<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 Gastrointestinal bleeding and can you explain it in depth? [/INST] Gastrointestinal bleeding (GI bleed), also called gastrointestinal hemorrhage (GIB), is all forms of bleeding in the gastrointestinal tract, from the mouth to the rectum. When there is significant blood loss over a short time, symptoms may include vomiting red blood, vomiting black blood, bloody stool, or black stool. Small amounts of bleeding over a long time may cause iron-deficiency anemia resulting in feeling tired or heart-related chest pain. Other symptoms may include abdominal pain, shortness of breath, pale skin, or passing out. Sometimes in those with small amounts of bleeding no symptoms may be present.Bleeding is typically divided into two main types: upper gastrointestinal bleeding and lower gastrointestinal bleeding. Causes of upper GI bleeds include: peptic ulcer disease, esophageal varices due to liver cirrhosis and cancer, among others.  Causes of lower GI bleeds include: hemorrhoids, cancer, and inflammatory bowel disease among others. Diagnosis typically begins with a medical history and physical examination, along with blood tests. Small amounts of bleeding may be detected by fecal occult blood test. Endoscopy of the lower and upper gastrointestinal tract may locate the area of bleeding. Medical imaging may be useful in cases that are not clear.Initial treatment focuses on resuscitation which may include intravenous fluids and blood transfusions. Often blood transfusions are not recommended unless the hemoglobin is less than 70 or 80 g/L. Treatment with proton pump inhibitors, octreotide, and antibiotics may be considered in certain cases. If other measures are not effective, an esophageal balloon may be attempted in those with presumed esophageal varices. Endoscopy of the esophagus, stomach, and duodenum or endoscopy of the large bowel are generally recommended within 24 hours and may allow treatment as well as diagnosis.An upper GI bleed is more common than lower GI bleed. An upper GI bleed occurs in 50 to 150 per 100,000 adults per year. A lower GI bleed is estimated to occur in 20 to 30 per 100,000 per year. It results in about 300,000 hospital admissions a year in the United States. Risk of death from a GI bleed is between 5% and 30%. Risk of bleeding is more common in males and increases with age.

Classification
Gastrointestinal bleeding can be roughly divided into two clinical syndromes: upper gastrointestinal bleeding and lower gastrointestinal bleeding. About 2/3 of all GI bleeds are from upper sources and 1/3 from lower sources. Common causes of gastrointestinal bleeding include infections, cancers, vascular disorders, adverse effects of medications, and blood clotting disorders. Obscure gastrointestinal bleeding (OGIB) is when a source is unclear following investigation.

Upper gastrointestinal
Upper gastrointestinal bleeding is from a source between the pharynx and the ligament of Treitz. An upper source is characterised by hematemesis (vomiting up blood) and melena (tarry stool containing altered blood). About half of cases are due to peptic ulcer disease (gastric or duodenal ulcers). Esophageal inflammation and erosive disease are the next most common causes. In those with liver cirrhosis, 50–60% of bleeding is due to esophageal varices. Approximately half of those with peptic ulcers have an H. pylori infection. Other causes include Mallory-Weiss tears, cancer, and angiodysplasia.A number of medications are found to cause upper GI bleeds. NSAIDs or COX-2 inhibitors increase the risk about fourfold. SSRIs, corticosteroids, and anticoagulants may also increase the risk. The risk with dabigatran is 30% greater than that with warfarin.

Lower gastrointestinal
Lower gastrointestinal bleeding is typically from the colon, rectum or anus. Common causes of lower gastrointestinal bleeding include hemorrhoids, cancer, angiodysplasia, ulcerative colitis, Crohns disease, and aortoenteric fistula. It may be indicated by the passage of fresh red blood rectally, especially in the absence of bloody vomiting. Lower gastrointestinal bleeding could also lead to melena if the bleeding occurs in the small intestine or proximal colon.

Signs and symptoms
Gastrointestinal bleeding can range from small non-visible amounts, which are only detected by laboratory testing, to massive bleeding where bright red blood is passed and shock develops. Rapid bleeding may cause syncope. The presence of bright red blood in stool, known as hematochezia, typically indicates lower gastrointestinal bleeding. Digested blood from the upper gastrointestinal tract may appear black rather than red, resulting in "coffee ground" vomit or melena. Other signs and symptoms include feeling tired, dizziness, and pale skin color.A number of foods and medications can turn the stool either red or black in the absence of bleeding. Bismuth found in many antacids may turn stools black as may activated charcoal. Blood from the vagina or urinary tract may also be confused with blood in the stool.

Diagnosis
Diagnosis is often based on direct observation of blood in the stool or vomit.  Although fecal occult blood testing has been used in an emergency setting, this use is not recommended as the test has only been validated for colon cancer screening. Differentiating between upper and lower bleeding in some cases can be difficult. The severity of an upper GI bleed can be judged based on the Blatchford score or Rockall score. The Rockall score is the more accurate of the two. As of 2008 there is no scoring system useful for lower GI bleeds.

Clinical
Gastric aspiration and or lavage, where a tube is inserted into the stomach via the nose in an attempt to determine if there is blood in the stomach, if negative does not rule out an upper GI bleed but if positive is useful for ruling one in. Clots in the stool indicate a lower GI source while melana stools an upper one.

Laboratory testing
Recommended laboratory blood testing includes: cross-matching blood, hemoglobin, hematocrit, platelets, coagulation time, and electrolytes. If the ratio of blood urea nitrogen to creatinine is greater than 30 the source is more likely from the upper GI tract.

Imaging
A CT angiography is useful for determining the exact location of the bleeding within the gastrointestinal tract. Nuclear scintigraphy is a sensitive test for detecting occult gastrointestinal bleeding when direct imaging with upper and lower endoscopies are negative. Direct angiography allows for embolization of a bleeding source, but requires a bleeding rate faster than 1mL/minute.

Prevention
In those with significant varices or cirrhosis nonselective β-blockers reduce the risk of future bleeding. With a target heart rate of 55 beats per minute they reduce the absolute risk of bleeding by 10%. Endoscopic band ligation (EBL) is also effective at improving outcomes. Either B-blockers or EBL are recommended as initial preventative measures. In those who have had a previous variceal bleed both treatments are recommended. Some evidence supports the addition of isosorbide mononitrate. Testing for and treating those who are positive for H. pylori is recommended. Transjugular intrahepatic portosystemic shunting (TIPS) may be used to prevent bleeding in people who re-bleed despite other measures.Among people admitted to the ICU who are at high risk, a PPI or H2RA if appears useful.

Treatment
The initial focus is on resuscitation beginning with airway management and fluid resuscitation using either intravenous fluids and or blood. A number of medications may improve outcomes depending on the source of the bleeding.

Peptic ulcers
Based on evidence from people with other health problems crystalloid and colloids are believed to be equivalent for peptic ulcer bleeding. Proton pump inhibitor (PPI) treatment before endoscopy may decrease the need for endoscopic hemostatic treatment, however it is not clear if this treatment reduces mortality, the risk of re-bleeding, or the and the need for surgery. Oral and intravenous formulations may be equivalent; however, the evidence to support this is suboptimal. In those with less severe disease and where endoscopy is rapidly available, they are of less immediate clinical importance. There is tentative evidence of benefit for tranexamic acid which inhibits clot breakdown. Somatostatin and octreotide, while recommended for varicial bleeding, have not been found to be of general use for non variceal bleeds. After treatment of a high risk bleeding ulcer endoscopically giving a PPI once or a day rather than as an infusion appears to work just as well and is less expensive (the method may be either by mouth or intravenously).

Variceal bleeding
For initial fluid replacement, colloids or albumin is preferred in people with cirrhosis. Medications typically include octreotide or, if not available, vasopressin and nitroglycerin to reduce portal venous pressures. Terlipressin appears to be more effective than octreotide, but it is not available in many areas of the world. It is the only medication that has been shown to reduce mortality in acute variceal bleeding. This is in addition to endoscopic banding or sclerotherapy for the varices. If this is sufficient then beta blockers and nitrates may be used for the prevention of re-bleeding. If bleeding continues, balloon tamponade with a Sengstaken-Blakemore tube or Minnesota tube may be used in an attempt to mechanically compress the varices. This may then be followed by a transjugular intrahepatic portosystemic shunt. In those with cirrhosis, antibiotics decrease the chance of bleeding again, shorten the length of time spent in hospital, and decrease mortality. Octreotide reduces the need for blood transfusions and may decrease mortality. No trials of vitamin K have been conducted.

