<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 Yellow fever and can you explain it in depth? [/INST] Yellow fever is a viral disease of typically short duration. In most cases, symptoms include fever, chills, loss of appetite, nausea, muscle pains – particularly in the back – and headaches. Symptoms typically improve within five days. In about 15% of people, within a day of improving the fever comes back, abdominal pain occurs, and liver damage begins causing yellow skin. If this occurs, the risk of bleeding and kidney problems is increased.The disease is caused by the yellow fever virus and is spread by the bite of an infected mosquito. It infects only humans, other primates, and several types of mosquitoes. In cities, it is spread primarily by Aedes aegypti, a type of mosquito found throughout the tropics and subtropics. The virus is an RNA virus of the genus Flavivirus. The disease may be difficult to tell apart from other illnesses, especially in the early stages. To confirm a suspected case, blood-sample testing with polymerase chain reaction is required.A safe and effective vaccine against yellow fever exists, and some countries require vaccinations for travelers. Other efforts to prevent infection include reducing the population of the transmitting mosquitoes. In areas where yellow fever is common, early diagnosis of cases and immunization of large parts of the population are important to prevent outbreaks. Once a person is infected, management is symptomatic; no specific measures are effective against the virus. Death occurs in up to half of those who get severe disease.In 2013, yellow fever resulted in about 127,050 severe infections and 45,000 deaths worldwide, with nearly 90 percent of these occurring in Africa. Nearly a billion people live in an area of the world where the disease is common. It is common in tropical areas of the continents of South America and Africa, but not in Asia. Since the 1980s, the number of cases of yellow fever has been increasing. This is believed to be due to fewer people being immune, more people living in cities, people moving frequently, and changing climate increasing the habitat for mosquitoes.The disease originated in Africa and spread to the Americas starting in the 15th century with the European trafficking of enslaved Africans from sub-Saharan Africa. Since the 17th century, several major outbreaks of the disease have occurred in the Americas, Africa, and Europe. In the 18th and 19th centuries, yellow fever was considered one of the most dangerous infectious diseases; numerous epidemics swept through major cities of the US and in other parts of the world.In 1927, yellow fever virus was the first human virus to be isolated.

Signs and symptoms
Yellow fever begins after an incubation period of three to six days. Most cases cause only a mild infection with fever, headache, chills, back pain, fatigue, loss of appetite, muscle pain, nausea, and vomiting. In these cases, the infection lasts only three to six days.But in 15% of cases, people enter a second, toxic phase of the disease characterized by recurring fever, this time accompanied by jaundice due to liver damage, as well as abdominal pain. Bleeding in the mouth, nose, the eyes, and the gastrointestinal tract cause vomit containing blood, hence the Spanish name for yellow fever, vómito negro ("black vomit"). There may also be kidney failure, hiccups, and delirium.Among those who develop jaundice, the fatality rate is 20 to 50%, while the overall fatality rate is about 3 to 7.5%. Severe cases may have a mortality greater than 50%.Surviving the infection provides lifelong immunity, and normally results in no permanent organ damage.

Complication
Yellow fever can lead to death for 20% to 50% of those who develop severe disease. Jaundice, fatigue, heart rhythm problems, seizures and internal bleeding may also appear as complications of yellow fever during recovery time.

Cause
Yellow fever is caused by yellow fever virus, an enveloped RNA virus 40–50 nm in width, the type species and namesake of the family Flaviviridae. It was the first illness shown to be transmissible by filtered human serum and transmitted by mosquitoes, by American doctor Walter Reed around 1900. The positive-sense, single-stranded RNA is around 10,862 nucleotides long and has a single open reading frame encoding a polyprotein.Host proteases cut this polyprotein into three structural (C, prM, E) and seven nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, NS5); the enumeration corresponds to the arrangement of the protein coding genes in the genome. Minimal yellow fever virus (YFV) 3UTR region is required for stalling of the host 5-3 exonuclease XRN1. The UTR contains PKS3 pseudoknot structure, which serves as a molecular signal to stall the exonuclease and is the only viral requirement for subgenomic flavivirus RNA (sfRNA) production. The sfRNAs are a result of incomplete degradation of the viral genome by the exonuclease and are important for viral pathogenicity. Yellow fever belongs to the group of hemorrhagic fevers.The viruses infect, amongst others, monocytes, macrophages, Schwann cells, and dendritic cells. They attach to the cell surfaces via specific receptors and are taken up by an endosomal vesicle. Inside the endosome, the decreased pH induces the fusion of the endosomal membrane with the virus envelope. The capsid enters the cytosol, decays, and releases the genome. Receptor binding, as well as membrane fusion, are catalyzed by the protein E, which changes its conformation at low pH, causing a rearrangement of the 90 homodimers to 60 homotrimers.After entering the host cell, the viral genome is replicated in the rough endoplasmic reticulum (ER) and in the so-called vesicle packets. At first, an immature form of the virus particle is produced inside the ER, whose M-protein is not yet cleaved to its mature form, so is denoted as precursor M (prM) and forms a complex with protein E. The immature particles are processed in the Golgi apparatus by the host protein furin, which cleaves prM to M. This releases E from the complex, which can now take its place in the mature, infectious virion.

Transmission
Yellow fever virus is mainly transmitted through the bite of the yellow fever mosquito Aedes aegypti, but other mostly Aedes mosquitoes such as the tiger mosquito (Aedes albopictus) can also serve as a vector for this virus. Like other arboviruses, which are transmitted by mosquitoes, yellow fever virus is taken up by a female mosquito when it ingests the blood of an infected human or another primate. Viruses reach the stomach of the mosquito, and if the virus concentration is high enough, the virions can infect epithelial cells and replicate there. From there, they reach the haemocoel (the blood system of mosquitoes) and from there the salivary glands. When the mosquito next sucks blood, it injects its saliva into the wound, and the virus reaches the bloodstream of the bitten person. Transovarial transmissionial and transstadial transmission of yellow fever virus within A. aegypti, that is, the transmission from a female mosquito to its eggs and then larvae, are indicated. This infection of vectors without a previous blood meal seems to play a role in single, sudden breakouts of the disease.Three epidemiologically different infectious cycles occur in which the virus is transmitted from mosquitoes to humans or other primates. In the "urban cycle", only the yellow fever mosquito A. aegypti is involved. It is well adapted to urban areas, and can also transmit other diseases, including Zika fever, dengue fever, and chikungunya. The urban cycle is responsible for the major outbreaks of yellow fever that occur in Africa. Except for an outbreak in Bolivia in 1999, this urban cycle no longer exists in South America.Besides the urban cycle, both in Africa and South America, a sylvatic cycle (forest or jungle cycle) is present, where Aedes africanus (in Africa) or mosquitoes of the genus Haemagogus and Sabethes (in South America) serve as vectors. In the jungle, the mosquitoes infect mainly nonhuman primates; the disease is mostly asymptomatic in African primates. In South America, the sylvatic cycle is currently the only way humans can become infected, which explains the low incidence of yellow fever cases on the continent. People who become infected in the jungle can carry the virus to urban areas, where A. aegypti acts as a vector. Because of this sylvatic cycle, yellow fever cannot be eradicated except by eradicating the mosquitoes that serve as vectors.In Africa, a third infectious cycle known as "savannah cycle" or intermediate cycle, occurs between the jungle and urban cycles. Different mosquitoes of the genus Aedes are involved. In recent years, this has been the most common form of transmission of yellow fever in Africa.Concern exists about yellow fever spreading to southeast Asia, where its vector A. aegypti already occurs.

Pathogenesis
After transmission from a mosquito, the viruses replicate in the lymph nodes and infect dendritic cells in particular. From there, they reach the liver and infect hepatocytes (probably indirectly via Kupffer cells), which leads to eosinophilic degradation of these cells and to the release of cytokines. Apoptotic masses known as Councilman bodies appear in the cytoplasm of hepatocytes.Fatality may occur when cytokine storm, shock, and multiple organ failure follow.

Diagnosis
Yellow fever is most frequently a clinical diagnosis, based on symptomatology and travel history. Mild cases of the disease can only be confirmed virologically. Since mild cases of yellow fever can also contribute significantly to regional outbreaks, every suspected case of yellow fever (involving symptoms of fever, pain, nausea, and vomiting 6–10 days after leaving the affected area) is treated seriously.If yellow fever is suspected, the virus cannot be confirmed until 6–10 days following the illness. A direct confirmation can be obtained by reverse transcription polymerase chain reaction, where the genome of the virus is amplified. Another direct approach is the isolation of the virus and its growth in cell culture using blood plasma; this can take 1–4 weeks.Serologically, an enzyme-linked immunosorbent assay during the acute phase of the disease using specific IgM against yellow fever or an increase in specific IgG titer (compared to an earlier sample) can confirm yellow fever. Together with clinical symptoms, the detection of IgM or a four-fold increase in IgG titer is considered sufficient indication for yellow fever. As these tests can cross-react with other flaviviruses, such as dengue virus, these indirect methods cannot conclusively prove yellow fever infection.Liver biopsy can verify inflammation and necrosis of hepatocytes and detect viral antigens. Because of the bleeding tendency of yellow fever patients, a biopsy is only advisable post mortem to confirm the cause of death.In a differential diagnosis, infections with yellow fever must be distinguished from other feverish illnesses such as malaria. Other viral hemorrhagic fevers, such as Ebola virus, Lassa virus, Marburg virus, and Junin virus, must be excluded as the cause.

