<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 Viral meningitis and can you explain it in depth? [/INST] Viral meningitis, also known as aseptic meningitis, is a type of meningitis due to a viral infection. It results in inflammation of the meninges (the membranes covering the brain and spinal cord). Symptoms commonly include headache, fever, sensitivity to light and neck stiffness.Viruses are the most common cause of aseptic meningitis. Most cases of viral meningitis are caused by enteroviruses (common stomach viruses). However, other viruses can also cause viral meningitis, such as West Nile virus, mumps, measles, herpes simplex types I and II, varicella and lymphocytic choriomeningitis (LCM) virus. Based on clinical symptoms, viral meningitis cannot be reliably differentiated from bacterial meningitis, although viral meningitis typically follows a more benign clinical course. Viral meningitis has no evidence of bacteria present in cerebral spinal fluid (CSF). Therefore, lumbar puncture with CSF analysis is often needed to identify the disease.In most cases, there is no specific treatment, with efforts generally aimed at relieving symptoms (headache, fever or nausea). A few viral causes, such as HSV, have specific treatments.
In the United States, viral meningitis is the cause of more than half of all cases of meningitis. With the prevalence of bacterial meningitis in decline, the viral disease is garnering more and more attention. The estimated incidence has a considerable range, from 0.26 to 17 cases per 100,000 people. For enteroviral meningitis, the most common cause of viral meningitis, there are up to 75,000 cases annually in the United States alone. While the disease can occur in both children and adults, it is more common in children.

Signs and symptoms
Viral meningitis characteristically presents with fever, headache and neck stiffness. Fever is the result of cytokines released that affect the thermoregulatory (temperature control) neurons of the hypothalamus. Cytokines and increased intracranial pressure stimulate nociceptors in the brain that lead to headaches. Neck stiffness is the result of inflamed meninges stretching due to flexion of the spine. The various layers of meninges act form a separation between the brain and the skull. In contrast to bacterial meningitis, symptoms associated with viral meningitis are often less severe and do not progress as quickly. Nausea, vomiting and photophobia (light sensitivity) also commonly occur, as do general signs of a viral infection, such as muscle aches and malaise. Increased cranial pressure from viral meningitis stimulates the area postrema, which causes nausea and vomiting. Widened pulse pressure (systolic - diastolic blood pressure), bradycardia, and irregular respiration would be alarming for Cushings reflex, a sign of acutely elevated intracranial pressure. Photophobia is due to meningeal irritation. In severe cases, people may experience concomitant encephalitis (meningoencephalitis), which is suggested by symptoms such as altered mental status, seizures or focal neurologic deficits.Babies with viral meningitis may only appear irritable, sleepy or have trouble eating. Infection in the neonatal period may be the result of infection during pregnancy. In severe cases, people may experience concomitant encephalitis (meningoencephalitis), which is suggested by symptoms such as altered mental status, seizures or focal neurologic deficits. The pediatric population may show some additional signs and symptoms that include jaundice and bulging fontanelles. A biphasic fever is more often seen in children compared to adults. The first fever arrives with the onset of general constitutional symptoms, and the second accompanying the onset of the neurological symptoms.Symptoms can vary depending on the virus responsible for infection. Enteroviral meningitis (the most common cause) typically presents with the classic headache, photophobia, fever, nausea, vomiting, and nuchal rigidity. With coxsackie and echo virus specifically, a maculopapular rash may be present, or even the typical vesicles seen with Herpangina. Lymphocytic choriomeningitis virus (LCMV) can be differentiated from the common presenting meningeal symptoms by the appearance of a prodromal influenza-like sickness about 10 days before other symptoms begin. Mumps meningitis can present similarly to isolated mumps, with possible parotid and testicular swelling. Interestingly, research has shown that HSV-2 meningitis most often occurs in people with no history of genital herpes, and that a severe frontal headache is among the most common presenting symptoms. Patients with varicella zoster meningitis may present with herpes zoster (Shingles) in conjunction with classic meningeal signs. Meningitis can be an indication that an individual with HIV is undergoing seroconversion, the time when the human body is forming antibodies in response to the virus.

Causes
The most common causes of viral meningitis in the United States are non-polio enteroviruses. The viruses that cause meningitis are typically acquired from sick contacts. However, in most cases, people infected with viruses that may cause meningitis do not actually develop meningitis.Viruses that can cause meningitis include:

Mechanism
Viral Meningitis is mostly caused by an infectious agent that has colonized somewhere in its host. People who are already in an immunocompromised state are at the highest risk of pathogen entry. Some of the most common examples of immunocompromised individuals include those with HIV, cancer, diabetes, malnutrition, certain genetic disorders, and patients on chemotherapy. Potential sites for this include the skin, respiratory tract, gastrointestinal tract, nasopharynx, and genitourinary tract. The organism invades the submucosa at these sites by invading host defenses, such as local immunity, physical barriers, and phagocytes or macrophages. After pathogen invasion, the immune system is activated. An infectious agent can enter the central nervous system and cause meningeal disease via invading the bloodstream, a retrograde neuronal pathway, or by direct contiguous spread. Immune cells and damaged endothelial cells release matrix metalloproteinases (MMPs), cytokines, and nitric oxide. MMPs and NO induce vasodilation in the cerebral vasculature. Cytokines induce capillary wall changes in the blood brain barrier, which leads to expression of more leukocyte receptors, thus increasing white blood cell binding and extravasation.The barrier that the meninges create between the brain and the bloodstream are what normally protect the brain from the bodys immune system. Damage to the meninges and endothelial cells increases cytotoxic reactive oxygen species production, which damages pathogens as well as nearby cells. In meningitis, the barrier is disrupted, so once viruses have entered the brain, they are isolated from the immune system and can spread. This leads to elevated intracranial pressure, cerebral edema, meningeal irritation, and neuronal death.

Diagnosis
The diagnosis of viral meningitis is made by clinical history, physical exam, and several diagnostic tests. Kernig and Brudzinski signs may be elucidated with specific physical exam maneuvers, and can help diagnose meningitis at the bedside. Most importantly however, cerebrospinal fluid (CSF) is collected via lumbar puncture (also known as spinal tap). This fluid, which normally surrounds the brain and spinal cord, is then analyzed for signs of infection. CSF findings that suggest a viral cause of meningitis include an elevated white blood cell count (usually 10-100  cells/µL) with a lymphocytic predominance in combination with a normal glucose level. Increasingly,  cerebrospinal fluid PCR tests have become especially useful for diagnosing viral meningitis, with an estimated sensitivity of 95-100%. Additionally, samples from the stool, urine, blood and throat can also help to identify viral meningitis. CSF vs serum c-reactive protein and procalcitonin have not been shown to elucidate whether meningitis is bacterial or viral.In certain cases, a CT scan of the head should be done before a lumbar puncture such as in those with poor immune function or those with increased intracranial pressure. If the patient has focal neurological deficits, papilledema, a Glasgow Coma Score less than 12, or a recent history of seizures, lumbar puncture should be reconsidered.Differential diagnosis for viral meningitis includes meningitis caused by bacteria, mycoplasma, fungus, and drugs such as NSAIDS, TMP-SMX, IVIG. Further considerations include brain tumors, lupus, vasculitis, and Kawasaki disease in the pediatric population.

Treatment
Because there is no clinical differentiation between bacterial and viral meningitis, people with suspected disease should be sent to the hospital for further evaluation. Treatment for viral meningitis is generally supportive. Rest, hydration, antipyretics, and pain or anti-inflammatory medications may be given as needed. However, if there is initial uncertainty as to whether the meningitis is bacterial or viral in origin, empiric antibiotics are often given until bacterial infection is ruled out.Herpes simplex virus, varicella zoster virus and cytomegalovirus have a specific antiviral therapy. For herpes the treatment of choice is aciclovir. If encephalitis is suspected, empiric treatment with IV aciclovir is often warranted.Surgical management is indicated where there is extremely increased intracranial pressure, infection of an adjacent bony structure (e.g. mastoiditis), skull fracture, or abscess formation.The majority of people that have viral meningitis get better within 7–10 days.

Epidemiology
From 1988 to 1999, about 36,000 cases occurred each year. As recently as 2017, the incidence in the U.S. alone increased to 75,000 cases per year for enteroviral meningitis </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 Craniopharyngioma and can you explain it in depth? [/INST] A craniopharyngioma is a rare type of brain tumor derived from pituitary gland embryonic tissue that occurs most commonly in children, but also affects adults. It may present at any age, even in the prenatal and neonatal periods, but peak incidence rates are childhood-onset at 5–14 years and adult-onset at 50–74 years. People may present with bitemporal inferior quadrantanopia leading to bitemporal hemianopsia, as the tumor may compress the optic chiasm. It has a point prevalence around two per 1,000,000. Craniopharyngiomas are distinct from Rathkes cleft tumours and intrasellar arachnoid cysts.

Symptoms and signs
Craniopharyngiomas are almost always benign. However, as with many brain tumors, their treatment can be difficult, and significant morbidities are associated with both the tumor and treatment.