Blood products
The evidence for benefit of blood transfusions in GI bleed is poor with some evidence finding harm. In those in shock O-negative packed red blood cells are recommended. If large amounts of pack red blood cells are used additional platelets and fresh frozen plasma (FFP) should be administered to prevent coagulopathies. In alcoholics FFP is suggested before confirmation of a coagulopathy due to presumed blood clotting problems. Evidence supports holding off on blood transfusions in those who have a hemoglobin greater than 7 to 8 g/dL and moderate bleeding, including in those with preexisting coronary artery disease.If the INR is greater than 1.5 to 1.8 correction with fresh frozen plasma or prothrombin complex may decrease mortality. Evidence of a harm or benefit of recombinant activated factor VII in those with liver diseases and gastrointestinal bleeding is not determined. A massive transfusion protocol may be used, but there is a lack of evidence for this indication.

Procedures
The benefits versus risks of placing a nasogastric tube in those with upper GI bleeding are not determined. Endoscopy within 24 hours is recommended, in addition to medical management. A number of endoscopic treatments may be used, including: epinephrine injection, band ligation, sclerotherapy, and fibrin glue depending on what is found. Prokinetic agents such as erythromycin before endoscopy can decrease the amount of blood in the stomach and thus improve the operators view. They also decrease the amount of blood transfusions required. Early endoscopy decreases hospital and the amount of blood transfusions needed. A second endoscopy within a day is routinely recommended by some but by others only in specific situations. Proton pump inhibitors, if they have not been started earlier, are recommended in those in whom high risk signs for bleeding are found. High and low dose PPIs appear equivalent at this point. It is also recommended that people with high risk signs are kept in hospital for at least 72 hours. Those at low risk of re-bleeding may begin eating typically 24 hours following endoscopy. If other measures fail or are not available, esophageal balloon tamponade may be attempted. While there is a success rate up to 90%, there are some potentially significant complications including aspiration and esophageal perforation.Colonoscopy is useful for the diagnosis and treatment of lower GI bleeding. A number of techniques may be employed including clipping, cauterizing, and sclerotherapy. Preparation for colonoscopy takes a minimum of six hours which in those bleeding briskly may limit its applicability. Surgery, while rarely used to treat upper GI bleeds, is still commonly used to manage lower GI bleeds by cutting out the part of the intestines that is causing the problem. Angiographic embolization may be used for both upper and lower GI bleeds. Transjugular intrahepatic portosystemic shunting (TIPS) may also be considered.

Prognosis
Death in those with a GI bleed is more commonly due to other illnesses (some of which may have contributed to the bleed, such as cancer or cirrhosis) than the bleeding itself. Of those admitted to a hospital because of a GI bleed, death occurs in about 7%. Despite treatment, re-bleeding occurs in about 7–16% of those with upper GI bleeding </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Diastematomyelia and can you explain it in depth? [/INST] Diastematomyelia (occasionally diastomyelia) is a congenital disorder in which a part of the spinal cord is split, usually at the level of the upper lumbar vertebra in the longitudinal (sagittal) direction. Females are affected much more commonly than males. This condition occurs in the presence of an osseous, cartilaginous or fibrous septum in the central portion of the spinal canal which then produces a complete or incomplete sagittal division of the spinal cord into two hemicords. When the split does not reunite distally to the spur, the condition is referred to as diplomyelia, which is true duplication of the spinal cord.

Signs and symptoms
The signs and symptoms of diastematomyelia may appear at any time of life, although the diagnosis is usually made in childhood. Cutaneous lesions (or stigmata), such as a hairy patch, dimple, Hemangioma, subcutaneous mass, Lipoma or Teratoma over the affected area of the spine is found in more than half of cases. Neurological symptoms are nonspecific, indistinguishable from other causes of cord tethering. The symptoms are caused by tissue attachments that limit the movement of the spinal cord within the spinal column.  These attachments cause an abnormal stretching of the spinal cord.
The course of the disorder is progressive.  In children, symptoms may include the "stigmata" mentioned above and/or foot and spinal deformities; weakness in the legs; low back pain; scoliosis; and incontinence.  In adulthood, the signs and symptoms often include progressive sensory and motor problems and loss of bowel and bladder control.  This delayed presentation of symptoms is related to the degree of strain placed on the spinal cord over time.
Tethered spinal cord syndrome appears to be the result of improper growth of the neural tube during fetal development, and is closely linked to spina bifida.
Tethering may also develop after spinal cord injury and scar tissue can block the flow of fluids around the spinal cord.  Fluid pressure may cause cysts to form in the spinal cord, a condition called syringomyelia.  This can lead to additional loss of movement, feeling or the onset of pain or autonomic symptoms.
Cervical diastematomyelia can become symptomatic as a result of acute trauma, and can cause major neurological deficits, like hemiparesis, to result from otherwise mild trauma.The following definitions may help to understand some of the related entities:

Diastematomyelia (di·a·stem·a·to·my·elia) is a congenital anomaly, often associated with spina bifida, in which the spinal cord is split into halves by a bony spicule or fibrous band, each half being surrounded by a dural sac.
Myeloschisis (my·elos·chi·sis) is a developmental anomaly characterized by a cleft spinal cord, owing to failure of the neural plate to form a complete neural tube or to rupture of the neural tube after closure.
Diplomyelia (diplo.my.elia) is a true duplication of spinal cord in which these are two dural sacs with two pairs of anterior and posterior nerve roots.

Pathophysiology
Diastematomyelia is a "dysraphic state" of unknown embryonic origin, but is probably initiated by an accessory neurenteric canal (an additional embryonic spinal canal.) This condition may be an isolated phenomenon or may be associated with other segmental anomalies of the vertebral bodies such as spina bifida, kyphoscoliosis, butterfly vertebra, hemivertebra and block vertebrae which are observed in most of the cases. Scoliosis is identified in more than half of these patients. In most of the symptomatic patients, the spinal cord is split into halves by a bony spicule or fibrous band, each half being surrounded by a dural sac. Other conditions, such as intramedullary tumors, tethered cord, dermoids, lipoma, syringomyelia, hydromyelia and Arnold–Chiari malformations have been described in medical literature, but they are exceptionally rare.
Diastematomyelia usually occurs between 9th thoracic and 1st sacral levels of the spinal column with most being at the level of the upper lumbar vertebra. Cervical diastematomyelia is a very rare entity. The extent (or length of spinal cord involved) varies from one affected individual to another. In approximately 60% of patients with diastematomyelia, the two hemicords, each covered by an intact layer of pia arachnoid, travel through a single subarachnoid space surrounded by a single dural sac. Each hemicord has its own anterior spinal artery. This form of diastematomyelia is not accompanied by any bony spur or fibrous band and is rarely symptomatic unless hydromyelia or tethering is present. The other 40% of patients have a bony spur or a fibrous band that passes through the two hemicords. In these cases, the dura and arachnoid are split into two separate dural and arachnoidal sacs, each surrounding the corresponding hemicord which are not necessarily symmetric. Each hemicord contains a central canal, one dorsal horn (giving rise to a dorsal nerve root), and one ventral horn (giving rise to a ventral nerve root.) One study showed the bony spur typically situated at the most inferior aspect of the dural cleft. They advised that if the imaging appears to show otherwise, a second spur (present in about 5% of patients with diastematomyelia) is likely to be present.
The conus medullaris is situated below the L2 level in more than 75% of these diastematomyelia patients. Thickening of the filum terminale is seen in over half of the cases. While the level of the cleft is variable, it is most commonly found in the lumbar region. The two hemicords usually reunite caudally to the cleft. Occasionally, however, the cleft will extend unusually low and the cord will end with two separate coni medullarae and two fila terminale ("Diplomyelia").

