerably. It is beneficial to know the species of snake that are common in local areas, or while travelling or hiking. Africa, Australia, the Neotropics, and South Asia in particular are populated by many dangerous species of snake. Being aware of—and ultimately avoiding—areas known to be heavily populated by dangerous snakes is strongly recommended.When in the wilderness, treading heavily creates ground vibrations and noise, which will often cause snakes to flee from the area. However, this generally only applies to vipers, as some larger and more aggressive snakes in other parts of the world, such as mambas and cobras, will respond more aggressively. If presented with a direct encounter, it is best to remain silent and motionless. If the snake has not yet fled, it is important to step away slowly and cautiously.The use of a flashlight when engaged in camping activities, such as gathering firewood at night, can be helpful. Snakes may also be unusually active during especially warm nights when ambient temperatures exceed 21 °C (70 °F). It is advised not to reach blindly into hollow logs, flip over large rocks, and enter old cabins or other potential snake hiding-places. When rock climbing, it is not safe to grab ledges or crevices without examining them first, as snakes are cold-blooded and often sunbathe atop rock ledges.In the United States, more than 40 percent of people bitten by snake intentionally put themselves in harms way by attempting to capture wild snakes or by carelessly handling their dangerous pets—40 percent of that number had a blood alcohol level of 0.1 percent or more.It is also important to avoid snakes that appear to be dead, as some species will actually roll over on their backs and stick out their tongue to fool potential threats. A snakes detached head can immediately act by reflex and potentially bite. The induced bite can be just as severe as that of a live snake.
As a dead snake is incapable of regulating the venom injected, a bite from a dead snake can often contain large amounts of venom.

Treatment
It may be difficult to determine if a bite by any species of snake is life-threatening. A bite by a North American copperhead on the ankle is usually a moderate injury to a healthy adult, but a bite to a childs abdomen or face by the same snake may be fatal. The outcome of all snakebites depends on a multitude of factors: the type of snake, the size, physical condition, and temperature of the snake, the age and physical condition of the person, the area and tissue bitten (e.g., foot, torso, vein or muscle), the amount of venom injected, the time it takes for the person to find treatment, and finally the quality of that treatment. An overview of systematic reviews on different aspects of snakebite management found that the evidence base from majority of treatment modalities is low quality. An analysis of World Health Organization guidelines found that they are of low quality, with  inadequate stakeholder involvement and poor methodological rigour.

Snake identification
Identification of the snake is important in planning treatment in certain areas of the world, but is not always possible. Ideally the dead snake would be brought in with the person, but in areas where snake bite is more common, local knowledge may be sufficient to recognize the snake. However, in regions where polyvalent antivenoms are available, such as North America, identification of snake is not a high priority item. Attempting to catch or kill the offending snake also puts one at risk for re-envenomation or creating a second person bitten, and generally is not recommended.The three types of venomous snakes that cause the majority of major clinical problems are vipers, kraits, and cobras. Knowledge of what species are present locally can be crucial, as is knowledge of typical signs and symptoms of envenomation by each type of snake. A scoring system can be used to try to determine the biting snake based on clinical features, but these scoring systems are extremely specific to particular geographical areas and might be compromised by the presence of escaped or released non-native species.

First aid
Snakebite first aid recommendations vary, in part because different snakes have different types of venom. Some have little local effect, but life-threatening systemic effects, in which case containing the venom in the region of the bite by pressure immobilization is desirable. Other venoms instigate localized tissue damage around the bitten area, and immobilization may increase the severity of the damage in this area, but also reduce the total area affected; whether this trade-off is desirable remains a point of controversy. Because snakes vary from one country to another, first aid methods also vary.
Many organizations, including the American Medical Association and American Red Cross, recommend washing the bite with soap and water. Australian recommendations for snake bite treatment recommend against cleaning the wound. Traces of venom left on the skin/bandages from the strike can be used in combination with a snake bite identification kit to identify the species of snake. This speeds determination of which antivenom to administer in the emergency room.

Pressure immobilization
As of 2008, clinical evidence for pressure immobilization via the use of an elastic bandage is limited. It is recommended for snakebites that have occurred in Australia (due to elapids which are neurotoxic). It is not recommended for bites from non-neurotoxic snakes such as those found in North America and other regions of the world. The British military recommends pressure immobilization in all cases where the type of snake is unknown.The object of pressure immobilization is to contain venom within a bitten limb and prevent it from moving through the lymphatic system to the vital organs. This therapy has two components: pressure to prevent lymphatic drainage, and immobilization of the bitten limb to prevent the pumping action of the skeletal muscles.

Antivenom
Until the advent of antivenom, bites from some species of snake were almost universally fatal. Despite huge advances in emergency therapy, antivenom is often still the only effective treatment for envenomation. The first antivenom was developed in 1895 by French physician Albert Calmette for the treatment of Indian cobra bites. Antivenom is made by injecting a small amount of venom into an animal (usually a horse or sheep) to initiate an immune system response. The resulting antibodies are then harvested from the animals blood.
Antivenom is injected into the person intravenously, and works by binding to and neutralizing venom enzymes. It cannot undo damage already caused by venom, so antivenom treatment should be sought as soon as possible. Modern antivenoms are usually polyvalent, making them effective against the venom of numerous snake species. Pharmaceutical companies which produce antivenom target their products against the species native to a particular area. Although some people may develop serious adverse reactions to antivenom, such as anaphylaxis, in emergency situations this is usually treatable and hence the benefit outweighs the potential consequences of not using antivenom. Giving adrenaline (epinephrine) to prevent adverse reactions to antivenom before they occur might be reasonable in cases where they occur commonly. Antihistamines do not appear to provide any benefit in preventing adverse reactions.

Chronic Complications
Chronic health effects of snakebite include but is not limited to non-healing and chronic ulcers, musculoskeletal disorders, amputations, chronic kidney disease, and other neurological and endocrine complications. The treatment of chronic complications of snakebite has not been well researched and there a systems approach consisting of a multi-component intervention.

Outmoded
The following treatments, while once recommended, are considered of no use or harmful, including tourniquets, incisions, suction, application of cold, and application of electricity. Cases in which these treatments appear to work may be the result of dry bites.

Application of a tourniquet to the bitten limb is generally not recommended. There is no convincing evidence that it is an effective first-aid tool as ordinarily applied. Tourniquets have been found to be completely ineffective in the treatment of Crotalus durissus bites, but some positive results have been seen with properly applied tourniquets for cobra venom in the Philippines. Uninformed tourniquet use is dangerous, since reducing or cutting off circulation can lead to gangrene, which can be fatal. The use of a compression bandage is generally as effective, and much safer.
Cutting open the bitten area, an action often taken prior to suction, is not recommended since it causes further damage and increases the risk of infection; the subsequent cauterization of the area with fire or silver nitrate (also known as infernal stone) is also potentially threatening.
Sucking out venom, either by mouth or with a pump, does not work and may harm the affected area directly. Suction started after three minutes removes a clinically insignificant quantity—less than one-thousandth of the venom injected—as shown in a human study. In a study with pigs, suction not only caused no improvement but led to necrosis in the suctioned area. Suctioning by mouth presents a risk of further poisoning through the mouths mucous tissues. The helper may also release bacteria into the persons wound, leading to infection.
Immersion in warm water or sour milk, followed by the application of snake-stones (also known as la Pierre Noire), which are believed to draw off the poison in much the way a sponge soaks up water.
Application of a one-percent solution of potassium permanganate or chromic acid to the cut, exposed area. The latter substance is notably toxic and carcinogenic.
Drinking abundant quantities of alcohol following the cauterization or disinfection of the wound area.
Use of electroshock therapy in animal tests has shown this treatment to be useless and potentially dangerous.In extreme cases, in remote areas, all of these misguided attempts at treatment have resulted in injuries far worse than an otherwise mild to moderate snakebite. In worst-case scenarios, thoroughly constricting tourniquets have been applied to bitten limbs, completely shutting off blood flow to the area. By the time the person finally reached appropriate medical facilities their limbs had to be amputated.