Headache (obstructive hydrocephalus)
Hypersomnia
Myxedema
Postsurgical weight gain
Polydipsia
Polyuria (diabetes insipidus)
Vision loss (bitemporal hemianopia)
VomitingOften occurs after treatment
Growth hormone (GH) insufficiency, caused by the reduction in GH production - symptoms include:
Stunted growth and delayed puberty (in children)
General fatigue, loss of muscle mass and tone (in adults)
Pituitary insufficiency
Often occurs to some degree because craniopharyngiomas develop in the area of the pituitary stalk, which can affect the function of the pituitary gland and many other hormones
Reduction in prolactin production is very uncommon and occurs with severe pituitary insufficiency.
Large pituitary tumors can paradoxically elevate blood prolactin levels due to the "stalk effect". This elevation occurs as a result of the compression of the pituitary stalk, which interferes with the brains control of prolactin production.
In premenopausal women, elevated prolactin can lead to reduction or loss of menstrual periods and/or breast milk production (galactorrhea).
With stalk effect, prolactin levels are usually only slightly elevated, as opposed to prolactinomas in which the prolactin level is usually very high.
Diabetes insipidus occurs due to the absence of a posterior pituitary hormone called antidiuretic hormone. Symptoms include:
Excessive thirst
Excessive urination
Adrenal insufficiency occurs because of a reduction in ACTH production, a reduction in cortisol. In severe cases, it can be fatal. Symptoms include:
Fatigue
Low blood pressure
Electrolyte abnormalities

Mechanisms
Craniopharyngioma is a rare, usually suprasellar neoplasm, which may be cystic, that develops from nests of epithelium derived from Rathkes pouch. Rathkes pouch is an embryonic precursor of the anterior pituitary.Craniopharyngiomas are typically very slow-growing tumors. They arise from the cells along the pituitary stalk, specifically from nests of odontogenic (tooth-forming) epithelium within the suprasellar/diencephalic region, so contain deposits of calcium that are evident on an X-ray.

Diagnosis
Imaging scans for craniopharyngioma
A physician can conduct a few scans and tests to diagnose a person with craniopharyngioma. High-resolution magnetic resonance imaging (MRI) is valuable because it allows the neuroradiologist to view the tumor from different angles.In some cases, a powerful 3T (Tesla) MRI scanner can help define the location of critical brain structures affected by the tumor. The histologic pattern consists of nesting of squamous epithelium bordered by radially arranged cells. It is frequently accompanied by calcium deposition and may have a microscopic papillary architecture. A computed tomography (CT) scan is also a good diagnostic tool, as it detects calcification in the tumor.Two distinct types are recognized:
Adamantinomatous craniopharyngiomas, which resemble ameloblastomas (the most common type of odontogenic tumor), are characterized by activating CTNNB1 mutations.
Papillary craniopharyngiomas are characterized by BRAFv600E mutations.In the adamantinomatous type, calcifications are visible on neuroimaging and are helpful in diagnosis.
The papillary type rarely calcifies. A vast majority of craniopharyngiomas in children are adamantiomatous, whereas both subtypes are common in adults. Mixed-type tumors also occur.On macroscopic examination, craniopharyngiomas are cystic or partially cystic with solid areas. On light microscopy, the cysts are seen to be lined by stratified squamous epithelium. Keratin pearls may also be seen. The cysts are usually filled with a yellow, viscous fluid rich in cholesterol crystals. Of a long list of possible symptoms, the most common presentations include headaches, growth failure, and bitemporal hemianopsia.

Malignant craniopharyngioma
Craniopharyngiomas are usually successfully managed with a combination of adjuvant chemotherapy and neurosurgery. Recent research describes the rare occurrence of malignant transformations of these normally benign tumors. Malignant craniopharyngiomas can occur at any age, are slightly more common in females, and are usually of the adamantinomatous type.The malignant transformations can take years to occur (although one in five of the diagnosed cases were de novo transformations), hence the need for lengthier follow-up in patients diagnosed with the more common benign forms.No link has been found between malignancy and initial chemoradiotherapy treatment, and the overall survival rate was very poor with median survival being 6 months after diagnosis of malignancy.

Prevention
Although the causes of craniopharyngioma are unknown, it can occur in both children and adults, with a peak in incidence at 9 to 14 years of age. About 120 cases are diagnosed each year in the United States in patients under the age of 19. More than 50% of all patients with craniopharyngioma are under the age of 18 years. No clear association of the tumor exists with a particular gender or race. Craniopharyngiomas do not appear to "run in families" or to be directly inherited from the parents.

Treatment
Treatment generally consists of subfrontal or transsphenoidal excision. Endoscopic surgery through the nose often performed by a joint team of neurosurgeons and ENT, is increasingly being considered as an alternative to transcranial surgery done by making an opening in the skull. Because of the location of the craniopharyngioma near the brain and skullbase, a surgical navigation system might be used to verify the position of surgical tools during the operation.Additional radiotherapy is also used if total removal is not possible. Due to the poor outcomes associated with damage to the pituitary and hypothalamus from surgical removal and radiation, experimental therapies using intracavitary phosphorus-32, yttrium, or bleomycin delivered via an external reservoir are sometimes employed, especially in young patients. The tumor, being in the pituitary gland, can cause secondary health problems. The immune system, thyroid levels, growth hormone levels, and testosterone levels can be compromised from craniopharygioma. All of these health problems can be treated with modern medicine. No high quality evidence has evaluated the use of bleomycin in this condition.Proton therapy affords a reduction in dose to critical structures compared to conventional photon radiation, including IMRT, for patients with craniopharyngioma.The most effective treatment package for the malignant craniopharyngiomas described in literature is a combination gross total resective surgery with adjuvant chemoradiotherapy. The chemotherapy drugs paclitaxel and carboplatin have shown a clinical (but not statistical) significance in increasing the survival rate in patients who have had gross total resections of their malignant tumours.

Prognosis
Craniopharyngiomas are generally benign but are known to recur after resection. Recent research has demonstrated a malignant (but rare) tendency of craniopharyngiomas. These malignant craniopharyngiomas are very rare but are associated with poor prognosis.

Recent research
Current research has shown ways of treating the tumors in a less invasive way while others have shown how the hypothalamus can be stimulated along with the tumor to prevent the child and adult with the tumor to become obese. Craniopharyngioma of childhood are commonly cystic in nature </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 Cerebral arteriovenous malformation and can you explain it in depth? [/INST] A cerebral arteriovenous malformation (cerebral AVM, CAVM, cAVM) is an abnormal connection between the arteries and veins in the brain—specifically, an arteriovenous malformation in the cerebrum.

Signs and symptoms
The most frequently observed problems, related to an AVM, are headaches and seizures, cranial nerve deficits, backaches, neckaches and eventual nausea, as the coagulated blood makes its way down to be dissolved in the individuals spinal fluid. It is supposed that 15% of the population, at detection, have no symptoms at all. Other common symptoms are a pulsing noise in the head, progressive weakness and numbness and vision changes as well as debilitating, excruciating pain.In serious cases, the blood vessels rupture and there is bleeding within the brain (intracranial hemorrhage). Nevertheless, in more than half of patients with AVM, hemorrhage is the first symptom. Symptoms due to bleeding include loss of consciousness, sudden and severe headache, nausea, vomiting, incontinence, and blurred vision, amongst others. Impairments caused by local brain tissue damage on the bleed site are also possible, including seizure, one-sided weakness (hemiparesis), a loss of touch sensation on one side of the body and deficits in language processing (aphasia).  Ruptured AVMs are responsible for considerable mortality and morbidity.AVMs in certain critical locations may stop the circulation of the cerebrospinal fluid, causing accumulation of the fluid within the skull and giving rise to a clinical condition called hydrocephalus. A stiff neck can occur as the result of increased pressure within the skull and irritation of the meninges.

Pathophysiology
AVMs are an abnormal connection between the arteries and veins in the human brain. Arteriovenous malformations are most commonly of prenatal origin. In a normal brain oxygen enriched blood from the heart travels in sequence through smaller blood vessels going from arteries, to arterioles and then capillaries. Oxygen is removed in the latter vessel to be used by the brain. After the oxygen is removed blood reaches venules and later veins which will take it back to the heart and lungs. On the other hand, when there is an AVM blood goes directly from arteries to veins through the abnormal vessels disrupting the normal circulation of blood.

Diagnosis
An AVM diagnosis is established by neuroimaging studies after a complete neurological and physical examination. Three main techniques are used to visualize the brain and search for AVM: computed tomography (CT), magnetic resonance imaging (MRI), and cerebral angiography. A CT scan of the head is usually performed first when the subject is symptomatic. It can suggest the approximate site of the bleed. MRI is more sensitive than CT in the diagnosis of AVMs and provides better information about the exact location of the malformation. More detailed pictures of the tangle of blood vessels that compose an AVM can be obtained by using radioactive agents injected into the blood stream. If a CT is used in conjunctiangiogram, this is called a computerized tomography angiogram; while, if MRI is used it is called magnetic resonance angiogram.  The best images of an AVM are obtained through cerebral angiography. This procedure involves using a catheter, threaded through an artery up to the head, to deliver a contrast agent into the AVM.  As the contrast agent flows through the AVM structure, a sequence of X-ray images are obtained.

Grading
Spetzler-Martin (SM) Grade
A common method of grading cerebral AVMs is the Spetzler-Martin (SM) grade.  This system was designed to assess the patients risk of neurological deficit after open surgical resection (surgical morbidity), based on characteristics of the AVM itself. Based on this system, AVMs may be classified as grades 1 - 5.  This system was not intended to characterize risk of hemorrhage.
"Eloquent" is defined as areas within the brain that, if removed will result in loss of sensory processing or linguistic ability, minor paralysis, or paralysis.  These include the basal ganglia, language cortices, sensorimotor regions, and white matter tracts. Importantly, eloquent areas are often defined differently across studies where deep cerebellar nuclei, cerebral peduncles, thalamus, hypothalamus, internal capsule, brainstem, and the visual cortex could be included.
The risk of post-surgical neurological deficit (difficulty with language, motor weakness, vision loss) increases with increasing Spetzler-Martin grade.

Supplemented Spetzler-Martin (SM-supp, Lawton-Young) Grade
A limitation of the Spetzler-Martin Grading system is that it does not include the following factors: Patient age, hemorrhage, diffuseness of nidus, and arterial supply. In 2010 a new supplemented Spetzler-Martin system (SM-supp, Lawton-Young) was devised adding these variables to the SM system. Under this new system AVMs are classified from grades 1 - 10. It has since been determined to have greater predictive accuracy that Spetzler-Martin grades alone.