Diagnosis
Adult presentation in diastematomyelia is unusual. With modern imaging techniques, various types of spinal dysraphism are being diagnosed in adults with increasing frequency. The commonest location of the lesion is at first to third lumbar vertebrae. Lumbosacral adult diastematomyelia is even rarer. Bony malformations and dysplasias are generally recognized on plain x-rays. MRI scanning is often the first choice of screening and diagnosis </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 Heredofamilial amyloidosis 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 H and can you explain it in depth? [/INST] H, or h, is the eighth letter in the Latin alphabet, used in the modern English alphabet, the alphabets of other western European languages and others worldwide. Its name in English is aitch (pronounced , plural aitches), or regionally haitch .

History
The original Semitic letter Heth most likely represented the voiceless pharyngeal fricative (ħ). The form of the letter probably stood for a fence or posts.
The Greek Eta Η in archaic Greek alphabets, before coming  to represent a long vowel, /ɛː/, still represented a similar sound, the voiceless glottal fricative /h/. In this context, the letter eta is also known as Heta to underline this fact. Thus, in the Old Italic alphabets, the letter Heta of the Euboean alphabet was adopted with its original sound value /h/.
While Etruscan and Latin had /h/ as a phoneme, almost all Romance languages lost the sound—Romanian later re-borrowed the /h/ phoneme from its neighbouring Slavic languages, and Spanish developed a secondary /h/ from /f/, before losing it again; various Spanish dialects have developed [h] as an allophone of /s/ or /x/ in most Spanish-speaking countries, and various dialects of Portuguese use it as an allophone of /ʀ/. H is also used in many spelling systems in digraphs and trigraphs, such as ch, which represents /tʃ/ in Spanish, Galician, and Old Portuguese; /ʃ/ in French and modern Portuguese; /k/ in Italian and French.

Name in English
For most English speakers, the name for the letter is pronounced as  and spelled "aitch" or occasionally "eitch". The pronunciation  and the associated spelling "haitch" is often considered to be h-adding and is considered non-standard in England. It is, however, a feature of Hiberno-English, and occurs sporadically in various other dialects.
The perceived name of the letter affects the choice of indefinite article before initialisms beginning with H: for example "an H-bomb" or "a H-bomb". The pronunciation /heɪtʃ/ may be a hypercorrection formed by analogy with the names of the other letters of the alphabet, most of which include the sound they represent.The haitch pronunciation of h has spread in England, being used by approximately 24% of English people born since 1982, and polls continue to show this pronunciation becoming more common among younger native speakers. Despite this increasing number, the pronunciation without the /h/ sound is still considered to be standard in England, although the pronunciation with /h/ is also attested as a legitimate variant. In Northern Ireland, the pronunciation of the letter has been used as a shibboleth, with Catholics typically pronouncing it with the /h/ and Protestants pronouncing the letter without it.Authorities disagree about the history of the letters name. The Oxford English Dictionary says the original name of the letter was [ˈaha] in Latin; this became [ˈaka] in Vulgar Latin, passed into English via Old French [atʃ], and by Middle English was pronounced [aːtʃ]. The American Heritage Dictionary of the English Language derives it from French hache from Latin haca or hic. Anatoly Liberman suggests a conflation of two obsolete orderings of the alphabet, one with H immediately followed by K and the other without any K: reciting the formers ..., H, K, L,... as [...(h)a ka el ...] when reinterpreted for the latter ..., H, L,... would imply a pronunciation [(h)a ka] for H.

Use in writing systems
English
In English, ⟨h⟩ occurs as a single-letter grapheme (being either silent or representing the voiceless glottal fricative () and in various digraphs, such as ⟨ch⟩ , , , or ), ⟨gh⟩ (silent, /ɡ/, /k/, /p/, or /f/), ⟨ph⟩ (/f/), ⟨rh⟩ (/r/), ⟨sh⟩ (), ⟨th⟩ ( or ), ⟨wh⟩ (/hw/). The letter is silent in a syllable rime, as in ah, ohm, dahlia, cheetah, pooh-poohed, as well as in certain other words (mostly of French origin) such as hour, honest, herb (in American but not British English) and vehicle (in certain varieties of English). Initial /h/ is often not pronounced in the weak form of some function words including had, has, have, he, her, him, his, and in some varieties of English (including most regional dialects of England and Wales) it is often omitted in all words (see ⟨h⟩-dropping). It was formerly common for an rather than a to be used as the indefinite article before a word beginning with /h/ in an unstressed syllable, as in "an historian", but use of a is now more usual (see English articles § Indefinite article). In English, The pronunciation of ⟨h⟩ as /h/ can be analyzed as a voiceless vowel. That is, when the phoneme /h/ precedes a vowel, /h/ may be realized as a voiceless version of the subsequent vowel. For example the word ⟨hit⟩, /hɪt/ is realized as [ɪ̥ɪt]. H is the eighth most frequently used letter in the English language (after S, N, I, O, A, T, and E), with a frequency of about 4.2% in words. When h is placed after certain other consonants, it modifies their pronunciation in various ways, e.g. for ch, gh, ph, sh, and th.

Other languages
In the German language, the name of the letter is pronounced /haː/. Following a vowel, it often silently indicates that the vowel is long: In the word erhöhen (heighten), the second ⟨h⟩ is mute for most speakers outside of Switzerland. In 1901, a spelling reform eliminated the silent ⟨h⟩ in nearly all instances of ⟨th⟩ in native German words such as thun (to do) or Thür (door). It has been left unchanged in words derived from Greek, such as Theater (theater) and Thron (throne), which continue to be spelled with ⟨th⟩ even after the last German spelling reform.
In Spanish and Portuguese, ⟨h⟩ ("hache" in Spanish, pronounced [atʃe], or agá in Portuguese, pronounced [aˈɣa] or [ɐˈɡa]) is a silent letter with no pronunciation, as in hijo [ˈixo] (son) and húngaro [ˈũɡaɾu] (Hungarian). The spelling reflects an earlier pronunciation of the sound /h/. In words where the ⟨h⟩ is derived from a Latin /f/, it is still sometimes pronounced with the value [h] in some regions of Andalusia, Extremadura, Canarias, Cantabria, and the Americas. Some words beginning with [je] or [we], such as hielo, ice and huevo, egg, were given an initial ⟨h⟩ to avoid confusion between their initial semivowels and the consonants ⟨j⟩ and ⟨v⟩. This is because ⟨j⟩ and ⟨v⟩ used to be considered variants of ⟨i⟩ and ⟨u⟩ respectively. ⟨h⟩ also appears in the digraph ⟨ch⟩, which represents /tʃ/ in Spanish and northern Portugal, and /ʃ/ in varieties that have merged both sounds (the latter originally represented by ⟨x⟩ instead), such as most of the Portuguese language and some Spanish dialects, prominently Chilean Spanish.
In French, the name of the letter is written as "ache" and pronounced /aʃ/. The French orthography classifies words that begin with this letter in two ways, one of which can affect the pronunciation, even though it is a silent letter either way. The H muet, or "mute" ⟨h⟩, is considered as though the letter were not there at all, so for example the singular definite article le or la, which is elided to l before a vowel, elides before an H muet followed by a vowel. For example, le + hébergement becomes lhébergement (the accommodation). The other kind of ⟨h⟩ is called h aspiré ("aspirated ⟨h⟩", though it is not normally aspirated phonetically), and does not allow elision or liaison. For example in le homard (the lobster) the article le remains unelided, and may be separated from the noun with a bit of a glottal stop. Most words that begin with an H muet come from Latin (honneur, homme) or from Greek through Latin (hécatombe), whereas most words beginning with an H aspiré come from Germanic (harpe, hareng) or non-Indo-European languages (harem, hamac, haricot); in some cases, an orthographic ⟨h⟩ was added to disambiguate the [v] and semivowel [ɥ] pronunciations before the introduction of the distinction between the letters ⟨v⟩ and ⟨u⟩: huit (from uit, ultimately from Latin octo), huître (from uistre, ultimately from Greek through Latin ostrea).
In Italian, ⟨h⟩ has no phonological value. Its most important uses are in the digraphs ch /k/ and gh /ɡ/, as well as to differentiate the spellings of certain short words that are homophones, for example some present tense forms of the verb avere (to have) (such as hanno, they have, vs. anno, year), and in short interjections (oh, ehi).
Some languages, including Czech, Slovak, Hungarian, Finnish, and Estonian use ⟨h⟩ as a breathy voiced glottal fricative [ɦ], often as an allophone of otherwise voiceless /h/ in a voiced environment.
In Hungarian, the letter has no fewer than five pronunciations, with three additional uses as a productive and non-productive element of digraphs </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 Cortical blindness and can you explain it in depth? [/INST] Cortical blindness is the total or partial loss of vision in a normal-appearing eye caused by damage to the brains occipital cortex. Cortical blindness can be acquired or congenital, and may also be transient in certain instances. Acquired cortical blindness is most often caused by loss of blood flow to the occipital cortex from either unilateral or bilateral posterior cerebral artery blockage (ischemic stroke) and by cardiac surgery. In most cases, the complete loss of vision is not permanent and the patient may recover some of their vision (cortical visual impairment). Congenital cortical blindness is most often caused by perinatal ischemic stroke, encephalitis, and meningitis.
Rarely, a patient with acquired cortical blindness may have little or no insight that they have lost vision, a phenomenon known as Anton–Babinski syndrome.
Cortical blindness and cortical visual impairment (CVI), which refers to the partial loss of vision caused by cortical damage, are both classified as subsets of neurological visual impairment (NVI). NVI and its three subtypes—cortical blindness, cortical visual impairment, and delayed visual maturation—must be distinguished from ocular visual impairment in terms of their different causes and structural foci, the brain and the eye respectively. One diagnostic marker of this distinction is that the pupils of individuals with cortical blindness will respond to light whereas those of individuals with ocular visual impairment will not.

