<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 Zoophilia and can you explain it in depth? [/INST] Zoophilia is a paraphilia involving a sexual fixation on non-human animals. Bestiality is cross-species sexual activity between humans and non-human animals. The terms are often used interchangeably, but some researchers make a distinction between the attraction (zoophilia) and the act (bestiality).In most countries, bestiality is illegal under animal abuse laws or laws dealing with sodomy or crimes against nature.

Terminology
General
Three key terms commonly used in regards to the subject—zoophilia, bestiality, and zoosexuality—are often used somewhat interchangeably. Some researchers distinguish between zoophilia (as a persistent sexual interest in animals) and bestiality (as sexual acts with animals), because bestiality is often not driven by a sexual preference for animals. Some studies have found a preference for animals is rare among people who engage in sexual contact with animals. Furthermore, some zoophiles report they have never had sexual contact with an animal. People with zoophilia are known as "zoophiles", though also sometimes as "zoosexuals", or even very simply "zoos". Zooerasty, sodomy, and zooerastia are other terms closely related to the subject but are less synonymous with the former terms, and are seldom used. "Bestiosexuality" was discussed briefly by Allen (1979), but never became widely established. Ernest Bornemann (1990, cited by Rosenbauer, 1997) coined the separate term zoosadism for those who derive pleasure – sexual or otherwise – from inflicting pain on animals. Zoosadism specifically is one member of the Macdonald triad of precursors to sociopathic behavior.

Zoophilia
The term zoophilia was introduced into the field of research on sexuality in Psychopathia Sexualis (1886) by Krafft-Ebing, who described a number of cases of "violation of animals (bestiality)", as well as "zoophilia erotica", which he defined as a sexual attraction to animal skin or fur. The term zoophilia derives from the combination of two nouns in Greek: ζῷον (zṓion, meaning "animal") and φιλία (philia, meaning "(fraternal) love"). In general contemporary usage, the term zoophilia may refer to sexual activity between human and non-human animals, the desire to engage in such, or to the specific paraphilia (i.e., the atypical arousal) which indicates a definite preference for animals over humans as sexual partners. Although Krafft-Ebing also coined the term zooerasty for the paraphilia of exclusive sexual attraction to animals, that term has fallen out of general use.

Zoosexuality
The term zoosexual was proposed by Hani Miletski in 2002 as a value-neutral term. Usage of zoosexual as a noun (in reference to a person) is synonymous with zoophile, while the adjectival form of the word – as, for instance, in the phrase "zoosexual act" – may indicate sexual activity between a human and an animal. The derivative noun "zoosexuality" is sometimes used by self-identified zoophiles in both support groups and on internet-based discussion forums to designate sexual orientation manifesting as sexual attraction to animals.

Bestiality
The legal term bestiality has three common pronunciations: [ˌbestʃiˈæləti] or [ˌbistʃiˈæləti] in the United States, and [ˌbestiˈæləti] in the United Kingdom. Some zoophiles and researchers draw a distinction between zoophilia and bestiality, using the former to describe the desire to form sexual relationships with animals, and the latter to describe the sex acts alone. Confusing the matter yet further, writing in 1962, Masters used the term bestialist specifically in his discussion of zoosadism.Stephanie LaFarge, an assistant professor of psychiatry at the New Jersey Medical School, and Director of Counseling at the ASPCA, writes that two groups can be distinguished: bestialists, who rape or abuse animals, and zoophiles, who form an emotional and sexual attachment to animals. Colin J. Williams and Martin Weinberg studied self-defined zoophiles via the internet and reported them as understanding the term zoophilia to involve concern for the animals welfare, pleasure, and consent, as distinct from the self-labelled zoophiles concept of "bestialists", whom the zoophiles in their study defined as focused on their own gratification. Williams and Weinberg also quoted a British newspaper saying that zoophilia is a term used by "apologists" for bestiality.

Extent of occurrence
The Kinsey reports rated the percentage of people in the general population who had at least one sexual interaction with animals as 8% for males and 5.1% for females (1.5% for pre-adolescents and 3.6% for post-adolescents females), and claimed it was 40–50% for the rural population and even higher among individuals with lower educational status, but some later writers dispute the figures, because the study lacked a random sample in that it included a disproportionate number of prisoners, causing sampling bias. Martin Duberman has written that it is difficult to get a random sample in sexual research, and that even when Paul Gebhard, Kinseys research successor, removed prison samples from the figures, he found the figures were not significantly  changed.By 1974, the farm population in the USA had declined by 80 percent compared with 1940, reducing the opportunity to live with animals; Hunts 1974 study suggests that these demographic changes led to a significant change in reported occurrences of bestiality. The percentage of males who reported sexual interactions with animals in 1974 was 4.9% (1948: 8.3%), and in females in 1974 was 1.9% (1953: 3.6%). Miletski believes this is not due to a reduction in interest but merely a reduction in opportunity.Nancy Fridays 1973 book on female sexuality, My Secret Garden, comprised around 190 fantasies from different women; of these, 23 involve zoophilic activity.In one study, psychiatric patients were found to have a statistically significant higher prevalence rate (55 percent) of reported bestiality, both actual sexual contacts (45 percent) and sexual fantasy (30 percent) than the control groups of medical in-patients (10 percent) and psychiatric staff (15 percent). Crépault and Couture (1980) reported that 5.3 percent of the men they surveyed had fantasized about sexual activity with an animal during heterosexual intercourse. In a 2014 study, 3% of women and 2.2% of men reported fantasies about having sex with an animal. A 1982 study suggested that 7.5 percent of 186 university students had interacted sexually with an animal. A 2021 review estimated zoophilic behavior occurs in 2% of the general population.
Sexual arousal from watching animals mate is known as faunoiphilia.

Perspectives on zoophilia
Research perspectives
Zoophilia has been partly discussed by several sciences: psychology (the study of the human mind), sexology (a relatively new discipline primarily studying human sexuality), ethology (the study of animal behavior), and anthrozoology (the study of human–animal interactions and bonds).
In the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), zoophilia is placed in the classification "other specified paraphilic disorder" ("paraphilias not otherwise specified" in the DSM-III and IV). The World Health Organization takes the same position, listing a sexual preference for animals in its ICD -10 as "other disorder of sexual preference". In the DSM-5, it rises to the level of a diagnosable disorder only when accompanied by distress or interference with normal functioning.Zoophilia may also be covered to some degree by other fields such as ethics, philosophy, law, animal rights and animal welfare. It may also be touched upon by sociology which looks both at zoosadism in examining patterns and issues related to sexual abuse and at non-sexual zoophilia in examining the role of animals as emotional support and companionship in human lives, and may fall within the scope of psychiatry if it becomes necessary to consider its significance in a clinical context.
The Journal of Forensic and Legal Medicine (Vol. 18, February 2011) states that sexual contact with animals is almost never a clinically significant problem by itself; it also states that there are several kinds of zoophiles:

Additionally, zoophiles in categories 2, 3, and 8 (romantic zoophiles, zoophilic fantasizers, and regular zoophiles) are the most common, while zoophiles found in categories 6 and 7 (sadistic bestials and opportunistic zoophiles) are the least common.Zoophilia may reflect childhood experimentation, sexual abuse or lack of other avenues of sexual expression. Exclusive desire for animals rather than humans is considered a rare paraphilia, and sufferers often have other paraphilias with which they present. Zoophiles will not usually seek help for their condition, and so do not come to the attention of psychiatrists for zoophilia itself.The first detailed studies of zoophilia date from prior to 1910. Peer reviewed research into zoophilia in its own right started around 1960. However, a number of the most oft-quoted studies, such as Miletski, were not published in peer-reviewed journals. There have been several significant modern books, from Masters (1962) to Beetz (2002); their research arrived at the following conclusions:

Most zoophiles have (or have also had) long term human relationships as well or at the same time as zoosexual ones, and that zoosexual partners are usually dogs and/or horses (Masters, Miletski, Beetz)
Zoophiles emotions and care for animals can be real, relational, authentic and (within animals abilities) reciprocal, and not just a substitute or means of expression. Beetz believes zoophilia is not an inclination which is chosen.
Society in general at present is considerably misinformed about zoophilia, its stereotypes, and its meaning. The distinction between zoophilia and zoosadism is a critical one to these researchers, and is highlighted by each of these studies. Masters (1962), Miletski (1999) and Weinberg (2003) each comment significantly on the social harm caused by misunderstandings regarding zoophilia: "This destroy[s] the lives of many citizens".Beetz also states the following:

The phenomenon of sexual contact with animals is starting to lose its taboo: it is appearing more often in scholarly publications, and the public are being confronted with it, too. ... Sexual contact with animals – in the form of bestiality or zoophilia – needs to be discussed more openly and investigated in more detail by scholars working in disciplines such as animal ethics, animal behavior, anthrozoology, psychology, mental health, sociology, and the law.
More recently, research has engaged three further directions: the speculation that at least some animals seem to enjoy a zoophilic relationship assuming sadism is not present, and can form an affectionate bond.Beetz described the phenomenon of zoophilia/bestiality as being somewhere between crime, paraphilia and love, although she says that most research has been based on criminological reports, so the cases have frequently involved violence and psychiatric illness. She says only a few recent studies have taken data from volunteers in the community. As with all volunteer surveys and sexual ones in particular, these studies have a potential for self-selection bias.Medical research suggests that some zoophiles only become aroused by a specific species (such as horses), some zoophiles become aroused by multiple species (which may or may not include humans), and some zoophiles are not attracted to humans at all.