In development
Several new drugs and treatments are under development for snakebite. For instance, the metal chelator dimercaprol has recently been shown to potently antagonize the activity of Zn2+-dependent snake venom metalloproteinases in vitro. New monoclonal antibodies, polymer gels and a small molecule inhibitor called Varespladib are in development.

Epidemiology
Estimates vary from 1.2 to 5.5 million snakebites, 421,000 to 2.5 million envenomings, and 20,000 to 125,000 deaths. Since reporting is not mandatory in much of the world, the data on the frequency of snakebites is not precise. Many people who survive bites have permanent tissue damage caused by venom, leading to disability. Most snake envenomings and fatalities occur in South Asia, Southeast Asia, and sub-Saharan Africa, with India reporting the most snakebite deaths of any country.Most snakebites are caused by non-venomous snakes. Of the roughly 3,000 known species of snake found worldwide, only 15% are considered dangerous to humans. Snakes are found on every continent except Antarctica. The most diverse and widely distributed snake family, the colubrids, has approximately 700 venomous species, but only five genera—boomslangs, twig snakes, keelback snakes, green snakes, and slender snakes—have caused human fatalities.Worldwide, snakebites occur most frequently in the summer season when snakes are active and humans are outdoors. Agricultural and tropical regions report more snakebites than anywhere else. In the United States, those bitten are typically male and between 17 and 27 years of age. Children and the elderly are the most likely to die.

Mechanics
When venomous snakes bite a target, they secrete venom through their venom delivery system. The venom delivery system generally consists of two venom glands, a compressor muscle, venom ducts, a fang sheath, and fangs. The primary and accessory venom glands store the venom quantities required during envenomation. The compressor muscle contracts during bites to increase the pressure throughout the venom delivery system. The pressurized venom travels through the primary venom duct to the secondary venom duct that leads down through the fang sheath and fang. The venom is then expelled through the exit orifice of the fang. The total volume and flow rate of venom administered into a target varies widely, sometimes as much as an order of magnitude. One of the largest factors is snake species and size, larger snakes have been shown to administer larger quantities of venom.

Predatory vs. defensive bites
Snake bites are classified as either predatory or defensive in nature. During defensive strikes, the rate of venom expulsion and total volume of venom expelled is much greater than during predatory strikes. Defensive strikes can have 10 times as much venom volume expelled at 8.5 times the flow rate. This can be explained by the snakes need to quickly subdue a threat. While employing similar venom expulsion mechanics, predatory strikes are quite different from defensive strikes. Snakes usually release the prey shortly after the envenomation allowing the prey to run away and die. Releasing prey prevents retaliatory damage to the snake. The venom scent allows the snake to relocate the prey once it is deceased. The amount of venom injected has been shown to increase with the mass of the prey animal. Larger venom volumes allow snakes to effectively euthanize larger prey while remaining economical during strikes against smaller prey. This is an important skill as venom is a metabolically expensive resource.

Venom Metering
Venom metering is the ability of a snake to have neurological control over the amount of venom released into a target during a strike based on situational cues. This ability would prove useful as venom is a limited resource, larger animals are less susceptible to the effects of venom, and various situations require different levels of force. There is a lot of evidence to support the venom metering hypothesis. For example, snakes frequently use more venom during defensive strikes, administer more venom to larger prey, and are capable of dry biting. A dry bite is a bite from a venomous snake that results in very little or no venom expulsion, leaving the target asymptomatic. However, there is debate among many academics about venom metering in snakes. The alternative to venom metering is the pressure balance hypothesis.
The pressure balance hypothesis cites the retraction of the fang sheath as the many mechanism for producing outward venom flow from the venom delivery system. When isolated, fang sheath retraction has experimentally been shown to induce very high pressures in the venom delivery system. A similar method was used to stimulate the compressor musculature, the main muscle responsible for the contraction and squeezing of the venom glad, and then measuring the induced pressures. It was determined that the pressure created from the fang sheath retraction was at times an order of magnitude greater than those created by the compressor musculature. Snakes do not have direct neurological control of the fang sheath, it can only be retracted as the fangs enter a target and the targets skin and body provide substantial resistance to retract the sheath. For these reasons, the pressure balance hypothesis concludes that external factors, mainly the bite and physical mechanics, are responsible for the quantity of venom expelled.

Venom Spitting
Venom spitting is another venom delivery method that is unique to some Asiatic and African cobras. In venom spitting, a stream of venom is propelled at very high pressures outwards up to 3 meters. The venom stream is usually aimed at the eyes and face of the target as a deterrent for predators. There are non-spitting cobras that provide useful information on the unique mechanics behind venom spitting. Unlike the elongated oval shaped exit orifices of non-spitting cobras, spitting cobras have circular exit orifice at their fang tips. This combined with the ability to partially retract their fang sheath by displacing the palato-maxillary arch and contracting the adductor mandibulae, allows the spitting cobras to create large pressures within the venom delivery system. While venom spitting is a less common venom delivery system, the venom can still cause the effects if ingested.

Society and culture
Snakes were both revered and worshipped and feared by early civilizations. The ancient Egyptians recorded prescribed treatments for snakebites as early as the Thirteenth Dynasty in the Brooklyn Papyrus, which includes at least seven venomous species common to the region today, such as the horned vipers. In Judaism, the Nehushtan was a pole with a snake made of copper fixed upon it. The object was regarded as a divinely empowered instrument of God that could bring healing to Jews bitten by venomous snakes while they were wandering in the desert after their exodus from Egypt. Healing was said to occur by merely looking at the object as it was held up by Moses.
Historically, snakebites were seen as a means of execution in some cultures </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Spasmodic dysphonia and can you explain it in depth? [/INST] Spasmodic dysphonia, also known as laryngeal dystonia, is a disorder in which the muscles that generate a persons voice go into periods of spasm. This results in breaks or interruptions in the voice, often every few sentences, which can make a person difficult to understand. The persons voice may also sound strained or they may be nearly unable to speak. Onset is often gradual and the condition is lifelong.The cause is unknown. Risk factors may include family history. Triggers may include an upper respiratory infection, injury to the larynx, overuse of the voice, and psychological stress. The underlying mechanism is believed to typically involve the central nervous system, specifically the basal ganglia. Diagnosis is typically made following examination by a team of healthcare providers.  It is a type of focal dystonia.While there is no cure, treatment may improve symptoms. Most commonly this involves injecting botulinum toxin into the affected muscles of the larynx. This generally results in improvement for a few months. Other measures include voice therapy, counselling, and amplification devices. If this is not effective, surgery may be considered; however, evidence to support surgery is limited.The disorder affects an estimated 2 per 100,000 people. Women are more commonly affected. Onset is typically between the ages of 30 and 50. Severity is variable between people. In some, work and social life are affected. Life expectancy is, however, normal.