Symptoms
The most common symptoms of acquired and transient cortical blindness include:

A complete loss of visual sensation and of vision
Preservation/sparing of the abilities to perceive light and/or moving, but not static objects (Riddoch syndrome)
A lack of visual fixation and tracking
Denial of visual loss (Anton–Babinski syndrome)
Visual hallucinations
Macular sparing, in which vision in the fovea is spared from the blindness.

Causes
The most common cause of cortical blindness is ischemia (oxygen deprivation) to the occipital lobes caused by blockage to one or both of the posterior cerebral arteries.  However, other conditions have also been known to cause acquired and transient cortical blindness, including:

Congenital abnormalities of the occipital lobe
Head trauma to the occipital lobe of the brain
Bilateral lesions of the primary visual cortex
Infection
Creutzfeldt–Jakob disease (CJD), in association with a rapid onset of dementia
rarely Dissociative identity disorder (DID)
Side effect of some anti-epilepsy drugs (AEDs)
Hyperammonemia
Eclampsia and, rarely, pre-eclampsiaThe most common causes of congenital cortical blindness are:

Traumatic brain injury (TBI) to the occipital lobe of the brain
Congenital abnormalities of the occipital lobe
Perinatal ischemia
Encephalitis
Meningitis

Diagnosis
A patient with cortical blindness has no vision but the response of his/her pupil to light is intact (as the reflex does not involve the cortex). Therefore, one diagnostic test for cortical blindness is to first objectively verify the optic nerves and the non-cortical functions of the eyes are functioning normally. This involves confirming that patient can distinguish light/dark, and that his/her pupils dilate and contract with light exposure. Then, the patient is asked to describe something he/she would be able to recognize with normal vision. For example, the patient would be asked the following:
"How many fingers am I holding up?"
"What does that sign (on a custodians closet, a restroom door, an exit sign) say?"
"What kind of vending machine (with a vivid picture of a well-known brand name on it) is that?"Patients with cortical blindness will not be able to identify the item being questioned about at all or will not be able to provide any details other than color or perhaps general shape. This indicates that the lack of vision is neurological rather than ocular. It specifically indicates that the occipital cortex is unable to correctly process and interpret the intact input coming from the retinas.
Fundoscopy should be normal in cases of cortical blindness.  Cortical blindness can be associated with visual hallucinations, denial of visual loss (Anton–Babinski syndrome), and the ability to perceive moving but not static objects. (Riddoch syndrome).

Outcome
The prognosis of a patient with acquired cortical blindness depends largely on the original cause of the blindness. For instance, patients with bilateral occipital lesions have a much lower chance of recovering vision than patients who suffered a transient ischemic attack or women who experienced complications associated with eclampsia. In patients with acquired cortical blindness, a permanent complete loss of vision is rare. The development of cortical blindness into the milder cortical visual impairment is a more likely outcome.  Furthermore, some patients regain vision completely, as is the case with transient cortical blindness associated with eclampsia and the side effects of certain anti-epilepsy drugs.
Recent research by Krystel R. Huxlin and others on the relearning of complex visual motion following V1 damage has offered potentially promising treatments for individuals with acquired cortical blindness. These treatments focus on retraining and retuning certain intact pathways of the visual cortex which are more or less preserved in individuals who sustained damage to V1. Huxlin and others found that specific training focused on utilizing the "blind field" of individuals who had sustained V1 damage improved the patients ability to perceive simple and complex visual motion </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Primary hyperparathyroidism and can you explain it in depth? [/INST] Primary hyperparathyroidism (or PHPT) is a medical condition where the parathyroid gland (or a benign tumor within it) produce excess amounts of parathyroid hormone (PTH). The symptoms of the condition relate to the resulting elevated serum calcium (hypercalcemia), which can cause digestive symptoms, kidney stones, psychiatric abnormalities, and bone disease.
The diagnosis is initially made on blood tests; an elevated level of calcium together with a raised (or inappropriately high) level of parathyroid hormone are typically found. To identify the source of the excessive hormone secretion, medical imaging may be performed. Parathyroidectomy, the surgical removal of one or more parathyroid glands, may be required to control symptoms.

Signs and symptoms
The signs and symptoms of primary hyperparathyroidism are those of hypercalcemia.  They are classically summarized by "stones, bones, abdominal groans, thrones and psychiatric overtones".
"Stones" refers to kidney stones, nephrocalcinosis, and diabetes insipidus (polyuria and polydipsia). These can ultimately lead to kidney failure.
"Bones" refers to bone-related complications. The classic bone disease in hyperparathyroidism is osteitis fibrosa cystica, which results in pain and sometimes pathological fractures.  Other bone diseases associated with hyperparathyroidism are osteoporosis, osteomalacia, and arthritis.
"Abdominal groans" refers to gastrointestinal symptoms of constipation, indigestion, nausea and vomiting.  Hypercalcemia can lead to peptic ulcers and acute pancreatitis. The peptic ulcers can be an effect of increased gastric acid secretion by hypercalcemia.
"Thrones" refers to polyuria and constipation
"Psychiatric overtones" refers to effects on the central nervous system.  Symptoms include lethargy, fatigue, depression, memory loss, psychosis, ataxia, delirium, and coma.Left ventricular hypertrophy may also be seen.Other signs include proximal muscle weakness, itching, and band keratopathy of the eyes.When subjected to formal research, symptoms of depression, pain, and gastric dysfunction seem to correlate with mild cases of hypercalcemia.

Causes
The most common cause of primary hyperparathyroidism is a sporadic, single parathyroid adenoma resulting from a clonal mutation (~97%).  Less common are parathyroid hyperplasia (~2.5%), parathyroid carcinoma (malignant tumor), and adenomas in more than one gland (together ~0.5%).Primary hyperparathyroidism is also a feature of several familial endocrine disorders:  Multiple endocrine neoplasia type 1 and type 2A (MEN type 1 and MEN type 2A), and familial hyperparathyroidism.Genetic associations include:

In all cases, the disease is idiopathic, but is thought to involve inactivation of tumor suppressor genes (Menin gene in MEN1), or involve gain of function mutations (RET proto-oncogene MEN 2a).Recently, it was demonstrated that liquidators of the Chernobyl power plant are faced with a substantial risk of primary hyperparathyroidism, possibly caused by radioactive strontium isotopes.

