<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 Speech disfluency and can you explain it in depth? [/INST] A speech disfluency, also spelled speech dysfluency, is any of various breaks, irregularities, or non-lexical vocables which occur within the flow of otherwise fluent speech. These include "false starts", i.e. words and sentences that are cut off mid-utterance; phrases that are restarted or repeated and repeated syllables; "fillers", i.e. grunts or non-lexical utterances such as "huh", "uh", "erm", "um", "well", "so", "like", and "hmm"; and "repaired" utterances, i.e. instances of speakers correcting their own slips of the tongue or mispronunciations (before anyone else gets a chance to). "Huh" is claimed to be a universal syllable.

Fillers
Fillers are parts of speech which are not generally recognized as purposeful or containing formal meaning, usually expressed as pauses such as "uh", "like" and "er", but also extending to repairs ("He was wearing a black—uh, I mean a blue, a blue shirt"), and articulation problems such as stuttering.  Use is normally frowned upon in mass media such as news reports or films, but they occur regularly in everyday conversation, sometimes representing upwards of 20% of "words" in conversation. Fillers can also be used as a pause for thought ("I arrived at, um—3 oclock"), and when used in this function are called hesitation markers or planners.

Language-dependence
Research in computational linguistics has revealed a correlation between native language and patterns of disfluencies in spontaneously uttered speech. Besides that research, there are other subjective accounts reported by individuals.
According to one commentator, Americans use pauses such as "um" or "em", the Irish commonly use the pause "em", the British say "uh" or "eh", the French use "euh", the Germans say "äh" (pronounced eh or er), the Dutch use "eh", Japanese use "ā", "anō" or "ēto", the Spanish say "ehhh" (also used in Hebrew) and "como" (normally meaning like), and Latin Americans but not the Spanish use "este" (normally meaning this). Besides "er" and "uh", the Portuguese use "hã" or "é".
In Mandarin, "那个(nà gè)" and "这个(zhè ge)" are used, meaning "that" or "this", respectively. Arabic speakers say "يعني", the pronunciation of which is close to "yaani", [jæʕni] or [jaʕni], (literally he means, there is no grammatical gender-neutral third person) and Turkish say "şey" in addition to "yani" (without the [ʕ] found in Arabic) and "ııı".Despite the differences between languages, pause fillers in different languages often sound similar because they tend to be the easiest and most neutral vowel sounds to make (such as the schwa), i.e the sounds that can be pronounced with a relaxed tongue or jaw.

Research
Recent linguistic research has suggested that non-pathological disfluencies may contain a variety of meaning; the frequency of "uh" and "um" in English is often reflective of a speakers alertness or emotional state. Some have hypothesized that the time of an "uh" or "um" is used for the planning of future words; other researchers have suggested that they are actually to be understood as full-fledged function words rather than accidents, indicating a delay of variable time in which the speaker wishes to pause without voluntarily yielding control of the dialogue. There is some debate as to whether to consider them a form of noise or as a meaning-filled part of language.
Speech disfluencies have also become important in recent years with the advent of speech-to-text programs and other attempts at enabling computers to make sense of human speech.

"Hmm"
Hmm is an exclamation (an emphatic interjection) typically used to express reflection, uncertainty,  thoughtful absorption, or hesitation. Hmm is technically categorized as an interjection, like um, huh, ouch, erm, and wow. The first h-sound is a mimic for breathing out, and the second m-sound, since the mouth is closed, is representing that the person is not currently sure what to say ("erm" and "um" are used similarly). The pause filler indicates that the person is temporarily speechless, but still engaged in thought. The variety of tones, pitches, and lengths used add nuances in meaning.

Etymology
The expression is used in many different languages, however the origin of "hmm" is difficult to find, mainly because "the word is so natural that it may have arisen at any time," as highlighted by linguist at the University of Minnesota and an expert on word origins, Anatoly Liberman. It is possible Neanderthals might have used "hmm". Nicholas Christenfeld, a psychologist at the University of California, San Diego, and an expert on filled pauses, attests "hmm" is popular largely since its such a neutral sound and that "its easier to say than anything else". The earliest attestations of "hmm" are from Shakespeare, "I cried hum... But markt him not a word" (1598 Shakespeare Henry IV, Pt. 1 iii. i. 154). It may be a vocable that grew out of lexicalized throat-clearing.