Historical and cultural perspectives
Instances of this behavior have been found in the Bible. In a cave painting from at least 8000 BC in the Northern Italian Val Camonica a man is shown about to penetrate an animal. Raymond Christinger interprets that as a show of power of a tribal chief, and so we do not know if this practice was then more acceptable, and if the scene depicted was usual or unusual or whether it was symbolic or imaginary. The "Cambridge Illustrated History of Prehistoric Art" says the scene may be humorous, as the penetrating man seems to be waving cheerfully with his hand at the same time. Potters seem to have spent time depicting the practice, but this may be because they found the idea amusing. Dr "Jacobus X", said to be the pen name of a French author, said this was clearly "before any known taboos against sex with animals existed". Marc Epprecht states that authors such as Jacobus X do not deserve respect because their methodology is based on hearsay, and was designed for voyeuristic titillation of the reader. Masters said that since pre-historic man is prehistoric it goes without saying that we know little of his sexual behaviour; depictions in cave paintings may only show the artists subjective preoccupations or thoughts.
Pindar, Herodotus, and Plutarch claimed the Egyptians engaged in ritual congress with goats. Such claims about other cultures do not necessarily reflect anything about which the author had evidence, but may be a form of propaganda or xenophobia, similar to blood libel.Bestiality has been accepted in a few North American and Middle Eastern indigenous cultures.Several cultures built temples (Khajuraho, India) or other structures (Sagaholm, barrow, Sweden) with zoophilic carvings on the exterior, however at Khajuraho, these depictions are not on the interior, perhaps depicting that these are things that belong to the profane world rather than the spiritual world, and thus are to be left outside.In the Church-oriented culture of the Middle Ages, zoophilic activity was met with execution, typically burning, and death to the animals involved either the same way or by hanging, as "both a violation of Biblical edicts and a degradation of man as a spiritual being rather than one that is purely animal and carnal". Some witches were accused of having congress with the devil in the form of an animal. As with all accusations and confessions extracted under torture in the witch trials in Early Modern Europe, their validity cannot be ascertained.

Religious perspectives
Passages in Leviticus 18 (Lev 18:23: "And you shall not lie with any beast and defile yourself with it, neither shall any woman give herself to a beast to lie with it: it is a perversion." RSV) and 20:15–16 ("If a man lies with a beast, he shall be put to death; and you shall kill the beast. If a woman approaches any beast and lies with it, you shall kill the woman and the beast; they shall be put to death, their blood is upon them." RSV) are cited by Jewish, Christian, and Muslim theologians as categorical denunciation of bestiality. However, the teachings of the New Testament have been interpreted by some as not expressly forbidding bestiality.In Part II of his Summa Theologica, medieval philosopher Thomas Aquinas ranked various "unnatural vices" (sex acts resulting in "venereal pleasure" rather than procreation) by degrees of sinfulness, concluding that "the most grievous is the sin of bestiality". Some Christian theologians extend Matthews view that even having thoughts of adultery is sinful to imply that thoughts of committing bestial acts are likewise sinful.

There are a few references in Hindu scriptures to religious figures engaging in symbolic sexual activity with animals such as explicit depictions of people having sex with animals included amongst the thousands of sculptures of "Life events" on the exterior of the temple complex at Khajuraho. The depictions are largely symbolic depictions of the sexualization of some animals and are not meant to be taken literally. According to the Hindu tradition of erotic painting and sculpture, having sex with an animal is believed to be actually a human having sex with a god incarnated in the form of an animal. However, in some Hindu scriptures, such as the Bhagavata Purana and the Devi Bhagavata Purana, having sex with animals, especially the cow, leads one to hell, where one is tormented by having ones body rubbed on trees with razor-sharp thorns.

Legal status
In many jurisdictions, all acts of bestiality are prohibited; others outlaw only the mistreatment of animals, without specific mention of sexual activity. In the United Kingdom, Section 63 of the Criminal Justice and Immigration Act 2008 (also known as the Extreme Pornography Act) outlaws images of a person performing or appearing to perform an act of intercourse or oral sex with an animal (whether dead or alive). Despite the UK Ministry of Justices explanatory note on extreme images saying "It is not a question of the intentions of those who produced the image. Nor is it a question of the sexual arousal of the defendant", "it could be argued that a person might possess such an image for the purposes of satire, political commentary or simple grossness," according to The Independent.Many new laws banning sex with animals have been made recently, such as in New Hampshire, Ohio, Germany, Sweden, Iceland, Denmark, Thailand, Costa Rica, Bolivia, and Guatemala. The number of jurisdictions around the world banning it has grown in the 2000s and 2010s.
Germany legalized bestiality in 1969, but banned it again in 2013. The 2013 law was unsuccessfully challenged in 2015.Laws on bestiality are sometimes triggered by specific incidents. While some laws are very specific, others employ vague terms such as "sodomy" or "bestiality", which lack legal precision and leave it unclear exactly which acts are covered. In the past, some bestiality laws may have been made in the belief that sex with an animal could result in monstrous offspring, as well as offending the community. Current anti-cruelty laws focus more specifically on animal welfare while anti-bestiality laws are aimed only at offenses to community "standards".
Notable legal views include Sweden, where a 2005 report by the Swedish Animal Welfare Agency for the government expressed concern over the increase in reports of horse-ripping incidents. The agency believed current animal cruelty legislation was not sufficient in protecting animals from abuse and needed updating, but concluded that on balance it was not appropriate to call for a ban. In New Zealand, the 1989 Crimes Bill considered abolishing bestiality as a criminal offense, and instead viewing it as a mental health issue, but they did not, and people can still be prosecuted for it. Under Section 143 of the Crimes Act 1961, individuals can serve a sentence of seven years duration for animal sexual abuse and the offence is considered complete in the event of penetration.Copulating with a female alpaca is still specifically against the law in Peru.As of 2022, bestiality is illegal in 48 U.S. states. Most state bestiality laws were enacted between 1999 and 2022. Until 2005, there was a farm near Enumclaw, Washington that was described as an "animal brothel", where people paid to have sex with animals. After an incident on 2 July 2005, when a man was pronounced dead in the emergency room of the Enumclaw community hospital after his colon ruptured due to having had anal sex with a horse, the farm garnered police attention. The state legislature of the State of Washington, which had been one of the few states in the United States without a law against bestiality, within six months passed a bill making bestiality illegal. Arizona, Alaska, Florida, Alabama, New Jersey, New Hampshire, Ohio, Texas, Vermont, and Nevada have banned sex with animals between 2006 and the present, with the latter five all banning it in 2017. In 2021, Wyoming and Hawaii passed legislation banning bestiality. When such laws are proposed, they are never questioned or debated.Bestiality remains legal in two states (West Virginia and New Mexico), while 19 other states have statutes that date to the 19th century or even the Colonial period. These new statutes are distinct from older sodomy statutes in that they define the proscribed acts with precision.

Pornography
In the United States, zoophilic pornography would be considered obscene if it did not meet the standards of the Miller Test and therefore is not openly sold, mailed, distributed or imported across state boundaries or within states which prohibit it. Under U.S. law, distribution includes transmission across the Internet.
Similar restrictions apply in Germany (see above). In New Zealand the possession, making or distribution of material promoting bestiality is illegal.
The potential use of media for pornographic movies was seen from the start of the era of silent film. Polissons and Galipettes (re-released 2002 as "The Good Old Naughty Days") is a collection of early French silent films for brothel use, including some animal pornography, dating from around 1905 – 1930.
Material featuring sex with animals is widely available on the Internet. An early film to attain great infamy was "Animal Farm", smuggled into Great Britain around 1980 without details as to makers or provenance. The film was later traced to a crude juxtaposition of smuggled cuts from many of Bodil Joensens 1970s Danish movies.
Today, in Hungary, where production faces no legal limitations, zoophilic materials have become a substantial industry that produces a number of films and magazines, particularly for Dutch companies such as Topscore and Book & Film International, and the genre has stars such as "Hector", a Great Dane dog starring in several films.
In Japan, animal pornography is used to bypass censorship laws, often featuring models performing fellatio on animals, because oral penetration of a non-human penis is not in the scope of Japanese pixelization censorship. While primarily underground, there are a number of animal pornography actresses who specialize in bestiality movies.
In the United Kingdom, Section 63 of the Criminal Justice and Immigration Act 2008 criminalises possession of realistic pornographic images depicting sex with animals (see extreme pornography), including fake images and simulated acts, as well as images depicting sex with dead animals. The law provides for sentences of up to two years in prison; a sentence of 12 months was handed down in one case in 2011.

Zoophiles
Non-sexual zoophilia
The love of animals is not necessarily sexual in nature. In psychology and sociology the word "zoophilia" is sometimes used without sexual implications. Being fond of animals in general, or as pets, is accepted in Western society, and is usually respected or tolerated. However, the word zoophilia is used to mean a sexual preference towards animals, which makes it a paraphilia. Some zoophiles may not act on their sexual attraction to animals. People who identify as zoophiles may feel their love for animals is romantic rather than purely sexual, and say this makes them different from those committing entirely sexually motivated acts of bestiality.