Diagnosis
The diagnosis of primary hyperparathyroidism is made by blood tests.Serum calcium levels are usually elevated, and the parathyroid hormone level is abnormally high compared with an expected low level in response to the high calcium. A relatively elevated parathyroid hormone has been estimated to have a sensitivity of 60–80% and a specificity of approximately 90% for primary hyperparathyroidism.A more powerful variant of comparing the balance between calcium and parathyroid hormone is to perform a 3-hour calcium infusion. After infusion, a parathyroid hormone level above a cutoff of 14 ng/L has a sensitivity of 100% and a specificity of 93% in detecting primary hyperparathyroidism, with a confidence interval of 80% to 100%.Urinary cAMP is occasionally measured; it is generally elevated due to activation of Gs proteins when PTH binds to its receptor.Biochemical confirmation of primary hyperparathyroidism is following by investigations to localize the culprit lesion. Primary hyperparathyroidism is most commonly due to solitary parathyroid adenoma. Less commonly it may be due to double parathyroid adenomas or parathyroid hyperplasia. Tc99 sestamibi scan of head, neck and upper thorax is the most commonly used test for localizing parathyroid adenomas having a sensitivity and specificity of 70–80%. Sensitivity falls down to 30% in case of double/multiple parathyroid adenomas or in case of parathyroid hyperplasia. Ultrasonography is also a useful test in localizing suspicious parathyroid lesions.

Normocalcemic Primary Hyperparathyroidism
Normocalcemic PHPT was first recognized in 2009 by an international panel of experts. By definition these patients have normal serum calcium (though usually in the upper range) and are typically found to have elevated PTH during workup for osteoporosis. In order to diagnose normocalcemic PHPT, ionized calcium levels should be normal, and all secondary causes for secondary hyperparathyroidism (such as vitamin D deficiency and chronic kidney disease) ruled out.

Treatment
Treatment is usually surgical removal of the gland(s) containing adenomas, but medication may also be required.

Surgery
The surgical removal of one or more of the parathyroid glands is known as a parathyroidectomy; this operation was first performed in 1925. The symptoms of the disease, listed above, are indications for surgery. Surgery reduces all cause mortality as well as resolving symptoms. However, cardiovascular mortality is not significantly reduced.The 2002 NIH Workshop on Asymptomatic Primary Hyperparathyroidism developed criteria for surgical intervention . The criteria were revised at the Third International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism . These criteria were chosen on the basis of clinical experience and observational and clinical trial data as to which patients are more likely to have end-organ effects of primary hyperparathyroidism (nephrolithiasis, skeletal involvement), disease progression if surgery is deferred, and the most benefit from surgery. The panel emphasized the need for parathyroidectomy to be performed by surgeons who are highly experienced and skilled in the operation. The Third International Workshop guidelines concluded that surgery is indicated in asymptomatic patients who meet any one of the following conditions:
Serum calcium concentration of 1.0 mg/dL (0.25 mmol/L) or more above the upper limit of normal
Creatinine clearance that is reduced to <60 mL/min
Bone density at the hip, lumbar spine, or distal radius that is more than 2.5 standard deviations below peak bone mass (T score <-2.5) and/or previous fragility fracture
Age less than 50 yearsOperative intervention can be delayed in patients over 50 years of age who are asymptomatic or minimally symptomatic and who have serum calcium concentrations <1.0 mg/dL (0.2 mmol/L) above the upper limit of normal, and in patients who are medically unfit for surgeryMore recently, three randomized controlled trials have studied the role of surgery in patients with asymptomatic hyperparathyroidism. The largest study reported that surgery resulted in an increase in bone mass, but no improvement in quality of life after one to two years among patients in the following groups:
Untreated, asymptomatic primary hyperparathyroidism
Serum calcium between 2.60 and 2.85 mmol/liter (10.4–11.4 mg/dL)
Age between 50 and 80 yr
No medications interfering with Ca metabolism
No hyperparathyroid bone disease
No previous operation in the neck
Creatinine level < 130 μmol/liter (<1.47 mg/dL)Two other trials reported improvements in bone density and some improvement in quality of life with surgery.

Medications
Medications are used when surgery is not indicated or for poor surgical candidates. Calcimimetics are used to reduce the amount of parathyroid hormone released by the parathyroid glands and subsequent hypercalcemia. Other medications used for PHPT includes treatments for osteoporosis such as estrogen replacement therapy, bisphosphonates or denosumab and for treatment hypercalciuria to reduce the risk for kidney stones.

Epidemiology
Primary hyperparathyroidism affects approximately 1 per 1,000 people (0.1%), while there are 25–30 new cases per 100,000 people per year in the United States. The prevalence of primary hyperparathyroidism has been estimated to be 3 in 1000 in the general population and as high as 21 in 1000 in postmenopausal women </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 Meningoencephalitis and can you explain it in depth? [/INST] Meningoencephalitis (; from Ancient Greek: μῆνιγξ, romanized: meninx, lit. membrane; Ancient Greek: ἐγκέφαλος, romanized: enképhalos, lit. brain; and the medical suffix -itis, "inflammation"), also known as herpes meningoencephalitis, is a medical condition that simultaneously resembles both meningitis, which is an infection or inflammation of the meninges, and encephalitis, which is an infection or inflammation of the brain.

Signs and symptoms
Signs of meningoencephalitis include unusual behavior, personality changes, and thinking problems.Symptoms may include headache, fever, pain in neck movement, light sensitivity, and seizure.

Causes
Causative organisms include protozoans, viral and bacterial pathogens.Specific types include:

Bacterial
Veterinarians have observed meningoencephalitis in animals infected with listeriosis, caused by the pathogenic bacteria L. monocytogenes. Meningitis and encephalitis already present in the brain or spinal cord of an animal may form simultaneously into meningeoencephalitis. The bacterium commonly targets the sensitive structures of the brain stem. L. monocytogenes meningoencephalitis has been documented to significantly increase the number of cytokines, such as IL-1β, IL-12, IL-15, leading to toxic effects on the brain.Meningoencephalitis may be one of the severe complications of diseases originating from several Rickettsia species, such as Rickettsia rickettsii (agent of Rocky Mountain spotted fever (RMSF)), Rickettsia conorii, Rickettsia prowazekii (agent of epidemic louse-borne typhus), and Rickettsia africae. It can cause impairments to the cranial nerves, paralysis to the eyes, and sudden hearing loss. Meningoencephalitis is a rare, late-stage manifestation of tick-borne ricksettial diseases, such as RMSF and human monocytotropic ehrlichiosis (HME), caused by Ehrlichia chaffeensis (a species of rickettsiales bacteria).Other bacteria that can cause it are Mycoplasma pneumoniae, Tuberculosis, Borrelia (Lyme disease) and Leptospirosis.

Viral
Tick-borne encephalitis
West Nile virus
Measles
Epstein–Barr virus
Varicella-zoster virus
Enterovirus
Herpes simplex virus type 1
Herpes simplex virus type 2
Rabies virus
Adenovirus, although meningoencephalitis is almost solely seen in heavily immunocompromised patients.
Mumps, a relatively common cause of meningoencephalitis.  However, most cases are mild, and mumps meningoencephalitis generally does not result in death or neurologic sequelae.
HIV, a very small number of individuals exhibit meningoencephalitis at the primary stage of infection.

Autoimmune
Antibodies targeting amyloid beta peptide proteins which have been used during research on Alzheimers disease.
Anti-N-methyl-D-aspartate (anti-NMDA) receptor antibodies, which are also associated with seizures and a movement disorder, and related to anti-NMDA receptor encephalitis.
NAIM or "Nonvasculitic autoimmune inflammatory meningoencephalitis" (NAIM) </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 Short stature and can you explain it in depth? [/INST] Short stature refers to a height of a human which is below typical. Whether a person is considered short depends on the context. Because of the lack of preciseness, there is often disagreement about the degree of shortness that should be called short. Dwarfism is the condition of being very short, often caused by a medical condition.
In a medical context, short stature is typically defined as an adult height that is more than two standard deviations below a population’s mean for age and gender, which corresponds to the shortest 2.3% of individuals in that population. The median or typical adult height in developed countries is about 178 centimetres (5 ft 10 in) for men and 165 centimetres (5 ft 5 in) for women.