Prevention
Personal prevention of yellow fever includes vaccination and avoidance of mosquito bites in areas where yellow fever is endemic. Institutional measures for prevention of yellow fever include vaccination programmes and measures to control mosquitoes. Programmes for distribution of mosquito nets for use in homes produce reductions in cases of both malaria and yellow fever. Use of EPA-registered insect repellent is recommended when outdoors. Exposure for even a short time is enough for a potential mosquito bite. Long-sleeved clothing, long pants, and socks are useful for prevention. The application of larvicides to water-storage containers can help eliminate potential mosquito breeding sites. EPA-registered insecticide spray decreases the transmission of yellow fever.
Use insect repellent when outdoors such as those containing DEET, picaridin, ethyl butylacetylaminopropionate (IR3535), or oil of lemon eucalyptus on exposed skin.
Mosquitoes may bite through thin clothing, so spraying clothes with repellent containing permethrin or another EPA-registered repellent gives extra protection. Clothing treated with permethrin is commercially available. Mosquito repellents containing permethrin are not approved for application directly to the skin.
The peak biting times for many mosquito species are dusk to dawn. However, A. aegypti, one of the mosquitoes that transmits yellow fever virus, feeds during the daytime. Staying in accommodations with screened or air-conditioned rooms, particularly during peak biting times, also reduces the risk of mosquito bites.

Vaccination
Vaccination is recommended for those traveling to affected areas, because non-native people tend to develop more severe illness when infected. Protection begins by the 10th day after vaccine administration in 95% of people, and had been reported to last for at least 10 years. The World Health Organization (WHO) now states that a single dose of vaccine is sufficient to confer lifelong immunity against yellow fever disease. The attenuated live vaccine stem 17D was developed in 1937 by Max Theiler. The WHO recommends routine vaccination for people living in affected areas between the 9th and 12th month after birth.Up to one in four people experience fever, aches, and local soreness and redness at the site of injection. In rare cases (less than one in 200,000 to 300,000), the vaccination can cause yellow fever vaccine-associated viscerotropic disease, which is fatal in 60% of cases. It is probably due to the genetic morphology of the immune system. Another possible side effect is an infection of the nervous system, which occurs in one in 200,000 to 300,000 cases, causing yellow fever vaccine-associated neurotropic disease, which can lead to meningoencephalitis and is fatal in less than 5% of cases.The Yellow Fever Initiative, launched by the WHO in 2006, vaccinated more than 105 million people in 14 countries in West Africa. No outbreaks were reported during 2015. The campaign was supported by the GAVI alliance and governmental organizations in Europe and Africa. According to the WHO, mass vaccination cannot eliminate yellow fever because of the vast number of infected mosquitoes in urban areas of the target countries, but it will significantly reduce the number of people infected.Demand for yellow fever vaccine has continued to increase due to the growing number of countries implementing yellow fever vaccination as part of their routine immunization programmes. Recent upsurges in yellow fever outbreaks in Angola (2015), the Democratic Republic of Congo (2016), Uganda (2016), and more recently in Nigeria and Brazil in 2017 have further increased demand, while straining global vaccine supply. Therefore, to vaccinate susceptible populations in preventive mass immunization campaigns during outbreaks, fractional dosing of the vaccine is being considered as a dose-sparing strategy to maximize limited vaccine supplies. Fractional dose yellow fever vaccination refers to administration of a reduced volume of vaccine dose, which has been reconstituted as per manufacturer recommendations. The first practical use of fractional dose yellow fever vaccination was in response to a large yellow fever outbreak in the Democratic Republic of the Congo in mid-2016.In March 2017, the WHO launched a vaccination campaign in Brazil with 3.5 million doses from an emergency stockpile. In March 2017 the WHO recommended vaccination for travellers to certain parts of Brazil. In March 2018, Brazil shifted its policy and announced it planned to vaccinate all 77.5 million currently unvaccinated citizens by April 2019.

Compulsory vaccination
Some countries in Asia are considered to be potentially in danger of yellow fever epidemics, as both mosquitoes with the capability to transmit yellow fever as well as susceptible monkeys are present. The disease does not yet occur in Asia. To prevent introduction of the virus, some countries demand previous vaccination of foreign visitors who have passed through yellow fever areas. Vaccination has to be proved by a vaccination certificate, which is valid 10 days after the vaccination and lasts for 10 years. Although the WHO on 17 May 2013 advised that subsequent booster vaccinations are unnecessary, an older (than 10 years) certificate may not be acceptable at all border posts in all affected countries. A list of the countries that require yellow fever vaccination is published by the WHO. If the vaccination cannot be given for some reason, dispensation may be possible. In this case, an exemption certificate issued by a WHO-approved vaccination center is required. Although 32 of 44 countries where yellow fever occurs endemically do have vaccination programmes, in many of these countries, less than 50% of their population is vaccinated.

Vector control
Control of the yellow fever mosquito A. aegypti is of major importance, especially because the same mosquito can also transmit dengue fever and chikungunya disease. A. aegypti breeds preferentially in water, for example, in installations by inhabitants of areas with precarious drinking water supplies, or in domestic refuse, especially tires, cans, and plastic bottles. These conditions are common in urban areas in developing countries.Two main strategies are employed to reduce A. aegypti populations. One approach is to kill the developing larvae. Measures are taken to reduce the water accumulations in which the larvae develop. Larvicides are used, along with larvae-eating fish and copepods, which reduce the number of larvae. For many years, copepods of the genus Mesocyclops have been used in Vietnam for preventing dengue fever. This eradicated the mosquito vector in several areas. Similar efforts may prove effective against yellow fever. Pyriproxyfen is recommended as a chemical larvicide, mainly because it is safe for humans and effective in small doses.The second strategy is to reduce populations of the adult yellow fever mosquito. Lethal ovitraps can reduce Aedes populations, using lesser amounts of pesticide because it targets the pest directly. Curtains and lids of water tanks can be sprayed with insecticides, but application inside houses is not recommended by the WHO. Insecticide-treated mosquito nets are effective, just as they are against the Anopheles mosquito that carries malaria.

Treatment
As with other Flavivirus infections, no cure is known for yellow fever. Hospitalization is advisable and intensive care may be necessary because of rapid deterioration in some cases. Certain acute treatment methods lack efficacy: passive immunization after the emergence of symptoms is probably without effect; ribavirin and other antiviral drugs, as well as treatment with interferons, are ineffective in yellow fever patients. Symptomatic treatment includes rehydration and pain relief with drugs such as paracetamol (acetaminophen). Acetylsalicylic acid (aspirin). However, aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) are often avoided because of an increased risk of gastrointestinal bleeding due to their anticoagulant effects.

Epidemiology
Yellow fever is common in tropical and subtropical areas of South America and Africa. Worldwide, about 600 million people live in endemic areas. The WHO estimates 200,000 cases of yellow fever worldwide each year. About 15% of people infected with yellow fever progress to a severe form of the illness, and up to half of those will die, as there is no cure for yellow fever.

Africa
An estimated 90% of yellow fever infections occur on the African continent. In 2016, a large outbreak originated in Angola and spread to neighboring countries before being contained by a massive vaccination campaign. In March and April 2016, 11 imported cases of the Angola genotype in unvaccinated Chinese nationals were reported in China, the first appearance of the disease in Asia in recorded history.Phylogenetic analysis has identified seven genotypes of yellow fever viruses, and they are assumed to be differently adapted to humans and to the vector A. aegypti. Five genotypes (Angola, Central/East Africa, East Africa, West Africa I, and West Africa II) occur only in Africa. West Africa genotype I is found in Nigeria and the surrounding region. West Africa genotype I appears to be especially infectious, as it is often associated with major outbreaks. The three genotypes found outside of Nigeria and Angola occur in areas where outbreaks are rare. Two outbreaks, in Kenya (1992–1993) and Sudan (2003 and 2005), involved the East African genotype, which had remained undetected in the previous 40 years.

South America
In South America, two genotypes have been identified (South American genotypes I and II). Based on phylogenetic analysis these two genotypes appear to have originated in West Africa and were first introduced into Brazil. The date of introduction of the predecessor African genotype which gave rise to the South American genotypes appears to be 1822 (95% confidence interval 1701 to 1911). The historical record shows an outbreak of yellow fever occurred in Recife, Brazil, between 1685 and 1690. The disease seems to have disappeared, with the next outbreak occurring in 1849. It was likely introduced with the trafficking of slaves through the slave trade from Africa. Genotype I has been divided into five subclades, A through E.In late 2016, a large outbreak began in Minas Gerais state of Brazil that was characterized as a sylvan or jungle epizootic. It began as an outbreak in brown howler monkeys, which serve as a sentinel species for yellow fever, that then spread to men working in the jungle. No cases had been transmitted between humans by the A. aegypti mosquito, which can sustain urban outbreaks that can spread rapidly. In April 2017, the sylvan outbreak continued moving toward the Brazilian coast, where most people were unvaccinated. By the end of May the outbreak appeared to be declining after more than 3,000 suspected cases, 758 confirmed and 264 deaths confirmed to be yellow fever. The Health Ministry launched a vaccination campaign and was concerned about spread during the Carnival season in February and March. The CDC issued a Level 2 alert (practice enhanced precautions.)A Bayesian analysis of genotypes I and II has shown that genotype I accounts for virtually all the current infections in Brazil, Colombia, Venezuela, and Trinidad and Tobago, while genotype II accounted for all cases in Peru. Genotype I originated in the northern Brazilian region around 1908 (95% highest posterior density interval [HPD]: 1870–1936). Genotype II originated in Peru in 1920 (95% HPD: 1867–1958). The estimated rate of mutation for both genotypes was about 5 × 10−4 substitutions/site/year, similar to that of other RNA viruses.