Zoophile community
An online survey which recruited participants over the internet concluded that prior to the arrival of widespread computer networking, most zoophiles would not have known other zoophiles, and for the most part, zoophiles engaged in bestiality secretly, or told only trusted friends, family or partners. The internet and its predecessors made people able to search for information on topics which were not otherwise easily accessible and to communicate with relative safety and anonymity. Because of the diary-like intimacy of blogs and the anonymity of the internet, zoophiles had the ideal opportunity to "openly" express their sexuality. As with many other alternate lifestyles, broader networks began forming in the 1980s when participating in networked social groups became more common at home and elsewhere. Such developments in general were described by Markoff in 1990; the linking of computers meant that people thousands of miles apart could feel the intimacy akin to being in a small village together. The popular newsgroup alt.sex.bestiality, said to be in the top 1% of newsgroup interest (i.e. number 50 out of around 5000), – and reputedly started in humor – along with personal bulletin boards and talkers, chief among them Sleepys multiple worlds, Lintilla, and Planes of Existence, were among the first group media of this kind in the late 1980s and early 1990s </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 Coronary artery aneurysm and can you explain it in depth? [/INST] Coronary artery aneurysm is an abnormal dilatation of part of the coronary artery. This rare disorder occurs in about 0.3–4.9% of patients who undergo coronary angiography.

Signs and symptoms
Causes
Acquired causes include atherosclerosis in adults, Kawasaki disease in children and coronary catheterization. With the invention of drug eluting stents, there has been more cases implying stents lead to coronary aneurysms. The pathophysiology, although not completely understood, might be comparable to that of aneurysms of larger vessels </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 Lebers hereditary optic neuropathy and can you explain it in depth? [/INST] Lebers hereditary optic neuropathy (LHON) is a mitochondrially inherited (transmitted from mother to offspring) degeneration of retinal ganglion cells (RGCs) and their axons that leads to an acute or subacute loss of central vision; it predominantly affects young adult males. LHON is  transmitted only through the mother, as it is primarily due to mutations in the mitochondrial (not nuclear) genome, and only the egg contributes mitochondria to the embryo. LHON is usually due to one of three pathogenic mitochondrial DNA (mtDNA) point mutations. These mutations are at nucleotide positions 11778 G to A, 3460 G to A and 14484 T to C, respectively in the ND4, ND1 and ND6 subunit genes of complex I of the oxidative phosphorylation chain in mitochondria. Men cannot pass on the disease to their offspring.

Signs and symptoms
Clinically, there is an acute onset of visual loss, first in one eye, and then a few weeks to months later in the other. Onset is usually young adulthood, but age range at onset from 7-75 is reported. The age of onset is slightly higher in females (range 19–55 years: mean 31.3 years) than males (range 15–53 years: mean 24.3). The male-to-female ratio varies between mutations: 3:1 for 3460 G>A, 6:1 for 11778 G>A and 8:1 for 14484 T>C.This typically evolves to very severe optic atrophy and a permanent decrease of visual acuity. Both eyes become affected either simultaneously (25% of cases) or sequentially (75% of cases) with a median inter-eye delay of 8 weeks. Rarely, only one eye is affected. In the acute stage, lasting a few weeks, the affected eye demonstrates an oedematous appearance of the nerve fiber layer, especially in the arcuate bundles and enlarged or telangiectatic and tortuous peripapillary vessels (microangiopathy). The main features are seen on fundus examination, just before or after the onset of visual loss. A pupillary defect may be visible in the acute stage as well. Examination reveals decreased visual acuity, loss of color vision and a cecocentral scotoma on visual field examination.

LHON with demyelinating lesions or LHON Plus
LHON Plus is a rare variant of the disorder with eye disease together with other conditions. Its symptoms include loss of the brains ability to control the movement of muscles, tremors, and cardiac arrhythmia. Many cases of LHON plus have been compared to multiple sclerosis because of the lack of muscular control and the presence of demyelinating lesions in the CNS. It is therefore a subtype of MS, according to McDonalds definition.

Genetics
Leber hereditary optic neuropathy is a condition related to changes in mitochondrial DNA. Although most DNA is packaged in chromosomes within the nucleus, mitochondria have a distinct mitochondrial genome composed of mtDNA.Mutations in the MT-ND1, MT-ND4, MT-ND4L, and MT-ND6 genes cause Leber hereditary optic neuropathy. These genes code for the NADH dehydrogenase protein involved in the normal mitochondrial function of oxidative phosphorylation. Oxidative phosphorylation uses a series of four large multienzyme complexes, all embedded in the inner mitochondrial membrane, to convert oxygen and simple sugars to energy. Mutations in any of the genes disrupt this process to cause a variety of syndromes depending on the type of mutation and other factors. It remains unclear how these genetic changes cause the death of cells in the optic nerve and lead to the specific features of Leber hereditary optic neuropathy.

Pathophysiology
The eye pathology is limited to the retinal ganglion cell layer, especially the maculopapillary bundle. Degeneration is evident from the retinal ganglion cell bodies to the axonal pathways leading to the lateral geniculate nuclei. Experimental evidence reveals impaired glutamate transport and increased reactive oxygen species (ROS) causing apoptosis of retinal ganglion cells. Also, experiments suggest that normal, non-LHON-affected retinal ganglion cells produce less of the potent superoxide radical than other normal central nervous system neurons. Viral vector experiments that augment superoxide dismutase 2 in LHON cybrids or LHON animal models or use of exogenous glutathione in LHON cybrids have been shown to rescue LHON-affected retinal ganglion cells from apoptotic death. These experiments may in part explain the death of LHON-affected retinal ganglion cells in preference to other central nervous system neurons that also carry LHON-affected mitochondria.

Diagnosis
Without a known family history of LHON the diagnosis usually requires a neuro-ophthalmological evaluation and blood testing for mitochondrial DNA assessment. It is important to exclude other possible causes of vision loss and associated syndromes such as heart electrical conduction system abnormalities.

Treatment
The prognosis for those left untreated is almost always continued significant visual loss in both eyes. Regular corrected visual acuity and perimetry checks are advised for affected people. There is beneficial treatment for some cases of LHON, especially for early-onset disease, and experimental treatment protocols are in progress. Genetic counseling should be offered. Health and lifestyle choices should be reassessed, particularly in light of toxic and nutritional theories of gene expression. Vision aids assistance and work rehabilitation should be used to assist in maintaining employment.For those who carry a LHON mutation, preclinical markers may be used to monitor progress. For example, fundus photography can monitor nerve fiber layer swelling. Optical coherence tomography can be used for more detailed study of retinal nerve fiber layer thickness. Red green color vision testing may detect losses. Contrast sensitivity may be diminished. There could be an abnormal electroretinogram or visual evoked potentials. Neuron-specific enolase and axonal heavy chain neurofilament blood markers may predict conversion to affected status.Cyanocobalamin (a form of B12) should be avoided as it may lead to blindness in LHON patients.Avoiding optic nerve toxins is generally advised, especially tobacco and alcohol. Certain prescription drugs are potential risks, so all drugs should be treated with suspicion and checked before use by those at risk. Ethambutol, in particular, has been implicated as triggering visual loss in carriers of LHON. In fact, toxic and nutritional optic neuropathies may have overlaps with LHON in symptoms, mitochondrial mechanisms of disease and management. And when a patient with LHON or toxic/nutritional optic neuropathy has a hypertensive crisis as a possible complication of the disease process, nitroprusside (trade name: Nipride) should not be used, due to increased risk of optic nerve ischemia in response to this anti-hypertensive.Idebenone  has been shown in a small placebo-controlled trial to have modest benefit in about half of patients. People most likely to respond best were those treated early in onset.
α-Tocotrienol-quinone, a vitamin E metabolite, has had some success in small open-label trials in reversing early onset vision loss.Various treatment approaches have had early trials or been proposed, but so far none with convincing evidence of usefulness or safety for treatment or prevention, including brimonidine, minocycline,   curcumin, glutathione, near infrared light treatment, and viral vector techniques."Three person in vitro fertilization" is a proof-of-concept research technique for preventing mitochondrial disease in developing human fetuses. So far, viable macaque monkeys have been produced. But ethical and knowledge hurdles remain before use of the technique in humans is established.

Idebenone
Idebenone is a short-chain benzoquinone that interacts with the mitochondrial electron transport chain to enhance cellular respiration. When used in people with LHON, it is believed to allow electrons to bypass the dysfunctional complex I. Successful treatment with idebenone was initially reported in a small number of patients.Two large-scale studies have demonstrated the benefits of idebenone. The Rescue of Hereditary Optic Disease Outpatient Study (RHODOS) evaluated the effects of idebenone in 85 patients with LHON who had lost vision within the prior five years. In this study, the group taking idebenone 900 mg per day for 24 weeks showed a slight improvement in visual acuity compared to the placebo group, though the difference was not statistically significant. But patients taking idebenone were protected from further vision loss, whereas the placebo group had a steady decline in visual acuity. Further, people taking idebenone demonstrated preservation of color vision and persistence of the effects of idebenone 30 months after discontinuing therapy. A retrospective analysis of 103 LHON patients by Carelli et al. builds upon these results. This study highlighted that 44 subjects who were treated with idebenone within one year of onset of vision loss had better outcomes, and that these improvements persisted for years.Idebenone, combined with avoidance of smoke and limitation of alcohol intake, is the preferred treatment protocol for people with LHON. Idebenone doses are prescribed to be taken spaced out throughout the day, rather than all at once. For example, to achieve a dose of 900 mg per day, patients take 300 mg three times daily with meals. Idebenone is fat-soluble, and may be taken with a moderate amount of dietary fat in each meal to promote absorption. It is recommended that patients on idebenone also take vitamin C 500 mg daily to keep idebenone in its reduced form, as it is most active in this state.