Causes
Shortness in children and young adults nearly always results from below-average growth in childhood, while shortness in older adults usually results from loss of height due to kyphosis of the spine or collapsed vertebrae from osteoporosis. The most common causes of short stature in childhood are constitutional growth delay  or familial short stature.
From a medical perspective, severe shortness can be a variation of normal, resulting from the interplay of multiple familial genes. It can also be due to one or more of many abnormal conditions, such as chronic (prolonged) growth hormone or thyroid hormone deficiency, malnutrition, disease of a major organ system, mistreatment, treatment with certain drugs, chromosomal deletions. Human growth hormone (HGH) deficiency may occur at any time during infancy or childhood, with the most obvious sign being a noticeable slowing of growth. The deficiency may be genetic. Among children without growth hormone deficiency, short stature may be caused by Turner syndrome or Noonan syndrome, chronic kidney disease, being small for gestational age at birth, Prader–Willi syndrome, Wiedemann-Steiner syndrome, or other conditions. Genetic skeletal dysplasias also known as osteochondrodysplasia usually manifest in short-limbed disproportionate short stature.When the cause is unknown, it is called idiopathic short stature.
Short stature can also be caused by the bone plates fusing at an earlier age than normal, therefore stunting growth. Normally, the bone age is the same as the biological age but for some people, it is older. For many people with advanced bone ages, they hit a growth spurt early on which propels them to average height but stop growing at an earlier age. However, in some cases, people who are naturally shorter combined with their advanced bone age, end up being even shorter than the height they normally would have been because of their stunted growth.
Some of the reasons growth development may slow include:
Genetics. When a child’s parents and grandparents are short, the child may also be short; this is known as familial short stature. Also, the target height is merely an estimate and some children simply dont grow as tall as expected.
Genetic conditions. Several genetic syndromes can lead to short stature, including Prader-Willi syndrome, Turner syndrome and Noonan syndrome.
Chronic diseases. Growth hormone is produced by the pituitary gland, located in the middle of the brain. Therefore, chronic medical problems that affect the pituitary gland may also affect growth. For example, radiation to the brain can affect pituitary function, so pediatric cancer or its treatment can lead to short stature. Gastrointestinal diseases that impair nutrition, such as inflammatory bowel disease and celiac can affect growth, can also be a cause. Many other conditions can also delay the growth rate, including hypothyroidism, heart disease, kidney disease, immunological disease and several other endocrine disorders.
Growth hormone deficiency. Some children simply dont produce enough growth hormone, including those born with a poorly developed pituitary gland.
Malnutrition. This is caused by an inadequate food supply, an eating disorder, or an underlying condition or treatment that affects appetite, lack of nourishment is a common cause of growth delay.
Psychosocial stress.exposure to violence because of war or famine or just being in a home environment that’s not very nurturing, children can also experience a psychosocial stress that keeps them from growing properly,” Dr. Patel says. “That can be reversed just by removing them from the stressful environment.”

Classification
Chronic illnesses, malnutrition, endocrine, metabolic disorders or chromosomal anomalies are characterized by proportionate short stature.
On the other hand, most genetic skeletal dysplasias are known for short stature that may be proportionate or disproportionate. Disproportionate short stature can be further subdivided as specified by the body segments affected by shortening, namely limbs versus trunk:
Short-limb short stature in which there is limb shortening as achondroplasia, hypochondroplasia, pseudoachondroplasia and multiple epiphyseal dysplasia.
Short-trunk short stature in which there is trunk shortening as spondyloepiphyseal dysplasia and mucopolysaccharidosisShort-limb short stature can be further subcategorised in accordance with limb segment affected by shortening. These subcategories of limb shortening include, rhizomelic (humerus and femur), mesomelic (radius, ulna, tibia and fibula) and acromelic (hands and feet). Anthropometric measurements provide are very beneficial tools to the diagnostic process of genetic skeletal dysplasias. The anthropometric measurements include height, sitting height, arm span, upper/ lower-body segment ratio, sitting height/height ratio, and arm span/height ratio for age. They also aid in the differential diagnosis of skeletal dysplasia subtypes.

Treatment
The decision to treat is based on a belief that the child will be disabled by being extremely short as an adult, so that the risks of treatment (including sudden death) will outweigh the risks of not treating the symptom of short stature. Although short children commonly report being teased about their height, most adults who are very short are not physically or psychologically disabled by their height. However, there is some evidence to suggest that there is an inverse linear relationship with height and with risk of suicide.Treatment is expensive and requires many years of injections with human growth hormones. The result depends on the cause, but is typically an increase in final height of about 5 to 10 centimetres (2.0 to 3.9 in) taller than predicted. Thus, treatment takes a child who is expected to be much shorter than a typical adult and produces an adult who is still obviously shorter than average. For example, several years of successful treatment in a girl who is predicted to be 146 centimetres (4 ft 9 in) as an adult may result in her being 151 centimetres (4 ft 11 in) instead.
Increasing final height in children with short stature may be beneficial and could enhance health-related quality of life outcomes, barring troublesome side effects and excessive cost of treatments.

Cost
The cost of treatment depends on the amount of growth hormone given, which in turn depends on the childs weight and age. One years worth of drugs normally costs about US$20,000 for a small child and over $50,000 for a teenager. These drugs are normally taken for five or more years.

Cultural issues
From a social perspective shortness can be a problem independently of the cause. In many societies there are advantages associated with taller stature and disadvantages associated with shorter stature, and vice versa.
Pharmaceutical companies Genentech and Eli Lilly, makers of human growth hormone, have worked to medicalize short stature by convincing the public that short stature is a disease rather than a natural variation in human height </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 Foot and can you explain it in depth? [/INST] The foot (PL: feet) is an anatomical structure found in many vertebrates. It is the terminal portion of a limb which bears weight and allows locomotion. In many animals with feet, the foot is a separate organ at the terminal part of the leg made up of one or more segments or bones, generally including claws or nails.

Etymology
The word "foot", in the sense of meaning the "terminal part of the leg of a vertebrate animal" comes from "Old English fot "foot," from Proto-Germanic *fot (source also of Old Frisian fot, Old Saxon fot, Old Norse fotr, Danish fod, Swedish fot, Dutch voet, Old High German fuoz, German Fuß, Gothic fotus "foot"), from PIE root *ped- "foot".
The "plural form feet is an instance of i-mutation."

Structure
The human foot is a strong and complex mechanical structure containing 26 bones, 33 joints (20 of which are actively articulated), and more than a hundred muscles, tendons, and ligaments. The joints of the foot are the ankle and subtalar joint and the interphalangeal joints of the foot. An anthropometric study of 1197 North American adult Caucasian males (mean age 35.5 years) found that a mans foot length was 26.3 cm with a standard deviation of 1.2 cm.The foot can be subdivided into the hindfoot, the midfoot, and the forefoot:
The hindfoot is composed of the talus (or ankle bone) and the calcaneus (or heel bone). The two long bones of the lower leg, the tibia and fibula, are connected to the top of the talus to form the ankle. Connected to the talus at the subtalar joint, the calcaneus, the largest bone of the foot, is cushioned underneath by a layer of fat.The five irregular bones of the midfoot, the cuboid, navicular, and three cuneiform bones, form the arches of the foot which serves as a shock absorber. The midfoot is connected to the hind- and fore-foot by muscles and the plantar fascia.The forefoot is composed of five toes and the corresponding five proximal long bones forming the metatarsus. Similar to the fingers of the hand, the bones of the toes are called phalanges and the big toe has two phalanges while the other four toes have three phalanges each. The joints between the phalanges are called interphalangeal and those between the metatarsus and phalanges are called metatarsophalangeal (MTP).
Both the midfoot and forefoot constitute the dorsum (the area facing upward while standing) and the planum (the area facing downward while standing).

The instep is the arched part of the top of the foot between the toes and the ankle.

Bones
tibia, fibula
tarsus (7): talus, calcaneus, cuneiformes (3), cuboid, and navicular
metatarsus (5): first, second, third, fourth, and fifth metatarsal bone
phalanges (14)There can be many sesamoid bones near the metatarsophalangeal joints, although they are only regularly present in the distal portion of the first metatarsal bone.