Asia
The main vector (A. aegypti) also occurs in tropical and subtropical regions of Asia, the Pacific, and Australia, but yellow fever has never occurred there, until jet travel introduced 11 cases from the 2016 Angola and DR Congo yellow fever outbreak in Africa. Proposed explanations include:
That the strains of the mosquito in the east are less able to transmit yellow fever virus.
That immunity is present in the populations because of other diseases caused by related viruses (for example, dengue).
That the disease was never introduced because the shipping trade was insufficient.But none is considered satisfactory. Another proposal is the absence of a slave trade to Asia on the scale of that to the Americas. The trans-Atlantic slave trade probably introduced yellow fever into the Western Hemisphere from Africa.

History
Early history
The evolutionary origins of yellow fever most likely lie in Africa, with transmission of the disease from nonhuman primates to humans. The virus is thought to have originated in East or Central Africa and spread from there to West Africa. As it was endemic in Africa, local populations had developed some immunity to it. When an outbreak of yellow fever would occur in an African community where colonists resided, most Europeans died, while the indigenous Africans usually developed nonlethal symptoms resembling influenza. This phenomenon, in which certain populations develop immunity to yellow fever due to prolonged exposure in their childhood, is known as acquired immunity. The virus, as well as the vector A. aegypti, were probably transferred to North and South America with the trafficking of slaves from Africa, part of the Columbian exchange following European exploration and colonization.The first definitive outbreak of yellow fever in the New World was in 1647 on the island of Barbados. An outbreak was recorded by Spanish colonists in 1648 in the Yucatán Peninsula, where the indigenous Mayan people called the illness xekik ("blood vomit"). In 1685, Brazil suffered its first epidemic in Recife. The first mention of the disease by the name "yellow fever" occurred in 1744.
(John Mitchell) (1805) (Mitchells account of the Yellow Fever in Virginia in 1741–2) Archived 2017-02-23 at the Wayback Machine, The Philadelphia Medical Museum, 1 (1) : 1–20.
(John Mitchell) (1814) "Account of the Yellow fever which prevailed in Virginia in the years 1737, 1741, and 1742, in a letter to the late Cadwallader Colden, Esq. of New York, from the late John Mitchell, M.D.F.R.S. of Virginia," Archived 2017-02-23 at the Wayback Machine American Medical and Philosophical Register, 4 : 181–215. The term "yellow fever" appears on p. 186. On p. 188, Mitchell mentions "… the distemper was what is generally called yellow fever in America". However, on pages 191–192, he states "… I shall consider the cause of the yellowness which is so remarkable in this distemper, as to have given it the name of the Yellow Fever."However, Dr. Mitchell misdiagnosed the disease that he observed and treated, and the disease was probably Weils disease or hepatitis. McNeill argues that the environmental and ecological disruption caused by the introduction of sugar plantations created the conditions for mosquito and viral reproduction, and subsequent outbreaks of yellow fever. Deforestation reduced populations of insectivorous birds and other creatures that fed on mosquitoes and their eggs.

In Colonial times and during the Napoleonic Wars, the West Indies were known as a particularly dangerous posting for soldiers due to yellow fever being endemic in the area. The mortality rate in British garrisons in Jamaica was seven times that of garrisons in Canada, mostly because of yellow fever and other tropical diseases. Both English and French forces posted there were seriously affected by the "yellow jack". Wanting to regain control of the lucrative sugar trade in Saint-Domingue (Hispaniola), and with an eye on regaining Frances New World empire, Napoleon sent an army under the command of his brother-in-law General Charles Leclerc to Saint-Domingue to seize control after a slave revolt. The historian J. R. McNeill asserts that yellow fever accounted for about 35,000 to 45,000 casualties of these forces during the fighting. Only one third of the French troops survived for withdrawal and return to France. Napoleon gave up on the island and his plans for North America, selling the Louisiana Purchase to the US in 1803. In 1804, Haiti proclaimed its independence as the second republic in the Western Hemisphere. Considerable debate exists over whether the number of deaths caused by disease in the Haitian Revolution was exaggerated.Although yellow fever is most prevalent in tropical-like climates, the northern United States were not exempted from the fever. The first outbreak in English-speaking North America occurred in New York City in 1668. English colonists in Philadelphia and the French in the Mississippi River Valley recorded major outbreaks in 1669, as well as additional yellow fever epidemics in Philadelphia, Baltimore, and New York City in the 18th and 19th centuries. The disease traveled along steamboat routes from New Orleans, causing some 100,000–150,000 deaths in total. The yellow fever epidemic of 1793 in Philadelphia, which was then the capital of the United States, resulted in the deaths of several thousand people, more than 9% of the population. One of these deaths was James Hutchinson, a physician helping to treat the population of the city. The national government fled the city to Trenton, New Jersey, including President George Washington.

The southern city of New Orleans was plagued with major epidemics during the 19th century, most notably in 1833 and 1853. A major epidemic occurred in both New Orleans and Shreveport, Louisiana in 1873. Its residents called the disease "yellow jack". Urban epidemics continued in the United States until 1905, with the last outbreak affecting New Orleans.At least 25 major outbreaks took place in the Americas during the 18th and 19th centuries, including particularly serious ones in Cartagena, Chile, in 1741; Cuba in 1762 and 1900; Santo Domingo in 1803; and Memphis, Tennessee, in 1878.In the early nineteenth century, the prevalence of yellow fever in the Caribbean "led to serious health problems" and alarmed the United States Navy as numerous deaths and sickness curtailed naval operations and destroyed morale. One episode began in April 1822 when the frigate USS Macedonian left Boston and became part of Commodore James Biddles West India Squadron. Unbeknownst to all, they were about to embark on a cruise to disaster and their assignment "would prove a cruise through hell". Secretary of the Navy Smith Thompson had assigned the squadron to guard United States merchant shipping and suppress piracy. During their time on deployment from 26 May to 3 August 1822, 76 of the Macedonians officers and men died, including John Cadle, surgeon USN. Seventy-four of these deaths were attributed to yellow fever. Biddle reported that another 52 of his crew were on sick-list. In their report to the secretary of the Navy, Biddle and Surgeons Mate Charles Chase stated the cause as "fever". As a consequence of this loss, Biddle noted that his squadron was forced to return to Norfolk Navy Yard early. Upon arrival, the Macedonians crew were provided medical care and quarantined at Craney Island, Virginia.

In 1853, Cloutierville, Louisiana, had a late-summer outbreak of yellow fever that quickly killed 68 of the 91 inhabitants. A local doctor concluded that some unspecified infectious agent had arrived in a package from New Orleans. In 1854, 650 residents of Savannah, Georgia, died from yellow fever. In 1858, St. Matthews German Evangelical Lutheran Church in Charleston, South Carolina, had 308 yellow fever deaths, reducing the congregation by half. A ship carrying persons infected with the virus arrived in Hampton Roads in southeastern Virginia in June 1855. The disease spread quickly through the community, eventually killing over 3,000 people, mostly residents of Norfolk and Portsmouth. In 1873, Shreveport, Louisiana, lost 759 citizens in an 80-day period to a yellow fever epidemic, with over 400 additional victims eventually succumbing. The total death toll from August through November was approximately 1,200.In 1878, about 20,000 people died in a widespread epidemic in the Mississippi River Valley. That year, Memphis had an unusually large amount of rain, which led to an increase in the mosquito population. The result was a huge epidemic of yellow fever. The steamship John D. Porter took people fleeing Memphis northward in hopes of escaping the disease, but passengers were not allowed to disembark due to concerns of spreading yellow fever. The ship roamed the Mississippi River for the next two months before unloading her passengers.Major outbreaks have also occurred in southern Europe. Gibraltar lost many lives to outbreaks in 1804, 1814, and 1828. Barcelona suffered the loss of several thousand citizens during an outbreak in 1821. The Duke de Richelieu deployed 30,000 French troops to the border between France and Spain in the Pyrenees Mountains, to establish a cordon sanitaire in order to prevent the epidemic from spreading from Spain into France.