Estrogen Replacement Therapy
Estrogens have been shown to have a protective role in the pathogenesis of LHON. Experiments using LHON cybrids have demonstrated that the estrogen receptor localizes to the mitochondria where it directly mediates mitochondrial biogenesis. Estrogens upregulate the antioxidant enzyme superoxide dismutase 2 and mitochondrial DNA synthesis. These experiments helped to explain the mechanism behind the lower penetrance of disease among female carriers. While additional factors have been theorized, the protective role of estrogens appears to be a significant contributor.In addition to the experimental evidence, clinical data also points towards the protective role of estrogens. Penetrance among female carriers is substantially lower (between 3 and 8 to 1 male to female ratios depending on the mutation) while average age at onset is significantly higher. Multiple case series of various LHON pedigrees have described female carriers converting after menopause or cessation of hormone replacement therapies. Together, these form a shifting paradigm towards considering reduced estrogen states, such as menopause, as potential triggers of visual loss similar to smoking or excessive alcohol consumption.
Hormone replacement therapy (HRT) is emerging as an effective therapeutic target for female mutation carriers. In one recent case study where the affected female converted following cessation of HRT, idebenone, and HRT were given together. Visual acuity improved much faster than is typically expected. The patients vision returned to 20/40 and 20/60 from 20/60 and 20/200 in the right and left eyes respectively after only one month and was back normal by 8 months compared to the months to years timeframe seen in most cases. While the balance between risks and benefits of HRT remains controversial, the decision to start HRT requires an individualized approach based on the patients context. While not applicable for all post-menopausal women, prophylactic (and therapeutic) HRT should be considered in all female carriers of a known LHON mutation given the substantial risk of vision loss associated with menopause.

Epidemiology
In Northern European populations about one in 9,000 people carries one of the three primary LHON mutations. There is a prevalence of between 1:30,000 to 1:50,000 in Europe.
The LHON ND4 G11778A mutation is the primary mutation in most of the world, with 70% of Northern European cases and 90% of Asian cases. Due to a Founder effect, the LHON ND6 T14484C mutation accounts for 86% of LHON cases in Quebec, Canada.More than 50% of males with a mutation and more than 85% of females with a mutation never experience vision loss or related medical problems. The particular mutation type may predict the likelihood of penetrance, severity of illness and probability of vision recovery in the affected. As a rule of thumb, a woman who harbors a homoplasmic primary LHON mutation has a ~40% risk of having an affected son and a ~10% risk of having an affected daughter.Additional factors may determine whether a person develops the signs and symptoms of this disorder. Environmental factors such as smoking and alcohol use may be involved, though studies of these factors have produced conflicting results. Researchers are also investigating whether changes in additional genes, particularly genes on the X chromosome, contribute to the development of signs and symptoms. The degree of heteroplasmy, the percentage of mitochondria that have mutant alleles, may play a role. Patterns of mitochondrial alleles called haplogroup may also affect expression of mutations.

History
LHON was first described by the German ophthalmologist Theodor Leber (1840–1917) in 1871. In a paper, Leber described four families in which a number of young men had abrupt loss of vision in both eyes either simultaneously or sequentially. This disease was initially thought to be X-linked but was subsequently shown to be mitochondrial. The nature of the causative mutation was first identified in 1988 by Wallace et al. who discovered the guanine (G) to adenosine (A) mutation at nucleotide position 11778 in nine families. This mutation converts a highly conserved arginine to histidine at codon 340 in the NADH dehydrogenase subunit 4 of complex I of the mitochondrial respiratory chain. The other two mutations known to cause this condition were identified in 1991 (G to A point mutation at nucleotide position 3460) and 1992 (thymidine (T) to cytosine (C) mutation at nucleotide 14484). These three mutations account for over 95% of cases: the 11778 mutation accounts for 50-70% of cases, the 14484 mutation for 10-15% and the 3460 mutation for 8-25%.

Research
Human clinical trials are underway at GenSight Biologics (ClinicalTrials.gov # NCT02064569) and the University of Miami (ClinicalTrials.gov # NCT02161380) to examine the safety and efficacy of mitochondrial gene therapy in LHON. In these trials, participants affected by LHON with the G11778A mutation will have a virus expressing the functional version of ND4—the gene mutated in this variant of LHON—injected into one eye. A sham injection will be administered to the other eye for comparison. It is hypothesized that introduction of the viral vector may be able to rescue the function of the mutant gene. Preliminary results have demonstrated tolerability of the injections in a small number of subjects.Stealth BioTherapeutics is investigating the use of elamipretide (MTP-131), a mitochondrial protective agent, as a therapy for LHON. Elamipretide helps stabilize cardiolipin—an important component of mitochondrial inner membranes—and has been shown to reduce damaging reactive oxygen species in animal models.

See also
Amaurosis
Dominant optic atrophy
Glaucoma
Ischemic optic neuropathy
Optic atrophy
Toxic and nutritional optic neuropathy

References
Further reading
Lebers hereditary optic neuropathy at NLM Genetics Home Reference
Kerrison JB, Newman NJ (1997). "Clinical spectrum of Lebers hereditary optic neuropathy" (IFOND reprints) </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 Membranoproliferative glomerulonephritis and can you explain it in depth? [/INST] Membranoproliferative glomerulonephritis (MPGN) is a type of glomerulonephritis caused by deposits in the kidney glomerular mesangium and basement membrane (GBM) thickening, activating complement and damaging the glomeruli.
MPGN accounts for approximately 4% of primary renal causes of nephrotic syndrome in children and 7% in adults.It should not be confused with membranous glomerulonephritis, a condition in which the basement membrane is thickened, but the mesangium is not.

Type
There are three types of MPGN, but this classification is becoming obsolete as the causes of this pattern are becoming understood.

Type I
Type I, the most common by far, is caused by immune complexes depositing in the kidney. It is characterised by subendothelial and mesangial immune deposits.
It is believed to be associated with the classical complement pathway.

Type II
Also called recently as ‘C3 nephropathy’
The preferred name is "dense deposit disease." Most cases of dense deposit disease do not show a membranoproliferative pattern. A 2012 review considers DDD to be in a continuum with C3 glomerulonephritis, one reason the use of the type I to type III classification system is falling out of favour.Most cases are associated with the dysregulation of the alternative complement pathway.DDD is associated with deposition of complement C3 within the glomeruli with little or no staining for immunoglobulin. The presence of C3 without significant immunoglobulin suggested to early investigators that DDD was due to abnormal activation of the complement alternative pathway (AP). There is now strong evidence that DDD is caused by uncontrolled AP activation.Spontaneous remissions of MPGN II are rare; approximately half of those affected with MPGN II will progress to end stage renal disease within ten years.In many cases, people with MPGN II can develop drusen caused by deposits within Bruchs membrane beneath the retinal pigment epithelium of the eye. Over time, vision can deteriorate, and subretinal neovascular membranes, macular detachment, and central serous retinopathy can develop.

Type III
Type III is very rare, it is characterized by a mixture of subepithelial and subendothelial immune and/or complement deposits. These deposits elicit an immune response, causing damage to cells and structures within their vicinity. Has similar pathological findings of Type I disease.A candidate gene has been identified on chromosome 1.Complement component 3 is seen under immunofluorescence </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 Cholinergic urticaria and can you explain it in depth? [/INST] Cholinergic urticaria (CU) presents with tiny very itchy wheals and small bumps on a reddish background.It is a type of physical urticaria (or hives) that appears when a person is sweating or their core body temperature increases.

Symptoms
Cholinergic urticaria typically presents with a number of small, short-lasting hives but may also involve cutaneous inflammation (wheals) and pain which develops usually in response to exercise, bathing, staying in a heated environment, or emotional stress. Although the symptoms subside rapidly, commonly within 1 hour, cholinergic urticaria may significantly impair quality of life, especially in relation to sporting activities.

Causes
Sweat hypersensitivity
Acquired anhidrosis and/or hypohidrosis
Idiopathic
Opioid use
Cholinesterase inhibitors

Subtypes
Sweat hypersensitivity
This subtype of CU refers to those who are hypersensitive to their own sweat.

Diagnosis
Diagnosis is made by injecting autologous (the persons own) sweat into the skin.

Features
The hives are observed to coincide with perspiration points of sweating.

Pathophysiology
Tanaka et al. found that the sweat hyper-sensitivities of CU and atopic dermatitis seem to be virtually the same, and therefore, the sweat-induced histamine release from basophils may also be mediated by a specific IgE for sweat in atopic dermatitis as well as CU.

Treatment
Proposed first-line treatment: Rapid desensitization protocol using autologous sweat.
Non-pharmacological treatment: Forced perspiration by excessive body warming (hot bath or exercise) used daily may reduce the symptoms through exhaustion of inflammatory mediators. This non-pharmacological treatment is contraindicated in those with CU as a result of hypohidrosis (see below).
Antihistamines are a commonly prescribed first-line treatment for conventional urticaria, but its effectiveness in the treatment of CU is rather limited in most cases. Some research suggests that first-generation antihistamines with anticholinergic properties such as diphenhydramine are most successful at treating CU.
Treatment(s) with mixed success: omalizumab (anti-IgE therapy), danazol (synthetic androgen), propranolol (beta blocker), zileuton (antileukotriene).

Acquired anhidrosis and/or hypohidrosis
This subtype of CU refers to those who have abnormally reduced sweating.

Diagnosis
Sweat is readily visualized by a topical indicator such as iodinated starch or sodium alizarin sulphonate. Both undergo a dramatic colour change when moistened by sweat. A thermoregulatory sweat test evaluates the bodys response to a thermal stimulus by inducing sweating through the use of a hot box ⁄ room, thermal blanket or exercise. Failure of the topical indicator to undergo a colour change during thermoregulatory sweat testing can indicate anhidrosis and/or hypohidrosis (see Minor test).A skin biopsy may reveal cellular infiltrates in sweat glands or ducts.

