<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 Delusional parasitosis and can you explain it in depth? [/INST] Delusional parasitosis (DP) is a mental disorder in which individuals have a persistent belief that they are infested with living or nonliving pathogens such as parasites, insects, or bugs, when no such infestation is present. They usually report tactile hallucinations known as formication, a sensation resembling insects crawling on or under the skin.  Morgellons is considered to be a subtype of this condition, in which individuals have sores that they believe contain harmful fibers.Delusional parasitosis is classified as a delusional disorder in the Diagnostic and Statistical Manual of Mental Disorders (DSM5). The cause is unknown, but is thought to be related to excess dopamine in the brain.  Delusional parasitosis is diagnosed when the delusion is the only symptom of psychosis and the delusion—that cannot be better explained by another condition—has lasted a month or longer. Few individuals with the condition willingly accept treatment, because they do not recognize the illness as a delusion. Antipsychotic medications offer a potential cure, while cognitive behavioral therapy and antidepressants can be used to help alleviate symptoms.The condition is rare, and is observed twice as often in women as men. The average age of people with the disorder is 57. An alternative name, Ekboms syndrome, refers to the neurologist Karl-Axel Ekbom, who published seminal accounts of the disease in 1937 and 1938.

Classification
Delusional infestation is classified as a delusional disorder of the somatic subtype in the Diagnostic and Statistical Manual of Mental Disorders (DSM5).  The name delusional parasitosis has been the most common name since 2015, but the condition has also been called delusional infestation, delusory parasitosis, delusional ectoparasitosis, psychogenic parasitosis, Ekbom syndrome, dermatophobia, parasitophobia, formication and "cocaine bugs".Morgellons is a form of delusional parasitosis in which people have painful skin sensations that they believe contain fibers of various kinds; its presentation is very similar to other delusional infestations, but people with this self-diagnosed condition also believe that strings or fibers are present in their skin lesions.Delusory cleptoparasitosis is a form of delusion of parasitosis where the person believes the infestation is in their dwelling, rather than on or in their body.

Signs and symptoms
People with delusional parasitosis believe that "parasites, worms, mites, bacteria, fungus" or some other living organism has infected them, and reasoning or logic will not dissuade them from this belief. Details vary among those who have the condition, though it typically manifests as a crawling and pin-pricking sensation that is most commonly described as involving perceived parasites crawling upon or burrowing into the skin, sometimes accompanied by an actual physical sensation (known as formication). Affected people may injure themselves in attempts to be rid of the "parasites"; resulting skin damage includes excoriation, bruising and cuts, as well as damage caused from using chemical substances and obsessive cleansing routines.A "preceding event such as a bug bite, travel, sharing clothes, or contact with an infected person" is often identified by individuals with DP; such events may lead the individual to misattribute symptoms because of more awareness of symptoms they were previously able to ignore. Nearly any marking upon the skin, or small object or particle found on the person or their clothing, can be interpreted as evidence for the parasitic infestation, and individuals with the condition commonly compulsively gather such "evidence" to present to medical professionals. This presentation is known as the "matchbox sign", "Ziploc bag sign" or "specimen sign", because the "evidence" is frequently presented in a small container, such as a matchbox. The matchbox sign is present in five to eight out of every ten people with DP.  Related is a "digital specimen sign", in which individuals bring collections of photographs to document their condition.Similar delusions may be present in close relatives—a shared condition known as a folie à deux—that occurs in 5 to 15% of cases and is considered a shared psychotic disorder. Because the internet and the media contribute to furthering shared delusions, DP has also been called folie à Internet; when affected people are separated, their symptoms typically subside, but most still require treatment.Approximately eight out of ten individuals with DP have co-occurring conditions—mainly depression, followed by substance abuse and anxiety; their personal and professional lives are frequently disrupted as they are extremely distressed about their symptoms.A 2011 Mayo Clinic study of 108 patients failed to find evidence of skin infestation in skin biopsies and patient-provided specimens; the study concluded that the feeling of skin infestation was DP.

Cause
The cause of delusional parasitosis is unknown. It may be related to excess dopamine in the brains striatum, resulting from diminished dopamine transporter (DAT) function, which regulates dopamine reuptake in the brain. Evidence supporting the dopamine theory is that medications that inhibit dopamine reuptake (for example cocaine and amphetamines) are known to induce symptoms such as formication. Other conditions that also demonstrate reduced DAT functioning are known to cause secondary DP; these conditions include "schizophrenia, depression, traumatic brain injury, alcoholism, Parkinsons and Huntingtons diseases, human immunodeficiency virus infection, and iron deficiency". Further evidence is that antipsychotics improve DP symptoms, which may be because they affect dopamine transmission.

Diagnosis
Delusional parasitosis is diagnosed when the delusion is the only symptom of psychosis, the delusion has lasted a month or longer, behavior is otherwise not markedly odd or impaired, mood disorders—if present at any time—have been comparatively brief, and the delusion cannot be better explained by another medical condition, mental disorder, or the effects of a substance. For diagnosis, the individual must attribute abnormal skin sensations to the belief that they have an infestation, and be convinced that they have an infestation even when evidence shows they do not.The condition is recognized in two forms: primary and secondary. In primary delusional parasitosis, the delusions are the only manifestation of a psychiatric disorder. Secondary delusional parasitosis occurs when another psychiatric condition, medical illness or substance (medical or recreational) use causes the symptoms; in these cases, the delusion is a symptom of another condition rather than the disorder itself. Secondary forms of DP can be functional (due to mainly psychiatric disorders) or organic (due to other medical illness or organic disease. The secondary organic form may be related to vitamin B12 deficiency, hypothyroidism, anemia, hepatitis, diabetes, HIV/AIDS, syphilis, or abuse of cocaine.Examination to rule out other causes is key to diagnosis.  Parasitic infestations are ruled out via skin examination and laboratory analyses. Bacterial infections may be present as a result of the individual constantly manipulating their skin. Other conditions that can cause itching skin are also ruled out; this includes a review of medications that may lead to similar symptoms.  Testing to rule out other conditions helps build a trusting relationship with the physician; this can include laboratory analysis such as a complete blood count, comprehensive metabolic panel, erythrocyte sedimentation rate, C-reactive protein, urinalysis for toxicology and thyroid-stimulating hormone, in addition to skin biopsies and dermatological tests to detect or rule out parasitic infestations.  Depending on symptoms, tests may be done for "human immunodeficiency virus, syphilis, viral hepatitis, B12 or folate deficiency," and allergies.

Differential
Delusional parasitosis must be distinguished from scabies, mites, and other psychiatric conditions that may occur along with the delusion; these include schizophrenia, dementia, anxiety disorders, obsessive–compulsive disorder, and affective or substance-induced psychoses or other conditions such as anemia that may cause psychosis.Pruritus and other skin conditions are most commonly caused by mites, but may also be caused by "grocers itch" from agricultural products, pet-induced dermatitis, caterpillar/moth dermatitis, or exposure to fiberglass.  Several drugs, legal or illegal, such as amphetamines, dopamine agonists, opioids, and cocaine may also cause the skin sensations reported.  Diseases that must be ruled out in differential diagnosis include hypothyroidism, and kidney or liver disease. Many of these physiological factors, as well as environmental factors such as airborne irritants, are capable of inducing a "crawling" sensation in otherwise healthy individuals; some people become fixated on the sensation and its possible meaning, and this fixation may then develop into DP.

Treatment
As of 2019, there have not been any studies that compare available treatments to placebo. The only treatment that provides a cure, and the most effective treatment, is low doses of antipsychotic medication.  Cognitive behavioral therapy (CBT) can also be useful. Risperidone is the treatment of choice.  For many years, the treatment of choice was pimozide, but it has a higher side effect profile than the newer antipsychotics.  Aripiprazole and ziprasidone are effective but have not been well studied for delusional parasitosis. Olanzapine is also effective. All are used at the lowest possible dosage, and increased gradually until symptoms remit.People with the condition often reject the professional medical diagnosis of delusional parasitosis, and few willingly undergo treatment, despite demonstrable efficacy, making the condition difficult to manage. Reassuring the individual with DP that there is no evidence of infestation is usually ineffective, as the patient may reject that. Because individuals with DP typically see many physicians with different specialties, and feel a sense of isolation and depression, gaining the patients trust, and collaborating with other physicians, are key parts of the treatment approach. Dermatologists may have more success introducing the use of medication as a way to alleviate the distress of itching. Directly confronting individuals about delusions is unhelpful because by definition, the delusions are not likely to change; confrontation of beliefs via CBT is accomplished in those who are open to psychotherapy. A five-phase approach to treatment is outlined by Heller et al. (2013) that seeks to establish rapport and trust between physician and patient.