Use as a filler word
"Hmm" is a "filler" word, such as "um" and "er". Use of "hmm" for "filled pauses" has been considered by many as stupidity and showing a lack of skill or competence, but many linguists  attest this judgement is unjustified. Typically, "hmm" is uttered when the person is being especially conscious about whom they are talking with, and as a result are thinking deeply about what to say. Moreover, the use of "hmm" is often interactional and cognitive. The interactional function is to do with politeness: if someone is invited to a party and responded "no" without a filled pause, they might appear rude, but a reply of "Hmm, sorry, no" might appear much more polite, as it seems the speaker is giving the offer some thought, rather than abruptly declining.

Thoughtful absorption
The use of "hmm" is typically used during "thoughtful absorption", which is when one is engrossed in their flow of ideas and associations, that lead to a reality-oriented conclusion. The utterance of "hmm" is key for listeners to understand that the speaker is currently engaged in thought; if the speaker thought silently instead, listeners may be unsure if the speaker had finished their utterance. "Um" and "er" are also used during thoughtful absorption; however, typically the extent of the absorption of thought is more limited since "um" and "er" are usually spoken mid-sentence and for shorter periods of time than "hmm". For this reason, thoughtful absorption is typically associated with the utterance of "hmm".

"Huh" – the universal syllable
Research has shown that the word/syllable "huh" is perhaps the most recognized syllable throughout the world.  It is an interrogative. This crosses geography, language, cultures and nationalities.

See also
References
Further reading
Clark, HH.; Fox Tree, JE. (May 2002). "Using uh and um in spontaneous speaking" (PDF). Cognition. 84 (1): 73–111. CiteSeerX 10.1.1.5.7958. doi:10.1016/S0010-0277(02)00017-3. PMID 12062148. S2CID 37642332. Archived from the original (PDF) on 2013-11-10.
Corley, Martin; Stewart, Oliver W. (2008). "Hesitation Disfluencies in Spontaneous Speech: The Meaning of Um" (PDF). Language and Linguistics Compass. 2 (4): 589–602. doi:10.1111/j.1749-818X.2008.00068.x. hdl:20.500.11820/0e5f2f2f-7383-42c5-a7ba-63f2587ad877. ISSN 1749-818X.
Daniel, Ari (5 Feb 2015). "Are we witnessing the death of uh? Um, maybe—and not just in English".
Eklund, Robert (2004). Disfluency in Swedish human-human and human-machine travel booking dialogues (PDF) (Thesis). Linköping Studies in Science and Technology Dissertation No. 882 (Corrected ed.). Department of Computer and Information Science, Linköping University. ISBN 91-7373-966-9. ISSN 0345-7524. OCLC 940753621. Retrieved 11 August 2021.
Erard, Michael (2008). Um...: Slips, Stumbles, and Verbal Blunders, and What They Mean </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 Pica 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 Dejerine–Roussy syndrome and can you explain it in depth? [/INST] Dejerine–Roussy syndrome or thalamic pain syndrome is a condition developed after a thalamic stroke, a stroke causing damage to the thalamus. Ischemic strokes and hemorrhagic strokes can cause lesioning in the thalamus. As initial stroke symptoms (numbness and tingling) dissipate, an imbalance in sensation causes these later syndromes, characterizing Dejerine–Roussy syndrome. Although some treatments exist, they are often expensive, chemically based, invasive, and only treat patients for some time before they need more treatment, called "refractory treatment".