Features
Severe heat intolerance (e.g., nausea, dizziness, and headache), and tingling, pricking, pinchy or burning pain over the entire body on exposure to hot environments or prolonged exercise which improve after cooling the body. Occurs in the absence of any causative skin, metabolic, or neurological disorders.

Pathophysiology
The wheals, hypohidrosis, and pain seems to result from the low expression levels of acetylcholinesterase (AchE) and cholinergic receptor, muscarinic 3 (CHRM3) in the eccrine gland epithelial cells.
Elevated expression levels of CCL2/MCP-1, CCL5/RANTES and CCL17/TARC which result in chemoattracted CD4+ and CD8+ T cell populations to the surrounding area may be responsible for exerting a downmodulatory effect on the AchE and CHRM3 expressions.
Corticosteroid inhibits the expressions of CCL2/MCP-1, CCL5/RANTES and CCL17/TARC. This further support the notion that CCL2/MCP-1, CCL5/RANTES and CCL17/TARC play a crucial role.

Treatment
First-line treatment:  H1RAs are first-line therapy for patients with CholU, but many patients show only a mild to moderate response to standard H1RA doses </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 Lichen ruber moniliformis 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 Neurogenic shock and can you explain it in depth? [/INST] Neurogenic shock is a distributive type of shock resulting in hypotension (low blood pressure), often with bradycardia (slowed heart rate), caused by disruption of autonomic nervous system pathways. It can occur after damage to the central nervous system, such as spinal cord injury and traumatic brain injury. Low blood pressure occurs due to decreased systemic vascular resistance resulting from loss of sympathetic tone, which in turn causes blood pooling within the extremities rather than being available to circulate throughout the body. The slowed heart rate results from a vagal response unopposed by a sympathetic nervous system (SNS) response.  Such cardiovascular instability is exacerbated by hypoxia, or treatment with endotracheal or endobronchial suction used to prevent pulmonary aspiration.Neurogenic shock is a potentially devastating complication, leading to organ dysfunction and death if not promptly recognized and treated.It is not to be confused with spinal shock, which is not circulatory in nature.

Signs and symptoms
Instantaneous hypotension due to sudden, massive vasodilation and decrease in blood oxygen saturation
Warm, flushed skin due to vasodilation and inability to constrict blood vessels.
Priapism, also due to vasodilation
The patient will be unable to mount a tachycardic response, and often becomes bradycardic
If the injury is below cervical vertebrae C5, the patient will exhibit diaphragmatic breathing due to loss of nervous control of the intercostal muscles (which are required for thoracic breathing).
If the injury is above C3, the patient will go into respiratory arrest immediately following the injury, due to loss of nervous control of the diaphragm.

Causes
Neurogenic shock can result from severe central nervous system damage (brain injury, cervical or high thoracic spinal cord). In simple terms, the trauma causes a sudden loss of background SNS stimulation to the blood vessels. This causes them to relax (vasodilation) resulting in a sudden decrease in blood pressure (secondary to a decrease in peripheral vascular resistance).
Neurogenic shock results from damage to the spinal cord above the level of the 6th thoracic vertebra.  It is found in about half of people who have a spinal cord injury within the first 24 hours, and usually persists for one to three weeks.Neurogenic shock may be caused by severe brain injury. However, in case of increased intracranial pressure, according to the Cushing triad, blood pressure will be increased (unless decreased from hypovolemia), respirations will be irregular and bradycardia will also be a feature.

Pathophysiology
Neurogenic shock is diagnosed based on a persons symptoms and blood pressure levels.
Neurogenic shocks presentation includes:- warm and pink skin
- labored breathing
- low blood pressure
- dizziness
- anxiety
- history of trauma to head or upper spine.
- if the injury is to the head or neck, hoarseness or difficulty swallowing may occur.
Symptoms of neurogenic shock are differentiated from other forms of shock by the lack of signs of the compensatory mechanisms triggered by the SNS, usual in other forms of shock. This SNS response is effected via release of epinephrine and norepinephrine, and signs of these neurotransmitters activity are typically absent  where shock is of neurogenic origin. Those signs - in non-neurogenic shock -  would include: tachycardia (increased heart rate), tachypnea (increased breath rate), sweating, and adaptive vasoconstriction, which serves in other forms of shock to shunt blood away from the extremities and to the vital organs.
In neurogenic shock, the body loses its ability to activate the SNS so that only parasympathetic tone remains.  The resulting loss of sympathetic tone, which plays a major role in other forms of shock, is responsible for the unique and atypical features mentioned above.<ref name=incidence>Mallek JT; Inaba K;  et al </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 Megalencephalic leukoencephalopathy with subcortical cysts and can you explain it in depth? [/INST] Megalencephalic leukoencephalopathy with subcortical cysts (MLC, or Van der Knaap disease) is a form of hereditary CNS demyelinating disease.  It belongs to a group of disorders called leukodystrophies. It is characterized by early-onset enlargement of the head (macrocephaly) as well as delayed-onset neurological deterioration to include spasticity, epilepsy, and lack of muscular coordination. MLC does not appear to be a disease that is fatal at birth or early in life despite its symptoms, although the number of patients throughout history known to have the disease is fairly limited.It belongs to a group of disorders called leukodystrophies. A series of cases with megalencephalic leukodystrophy were described by the Indian neurologist Bhim Sen Singhal (1933-) in 1991. However, it is sometimes referred to as Van der Knaap disease after the Dutch neurologist Marjo van der Knaap who described another series of cases with clinical and radiological features in 1995.There are three types of Megalencephalic leukoencephalopathy distinguished by the affected gene: Type 1 caused by autosomal recessive mutations on the MLC1 gene, Type 2A an autosomal recessive mutation on the HEPACAM gene, and Type 2B an autosomal dominant mutation on the HEPACAM gene.

Signs and Symptoms
Head
Macrocephaly
The disease is characterized by megalencephaly, the enlargement of the brain, which is followed by an increase in the size of the actual head.
Central Nervous System
Megalencephaly
The M in MLC stands for “megalencephaly”, the enlargement of the brain
Ataxia
Slow, progressive and early-onset cerebellar ataxia has been noted in many patients
Spasticity
Patients with MLC often have muscle spasms
Seizures
Delay in motor development
 Mild mental retardation
Diffuse swelling of cerebral white matter
 Large subcortical cysts in frontal and temporal lobes
Patients develop cysts on the tips of the temporal and subcortical area
Diffuse spongiform leukoencephalopathy
Vacuolizing myelinopathy
The protective myelin sheath on neurons pulls away from their cells forming small holes in nerve fibers – in turn affecting coordination and walking ability.

Genetics
It is associated with MLC1. The MLC1 gene is located in chromosome 22q13.33 and is in the genomic coordinates 22:50,059,390 – 50,085874. The gene contains 12 exons and that contain a start codon in exon 2 and an untranslated region in the 3’ end. The MLC1 gene product is a 377 amino acid protein highly expressed in the brain. The disease is caused by a homozygous or compound heterozygous mutation in the gene, MLC1. Previous research indicates that deficiency of cell surface protein expression of the MLC1 gene is the basis for the disorder. The mutant protein is expressed in intracellular compartments reducing the membrane surface expression when compared to the wild type.

Diagnosis
Diagnosis of Megalencephalic leukoencephalopathy with subcortical cysts is made with a combination of physical and clinical evaluations </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 Pilotto syndrome 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 Sphingolipidoses 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 Wasting and can you explain it in depth? [/INST] In medicine, wasting, also known as wasting syndrome, refers to the process by which a debilitating disease causes muscle and fat tissue to "waste" away </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 Seal finger 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 Palindromic rheumatism and can you explain it in depth? [/INST] Palindromic rheumatism (PR) is a syndrome characterised by recurrent, self-resolving inflammatory attacks in and around the joints, consists of arthritis or periarticular soft tissue inflammation. The course is often acute onset, with sudden and rapidly developing attacks or flares. There is pain, redness, swelling, and disability of one or multiple joints. The interval between recurrent palindromic attacks and the length of an attack is extremely variable from few hours to days. Attacks may become more frequent with time but there is no joint damage after attacks. It is thought to be an autoimmune disease, possibly an abortive form of rheumatoid arthritis.

Presentation
The exact prevalence of palindromic rheumatism in general population is unknown, and this condition is often considered a rare disease by nonrheumatologists. However, recent Canadian study showed that the incidence of PR in a cohort of incident arthritis was one case of PR for every 1.8 cases of rheumatoid arthritis (RA). The incidence of PR is less than that of RA but is not as rare as that was thought to be.
Palindromic rheumatism is a syndrome presented with inflammatory para-arthritis (soft tissue rheumatism) and inflammatory arthritis both of which cause sudden inflammation in one or several joints or soft tissue around joints. The flares usually present with  mono- or oligo-articular involvement, which have onset over hours and last a few hours to a few days, and then go away completely. However episodes of recurrence form a pattern, with symptom-free periods between attacks lasting for weeks to months. The most commonly involved joints were knees, metacarpophalangeals and proximal interphalangeals.  Constitutionally, there may or may not be a fever, and swelling of the joints. The soft tissues are involved with swelling of the periarticular tissues, especially heel pads and finger pads. Nodules may be found in the subcutaneous tissues. The frequency of attacks may be variable over the course but there is no joint damage after attacks.It typically affects people between the ages of 20 and 50. One study showed an average age of onset of 49.A population cohort study in Taiwan suggested that patients with PR had an increased risk of developing rheumatoid arthritis, systemic lupus erythematosus, Sjogrens syndrome, systemic sclerosis, and polymyositis.