Causes and transmission
Ezekiel Stone Wiggins, known as the Ottawa Prophet, proposed that the cause of a yellow fever epidemic in Jacksonville, Florida, in 1888, was astrological.
The planets were in the same line as the sun and earth and this produced, besides Cyclones, Earthquakes, etc., a denser atmosphere holding more carbon and creating microbes. Mars had an uncommonly dense atmosphere, but its inhabitants were probably protected from the fever by their newly discovered canals, which were perhaps made to absorb carbon and prevent the disease.
In 1848, Josiah C. Nott suggested that yellow fever was spread by insects such as moths or mosquitoes, basing his ideas on the pattern of transmission of the disease. Carlos Finlay, a Cuban doctor and scientist, proposed in 1881 that yellow fever might be transmitted by previously infected mosquitoes rather than by direct contact from person to person, as had long been believed. Since the losses from yellow fever in the Spanish–American War in the 1890s were extremely high, Army doctors began research experiments with a team led by Walter Reed, and composed of doctors James Carroll, Aristides Agramonte, and Jesse William Lazear. They successfully proved Finlays "mosquito hypothesis". Yellow fever was the first virus shown to be transmitted by mosquitoes. The physician William Gorgas applied these insights and eradicated yellow fever from Havana. He also campaigned against yellow fever during the construction of the Panama Canal. A previous effort of canal building by the French had failed in part due to mortality from the high incidence of yellow fever and malaria, which killed many workers.Although Reed has received much of the credit in United States history books for "beating" yellow fever, he had fully credited Finlay with the discovery of the yellow fever vector, and how it might be controlled. Reed often cited Finlays papers in his own articles, and also credited him for the discovery in his personal correspondence. The acceptance of Finlays work was one of the most important and far-reaching effects of the U.S. Army Yellow Fever Commission of 1900. Applying methods first suggested by Finlay, the United States government and Army eradicated yellow fever in Cuba and later in Panama, allowing completion of the Panama Canal. While Reed built on the research of Finlay, historian François Delaporte notes that yellow fever research was a contentious issue. Scientists, including Finlay and Reed, became successful by building on the work of less prominent scientists, without always giving them the credit they were due. Reeds research was essential in the fight against yellow fever. He is also credited for using the first type of medical consent form during his experiments in Cuba, an attempt to ensure that participants knew they were taking a risk by being part of testing.Like Cuba and Panama, Brazil also led a highly successful sanitation campaign against mosquitoes and yellow fever. Beginning in 1903, the campaign led by Oswaldo Cruz, then director general of public health, resulted not only in eradicating the disease but also in reshaping the physical landscape of Brazilian cities such as Rio de Janeiro. During rainy seasons, Rio de Janeiro had regularly suffered floods, as water from the bay surrounding the city overflowed into Rios narrow streets. Coupled with the poor drainage systems found throughout Rio, this created swampy conditions in the citys neighborhoods. Pools of stagnant water stood year-long in city streets and proved to be a fertile ground for disease-carrying mosquitoes. Thus, under Cruzs direction, public health units known as "mosquito inspectors" fiercely worked to combat yellow fever throughout Rio by spraying, exterminating rats, improving drainage, and destroying unsanitary housing. Ultimately, the citys sanitation and renovation campaigns reshaped Rio de Janeiros neighborhoods. Its poor residents were pushed from city centers to Rios suburbs, or to towns found in the outskirts of the city. In later years, Rios most impoverished inhabitants would come to reside in favelas.

During 1920–1923, the Rockefeller Foundations International Health Board  undertook an expensive and successful yellow fever eradication campaign in Mexico. The IHB gained the respect of Mexicos federal government because of the success. The eradication of yellow fever strengthened the relationship between the US and Mexico, which had not been very good in the years prior. The eradication of yellow fever was also a major step toward better global health.In 1927, scientists isolated the yellow fever virus in West Africa. Following this, two vaccines were developed in the 1930s. Max Theiler led the completion of the 17D yellow fever vaccine in 1937, for which he was subsequently awarded the Nobel Prize in Physiology or Medicine. That vaccine, 17D, is still in use, although newer vaccines, based on vero cells, are in development (as of 2018).

Current status
Using vector control and strict vaccination programs, the urban cycle of yellow fever was nearly eradicated from South America. Since 1943, only a single urban outbreak in Santa Cruz de la Sierra, Bolivia, has occurred. Since the 1980s, however, the number of yellow fever cases has been increasing again, and A. aegypti has returned to the urban centers of South America. This is partly due to limitations on available insecticides, as well as habitat dislocations caused by climate change. It is also because the vector control program was abandoned. Although no new urban cycle has yet been established, scientists believe this could happen again at any point. An outbreak in Paraguay in 2008 was thought to be urban in nature, but this ultimately proved not to be the case.In Africa, virus eradication programs have mostly relied upon vaccination. These programs have largely been unsuccessful because they were unable to break the sylvatic cycle involving wild primates. With few countries establishing regular vaccination programs, measures to fight yellow fever have been neglected, making the future spread of the virus more likely.

Research
In the hamster model of yellow fever, early administration of the antiviral ribavirin is an effective treatment of many pathological features of the disease. Ribavirin treatment during the first five days after virus infection improved survival rates, reduced tissue damage in the liver and spleen, prevented hepatocellular steatosis, and normalised levels of alanine aminotransferase, a liver damage marker. The mechanism of action of ribavirin in reducing liver pathology in yellow fever virus infection may be similar to its activity in treatment of hepatitis C, a related virus </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 Animal bite and can you explain it in depth? [/INST] An animal bite is a wound, usually a puncture or laceration, caused by the teeth. An animal bite usually results in a break in the skin but also includes contusions from the excessive pressure on body tissue from the bite. The contusions can occur without a break in the skin. Bites can be provoked or unprovoked. Other bite attacks may be apparently unprovoked.  Biting is a physical action not only describing an attack but it is a normal response in an animal as it eats, carries objects, softens and prepares food for its young, removes ectoparasites from its body surface, removes plant seeds attached to its fur or hair, scratching itself, and grooming other animals. Animal bites often result in serious infections and mortality. Animal bites not only include injuries from the teeth of reptiles, mammals, but fish, and amphibians. Arthropods can also bite and leave injuries.

Signs and symptoms
Bite wounds can cause a number of signs and symptoms

Generalized tissue damage due to tearing and scratching
Serious hemorrhage if major blood vessels are pierced
Infection by bacteria or other pathogens, including rabies
Introduction of venom into the wound by venomous animals such as some snakes
Introduction of other irritants into the wound, causing inflammation and itching

Classification
Bites are usually classified by the type of animal causing the wound.
Many different animals are known to bite humans.

Vertebrates
Companion animals, including dogs, cats, rats, ferrets, and parrots, may bite humans.
Wildlife may sometimes bite humans. The bites of various mammals such as bats, skunks, wolves, raccoons, etc. may transmit rabies, which is almost always fatal if left untreated.
Human bites are themselves capable of doing great flesh damage, but are particularly known for spreading communicable diseasesInvoluntary biting injuries due to closed-fist injuries from fists striking teeth (referred to as reverse bite injuries) are a common consequence of fist fights. These have been termed "fight bites". Injuries in which the knuckle joints or tendons of the hand are bitten into tend to be the most serious.
Teething infants are known to bite objects to relieve pressure on their growing teeth, and may inadvertently bite peoples hands or arms while doing so. Young children may also bite people out of anger or misbehaviour, although this is usually corrected early in the childs life.

Reverse bite injury
A reverse bite injury (also called a clenched fist injury, closed fist injury, or fight bite) results when a person punches another person in the face, and the skin (and sometimes tendons) of their knuckles are cut against the teeth of the person they are punching. The proximity of the wound is often located over the metacarpophalangeal joint resulting in tendon injury.The medical treatment of this injury is similar to those of a human bite, but may also involve damage of the underlying tendons.These injuries should be managed as other human bites: wound irrigation and antibiotics are essential as human saliva can contain a number of bacteria. The nature of these injuries is such that even if the injury is optimally managed, poor outcomes may still occur.

Arthropods
The bites of arthropods have some of the most serious health consequences known. Mosquito bites transmit serious disease and result in millions of deaths and illnesses in the world. Ticks also transmit many diseases such as Lyme disease.

Spider bite
Insect bites and stings
Flea bites are responsible for the transmission of plague.
Mosquito bites are responsible for the transmission of dengue fever and malaria.
Leech bite

Mechanism
Trauma
A natural consequence of a bite is tissue trauma at the site. Trauma may consist of scratching, tearing, punture or laceration of the skin, hematoma (bruising), embedding of foreign objects, for example a tooth or hair, damage to or severing of underlying structures such as connective tissue or muscle, amputations, and the ripping off of skin and hair. If major blood vessels are damaged, severe blood loss can occur.

Infection
Pathogen organisms can be introduced into the bite. Some of the pathogens can originate from the mouth of the biter, the substrate onto which the injured person or animal can fall or from the naturally occurring microorganisms that are present on the skin or hair of the animal. The advent of antibiotics improved the outcome of bite wound infections.

Rabies
Animal bites where skin has been penetrated, most commonly by dogs and bats, transmit rabies to humans. Rabies from other animals is rare. If the animal is caught alive or dead with its head preserved, the head can be analyzed to detect the disease. Signs of rabies include foaming at the mouth, growling, self-mutilation, jerky behavior, red eyes, and hydrophobia.
If the animal cannot be captured, preventative rabies treatment is recommended in many places. Several countries are known not to have native rabies, see the Wikipedia page for prevalence of rabies.

Treatment
The first step in treatment includes washing the bite wound. If there is a low risk of infection the wound may be sutured. Debridement and drainage of bite wounds was practiced in the pre-antibiotic era, but high rates of infection still occurred. A 2019 Cochrane systematic review aimed to evaluate the healing and infection rates in bite wounds based on if/when they were stitched closed. The review authors looked for studies that compared stitching wounds closed straight away, leaving them open for a short time or not stitching them at all. Due to a lack of high-certainty evidence, the review authors concluded that more robust randomised controlled trials were needed to fully answer this question.

Antibiotics
Antibiotics to prevent infection are recommended for dog and cat bites of the hand, and human bites if they are more than superficial. They are also recommended in those who have poor immune function. Evidence for antibiotics to prevent infection in bites in other areas is not clear.The first choice is amoxicillin with clavulanic acid, and if the person is penicillin-allergic, doxycycline and metronidazole. The antistaphylococcal penicillins (e.g., cloxacillin, nafcillin, flucloxacillin) and the macrolides (e.g., erythromycin, clarithromycin) are not used for empirical therapy, because they do not cover Pasteurella species.

Vaccinations
Rabies prevention is generally available in North America and the Northern European states.
Tetanus toxoid treatment is recommended in those whose vaccinations are not up to date and have a bite that punctures the skin. Tetanus immune globulin is indicated in people with more than 10 years since prior vaccination. Tetanus boosters (Td) should be given every ten years.