Symptoms and signs
Dejerine–Roussy syndrome is most commonly preceded by numbness in the affected side. In these cases, numbness is replaced by burning and tingling sensations, widely varying in degree of severity across all cases. The majority of those reported are cases in which the symptoms are severe and debilitating. Burning and tingling can also be accompanied by hypersensitivity, usually in the form of dysaesthesia or allodynia. Less commonly, some patients develop severe ongoing pain with little or no stimuli.Allodynia is pain from a stimulus that would normally not cause pain. For example, there is a patient who experiences unrelenting pain when a breeze touches his skin. Most patients experiencing allodynia, experience pain with touch and pressure, however some can be hypersensitive to temperature.Dysaesthesia is defined as an unpleasant, abnormal sense of touch. It often presents as pain. In this condition it is due to thalamic lesioning. This form of neuropathic pain can be any combination of itching, tingling, burning, or searing experienced spontaneously or from stimuli.Allodynia and dysaesthesia replace numbness between one week and a few months after a thalamic stroke. In general, once the development of pain has stopped, the type and severity of pain will be unchanging and if untreated, persist throughout life. Consequentially, many will undergo some form of pain treatment and adjust to their new lives as best they can.Pain associated with Dejerine–Roussy syndrome is sometimes coupled with anosognosia or somatoparaphrenia which causes a patient having undergone a right-parietal, or right-sided stroke to deny any paralysis of the left side when indeed there is, or deny the paralyzed limb(s) belong to them. Although debatable, these symptoms are rare and considered part of a "thalamic phenomenon", and are not normally considered a characteristic of Dejerine–Roussy syndrome.

Mechanism
Although there are many contributing factors and risks associated with strokes, there are very few associated with Dejerine–Roussy syndrome and thalamic lesions specifically. In general, strokes damage one hemisphere of the brain, which can include the thalamus. The thalamus is generally believed to relay sensory information between a variety of subcortical areas and the cerebral cortex. It is known that sensory information from environmental stimuli travels to the thalamus for processing and then to the somatosensory cortex for interpretation. The final product of this communication is the ability to see, hear or feel something as interpreted by the brain. Dejerine–Roussy syndrome most often compromises tactile sensation. Therefore, the damage in the thalamus causes miscommunication between the afferent pathway and the cortex of the brain, changing what or how one feels. The change could be an incorrect sensation experienced, or inappropriate amplification or dulling of a sensation. Because the brain is considered plastic and each individuals brain is different, it is almost impossible to know how a sensation will be changed without brain mapping and individual consultation.Recently, magnetic resonance imaging has been utilized to correlate lesion size and location with area affected and severity of condition. Although preliminary, these findings hold promise for an objective way to understand and treat patients with Dejerine–Roussy syndrome.

Diagnosis
Dejerine-Roussy is a rare pain syndrome.  Individuals with emerging Dejerine–Roussy syndrome usually report they are experiencing unusual pain or sensitivity that can be allodynic in nature or triggered by seemingly unrelated stimuli (sounds, tastes).  Symptoms are typically lateralized and may include vision loss or loss of balance (position sense).  Workup should be performed by a neurologist and brain imaging to look for evidence of infarction or tumor should be obtained.

Treatments
Many chemical medications have been used for a broad range of neuropathic pain including Dejerine–Roussy syndrome. Symptoms are generally not treatable with ordinary analgesics. Traditional chemicals include opiates and anti-depressants. Newer pharmaceuticals include anti-convulsants and Kampo medicine. As there is no scientific basis in the analgesic efficacy of Kampo medicine beyond placebo, mainstream methods are preferred. Pain treatments are most commonly administered via oral medication or periodic injections. Topical In addition, physical therapy has traditionally been used alongside a medication regimen. More recently, electrical stimulation of the brain and spinal cord and caloric stimulation have been explored as treatments.The most common treatment plans involve a schedule of physical therapy with a medication regimen. Because the pain is mostly unchanging after development, many patients test different medications and eventually choose the regimen that best adapts to their lifestyle, the most common of which are orally and intravenously administered.