Causes
Palindromic rheumatism is a disease of unknown cause. It has been suggested that it is an abortive form of rheumatoid arthritis (RA), since anti-cyclic citrullinated peptide antibodies (anti-CCP) and antikeratin antibodies (AKA) are present in a high proportion of patients, as is the case in rheumatoid arthritis. Unlike RA and some other forms of arthritis, palindromic rheumatism affects men and women equally. Palindromic rheumatism is frequently the presentation for Whipple disease which is caused by the infectious agent Tropheryma whipplei (formerly T. whippelii).

Diagnosis
Due to the symptoms of palindromic arthritis and the nature of the attacks, diagnosis can be difficult or take a long time. The symptoms can be similar to many other forms of arthritis or other autoimmune diseases </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 Craniometaphyseal dysplasia 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 Lymphocytic choriomeningitis and can you explain it in depth? [/INST] Lymphocytic choriomeningitis (LCM) is a rodent-borne viral infectious disease that presents as aseptic meningitis, encephalitis or meningoencephalitis. Its causative agent is lymphocytic choriomeningitis mammarenavirus (LCMV), a member of the family Arenaviridae. The name was coined by Charles Armstrong in 1934.Lymphocytic choriomeningitis (LCM) is "a viral infection of the membranes surrounding the brain and spinal cord and of the cerebrospinal fluid". The name is based on the tendency of an individual to have abnormally high levels of lymphocytes during infection.  Choriomeningitis is "cerebral meningitis in which there is marked cellular infiltration of the meninges, often with a lymphocytic infiltration of the choroid plexuses".

Signs and symptoms
LCMV infection manifests itself in a wide range of clinical symptoms, and may even be asymptomatic for immunocompetent individuals. Onset typically occurs between one or two weeks after exposure to the virus and is followed by a biphasic febrile illness.  During the initial or prodromal phase, which may last up to a week, common symptoms include fever, lack of appetite, headache, muscle aches, malaise, nausea, and/or vomiting.  Less frequent symptoms include a sore throat and cough, as well as joint, chest, and parotid pain.  The onset of the second phase occurs several days after recovery, and consists of symptoms of meningitis or encephalitis.  Pathological findings during the first stage consist of leukopenia and thrombocytopenia.  During the second phase, typical findings include elevated protein levels, increased leukocyte count, or a decrease in glucose levels of the cerebrospinal fluid).Occasionally, a patient improves for a few days, then relapses with aseptic meningitis, or very rarely, meningoencephalitis.
Patients with meningitis may have a stiff neck, fever, headache, myalgia, nausea and malaise. In some occasions, meningitis occurs without a prodromal syndrome. Meningoencephalitis is characterized by more profound neurological signs such as confusion, drowsiness, sensory abnormalities and motor signs. Under reported complications include myelitis, Guillain–Barré-type syndrome, cranial nerve palsies, transient or permanent hydrocephalus, sensorineural hearing loss, orchitis, arthritis and parotitis. LCMV infections have also been associated with pancreatitis, pneumonitis, myocarditis and pericarditis. The entire illness usually lasts 1 to 3 weeks, nonetheless, temporary or permanent neurological damage is possible in all central nervous system infections, especially in cases of meningoencephalitis. Chronic infections have not been reported in humans and deaths rarely occur.

Cause
Virus biology
There are several strains of LCM virus, among which the most widely used are LCMV Armstrong and LCMV Clone 13. Armstrong is the original virus strain which was isolated from the brain by Charles Armstrong in 1934. It triggers a vigorous cytotoxic T lymphocytes(CTL) response and thus, it is cleared rapidly by the host. This is referred to as acute (Armstrong) LCMV infection. On the other hand, Clone 13 is a variant of the Armstrong viral strain, isolated from the spleen and is consequently tropic for visceral organs. It was first isolated from mice which sustained a persistent LCMV infection from birth. This variant potentiates a less vigorous CTL response in the immune system, and thus can ultimately persist in the host organism indefinitely. The latter is referred to as chronic (Clone 13) LCMV infection.LCMV is a spherical enveloped virus with a diameter between 60 and 300 nm. The helical nucleocapsid contains an RNA genome consisting of two negative single-stranded RNA segments. The negative RNA strand, complementary to the necessary mRNA strand, indicates that it must first be transcribed into a positive mRNA strand before it can be translated into the required proteins. The L strand is ambisense RNA, encoding multiple proteins in opposite directions, separated by an intergenic region. It is approximately 7.2 kb in size and encodes a high-molecular-mass protein (L; 200 kDa) and an 11 kDa small polypeptide Z with unknown function and a ring finger motif. The viral RNA-dependent RNA polymerase is encoded by the L protein which contains conserved characteristic motifs throughout all the RNA-dependent, RNA-polymerases.  The S strand is ambisense and approximately 3.4 kb in size. It encodes the two main structural proteins: nucleo-protein (NP) (63 kDa) and glycoprotein precursor complex (GPC) (75kDa). The latter undergoes posttranslational cleavage at two separate steps: first in the endoplasmic reticulum, where following translation on the membrane, the stable signal peptide region is cleaved by signal peptidase (SPase); notably, this signal peptide is retained, in contrast to other viruses. The second cleavage occurs at the Golgi apparatus, where GP1-GP2, having been trafficked to the Golgi, is cleaved into separate mature viral glycoproteins, GP1 and GP2 (with cleavage mediated by SK1-/PS1 or MTBPS1). The spikes present on the virion envelope are dictated by tetramer formation of GP-1 and GP-2.When LCMV attacks a cell, the process of replication starts by attachment of the virus to host receptors through its surface glycoproteins. It is then endocytosed into a vesicle inside the host cell and creates a fusion of the virus and vesicle membranes. The ribonucleocapsid is then released in the cytoplasm. The RNA-dependent, RNA-polymerase brought along with the virus initially binds to a promoter on the L and S segments and begins transcription from negative-stranded to a positive-stranded mRNA. The formation of a strong hairpin sequence at the end of each gene terminates transcription. The mRNA strands are capped by the RNA-dependent, RNA-polymerase in the cytoplasm and are then subsequently translated into the four proteins essential for LCMV assembly. The ribonucleocapsid interacts with the Z matrix protein and buds on the cell membrane, releasing the virion out from the infected cell.
The first arenavirus, Lymphocytic choriomeningitis mammarenavirus (LCMV), was isolated in 1933 by Charles Armstrong during a study of an epidemic in St. Louis. Although not the cause of the outbreak, LCMV was found to be a cause of nonbacterial or aseptic meningitis.In 1996, Peter Doherty and Rolf Zinkernagel shared the Nobel Prize in Medicine and Physiology, for their work with LCMV which led to a fundamental understanding of the adaptive immune response, MHC restriction. In the 1970s, studies concerning the importance of MHC locus were done exclusively in transplantation and tumor rejection. Taking this into consideration, Doherty and Zinkernagel were working on the response of mice to virus infections. They observed that T-cell receptors must recognise a complex of foreign antigen and an MHC antigen in order to destroy infected cells. Their key experiment involved harvesting of splenocytes containing LCMV-specific cytotoxic T lymphocytes(CTL) from an infected mouse strain A. These were then mixed in vitro with virus infected fibroblasts or macrophages from two different mouse strains, A and B. By the method of Cr-release cytotoxicity assay, thereby tagging the CTL with chromium-51 (Cr-51), the CTL destruction of infected cells was quantified by release of Cr-51. The results showed that CTL killed only the infected cells from strain A, and they did not lyse uninfected cells or infected cells from strain B. They concluded that these virus specific CTLs only lyse cells carrying the same molecules of the major histocompatibility site (MHC) as the CTLs themselves. Thus, the virus-specific CTLs are "MHC-restricted". This discovery lead to a greater understanding of an important aspect of the immune system.

Spread
LCMV is naturally spread by the common house mouse, Mus musculus. Once infected, these mice can become chronically infected by maintaining virus in their blood or persistently shedding virus in their urine.
Chronically infected female mice usually transmit infection to their offspring (vertical transmission), which in turn become chronically infected. Other modes of mouse-to-mouse transmission include nasal secretions, milk from infected dams, bites, and during social grooming within mouse communities. Airborne transmission also occurs.The virus seems to be relatively resistant to drying and therefore humans can become infected by inhaling infectious aerosolized particles of rodent urine, feces, or saliva, by ingesting food contaminated with virus, by contamination of mucous membranes with infected body fluids, or by directly exposing cuts or other open wounds to virus-infected blood.  The only documented cases of transmission from animals have occurred between humans and mice or hamsters.Cases of lymphocytic choriomeningitis have been reported in North and South America, Europe, Australia, and Japan, particularly during the 1900s. However, infection may occur wherever an infected rodent host population exists. LCMV occurs worldwide and its natural host, the rodent, has become established on all continents, except Antarctica.Seroprevalence is approximately 5% (0.7–4.7%) of the US population. It tends to be more common among lower socio-economic groupings, probably reflecting more frequent and direct contacts with mice.  However, obtaining an accurate sense of prevalence by geographic region is difficult due to underreporting.