TT = tetanus toxoid; TIG: tetanus immune globulin

Mosquito bites
Antihistamines are effective treatment for the symptoms from bites. Many diseases such as malaria and dengue are transmitted by mosquitoes.

Epidemiology
Human bites are the third most frequent type of bite after dog and cat bites. Dog bites are commonplace, with children the most commonly bitten and the face and scalp the most common target. About 4.7 million dog bites are reported annually in the United States. The US estimated annual count of animal bites is 250,000 human bites, 1 to 2 million dog bites, 400,000 cat bites, and 45,000 bites from snakes. Bites from skunks, horses, squirrels, rats, rabbits, pigs, and monkeys may be up to 1 percent of bite injuries. Pet ferrets attacks that were unprovoked have caused serious facial injuries. Non-domesticated animals though assumed to be more common especially as a cause of rabies infection, make up less than one percent of reported bite wounds. When a person is bitten, it is more likely to occur on the right arm, most likely due to defensive reactions when the person uses their dominant arm. Estimates are that three-quarters of bites are located on the arms or legs of humans. Bites to the face of humans constitute only 10 percent of the total. Two-thirds of bite injuries in humans are suffered by children aged ten and younger.Up to three-fourths of dog bites happen to those younger than 20 years-old. In the United States, the costs associated with dog bites are estimated to be more than $1 billion annually </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 Absence seizure and can you explain it in depth? [/INST] Absence seizures are one of several kinds of generalized seizures. These seizures are sometimes referred to as petit mal seizures (from the French for "little illness", a term dating from the late 18th century). Absence seizures are characterized by a brief loss and return of consciousness, generally not followed by a period of lethargy (i.e. without a notable postictal state). Absence seizure is very common in children. It affects both sides of the brain.

Epidemiology
Absence seizures affect between 0.7 and 4.6 per 100,000 in the general population and 6% to 8% in children younger than 15 years. Childhood absence seizures account for 10% to 17% of all absence seizures. Onset is between 4 and 10 years and peaks at 5 to 7 years. It is more common in girls than in boys.

Etiology
An absence seizure is specifically caused by multifactorial inheritance. The voltage-gated T-type calcium channel is regulated by GABRG2, GABRG3, and CACNA1A2 genes. Inheritance of these genes is involved in etiology of absence seizure. The factors that trigger an absence seizure are lack of sleep and compliance, drinking alcohol, and benzodiazepine withdrawal, and use of medication that reduces the threshold of seizure such as Isoniazid, antipsychotics.

Signs and symptoms
The clinical manifestations of absence seizures vary significantly among patients. Impairment of consciousness is the essential symptom, and may be the only clinical symptom, but this can be combined with other manifestations.  The hallmark of the absence seizures is abrupt and sudden-onset impairment of consciousness, interruption of ongoing activities, a blank stare, possibly a brief upward rotation of the eyes. If the patient is speaking, speech is slowed or interrupted; if walking, they stand transfixed; if eating, the food will stop on its way to the mouth. Usually, the patient will be unresponsive when addressed. In some cases, attacks are aborted when the patient is called.  The attack lasts from a few seconds to half a minute and evaporates as rapidly as it commenced. Absence seizures generally are not followed by a period of disorientation or lethargy (postictal state), in contrast to the majority of seizure disorders.
Absence with impairment of consciousness only as per the above description.
Absence with mild clonic components.  Here the onset of the attack is indistinguishable from the above, but clonic components may occur in the eyelids, at the corner of the mouth, or in other muscle groups which may vary in severity from almost imperceptible movements to generalised myoclonic jerks. Objects held in the hand may be dropped.
Absence with atonic components.  Here there may be a diminution in tone of muscles subserving posture as well as in the limbs leading to dropping of the head, occasionally slumping of the trunk, dropping of the arms, and relaxation of the grip.  Rarely tone is sufficiently diminished to cause this person to fall.
Absence with tonic components.  Here during the attack tonic muscular contraction may occur, leading to increase in muscle tone which may affect the extensor muscles or the flexor muscles symmetrically or asymmetrically.  If the patient is standing, the head may be drawn backward and the trunk may arch. This may lead to retropulsion, which may cause eyelids to twitch rapidly; eyes may jerk upwards or the patients head may rock back and forth slowly, as if nodding. The head may tonically draw to one or another side.
Absence with automatisms.  Purposeful or quasi-purposeful movements occurring in the absence of awareness during an absence attack are frequent and may range from lip licking and swallowing to clothes fumbling or aimless walking.  If spoken to, the patient may grunt, and when touched or tickled may rub the site.  Automatisms are quite elaborate and may consist of combinations of the above described movements or may be so simple as to be missed by casual observation.
Absence with autonomic components.  These may be pallor, and less frequently flushing, sweating, dilatation of pupils and incontinence of urine.Mixed forms of absence frequently occur.
These seizures can happen a few times a day or in some cases, hundreds of times a day, to the point that the person cannot concentrate in school or in other situations requiring sustained, concentrated attention.

Risk factors
Typical absences are easily induced by hyperventilation (over-breathing) in more than 90% of people with typical absences. This is a reliable test for the diagnosis of absence seizures: a patient suspected of typical absences should be asked to hyperventilate for three minutes, counting breaths. During hyperventilation, the oxygen and carbon dioxide level will become abnormal. This results in weakening of electrical signal which leads to a reduction in the seizure threshold. Intermittent photic stimulation may precipitate or facilitate absence seizures; eyelid myoclonia is a common clinical feature.A specific mechanism difference exists in absence seizures in that T-type Ca++ channels are believed to be involved. Ethosuximide is specific for these channels and thus it is not effective for treating other types of seizures. Valproate and gabapentin (among others) have multiple mechanisms of action including blockade of T-type Ca++ channels, and are useful in treating multiple seizure types. Gabapentin can aggravate absence seizures.

Pathophysiology
The corticothalamic cortical circuit plays an important role in the pathophysiology of absence seizure. Some of the neurons are important in their occurrence. They are

Cortical glutamatergic neurons
Thalamic relay neurons
Neurons of thalamic nucleus reticularisAbnormal oscillatory rhythms develop in the thalamic nucleus reticularis. This causes inhibition of GABAergic neurotransmission and excitation of glutamate neurotransmission. Abnormal oscillatory spikes are produced by the low threshold T-type calcium channel. This explains how inheritance of gene code for T-type calcium channel leads to an absence seizure. Antiepileptic drugs such as Gabapentin, Tiagabine and Vigabatrin cause inhibition of GABA results in exacerbation of absence seizures.

Diagnosis
The primary diagnostic test for absence seizures is electroencephalography (EEG). However, brain scans such as by an MRI can help rule out other diseases, such as a stroke or a brain tumor.During EEG, hyperventilation can be used to provoke these seizures. Ambulatory EEG monitoring over 24 hours can quantify the number of seizures per day and their most likely times of occurrence.Absence seizures are brief (usually less than 20 seconds) generalized epileptic seizures of sudden onset and termination. When someone experiences an absence seizure they are often unaware of their episode. Those most susceptible to this are children, and the first episode usually occurs between 4–12 years old. It is very rare that someone older will experience their first absence seizure. Episodes of absence seizures can often be mistaken for inattentiveness when misdiagnosed, and can occur 50–100 times a day. They can be so difficult to detect that some people may go months or years before being given a proper diagnosis. There are no known before or after effects of absence seizures.Absence seizures have two essential components:
Clinical - the impairment of consciousness (absence)
EEG - the EEG shows generalized spike-and-slow wave dischargesAbsence seizures are broadly divided into typical and atypical types:

Typical absence seizures usually occur in the context of idiopathic generalised epilepsies and an EEG shows fast >2.5 Hz generalised spike-wave discharges.  The prefix "typical" is to differentiate them from atypical absences rather than to characterise them as "classical" or characteristic of any particular syndrome.
Atypical absence seizures:
Occur only in the context of mainly severe symptomatic or cryptogenic epilepsies of children with learning difficulties who also have frequent seizures of other types, such as atonic, tonic and myoclonic.
Have slower onset and termination and changes in tone are more pronounced.
Have particular ictal characteristics: EEG is of slow (less than 2.5 Hz) spike and slow wave. The discharge is heterogeneous, often asymmetrical and may include irregular spike and slow wave complexes, fast and other paroxysmal activity. Background interictal EEG is usually abnormal.

Syndromes
Absence seizure syndromes are childhood absence epilepsy, epilepsy with myoclonic absences, juvenile absence epilepsy and juvenile myoclonic epilepsy. Other proposed syndromes are Jeavons syndrome (eyelid myoclonia with absences), and genetic generalised epilepsy with phantom absences.
Absence seizures are also known to occur to patients with porphyria and can be triggered by stress or other porphyrin-inducing factors.