Prognosis
The average duration of the condition is about three years.  The condition leads to social isolation and affects employment.  Cure may be achieved with antipsychotics or by treating underlying psychiatric conditions.

Epidemiology
While a rare disorder, delusional parasitosis is the most common of the hypochondriacal psychoses, and more common than other types of delusions such as those associated with body odor or halitosis.  It may be undetected because those who have it do not see a psychiatrist because they dont recognize the condition as a delusion.  A population-based study in Olmsted County, Minnesota found a prevalence of 27 per 100,000 person-years and an incidence of almost 2 cases per 100,000 person-years. The majority of dermatologists will see at least one person with DP during their career.It is observed twice as often in women than men. The highest incidence occurs in people in their 60s, but there is also a higher occurrence in people in their 30s, associated with substance use.  It occurs most often in "socially isolated" women with an average age of 57.Since the early 2000s, a strong internet presence has led to increasing self-diagnosis of Morgellons.

History
Karl-Axel Ekbom, a Swedish neurologist, first described delusional parasitosis as "pre-senile delusion of infestation" in 1937. The common name has changed many times since then.  Ekbom originally used the German word dermatozoenwahn, but other countries used the term Ekboms syndrome. That term fell out of favor because it also referred to restless legs syndrome. Other names that referenced "phobia" were rejected because anxiety disorder was not typical of the symptoms. The eponymous Ekboms disease was changed to "delusions of parasitosis" in 1946 in the English literature, when researchers J Wilson and H Miller described a series of cases, and to "delusional infestation" in 2009. The most common name since 2015 has been "delusional parasitosis".Ekboms original was translated to English in 2003; the authors hypothesized that James Harrington (1611–1677) may have been the "first recorded person to suffer from such delusions when he began to imagine that his sweat turned to flies, and sometimes to bees and other insects."

Morgellons
Mary Leitao, the founder of the Morgellons Research Foundation, coined the name Morgellons in 2002, reviving it from a letter written by a physician in the mid-1600s. Leitao and others involved in her foundation (who self-identified as having Morgellons) successfully lobbied members of the U.S. Congress and the U.S. Centers for Disease Control and Prevention (CDC) to investigate the condition in 2006. The CDC published the results of its multi-year study in January 2012. The study found no underlying infectious condition and few disease organisms were present in people with Morgellons; the fibers found were likely cotton, and the condition was "similar to more commonly recognized conditions such as delusional infestation".An active online community has supported the notion that Morgellons is an infectious disease, and propose an association with Lyme disease. Publications "largely from a single group of investigators" describe findings of spirochetes, keratin and collagen in skin samples of a small number of individuals; these findings are contradicted by the much larger studies conducted by the CDC.

Society and culture
Jay Traver (1894–1974), a University of Massachusetts entomologist, was known for "one of the most remarkable mistakes ever published in a scientific entomological journal", after publishing a 1951 account of what she called a mite infestation which was later shown to be incorrect, and that has been described by others as a classic case of delusional parasitosis as evidenced by her own detailed description.  Matan Shelomi argues that the historical paper should be retracted because it has misled people about their delusion </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 Hematometra and can you explain it in depth? [/INST] Hematometra is a medical condition involving collection or retention of blood in the uterus. It is most commonly caused by an imperforate hymen or a transverse vaginal septum.

Signs and symptoms
Hematometra typically presents as cyclic, cramping pain in the midline of the pelvis or lower abdomen. Patients may also report urinary frequency and urinary retention. Premenopausal women with hematometra often experience abnormal vaginal bleeding, including dysmenorrhea (pain during menstruation) or amenorrhea (lack of menstruation), while postmenopausal women are more likely to be asymptomatic </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 Interstitial pregnancy and can you explain it in depth? [/INST] An interstitial pregnancy is a uterine but ectopic pregnancy; the pregnancy is located outside the uterine cavity in that part of the fallopian tube that penetrates the muscular layer of the uterus. The term cornual pregnancy is sometimes used as a synonym, but remains ambiguous as it is also applied to indicate the presence of a pregnancy located within the cavity in one of the two upper "horns" of a bicornuate uterus. Interstitial pregnancies have a higher mortality than ectopics in general.

Anatomy
The part of the Fallopian tube that is located in the uterine wall and connects the remainder of the tube to the endometrial cavity is called its "interstitial" part, hence the term "interstitial pregnancy"; it has a length of 1–2 cm and a width of 0.7 cm. Its borders are the opening (ostium) of the tube to the endometrial cavity within the uterus and, laterally, the visible narrow segment of the tube. The area is well supplied by the Sampson artery which is connected to both the uterine and the ovarian arteries. Surrounded by uterine muscle (myometrium) it can expand significantly when it hosts a pregnancy.
Interstitial pregnancies can be confused with angular pregnancies; the latter, however, are located within the endometrial cavity in the corner where the tube connects; typically those pregnancies are viable although a high rate of miscarriage has been reported. A pregnancy located next to the interstitial section laterally is an isthmic tubal pregnancy.
The definition of an ectopic pregnancy is a pregnancy outside the uterine cavity, not outside the uterus, as the interstitial pregnancy is still a uterine pregnancy.

Diagnosis
Early diagnosis is important and today facilitated by the use of sonography and the quantitative human chorionic gonadotropin (hCG) assay.  As in other cases of ectopic pregnancy, risk factors are:  previous tubal pregnancy, IVF therapy, tubal surgery, and a history of sexual infection.
Typical symptoms of an interstitial pregnancy are the classic signs of ectopic pregnancy, namely abdominal pain and vaginal bleeding. Hemorrhagic shock is found in almost a quarter of patients.; this explains the relatively high mortality rate.
In pregnant patients, sonography is the primary method to make the diagnosis, even when patients have no symptoms. The paucity of myometrium around the gestational sac is diagnostic, while, in contrast, the angular pregnancy has at least 5 mm of myometrium on all of its sides.  Ultrasonic criteria for the diagnosis include an empty uterine cavity, a gestational sac separate from the uterine cavity, and a myometrial thinning of less than 5 mm around the gestational sac; typically the interstitial line sign—an echogenic line from the endometrial cavity to the corner next to the gestational mass—is seen. MRI can be used particularly when it is important to distinguish between an interstitial and angular pregnancy.
On average, the gestational age at presentation is about 7–8 weeks. In a 2007 series, 22% of patients presented with rupture and hemorrhagic shock, while a third of the patients were asymptomatic; the remainder had abdominal pain and/or vaginal bleeding </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Acroosteolysis 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 Primary lateral sclerosis and can you explain it in depth? [/INST] Primary lateral sclerosis (PLS) is a very rare neuromuscular disease characterized by progressive muscle weakness in the voluntary muscles. PLS belongs to a group of disorders known as motor neuron diseases. Motor neuron diseases develop when the nerve cells that control voluntary muscle movement degenerate and die, causing weakness in the muscles they control.
PLS only affects upper motor neurons.  There is no evidence of the degeneration of spinal motor neurons or muscle wasting (amyotrophy) that occurs in amyotrophic lateral sclerosis (ALS).

Symptoms and signs
Onset of PLS usually occurs spontaneously after age 50 and progresses gradually over a number of years, or even decades. The disorder usually begins in the legs, but it may start in the tongue or the hands. Symptoms may include difficulty with balance, weakness and stiffness in the legs, and clumsiness. Other common symptoms are spasticity (involuntary muscle contraction due to the stretching of muscle, which depends on the velocity of the stretch) in the hands, feet, or legs, foot dragging, and speech and swallowing problems due to involvement of the facial muscles. Breathing may also become compromised in the later stages of the disease, causing those patients who develop ventilatory failure to require noninvasive ventilatory support. Hyperreflexia is another key feature of PLS as seen in patients presenting with the Babinskis sign.  Some people present with emotional lability and bladder urgency, and occasionally people with PLS experience mild cognitive changes detectable on neuropsychological testing, particularly on measures of executive function.PLS is not considered hereditary when onset is in adulthood; however, juvenile primary lateral sclerosis (JPLS) has been linked to a mutation in the ALS2 gene which encodes the cell-signalling protein alsin.The issue of whether PLS exists as a different entity from ALS is not clear, as some patients initially diagnosed as having PLS ultimately develop lower motor neuron signs. When this happens it is classed as ALS.