Congenital infection
Lymphocytic choriomeningitis is a particular concern in obstetrics, as vertical transmission is known to occur. For immunocompetent mothers, there is no significant threat, but the virus has damaging effects upon the fetus.  If infection occurs during the first trimester, LCMV results in an increased risk of spontaneous abortion. Later congenital infection may lead to malformations such as intracranial calcifications, hydrocephalus, microcephaly or macrocephaly, intellectual disabilities, and seizures. Other findings include chorioretinal scars, and optic atrophy. Chorioretinitis, which is followed by chorioretinal scarring, is the most common ocular lesion. Mortality among infants is approximately 30%.  Among the survivors, two-thirds have lasting neurologic abnormalities.Other ocular defects including optic atrophy, microphthalmia, vitreitis, leukokoria and cataracts can also be seen. Most of the infants in one case series were of normal birth weight, although 30% were underweight. Aspiration pneumonia can be a fatal complication. Infants who survive may have severe neurological defects including epilepsy, impaired coordination, visual loss or blindness, spastic diplegia or quadriparesis/quadriplegia, delayed development and intellectual disability. Less severe cases with isolated cerebellar hypoplasia and symptoms of ataxia and jitteriness have been reported occasionally. There have also been rare cases with evidence of chorioretinitis but without neurological signs. Systemic signs seem to be rare, but hepatosplenomegaly, thrombocytopenia and hyperbilirubinemia have been documented in a few cases, and skin blisters were reported in one infant.If a woman has come into contact with a rodent during pregnancy and LCM symptoms are manifested, a blood test is available to determine previous or current infection.  A history of infection does not pose a risk for future pregnancies.

Organ donation
Patients infected in solid organ transplants have developed a severe fatal illness, starting within weeks of the transplant. In all reported cases, the initial symptoms included fever, lethargy, anorexia and leukopenia, and quickly progressed to multisystem organ failure, hepatic insufficiency or severe hepatitis, dysfunction of the transplanted organ, coagulopathy, hypoxia, multiple bacteremias and shock. Localized rash and diarrhea were also seen in some patients. Nearly all cases have been fatal.In May 2005, four solid-organ transplant recipients contracted an illness that was later diagnosed as lymphocytic choriomeningitis. All received organs from a common donor, and within a month of transplantation, three of the four recipients had died as a result of the viral infection. Epidemiologic investigation traced the source to a pet hamster that the organ donor had recently purchased from a Rhode Island pet store. Similar cases occurred in Massachusetts in 2008, and Australia in 2013. There is not a LCMV infection test that is approved by the Food and Drug Administration for organ donor screening.  The Morbidity and Mortality Weekly Report advises health-care providers to "consider LCMV infection in patients with aseptic meningitis and encephalitis and in organ transplant recipients with unexplained fever, hepatitis, or multisystem organ failure."

Diagnosis
Current or previous infection can be detected through a blood test. However, some authors note that such complement-fixation tests are insensitive and should not be used for diagnosis. Dr. Clare A. Dykewicz, et al. state,

Infection with LCMV should be considered in the differential diagnosis of any compatible, severe viral infection or aseptic meningitis, especially when there is a history of occupational exposure to laboratory rodents. Timeliness of diagnosis is important not only in expediting treatment of infected persons, but also in preventing further LCMV transmission to other workers and animals.Clinical diagnosis of LCM can be made by the history of prodrome symptoms and by considering the period of time before the onset of meningitis symptoms, typically 15–21 days for LCM.Pathological diagnosis of congenital infection is performed using either an immunofluorescent antibody (IFA) test or an enzyme immunoassay to detect specific antibody in blood or cerebrospinal fluid.  A PCR assay has been recently developed which may be used in the future for prenatal diagnosis; however, the virus is not always present in the blood or CSF when the affected child is born." Diagnoses is subject to methodological shortcomings in regard to specificity and sensitivity of assays used. For this reason, LCMV may be more common than is realized.Another detection assay is the reverse transcription polymerase chain reaction (RT-PCR) tests which may detect nucleic acids in the blood and cerebrospinal fluid.(CSF) Virus isolation is not used for diagnosis in most cases but it can be isolated from the blood or nasopharyngeal fluid early in the course of the disease, or from CSF in patients with meningitis. LCMV can be grown in a variety of cell lines including BHK21, L and Vero cells, and it may be identified with immuno-fluorescence. A diagnosis can also be made by the intracerebral inoculation of blood or CSF into mice.

Prevention
LCMV is susceptible to most detergents and disinfectants including 1% sodium hypochlorite, 70%
ethanol, 2% glutaraldehyde and formaldehyde. The effectiveness of infection quickly declines below pH 5.5 and above pH 8.5. In addition, LCMV can also be inactivated by heat, ultraviolet light or gamma irradiation.Studies have indicated that human infection of the virus occurs primarily during the fall and winter months, presumably due to the movement of mice indoors. Several measures can be taken to prevent exposure to LCM from wild rodents in the home. A checklist of precautions is provided by the Centers for Disease Control and Prevention, providing tips for sealing the home to keep rodents out, using traps to eliminate existing rodents, and maintaining a clean, healthy home. New technology reflects a growing trend for more humane means of eliminating rodents.  Products include devices that emit ultrasonic sound that allegedly irritates mice and drives them away, and more swift, painless means of death such as mini electrocution or gas chambers.  However, the traditional snap trap remains an economic and popular option.

Treatment
Treatment is symptomatic and supportive. Children with hydrocephalus often need a ventriculoperitoneal shunt. Nucleoside analog ribavirin is used in some cases due to the inhibitory effect the agent has in vitro on arenaviruses. However, there is not sufficient evidence for efficacy in humans to support routine use. The only survivor of a transplant-associated LCMV infection was treated with ribavirin and simultaneous tapering of the immunosuppressive medications. Early and intravenous ribavirin treatment is required for maximal efficacy, and it can produce considerable side effects. Ribavirin has not been evaluated yet in controlled clinical trials.Use of ribavirin during pregnancy is generally not recommended, as some studies indicate the possibility of teratogenic effects. If aseptic meningitis, encephalitis, or meningoencephalitis develops in consequence to LCMV, hospitalization and supportive treatment may be required.  In some circumstances, anti-inflammatory drugs may also be considered. In general, mortality is less than one percent.

Prognosis
Lymphocytic choriomeningitis is not a commonly reported infection in humans, though most infections are mild and are often never diagnosed. Serological surveys suggest that approximately 1–5% of the population in the U.S. and Europe has antibodies to LCMV. The prevalence varies with the living conditions and exposure to mice, and it has been higher in the past due to lower standards of living. The island of Vir in Croatia is one of the biggest described endemic places of origin of LCMV in the world, with IFA testing having found LCMV antibodies in 36% of the population. Individuals with the highest risk of infection are laboratory personnel who handle rodents or infected cells. Temperature and time of year is also a critical factor that contributes to the number of LCMV infections, particularly during fall and winter when mice tend to move indoors. Approximately 10–20% of the cases in immunocompetent individuals are thought to progress to neurological disease, mainly as aseptic meningitis. The overall case fatality rate is less than 1% and people with complications, including meningitis, almost always recover completely. Rare cases of meningoencephalitis have also been reported. More severe disease is likely to occur in people who are immunosuppressed.More than 50 infants with congenital LCMV infection have been reported worldwide. The probability that a woman will become infected after being exposed to rodents, the frequency with which LCMV crosses the placenta, and the likelihood of clinical signs among these infants are still poorly understood. In one study, antibodies to LCMV were detected in 0.8% of normal infants, 2.7% of infants with neurological signs and 30% of infants with hydrocephalus. In Argentina, no congenital LCMV infections were reported among 288 healthy mothers and their infants. However, one study found that two of 95 children in a home for people with severe mental disabilities had been infected with this virus. The prognosis for severely affected infants appears to be poor. In one series, 35% of infants diagnosed with congenital infections had died by the age of 21 months.Transplant-acquired lymphocytic choriomeningitis proves to have a very high morbidity and mortality rate. In the three clusters reported in the U.S. from 2005 to 2010, nine of the ten infected recipients died. One donor had been infected from a recently acquired pet hamster while the sources of the virus in the other cases were unknown.

Epidemiology
LCMV has been isolated from fleas, ticks, cockroaches, Culicoides and Aedes mosquitoes. Ticks, lice and mosquitoes have been shown to transmit this virus mechanically in the laboratory. The presence of LCMV in laboratories may cause serious long-term repercussions to worker safety. In 1989, an outbreak among humans occurred in a US cancer research institute that studied the effects of various therapeutic and diagnostic agents in animal models. Such agents had been developed in the animal care facility, which periodically screened sentinel animals for extraneous infection. Due to an oversight, no sentinel animals were monitored from August 1988 to March 1989.  When testing resumed, LCMV antibodies were found in the oldest sentinel hamsters. Several workers reported symptoms consistent with LCMV infection, leading to an investigation. Blood samples were obtained and tested for LCMV antibodies. Of the 82 workers that were tested, seven had definite serologic evidence of past LCMV infection, and two were hospitalized for an acute febrile illness.  All seven reported direct contact with the animals at the institute.An additional hazard associated with LCMV in laboratories misleading experimental results. Interference with research may involve:

[Inhibition of] tumor induction due to polyoma virus, and mammary tumor virus in the mouse, and [interference] with transplantable leukaemia in the guinea pig and the mouse. Infection is associated with depression of cellular immunity in the mouse. Rejection of cutaneous grafts or transplantable tumors may be delayed. In addition, infection will increase the sensitivity of the mouse to ectromelia virus and to bacterial endotoxins.Reported outbreaks have decreased, perhaps due to improved biohazard management in laboratories. However, it is possible that sporadic cases have been overlooked because of the wide range of clinical presentations. Clare A. Dykewicz, et al. recommend vigilant screening laboratory animals to be used in research facilities either through serum samples or cell line aliquots, as well as ensuring adequate ventilation in housing areas and use of appropriate sanitation products. Other practices to reduce cross-contamination in rodents include washing hands or changing gloves between animal care activities, thoroughly decontaminating cages before reusing them, and avoiding housing healthy rodents in the vicinity of potentially infected rodents.