Arches
The human foot has two longitudinal arches and a transverse arch maintained by the interlocking shapes of the foot bones, strong ligaments, and pulling muscles during activity. The slight mobility of these arches when weight is applied to and removed from the foot makes walking and running more economical in terms of energy. As can be examined in a footprint, the medial longitudinal arch curves above the ground. This arch stretches from the heel bone over the "keystone" ankle bone to the three medial metatarsals. In contrast, the lateral longitudinal arch is very low. With the cuboid serving as its keystone, it redistributes part of the weight to the calcaneus and the distal end of the fifth metatarsal. The two longitudinal arches serve as pillars for the transverse arch which run obliquely across the tarsometatarsal joints. Excessive strain on the tendons and ligaments of the feet can result in fallen arches or flat feet.

Muscles
The muscles acting on the foot can be classified into extrinsic muscles, those originating on the anterior or posterior aspect of the lower leg, and intrinsic muscles, originating on the dorsal (top) or plantar (base) aspects of the foot.

Extrinsic
All muscles originating on the lower leg except the popliteus muscle are attached to the bones of the foot. The tibia and fibula and the interosseous membrane separate these muscles into anterior and posterior groups, in their turn subdivided into subgroups and layers.

Anterior group
Extensor group: the tibialis anterior originates on the proximal half of the tibia and the interosseous membrane and is inserted near the tarsometatarsal joint of the first digit. In the non-weight-bearing leg, the tibialis anterior dorsiflexes the foot and lift its medial edge (supination). In the weight-bearing leg, it brings the leg toward the back of the foot, like in rapid walking. The extensor digitorum longus arises on the lateral tibial condyle and along the fibula, and is inserted on the second to fifth digits and proximally on the fifth metatarsal. The extensor digitorum longus acts similar to the tibialis anterior except that it also dorsiflexes the digits. The extensor hallucis longus originates medially on the fibula and is inserted on the first digit. It dorsiflexes the big toe and also acts on the ankle in the unstressed leg. In the weight-bearing leg, it acts similarly to the tibialis anterior.Peroneal group: the peroneus longus arises on the proximal aspect of the fibula and peroneus brevis below it. Together, their tendons pass behind the lateral malleolus. Distally, the peroneus longus crosses the plantar side of the foot to reach its insertion on the first tarsometatarsal joint, while the peroneus brevis reaches the proximal part of the fifth metatarsal. These two muscles are the strongest pronators and aid in plantar flexion. The peroneus longus also acts like a bowstring that braces the transverse arch of the foot.

Posterior group
The superficial layer of posterior leg muscles is formed by the triceps surae and the plantaris. The triceps surae consists of the soleus and the two heads of the gastrocnemius. The heads of gastrocnemius arise on the femur, proximal to the condyles, and the soleus arises on the proximal dorsal parts of the tibia and fibula. The tendons of these muscles merge to be inserted onto the calcaneus as the Achilles tendon. The plantaris originates on the femur proximal to the lateral head of the gastrocnemius and its long tendon is embedded medially into the Achilles tendon. The triceps surae is the primary plantar flexor. Its strength becomes most obvious during ballet dancing. It is fully activated only with the knee extended, because the gastrocnemius is shortened during flexion of the knee. During walking it not only lifts the heel, but also flexes the knee, assisted by the plantaris.In the deep layer of posterior muscles, the tibialis posterior arises proximally on the back of the interosseous membrane and adjoining bones, and divides into two parts in the sole of the foot to attach to the tarsus. In the non-weight-bearing leg, it produces plantar flexion and supination, and, in the weight-bearing leg, it proximates the heel to the calf. The flexor hallucis longus arises on the back of the fibula on the lateral side, and its relatively thick muscle belly extends distally down to the flexor retinaculum where it passes over to the medial side to stretch across the sole to the distal phalanx of the first digit. The popliteus is also part of this group, but, with its oblique course across the back of the knee, does not act on the foot.

Intrinsic
On the top of the foot, the tendons of extensor digitorum brevis and extensor hallucis brevis lie deep in the system of long extrinsic extensor tendons. They both arise on the calcaneus and extend into the dorsal aponeurosis of digits one to four, just beyond the penultimate joints. They act to dorsiflex the digits. Similar to the intrinsic muscles of the hand, there are three groups of muscles in the sole of foot, those of the first and last digits, and a central group:

Muscles of the big toe: the abductor hallucis stretches medially along the border of the sole, from the calcaneus to the first digit. Below its tendon, the tendons of the long flexors pass through the tarsal canal. The abductor hallucis is an abductor and a weak flexor, and also helps maintain the arch of the foot. The flexor hallucis brevis arises on the medial cuneiform bone and related ligaments and tendons. An important plantar flexor, it is crucial to ballet dancing. Both these muscles are inserted with two heads proximally and distally to the first metatarsophalangeal joint. The adductor hallucis is part of this group, though it originally formed a separate system (see Contrahens). It has two heads, the oblique head originating obliquely across the central part of the midfoot, and the transverse head originating near the metatarsophalangeal joints of digits five to three. Both heads are inserted into the lateral sesamoid bone of the first digit. The adductor hallucis acts as a tensor of the plantar arches and also adducts the big toe and might plantar flex the proximal phalanx.Muscles of the little toe: Stretching laterally from the calcaneus to the proximal phalanx of the fifth digit, the abductor digiti minimi form the lateral margin of the foot and are the largest of the muscles of the fifth digit. Arising from the base of the fifth metatarsal, the flexor digiti minimi is inserted together with abductor on the first phalanx. Often absent, the opponens digiti minimi originates near the cuboid bone and is inserted on the fifth metatarsal bone. These three muscles act to support the arch of the foot and to plantar flex the fifth digit.

Central muscle group: The four lumbricals arise on the medial side of the tendons of flexor digitorum longus and are inserted on the medial margins of the proximal phalanges. The quadratus plantae originates with two slips from the lateral and medial margins of the calcaneus and inserts into the lateral margin of the flexor digitorum tendon. It is also known as the flexor accessorius. The flexor digitorum brevis arises inferiorly on the calcaneus and its three tendons are inserted into the middle phalanges of digits two to four (sometimes also the fifth digit). These tendons divide before their insertions and the tendons of flexor digitorum longus pass through these divisions. Flexor digitorum brevis flexes the middle phalanges. It is occasionally absent. Between the toes, the dorsal and plantar interossei stretch from the metatarsals to the proximal phalanges of digits two to five. The plantar interossei adduct and the dorsal interossei abduct these digits, and are also plantar flexors at the metatarsophalangeal joints.

Clinical significance
Due to their position and function, feet are exposed to a variety of potential infections and injuries, including athletes foot, bunions, ingrown toenails, Mortons neuroma, plantar fasciitis, plantar warts, and stress fractures. In addition, there are several genetic disorders that can affect the shape and function of the feet, including clubfoot or flat feet.
This leaves humans more vulnerable to medical problems that are caused by poor leg and foot alignments. Also, the wearing of shoes, sneakers and boots can impede proper alignment and movement within the ankle and foot. For example, high-heeled shoes are known to throw off the natural weight balance (this can also affect the lower back). For the sake of posture, flat soles with no heels are advised.
A doctor who specializes in the treatment of the feet practices podiatry and is called a podiatrist. A pedorthist specializes in the use and modification of footwear to treat problems related to the lower limbs.

Fractures of the foot include:

Lisfranc fracture – in which one or all of the metatarsals are displaced from the tarsus
Jones fracture – a fracture of the fifth metatarsal
March fracture – a fracture of the distal third of one of the metatarsals occurring because of recurrent stress
Calcaneal fracture
Broken toe – a fracture of a phalanx
Cuneiform fracture – Due to the ligamentous support of the midfoot, isolated cuneiform fractures are rare.

Pronation
In anatomy, pronation is a rotational movement of the forearm (at the radioulnar joint) or foot (at the subtalar and talocalcaneonavicular joints). Pronation of the foot refers to how the body distributes weight as it cycles through the gait. During the gait cycle the foot can pronate in many different ways based on rearfoot and forefoot function. Types of pronation include neutral pronation,  underpronation (supination), and overpronation.