Pharmaceutical treatment
Opiates contain the narcotics morphine, codeine, and papaverine which provide pain relief. Opiates activate μ-opioid receptors in the brain which alter the brains perception of sensory input, alleviating pain and sometimes inducing pleasure for a short time period. When intravenously administered, opiates can relieve neuropathic pain but only for a time between 4 and 24 hours. After this time window, the pain returns and the patient must be treated again. Although this method of treatment has been proven to reduce pain, the repetitive use of opiates has also been linked to the activation of the brains reward system and therefore poses a threat of addiction. Heavy doses of opiates can also cause constipation, and respiratory depression.  More common side effects include light-headedness, dizziness, sedation, itching, nausea, vomiting, and sweating.
Anti-depressants are traditionally administered for treatment of mood disorders, also linked to the thalamus, and can be used to treat Dejerine–Roussy symptoms. Specifically, tricyclic anti-depressants such as amitriptyline and selective serotonin reuptake inhibitors have been used to treat this symptom and they are effective to some degree within a short time window.
Anti-convulsants reduce neuronal hyperexcitability, effectively targeting Dejerine–Roussy syndrome. Gabapentin and pregabalin are the most common anti-convulsants. They have significant efficacy in treatment of peripheral and central neuropathic pain. Treatments last 4–12 hours and in general are well tolerated, and the occurrence of adverse events does not differ significantly across patients. Commonly reported side-effects are dizziness, decreased intellectual performance, somnolence, and nausea.
Topical treatment such as lidocaine patches can be used to treat pain locally. The chemical is released to the skin to act as a numbing agent that feels cool, then feels warm, much like IcyHot.

Stimulation treatments
Electrode stimulation from surgically implanted electrodes has been studied in the past decade in hopes of a permanent pain treatment without refraction. Electric stimulation utilizing implants deliver specific voltages to a specific part of the brain for specific durations. More recently, research is being done in radiation therapy as long-term treatment of Dejerine–Roussy syndrome. In general, these studies have concluded initial efficacy in such implants, but pain often re-appears after a year or so. Long-term efficacy of stimulation treatments must be further tested and evaluated.Expensive and invasive, the above treatments are not guaranteed to work, and are not meeting the needs of patients. There is a need for a new, less expensive, less invasive form of treatment, two of which are postulated below.
Spinal cord stimulation has been studied in the last couple of years. In a long case study, 8 patients were given spinal cord stimulation via insertion of a percutaneous lead at the appropriate level of the cervical or thoracic spine. Between 36 and 149 months after the stimulations, the patients were interviewed </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 Hydropneumothorax 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 Cryoglobulinemic vasculitis 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 Carbuncle and can you explain it in depth? [/INST] A carbuncle is a cluster of boils caused by bacterial infection, most commonly with Staphylococcus aureus or Streptococcus pyogenes.  The presence of a carbuncle is a sign that the immune system is active and fighting the infection. The infection is contagious and may spread to other areas of the body, or other people; those living in the same residence may develop carbuncles at the same time </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 Pituitary adenoma and can you explain it in depth? [/INST] Pituitary adenomas are benign tumors that occur in the pituitary gland. Most pituitary tumors are benign, approximately 35% are invasive and just 0.1% to 0.2% are carcinomas. Pituitary adenomas represent from 10% to 25% of all intracranial neoplasms and the estimated prevalence rate in the general population is approximately 17%.Non-invasive and non-secreting pituitary adenomas are considered to be benign in the literal as well as the clinical sense; however a recent meta-analysis (Fernández-Balsells, et al. 2011) of available research has shown there are to date scant studies – of poor quality – to either support or refute this assumption.
Adenomas exceeding 10 mm (0.39 in) in size are defined as macroadenomas, with those smaller than 10 mm (0.39 in) referred to as microadenomas. Most pituitary adenomas are microadenomas and have an estimated prevalence of 16.7% (14.4% in autopsy studies and 22.5% in radiologic studies). A majority of pituitary microadenomas often remain undiagnosed, and those that are diagnosed are often found as an incidental finding and are referred to as incidentalomas.
Pituitary macroadenomas are the most common cause of hypopituitarism.While pituitary adenomas are common, affecting approximately one in 6 of the general population, clinically active pituitary adenomas that require surgical treatment are more rare, affecting approximately one in 1,000 of the general population.