Spasticity
Primary lateral sclerosis (PLS) usually presents with gradual-onset, progressive, lower-extremity stiffness and pain due to muscle spasticity. Onset is often asymmetrical. Although the muscles do not appear to atrophy as in ALS (at least initially), the disabling aspect of PLS is muscle spasticity and cramping, and intense pain when those muscles are stretched, resulting in joint immobility. A  normal walking stride may become a tiny step shuffle with related instability and falling.

Cause
Researchers do not fully understand what causes PLS, although it is thought it could be due to a combination of environmental and genetic factors. Studies are being done to evaluate the possible causes, although linking causality can be difficult due to the relatively low number of people who are diagnosed with PLS.Juvenile PLS may be caused by the ALS2 gene, although this condition is very rare.

Diagnosis
There are no specific tests for the diagnosis of PLS. Therefore, the diagnosis occurs as the result of eliminating other possible causes of the symptoms and by an extended observation period.Like ALS, diagnosing PLS is a diagnosis of exclusion, as there is no one test that can confirm a diagnosis of PLS. The Pringle Criteria, proposed by Pringle et al., provides a guideline of nine points that, if confirmed, can suggest a diagnosis of PLS. Due to the fact that a person with ALS may initially present with only upper motor neuron symptoms, indicative of PLS, one key aspect of the Pringle Criteria is requiring a minimum of three years between symptom onset and symptom diagnosis. When these criteria are met, a diagnosis of PLS is highly likely. Other aspects of Pringle Criteria include normal EMG findings, thereby ruling out lower motor neuron involvement that is indicative of ALS, and absence of family history for Hereditary Spastic Paraplegia (HSP) and ALS. Imaging studies to rule out structural or demyelinating lesions may be done as well. Hoffmans sign and Babinski reflex may be present and indicative of upper motor neuron damage.

Treatment
Treatment for individuals with PLS is symptomatic </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 Epithelial basement membrane dystrophy 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 Visceral leishmaniasis and can you explain it in depth? [/INST] Visceral leishmaniasis (VL), also known as kala-azar (Hindi: kālā āzār, "black sickness") or "black fever", is the most severe form of leishmaniasis and, without proper diagnosis and treatment, is associated with high fatality. Leishmaniasis is a disease caused by protozoan parasites of the genus Leishmania.
The parasite migrates to the internal organs such as the liver, spleen (hence "visceral"), and bone marrow, and, if left untreated, will almost always result in the death of the host. Signs and symptoms include fever, weight loss, fatigue, anemia, and substantial swelling of the liver and spleen. Of particular concern, according to the World Health Organization (WHO), is the emerging problem of HIV/VL co-infection.VL is the second-largest parasitic killer in the world (after malaria), responsible for an estimated 20,000 to 30,000 deaths each year worldwide.Upendranath Brahmachari synthesised urea stibamine (carbostibamide) in 1922 and determined that it was an effective substitute for the other antimony-containing compounds in the treatment of VL caused by Leishmania donovani.

Signs and symptoms
When people develop visceral leishmaniasis, the most typical symptoms are fever and the enlargement of the spleen, with enlargement of the liver sometimes being seen as well. The blackening of the skin that gave the disease its common name in India does not appear in most strains of the disease, and the other symptoms are very easy to mistake for those of malaria. Misdiagnosis is dangerous, as without proper treatment the mortality rate for kala-azar is close to 100%. L. donovani itself is not usually the direct cause of death in people with kala-azar, however. Pneumonia, tuberculosis, and dysentery are omnipresent in the immuno-depressed regions where leishmaniasis thrives, and, as with AIDS, it is these opportunistic infections that are more likely to kill, flaring up in a host whose immune system has been weakened by the L. donovani infection. Progress of the disease is extremely variable, taking anywhere from one to twenty weeks, but a typical duration for the Sudanese strain of the disease is narrower, between twelve and sixteen weeks.Even with recovery, kala-azar does not always leave its hosts unmarked. Some time after successful treatment—generally a few months with African kala-azar, or as much as several years with the Indian strain—a secondary form of the disease may set in, called post kala-azar dermal leishmaniasis, or PKDL. This condition manifests first as small, measle-like skin lesions on the face, which gradually increase in size and spread over the body. Eventually the lesions may coalesce to form disfiguring, swollen structures resembling leprosy, and occasionally causing blindness if they spread to the eyes. (This disease is not the same as cutaneous leishmaniasis, a milder disease caused by another protozoan of the Leishmania genus which also causes skin lesions.)

Cause
Two species of Leishmania are known to give rise to the visceral form of the disease. The species commonly found in East Africa and the Indian subcontinent is L. donovani and the species found in Europe, North Africa, and Latin America is L. infantum, also known as L. chagasi.The insect vectors are species of sandfly of the genus Phlebotomus in the Old World, and of Lutzomyia in the New World. Sandflies are tiny flies, measuring 3–6 mm long by 1.5–3 mm in diameter, and are found in tropical or temperate regions throughout the world. The sandfly species Lutzomyia longipalpis is the primary vector of this disease. The larvae grow in warm, moist organic matter (such as old trees, house walls, or waste) making them hard to eradicate.Visceral Leishmaniasis/kala-azar samples from India revealed the presence of not only the primary causative protozoan parasite, i.e. Leishmania donovani (LD) but also co-infection with another protozoan member called Leptomonas seymouri (LS). The latter parasite (LS) further contained a RNA virus known as Leptomonas seymouri narna-like virus 1 (Lepsey NLV1). So, it appears that a great majority of kala-azar patients in  the Indian subcontinent are exposed to a RNA virus in LS, the co-infecting parasite with LD i.e. the "LD-LS-Lepsey NLV1 triple pathogen" phenomenon.

Life cycle
The life cycle of Leishmania is completed in two hosts, humans and sandflies. The adult female sandfly is a bloodsucker, usually feeding at night on sleeping prey. When the fly bites an individual infected with Leishmania, the pathogen is ingested along with the preys blood. The protozoan is in the smaller of its two forms, called an amastigote, which is round, non-motile, and only 3–7 micrometers in diameter. Inside the stomach of the sandfly, the amastigotes quickly transform into elongated and motile forms called the promastigotes. Promastigote is spindle-shaped, triple the size of the amastigote, and has a single flagellum that allows mobility. The promastigotes live extracellularly in the alimentary canal, reproducing asexually, then migrate to the proximal end of the gut where they become poised for a regurgitational transmission. As the fly bites, the promastigotes are released from the proboscis and introduced locally at the bite site.Once inside the human host, promastigotes invade macrophages. Inside the cells they transform back into the smaller amastigote form. The amastigotes replicate in the most hostile part of the macrophage cell, inside the phagolysosome, whose normal defensive response they are able to prevent. After repeated multiplication, they break down their host cell by sheer pressure of mass, but there is some recent speculation that they are able to leave the cell by triggering the exocytosis response of the macrophage. The daughter cells protozoans then migrate to fresh cells or through the bloodstream to find new hosts. In this way the infection is progressive, spreading to the hosts mononuclear phagocyte system, particularly the spleen and liver. The free amastigotes in peripheral tissues are then ingested by sandfly to enter another cycle.