Treatment
Treatment depends on the location and size of the AVM and whether there is bleeding or not.The treatment in the case of sudden bleeding is focused on restoration of vital function.Medical management
Anticonvulsant medications such as phenytoin are often used to control seizure; medications or procedures may be employed to relieve intracranial pressure.  Eventually, curative treatment may be required to prevent recurrent hemorrhage. However, any type of intervention may also carry a risk of creating a neurological deficit.Preventive treatment of as yet unruptured brain AVMs has been controversial, as several studies suggested favorable long-term outcome for unruptured AVM patients not undergoing intervention. The NIH-funded longitudinal ARUBA study ("A Randomized trial of Unruptured Brain AVMs) compares the risk of stroke and death in patients with preventive AVM eradication versus those followed without intervention. Interim results suggest that fewer strokes occur as long as patients with unruptured AVM do not undergo intervention. Because of the higher than expected event rate in the interventional arm of the ARUBA study, NIH/NINDS stopped patient enrollment in April 2013, while continuing to follow all participants to determine whether the difference in stroke and death in the two arms changes over time.Surgical management
Surgical elimination of the blood vessels involved is the preferred curative treatment for many types of AVM. Surgery is performed by a neurosurgeon who temporarily removes part of the skull (craniotomy), separates the AVM from surrounding brain tissue, and resects the abnormal vessels. While surgery can result in an immediate, complete removal of the AVM, risks exist depending on the size and the location of the malformation. The AVM must be resected en bloc, for partial resection will likely cause severe hemorrhage. The preferred treatment of Spetzler-Martin grade 1 and 2 AVMs in young, healthy patients is surgical resection due to the relatively small risk of neurological damage compared to the high lifetime risk of hemorrhage. Grade 3 AVMs may or may not be amenable to surgery. Grade 4 and 5 AVMs are not usually surgically treated.Radiosurgical management
Radiosurgery has been widely used on small AVMs with considerable success.  The Gamma Knife is an apparatus used to precisely apply a controlled radiation dosage to the volume of the brain occupied by the AVM. While this treatment does not require an incision and craniotomy (with their own inherent risks), three or more years may pass before the complete effects are known, during which time patients are at risk of bleeding. Complete obliteration of the AVM may or may not occur after several years, and repeat treatment may be needed. Radiosurgery is itself not without risk. In one large study, nine percent of patients had transient neurological symptoms, including headache, after radiosurgery for AVM. However, most symptoms resolved, and the long-term rate of neurological symptoms was 3.8%.Neuroendovascular therapy
Embolization is performed by interventional neuroradiologists and the occlusion of blood vessels most commonly is obtained with Ethylene-vinyl alcohol copolymer (Onyx) or N-butyl cyanoacrylate (NBCA). These substances are introduced by a radiographically guided catheter, and block vessels responsible for blood flow into the AVM. Embolization is frequently used as an adjunct to either surgery or radiation treatment. Embolization reduces the size of the AVM and during surgery it reduces the risk of bleeding. However, embolization alone may completely obliterate some AVMs. In high flow intranidal fistulas balloons can also be used to reduce the flow so that embolization can be done safely.

Prognosis
The main risk is intracranial hemorrhage. This risk is difficult to quantify since many patients with asymptomatic AVMs will never come to medical attention </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 Varicocele and can you explain it in depth? [/INST] A varicocele is an abnormal enlargement of the pampiniform venous plexus in the scrotum. This plexus of veins drains blood from the testicles back to the heart. The vessels originate in the abdomen and course down through the inguinal canal as part of the spermatic cord on their way to the testis. Varicoceles occur in around 15% to 20% of all men. The incidence of varicocele increase with age.

Signs and symptoms
Varicocele might be noticed as soft lumps, usually above the testicle and mostly on the left side of the scrotum. Right-sided and bilateral varicocele does also occur. Men with varicocele can feel symptoms of pain or heaviness in their scrotum. Large varicoceles present as plexus of veins and may be described as "bag of worms". Varicocele is sometimes discovered when investigating the cause of male infertility.

Cause
There are three main theories as to the anatomical cause; the first has to do with the geometry of the veins, wherein the vein on the left side connects to the larger outflowing vein at a right angle, which tends to fail; the second is that valves that are supposed to prevent backflow fail (venous insufficiency); the third is due to excessive pressure in upstream arteries, created by nutcracker syndrome.

Pathophysiology
Often the greatest concern with respect to varicocele is its effect on male fertility. The relationship between varicocele and infertility is unclear. Some men with the condition are fertile, some have sperm that are normal in shape and move normally but are compromised in function, and some have sperm with abnormal shapes or that do not move well </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 Astigmatism and can you explain it in depth? [/INST] Astigmatism is a type of refractive error due to rotational asymmetry in the eyes refractive power.  This results in distorted or blurred vision at any distance. Other symptoms can include eyestrain, headaches, and trouble driving at night. Astigmatism often occurs at birth and can change or develop later in life. If it occurs in early life and is left untreated, it may result in amblyopia.The cause of astigmatism is unclear; however, it is believed to be partly related to genetic factors. The underlying mechanism involves an irregular curvature of the cornea or abnormalities in the lens of the eye. Diagnosis is by an eye examination, through objective and subjective refraction.Three treatment options are available: glasses, contact lenses, and surgery. Glasses are the simplest. Contact lenses can provide a wider field of vision. Refractive surgery permanently changes the shape of the eye.In Europe and Asia, astigmatism affects between 30 and 60% of adults. People of all ages can be affected by astigmatism. Astigmatism was first reported by Thomas Young in 1801.

Signs and symptoms
Although astigmatism may be asymptomatic, higher degrees of astigmatism may cause symptoms such as blurred vision, double vision, squinting, eye strain, fatigue, or headaches. Some research has pointed to the link between astigmatism and higher prevalence of migraine headaches.

Causes
Congenital
The cause of congenital astigmatism is unclear, however it is believed to be partly related to genetic factors. Genetics, based on twin studies, appear to play only a small role in astigmatism as of 2007.Genome-wide association studies (GWAS) have been used to investigate the genetic foundation of astigmatism. Although no conclusive result has been shown, various candidates have been identified. In a study conducted in 2011 on various Asian populations, variants in the PDGFRA gene on chromosome 4q12 were identified to be associated with corneal astigmatism. A follow-up study in 2013 on the European population, however, found no variant significantly associated with corneal astigmatism at the genome-wide level (single-nucleotide polymorphism rs7677751 at PDGFRA). Facing the inconsistency, a study by Shah and colleagues in 2018 included both populations with Asian and Northern European ancestry. They successfully replicated the previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, with a further success of identifying three novel candidate genes: CLDN7, ACP2, and TNFAIP8L3. Other GWAS studies also provided inconclusive results: Lopes and colleagues identified a susceptibility locus with lead single nucleotide polymorphism rs3771395 on chromosome 2p13.3 in the VAX2 gene (VAX2 plays an important role in the development of the dorsoventral axis of the eye); Li and associates, however, found no consistent or strong genetic signals for refractive astigmatism while suggesting a possibility of widespread genetic co-susceptibility for spherical and astigmatic refractive errors. They also found that the TOX gene region previously identified for spherical equivalent refractive error was the second most strongly associated region. Another recent follow-up study again had identified four novel loci for corneal astigmatism, with two also being novel loci for astigmatism: ZC3H11B (associated with axial length), NPLOC4 (associated with myopia), LINC00340 (associated with spherical equivalent refractive error) and HERC2 (associated with eye color).

Acquired
Astigmatism may also occur following a cataract surgery or a corneal injury. Contraction of the scar due to wound or cataract extraction causes astigmatism due to flattening of the cornea in one direction. In keratoconus, progressive thinning and steepening of the cornea cause irregular astigmatism.

Pathophysiology
Axis of the principal meridian
Regular astigmatism – principal meridians are perpendicular. (The steepest and flattest meridians of the eye are called principal meridians.)
With-the-rule astigmatism – the vertical meridian is steepest (a rugby ball or American football lying on its side).
Against-the-rule astigmatism – the horizontal meridian is steepest (a rugby ball or American football standing on its end).
Oblique astigmatism – the steepest curve lies in between 120 and 150 degrees and 30 and 60 degrees.
Irregular astigmatism – principal meridians are not perpendicular.In with-the-rule astigmatism, the eye has too much "plus" cylinder in the horizontal axis relative to the vertical axis (i.e., the eye is too "steep" along the vertical meridian relative to the horizontal meridian). Vertical beams of light focus in front (anterior) to horizontal beams of light, in the eye. This problem may be corrected using spectacles which have a "minus" cylinder placed on this horizontal axis. The effect of this will be that when a vertical beam of light in the distance travels towards the eye, the "minus" cylinder (which is placed with its axis lying horizontally – meaning in line with the patients horizontal meridian relative to the excessively steep vertical meridian) will cause this vertical beam of light to slightly "diverge", or "spread out vertically", before it reaches the eye. This compensates for the fact that the patients eye converges light more powerfully in the vertical meridian than the horizontal meridian. Hopefully, after this, the eye will focus all light on the same location at the retina, and the patients vision will be less blurred.In against-the-rule astigmatism, a plus cylinder is added in the horizontal axis (or a minus cylinder in the vertical axis).Axis is always recorded as an angle in degrees, between 0 and 180 degrees in a counter-clockwise direction. Both 0 and 180 degrees lie on a horizontal line at the level of the center of the pupil, and as seen by an observer, 0 lies on the right of both the eyes.Irregular astigmatism, which is often associated with prior ocular surgery or trauma, is also a common naturally occurring condition. The two steep hemimeridians of the cornea, 180° apart in regular astigmatism, may be separated by less than 180° in irregular astigmatism (called nonorthogonal irregular astigmatism); and/or the two steep hemimeridians may be asymmetrically steep—that is, one may be significantly steeper than the other (called asymmetric irregular astigmatism). Irregular astigmatism is quantified by a vector calculation called topographic disparity.