Signs and symptoms
Symptoms of spasmodic dysphonia can come on suddenly or gradually appear over the span of years. They can come and go for hours or even weeks at a time, or remain consistent. Gradual onset can begin with the manifestation of a hoarse voice quality, which may later transform into a voice quality described as strained with breaks in phonation. These phonation breaks have been compared to stuttering in the past, but there is a lack of research in support of spasmodic dysphonia being classified as a fluency disorder. It is commonly reported by people with spasmodic dysphonia that symptoms almost only occur on vocal sounds that require phonation. Symptoms are less likely to occur at rest, while whispering, or on speech sounds that do not require phonation. It is hypothesized this occurs because of an increase in sporadic, sudden, and prolonged tension found in the muscles around the larynx during phonation. This tension affects the abduction and adduction (opening and closing) of the vocal folds. Consequently, the vocal folds are unable to retain subglottal air pressure (required for phonation) and breaks in phonation can be heard throughout the speech of people with spasmodic dysphonia.Regarding types of spasmodic dysphonia, the main characteristic of spasmodic dysphonia, breaks in phonation, is found along with other varying symptoms. The voice quality of adductor spasmodic dysphonia can be described as “strained-strangled” from tension in the glottal region. Voice quality for abductor spasmodic dysphonia can be described as breathy from variable widening of the glottal region. Vocal tremor may also be seen in spasmodic dysphonia. A mix and variance of these symptoms are found in mixed spasmodic dysphonia.Symptoms of spasmodic dysphonia typically appear in middle aged people, but have also been seen in people in their twenties, with symptoms emerging as young as teenage years.

Cause
Although the exact cause of spasmodic dysphonia is still unknown, epidemiological, genetic, and neurological pathogenic factors have been proposed in recent research.Risk factors include:
Being female
Being middle aged
Having a family history of neurological diseases (e.g., tremor, dystonia, meningitis, and other neurological diseases)
Stressful events
Upper respiratory tract infections
Sinus and throat illnesses
Heavy voice use
Cervical dystonia
Childhood measles or mumps
Pregnancy and parturitionIt has not been established whether these factors directly affect the development of spasmodic dysphonia (SD), however these factors could be used to identify possible and/or at-risk patients.Researchers have also explored the possibility of a genetic component to SD. Three genes have been identified that may be related to the development of focal or segmental dystonia: TUBB4A, THAP1 and TOR1A genes. However, a recent study that examined the mutation of these three genes in 86 SD patients found that only 2.3% of the patients had novel/rare variants in THAP1 but none in TUBB4A and TOR1A. Evidence of a genetic contribution for dystonia involving the larynx is still weak and more research is needed in order to establish a causal relationship between SD and specific genes.SD is a neurological disorder rather than a disorder of the larynx, and as in other forms of dystonia, interventions at the end organ (i.e., larynx) have not offered a definitive cure, only symptomatic relief. The pathophysiology underlying dystonia is becoming better understood as a result of discoveries about genetically based forms of the disorder, and this approach is the most promising avenue to a long-term solution.SD is classified as a neurological disorder. However, because the voice can sound normal or near normal at times, some practitioners believe it to be psychogenic; that is, originating in the affected persons mind rather than from a physical cause. This was especially true in the 19th and 20th centuries. No medical organizations or groups take this position. A comparison of SD patients compared with vocal fold paralysis (VFP) patients found that 41.7% of the SD patients met the DSM-IV criteria for psychiatric comorbidity compared with 19.5% of the VFP group. However, another study found the opposite, with SD patients having significantly less psychiatric comorbidity compared to VFP patients: "The prevalence of major psychiatric cases varied considerably among the groups, from a low of seven percent (1/14) for spasmodic dysphonia, to 29.4 percent (5/17) for functional dysphonia, to a high of 63.6 percent (7/11) for vocal cord paralysis." A review in the journal Swiss Medicine Weekly states that "Psychogenic causes, a psychological disequilibrium, and an increased tension of the laryngeal muscles are presumed to be one end of the spectrum of possible factors leading to the development of the disorder". Alternatively, many investigations into the condition feel that the psychiatric comorbidity associated with voice disorders is a result of the social isolation and anxiety that patients with these conditions feel as a consequence of their difficulty with speech, as opposed to the cause of their dysphonia. The opinion that SD is psychogenic is not upheld by experts in the scientific community.SD is formally classified as a movement disorder; it is a type of focal dystonia known as laryngeal dystonia.

Diagnosis
Diagnosis of spasmodic dysphonia requires a multidisciplinary team and consideration of both perceptual and physiological factors. There is currently no universally accepted diagnostic test for spasmodic dysphonia, which presents a challenge for diagnosis. Additionally, diagnostic criteria have not been agreed upon as the distinguishing features of this disorder have not been well-characterized.A team of professionals including a speech-language pathologist, an otolaryngologist, and a neurologist, are typically involved in spasmodic dysphonia assessment and diagnosis. The speech-language pathologist conducts a speech assessment including case history questions to gather information about voice use and symptoms. This is followed by clinical observation and perceptual rating of voice characteristics such as voice breaks or strain, which are selectively present in normal speech over other voice activities such as whispering or laughing. Symptoms also vary across types of spasmodic dysphonia. For example, voiced sounds are more affected in adductor spasmodic dysphonia, while unvoiced sounds are more affected in abductor spasmodic dysphonia. Following speech assessment, the otolaryngologist conducts a flexible transnasal laryngoscopy to view the vocal folds and activity of the muscles controlling them in order to eliminate other possible causes of the voice disorder. In spasmodic dysphonia, producing long vowels or speaking sentences results in muscle spasms which are not observed during other vocal activities such as coughing, breathing, or whispering. To evaluate the individual for any other neurological problems, this examination is followed up with an assessment by the neurologist.

Voice quality symbol
The voice quality symbol for spasmodic dysphonia is ꟿ.

Differential diagnosis
Because spasmodic dysphonia shares many characteristics with other voice disorders, misdiagnosis frequently occurs. A common misdiagnosis is muscle tension dysphonia, a functional voice disorder which results from use of the voice, rather than a structural abnormality. Some parameters can help guide the clinician towards a decision. In muscle tension dysphonia, the vocal folds are typically hyperadducted in constant way, not in a spasmodic way. Additionally, the voice difficulties found in spasmodic dysphonia can be task specific, as opposed to those found in muscle tension dysphonia. Being able to differentiate between muscle tension dysphonia and spasmodic dysphonia is important because muscle tension dysphonia typically responds well to behavioural voice treatment but spasmodic dysphonia does not. This is crucial to avoid providing inappropriate treatment, but in some cases a trial of behavioural voice treatment can also be helpful to establish a differential diagnosis.Spasmodic dysphonia can also be misdiagnosed as voice tremor. The movements that are found in this disorder are typically rhythmic in nature, as opposed to the muscle spasms of spasmodic dysphonia. It is important to note that voice tremor and spasmodic dysphonia can co-occur in some patients.Differential diagnosis is particularly important for determining appropriate interventions, as the type and cause of the disorder determine the most effective treatment. Differences in treatment effectiveness are present even between the types of spasmodic dysphonia. Diagnosis of spasmodic dysphonia is often delayed due to these challenges, which in turn presents difficulties in choosing the proper interventions.

Types
The three types of spasmodic dysphonia (SD) are adductor spasmodic dysphonia, abductor spasmodic dysphonia, and mixed spasmodic dysphonia. A fourth type called whispering dysphonia has also been proposed. Adductor spasmodic dysphonia is the most common type.

Adductor spasmodic dysphonia
Adductor spasmodic dysphonia (ADSD) is the most common type, affecting around 87% of individuals with SD. In ADSD, sudden involuntary muscle movements or spasms cause the vocal folds (or vocal cords) to squeeze together and stiffen. As the name suggests, these spasms occur in the adductor muscles of the vocal folds, specifically the thyroarytenoid and the lateral cricoarytenoid. These spasms make it difficult for the vocal folds to vibrate and produce voice. Words are often cut off or are difficult to start because of the muscle spasms. Therefore, speech may be choppy but differs from stuttering. The voice of an individual with adductor spasmodic dysphonia is commonly described as strained or strangled and full of effort. Surprisingly, the spasms are usually absent while laughing, speaking at a high pitch, or speaking while singing, but singers can experience a loss of range or the inability to produce certain notes of a scale or with projection. Stress, however, often makes the muscle spasms more severe.