Regulatory T and B cells
The cell-mediated immunity (CMI) that kills Leishmania also produces inflammation. If the inflammation is excessive, it can cause tissue damage. The role of regulatory T and regulatory B cells is to suppress CMI enough to prevent tissue damage. However, an excessive regulatory response can prevent clearance of Leishmania and could explain the anergy of VL, poor response to drug treatment, development of PKDL, and relapses. A role for regulatory cells in VL has long been suspected. A variety of regulatory T and B cells have been implicated in VL, including Type 1 T helper cells that secrete IL-10 in addition to IFN-γ, natural T reg, Tr1, CD8+ T reg, and B reg. All of these lymphocytes act, at least in part, by secreting IL-10 and other suppressive cytokines.CD4+ T regs are present at increased frequency in the bone marrow of VL patients, are one source of IL-10, and proliferate in response to Leishmania antigen. Levels of FoxP3 mRNA were also up-regulated in lesional tissue from PKDL patients. However, T regs are not elevated in spleen cells from VL patients nor does depletion of T regs increase Leishmania antigen specific IFN-γ secretion The highest levels of IL-10 mRNA in spleen cells is in CD8+ and other non-FoxP3+ T cells. White blood cell CD8+ T cells from VL patients have elevated IL-10 levels. There is a 9.6 fold increase in IL-10 expressing CD8+ T cells among PBMC lymphocytes from PKDL patients. In the one study of T cell clones from VL patients, the clones isolated from VL PBMC were 100% CD8+. When mixed with self PBMC one or three years after successful treatment the CD8+ T cells decreased Leishmania antigen specific proliferation and IFN-γ secretion and increased IL-10 secretion. Depletion of CD8+ T cells from VL PBMC stopped endogenous IL-10 secretion but increased Leishmania antigen specific IL-10 secretion, suggesting that CD8+ regulatory T cells are responsible for endogenous IL-10 secretion. CD4+ clones could only be isolated from VL PBMC after CD8+ T cell depletion. The CD4+ clones had little effect on IL-10 secretion but decreased IFN-γ secretion when mixed with self PBMC collected after successful treatment.Regulatory B cells are known to favor development of regulatory T cells and suppress development of Type 1 T helper cells by producing IL-10 and other down-regulatory cytokines. IL-10 levels are elevated in B cells from VL PBMC. A study of dogs with naturally acquired VL showed that the percentage of regulatory B cells increased three-fold during VL. Depletion of B cells increased CD4+ T cell proliferation and IFN-γ secretion but decreased IL-10 secretion. Blocking IL-10 or programmed cell death receptors on B cells increased Leishmania antigen specific T cell proliferation and IFN-γ secretion. Co-culture of T cells with B cells decreased the percentage of CD4+ T cell proliferation and IFN-γ secretion four-fold.

Diagnosis
The gold standard for diagnosis is visualization of the amastigotes in splenic aspirate or bone marrow aspirate. This is a technically challenging procedure that is frequently unavailable in areas of the world where visceral leishmaniasis is endemic.Serological testing is much more frequently used in areas where leishmaniasis is endemic. A 2014 Cochrane review evaluated different rapid diagnostic tests. One of them (the rK39 immunochromatographic test) gave correct, positive results in 92% of the people with visceral leishmaniasis and it gave correct, negative results in 92% of the people who did not have the disease. A second rapid test (called latex agglutination test) gave correct, positive results in 64% of the people with the disease and it gave correct, negative results in 93% of the people without the disease. Other types of tests have not been studied thoroughly enough to ascertain their efficacy.The K39 dipstick test is easy to perform, and village health workers can be easily trained to use it. The kit may be stored at ambient temperature and no additional equipment needs to be carried to remote areas. The DAT anti-leishmania antigen test, standard within MSF, is much more cumbersome to use and appears not to have any advantages over the K39 test.There are a number of problems with serological testing: in highly endemic areas, not everyone who becomes infected will actually develop clinical disease or require treatment. Indeed, up to 32% of the healthy population may test positive, but not require treatment.  Conversely, because serological tests look for an immune response and not for the organism itself, the test does not become negative after the patient is cured, it cannot be used as a check for cure, or to check for re-infection or relapse. Likewise, patients with abnormal immune systems (e.g., HIV infection) will have false-negative tests.Other tests being developed include detects erythrosalicylic acid.

Prevention
As of 2018, there are no vaccines or preventive drugs for visceral leishmaniasis, but vaccines are in development. The most effective method to prevent infection is to protect from sand fly bites. To decrease the risk of being bitten, these precautionary measures are suggested:
Outdoors:1. Avoid outdoor activities, especially from dusk to dawn, when sand flies generally are the most active.
2. When outdoors (or in unprotected quarters), minimize the amount of exposed (uncovered) skin to the extent that is tolerable in the climate. Wear long-sleeved shirts, long pants, and socks; and tuck your shirt into your pants.
3. Apply insect repellent to exposed skin and under the ends of sleeves and pant legs. Follow the instructions on the label of the repellent. The most effective repellents generally are those that contain the chemical DEET (N,N-diethylmetatoluamide).

Indoors:1. Stay in well-screened or air-conditioned areas.
2. Keep in mind that sand flies are much smaller than mosquitoes and therefore can get through smaller holes.
3. Spray living/sleeping areas with an insecticide to kill insects.
4. If you are not sleeping in a well-screened or air-conditioned area, use a bed net and tuck it under your mattress. If possible, use a bed net that has been soaked in or sprayed with a pyrethroid-containing insecticide. The same treatment can be applied to screens, curtains, sheets, and clothing (clothing should be retreated after five washings)."

Treatments
As with many diseases in developing nations, (including trypanosomiasis and malaria) effective and affordable chemotherapy is sorely lacking and parasites or insect vectors are becoming increasingly resistant to existing anti-parasite drugs. Possibly due to the lack of financial return, new drugs are slow to emerge and much of the basic research into potential drug targets takes place in universities, funded by charitable organizations. Product Development Partnership, Drugs for Neglected Diseases initiative works on the development of new treatments (combination treatments and new chemical entities) for visceral leishmaniasis.The traditional treatment is with pentavalent antimonials such as sodium stibogluconate and meglumine antimoniate. Resistance is now common in India, and rates of resistance have been shown to be as high as 60% in parts of Bihar, India.The treatment of choice for visceral leishmaniasis acquired in India is now amphotericin B in its various liposomal preparations. In East Africa, the WHO recommended treatment is SSG&PM (sodium stibogluconate and paromomycin) developed by Drugs for Neglected Diseases initiative (DNDi) in 2010.Miltefosine is the first oral treatment for this disease. The cure rate of miltefosine in Phase III clinical trials is 95%; Studies in Ethiopia show that is also effective in Africa. In HIV immunosuppressed people which are coinfected with leishmaniasis it has shown that even in resistant cases 2/3 of the people responded to this new treatment.
Miltefosine has received approval by the Indian regulatory authorities in 2002, in Germany in 2004 and in U.S.A. in 2014. It is now registered in many countries.The drug is generally better tolerated than other drugs. Main side effects are gastrointestinal disturbance in the first or second day of treatment (a course of treatment is 28 days) which does not affect the efficacy. Because it is available as an oral formulation, the expense and inconvenience of hospitalization is avoided, and outpatient distribution of the drug becomes an option, making miltefosine a drug of choice. However, there are some important disadvantages: 1) there is evidence of reduced efficacy after a decade of use 2) it is teratogenic and cannot be used in women of child-bearing age without anticonception during and for 4 months after treatment.Incomplete treatment has been cited as a major reason of death from visceral leishmaniasis.The nonprofit Institute for OneWorld Health has adopted the broad spectrum antibiotic paromomycin for use in treating VL; its antileishmanial properties were first identified in the 1980s.  A treatment with paromomycin costs about US$15. The drug had originally been identified in the 1960s. The Indian government approved paromomycin for sale and use in August 2006.

Prognosis
Protective immunity
Immunity to Leishmania is determined by the interplay of white blood cells, cytokines, immune complexes, and genetic and environmental factors.
Protective immunity develops either after successful treatment of VL (cured) or after asymptomatic infections that resolve without development of VL (asymptomatic). Both types of immunity are characterized by cell-mediated immunity (CMI), including skin test positivity, proliferation, and interleukin 2 (IL-2), interferon gamma (IFN-γ), and interleukin 12 (IL-12) secretion by peripheral blood mononuclear cells (PBMC) in response to Leishmania antigens. T cells isolated from both cured and asymptomatic PBMC activate autologous macrophages to kill intracellular amastigotes. IFN-γ activates macrophages to kill intracellular parasites so its role in VL has been studied extensively and IFN-γ production is often used as a marker of protective immunity. Cured PBMC generally secrete less IFN-γ and more interleukin 10 (IL-10) in response to Leishmania antigens than asymptomatic PBMC. IL-12 is important in the development and maintenance of Type 1 T helper cell responses and protective immunity so its role in VL has also been studied. Addition of IL-12 to some VL PBMC increases proliferation and IFN-γ secretion in response to Leishmania antigens and anti-IL-12 inhibits proliferation and IFN-γ secretion by some cured PBMC. Other cytokines also appear to be important in immunity to Leishmania but their roles are not as well characterized.Leishmania antigen stimulation of PBMC from cured patients show a mixed T helper cell and regulatory T cell response. Both CD4+ and CD8+ T cells contributed to IFN-γ production. Studies of Leishmania antigen specific T cell clones from cured patient PBMC confirm that cured patients have a mixed T cell response that involves both CD4+ helper T cells and CD4+ and CD8+ regulatory T cells.  Two studies of asymptomatic T cell clones show that most have Type 1 profiles and secrete more IFN-γ than T cell clones from cured patients. Neither study revealed the presence of Type 2 or regulatory T cells. Some clones secreted soluble factors that caused the death of CD8+ regulatory T cells but not CD4+ T cells from VL patients, which might explain the strong protective immunity of asymptomatic patients.