Signs and symptoms
Physical
Hormone secreting pituitary adenomas cause one of several forms of hyperpituitarism. The specifics depend on the type of hormone. Some tumors secrete more than one hormone, the most common combination  being GH and prolactin, which present as unexpected bone growth and unexpected lactation (in both men and women).A patient with pituitary adenoma may present with visual field defects, classically bitemporal hemianopsia. It arises from the compression of the optic nerve by the tumor. The specific area of the visual pathway at which compression by these tumours occurs is at the optic chiasma.
The anatomy of this structure causes pressure on it to produce a defect in the temporal visual field on both sides, a condition called bitemporal hemianopsia. If originating superior to the optic chiasm, more commonly in a craniopharyngioma of the pituitary stalk, the visual field defect will first appear as bitemporal inferior quadrantanopia, if originating inferior to the optic chiasm the visual field defect will first appear as bitemporal superior quadrantanopia. Lateral expansion of a pituitary adenoma can also compress the abducens nerve, causing a lateral rectus palsy.Also, a pituitary adenoma can cause symptoms of increased intracranial pressure. Prolactinomas often start to give symptoms especially during pregnancy, when the increased hormone level estrogen can increase the tumors growth rate.Various types of headaches are common in patients with pituitary adenomas. The adenoma may be the prime causative factor behind the headache or may serve to exacerbate a headache caused by other factors. Amongst the types of headaches experienced are both chronic and episodic migraine, and more uncommonly various unilateral headaches; primary stabbing headache, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) - another type of stabbing headache characterized by short stabs of pain -, cluster headache, and hemicrania continua (HS).Compressive symptoms of pituitary adenomas (visual field deficits, decreased visual acuity, headaches) are more commonly seen with macroadenomas (which are greater than 10 mm in diameter) than with microadenomas (which are less than 10 mm in diameter).Non-secreting adenomas can go undetected for an extended time because no obvious abnormalities are seen; the gradual reduction in normal activities due to decreased production of hormones is rather less evident. For example, insufficient adrenocorticotropic hormone means that the adrenal glands will not produce sufficient cortisol, resulting in slow recovery from illness, inflammation, and chronic fatigue; insufficient growth hormone in children and adolescents leads to diminished stature but which can have many other explanations.

Psychiatric
Various psychiatric manifestations have been associated with pituitary disorders including pituitary adenomas. Psychiatric symptoms such as depression, anxiety apathy, emotional instability, easy irritability and hostility have been noted.

Complications
Acromegaly is a syndrome that results when the anterior pituitary  gland produces excess growth hormone (GH). Approximately 90–95% of acromegaly cases are caused by a pituitary adenoma and it most commonly affects middle aged adults, Acromegly can result in severe disfigurement, serious complicating conditions, and premature death if unchecked. The disease which is often also associated with gigantism, is difficult to diagnose in the early stages and is frequently missed for many years, until changes in external features, especially of the face, become noticeable with the median time from the development of initial symptoms to diagnosis being twelve years.
Cushings syndrome is a hormonal disorder that causes hypercortisolism, which is elevated levels of cortisol in the blood. Cushings disease (CD) is the most frequent cause of Cushings syndrome, responsible for approximately 70% of cases. CD results when a pituitary adenoma causes excessive secretion of adrenocorticotropic hormone (ACTH) that stimulates the adrenal glands to produce excessive amounts of cortisol.Cushings disease may cause fatigue, weight gain, fatty deposits around the abdomen and lower back (truncal obesity) and face ("moon face"), stretch marks (striae) on the skin of the abdomen, thighs, breasts, and arms, hypertension, glucose intolerance, and various infections. In women, it may cause excessive growth of facial hair (hirsutism) and in men erectile dysfunction. Psychiatric manifestations may include depression, anxiety, easy irritability, and emotional instability. It may also result in various cognitive difficulties.Hyperpituitarism is a disease of the anterior lobe of the pituitary gland which is usually caused by a functional pituitary adenoma and results in hypersecretion of adenohypophyseal hormones such as growth hormone; prolactin; thyrotropin; luteinizing hormone; follicle-stimulating hormone; and adrenocorticotropic hormone.
Pituitary apoplexy is a condition that occurs when pituitary adenomas suddenly hemorrhage internally, causing a rapid increase in size or when the tumor outgrows its blood supply which causes tissue necrosis and subsequent swelling of the dead tissue. Pituitary apoplexy often presents with visual loss and sudden onset headache and requires timely treatment often with corticosteroids and if necessary surgical intervention.
Central diabetes insipidus is caused by diminished production of the antidiuretic hormone vasopressin that causes severe thirst and excessive production of very dilute urine (polyuria) which can lead to dehydration. Vasopressin is produced in the hypothalamus and is then transported down the pituitary stalk and stored in the posterior lobe of the pituitary gland which then secretes it into the bloodstream.As the pituitary gland is in close proximity to the brain, invasive adenomas may invade the dura mater, cranial bone, or sphenoid bone.