Abductor spasmodic dysphonia
Abductor spasmodic dysphonia (ABSD) is the second most common type, affecting around 13% of individuals with SD. In ABSD, sudden involuntary muscle movements or spasms cause the vocal folds to open. As the name suggests, these spasms occur in the single abductor muscle of the vocal folds, called the posterior cricoarytenoid. The vocal folds cannot vibrate when they are open. The open position of the vocal folds also allows air to escape from the lungs during speech. As a result, the voices of these individuals often sound weak, quiet, and breathy or whispery. As with adductor spasmodic dysphonia, the spasms are often absent during activities such as laughing or singing, but singers can experience a loss of range or the inability to produce certain notes of a scale or with projection.

Mixed spasmodic dysphonia
Mixed spasmodic dysphonia is the most rare type. Mixed spasmodic dysphonia involves both muscles that open the vocal folds and those that close them and therefore has features of both adductor and abductor spasmodic dysphonia. Some researchers believe that a subset of cases classified as mixed spasmodic dysphonia may actually be ADSD or ABSD subtype with the addition of compensatory voice behaviours that make it appear mixed. This further adds to the difficulty in achieving accurate diagnosis.

Whispering dysphonia
A fourth type has also been described. This appears to be caused by mutations in the TUBB4 gene on the short arm of chromosome 19 (19p13.2-p13.3). This gene encodes a tubulin gene. The pathophysiology of this condition has yet to be determined.

Treatment
There are a number of potential treatments for spasmodic dysphonia, including Botox, voice therapy, and surgery. A number of medications have also been tried including anticholinergics (such as benztropine) which have been found to be effective in 40-50% of people, but which are associated with a number of side effects.

Botulinum toxin
Botulinum toxin (Botox) is often used to improve some symptoms of spasmodic dysphonia through weakening or paralyzing the vocal folds, thus preventing muscle spasms. The level of evidence for its use is currently limited; little is known about optimal dosage, frequency of injections, or exact location of injection. However, it remains a choice for many people due to the predictability and low chance of long term side effects. It results in periods of some improvement, with the duration of benefit lasting for 10–12 weeks on average before symptoms return to baseline. Repeat injection is required to sustain good vocal production, as results are only temporary. Some transient side effects observed in adductor spasmodic dysphonia include reduced speaking volume, difficulty swallowing, and a breathy and hoarse voice quality. While treatment outcomes are generally positive, it is presently unclear whether this treatment approach is more or less effective than others.

Voice therapy
Voice therapy appears to be ineffective in cases of true spasmodic dysphonia. However, as it is difficult to distinguish between spasmodic dysphonia and functional dysphonias, and misdiagnosis is relatively common, trial of voice therapy is often recommended before more invasive procedures are tried. Some also state that it is useful for mild symptoms and as an add-on to botox therapy and others report success in more severe cases. Laryngeal manual therapy, which is massaging of the neck and cervical structures, also shows positive results for intervention of functional dysphonia.

Surgery
If other measures are not effective, surgery may be considered; however, evidence to support surgery as a treatment for SD is limited. Treatment outcomes are generally positive, though more research is required to determine its effectiveness. Post-surgery voices can be imperfect and about 15% of people have significant difficulties </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Spider bite and can you explain it in depth? [/INST] A spider bite, also known as arachnidism, is an injury resulting from the bite of a spider. The effects of most bites are not serious. Most bites result in mild symptoms around the area of the bite. Rarely they may produce a necrotic skin wound or severe pain.: 455 Most spiders do not cause bites that are of importance. For a bite to be significant, substantial envenomation is required. Bites from the widow spiders involve a neurotoxic venom which produces a condition known as latrodectism. Symptoms may include pain which may be at the bite or involve the chest and abdomen, sweating, muscle cramps and vomiting among others. Bites from the recluse spiders cause the condition loxoscelism, in which local necrosis of the surrounding skin and widespread breakdown of red blood cells may occur. Headaches, vomiting and a mild fever may also occur. Other spiders that can cause significant bites include the Australian funnel-web spider and South American wandering spider.Efforts to prevent bites include clearing clutter and the use of pesticides. Most spider bites are managed with supportive care such as nonsteroidal anti-inflammatory drugs (including ibuprofen) for pain and antihistamines for itchiness. Opioids may be used if the pain is severe. While an antivenom exists for black widow spider venom, it is associated with anaphylaxis and therefore not commonly used in the United States. Antivenom against funnel web spider venom improves outcomes. Surgery may be required to repair the area of injured skin from some recluse bites.Spider bites may be overdiagnosed or misdiagnosed. In many reports of spider bites it is unclear if a spider bite actually occurred. Historically a number of conditions were attributed to spider bites. In the Middle Ages a condition claimed to arise from spider bites was tarantism, where people danced wildly. While necrosis has been attributed to the bites of a number of spiders, good evidence only supports this for recluse spiders.

Signs and symptoms
Almost all spiders are venomous, but not all spider bites result in the injection of venom. Pain from non-venomous bites, so-called "dry bites", typically lasts for 5 to 60 minutes while pain from envenomating spider bites may last for longer than 24 hours. Bleeding also may occur with a bite. Signs of a bacterial infection due to a spider bite occur infrequently (0.9%).A study of 750 definite spider bites in Australia indicated that 6% of spider bites cause significant effects, the vast majority of these being redback spider bites causing significant pain lasting more than 24 hours. Activation of the sympathetic nervous system can lead to sweating, high blood pressure and gooseflesh.Most recluse spider bites are minor with little or no necrosis. However, a small number of bites produce necrotic skin lesions. First pain and tenderness at the site begin. The redness changes over two to three days to a bluish sinking patch of dead skin—the hallmark of necrosis. The wound heals slowly over months but usually completely. Rarely, bites may cause widespread symptoms, with occasional fatalities.There are a few spiders that can bite human skin and cause a skin reaction, but spiders are blamed for many more reactions. In particular the misdiagnosis of infections and other skin ailments are commonly attributed to brown recluses.

Cause
Spiders do not feed on humans and typically bites occur as a defense mechanism. This can occur from unintentional contact or trapping of the spider. Most spiders have fangs too small to penetrate human skin. Most bites by species large enough for their bites to be noticeable will have no serious medical consequences.Medically significant spider venoms include various combinations and concentrations of necrotic agents, neurotoxins, and pharmacologically active compounds such as serotonin. Worldwide only two spider venoms have impact on humans—those of the widow and recluse spiders. Unlike snake and scorpion envenomation, widow and recluse species bites rarely have fatal consequences. In addition to the widespread widow and recluse spiders, some spider families found exclusively in remote tropical regions have a lethal neurotoxic venom: the wandering spider in Brazil and the funnel web in Australia. However, due to limited contact between these spiders and humans, deaths have always been rare, and since the introduction of anti-venom in Australia, there have been no funnel web related deaths.