Treatment
Treatment of patients with absence seizures only is mainly with ethosuximide or valproic acid, which are of equal efficacy controlling absences in around 75% of patients. Lamotrigine monotherapy is less effective, controlling absences in around 50% of patients.  This summary has been recently confirmed by Glauser et al. (2010), who studied the effects of ethosuximide, valproic acid, and lamotrigine in children with newly diagnosed childhood absence epilepsy. Drug dosages were incrementally increased until the child was free of seizures, the maximal allowable dose was reached, or a criterion indicating treatment failure was met. The primary outcome was freedom from treatment failure after 16 weeks of therapy; the secondary outcome was attentional dysfunction. After 16 weeks of therapy, the freedom-from-failure rates for ethosuximide and valproic acid were similar and were higher than the rate for lamotrigine. There were no significant differences between the three drugs with regard to discontinuation because of adverse events. Attentional dysfunction was more common with valproic acid than with ethosuximide.
If monotherapy fails or unacceptable adverse reactions appear, replacement of one by another of the three antiepileptic drugs is the alternative </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 Meckels diverticulum and can you explain it in depth? [/INST] A Meckels diverticulum, a true congenital diverticulum, is a slight bulge in the small intestine present at birth and a vestigial remnant of the omphalomesenteric duct (also called the vitelline duct or yolk stalk). It is the most common malformation of the gastrointestinal tract and is present in approximately 2% of the population, with males more frequently experiencing symptoms.
Meckels diverticulum was first explained by Fabricius Hildanus in the sixteenth century and later named after Johann Friedrich Meckel, who described the embryological origin of this type of diverticulum in 1809.

Signs and symptoms
The majority of people with a Meckels diverticulum are asymptomatic. An asymptomatic Meckels diverticulum is called a silent Meckels diverticulum. If symptoms do occur, they typically appear before the age of two years. The most common presenting symptom is painless rectal bleeding such as melaena-like black offensive stools, followed by intestinal obstruction, volvulus and intussusception. Occasionally, Meckels diverticulitis may present with all the features of acute appendicitis. Also, severe pain in the epigastric region is experienced by the person along with bloating in the epigastric and umbilical regions. At times, the symptoms are so painful that they may cause sleepless nights with acute pain felt in the foregut region, specifically in the epigastric and umbilical regions. In some cases, bleeding occurs without warning and may stop spontaneously. The symptoms can be extremely painful, often mistaken as just stomach pain resulting from not eating or constipation. Rarely, a Meckels diverticulum containing ectopic pancreatic tissue can present with abdominal pain and increased serum amylase levels, mimicking acute pancreatitis.

Complications
The lifetime risk for a person with Meckels diverticulum to develop certain complications is about 4–6%. Gastrointestinal bleeding, peritonitis or intestinal obstruction may occur in 15–30% of symptomatic people (Table 1). Only 6.4% of all complications require surgical treatment, and untreated Meckels diverticulum has a mortality rate of 2.5–15%.Table 1 – Complications of Meckels Diverticulum:

Bleeding
Bleeding of the diverticulum is most common in young children, especially in males who are less than 2 years of age. Symptoms may include bright red blood in stools (hematochezia), weakness, abdominal tenderness or pain, and even anaemia in some cases.Bleeding may be caused by:

Ectopic gastric or pancreatic mucosa:Where diverticulum contains embryonic remnants of mucosa of other tissue types.
Secretion of gastric acid or alkaline pancreatic juice from the ectopic mucosa leads to ulceration in the adjacent ileal mucosa i.e. peptic or pancreatic ulcer.
Pain, bleeding or perforation of the bowel at the diverticulum may result.
Mechanical stimulation may also cause erosion and ulceration.Gastrointestinal bleeding may be self-limiting but chronic bleeding may lead to iron deficiency anaemia.The appearance of stools may indicate the nature of the bleeding:

Tarry stools: Alteration of blood produced by slow bowel transit due to minor bleeding in upper gastrointestinal tract
Bright red blood stools: Brisk bleeding
Stools with blood streak: Anal fissure
"Currant jelly" stools: Ischaemia of the intestine leads to copious mucus production and may indicate that one part of the bowel invaginates into another intussusception.

Diverticulitis
Inflammation of the diverticulum can mimic symptoms of appendicitis, i.e., periumbilical tenderness and intermittent crampy abdominal pain. Perforation of the inflamed diverticulum can result in peritonitis. Diverticulitis can also cause adhesions, leading to intestinal obstruction.Diverticulitis may result from:

Association with the mesodiverticular band attaching to the diverticulum tip where torsion has occurred, causing inflammation and ischaemia.
Peptic ulceration resulting from ectopic gastric mucosa of the diverticulum
Following perforation by trauma or ingested foreign material e.g. stalk of vegetable, seeds or fish/chicken bone that become lodged in Meckels diverticulum.
Luminal obstruction due to tumors, enterolith, foreign body, causing stasis or bacterial infection.
Association with acute appendicitis

Intestinal obstruction
Symptoms: Vomiting, abdominal pain and severe or complete constipation.
The vitelline vessels remnant that connects the diverticulum to the umbilicus may form a fibrous or twisting band (volvulus), trapping the small intestine and causing obstruction. Localised periumbilical pain may be experienced in the right lower quadrant (like appendicitis).
"Incarceration": when a Meckels diverticulum is constricted in an inguinal hernia, forming a Littré hernia that obstructs the intestine.
Chronic diverticulitis causing stricture
Strangulation of the diverticulum in the obturator foramen.
Tumors e.g. carcinoma: direct spread of an adenocarcinoma arising in the diverticulum may lead to obstruction
Lithiasis, stones that are formed in Meckels diverticulum can:Extrude into the terminal ileum, leading to obstruction
Induce local inflammation and intussusception.The diverticulum itself or tumour within it may cause intussusception. For example, from the ileum to the colon, causing obstruction. Symptoms of this include "currant jelly" stools and a palpable lump in the lower abdomen. This occurs when the diverticulum inverts into the lumen of the ileum, due to either:An active peristaltic mechanism of the diverticulum that attempts to remove irritating factors
A passive process such as the transit of food

Umbilical anomalies
Anomalies between the diverticulum and umbilicus may include the presence of fibrous cord, cyst, fistula, or sinus, leading to:
Infection or excoriation of periumbilical skin, resulting in a discharging sinus
Recurrent infection and healing of sinus
Abscess formation in the abdominal wall
Fibrous cord increases the risk of volvulus formation and internal herniation

Neoplasm
Tumors in Meckels diverticulum may cause bleeding, acute abdominal pain, gastrointestinal obstruction, perforation or intussusception.
Benign tumors:Leiomyoma
Lipoma
Vascular and neuromuscular hamartomaMalignant tumors:Carcinoids: most common, 44%
Mesenchymal tumors: Leiomyosarcoma, peripheral nerve sheath and gastrointestinal stromal tumors, 35%
Adenocarcinoma, 16%
Desmoplastic small round cell tumor

Other complications
A diverticulum inside a Meckels diverticulum (daughter diverticula)
Stones and phytobezoar (a bezoar of vegetable fibers) in Meckels diverticulum
Vesicodiverticular fistula

Pathophysiology
The omphalomesenteric duct (omphaloenteric duct, vitelline duct, or yolk stalk) normally connects the embryonic midgut to the yolk sac ventrally, providing nutrients to the midgut during embryonic development. The vitelline duct narrows progressively and disappears between the 5th and 8th weeks of gestation.In Meckels diverticulum, the proximal part of vitelline duct fails to regress and involute, which remains as a remnant of variable length and location. The solitary diverticulum lies on the antimesenteric border of the ileum (opposite to the mesenteric attachment) and extends into the umbilical cord of the embryo. The left and right vitelline arteries originate from the primitive dorsal aorta, and travel with the vitelline duct. The right becomes the superior mesenteric artery that supplies a terminal branch to the diverticulum, while the left involutes. Having its own blood supply, Meckels diverticulum is susceptible to obstruction or infection.
Meckels diverticulum is located in the distal ileum, usually within 60–100 cm (2 feet) of the ileocecal valve. This blind segment or small pouch is about 3–6 cm (2 inch) long and may have a greater lumen diameter than that of the ileum. It runs antimesenterically and has its own blood supply. It is a remnant of the connection from the yolk sac to the small intestine present during embryonic development. It is a true diverticulum, consisting of all 3 layers of the bowel wall which are mucosa, submucosa and muscularis propria.As the vitelline duct is made up of pluripotent cell lining, Meckels diverticulum may harbor abnormal tissues, containing embryonic remnants of other tissue types. Jejunal, duodenal mucosa or Brunners tissue were each found in 2% of ectopic cases. Heterotopic rests of gastric mucosa and pancreatic tissue are seen in 60% and 6% of cases respectively. Heterotopic means the displacement of an organ from its normal anatomic location. Inflammation of this Meckels diverticulum may mimic appendicitis. Therefore, during appendectomy, ileum should be checked for the presence of Meckels diverticulum, if it is found to be present it should be removed along with appendix.A memory aid is the rule of 2s:
2% (of the population)
2 feet (proximal to the ileocecal valve)
2 inches (in length)
2 types of common ectopic tissue (gastric and pancreatic)
2 years is the most common age at clinical presentation
2:1 male:female ratioHowever, the exact values for the above criteria range from 0.2–5 (for example, prevalence is probably 0.2–4%).It can also be present as an indirect hernia, typically on the right side, where it is known as a "Hernia of Littré". A case report of strangulated umbilical hernia with Meckels diverticulum has also been published in the literature. Furthermore, it can be attached to the umbilical region by the vitelline ligament, with the possibility of vitelline cysts, or even a patent vitelline canal forming a vitelline fistula when the umbilical cord is cut. Torsions of intestine around the intestinal stalk may also occur, leading to obstruction, ischemia, and necrosis.