Risk factors
Multiple endocrine neoplasia
Adenomas of the anterior pituitary gland are a major clinical feature of multiple endocrine neoplasia type 1 (MEN1), a rare inherited endocrine syndrome that affects 1 person in every 30,000. MEN causes various combinations of benign or malignant tumors in various glands in the endocrine system or may cause the glands to become enlarged without forming tumors. It often affects the parathyroid glands, pancreatic islet cells, and anterior lobe of the pituitary gland. MEN1 may also cause non-endocrine tumors such as facial angiofibromas, collagenomas, lipomas, meningiomas, ependymomas, and leiomyomas. Approximately 25 percent of patients with MEN1 develop pituitary adenomas.

Carney complex
Carney complex (CNC), also known as LAMB syndrome and NAME syndrome is an autosomal dominant condition comprising myxomas of the heart and skin, hyperpigmentation of the skin (lentiginosis), and endocrine overactivity and is distinct from Carneys triad. Approximately 7% of all cardiac myxomas are associated with Carney complex. Patients with CNC develop growth hormone (GH)-producing pituitary tumors and in some instances these same tumors also secrete prolactin. There are however no isolated prolactinomas or any other type of pituitary tumor. In some patients with CNC, the pituitary gland is characterized by hyperplastic areas with the hyperplasia most likely preceding the formation of GH-producing adenomas.

Familial isolated pituitary adenoma
Familial isolated pituitary adenoma (FIPA) is a term that is used to identify a condition that displays an autosomal dominant inheritance and is characterised by the presence of two or more related patients affected by adenomas of the pituitary gland only, with no other associated symptoms that occur in multiple endocrine neoplasia type 1 (MEN-1), Carney complex and with mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene. FIPA was first described in a limited cohort of families by Albert Beckers group in Liège, Belgium; later FIPA was fully characterized in a multicenter international study of 64 families.  FIPA families are divided into those that are homogenous and have the same type of pituitary adenoma in all the affected family members (e.g. only acromegaly, only prolactinoma, etc.), while heterogeneous FIPA families can have  different pituitary adenomas in affected family members.

Genetics of FIPA
FIPA has two known genetic causes, mutations in the AH receptor-interacting protein (AIP) gene and duplications in chromosome Xq26.3 that include the GPR101 gene that also causes X-linked acrogigantism (X-LAG) syndrome.  About 15-20% of FIPA families carry a germline AIP gene mutation or deletion, and the disease occurs as autosomal dominant with incomplete penetrance, meaning that about 20% of AIP mutation carriers will develop a pituitary adenoma.  AIP mutation associated pituitary adenomas (either presenting as FIPA or as individual, non familial cases) are usually growth hormone-secreting (acromegaly) or prolactin-secreting (prolactinoma) adenomas that are large (macroadenomas) and often occur in children, adolescents and young adults.  Daly and colleagues showed that acromegaly cases with AIP mutations occurred about 20 years before acromegaly cases without AIP mutations and these tumors are large and relatively treatment-resistant.  Due to their young age at onset, AIP mutations are the most frequent genetic cause of pituitary gigantism (29% of cases).X-LAG is a rare syndrome of very early childhood onset pituitary tumors/hyperplasia that leads to growth hormone excess and severe overgrowth and pituitary gigantism.  Three FIPA families with X-LAG have been reported to date all of which had transmission of a chromosome Xq26.3 duplication from affected mother to affected son.  The disease characteristics of very young onset pituitary gigantism leads to severe overgrowth if not treated adequately; many of the tallest humans in history (e.g. Robert Pershing Wadlow; Sandy Allen, André Rousimoff (Andre the Giant), Zeng Jinlian) had a similar clinical history to patients with X-LAG syndrome.   The tallest historical individual with a known genetic cause was Julius Koch (Geant Constantin) who was found to have X-LAG on genetic study of his skeleton.   X-LAG has 100% penetrance so far (all affected with the Xq26.3 duplication have the disease and it affects predominantly females.  Isolated non familial cases of X-LAG can either have a constitutional duplication of a chromosome Xq26.3 including GPR101, or mosaicism for the duplication (present in a minority of cells) in the case of isolated male patients.  X-LAG causes about 10% of cases of pituitary gigantism.