Pathophysiology
A primary concern of the bite of a spider is the effect of its venom. A spider envenomation occurs whenever a spider injects venom into the skin. Not all spider bites involve injection of venom, and the amount of venom injected can vary based on the type of spider and the circumstances of the encounter. The mechanical injury from a spider bite is not a serious concern for humans. However, it is generally the toxicity of spider venom that poses the most risk to human beings; several spiders are known to have venom that can cause injury to humans in the amounts that a spider could inject when biting.
While venoms are by definition toxic substances, most spiders do not have venom that is directly toxic (in the quantities delivered) to require medical attention and, of those that do, severity is typically mild.
Spider venoms work on one of two fundamental principles; they are either neurotoxic (attacking the nervous system) or necrotic (attacking tissues surrounding the bite). In some cases, the venom affects vital organs and systems. The venoms of the widow spiders, Brazilian wandering spider and Australian funnel-web are neurotoxic. Heart muscle damage is an unusual complication of widow venom that may lead to death. Pulmonary edema, which is fluid accumulation in the lungs, is a feared and potentially serious but uncommon complication of funnel-web venom. Recluse and South African sand spider venoms are necrotic. Recluse venom may also cause severe hemolysis (destruction of red blood cells), though this is typically uncommon.

Diagnosis
Reliable diagnoses of spider bites require three conditions: first, there should be clinical effects of the bite at the time or soon afterwards, although there are no symptoms universally diagnostic of a spider bite, and bites by some spiders, e.g. Loxosceles species, may initially be painless; second, the spider should be collected, either at the time of the bite or immediately afterwards; and third, the spider should be identified by an expert arachnologist.Spider bites are commonly misdiagnosed. A review published in 2016 showed that 78% of 134 published medical case studies of supposed spider bites did not meet the necessary criteria for a spider bite to be verified. In the case of the two genera with the highest reported number of bites, Loxosceles and Latrodectus, spider bites were not verified in over 90% of the reports. Even when verification had occurred, details of the treatment and its effects were often lacking. Unverified bite reports likely represent many other conditions, both infectious and non-infectious, which can be confused with spider bites. Many of these conditions are far more common and more likely to be the source of necrotic wounds. An affected person may think that a wound is a spider bite when it is actually an infection with methicillin-resistant Staphylococcus aureus (MRSA).  False reports of spider bites in some cases have led to misdiagnosis and mistreatment, with potentially life-threatening consequences.

Prevention
Efforts to prevent bites include clearing clutter and the use of pesticides.OSHA recommends that workers take following measures to prevent spider bite:

Wear a long-sleeved shirt, hat, gloves, and boots when handling boxes, firewood, lumber, rocks, etc.
Inspect and shake out clothing and shoes before getting dressed.
Use insect repellents, such as DEET or Picaridin, on clothing and footwear.

Management
Most spider bites are harmless, and require no specific treatment. Treatment of bites may depend on the type of spider; thus, capture of the spider—either alive, or in a well-preserved condition, is useful.Treatment of spider bites includes washing the wound with soap and water and ice to reduce inflammation. Analgesics and antihistamines may be used; however, antibiotics are not recommended unless there is also a bacterial infection present. Black widow post-envenomation treatment seeks to control resulting pain and nausea.
In the case of bites by widow spiders, Australian funnel-web spiders, or Brazilian wandering spiders, medical attention should be sought immediately as in some cases the bites of these spiders develop into a medical emergency. Antivenom is available for severe widow and funnel-web envenomation.

Necrosis
In almost all cases, recluse bites are self-limited and typically heal without any medical intervention. Recommendations to limit the extent of damage include elevation and immobilization of the affected limb, application of ice. Both local wound care, and tetanus prophylaxis, are simple standards. There is no established treatment for more extensive necrosis. Many therapies have been used including hyperbaric oxygen, dapsone, antihistamines (e.g., cyproheptadine), antibiotics, dextran, glucocorticoids, vasodilators, heparin, nitroglycerin, electric shock, curettage, surgical excision, and antivenom. None of these treatments conclusively show benefit. Studies have shown surgical intervention is ineffective and may worsen outcome. Excision may delay wound healing, cause abscesses, and lead to objectionable scarring.Dapsone, an antibiotic, is commonly used in the United States and Brazil for the treatment of necrosis. There have been conflicting reports with some supporting its efficacy and others have suggested it should no longer be used routinely, if at all.

Antivenom
Use of antivenom for severe spider bites may be indicated, especially in the case of neurotoxic venoms. Effective antivenoms exist for Latrodectus, Atrax, and Phoneutria venom. Antivenom in the United States is in intravenous form but is rarely used, as anaphylactic reaction to the antivenom has resulted in deaths. In Australia, antivenom in intramuscular form was once commonly used, but use has declined. In 2014 some doubt as to antivenom effectiveness has been raised. In South America an antivenom is available for Loxosceles bites, and it appears antivenom may be the most promising therapy for recluse bites. However, in experimental trials recluse antivenom is more effective  when given early, and patients often do not present for 24 or more hours after envenomation, possibly limiting the effect of such intervention.

Epidemiology
Estimating the number of spider bites that occur is difficult as the spider involvement may not be confirmed or identified. Several researchers recommend only evaluating verified bites: those that have an eyewitness to the bite, the spider is brought in, and identified by expert. With "suspected arachnidism" the diagnosis came without a spider positively identified.

Africa
Several Latrodectus species (button spiders) live in Africa. South Africa also has six-eyed sand spiders (Hexophthalma species), whose bite may potentially cause skin necrosis. Physicians are advised that the diagnosis may be difficult without a spider.

Australia
Bites by the redbacks (Latrodectus hasselti) number a few thousand yearly throughout the country. Antivenom use is frequent but declining. Children may have fewer complications from bites. Funnel web spider bites are few 30–40 per year and 10% requiring intervention. The Sydney funnel web and related species are only on the east coast of Australia.

Europe
In Switzerland about ten to one hundred spider bites occur per one million people per year. During epidemics of latrodectism from the European black widow upwards of 150 bites a year were documented.

North America
The American Association of Poison Control Centers reported that they received calls regarding nearly 10,000 spider bites in 1994. The spiders of most concern in North America are brown recluse spiders, with nearly 1,500 bites in 2013 and black widow spiders with 1,800 bites </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Spontaneous bacterial peritonitis and can you explain it in depth? [/INST] Spontaneous bacterial peritonitis (SBP) is the development of a bacterial infection in the peritoneum,  despite the absence of an obvious source for the infection. It is specifically an infection of the ascitic fluid – an increased volume of peritoneal fluid. Ascites is most commonly a complication of cirrhosis of the liver. It can also occur in patients with nephrotic syndrome. SBP has a high mortality rate.The diagnosis of SBP requires paracentesis, a sampling of the peritoneal fluid  taken from the peritoneal cavity. If the fluid contains large numbers of white blood cells known as neutrophils (>250 cells/µL), infection is confirmed and antibiotics will be given, without waiting for culture results. In addition to antibiotics, infusions of albumin are usually administered.Other life-threatening complications such as kidney malfunction and increased liver insufficiency can be triggered by spontaneous bacterial peritonitis. 30% of SBP patients develop kidney malfunction, one of the strongest predictors for mortality. Where there are signs of this development albumin infusion will also be given.Spontaneous fungal peritonitis (SFP) can also occur and this can sometimes accompany a bacterial infection.

Signs and symptoms
Signs and symptoms of spontaneous bacterial peritonitis (SBP) include fevers, chills, nausea, vomiting, abdominal pain and tenderness, general malaise, altered mental status, and worsening ascites. Thirteen percent of patients have no signs or symptoms. In cases of acute or chronic liver failure SBP is one of the main triggers for hepatic encephalopathy, and where there is no other clear causal indication for this, SBP may be suspected.These symptoms can also be the same for a spontaneous fungal peritonitis (SFP) and therefore make a differentiation difficult. Delay of diagnosis can delay antifungal treatment and lead to a higher mortality rate.