Non-protective immunity
VL patients are unable to clear their infections because they lack CMI. This anergy may be limited to Leishmania antigens or extend to mitogens and other antigens as the disease progresses. In addition to skin test negativity, VL patient PBMC do not proliferate or secrete IL-2 or IFN-γ in response to Leishmania antigens. Memory T cells may be depleted in VL patient PBMC. Since IL-10 is known to suppress innate and acquired immunity and prevent IFN-γ from activating macrophages, its role in VL has been studied extensively and elevated IL-10 production is often used as a marker of non-protective immunity in VL. Elevated levels of IL-10 in the plasma, infected tissues, and PBMC of VL patients accompany the anergy of VL. PKDL patients also have elevated IL-10 levels. VL patients with the highest IL-10 levels are more likely to be unresponsive to treatment and progress to PKDL. PBMC secretion of IL-10 without the addition of Leishmania antigen (endogenous) is inversely correlated with antigen specific IFN-γ secretion but Leishmania antigen specific IL-10 and IFN-γ secretion are not correlated, suggesting that endogenous secretion is more important in pathology. Addition of anti-IL-10 increases proliferation and IFN-γ secretion by PBMC from some patients. Both CD4+ and CD8+ T cells have been shown to contribute to IL-10 secretion by VL PBMC. The high level of immune complexes characteristic of VL have also been shown to increase IL-10 levels.

Epidemiology
More than 90% of the global burden of visceral leishmaniasis (VL) was contributed by seven countries in 2015: Brazil, Ethiopia, India, Kenya, Somalia, South Sudan and Sudan. In India, more than 70% of VL cases are reported from the state of Bihar. North Bihar, India (including Araria, Purnea, and Kishanganj) is the endemic zone of this disease. The disease is endemic in more than 60 countries. In Iran this includes Ardabil, Fars, and North Khorasan.However, while the diseases geographical range is broad, it is not continuous. The disease clusters around areas of drought, famine, and high population density. In Africa, this has meant a knot of infection centers mostly in South Sudan, Sudan, Ethiopia, Kenya, and Somalia. Living conditions here have changed very little in the past century, and the people are not normally very mobile. Parts of South Sudan, in particular the Upper Nile region, are almost totally cut off from the rest of the country, and most people tend to remain at their place of birth although there have been huge population movements due to the civil war, leading to severe epidemics.

History
Kala-azar first came to the attention of Western doctors in 1824 in Jessore, India (now Bangladesh), where it was initially thought to be a form of malaria. Assam gave kala-azar one of its common names, Assam fever. Another common name, kala-azar (Hindustani: काला आज़ार (Devanagari) کالا آزار (Nastaleeq) kālā āzār), is derived from kala which means black in Sanskrit, as well as in the languages descended from it, including Assamese, Hindi and Urdu; the word azar means Fever in Persian and Hindustani; as such the disease is named for the darkening of the skin on the extremities and abdomen that is a symptom of the Indian form of the disease. The agent of the disease was also first isolated in India by Scottish doctor William Leishman (who observed the parasite in spleen smears of a soldier who died of the disease in Dumdum, Calcutta, India - hence the name dumdum fever) and Irish physician Charles Donovan, working independently of each other. As they published their discovery almost simultaneously, the species was named for both of them—Leishmania donovani.

Today, the name kala-azar is used interchangeably with the scientific name visceral leishmaniasis for the most acute form of the disease caused by L. donovani. The disease is endemic in West Bengal, where it was first discovered, but is seen at its most deadly in north and east Africa. It can also be found throughout the Arab world and southern Europe (where the causative organism is L. infantum), and a slightly different strain of the pathogen, L. chagasi, is responsible for leishmaniasis in the new world. Several species of canines serve as reservoir hosts of L. infantum (chagasi).Contemporary life has made itself felt even here, however—not as "progress" but in the form of the many small wars of Africas post-colonial era. In the Sudan, where civil war has been continuous since 1983, the violence has been concentrated in the more populated south, and kala-azar was concentrated there too. But the wars have driven a steady stream of refugees out of the region, and these traveled either across the southern border or into the remoter western part of the country called the Upper Nile, where both war and the disease that went with it had not yet penetrated.These refugees, moving at foot-speed, carried the disease with them, and when it arrived it hit the Upper Nile with a force comparable to smallpox hitting the American Indians. The isolated people of the Upper Nile had no access to medicine or education about the new disease among them. Worse, their immune systems were defenseless against this new pathogen, foreign to them though it came only from another part of their own country. One village at the center of the epidemic, Duar, was left with four survivors out of a population of a thousand, and from the late eighties to the mid-nineties a total of 100,000 died from the sickness in that region alone. In the words of Jill Seaman, the doctor who led relief efforts in the Upper Nile for the French organization Médecins Sans Frontières, "Where else in the world could 50% of a population die without anyone knowing?" Due to the South Sudanese Civil War, kala-azar has spread rapidly among the population.

The Indian medical practitioner Upendra Nath Brahmachari was nominated for the Nobel Prize in Physiology or Medicine in 1929 for his discovery of ureastibamine (an antimonial compound for the treatment of kala-azar) and a new disease, post kala-azar dermal leishmaniasis. Brahmacharis cure for visceral leishmaniasis was the urea salt of para-amino-phenyl stibnic acid which he called Urea Stibamine.During the nineteenth century, kala-azar was discovered near moving bodies of water in southeast Asia. Dr </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 Hematidrosis and can you explain it in depth? [/INST] Hematidrosis, also called blood sweat, is a very rare condition in which a human sweats blood. The term is from Ancient Greek haîma/haímatos (αἷμα/αἵματος), meaning blood, and hīdrṓs (ἱδρώς), meaning sweat.

Signs and symptoms
Blood usually oozes from the forehead, nails, umbilicus, and other skin surfaces. In addition, oozing from mucocutaneous surfaces causing nosebleeds, bloodstained tears, and vicarious menstruation are common </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 Congenital generalized lipodystrophy and can you explain it in depth? [/INST] Congenital generalized lipodystrophy (also known as Berardinelli–Seip lipodystrophy) is an extremely rare autosomal recessive condition, characterized by an extreme scarcity of fat in the subcutaneous tissues. It is a type of lipodystophy disorder where the magnitude of fat loss determines the severity of metabolic complications. Only 250 cases of the condition have been reported, and it is estimated that it occurs in 1 in 10 million people worldwide.

Presentation
Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder which manifests with insulin resistance, absence of subcutaneous fat and muscular hypertrophy. Homozygous or compound heterozygous mutations in four genes are associated with the four subtypes of CGL. The condition appears in early childhood with accelerated linear growth, quick aging of bones, and a large appetite. As the child grows up, acanthosis nigricans (hyperpigmentation and thickening of skin) will begin to present itself throughout the body – mainly in the neck, trunk, and groin. The disorder also has characteristic features like hepatomegaly or an enlarged liver which arises from fatty liver and may lead to cirrhosis, muscle hypertrophy, lack of adipose tissue, splenomegaly, hirsutism (excessive hairiness) and hypertriglyceridemia. Fatty liver and muscle hypertrophy arise from the fact that lipids are instead stored in these areas; whereas in a healthy individual, lipids are distributed more uniformly throughout the body subcutaneously. The absence of adipose tissue where they normally occur causes the body to store fat in the remaining areas. Common cardiovascular problems related to this syndrome are cardiac hypertrophy and arterial hypertension (high blood pressure). This disorder can also cause metabolic syndrome. Most with the disorder also have a prominent umbilicus or umbilical hernia. Commonly, patients will also have acromegaly with enlargement of the hands, feet, and jaw. After puberty, additional symptoms can develop. In women, clitoromegaly and polycystic ovary syndrome can develop. This impairs fertility for women, and only a few documented cases of successful pregnancies in women with CGL exist. However, the fertility of men with the disorder is unaffected.

Type 1 vs Type 2 Differences
There are differences in how Type 1 vs Type 2 patients are affected by the disease. In type 1 patients, they still have mechanical adipose tissue, but type 2 patients do not have any adipose tissue, including mechanical. In type 2 patients, there is a greater likelihood of psychomotor retardation and intellectual impairment.