Focus of the principal meridian
With accommodation relaxed:

Simple astigmatism
Simple hyperopic astigmatism – first focal line is on the retina, while the second is located behind the retina.
Simple myopic astigmatism – first focal line is in front of the retina, while the second is on the retina.
Compound astigmatism
Compound hyperopic astigmatism – both focal lines are located behind the retina.
Compound myopic astigmatism – both focal lines are located in front of the retina.
Mixed astigmatism – focal lines are on both sides of the retina (straddling the retina).

Throughout the eye
Astigmatism, whether it is regular or irregular, is caused by some combination of external (corneal surface) and internal (posterior corneal surface, human lens, fluids, retina, and eye-brain interface) optical properties. In some people, the external optics may have the greater influence, and in other people, the internal optics may predominate. Importantly, the axes and magnitudes of external and internal astigmatism do not necessarily coincide, but it is the combination of the two that by definition determines the overall optics of the eye. The overall optics of the eye are typically expressed by a persons refraction; the contribution of the external (anterior corneal) astigmatism is measured through the use of techniques such as keratometry and corneal topography. One method analyzes vectors for planning refractive surgery such that the surgery is apportioned optimally between both the refractive and topographic components.

Diagnosis
A number of tests are used during eye examinations to determine the presence of astigmatism and to quantify its amount and axis. A Snellen chart or other eye charts may initially reveal reduced visual acuity. A keratometer may be used to measure the curvature of the steepest and flattest meridians in the corneas front surface. Corneal topography may also be used to obtain a more accurate representation of the corneas shape. An autorefractor or retinoscopy may provide an objective estimate of the eyes refractive error and the use of Jackson cross cylinders in a phoropter or trial frame may be used to subjectively refine those measurements. An alternative technique with the phoropter requires the use of a "clock dial" or "sunburst" chart to determine the astigmatic axis and power. A keratometer may also be used to estimate astigmatism by finding the difference in power between the two primary meridians of the cornea. Javals rule can then be used to compute the estimate of astigmatism.
A method of astigmatism analysis by Alpins may be used to determine both how much surgical change of the cornea is needed and after surgery to determine how close treatment was to the goal.Another rarely used refraction technique involves the use of a stenopaeic slit (a thin slit aperture) where the refraction is determined in specific meridians – this technique is particularly useful in cases where the patient has a high degree of astigmatism or in refracting patients with irregular astigmatism.

Classification
There are three primary types of astigmatism: myopic astigmatism, hyperopic astigmatism, and mixed astigmatism. Cases can be classified further, such as regular or irregular and lenticular or corneal.

Treatment
Astigmatism may be corrected with eyeglasses, contact lenses, or refractive surgery. Glasses are the simplest and safest, although contact lenses can provide a wider field of vision. Refractive surgery can eliminate the need to wear corrective lenses altogether by permanently changing the shape of the eye but, like all elective surgery, comes with both greater risk and expense than the non-invasive options. Various considerations involving eye health, refractive status, and lifestyle determine whether one option may be better than another. In those with keratoconus, certain contact lenses often enable patients to achieve better visual acuity than eyeglasses. Once only available in a rigid, gas-permeable form, toric lenses are now also available as soft lenses.
In older people, astigmatism can also be corrected during cataract surgery. This can either be done by inserting a toric intraocular lens or by performing special incisions (limbal relaxing incisions). Toric intraocular lenses probably provide a better outcome with respect to astigmatism in these cases than limbal relaxing incisions.Toric intraocular lenses can additionally be used in patients with complex ophthalmic history, such as previous ophthalmic surgery </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 Phytophotodermatitis and can you explain it in depth? [/INST] Phytophotodermatitis, also known as berloque dermatitis or margarita photodermatitis, is a cutaneous phototoxic inflammatory reaction resulting from contact with a light-sensitizing botanical agent followed by exposure to ultraviolet light (from the sun, for instance). Symptoms include erythema, edema, blisters (vesicles and/or bullae), and delayed hyperpigmentation. Heat and moisture tend to exacerbate the reaction.
A reaction may be elicited in any person who has been exposed to adequate amounts of both a photosensitizer and ultraviolet light. Phytophotodermatitis is not an immunologic response; no prior exposure to the photosensitizing agent is required.
The photosensitizing substances found in phototoxic plants belong to a class of chemical compounds called the furanocoumarins, which are activated by long-wavelength ultraviolet (UVA) light. The most toxic of these organic compounds are the linear furanocoumarins, so called since they exhibit a linear chemical structure. Bergapten and xanthotoxin (also known as methoxsalen), two linear furanocoumarins derived from psoralen, are invariably found in plants associated with phytophotodermatitis.

Symptoms and signs
A reaction typically begins within 24 hours of exposure and peaks at 48–72 hours after exposure. Initially, the skin turns red and starts to itch and burn. Large blisters (or bullae) form within 48 hours. The blisters may leave black, brown, or purplish scars that can last for several years. This hyperpigmentation of the skin is caused by the production of melanin triggered by the furanocoumarins.
Although media reports have suggested that eye exposure to the agent can lead to temporary or permanent blindness, the risk of permanent blindness is not supported by existing research.Phytophotodermatitis can affect people of any age. In children, it has sometimes been mistaken for child abuse.

Phototoxic species
Plants associated with phytophotodermatitis mainly come from four plant families: the carrot family (Apiaceae), the citrus family (Rutaceae), the mulberry family (Moraceae), and the legume family (Fabaceae).

Apiaceae
The carrot family Apiaceae (or Umbelliferae) is the main family of plants associated with phytophotodermatitis. Of all the plant species that have been reported to induce phytophotodermatitis, approximately half belong to the family Apiaceae.False bishops weed (Ammi majus), the worlds major source of the linear furanocoumarin xanthotoxin, has been used since antiquity to treat vitiligo but accidental or inappropriate use of this plant can lead to phytophotodermatitis. Despite this danger, A. majus continues to be cultivated for its furanocoumarins, which are still used for the treatment of skin disease.
Numerous species in the family Apiaceae are cultivated as food products, some of which exhibit phototoxic effects. In particular, celery, parsnip, and parsley have been reported to cause phytophotodermatitis among agricultural workers, grocery workers, and other occupational food handlers.A number of phototoxic plant species in the carrot family have become invasive species, including wild parsnip (Pastinaca sativa) and the tall hogweeds of the genus Heracleum, namely, Persian hogweed (Heracleum persicum), Sosnowskys hogweed (Heracleum sosnowskyi), and giant hogweed (Heracleum mantegazzianum). In particular, the public health risks of giant hogweed are well known.Other plant species in the family Apiaceae that are associated with phytophotodermatitis include blister bush (Notobubon galbanum), cow parsley (Anthriscus sylvestris), wild carrot (Daucus carota), various species of the genus Angelica (e.g., Korean angelica Angelica gigas), and most (if not all) species of the genus Heracleum (esp. the tall invasive hogweeds and the cow parsnips, Heracleum sphondylium and Heracleum maximum).

Rutaceae
The citrus family Rutaceae is the second most widely distributed family of plants associated with phytophotodermatitis.

Numerous citrus fruits in the family Rutaceae exhibit phototoxic effects. Of these, perhaps the best known is lime. Phytophotodermatitis associated with limes is sometimes colloquially referred to as "lime disease," not to be confused with Lyme disease.
In the family Rutaceae, the most severe reactions are caused by the essential oil of the bergamot orange (Citrus bergamia). Bergamot essential oil has a higher concentration of bergapten (3000–3600 mg/kg) than any other citrus-based essential oil, even lime oil, which contains 1700–3300 mg/kg of bergapten.Other plant species in the family Rutaceae that are associated with phytophotodermatitis include burning bush (Dictamnus albus), common rue (Ruta graveolens), and other plants in the genus Ruta.

Moraceae
The mulberry family Moraceae is often associated with phytophotodermatitis. Multiple species in the genus Ficus are known to exhibit phototoxic effects. Of these, the common fig (Ficus carica) is well known and thoroughly documented.
Like Ammi majus in the family Apiaceae, the common fig has been used since antiquity to treat vitiligo but the milky sap of fig leaves can cause phytophotodermatitis if used accidentally or inappropriately. A literature search revealed 19 cases of fig leaf-induced phytophotodermatitis reported between 1984 and 2012. In Brazil, several hospitals reported more than 50 cases of fig leaf-induced burn in one summer. In most cases, patients reportedly used the leaves of the fig plant for folk remedies, tanning, or gardening.
Other plant species in the family Moraceae that are associated with phytophotodermatitis include Ficus pumila and Brosimum gaudichaudii. Like Ficus carica, the South American species Brosimum gaudichaudii has been shown to contain both psoralen and bergapten.