Causes
SBP is most commonly caused by gram-negative E. coli, followed by Klebsiella. Common gram-positive bacteria identified include species of Streptococcus, Staphylococcus, and Enterococcus. The percentage of gram-positive bacteria responsible has been increasing.A spontaneous fungal infection can often follow a spontaneous bacterial infection that has been treated with antibiotics. The use of antibiotics can result in an excessive growth of fungi in the gut flora which can then translocate into the peritoneal cavity. Although fungi are much larger than bacteria, the increased intestinal permeability resulting from advanced cirrhosis makes their translocation easier. SFP is mostly caused by species of Candida and most commonly by Candida albicans.

Pathophysiology
H2 antagonists and proton-pump inhibitors are medications that decrease or suppress the secretion of acid by the stomach. Their use in treating cirrhosis is associated with the development of SBP. Bacterial translocation is thought to be the key mechanism for the development of SBP </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Sporotrichosis and can you explain it in depth? [/INST] Sporotrichosis, also known as rose handlers disease, is a fungal infection that affects skin, lungs, bone and joint, and can be widespread. It presents with firm painless nodules that later ulcerate. It can be localized or widespread. The disease progresses over a week to several months after the initial exposure to the fungus. Serious complications can also develop in people who have a weakened immune system.Sporotrichosis is caused by fungi of the Sporothrix schenckii species complex. Because S. schenckii is naturally found in soil, hay, sphagnum moss, and plants, it usually affects farmers, gardeners, and agricultural workers. It enters through small cuts in the skin to cause the infection. In case of sporotrichosis affecting the lungs, the fungal spores enter by breathing in. Sporotrichosis can also be acquired from handling cats with the disease; it is an occupational hazard for veterinarians.Treatment depends on the site and extent of infection. Topical antifungals can be applied to skin lesions.  Deep infection in lungs may require surgery.  Medications used include Itraconazole, posaconazole and amphotericin B. With treatment most people recover. The outcome may not be so good if there is a weak immune system or widespread disease.The causal fungus is found worldwide. The species was named for Benjamin Schenck, a medical student who in 1896 was the first to isolate it from a human specimen.It has been reported in cats, mules, dogs, mice and rats.

Signs and symptoms
Cutaneous or skin sporotrichosisThis is the most common form of this disease.  Symptoms of this form include nodular lesions or bumps in the skin, at the point of entry and also along lymph nodes and vessels.  The lesion starts off small and painless, and ranges in color from pink to purple.  Left untreated, the lesion becomes larger and look similar to a boil and more lesions will appear, until a chronic ulcer develops.Usually, cutaneous sporotrichosis lesions occur in the finger, hand, and arm.Pulmonary sporotrichosisThis rare form of the disease occur when S. schenckii spores are inhaled.  Symptoms of pulmonary sporotrichosis include productive coughing, nodules and cavitations of the lungs, fibrosis, and swollen hilar lymph nodes.  Patients with this form of sporotrichosis are susceptible to developing tuberculosis and pneumoniaDisseminated sporotrichosisWhen the infection spreads from the primary site to secondary sites in the body, the disease develops into a rare and critical form called disseminated sporotrichosis.  The infection can spread to joints and bones (called osteoarticular sporotrichosis) as well as the central nervous system and the brain (called sporotrichosis meningitis).The symptoms of disseminated sporotrichosis include weight loss, anorexia, and appearance of bony lesions.

Complications
Sporotrichosis lesions on the skin can become infected with bacteria. Cellulitis may also occur.

Diagnosis
Sporotrichosis is a chronic disease with slow progression and often subtle symptoms.  It is difficult to diagnose, as many other diseases share similar symptoms and therefore must be ruled out.
Patients with sporotrichosis will have antibody against the fungus S. schenckii, however, due to variability in sensitivity and specificity, it may not be a reliable diagnosis for this disease.  The confirming diagnosis remains culturing the fungus from the skin, sputum, synovial fluid, and cerebrospinal fluid. Smears should be taken from the draining tracts and ulcers.
Cats with sporotrichosis are unique in that the exudate from their lesions may contain numerous organisms. This makes cytological evaluation of exudate a valuable diagnostic tool in this species. Exudate is pyogranulomatous and phagocytic cells may be packed with yeast forms. These are variable in size, but many are cigar-shaped.

Differential diagnosis
Differential diagnosis includes: leishmaniasis, nocardiosis, mycobacterium marinum, cat-scratch disease, leprosy, syphilis, sarcoidosis and tuberculosis.

Prevention
The majority of sporotrichosis cases occur when the fungus is introduced through a cut or puncture in the skin while handling vegetation containing the fungal spores.  Prevention of this disease includes wearing long sleeves and gloves while working with soil, hay bales, rose bushes, pine seedlings, and sphagnum moss.
The risk of sporotrichosis in cats is increased in male cats that roam outdoors. Accordingly, the risk may be reduced by keeping cats indoors or neutering them. Isolating infected animals can also be a preventive measure. The risk of spread from infected cats to humans can be reduced by appropriate biosafety measures, including wearing protective equipment when handling a cat with suspected sporotrichosis and by washing hands, arms and clothing after handling the cat.

Treatment
Treatment of sporotrichosis depends on the severity and location of the disease.  The following are treatment options for this condition:
Oral potassium iodidePotassium iodide is an anti-fungal drug that is widely used as a treatment for cutaneous sporotrichosis. Despite its wide use, there is no high-quality evidence for or against this practice. Further studies are needed to assess the efficacy and safety of oral potassium iodide in the treatment of sporotrichosis.Itraconazole (Sporanox) and fluconazoleThese are antifungal drugs.  Itraconazole is currently the drug of choice and is significantly more effective than fluconazole. Fluconazole should be reserved for patients who cannot tolerate itraconazole.Amphotericin BThis antifungal medication is delivered intravenously.  Many patients, however, cannot tolerate Amphotericin B due to its potential side effects of fever, nausea, and vomiting.
Lipid formulations of amphotericin B are usually recommended instead of amphotericin B deoxycholate because of a better adverse-effect profile. Amphotericin B can be used for severe infection during pregnancy. For children with disseminated or severe disease, amphotericin B deoxycholate can be used initially, followed by itraconazole.In case of sporotrichosis meningitis, the patient may be given a combination of Amphotericin B and 5-fluorocytosine/Flucytosine.Terbinafine500mg and 1000mg daily dosages of terbinafine for twelve to 24 weeks has been used to treat cutaneous sporotrichosis.Newer triazolesSeveral studies have shown that posaconazole has in vitro activity similar to that of amphotericin B and itraconazole; therefore, it shows promise as an alternative therapy </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Strabismus and can you explain it in depth? [/INST] Strabismus is a vision disorder in which the eyes do not properly align with each other when looking at an object. The eye that is focused on an object can alternate. The condition may be present occasionally or constantly. If present during a large part of childhood, it may result in amblyopia, or lazy eyes, and loss of depth perception. If onset is during adulthood, it is more likely to result in double vision.Strabismus can occur due to muscle dysfunction, farsightedness, problems in the brain, trauma or infections. Risk factors include premature birth, cerebral palsy and a family history of the condition. Types include esotropia, where the eyes are crossed ("cross eyed"); exotropia, where the eyes diverge ("lazy eyed" or "wall eyed"); and hypertropia or hypotropia where they are vertically misaligned. They can also be classified by whether the problem is present in all directions a person looks (comitant) or varies by direction (incomitant). Diagnosis may be made by observing the light reflecting from the persons eyes and finding that it is not centered on the pupil. This is known as the Hirschberg reflex.  Another condition that produces similar symptoms is a cranial nerve disease.Treatment depends on the type of strabismus and the underlying cause. This may include the use of glasses and possibly surgery. Some types benefit from early surgery. Strabismus occurs in about 2% of children. The term comes from the Ancient Greek word στραβισμός (strabismós), meaning a squinting. Other terms for the condition include "squint" and "cast of the eye". "Wall-eye" has been used when the eyes turn away from each other.