Genetics
Mechanism
Type 1
In individuals with Type 1 CGL, the disorder is caused by a mutation at the AGPAT2 gene encoding 1-acylglycerol-3-phosphate O-acyltransferase 2 and located at 9q34.3. This enzyme catalyzes the acylation of lysophosphatidic acid to form phosphatidic acid, which is important in the biosynthesis of fats. This enzyme is highly expressed in adipose tissue, so it can be concluded that when the enzyme is defective in CGL, lipids cannot be stored in the adipose tissue.

Type 2
In those who have Type 2 CGL, a mutation in the BSCL2 gene encoding the Seipin protein and located at 11q13. This gene encodes a protein, Seipin, whose function is unknown.  Expression of mRNA for the seipin protein is high in the brain, yet low in adipose tissues. Additionally, patients which have mutations in this protein have a higher incidence of mental retardation and lack mechanically active adipose tissue, which is present in those with AGPAT2 mutations.

Type 3
Type 3 CGL involves a mutation in the CAV1 gene. This gene codes for the Caveolin protein, which is a scaffolding membrane protein. This protein plays a role in lipid regulation. High levels of Cav1 are normally expressed in adipocytes. Thus, when the CAV1 gene mutates the adipocytes do not have Cav1 and are unable to properly regulate lipid levels.

Type 4
A mutation in the PTRF gene causes Type 4 CGL. This gene codes for a protein called polymerase I and transcript release factor. One of the roles the PTRF product has it to stabilize and aid in formation of caveolae. Thus, the mechanism is similar to Type 3, in that the caveolae are unable to properly form and carry out their role in lipid regulation in both. Types 3 and 4 are two different mutations but they share a common defective pathway.

Diagnosis
Medical diagnosis of CGL can be made after observing the physical symptoms of the disease: lipoatrophy (loss of fat tissues) affecting the trunk, limbs, and face; hepatomegaly; acromegaly; insulin resistance; and high serum levels of triglycerides. Genetic testing can also confirm the disease, as mutations in the AGPAT2 gene is indicative of CGL1, a mutation in the BSCL2 gene is indicative of CGL2, and mutations in the CAV1 and PTRF genes are indicative of CGL3 and CGL4 respectively. Physical diagnosis of CGL is easier, as CGL patients are recognizable from birth, due to their extreme muscular appearance, which is caused by the absence of subcutaneous fat.CGL3 patients have serum creatine kinase concentrations much higher than normal (2.5 to 10 times the normal limit) </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 Camptodactyly and can you explain it in depth? [/INST] Camptodactyly is a medical condition that causes one or more fingers or toes to be permanently bent </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 Acquired idiopathic generalized anhidrosis 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 Meacham 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 Dacryocystitis and can you explain it in depth? [/INST] Dacryocystitis is an infection of the lacrimal sac, secondary to obstruction of the nasolacrimal duct at the junction of lacrimal sac. The term derives from the Greek dákryon (tear), cysta (sac), and -itis (inflammation) </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 Finger and can you explain it in depth? [/INST] A finger is a limb of the body and a type of digit, an organ of manipulation and sensation found in the hands of most of the Tetrapods, so also with humans and other primates. Most land vertebrates have five fingers (Pentadactyly).

Land vertebrate fingers
The five-rayed anterior limbs of terrestrial vertebrates can be derived phylogenetically from the pectoral fins of fish. Within the taxa of the terrestrial vertebrates, the basic pentadactyl plan, and thus also the fingers and phalanges, undergo many variations.Morphologically the different fingers of terrestrial vertebrates are homolog. The wings of birds and those of bats are not homologous, they are analogue flight organs. However, the phalanges within them are homologous.Chimpanzees have lower limbs that are specialized for manipulation, and (arguably) have fingers on their lower limbs as well. In the case of Primates in general, the digits of the hand are overwhelmingly referred to as "fingers". Primate fingers have both fingernails and fingerprints.Research has been carried out on the embryonic development of domestic chickens showing that an interdigital webbing forms between the tissues that become the toes, which subsequently regresses by apoptosis. If apoptosis fails to occur, the interdigital skin remains intact. Many animals have developed webbed feet or skin between the fingers from this like the Wallaces flying frog.

Human fingers
Usually humans have five digits, the bones of which are termed phalanges, on each hand, although some people have more or fewer than five due to congenital disorders such as polydactyly or oligodactyly, or accidental or intentional amputations. The first digit is the thumb, followed by index finger, middle finger, ring finger, and little finger or pinkie. According to different definitions, the thumb can be called a finger, or not.
English dictionaries describe finger as meaning either one of the five digits including the thumb, or one of the four excluding the thumb (in which case they are numbered from 1 to 4 starting with the index finger closest to the thumb).

Anatomy
Skeleton
The thumb (connected to the trapezium) is located on one of the sides, parallel to the arm.
The palm has five bones known as metacarpal bones, one to each of the five digits. Human hands contain fourteen digital bones, also called phalanges, or phalanx bones: two in the thumb (the thumb has no middle phalanx) and three in each of the four fingers. These are the distal phalanx, carrying the nail, the middle phalanx, and the proximal phalanx.
Joints are formed wherever two or more of these bones meet. Each of the fingers has three joints:

metacarpophalangeal joint (MCP) – the joint at the base of the finger
proximal interphalangeal joint (PIP) –  the joint in the middle of the finger
distal interphalangeal joint (DIP)  – the joint closest to the fingertip.Sesamoid bones are small ossified nodes embedded in the tendons to provide extra leverage and reduce pressure on the underlying tissue. Many exist around the palm at the bases of the digits; the exact number varies between different people.
The articulations are: interphalangeal articulations between phalangeal bones, and metacarpophalangeal joints connecting the phalanges to the metacarpal bones.

Muscles
Each finger may flex and extend, abduct and adduct, and so  also circumduct. Flexion is by far the strongest movement. In humans, there are two large muscles that produce flexion of each finger, and additional muscles that augment the movement. The muscle bulks that move each finger may be partly blended, and the tendons may be attached to each other by a net of fibrous tissue, preventing completely free movement. Although each finger seems to move independently, moving one finger also moves the other fingers slightly which is called finger interdependence or finger enslaving.Fingers do not contain muscles (other than arrector pili). The muscles that move the finger joints are in the palm and forearm. The long tendons that deliver motion from the forearm muscles may be observed to move under the skin at the wrist and on the back of the hand.
Muscles of the fingers can be subdivided into extrinsic and intrinsic muscles.
The extrinsic muscles are the long flexors and extensors. They are called extrinsic because the muscle belly is located on the forearm.
The fingers have two long flexors, located on the underside of the forearm. They insert by tendons to the phalanges of the fingers. The deep flexor attaches to the distal phalanx, and the superficial flexor attaches to the middle phalanx. The flexors allow for the actual bending of the fingers. The thumb has one long flexor and a short flexor in the thenar muscle group. The human thumb also has other muscles in the thenar group (opponens and abductor brevis muscle), moving the thumb in opposition, making grasping possible.
The extensors are located on the back of the forearm and are connected in a more complex way than the flexors to the dorsum of the fingers. The tendons unite with the interosseous and lumbrical muscles to form the extensorhood mechanism. The primary function of the extensors is to straighten out the digits. The thumb has two extensors in the forearm; the tendons of these form the anatomical snuff box. Also, the index finger and the little finger have an extra extensor, used for instance for pointing. The extensors are situated within six separate compartments. The first compartment contains abductor pollicis longus and extensor pollicis brevis. The second compartment contains extensors carpi radialis longus and brevis. The third compartment contains extensor pollicis longus. The extensor digitorum indicis and extensor digitorum communis are within the fourth compartment. Extensor digiti minimi is in the fifth, and extensor carpi ulnaris is in the sixth.
The intrinsic muscle groups are the thenar and hypothenar muscles (thenar referring to the thumb, hypothenar to the small finger), the dorsal and palmar interossei muscles (between the metacarpal bones) and the lumbrical muscles. The lumbricals arise from the deep flexor (and are special because they have no bony origin) and insert on the dorsal extensor hood mechanism.

Skin
Aside from the genitals, the fingertips possess the highest concentration of touch receptors and thermoreceptors among all areas of the human skin, making them extremely sensitive to temperature, pressure, vibration, texture and moisture. Recent studies suggest fingers can feel nano-scale wrinkles on a seemingly smooth surface, a level of sensitivity not previously recorded.  This makes the fingers commonly used sensory probes to ascertain properties of objects encountered in the world, making them prone to injury.
The pulp of a finger is the fleshy mass on the palmar aspect of the extremity of the finger.