Prevention
The first and best line of defense against phytophotodermatitis is to avoid contact with phototoxic substances in the first place:

Avoid contact with the plant family Apiaceae, citrus fruits, and other biological agents known to have phototoxic effects. Do not incinerate phototoxic plants and agents since this will serve to disperse the phototoxic substances more widely.
In outdoor situations where contact with phototoxic plants is likely, wear long pants and a long-sleeve shirt. Wear gloves and protective eyewear before handling such plants.
If protective clothing is not available, apply sunscreen to exposed areas. This will provide some measure of protection if contact is made.
After an outdoor activity, take a shower or a bath as soon as possible. Wash your clothing and then wash your hands after handling the dirty clothes.A second line of defense is to avoid sunlight, so as not to activate a phototoxic substance:

If you come in contact with a phototoxic substance, immediately wash the affected area with soap and cold water, and avoid any further exposure to sunlight for at least 48 hours. Heat and moisture can worsen the skin reaction, which is why it’s important to wash the affected area with soap and cold water.
Stay indoors, if possible. Be sure to avoid light shining through windows.
If staying indoors is not an option, cover the affected area with sun protective clothing.
In lieu of sun-protective clothing, apply sunscreen to the affected areas after washing.Phytophotodermatitis is triggered by long wavelength ultraviolet light (called UVA) in the range of 320–380 nanometers, so the best sun-protective clothing and sunscreen products will block these wavelengths of UVA radiation.
In 2011, the U.S. Food and Drug Administration (FDA) established a "broad spectrum" test for determining a sunscreen products UVA protection. Sunscreen products that pass the test are allowed to be labeled as "Broad Spectrum" sunscreens, which protect against both UVA and UVB rays.
There is no equivalent test or FDA-approved labeling for sun-protective clothing. Some clothing is labeled with an Ultraviolet Protection Factor (UPF) but test results from Consumer Reports suggest that UPF is an unreliable indicator of UV protection.

Treatment
Many different topical and oral medications may be used to treat the inflammatory reaction of phytophotodermatitis. A dermatologist may also prescribe a whitening cream to help treat the hyperpigmentation and return the skin pigmentation back to normal. If the patient does not receive treatment, the affected sites may develop permanent hyperpigmentation or hypopigmentation.

History
The photosensitizing effects of plants have been known since antiquity. In Egypt around 2000 B.C., the juice of Ammi majus "was rubbed on patches of vitiligo after which patients were encouraged to lie in the sun." In A.D. 50, the Greek physician Dioscorides observed that pigment would return to patches of vitiligo if "cataplasmed with ye leaves or ye boughes of ye Black Figge," an apparent reference to Ficus carica, the common fig </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 Trigonocephaly and can you explain it in depth? [/INST] Trigonocephaly is a congenital condition of premature fusion of the metopic suture (from the Greek metopon, "forehead"), leading to a triangular forehead. The merging of the two frontal bones leads to transverse growth restriction and parallel growth expansion. It may occur syndromic, involving other abnormalities, or isolated. The term is from the Greek trigonon, "triangle", and kephale, "head".

Cause
Trigonocephaly can either occur syndromatic or isolated. Trigonocephaly is associated with the following syndromes: Opitz syndrome, Muenke syndrome, Jacobsen syndrome, Baller–Gerold syndrome and Say–Meyer syndrome. The etiology of trigonocephaly is mostly unknown although there are three main theories. Trigonocephaly is probably a multifactorial congenital condition, but due to limited proof of these theories this cannot safely be concluded.

Intrinsic bone malformation
The first theory assumes that the origin of pathological synostosis lies within disturbed bone formation early on in the pregnancy. Causes can either be genetic (9p22–24, 11q23, 22q11, FGFR1 mutation), metabolic (TSH suppletion in hypothyroidism) or pharmaceutical (valproate in epilepsy).

Fetal-head constraint
The second theory says that synostosis begins when the fetal head gets hindered in the pelvic outlet during birth.

Intrinsic brain malformation
The third theory predominates disturbed brain formation of the two frontal lobes as the main issue behind synostosis. Limited growth of the frontal lobes leads to an absence of stimuli for cranial growth, therefore causing premature fusion of the metopic suture.

Diagnosis
Diagnosis can be characterized by typical facial and cranial deformities.Observatory signs of trigonocephaly are:

a triangular forehead seen from top view leading to a smaller anterior cranial fossa
a visible and palpable midline ridge
hypotelorism inducing ethmoidal hypoplasiaImaging techniques (3D-CT, Röntgenography, MRI) show:

epicanthal folds in limited cases
teardrop-shaped orbits angulated towards the midline of the forehead (surprised coon sign) in severe cases
a contrast difference between a röntgenograph of a normal and a trigonocephalic skull
anterior curving of the metopic suture seen from lateral view of the cranium on a röntgenograph
a normal cephalic index (maximum cranium width / maximum cranium length) however, there is bitemporal shortening and biparietal broadeningThe neuropsychological development is not always affected. These effects are only visible in a small percentage of children with trigonocephaly or other suture synostoses.
Neuropsychological signs are:

problems in behaviour, speech and language
mental retardation
neurodevelopmental delays such as attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), autism spectrum disorder (ASD), and conduct disorder (CD). Many of these delays become evident at school age.

Treatment
Treatment is surgical with attention to form and volume. Surgery usually takes place before the age of one since it has been reported that the intellectual outcome is better.

Fronto-supraorbital advancement and remodelling
A form of surgery is the so-called fronto-supraorbital advancement and remodelling. Firstly, the supraorbital bar is remodelled by a wired greenstick fracture to straighten it. Secondly, the supraorbital bar is moved 2 cm. forward and fixed only to the frontal process of the zygoma without fixation to the cranium. Lastly, the frontal bone is divided into two, rotated and attached to the supraorbital bar causing a nude area (craniectomy) between the parietal bone and frontal bone. Bone will eventually regenerate since the dura mater lies underneath (the dura mater has osteogenic capabilities). This results in an advancement and straightening of the forehead.

Floating forehead technique
The so-called floating forehead technique combined with the remodelling of the supraorbital bar is derived from the fronto-supraorbital advancement and remodelling. The supraorbital bar is remodelled as described above. The frontal bone is split in two pieces. Instead of using both pieces as in fronto-supraorbital advancement and remodelling, only one piece is rotated and attached to the supraorbital bar. This technique also leaves a craniectomy behind.

Other
SuturectomyThe simplest form of surgery for trigonocephaly was suturectomy. However, as this technique was insufficient to correct the deformities, it is not used anymore.
Distraction osteogenesisDistraction osteogenesis is based on creating more cranial space for the brain by gradually moving the bones apart. This can be achieved by using springs.
Minimal invasive endoscopic surgeryThese approaches are 2D solutions for a 3D problem, therefore the results are not optimal. Distraction osteogenesis and minimal invasive endoscopic surgery are yet in experimental phase.

Outcomes
Surgical
Trigonocephaly seems to be the most compliant form of craniosynostosis for surgery. Because of standardization of current surgical approaches there is no surgical mortality and complications are few to none.
The simple suturectomy is presently insufficient to adjust the complicated growth restrictions caused by metopic synostosis. On the other hand, the fronto-supraorbital advancement and remodelling and the floating forehead technique create sufficient space for brain growth and result in a normal horizontal axis of the orbits and supraorbital bar. The fronto-supraorbital advancement and remodelling is the most used method nowadays.
Over the past few years distraction osteogenesis has been gradually acknowledged since it has a positive effect on hypotelorism. Expanding the distance between the orbits using springs seems to be successful. However, there are discussions whether hypotelorism really needs to be corrected.
The minimal invasive endoscopic surgery has been gaining attention since the early 90s, however, it has technical limitations (only strip craniectomy is possible). Attempts have been made to reach beyond these limits.

Aesthetic
Aesthetic outcome of metopic  synostosis surgery is persistently good with reoperation hazards below 20%. In 1981 Anderson advised that craniofacial operations for synostosis should be as extensive as necessary after a study of 107 cases of metopic and coronal synostosis. Surgery does not provide a 100% natural outcome, mostly there will be minor irregularities. Reoperations are usually performed on more severe cases (including syndromic metopic synostosis). The hypotelorism  and temporal hollowing are the most difficult to correct: the hypotelorism usually remains under corrected and a second operation is often needed for correction of temporal hollowing.

Neurological
The highest rate of neurological problems of single suture synostosis are seen in patients with trigonocephaly. Surgery is performed generally before the age of one because of claims of better intellectual outcome. Seemingly surgery does not influence the high incidence of neurodevelopment problems in patients with metopic synostosis. Neurological disorders such as ADHD, ASD, ODD and CD are seen in patients with trigonocephaly. These disorders are usually also associated with decreased IQ. The presence of ADHD, ASD and ODD is higher in cases with an IQ below 85 </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 Urogenital fistula and can you explain it in depth? [/INST] A urogenital fistula is an abnormal tract that exists between the urinary tract and bladder, ureters, or urethra. A urogenital fistula can occur between any of the organs and structures of the pelvic region. A fistula allows urine to continually exit through and out the urogenital tract. This can result in significant disability, interference with sexual activity, and other physical health issues, the effects of which may in turn have a negative impact on mental or emotional state, including an increase in social isolation.  Urogenital fistulas vary in etiology (medical cause). Fistulas are usually caused by injury or surgery, but they can also result from malignancy, infection, prolonged and obstructed labor and deliver in childbirth, hysterectomy, radiation therapy or inflammation.  Of the fistulas that develop from difficult childbirth, 97 percent occur in developing countries.  Congenital urogenital fistulas are rare; only ten cases have been documented. Abnormal passageways can also exist between the vagina and the organs of the gastrointestinal system, and these may also be termed fistulas.: 673

Classification
Abnormal passageways or fistulas can exist between the vagina and bladder, ureters, uterus, and rectum with the resulting passage of urine from the vagina, or intestinal gas and feces into the vagina, in the case of a vaginal–rectal fistula. These vaginal fistulas are named according to the origin of the defect:

vesicovaginal
urethrovaginal
ureterovaginal
vesicocervical
vesicouterine
vesicouretovaginal
uterocervical
vesicocervical
uretercervical
ureteruterineThe vagina is susceptible to fistula formation because the gastrointestinal tract and urinary system are relatively close to the vagina. A small number of vaginal fistulas are congenital. The presence of a vaginal fistula has a profound effect on the quality of life since there is little control over the passage of urine and feces through the vagina.Urogenital fistulas are often classified according to their cause: obstetric fistula, congenital fistula and iatrogenic fistula. Urogenital fistulas can be classified by size and more specific anatomical location such as upper vagina or posterior vaginal wall.