Diagnosis
A technetium-99m (99mTc) pertechnetate scan, also called Meckel scan or nuclear scintigraphy scan, is the investigation of choice to diagnose Meckels diverticula in children. This scan detects gastric mucosa; since approximately 50% of symptomatic Meckels diverticula have ectopic gastric or pancreatic cells contained within them, this is displayed as a spot on the scan distant from the stomach itself. In children, this scan is highly accurate and noninvasive, with 95% specificity and 85% sensitivity; however, in adults the test is only 9% specific and 62% sensitive.
Patients with these misplaced gastric cells may experience peptic ulcers as a consequence. Therefore, other tests such as colonoscopy and screenings for bleeding disorders should be performed, and angiography can assist in determining the location and severity of bleeding </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 Foreign body in alimentary tract and can you explain it in depth? [/INST]  </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 Adhesive capsulitis of the shoulder and can you explain it in depth? [/INST] Adhesive capsulitis, also known as frozen shoulder, is a condition associated with shoulder pain and stiffness. It is a common shoulder ailment that is marked by pain and a loss of range of motion, particularly in external rotation. There is a loss of the ability to move the shoulder, both voluntarily and by others, in multiple directions. The shoulder itself, however, does not generally hurt significantly when touched. Muscle loss around the shoulder may also occur. Onset is gradual over weeks to months. Complications can include fracture of the humerus or biceps tendon rupture.The cause in most cases is unknown. The condition can also occur after injury or surgery to the shoulder. Risk factors include diabetes and thyroid disease. The underlying mechanism involves inflammation and scarring. The diagnosis is generally based on a persons symptoms and a physical exam. The diagnosis may be supported by an MRI. Adhesive capsulitis has been linked to diabetes and hypothyroidism, according to research. Adhesive capsulitis was five times more common in diabetic patients than in the control group, according to a meta-analysis published in 2016.The condition often resolves itself over time without intervention but this may take several years. While a number of treatments, such as NSAIDs, physical therapy, steroids, and injecting the shoulder at high pressure, may be tried, it is unclear what is best. Surgery may be suggested for those who do not get better after a few months. About 4% of people are affected. It is more common in people 40–60 years of age and in women.

Signs and symptoms
Symptoms include shoulder pain and limited range of motion although these symptoms are common in many shoulder conditions. An important symptom of adhesive capsulitis is the severity of stiffness that often makes it nearly impossible to carry out simple arm movements. Pain due to frozen shoulder is usually dull or aching and may be worse at night and with any motion.The symptoms of primary frozen shoulder have been described as having three or four stages. Sometimes a prodromal stage is described that can be present up to three months prior to the shoulder freezing. During this stage people describe sharp pain at end ranges of motion, achy pain at rest, and sleep disturbances.

Stage one: The "freezing" or painful stage, which may last from six weeks to nine months, and in which the patient has a slow onset of pain. As the pain worsens, the shoulder loses motion.
Stage two: The "frozen" or adhesive stage is marked by a slow improvement in pain but the stiffness remains. This stage generally lasts from four to twelve months.
Stage three: The "thawing" or recovery, when shoulder motion slowly returns toward normal. This generally lasts from 5 to 26 months.Physical exam findings include restricted range of motion in all planes of movement in both active and passive range of motion. This contrasts with conditions such as shoulder impingement syndrome or rotator cuff tendinitis in which the active range of motion is restricted but passive range of motion is normal. Some exam maneuvers of the shoulder may be impossible due to pain.

Causes
The causes of adhesive capsulitis are incompletely understood; however, there are several factors associated with higher risk. Risk factors for secondary adhesive capsulitis include injury or surgery leading to prolonged immobility. Risk factors for primary, or idiopathic adhesive capsulitis include many systemic diseases, such as diabetes mellitus, stroke, lung disease, connective tissue diseases, thyroid disease, heart disease, autoimmune disease, and Dupuytrens contracture. Both type 1 diabetes and type 2 diabetes are risk factors for the condition.

Primary
Primary adhesive capsulitis, also known as idiopathic adhesive capsulitis, occurs with no known trigger. It is more likely to develop in the non-dominant arm.

Secondary
Adhesive capsulitis is called secondary when it develops after an injury or surgery to the shoulder.

Pathophysiology
The underlying pathophysiology is incompletely understood, but is generally accepted to have both inflammatory and fibrotic components. The hardening of the shoulder joint capsule is central to the disease process. This is the result of scar tissue (adhesions) around the joint capsule. There also may be a reduction in synovial fluid, which normally helps the shoulder joint, a ball and socket joint, move by lubricating the gap between the humerus and the socket in the shoulder blade. In the painful stage (stage I), there is evidence of inflammatory cytokines in the joint fluid. Later stages are characterized by dense collagenous tissue in the joint capsule.Under the microscope, the appearance of the affected shoulder joint capsule tissue is similar to the appearance of the tissue that restricts finger movement in Dupuytrens contracture.

Diagnosis
Adhesive capsulitis can be diagnosed by history and physical exam. It is often a diagnosis of exclusion, as other causes of shoulder pain and stiffness must first be ruled out. On physical exam, adhesive capsulitis can be diagnosed if limits of the active range of motion are the same or similar to the limits to the passive range of motion. The movement that is most severely inhibited is external rotation of the shoulder.Imaging studies are not required for diagnosis, but may be used to rule out other causes of pain. Radiographs will often be normal, but imaging features of adhesive capsulitis can be seen on ultrasound or non-contrast MRI. Ultrasound and MRI can help in diagnosis by assessing the coracohumeral ligament, with a width of greater than 3 mm being  60% sensitive and 95% specific for the diagnosis. Shoulders with adhesive capsulitis also characteristically fibrose and thicken at the axillary pouch and "rotator interval", best seen as a dark signal on T1 sequences with edema and inflammation on T2 sequences. A finding on ultrasound associated with adhesive capsulitis is hypoechoic material surrounding the long head of the biceps tendon at the rotator interval, reflecting fibrosis. In the painful stage, such hypoechoic material may demonstrate increased vascularity with Doppler ultrasound.Grey-scale ultrasound can play a key role in timely diagnosis of adhesive capsulitis due to its high sensitivity and specificity. It is also widely available, convenient, and cost efficient. Thickening in the coracohumeral ligament, inferior capsule/ axillary recess capsule, and rotator interval abnormality, as well as restriction in range of motion in the shoulder can be detected using ultrasound. The range of motion is prohibited due to scapulohumeral rhythm changes occurring in the shoulder joint. The altered scapular kinematics can restrict anterior and posterior tilting, downward rotation and depression as well as external rotation. All of these restrictions lead the scapula to be excessively upwardly rotated. The restriction of the scapular posterior tilt is due to tightness in the lower serratus anterior, anterior capsule and the pectoralis minor. Downward rotation and depression are restricted due to the tightness of the rhomboids, upper trapezius and the superior capsule. Respective sensitivity values were 64.4, 82.1, 82.6, and 94.3, and respective specificity levels were 88.9, 95.7, 93.9, and 90.9.

Management
Management of this disorder focuses on restoring joint movement and reducing shoulder pain, involving medications, occupational therapy, physical therapy, or surgery. Treatment may continue for months; there is no strong evidence to favor any particular approach. The main treatment for adhesive capsulitis is a trial of conservative therapies, including analgesia, exercise, physiotherapy, oral nonsteroidal anti-inflammation drugs, and intra-articular corticosteroid injections.Medications such as NSAIDs can be used for pain control. Corticosteroids are used in some cases either through local injection or systemically. In the short term, intra-articular corticosteroid injections were more effective in pain alleviation. Unfortunately, this pain reduction was not long-lasting. In both the short and long term, intra-articular corticosteroid injections improved passive range of motion (ROM). Oral steroids may provide short-term benefits in range of movement and pain but have side effects such as hyperglycemia. Steroid injections compared to physical therapy have a similar effect in improving shoulder function and decreasing pain. The benefits of steroid injections appear to be short-term. The results of this study imply that using an IA corticosteroid early in individuals with frozen shoulder who have had it for less than a year had a better prognosis. To increase the chances of recovery, this treatment should be combined with a home exercise program. Oral corticosteroids should not be used consistently to treat adhesive capsulitis because of the dangers associated with long-term use and the lack of long-term benefit.The role for occupational therapy (OT) in adhesive capsulitis is dependent on restrictions on daily activities, pain, and limitations the person is experiencing; an occupational therapist usually makes an initial evaluation. Pain and limited joint mobility are primary complaints that impact a persons daily life. OT will usually start by using a preparatory method, like physical agent modalities to be used as part of a comprehensive occupational therapy program. The occupational therapist may teach strengthening exercises and provide a home exercise program. The goal of OT would be for the client to resume meaningful functional daily activities.The role for physical therapy in adhesive capsulitis is not settled. Physical therapy is used as an initial treatment in adhesive capsulitis with the use of range of motion (ROM) exercises and manual therapy techniques to restore range and function. A low-dose corticosteroid injection and home exercise programs in those with symptoms for less than 6 months may be useful. There may be some benefit with manual therapy and stretching as part of a rehabilitation program, but, due to the time required, such use should be carefully considered. Physical therapists may utilize joint mobilization directly at the glenohumeral joint to decrease pain, increase function, and increase range of motion as another form of treatment. There are some studies that have shown that intensive passive stretching can promote healing. Additional interventions include modalities such as ultrasound, shortwave diathermy, laser therapy and electrical stimulation. Another osteopathic technique used to treat the shoulder is called the Spencer technique. Mobilization techniques and other therapeutic modalities are most commonly used by physical therapists; however, there is not strong evidence that these methods can change the course of the disease.If these measures are unsuccessful, more aggressive interventions such as surgery can be trialed.  Manipulation of the shoulder under general anesthesia to break up the adhesions is sometimes used. Hydrodilatation or distension arthrography is controversial. However, some studies show that arthrographic distension may play a positive role in reducing pain and improve range of movement and function. Surgery to cut the adhesions (capsular release) may be indicated in prolonged and severe cases; the procedure is usually performed by arthroscopy. Surgical evaluation of other problems with the shoulder, e.g., subacromial bursitis or rotator cuff tear, may be needed. Resistant adhesive capsulitis may respond to open release surgery. This technique allows the surgeon to find and correct the underlying cause of restricted glenohumeral movement such as contracture of coracohumeral ligament and rotator interval. Physical therapy may achieve improved results after surgical procedure and postoperative rehabilitation.Physical therapy is an effective procedure that provides essential exercises to improve range of motion. Patients who receive the proper training from an authorized physiotherapist can perform these exercises independently at home. The physiotherapy treatment for frozen shoulder will include manual therapy to mobilize the affected joints and release their muscles. "Pendulum stretch", "finger walk", "towel stretch", "armpit stretch" and "crossbody reach" are some essential mobility exercises specifically designed to improve the shoulder mobility of patients with frozen shoulders. There are also limited case reports of therapy utilizing vibration platforms obtaining fast results, not as a post-operative aid, but instead of surgery.Acupuncture has been found to decrease pain levels and improve shoulder function and range of motion, particularly in shoulder flexion </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 Takayasus arteritis and can you explain it in depth? [/INST] Takayasus arteritis (TA), also known as aortic arch syndrome, nonspecific aortoarteritis, and pulseless disease, is a form of large vessel granulomatous vasculitis with massive intimal fibrosis and vascular narrowing, most commonly affecting young or middle-aged women of Asian descent, though anyone can be affected. It mainly affects the aorta (the main blood vessel leaving the heart) and its branches, as well as the pulmonary arteries. Females are about 8–9 times more likely to be affected than males.Those with the disease often notice symptoms between 15 and 30 years of age. In the Western world, atherosclerosis is a more frequent cause of obstruction of the aortic arch vessels than Takayasus arteritis. Takayasus arteritis is similar to other forms of vasculitis, including giant cell arteritis which typically affects older individuals. Due to obstruction of the main branches of the aorta, including the left common carotid artery, the brachiocephalic artery, and the left subclavian artery, Takayasus arteritis can present as pulseless upper extremities (arms, hands, and wrists with weak or absent pulses on the physical examination) which may be why it is also commonly referred to as the "pulseless disease." Involvement of renal arteries may lead to a presentation of renovascular hypertension.