Fingertip wrinkling in water
Although a common phenomenon, the underlying functions and mechanism of fingertip wrinkling following immersion in water are relatively unexplored. Originally it was assumed that the wrinkles were simply the result of the skin swelling in water, but it is now understood that the furrows are caused by the blood vessels constricting due to signalling by the sympathetic nervous system in response to water exposure. One hypothesis for why this occurs, the “rain tread” hypothesis, posits that the wrinkles may help the fingers grip things when wet, possibly being an adaption from a time when humans dealt with rain and dew in forested primate habitats. A 2013 study supporting this hypothesis found that the wrinkled fingertips provided better handling of wet objects but gave no advantage for handling dry objects. However, a 2014 study attempting to reproduce these results was unable to demonstrate any improvement of handling wet objects with wrinkled fingertips.

Regrowth of the fingertips
Fingertips, after having been torn off children, have been observed to regrow in less than 8 weeks. However, these fingertips do not look the same, although they do look more appealing than a skin graft or a sewn fingertip. No healing occurs if the tear happens below the nail. This works because the distal phalanges are regenerative in youth, and stem cells in the nails create new tissue that ends up as the fingertip.

Brain representation
Each finger has an orderly somatotopic representation on the cerebral cortex in the somatosensory cortex area 3b, part of area 1 and a distributed, overlapping representations in the supplementary motor area and primary motor area.The somatosensory cortex representation of the hand is a dynamic reflection of the fingers on the external hand: in syndactyly people have a clubhand of webbed, shortened fingers. However, not only are the fingers of their hands fused, but the cortical maps of their individual fingers also form a club hand. The fingers can be surgically divided to make a more useful hand. Surgeons did this at the Institute of Reconstructive Plastic Surgery in New York to a 32-year-old man with the initials O. G.. They touched O. G.’s fingers before and after surgery while using MRI brain scans. Before the surgery, the fingers mapped onto his brain were fused close together; afterward, the maps of his individual fingers did indeed separate and take the layout corresponding to a normal hand.

Clinical significance
Anomalies, injuries and diseases
A rare anatomical variation affects 1 in 500 humans, in which the individual has more than the usual number of digits; this is known as polydactyly. A human may also be born without one or more fingers or underdevelopment of some fingers such as symbrachydactyly. Extra fingers can be functional </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 Stimmler 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 Ovarian pregnancy and can you explain it in depth? [/INST] Ovarian pregnancy refers to an ectopic pregnancy that is located in the ovary. Typically the egg cell is not released or picked up at ovulation, but fertilized within the ovary where the pregnancy implants. Such a pregnancy usually does not proceed past the first four weeks of pregnancy. An untreated ovarian pregnancy causes potentially fatal intra-abdominal bleeding and thus may become a medical emergency.

Cause and pathology
The cause of ovarian pregnancy is unknown, specifically as the usual causative factors – pelvic inflammatory disease and pelvic surgery – implicated in tubal ectopic pregnancy seem to be uninvolved. There appears to be a link to the intrauterine device (IUD), however, it cannot be concluded that this is causative as it could be that IUDs prevent other but not ovarian pregnancies. Some have suggested that patients who undergo IVF therapy are at higher risk for ovarian pregnancy.An ovarian pregnancy is usually understood to begin when a mature egg cell is not expelled or picked up from its follicle and a sperm enters the follicle and fertilizes the egg, giving rise to an intrafollicular pregnancy. It has also been debated that an egg cell fertilized outside of the ovary could implant on the ovarian surface, perhaps aided by a decidual reaction or endometriosis. Ovarian pregnancies rarely go longer than 4 weeks; nevertheless, there is the possibility that the trophoblast finds further support outside the ovary and thus may affect the tube and other organs. In very rare occasions the pregnancy may find a sufficient foothold outside the ovary to continue as an abdominal pregnancy, and an occasional delivery has been reported.y

Diagnosis
The diagnosis is made in asymptomatic pregnant women by obstetric ultrasonography. On pelvic examination a unilateral adnexal mass may be found. Typical symptoms are abdominal pain and, to a lesser degree, vaginal bleeding during pregnancy. Patients may present with hypovolemia or be in circulatory shock because of internal bleeding.Ideally, ultrasound will show the location of the gestational sac in the ovary, while the uterine cavity is "empty", and if there is internal bleeding, it can be identified. Because of the proximity of the tube, the sonographic distinction between a tubal and an ovarian pregnancy may be difficult. Serial hCG levels generally show not the normal progressive rise.
In a series of 12 patients the mean gestation age was 45 days.Histologically, the diagnosis has been made by Spiegelberg criteria on the surgical specimen of the removed ovary and tube. However, the tube and ovary are not usually removed as sonography allows for earlier diagnosis and surgeons strive to preserve the ovary. Prior to the introduction of Spiegelbergs criteria in 1878, the existence of ovarian pregnancy was in doubt; his criteria helped to identify the ovarian pregnancy from other ectopics:
The gestational sac is located in the region of the ovary.
The gestational sac is attached to the uterus by the ovarian ligament.
Ovarian tissue is histologically proven in the wall of the gestational sac.
The oviduct on the affected side is intact (this criterion, however, holds not true for a longer ongoing ovarian pregnancy).An ovarian pregnancy can be mistaken for a tubal pregnancy or a hemorrhagic ovarian cyst or corpus luteum prior to surgery. Sometimes, only the presence of trophoblastic tissue during the histologic examination of material of a bleeding ovarian cyst shows that an ovarian pregnancy was the cause of the bleeding.

Management
Ovarian pregnancies are dangerous and prone to internal bleeding. Thus, when suspected, intervention is called for.
Traditionally, an explorative laparotomy was performed, and once the ovarian pregnancy was identified, an oophorectomy or salpingo-oophorectomy was performed, including the removal of the pregnancy. Today, the surgery can often be performed via laparoscopy. The extent of surgery varies according to the amount of tissue destruction that has
occurred. Patients with an ovarian pregnancy have a good prognosis for future fertility and therefore conservative surgical management is advocated. Further, in attempts to preserve ovarian tissue, surgery may involve just the removal of the pregnancy with only a part of the ovary. This can be accomplished by an ovarian wedge resection.Ovarian pregnancies have been successfully treated with methotrexate since it was introduced in the management of ectopic pregnancy in 1988.An ovarian pregnancy can develop together with a normal intrauterine pregnancy; such a heterotopic pregnancy will call for expert management as not to endanger the intrauterine pregnancy.

Epidemiology
Ovarian pregnancies are rare: the vast majority of ectopic pregnancies occur in the fallopian tube; only about 0.15-3% of ectopics occur in the ovary. The incidence has been reported to be about 1:3,000 to 1:7,000 deliveries.

History
In 1614 Mercier (also shown as Mercerus) described ovarian pregnancy for the first time, as a condition separate from a tubal pregnancy. Once the study of physiology emerged, Boehmer classified extra-uterine pregnancy into three classes: abdominal, ovarian, and tubal. There were many doubters that such a condition existed, particularly Mayer, who wrote an essay not only denying the existence of ovarian pregnancy, but demonstrating that recorded cases to that time were other conditions. Then Cohnstein proposed four criteria that would need to be present for ovarian pregnancy exist. His requirements were: 1) absence of the ovary on the side in which the alleged pregnancy was located; 2) connection of the uterus and sac via an ovarian ligament; 3) cylindrical tissue must line the layers of the sac with direct connection between the tunica albuginea and sac wall; and 4) evidence of the amniotic cavity connection to the ovarian follicle or corpus luteum. These were replaced by Otto Spiegelbergs criteria in 1878, which have been used into the 20th century with additions and modifications.Up to 1845, about 80 cases of ovarian pregnancy were proposed. With Mayers 1845 denial that ovarian pregnancy could exist, physicians began taking more care in their descriptions and analysis of cases. Though numerous cases were evaluated, some failed to provide microscopic evidence and others failed to show the necessary histological changes of pregnancy, or failed on one or more of the criteria. In 1899, Catharine van Tussenbroek finally settled the question of the existence of ovarian pregnancy, by providing the first accurate clinical and histological description of a case. Though doubted, her results were confirmed three years later in a case by Thompson.