Causes
In developed countries, the causes of fistulas are iatrogenic (caused by surgical accidents). Physician error and lack of training contribute to the unsuccessful treatment of obstetric fistulas in developing countries. Injuries to pelvic organs are a cause of fistulas. Most of those not caused by obstructed labor develop from injuries. An example of this would be the improper placement of an instrument during a hysterectomy. Fistulas can form after long-term pessary use, hysterectomies, malignant disease and pelvic irradiation, pelvic surgery, cancer or a pelvic fracture. Fistulas are sometimes found after a cesarean section. Providers can also inadvertently cause a fistula when performing obstetric or gynecological surgery. The more training the physician has had, the less likely a uro-vaginal fistula will occur. Some women develop more than one fistula.

Treatment
Surgery is often needed to correct a fistula leading to the vagina. Conservative treatment with an in-dwelling catheter can be effective for small and recently formed urinary fistulas. It has a success rate of 93%. Collagen plugs are used but have been found not to be successful. The surgical treatment to correct can be approached in different ways. Surgery through the vagina is successful  90% of the time. Surgical correction can be accomplished by abdominal surgery, by laparoscopic and robot-assisted laparoscopic surgery.  The various treatments vary in frequency. The transvaginal approach is used 39% of the time,  transabdominal/transvesical approach is used 36% of the time, the laparoscopic/robotic approach is used to treat 15% of urogenital fistulas and a combination of transabdominal-transvaginal approach is used 3% of the time.

Epidemiology
Globally, 75 percent of urogenital fistulas are obstructive labor fistulas </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 Senter 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 Stye and can you explain it in depth? [/INST] A stye, also known as a hordeolum, is a bacterial infection of an oil gland in the eyelid. This results in a red tender bump at the edge of the eyelid. The outside or the inside of the eyelid can be affected.The cause of a stye is usually a bacterial infection by Staphylococcus aureus. The internal ones are due to infection of the meibomian gland while the external ones are due to an infection of the gland of Zeis. A chalazion on the other hand is a blocked oil gland without infection. A chalazion is typically in the middle of the eyelid and not painful.Often a stye will go away without any specific treatment in a few days or weeks. Recommendations to speed improvement include warm compresses. Occasionally antibiotic eye ointment may be recommended. While these measures are often recommended, there is little evidence for use in internal styes. The frequency at which styes occur is unclear, though they may occur at any age.

Signs and symptoms
The first sign of a stye is a small, yellowish spot at the center of the bump that develops as pus and expands in the area.Other stye symptoms may include:

A lump on the top or bottom eyelid
Localized swelling of the eyelid
Localized pain
Redness
Tenderness
Crusting of the eyelid margins
Burning in the eye
Droopiness of the eyelid
Scratchy sensation on the eyeball (itching)
Blurred vision
Mucous discharge in the eye
Irritation of the eye
Light sensitivity
Tearing
Discomfort during blinking
Sensation of a foreign body in the eye

Complications
Stye complications occur in very rare cases. However, the most frequent complication of styes is progression to a chalazion that causes cosmetic deformity, corneal irritation, and often requires surgical removal.  Complications may also arise from the improper surgical lancing, and mainly consist of disruption of lash growth, lid deformity or lid fistula. Large styes may interfere with ones vision.
Eyelid cellulitis is another potential complication of eye styes, which is a generalized infection of the eyelid. Progression of a stye to a systemic infection (spreading throughout the body) is extremely rare, and only a few instances of such spread have been recorded.

Cause
A stye is caused by a bacterial infection. The bacteria are Staphylococcus aureus in about 95% of cases. The infection leads to the blocking of an oil gland at the base of the eyelash. Styes are experienced by people of all ages. Styes can be triggered by poor nutrition, sleep deprivation, lack of hygiene, lack of water, and rubbing of the eyes. Styes can be secondary to blepharitis or a deficiency in immunoglobulin.

Prevention
Stye prevention is closely related to proper hygiene. Proper hand washing can reduce the risks of developing not only styes, but also many other types of infections.
Upon awakening, application of a warm washcloth to the eyelids for one to two minutes may be beneficial in decreasing the occurrence of styes by liquefying the contents of the oil glands of the eyelid and thereby preventing blockage.To prevent styes, cosmetics and cosmetic eye tools should not be shared among people. Like with all infections, regular hand washing is essential, and the eyes should not be rubbed or touched with unclean hands. Contaminated eye makeup should be discarded and sharing of washcloths or face towels should be curtailed, to avoid spreading the infection between individuals. Breaking the stye may spread bacteria contained in the pus and should be avoided.

Treatment
Most cases of styes resolve on their own within one to two weeks, without professional care. The primary treatment is application of warm compresses. As a part of self-care at home, people may cleanse the affected eyelid with tap water or with a mild, nonirritating soap or shampoo (such as baby shampoo) to help clean crusted discharge. Cleansing must be done gently and while the eyes are closed to prevent eye injuries.People with styes should avoid eye makeup (e.g., eyeliner), lotions, and wearing contact lenses, since these can aggravate and spread the infection (sometimes to the cornea). People are advised not to lance the stye themselves, as serious infection can occur. Pain relievers such as acetaminophen may be used.

Antibiotics
Evidence to support the use of antibiotic eye ointment is poor. Occasionally erythromycin ophthalmic ointment is recommended. Other antibiotics, such as chloramphenicol or amoxicillin may also be used. Chloramphenicol is used successfully in many parts of the world, but contains a black box warning in the United States due to concerns about aplastic anemia, which on rare occasions can be fatal.
Antibiotics are normally given to people with multiple styes or with styes that do not seem to heal, and to people who have blepharitis or rosacea.

Procedures
Incision and drainage is performed if resolution does not begin in the next 48 hours after warm compresses are started. Medical professionals will sometimes lance a particularly persistent or irritating stye with a needle to accelerate its draining.Surgery is the last resort in stye treatment. Styes that do not respond to any type of therapies are usually surgically removed. Stye surgery is performed by an ophthalmologist, and generally under local anesthesia. The procedure consists of making a small incision on the inner or outer surface of the eyelid, depending if the stye is pointing externally or not. After the incision is made, the pus is drained out of the gland, and very small sutures are used to close the lesion. Sometimes the removed stye is sent for a histopathological examination to investigate possibility of skin cancer.

Alternative medicine
A 2017 Cochrane review found low-certainty evidence that acupuncture helps in hordeolum compared with antibiotics or warm compresses. There was also low-certainty evidence that acupuncture plus usual treatment may increase the chance of hordeolum getting better, though they could not rule out placebo or observer effect, since the studies reviewed either had no positive control, were not blinded, or both.

Prognosis
Although styes are harmless in most cases and complications are very rare, styes often recur. They do not cause intraocular damage, meaning they do not affect the eye. Styes normally heal on their own by rupturing within a few days to a week causing the relief of symptoms, but if it does not improve or it worsens within two weeks, a doctors opinion should be sought. Few people require surgery as part of stye treatment. With adequate treatment, styes tend to heal quickly and without complications.
The prognosis is better if one does not attempt to squeeze or puncture the stye, as infection may spread to adjacent tissues. Also, patients are recommended to call a doctor if they encounter problems with vision, the eyelid bump becomes very painful, the stye bleeds or reoccurs, or the eyelid or eyes becomes red.

Etymology
The word stye  (first recorded in the 17th century) is probably a back-formation from styany (first recorded in the 15th century), which in turn comes from styan plus eye, the former of which in turn comes from the old English stīġend, meaning "riser", from the verb stīgan, "to rise". The older form styan is still used in Ulster Scots today.
The homonym sty found in the combination pigsty has a slightly different origin, namely it comes from the Old English stiġ-fearh—fearh (farrow) is the Old English word for "piglet"—where stiġ meant "hall" (cf. steward), possibly an early Old Norse loanword, which could be cognate with the word stīgan above.The synonymous late Latin expression is hordeolum a modulation of the word hordeolus simply related to hordeum ("barley"), after its resemblance to a barleycorn </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 Vitamin deficiency and can you explain it in depth? [/INST] Vitamin deficiency is the condition of a long-term lack of a vitamin. When caused by not enough vitamin intake it is classified as a primary deficiency, whereas when due to an underlying disorder such as malabsorption it is called a secondary deficiency. An underlying disorder may be metabolic – as in a genetic defect for converting tryptophan to niacin – or from lifestyle choices that increase vitamin needs, such as smoking or drinking alcohol. Government guidelines on vitamin deficiencies advise certain intakes for healthy people, with specific values for women, men, babies, the elderly, and during pregnancy or breastfeeding. Many countries have mandated vitamin food fortification programs to prevent commonly occurring vitamin deficiencies.Conversely, hypervitaminosis refers to symptoms caused by vitamin intakes in excess of needs, especially for fat-soluble vitamins that can accumulate in body tissues.The history of the discovery of vitamin deficiencies progressed over centuries from observations that certain conditions – for example, scurvy – could be prevented or treated with certain foods having high content of a necessary vitamin, to the identification and description of specific molecules essential for life and health. During the 20th century, several scientists were awarded the Nobel Prize in Physiology or Medicine or the Nobel Prize in Chemistry for their roles in the discovery of vitamins.