Neutral pronationAn individual who neutrally pronates initially strikes the ground on the lateral side of the heel. As the individual transfers weight from the heel to the metatarsus, the foot will roll in a medial direction, such that the weight is distributed evenly across the metatarsus. In this stage of the gait, the knee will generally, but not always, track directly over the hallux.
This rolling inward motion as the foot progresses from heel to toe is the way that the body naturally absorbs shock. Neutral pronation is the most ideal, efficient type of gait when using a heel strike gait; in a forefoot strike, the body absorbs shock instead via flexion of the foot.

OverpronationAs with a neutral pronator, an individual who overpronates initially strikes the ground on the lateral side of the heel. As the individual transfers weight from the heel to the metatarsus, however, the foot will roll too far in a medial direction, such that the weight is distributed unevenly across the metatarsus, with excessive weight borne on the hallux. In this stage of the gait, the knee will generally, but not always, track inward.
An overpronator does not absorb shock efficiently. Imagine someone jumping onto a diving board, but the board is so flimsy that when it is struck, it bends and allows the person to plunge straight down into the water instead of back into the air. Similarly, an overpronators arches will collapse, or the ankles will roll inward (or a combination of the two) as they cycle through the gait. An individual whose bone structure involves external rotation at the hip, knee, or ankle will be more likely to overpronate than one whose bone structure has internal rotation or central alignment. An individual who overpronates tends to wear down their running shoes on the medial (inside) side of the shoe toward the toe area.When choosing a running or walking shoe, a person with overpronation can choose shoes that have good inside support—usually by strong material at the inside sole and arch of the shoe.  It is usually visible.  The inside support area is marked by strong greyish material to support the weight when a person lands on the outside foot and then roll onto the inside foot.

Underpronation (supination)
An individual who underpronates also initially strikes the ground on the lateral side of the heel. As the individual transfers weight from the heel to the metatarsus, the foot will not roll far enough in a medial direction. The weight is distributed unevenly across the metatarsus, with excessive weight borne on the fifth metatarsal, toward the lateral side of the foot. In this stage of the gait, the knee will generally, but not always, track laterally of the hallux.
Like an overpronator, an underpronator does not absorb shock efficiently – but for the opposite reason. The underpronated foot is like a diving board that, instead of failing to spring someone in the air because it is too flimsy, fails to do so because it is too rigid. There is virtually no give. An underpronators arches or ankles dont experience much motion as they cycle through the gait. An individual whose bone structure involves internal rotation at the hip, knee, or ankle will be more likely to underpronate than one whose bone structure has external rotation or central alignment. Usually – but not always – those who are bow-legged tend to underpronate. An individual who underpronates tends to wear down their running shoes on the lateral (outside) side of the shoe toward the rear of the shoe in the heel area.

Society and culture
Humans usually wear shoes or similar footwear for protection from hazards when walking outside. There are a number of contexts where it is considered inappropriate to wear shoes. Some people consider it rude to wear shoes into a house and a Māori Marae should only be entered with bare feet.
Foot fetishism is the most common sexual fetish.

Other animals
A paw is the soft foot of a mammal, generally a quadruped, that has claws or nails (e.g., a cat or dogs paw). A hard foot is called a hoof. Depending on style of locomotion, animals can be classified as plantigrade (sole walking), digitigrade (toe walking), or unguligrade (nail walking).
The metatarsals are the bones that make up the main part of the foot in humans, and part of the leg in large animals or paw in smaller animals. The number of metatarsals are directly related to the mode of locomotion with many larger animals having their digits reduced to two (elk, cow, sheep) or one (horse). The metatarsal bones of feet and paws are tightly grouped compared to, most notably, the human hand where the thumb metacarpal diverges from the rest of the metacarpus.

Metaphorical and cultural usage
The word "foot" is used to refer to a "...linear measure was in Old English (the exact length has varied over time), this being considered the length of a mans foot; a unit of measure used widely and anciently. In this sense the plural is often foot. The current inch and foot are implied from measurements in 12c."
The word "foot" also has a musical meaning; a "...metrical foot (late Old English, translating Latin pes, Greek pous in the same sense) is commonly taken to represent one rise and one fall of a foot: keeping time according to some, dancing according to others."The word "foot" was used in Middle English to mean "a person" (c. 1200).
The expression "...to put ones best foot foremost first recorded 1849 (Shakespeare has the better foot before, 1596)". The expression to "...put ones foot in (ones) mouth "say something stupid" was first used in 1942. The expression "put (ones) foot in something" meaning to "make a mess of it" was used in 1823.The word "footloose" was first used in the 1690s, meaning "free to move the feet, unshackled"; the more "figurative sense of "free to act as one pleases" was first used in 1873. Like "footloose", "flat-footed" at first had its obvious literal meaning (in 1600, it meant "with flat feet") but by 1912 it meant "unprepared" (U.S. baseball slang).

See also
References
Bibliography
France, Diane L. (2008). Human and Nonhuman Bone Identification: A Color Atlas. CRC Press. ISBN 978-1-4200-6286-1.
Marieb, Elaine Nicpon; Hoehn, Katja (2007) </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 Stridor and can you explain it in depth? [/INST] Stridor (Latin for "creaking or grating noise") is a high-pitched extra-thoracic breath sound resulting from turbulent air flow in the larynx or lower in the bronchial tree. It is different from a stertor which is a noise originating in the pharynx. Stridor is a physical sign which is caused by a narrowed or obstructed airway. It can be inspiratory, expiratory or biphasic, although it is usually heard during inspiration. Inspiratory stridor often occurs in children with croup. It may be indicative of serious airway obstruction from severe conditions such as epiglottitis, a foreign body lodged in the airway, or a laryngeal tumor. Stridor should always command attention to establish its cause </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 Perforation and can you explain it in depth? [/INST] A perforation is a small hole in a thin material or web. There is usually more than one perforation in an organized fashion, where all of the holes collectively are called a perforation. The process of creating perforations is called perforating, which involves puncturing the workpiece with a tool.
Perforations are usually used to allow easy separation of two sections of the material, such as allowing paper to be torn easily along the line. Packaging with perforations in paperboard or plastic film is easy for consumers to open.   Other purposes include filtrating fluids, sound deadening, allowing light or fluids to pass through, and to create an aesthetic design.Various applications include plastic films to allow the packages to breathe, medical films, micro perforated plate and sound and vapor barriers.

Processes
Pins and needles
Rotary pinned perforation rollers are precision tools that can be used to perforate a wide variety of materials. The pins or needles can be used cold or heated. Cold perforation tools include needle punches.
There are a handful of manufacturers that specialize in hot and cold needle perforation tooling and equipment. In materials that have elasticity this can result in a "volcano" hole that is preferred in many applications.
Pinned rollers can be made from a variety of materials, including plastic, steel, and aluminum.
In more brittle films, cold perforation can cause slitting rather than creating a round hole, which can jeopardize the materials integrity under pressure.  The solution to this is often heating the pin; i.e. hot pin perforation. Hot perforation melts a hole in the material, causing a reinforced ring around the hole. Hot needle perforation also assists when high density pin patterns are utilized, as the heat aids the perforation of the material.

Die and punch
Die and punch sets can be used for thicker materials or materials that require large holes; this process is the most common for metalworking. The workpiece is sheared by pressing (either by machine or hand tool) the punch through the workpiece and into the die. The middle section of the workpiece is scrap; commonly known as the chad in paper and similar materials. The punch and die are shaped to produce the desired shaped hole. The clearance (the distance between the outside circumference of the punch and the inner circumference of the die) must be properly maintained to ensure a clean cut. Burrs are produced on the side of the workpiece that is against the die.Common applications are fruit and vegetable bags, hole punching and ticket punching.

Laser perforation
Laser cutting can place many precise holes in a web. Laser perforations look similar in many respects to hot needle perforations. However, laser systems are expensive. The big advantage of laser perforation is the consistency of the hole size, compared to mechanical perforation. This is very important in modified atmosphere packaging for fresh produce. The laser perforation is often carried out on roll slitting machines (slitter rewinder) as the printed material is slit down to the finished roll size.

Applications
Perforation frequently refers to the practice of creating a long series of holes or slits so that paper or plastics can be torn more easily along a given line: this is used in easy-open packaging.  Since the creation of perforation devices in the 1840s and 1850s, it has seen use in several areas.
Postage stamps are one common application of this, where small round holes are cut in lines to create individual pieces </s>