Signs and symptoms
When observing a person with strabismus, the misalignment of the eyes may be quite apparent. A person with a constant eye turn of significant magnitude is very easy to notice. However, a small magnitude or intermittent strabismus can easily be missed upon casual observation. In any case, an eye care professional can conduct various tests, such as cover testing, to determine the full extent of the strabismus.Symptoms of strabismus include double vision and eye strain. To avoid double vision, the brain may adapt by ignoring one eye. In this case, often no noticeable symptoms are seen other than a minor loss of depth perception. This deficit may not be noticeable in someone who has had strabismus since birth or early childhood, as they have likely learned to judge depth and distances using monocular cues. However, a constant unilateral strabismus causing constant suppression is a risk for amblyopia in children. Small-angle and intermittent strabismus are more likely to cause disruptive visual symptoms. In addition to headaches and eye strain, symptoms may include an inability to read comfortably, fatigue when reading, and unstable or "jittery" vision.

Psychosocial effects
People of all ages who have noticeable strabismus may experience psychosocial difficulties. Attention has also been drawn to potential socioeconomic impact resulting from cases of detectable strabismus. A socioeconomic consideration exists as well in the context of decisions regarding strabismus treatment, including efforts to re-establish binocular vision and the possibility of stereopsis recovery.One study has shown that strabismic children commonly exhibit behaviors marked by higher degrees of inhibition, anxiety, and emotional distress, often leading to outright emotional disorders. These disorders are often related to a negative perception of the child by peers. This is due not only to an altered aesthetic appearance, but also because of the inherent symbolic nature of the eye and gaze, and the vitally important role they play in an individuals life as social components. For some, these issues improved dramatically following strabismus surgery. Notably, strabismus interferes with normal eye contact, often causing embarrassment, anger, and feelings of awkwardness, thereby affecting social communication in a fundamental way, with a possible negative effect on self esteem.Children with strabismus, particularly those with exotropia, an outward turn, may be more likely to develop a mental health disorder than normal-sighted children. Researchers have theorized that esotropia (an inward turn) was not found to be linked to a higher propensity for mental illness due to the age range of the participants, as well as the shorter follow-up time period; esotropic children were monitored to a mean age of 15.8 years, compared with 20.3 years for the exotropic group.A subsequent study with participants from the same area monitored people with congenital esotropia for a longer time period; results indicated that people who are esotropic were also more likely to develop mental illness of some sort upon reaching early adulthood, similar to those with constant exotropia, intermittent exotropia, or convergence insufficiency. The likelihood was 2.6 times that of controls. No apparent association with premature birth was observed, and no evidence was found linking later onset of mental illness to psychosocial stressors frequently encountered by those with strabismus.Investigations have highlighted the impact that strabismus may typically have on quality of life. Studies in which subjects were shown images of strabismic and non-strabismic persons showed a strong negative bias towards those visibly displaying the condition, clearly demonstrating the potential for future socioeconomic implications with regard to employability, as well as other psychosocial effects related to an individuals overall happiness.Adult and child observers perceived a right heterotropia as more disturbing than a left heterotropia, and child observers perceived an esotropia as "worse" than an exotropia. Successful surgical correction of strabismus, for adult as well as children, has been shown to have a significantly positive effect on psychological well-being.Very little research exists regarding coping strategies employed by adult strabismics. One study categorized coping methods into three subcategories: avoidance (refraining from participation in an activity), distraction (deflecting attention from the condition), and adjustment (approaching an activity differently). The authors of the study suggested that individuals with strabismus may benefit from psychosocial support such as interpersonal skills training. No studies have evaluated whether psychosocial interventions have had any benefits on individuals undergoing strabismus surgery.

Pathophysiology
The extraocular muscles control the position of the eyes.  Thus, a problem with the muscles or the nerves controlling them can cause paralytic strabismus.  The extraocular muscles are controlled by cranial nerves III, IV, and VI. An impairment of cranial nerve III causes the associated eye to deviate down and out and may or may not affect the size of the pupil.  Impairment of cranial nerve IV, which can be congenital, causes the eye to drift up and perhaps slightly inward. Sixth nerve palsy causes the eyes to deviate inward and has many causes due to the relatively long path of the nerve.  Increased cranial pressure can compress the nerve as it runs between the clivus and brain stem. Also, if the doctor is not careful, twisting of the babys neck during forceps delivery can damage cranial nerve VI.Evidence indicates a cause for strabismus may lie with the input provided to the visual cortex. This allows for strabismus to occur without the direct impairment of any cranial nerves or extraocular muscles.Strabismus may cause amblyopia due to the brain ignoring one eye. Amblyopia is the failure of one or both eyes to achieve normal visual acuity despite normal structural health. During the first seven to eight years of life, the brain learns how to interpret the signals that come from an eye through a process called visual development.  Development may be interrupted by strabismus if the child always fixates with one eye and rarely or never fixates with the other. To avoid double vision, the signal from the deviated eye is suppressed, and the constant suppression of one eye causes a failure of the visual development in that eye.Also, amblyopia may cause strabismus.  If a great difference in clarity occurs between the images from the right and left eyes, input may be insufficient to correctly reposition the eyes.  Other causes of a visual difference between right and left eyes, such as asymmetrical cataracts, refractive error, or other eye disease, can also cause or worsen strabismus.Accommodative esotropia is a form of strabismus caused by refractive error in one or both eyes.  Due to the near triad, when a person engages accommodation to focus on a near object, an increase in the signal sent by cranial nerve III to the medial rectus muscles results, drawing the eyes inward; this is called the accommodation reflex.  If the accommodation needed is more than the usual amount, such as with people with significant hyperopia, the extra convergence can cause the eyes to cross.

Diagnosis
During an eye examination, a test such as cover testing or the Hirschberg test is used in the diagnosis and measurement of strabismus and its impact on vision. Retinal birefringence scanning can be used for screening of young children for eye misalignment. A Cochrane review to examine different types of diagnosis test found only one study. This study used a photoscreener which was found to have high specificity (accurate in identifying those without the condition) but low sensitivity (inaccurate in identifying those with the condition).Several classifications are made when diagnosing strabismus.

Latency
Strabismus can be manifest (-tropia) or latent (-phoria).  A manifest deviation, or heterotropia (which may be eso-, exo-, hyper-, hypo-, cyclotropia or a combination of these), is present while the person views a target binocularly, with no occlusion of either eye.  The person is unable to align the gaze of each eye to achieve fusion.  A latent deviation, or heterophoria (eso-, exo-, hyper-, hypo-, cyclophoria or a combination of these), is only present after binocular vision has been interrupted, typically by covering one eye.  This type of person can typically maintain fusion despite the misalignment that occurs when the positioning system is relaxed.  Intermittent strabismus is a combination of both of these types, where the person can achieve fusion, but occasionally or frequently falters to the point of a manifest deviation.

Onset
Strabismus may also be classified based on time of onset, either congenital, acquired, or secondary to another pathological process. Many infants are born with their eyes slightly misaligned, and this is typically outgrown by six to 12 months of age.  Acquired and secondary strabismus develop later. The onset of accommodative esotropia, an overconvergence of the eyes due to the effort of accommodation, is mostly in early childhood. Acquired non-accommodative strabismus and secondary strabismus are developed after normal binocular vision has developed. In adults with previously normal alignment, the onset of strabismus usually results in double vision.
Any disease that causes vision loss may also cause strabismus, but it can also result from any severe and/or traumatic injury to the affected eye. Sensory strabismus is strabismus due to vision loss or impairment, leading to horizontal, vertical or torsional misalignment or to a combination thereof, with the eye with poorer vision drifting slightly over time. Most often, the outcome is horizontal misalignment. Its direction depends on the persons age at which the damage occurs: people whose vision is lost or impaired at birth are more likely to develop esotropia, whereas people with acquired vision loss or impairment mostly develop exotropia. In the extreme, complete blindness in one eye generally leads to the blind eye reverting to an anatomical position of rest.Although many possible causes of strabismus are known, among them severe and/or traumatic injuries to the affected eye, in many cases no specific cause can be identified. This last is typically the case when strabismus is present since early childhood.Results of a U.S. cohort study indicate that the incidence of adult-onset strabismus increases with age, especially after the sixth decade of life, and peaks in the eighth decade of life, and that the lifetime risk of being diagnosed with adult-onset strabismus is approximately 4%.