Defining deficiency
A number of regions have published guidelines defining vitamin deficiencies and advising specific intakes for healthy people, with different recommendations for women, men, infants, the elderly, and during pregnancy and breast feeding including Japan, the European Union, the United States, and Canada. These documents have been updated as research is published. In the US, Recommended Dietary Allowances (RDAs) were first set in 1941 by the Food and Nutrition Board of the National Academy of Sciences. There were periodic updates, culminating in the Dietary Reference Intakes. Updated in 2016, the US Food and Drug Administration published a set of tables that define Estimated Average Requirements (EARs) and (RDAs). RDAs are higher to cover people with higher than average needs. Together, these are part of Dietary Reference Intakes. For a few vitamins, there is not sufficient information to set EARs and RDAs. For these, an Adequate Intake is shown, based on an assumption that what healthy people consume is sufficient. Countries do not always agree on the amounts of vitamins needed to safeguard against deficiency. For example, for vitamin C, the RDAs for women for Japan, the European Union (called Population Reference Intakes) and the US are 100, 95 and 75 mg/day, respectively. India sets its recommendation at 40 mg/day.

Individual vitamin deficiencies
Water-soluble vitamins
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Fat-soluble vitamins
Prevention
Food fortification
Food fortification is the process of adding micronutrients (essential trace elements and vitamins) to food as a public health policy which aims to reduce the number of people with dietary deficiencies within a population. Staple foods of a region can lack particular nutrients due to the soil of the region or from inherent inadequacy of a normal diet. Addition of micronutrients to staples and condiments can prevent large-scale deficiency diseases in these cases.As defined by the World Health Organization (WHO) and the Food and Agriculture Organization of the United Nations (FAO), fortification refers to "the practice of deliberately increasing the content of an essential micronutrient, i.e., vitamins and minerals in a food irrespective of whether the nutrients were originally in the food before processing or not, so as to improve the nutritional quality of the food supply and to provide a public health benefit with minimal risk to health", whereas enrichment is defined as "synonymous with fortification and refers to the addition of micronutrients to a food which are lost during processing". The Food Fortification Initiative lists all countries in the world that conduct fortification programs, and within each country, what nutrients are added to which foods. Vitamin fortification programs exist in one or more countries for folate, niacin, riboflavin, thiamin, vitamin A, vitamin B6, vitamin B12, vitamin D and vitamin E. As of 21 December 2018, 81 countries required food fortification with one or more vitamins. The most commonly fortified vitamin – as used in 62 countries – is folate; the most commonly fortified food is wheat flour.

Genetic engineering
Starting in 2000, rice was experimentally genetically engineered to produce higher than normal beta-carotene content, giving it a yellow/orange color. The product is referred to as golden rice (Oryza sativa). Biofortified sweet potato, maize, and cassava were other crops introduced to enhance the content of beta-carotene and certain minerals.When eaten, beta-carotene is a provitamin, converted to retinol (vitamin A). The concept is that in areas of the world where vitamin A deficiency is common, growing and eating this rice would reduce the rates of vitamin A deficiency, particularly its effect on childhood vision problems. As of 2018, fortified golden crops were still in the process of government approvals, and were being assessed for taste and education about their health benefits to improve acceptance and adoption by consumers in impoverished countries.

Hypervitaminosis
Some vitamins cause acute or chronic toxicity, a condition called hypervitaminosis, which occurs mainly for fat-soluble vitamins if over-consumed by excessive supplementation. Hypervitaminosis A and hypervitaminosis D are the most common examples. Vitamin D toxicity does not result from sun exposure or consuming foods rich in vitamin D, but rather from excessive intake of vitamin D supplements, possibly leading to hypercalcemia, nausea, weakness, and kidney stones.The United States, European Union and Japan, among other countries, have established "tolerable upper intake levels" for those vitamins which have documented toxicity.

History
In 1747, the Scottish surgeon James Lind discovered that citrus foods helped prevent scurvy, a particularly deadly disease in which collagen is not properly formed, causing poor wound healing, bleeding of the gums, severe pain, and death. In 1753, Lind published his Treatise on the Scurvy, which recommended using lemons and limes to avoid scurvy, which was adopted by the British Royal Navy. This led to the nickname limey for British sailors. Linds discovery, however, was not widely accepted by individuals in the Royal Navys Arctic expeditions in the 19th century, where it was widely believed that scurvy could be prevented by practicing good hygiene, regular exercise, and maintaining the morale of the crew while on board, rather than by a diet of fresh food.During the late 18th and early 19th centuries, the use of deprivation studies allowed scientists to isolate and identify a number of vitamins. Lipid from fish oil was used to cure rickets in rats, and the fat-soluble nutrient was called "antirachitic A". Thus, the first "vitamin" bioactivity ever isolated, which cured rickets, was initially called "vitamin A"; however, the bioactivity of this compound is now called vitamin D. In 1881, Russian medical doctor Nikolai I. Lunin studied the effects of scurvy at the University of Tartu. He fed mice an artificial mixture of all the separate constituents of milk known at that time, namely the proteins, fats, carbohydrates, and salts. The mice that received only the individual constituents died, while the mice fed by milk itself developed normally. He made a conclusion that substances essential for life must be present in milk other than the known principal ingredients. However, his conclusions were rejected by his advisor, Gustav von Bunge.In East Asia, where polished white rice was the common staple food of the middle class, beriberi resulting from lack of vitamin B1 was endemic. In 1884, Takaki Kanehiro, a British-trained medical doctor of the Imperial Japanese Navy, observed that beriberi was endemic among low-ranking crew who often ate nothing but rice, but not among officers who consumed a Western-style diet. With the support of the Japanese Navy, he experimented using crews of two battleships; one crew was fed only white rice, while the other was fed a diet of meat, fish, barley, rice, and beans. The group that ate only white rice documented 161 crew members with beriberi and 25 deaths, while the latter group had only 14 cases of beriberi and no deaths. This convinced Takaki and the Japanese Navy that diet was the cause of beriberi, but they mistakenly believed that sufficient amounts of protein prevented it. That diseases could result from some dietary deficiencies was further investigated by Christiaan Eijkman, who in 1897 discovered that feeding unpolished rice instead of the polished variety to chickens helped to prevent beriberi. The following year, Frederick Hopkins postulated that some foods contained "accessory factors" — in addition to proteins, carbohydrates, fats etc. — that are necessary for the functions of the human body. Hopkins and Eijkman were awarded the Nobel Prize for Physiology or Medicine in 1929 for their discoveries.

In 1910, the first vitamin complex was isolated by Japanese scientist Umetaro Suzuki, who succeeded in extracting a water-soluble complex of micronutrients from rice bran and named it aberic acid (later Orizanin). He published this discovery in a Japanese scientific journal. When the article was translated into German, the translation failed to state that it was a newly discovered nutrient, a claim made in the original Japanese article, and hence his discovery failed to gain publicity. In 1912 Polish-born biochemist Casimir Funk, working in London, isolated the same complex of micronutrients and proposed the complex be named "vitamine". It was later to be known as vitamin B3 (niacin), though he described it as "anti-beri-beri-factor" (which would today be called thiamine or vitamin B1). Funk proposed the hypothesis that other diseases, such as rickets, pellagra, coeliac disease, and scurvy could also be cured by vitamins </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 Euthyroid sick syndrome and can you explain it in depth? [/INST] Euthyroid sick syndrome (ESS) is a state of adaptation or dysregulation of thyrotropic feedback control wherein the levels of T3 and/or T4 are abnormal, but the thyroid gland does not appear to be dysfunctional. This condition may result from allostatic responses of hypothalamus-pituitary-thyroid feedback control, dyshomeostatic disorders, drug interferences, and impaired assay characteristics in critical illness.
The classical phenotype of this condition is often seen in starvation, critical illness, or patients in the intensive care unit. Similar endocrine phenotypes are observed in fetal life and in hibernating mammals. The most common hormone pattern in nonthyroidal illness syndrome is low total and free T3, elevated rT3, and normal T4 and TSH levels, although T4 and TSH suppression may occur in more severe or chronic illness. This classical pattern results from type 1 allostatic load, i.e. a stress response resulting from lacking energy, oxygen, and glutathione.An alternative phenotype with a largely inverse hormonal pattern is seen in several physiological and pathological conditions, including pregnancy, obesity, endurance training, and psychiatric diseases. It is typically associated with high-T3 syndrome, increased plasma protein binding of thyroid hormones, and an elevated set point of the homeostatic system. It represents a response to type-2 allostatic load.

Classical phenotype (type 1 thyroid allostasis)
Causes
Causes of classical euthyroid sick syndrome include a number of acute and chronic conditions, including pneumonia, fasting, starvation, anorexia nervosa, sepsis, trauma, cardiopulmonary bypass, malignancy, stress, heart failure, hypothermia, myocardial infarction, kidney failure, cirrhosis, diabetic ketoacidosis, surgery, infection, brain injury, shock, cancer, and HIV.Outside the hospital setting, euthyroid sick syndrome (nonthyroidal illness syndrome - NTIS) has been assumed closely related with a series of chronic diseases, such as inflammatory bowel disease, chronic fatigue syndrome, and autoimmune diseases.Additionally, an NTIS-like phenotype can be present in major depressive disorder, as well as overexercise.

Pathophysiology
In critical illness, the activity of different deiodinases is altered. Humoral and neuronal inputs at the level of the hypothalamus may adjust the set point of thyroid homeostasis. This may play an important role in the pathogenesis of the central component of thyroid allostasis in critical illness, tumors, uremia and starvation (TACITUS). In addition, both illness and medication (e.g. salicylates and heparin) may impair plasma protein binding of thyroid hormones, resulting in reduced levels of total hormones, while free hormone concentrations may be temporarily elevated.Euthyroid sick syndrome probably represents an overlap of an allostatic response with pathologic reactions and drug interferences. Allostatic overload may result in wasting syndrome and myxedema coma. Thyroid storm, though, represents allostatic failure, where the organism is unable to develop NTIS in the situation of thyrotoxicosis.