Sign and symptoms
Some people develop an initial "inflammatory phase" characterized by systemic illness with signs and symptoms of malaise, fever, night sweats, weight loss, joint pain, fatigue, and fainting. Fainting may result from subclavian steal syndrome or carotid sinus hypersensitivity. There is also often anemia and marked elevation of the ESR or C-reactive protein (nonspecific markers of inflammation). The initial "inflammatory phase" is often followed by a secondary "pulseless phase". The "pulseless phase" is characterized by vascular insufficiency from intimal narrowing of the vessels manifesting as arm or leg claudication, renal artery stenosis causing hypertension, and neurological manifestations due to decreased blood flow to the brain.Of note is the function of renal artery stenosis in the causation of high blood pressure: Normally perfused kidneys produce a proportionate amount of a substance called renin. Stenosis of the renal arteries causes hypoperfusion (decreased blood flow) of the juxtaglomerular apparatus, resulting in exaggerated secretion of renin, and high blood levels of aldosterone, eventually leading to water and salt retention and high blood pressure. The neurological symptoms of the disease vary depending on the degree; the nature of the blood vessel obstruction; and can range from lightheadedness to seizures (in severe cases). One rare, important feature of the Takayasus arteritis is ocular involvement in form of visual field defects, vision loss, or retinal hemorrhage. Some individuals with Takayasus arteritis may present with only late vascular changes, without a preceding systemic illness. In the late stage, weakness of the arterial walls may give rise to localized aneurysms. As with all aneurysms, the possibility of rupture and vascular bleeding is existent and requires monitoring. In view of the chronic process and good collateral development, Raynauds phenomenon or digital gangrene are very rare in Takayasu arteritis. A rare complication of this condition are coronary artery aneurysms.

Laser Doppler imaging by near-infrared digital holography can reveal characteristic blood flow waveforms in the central artery and vein of the retina in patients with vascular insufficiency who may exhibit a smooth systo-diastolic pulse in the central retinal artery. This technique enables non invasive functional microangiography by high-contrast measurement of endoluminal blood flow profiles in vessels in the posterior segment of the eye with a spatial resolution comparable to state-of-the-art indocyanine green angiography.

Pathophysiology
Although the cause of Takayasu arteritis is unknown, the condition is characterized by segmental and patchy granulomatous inflammation of the aorta and its major derivative branches. This inflammation leads to arterial stenosis, thrombosis, and aneurysms. There is irregular fibrosis of the blood vessels due to chronic vasculitis, leading to sometimes massive intimal fibrosis (fibrosis of the inner section of the blood vessels). Prominent narrowing due to inflammation, granuloma, and fibrosis is often seen in arterial studies such as magnetic resonance angiography (MRA), computed tomography angiography (CTA), or arterial angiography (DSA).

Genetics
The genetic contribution to the pathogenesis of Takayasus arteritis is supported by the genetic association with HLA-B∗52. A 2013 large collaborative study uncovered multiple additional susceptibility loci for this disease, increasing its number of genetic loci to five risk loci across the genome. About 200,000 genetic variants were genotyped in two ethnically divergent Takayasus arteritis cohorts from Turkey and North America by using a custom-designed genotyping platform (Immunochip). Additional genetic variants and the classical HLA alleles were imputed and analyzed. The study identified and confirmed two independent susceptibility loci within the HLA region (r2 < 0.2): HLA-B/MICA (rs12524487, OR = 3.29, p = 5.57 × 10-16) and HLA-DQB1/HLA-DRB1 (rs113452171, OR = 2.34, p = 3.74 × 10-9; and rs189754752, OR = 2.47, p = 4.22 × 10-9). In addition, a genetic association was identified and confirmed between Takayasus arteritis and the FCGR2A/FCGR3A locus on chromosome 1 (rs10919543, OR = 1.81, p = 5.89 × 10-12). The risk allele at this locus results in increased mRNA expression of FCGR2A. In addition, a genetic association between IL12B and Takayasu arteritis was established (rs56167332, OR = 1.54, p = 2.18 × 10-8). A fifth genetic locus for the disease in an intergenic region on chromosome 21q22 downstream of PSMG1 was revealed (P=4.39X10-7). A recent genome-wide association study (GWAS) identified genetic susceptibility loci for Takayasu arteritis with a genome-wide level of significance in IL6 (rs2069837) (odds ratio [OR] 2.07, P = 6.70 × 10(-9)), RPS9/LILRB3 (rs11666543) (OR 1.65, P = 2.34 × 10(-8)), and the intergenic locus on chromosome 21q22 (rs2836878) (OR 1.79, P = 3.62 × 10(-10)). The genetic susceptibility locus in RPS9/LILRB3 lies within the leukocyte receptor complex gene cluster on chromosome 19q13.4, and the disease risk variant in this locus correlates with reduced expression of multiple genes including the inhibitory leukocyte immunoglobulin-like receptor gene LILRB3 (P = 2.29 × 10(-8)). In addition, this study identified additional candidate susceptibility genes with suggestive levels of association (P < 1 × 10(-5)) including PCSK5, LILRA3, PPM1G/NRBP1, and PTK2B.Another gene associated with this condition is MLX (Max-like protein X)

Diagnosis
Diagnosis is based on the demonstration of vascular lesions in large and middle-sized vessels on angiography, CT scan, magnetic resonance angiography or FDG PET. Seeing abnormal diffuse arterial wall thickening, the macaroni sign, with ultrasound is highly suggestive of the condition. FDG PET can help in diagnosis of active inflammation not just in patients with active Takayasu arteritis prior to treatment but also in addition in relapsing patients receiving immunosuppressive agents.Contrast angiography has been the gold standard. The earliest detectable lesion is a local narrowing or irregularity of the lumen. This may develop into stenosis and occlusion. The characteristic finding is the presence of "skip lesions," where stenosis or aneurysms alternate with normal vessels. Angiography provides information on vessel anatomy and patency but does not provide information on the degree of inflammation in the wall.The age at onset helps to differentiate Takayasus arteritis from other types of large vessel vasculitis. For example, Takaysus arteritis has an age of onset of <40 years, while giant cell arteritis has an age of onset >60 years.Takayasu arteritis is not associated with ANCA, rheumatoid factor, ANA, and anticardiolipin antibodies.

Treatments
Most people with Takayasu’s arteritis respond to steroids such as prednisone. The usual starting dose is approximately 1 milligram per kilogram of body weight per day (for most people, this is approximately 60 milligrams a day). Because of the significant side effects of long-term high-dose prednisone use, the starting dose is tapered over several weeks to a dose that controls symptoms while limiting the side effects of steroids.Promising results are achieved with mycophenolate and tocilizumab. If treatment is not kept to a high standard, long-term damage or death can occur.Patients who do not respond to steroids may require revascularization, either via vascular bypass or angioplasty and stenting. Outcomes following revascularization vary depending on the severity of the underlying disease.

History
The first case of Takayasu’s arteritis was described in 1908 by Japanese ophthalmologist Mikito Takayasu at the Annual Meeting of the Japan Ophthalmology Society </s>