Laterality
Strabismus may be classified as unilateral if the one eye consistently deviates, or alternating if either of the eyes can be seen to deviate. Alternation of the strabismus may occur spontaneously, with or without subjective awareness of the alternation. Alternation may also be triggered by various tests during an eye exam. Unilateral strabismus has been observed to result from a severe or traumatic injury to the affected eye.

Direction and latency
Horizontal deviations are classified into two varieties, using prefixes: eso- describes inward or convergent deviations towards the midline, while exo- describes outward or divergent misalignment. Vertical deviations are also classified into two varieties, using prefixes: hyper- is the term for an eye whose gaze is directed higher than the fellow eye, while hypo- refers to an eye whose gaze is directed lower. Finally, the prefix cyclo- refers to torsional strabismus, which occurs when the eyes rotate around the anterior-posterior axis to become misaligned and is quite rare.
These five directional prefixes are combined with -tropia (if manifest) or -phoria (if latent) to describe various types of strabismus. For example, a constant left hypertropia exists when a persons left eye is always aimed higher than the right. A person with an intermittent right esotropia has a right eye that occasionally drifts toward the persons nose, but at other times is able to align with the gaze of the left eye. A person with a mild exophoria can maintain fusion during normal circumstances, but when the system is disrupted, the relaxed posture of the eyes is slightly divergent.

Other considerations
Strabismus can be further classified as follows:

Paretic strabismus is due to paralysis of one or several extraocular muscles.
Nonparetic strabismus is not due to paralysis of extraocular muscles.
Comitant (or concomitant) strabismus is a deviation that is the same magnitude regardless of gaze position.
Noncomitant (or incomitant) strabismus has a magnitude that varies as the person shifts his or her gaze up, down, or to the sides.Nonparetic strabismus is generally concomitant. Most types of infant and childhood strabismus are comitant. Paretic strabismus can be either comitant or noncomitant. Incomitant strabismus is almost always caused by a limitation of ocular rotations that is due to a restriction of extraocular eye movement (ocular restriction) or due to extraocular muscle paresis. Incomitant strabismus cannot be fully corrected by prism glasses, because the eyes would require different degrees of prismatic correction dependent on the direction of the gaze. Incomitant strabismus of the eso- or exo-type are classified as "alphabet patterns": they are denoted as A- or V- or more rarely λ-, Y- or X-pattern depending on the extent of convergence or divergence when the gaze moves upward or downward. These letters of the alphabet denote ocular motility pattern that have a similarity to the respective letter: in the A-pattern there is (relatively speaking) more convergence when the gaze is directed upwards and more divergence when it is directed downwards, in the V-pattern it is the contrary, in the  λ-, Y- and X-patterns there is little or no strabismus in the middle position but relatively more divergence in one or both of the upward and downward positions, depending on the "shape" of the letter.Types of incomitant strabismus include: Duane syndrome, horizontal gaze palsy, and congenital fibrosis of the extraocular muscles.When the misalignment of the eyes is large and obvious, the strabismus is called large-angle, referring to the angle of deviation between the lines of sight of the eyes. Less severe eye turns are called small-angle strabismus. The degree of strabismus can vary based on whether the person is viewing a distant or near target.
Strabismus that sets in after eye alignment had been surgically corrected is called consecutive strabismus.

Differential diagnosis
Pseudostrabismus is the false appearance of strabismus. It generally occurs in infants and toddlers whose bridge of the nose is wide and flat, causing the appearance of esotropia due to less sclera being visible nasally. With age, the bridge of the childs nose narrows and the folds in the corner of the eyes become less prominent.

Management
Retinoblastoma may also result in abnormal light reflection from the eye.
Strabismus is usually treated with a combination of eyeglasses, vision therapy, and surgery, depending on the underlying reason for the misalignment. As with other binocular vision disorders, the primary goal is comfortable, single, clear, normal binocular vision at all distances and directions of gaze.Whereas amblyopia (lazy eye), if minor and detected early, can often be corrected with use of an eye patch on the dominant eye or vision therapy, the use of eye patches is unlikely to change the angle of strabismus.

Glasses
In cases of accommodative esotropia, the eyes turn inward due to the effort of focusing far-sighted eyes, and the treatment of this type of strabismus necessarily involves refractive correction, which is usually done via corrective glasses or contact lenses, and in these cases surgical alignment is considered only if such correction does not resolve the eye turn.
In case of strong anisometropia, contact lenses may be preferable to spectacles because they avoid the problem of visual disparities due to size differences (aniseikonia) which is otherwise caused by spectacles in which the refractive power is very different for the two eyes. In a few cases of strabismic children with anisometropic amblyopia, a balancing of the refractive error eyes via refractive surgery has been performed before strabismus surgery was undertaken.Early treatment of strabismus when the person is a baby may reduce the chance of developing amblyopia and depth perception problems. However, a review of randomized controlled trials concluded that the use of corrective glasses to prevent strabismus is not supported by existing research. Most children eventually recover from amblyopia if they have had the benefit of patches and corrective glasses. Amblyopia has long been considered to remain permanent if not treated within a critical period, namely before the age of about seven years; however, recent discoveries give reason to challenge this view and to adapt the earlier notion of a critical period to account for stereopsis recovery in adults.
Eyes that remain misaligned can still develop visual problems. Although not a cure for strabismus, prism lenses can also be used to provide some temporary comfort and to prevent double vision from occurring.
Glasses affect the position by changing the persons reaction to focusing. Prisms change the way light, and therefore images, strike the eye, simulating a change in the eye position.

Surgery
Strabismus surgery does not remove the need for a child to wear glasses. Currently it is unknown whether there are any differences for completing strabismus surgery before or after amblyopia therapy in children.Strabismus surgery attempts to align the eyes by shortening, lengthening, or changing the position of one or more of the extraocular eye muscles. The procedure can typically be performed in about an hour, and requires about six to eight weeks for recovery. Adjustable sutures may be used to permit refinement of the eye alignment in the early postoperative period. It is unclear if there are differences between adjustable versus non-adjustable sutures as it has not been sufficiently studied. An alternative to the classical procedure is minimally invasive strabismus surgery (MISS) that uses smaller incisions than usual.

Medication
Medication is used for strabismus in certain circumstances. In 1989, the US FDA approved botulinum toxin therapy for strabismus in people over 12 years old. Most commonly used in adults, the technique is also used for treating children, in particular children affected by infantile esotropia. The toxin is injected in the stronger muscle, causing temporary and partial paralysis. The treatment may need to be repeated three to four months later once the paralysis wears off. Common side effects are double vision, droopy eyelid, overcorrection, and no effect. The side effects typically resolve also within three to four months. Botulinum toxin therapy has been reported to be similarly successful as strabismus surgery for people with binocular vision and less successful than surgery for those who have no binocular vision.

Prognosis
When strabismus is congenital or develops in infancy, it can cause amblyopia, in which the brain ignores input from the deviated eye </s>