Deiodinases
Three primary deiodinases are responsible for thyroid hormone conversion and breakdown. Type 1 (D1) deiodinates T4 to the biologically active T3, as well as the hormonally inactive and possibly inhibitory rT3. Type 2 (D2) converts T4 into T3, and breaks down rT3. D3 produces rT3 from T4, and breaks down T3. The balance of D2 and D3 is important for overall T3/rT3 balance.In NTIS, the concentrations of these deiodinases are altered, although  whether NTIS is the cause or effect of this in peripheral tissues is unclear; in some studies, the alterations in thyroid hormone concentrations occurred before the changes in deiodinase activity. Typically, peripheral D1 and D2 are downregulated, while peripheral D3 is upregulated; this is associated with lower T4 and increased rT3.

Hypothalamic-pituitary-thyroid axis downregulation
Thyrotropin releasing hormone (TRH) neurons in the hypothalamus integrate global signals about the bodys energy state. They may be stimulated by signals such as leptin, alpha-MSH, and catecholamines; and inhibited by glucocorticoids, neuropeptide Y, and agouti-related peptide.

In critical illness, inflammation increases tanycyte D2 in the paraventricular nucleus (PVN) of the hypothalamus, leading to local tissue hyperthyroidism. There may also be decreased central D3. This causes negative feedback on the HPT axis, and therefore reduced TRH gene expression in the PVN. This is exemplified by the common NTIS phenotype of low TSH even in the face of peripheral hypothyroidism.

Cytokines
Illness can cause inflammation, which often involves an increase in cytokines such as TNFa, IL-1, and IL-6. Cytokines are implicated in NTIS. IL-1β has been shown to decrease liver D1, as well as thyroid hormone receptor (THR) levels. IL-6 and TNFa downregulate D1 and suppress TSH, are negatively correlated with fT3, and are positively correlated with rT3. NF-κB also inhibits D1, and decreases the expression of Thyroid receptors α and β. IFNy inhibits thyroid and Tg release, and also inhibits the upregulation of TSH receptors.

Thyroid hormone receptors
In chronic liver and renal (kidney) failure,  increased THR expression occurs. In contrast, in acute illness such as sepsis and trauma,  decreased THR expression occurs.

Thyroid hormone transporters
During NTIS,  alterations arise in the concentrations of thyroid hormone transporters such as MCT8 and MCT10, although whether the levels are increased or decreased depends on the study. The altered concentrations are thought to be a result of NTIS, rather than a cause; a study in rabbits showed that administering thyroid hormones normalized transporter expression.

Binding proteins
Decreased thyroxine-binding globulin (TBG) occurs following bypass surgery, and in chronic illness, a less effective form of TBG with lower affinity for thyroxine is synthesized. Reduced quantities of bound thyroid result, leading to decreased total thyroid measurements. Decreases in total thyroid may be more severe than alternations in free hormone levels.

Drugs
Dopamine and corticosteroids, commonly given in the hospital setting, can suppress TSH and suppress conversion of T4 to T3. Other drugs such as estrogen, contraceptives, salicylates, and phenytoin can alter the binding of TBG to TH, resulting in different TH concentrations. Additionally, lithium disrupts thyroid function, and thyromimetic endocrine disrupters may downregulate the HPT axis.

Fasting
Fasting is a common response in inflammation and critical illness. Originally, selenium deficiency as a result of malnutrition was thought to reduce D1 catalytic activity, but this theory has not been supported as a cause of NTIS.
NTIS as a result of fasting may be regarded as a healthy and adaptive mechanism that reduces energy expenditure. Fasting in healthy, euthyroid people causes reduced T3 and elevated rT3, although TSH is usually unchanged. Even moderate weight loss can lower T3.This may be primarily via reduced levels of leptin (the satisfaction hormone). Low leptin levels can downregulate hypothalamic TRH neurons and cause a reduction in TSH. Ιn fasting animals, administering leptin reverses NTIS symptoms and restores thyroid hormone concentrations. In obesity, increased leptin increases TSH and T3, and lowers rT3, possibly as an attempt to increase energy expenditure and return to weight set point.Other signals associated with hunger also affect the HPT axis. Insulin and bile acids, which are elevated after a meal, lead to increased D2 activity, therefore increasing T3 and reducing rT3. Low leptin increases NPY and AGRP (associated with appetite), which inhibit TRH gene expression; this effect is enhanced by ghrelin (the hunger hormone). a-MSH stimulates TRH gene expression in the PVN. This is enhanced by leptin, and inhibited by low leptin. a-MSH is also antagonized by AGRP.

Alternative phenotype (type 2 thyroid allostasis)
An anti-NTIS phenotype is observed in some circumstances, wherein TSH, T3, and T4 are generally elevated rather than suppressed. This can occur during pregnancy, obesity, cold adaptation, stay in high altitudes, endurance exercise, acute psychosis, and post-traumatic stress disorder.According to newer theories, elevated concentrations of TSH and thyroid hormones in type 2 allostasis result from an up-regulated set point of the feedback loop, which ensues from increased TRH expression in the basolateral amygdala and the paraventricular nucleus of the hypothalamus in response to stress.High-T3 syndrome in thyroid carcinoma may result from autonomous thyroid hormone secretion or overexpression of type 2 deiodinase in cancer cells rather than from type 2 allostasis.

Conditions with mixed phenotypes
Psychiatry
Stress suppresses TSH, and alterations in thyroid hormone levels may arise  in psychiatric illness. In major depressive disorder, an NTIS-like phenotype may be observed, with reduced T3 and increased rT3. T4 may be elevated, and TSH is usually normal, although TSHs normal circadian rhythm may be disrupted. Bipolar 1 and PTSD can exemplify an anti-NTIS phenotype, with upregulation of the HPT axis and increased T3. This may also occur during acute schizophrenic episodes.

Exercise
After exercise, a transient increase occurs in TSH, T4, and T3, but this is thought to be due to increased blood concentration as a result of dehydration. The effects normalize after rest. After long-term heavy strain, levels of thyroid hormones decrease. This is exacerbated by other stressors such as undernutrition and lack of sleep, such as in a military training setting. During endurance exercise, before exhaustion, elevated thyroid hormone levels may happen due to increased expected energy demand (type 2 allostatic load).

Environmental conditions
Cold exposure and stay at high altitude may lead to type 1 or type 2 phenotype, depending on duration and other boundary conditions (which determine whether or not stress is associated with energy deprivation).

Diagnosis
Affected patients may have normal, low, or slightly elevated TSH depending on the spectrum and phase of illness. Total T4 and T3 levels may be altered by binding protein abnormalities, and medications. Reverse T3 levels are generally increased, while FT3 is decreased. FT4 levels may have a transient increase, before becoming subnormal during severe illness. Correspondingly, in the majority of cases calculated sum activity of peripheral deiodinases (SPINA-GD) is reduced. Generally the levels of free T3 will be lowered, followed by the lowering of free T4 in more severe disease. Several studies described elevated concentrations of 3,5-T2, an active thyroid hormone, in NTIS. 3,5-T2 levels were also observed to correlate with concentrations of rT3 (reverse T3) in patients with euthyroid sick syndrome.
NTIS is a component of a complex endocrine adaptation process, so affected patients might also have hyperprolactinemia and elevated levels of corticosteroids (especially cortisol) and growth hormone. NTIS can be difficult to distinguish from other forms of thyroid dysfunction in the hospital setting. Both NTIS and primary hypothyroidism may have reduced fT3 and fT4, and elevated TSH (which is common in the hospital, during the recovery phase of NTIS). Prescribing thyroxine to treat this may lead to lifelong thyroid overtreatment.Hyperthyroidism may be assumed due to decreased TSH and a transient fT4 increase. In some cases, this can be distinguished from NTIS by a thyroid ultrasound, which is commonly available in the hospital intensive care unit.NTIS looks similar to central hypopituitarism; both frequently have reduced TSH and thyroid hormone levels.

Treatment
Debate is ongoing as to whether NTIS is an adaptive or maladaptive mechanism in response to physiological stress. Some sources indicate that NTIS is beneficial as an acute-phase response, but detrimental during the chronic phase of illness. Several trials have investigated a possible therapy for NTIS, but they yielded inconsistent and partly contradictory results. This may be due to the heterogeneity of investigated populations, and to the lack of a consistent definition of NTIS.Administering exogenous T3 and T4 has variable results, but overall seems to confer no improvements to health outcome. Administering TRH to patients with chronic illness, however, seems to normalize thyroid levels and improve catabolic function.When NTIS is caused by the normal fasting response to illness, early parenteral nutrition has been shown to attenuate alterations in thyroid hormone (TSH, T3, T4, rT3) levels, whereas late parenteral nutrition exacerbates it. Late parenteral nutrition, though,  also reduced complications and accelerated recovery in one study.

History
In 1968, a reduced T4 half-life in athletes was discovered. This was the first awareness of thyroid hormone concentration alterations that were not a result of thyroid gland or pituitary dysfunction </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 Intertrigo and can you explain it in depth? [/INST] Intertrigo refers to a type of inflammatory rash (dermatitis) of the superficial skin that occurs within a persons body folds. These areas are more susceptible to irritation and subsequent infection due to factors that promote skin breakdown such as moisture, friction, and exposure to bodily secretions such as sweat, urine, or feces. Areas of the body which are more likely to be affected by intertrigo include the inframammary fold, intergluteal cleft, armpits, and spaces between the fingers or toes. Skin affected by intertrigo is more prone to infection than intact skin.The term "intertrigo" commonly refers to a secondary infection with bacteria (such as Corynebacterium minutissimum), fungi (such as Candida albicans), or viruses. A frequent manifestation is candidal intertrigo.
Intertrigo occurs more often in warm and humid conditions </s>