Other animals
Although the house mouse (Mus musculus) is the primary reservoir host for LCMV, it is also often found in the wood mouse (Apodemus sylvaticus) and the yellow-necked mouse (Apodemus flavicollis). Hamster populations can act as reservoir hosts. Other rodents including guinea pigs, rats and chinchillas can be infected but do not appear to maintain the virus. LCMV has been shown to cause illness in New World primates such as macaques, marmosets and tamarins. Infections have also been reported in rabbits, dogs and pigs. After experimental inoculation, the incubation period in adult mice is 5 to 6 days. Congenitally or neonatally infected mice and hamsters do not become symptomatic for several months or longer.

Mice
A study conducted by John Hotchin and Heribert Weigand, of the New York State Department of Health, concluded, "The age of the mouse when first exposed to the virus determines its immune response."  If LCMV infection occurs in utero or within the first few hours of life, during the immunologically unresponsive period, the mouse will develop immune tolerance.  The virus will continue to proliferate for an indefinite time.  However, if a mouse is infected after the neonatal period, when the immune system is responsive, the immune response is active.  This immunological conflict can result in one of three ways; immunological paralysis, significant or complete suppression of virus with immunity to reinfection, or death.  Mice that are infected after the neonatal period often pass through a "runt" stage, which may last for several weeks.  Clinical symptoms include excitability, weight loss, and severe retardation of growth and hair development. In general, as the period of time between birth and inoculation decreases, less disease and mortality occurs.Post mortem lesions in mice show signs of hepatomegaly, splenomegaly, lymphadenopathy, and swollen or shrunken and pitted kidneys due to glomerulonephritis. Histological findings in persistently infected mice often show chronic glomerulonephritis. In these mice, and some hamsters, vasculitis and lymphocytic infiltrates in many organs and tissues including the liver, spleen, lung, kidneys, pancreas, blood vessels, meninges and brain are present.

Hamsters
Pathogenesis occurs in the same manner in hamsters as in mice. Symptoms in hamsters are highly variable, and typically indicate that the pet has been infected and shedding the virus for several months.  Early signs may include inactivity, loss of appetite, and a rough coat.  As the disease progresses, the animal may experience weight loss, hunched posture, inflammation around the eyes, and eventually death.  Alternatively, some infected hamsters may be asymptomatic.

Rats
Experimental intracerebral infection of suckling rats results in microcephaly, retinitis and the destruction of several brain regions, leading to permanent abnormalities of movement, coordination, vision and behavior.

Primates
LCMV causes callitrichid hepatitis in New World primates. The onset of the infection is nonspecific and may include fever, anorexia, dyspnea, weakness and lethargy. Jaundice is characteristic and petechial hemorrhages may develop. Prostration and death usually follow.Necropsy lesions in primates with callitrichid hepatitis show signs of jaundice, hepatomegaly, splenomegaly, and subcutaneous and intramuscular hemorrhages. Pleural and pericardial effusion, sometimes sanguineous, has also been reported. On histology, multifocal necrosis with acidophilic bodies and mild inflammatory infiltrates are typically found in the liver.

Diagnosis
As in humans, the sensitivity of testing methods for rodents contributes to the accuracy of diagnosis.  LCMV is typically identified through serology. However, in an endemically infected colony, more practical methods include MAP (mouse antibody production) and PCR testing. Another means of diagnosis is introducing a known naïve adult mouse to the suspect rodent colony. The introduced mouse will seroconvert, allowing use of immunofluorescence antibody (IFA), MFIA or ELISA to detect antibodies.

Treatment
Immunosuppressive therapy has been effective in halting the disease for laboratory animals.

Morbidity and mortality
LCMV infections are focal Estimates of its prevalence in wild mouse populations range from 0% to 60%, with an average prevalence of 9%. The incidence of LCMV in pet rodents is unknown, yet very few human cases have been associated with exposure to pets. In the transplant-associated cases linked to a pet hamster in 2005, two other hamsters and a guinea pig at the pet shop, and approximately 4% of the hamsters at the distributor, were also infected. Morbidity and mortality rates vary with the species of animal and its age at infection, as well as the strain of the virus and route of exposure. Neonatally and congenitally infected mice remain asymptomatic for many months, but the onset of glomerulonephritis reduces overall life expectancy. The morbidity rate in naturally infected post-neonatal mice is unknown; however, subclinical disease may be the most common form, as few natural outbreaks have been reported. In hamsters, approximately half of all congenitally infected animals clear the virus when they are approximately three months old and remain healthy; the remaining animals develop chronic disease. Hamsters infected as adults usually remain asymptomatic. Callitrichid hepatitis is reported to be highly fatal in naturally infected marmosets and tamarins in zoos. Since 1980, 12 outbreaks with 57 deaths have been reported in the U.S. In experimentally infected rhesusmacaques, three of four animals became fatally ill when inoculation was by the intravenous route. In contrast, inoculation by the intragastric route usually led to asymptomatic infections, with occasional disease and few deaths.

In pets
Pet rodents are not known to be natural reservoirs for lymphocytic choriomeningitis virus.  However, pets can become vectors if they are exposed to wild house mice in a breeding facility, pet store, or home. Such infections are rare. To date, (January 2017) documented infections in humans have occurred only after introduction to infected mice, guinea pigs, and hamsters, with the majority of cases transmitted by mice. LCMV infection in other animals, including zoo animals, may be possible.In choosing a pet, the CDC advises looking for general indications of health both in the prospective pet and others in the facility.  The rodent of choice should be lively and alert, have a glossy coat, breathe normally and have no discharge from eyes or nose.  If one of the animals in the facility looks ill, the others may have been exposed, and none of the rodents at that location should be purchased.Serologic testing is not recommended for pet rodents, as it has been unreliable in detecting antibodies in animals with active infections.  For laboratory purposes, immunohistochemistry staining of tissues and virus isolation are used for more accurate testing, but this is unnecessary for the general house pet.  The greatest risk of infection to humans occurs shortly after purchase of a pet, so that exposure to the virus, if present, has likely already occurred to existing pet owners.  Continued ownership poses negligible additional risk.The National Center for Infectious Disease suggests the following precautions to reduce the risk of LCMV infection:

Wash hands with soap and water after handling pet rodents; use waterless alcohol-based hand rubs when soap is not available.
Keep rodent cages clean and free of soiled bedding.
Clean the cage in a well-ventilated area or outside.
Wash hands thoroughly with soap and water after cleaning up pet droppings.  Closely supervise young children, especially those less than five years old, when cleaning cages, and make sure they wash their hands immediately after handling rodents and rodent caging or bedding.
Do not kiss pet rodents or hold them close to your face.Rodent owners who no longer wish to keep their pet should consult a veterinarian.  Pets should not be released into the wild for humane, legal, and ecological reasons.  After a rodent has been purchased, it should not be returned to the pet store as it may have been exposed to LCMV through house mice.

Research
LCM is the archetypal arenavirus, and was instrumental in research which uncovered the major pathogenetic mechanisms of all arenaviruses.The field of viral immunology will continue to be uncovered by the model system of LCMV. Specifically, the study of persistent viral infections as well as vaccine development, represent two essential areas. LCMV is already identified as the best model to examine the difference between acute and persistent infection in its natural host Mus musculus, the common house mouse. Conveniently, the mouse is also the most widely used genetic model for mammalian genetics. A major phenotypic difference results from only two nucleotide differences between acute LCMV, also known as Armstrong LCMV, and one of its variant, Clone 13, which leads to persistent LCMV infection.  One of the nucleotide mutations is in the process of glycoprotein formation and affects tropism. The second base pair mutation affects the polymerase which influences replicative capacity. The mechanism by which these mutations cause acute versus chronic LCMV infection is not understood.
An important aspect of the present modern society is the thorough understanding of the burden of cancer. In many ways, this disease mirrors persistent viral infection, in the way that it evades and progresses despite the immune systems effort to eliminate it. The LCMV model will be a great path towards advancements in cancer studies.  Furthermore, LCMV has been a widely used model system for understanding T cell memory and vaccine synthesis. It was the original model when first studied focused on CD-8 T cells response towards LCMV infection. In addition, a better understanding of CD-4 T cell memory is also a result of studies with LCMV and will continue to contribute to a more efficient mechanism of vaccine formation. Specifically, LCMV has been recently used to quantify the efficiency of a new hydrogen peroxide-based vaccine formation mechanism. The future enhancement of the field of vaccinology will greatly depend on the LCMV model system.LCMV is a prototype of more severe hemorrhagic fever viruses, especially Lassa virus with the greatest prevalence in sub-Saharan Africa. However, other strains of this virus (Junin and Machupo viruses) are present in parts of South America and other strains continue to significantly affect the southern African population. Since the modern society continue to become a more inter-connected world, the spread of these virus strains will continue to pose a severe threat around the globe. Understanding the biology of the LCMV model virus will help in advancing the understanding of this important class of viruses and more specifically will give insight into the biology of the Lassa virus which proves to be a growing threat around the world. Furthermore, the United States National Institute for Allergy and Infectious Diseases (NIAID) has appointed the family of arenaviridae to be "Category A Priority Pathogens". This translates to the highest level of importance for the high potential for morbidity and mortality from an infectious agent which is relatively easy to produce and transmit.

Footnotes
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