References
Citations
Sources
Jacobson, Sidney D. (1908). "True Primary Ovarian Pregnancy: Operation; Recovery".  In Brooks, Henry T. (ed.). Contributions to the Science of Medicine and Surgery: In celebration of the twenty-fifth anniversary, 1882-1907, of the founding of the New York Post-Graduate Medical School and Hospital. New York: Jacobson New York Post-graduate Medical School and Hospital Faculty / Royal College of Physicians of Edinburgh.
McDonald, Ellice (1914). Studies in gynecology and obstetrics. New York: American Medical Publishing Co. OCLC 11339026.
Ray, Henry M. (June 1921). "Primary Ovarian and Primary Abdominal Pregnancy: Their Morphological Possibility". Surgery, Gynecology & Obstetrics. Chicago: Journal of the American College of Surgeons / Franklin H. Martin Memorial Foundation. 32. Retrieved 21 March 2016.
Rizk, Botros R. M. B. (2010). Ultrasonography in Reproductive Medicine and Infertility. Cambridge, England: Cambridge University Press. ISBN 978-1-139-48457-2.
Thorek, Max (February 1926) </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 Sarcoma botryoides 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 Lower urinary tract symptoms and can you explain it in depth? [/INST] Lower urinary tract symptoms (LUTS) refer to a group of clinical symptoms involving the bladder, urinary sphincter, urethra and, in men, the prostate. The term is more commonly applied to men—over 40% of older men are afected—but lower urinary tract symptoms also affect women. The condition is also termed prostatism in men, but LUTS is preferred.

Symptoms and signs
Symptoms can be categorised into:

Filling (storage) or irritative symptoms
Increased frequency of urination
Increased urgency of urination
Urge incontinence
Excessive passage of urine at night

Voiding or obstructive symptoms
Poor stream (unimproved by straining)
Hesitancy (worsened if bladder is very full)
Terminal dribbling
Incomplete voiding
Urinary retention
Overflow incontinence (occurs in chronic retention)
Episodes of near retentionAs the symptoms are common and non-specific, LUTS is not necessarily a reason to suspect prostate cancer </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 Childhood absence epilepsy and can you explain it in depth? [/INST] Childhood absence epilepsy (CAE), is one of the most frequent pediatric epilepsy syndromes. CAE is an idiopathic generalized epilepsy that occurs in otherwise normal children. The only seizure type at the time of diagnosis is the typical absence seizure. CAE is a well-known pediatric epilepsy syndrome affecting 10–17% of all children with epilepsy. It was previously known as pyknolepsy. The word pyknolepsy originates from the Greek piknoz (picnós), which means recurrent or grouped. The usual age of onset of CAE is between 4 and 10 years, with peak between 5 and 7 years.The typical absence seizure has a sudden onset of altered awareness and ends also abruptly. Electroencephalogram demonstrate characteristic "typical 3Hz spike-wave" generalized rhythmic discharges that begin and end abruptly. Prognosis is generally good with fair rates of response to treatment and with most patients growing out of their absencese. However, learning difficulties and seizure occurrence rates remain higher than the general population even after several years. When typical absence seizures start the age of 8– 9 years old when the absence seizures are infrequent or when the absence seizures are observed in a patient that had experienced a generalized tonic-clonic seizure, a diagnosis of juvenile absence epilepsy should be considered.

Signs and symptoms
CAE is characterized by the presence of absence seizures. The absence seizures are usually brief (about 4 to 30 seconds) but occur frequently, usually around a dozen per day but sometimes even hundreds of times per day. They involve abrupt impairment of consciousness with loss of awareness and responsiveness, behavioral arrest, and arrest of the activity that may vary from complete arrest to continuing the activity with an altered status. Other seizure features include starring, eyelid movement or eye-opening and pallor. Mild automatisms and mild movements at the beginning of the seizures are frequent, but major motor involvement, as atonic falls, early in the course of the disease excludes this diagnosis.The International League Against Epilepsy commission defined absence seizure as “of sudden onset, interruption of ongoing activities, staring, possible upwards version of eyes with few seconds duration, associated with symmetrical 2–4 Hz, mainly 3 Hz spike-wave complexes, normal background activity. Absence seizure was divided into two subgroups (Penry et al. 1975), first with consciousness impairment, and others were associated with the other clinical component, namely clonic, atonic, tonic, autonomic, and with automatisms. Though CAE usually occurs in children with normal neurodevelopment and are sensitive to antiepileptic treatments children with CAE have a risk of academic failure and high rates of attention deficits.

Neuropsychological impairment
Neuropsychological impairment in children with CAE is frequent and includes executive dysfunction, attention problems, learning disabilities, and language problems. These problems even persist after seizures are treated. Monitoring with validated cognition scales should be performed. Many existing data illustrate that children with CAE have an average IQ but present subtle cognitive difficulties. In cases with lower IQ, significant social difficulties can be often seen. Behavioral issues may also be present and their occurrence might be associated with significantly worse cognitive development. Some evidence suggest that  are impairment is more prominent in verbal rather than non-verbal capacities of children with CAE  or are even limited to few areas of verbal expression as phonological and category fluency. Attention deficit disorder and specific learning disorders are also frequently found in the CAE and can interfere with academic performance as well as with day to day activities of the children.

Causes
CAE is considered as a complex polygenic disorder. This fact is supported by the high occurrence (up to 20%) of generalized epilepsies or febrile seizures in family members of children with CAE. In cases with early onset or accompanying features, Glut-1 deficiency (a metabolic disorder responding well to ketogenic diet) could be the cause of the absence seizures. Genetic mutations have been identified in recent years involving mainly GABA receptors and calcium channel modulator genes.

Pathophysiology
Pathophysiology of absence seizures has been widely studied in animal models but is not fully decoded to date. There is however solid evidence for the involvement of bilateral cortical and subcortical networks which are part of the default state system. Pathophysiology when genetic mutations are present is further discussed below. Particularly in the Han Chinese population, there is an association between mutations in the calcium channel, voltage-dependent, T type, alpha 1H subunit (CACNA1H), and childhood absence epilepsy. These mutations cause increased channel activity and associated increased neuronal excitability. Seizures are believed to originate in the thalamus, where there is an abundance of T-type calcium channels such as those encoded by the CACNA1H gene (12). In a European study CACNA1H associated with CAE, 20 mutations have been identified. These mutations are likely not wholly causative and should instead be thought of as giving susceptibility. This is particularly true since some groups have found no connection between CAE and CACNA1H mutations. Many of the CACNA1H mutations have a measurable effect on channel kinetics on activation time constant and voltage dependence, on deactivation time constant, and on inactivation time constant and voltage dependence. should leading either to neuronal excitability or hypo excitability. However, these predictions result from mathematical modeling and may differ from what occurs in neurons (in vivo) where other proteins, some of which may interact with CACNA1H, are present. Along with mutations in the CACNA1H gene, two mutations in gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2), the gene encoding a GABAA receptor gamma subunit, are also associated with a CAE-like phenotype that also overlaps with generalized epilepsy with febrile seizures plus type-3. The first of these, R43Q, abolishes benzodiazepine potentiation of gamma-aminobutyric acid induced currents. The second associated mutation, C588T, has not been further characterized.

Diagnosis
CAE can be diagnosed during an outpatient clinic visit with a careful history, physical exam including hyperventilation, and a routine electroencephalogram. The diagnosis is made upon the history of absence seizures during early childhood without other seizure types and the observation of 3 Hz generalized spike waves paroxysmal discharges on the EEG. In children with CAE without atypical features electroclinical features, no neuroimaging is needed.

Management
There are three antiepileptic drugs that have been used for the first-line treatment for CAE; these are ethosuximide (ETX), valproic acid (VPA), and lamotrigine (LTG). ETX is an effective first-line treatment for seizures only by blocking the low-threshold calcium currents produced by T-type calcium channels in the thalamus. The peak level occurs after 3–5 hours of intake; steady levels of the drug in the blood are achieved after 7–10 days of the same daily dose. The usual dosage is 20–30 mg/kg/day divided into two doses. Common side effects include gastrointestinal disturbances such as hiccups, vomiting, abdominal discomfort, and diarrheic and exceptionally. The other symptoms, like fatigue, insomnia, dizziness and ataxia. Valproate (VPA) has also been proven effective monotherapy in CAE although ETX is usually preferred as it has a lower impact on attention according to the Childhood Epilepsy study. There are several mechanisms related to VPA’s antiepileptic action, including raising the level of gamma-aminobutyric acid (GABA), calcium-dependent potassium activating, and blocking of voltage-sensitive sodium channels, but there is no specific evidence for the mechanism by which VPA controls absence seizures </s>