Mechanism
The pituitary gland or hypophysis is often referred to as the "master gland" of the human body. Part of the hypothalamic-pituitary axis, it controls most of the bodys endocrine functions via the secretion of various hormones into the circulatory system. The pituitary gland is located below the brain in a depression (fossa) of the sphenoid bone known as the sella turcica. Although anatomically and functionally connected to the brain, the pituitary gland sits outside the blood–brain barrier. It is separated from the subarachnoid space by the diaphragma sella, therefore the arachnoid mater and thus cerebral spinal fluid cannot enter the sella turcica.The pituitary gland is divided into two lobes, the anterior lobe (which accounts for two thirds of the volume of the gland), and the posterior lobe (one third of the volume) separated by the pars intermedia.The posterior lobe (the neural lobe or neurohypophysis) of the pituitary gland is not, despite its name, a true gland. The posterior lobe contains axons of neurons that extend from the hypothalamus to which it is connected via the pituitary stalk. The hormones vasopressin and oxytocin, produced by the neurons of the supraoptic and paraventricular nuclei of the hypothalamus, are stored in the posterior lobe and released from axon endings (dendrites) within the lobe.The pituitary glands anterior lobe (adenohypophysis) is a true gland which produces and secretes six different hormones: thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), growth hormone (GH), and prolactin (PRL).

Diagnosis
Diagnosis of pituitary adenoma can be made, or at least suspected, by a constellation of related symptoms presented above.The differential diagnosis includes pituitary tuberculoma, especially in developing countries and in immumocompromised patients. The diagnosis is confirmed by testing hormone levels, and by radiographic imaging of the pituitary (for example, by CT scan or MRI).

Classification
Unlike tumors of the posterior Pituitary, Pituitary adenomas are classified as endocrine tumors (not brain tumors). Pituitary adenomas are classified based upon anatomical, histological and functional criteria.
Anatomically pituitary tumors are classified by their size based on radiological findings; either microadenomas (less than <10 mm) or macroadenomas (equal or greater than ≥10 mm).Classification based on radioanatomical findings places adenomas into 1 of 4 grades (I–IV):Stage I: microadenomas (<1 cm) without sella expansion.Stage II:  macroadenomas (≥1 cm) and may extend above the sella.Stage III:  macroadenomas with enlargement and invasion of the floor or suprasellar extension.Stage IV: destruction of the sella.Histological classification utilizes an immunohistological characterization of the tumors in terms of their hormone production.  Historically they were classed as either basophilic, acidophilic, or chromophobic on the basis of whether or not they took up the tinctorial stains hematoxylin and eosin. This classification has fallen into disuse, in favor of a classification based on what type of hormone is secreted by the tumor. Approximately 20–25% of adenomas do not secrete any readily identifiable active hormones (non-functioning tumors) yet they are still sometimes referred to as chromophobic.
Functional classification is based upon the tumors endocrine activity as determined by serum hormone levels and pituitary tissue cellular hormone secretion detected via immunohistochemical staining. The "Percentage of hormone production cases" values are the fractions of adenomas producing each related hormone of each tumor type as compared to all cases of pituitary tumors, and does not directly correlate to the percentages of each tumor type because of smaller or greater incidences of absence of secretion of the expected hormone. Thus, non secretive adenomas may be either null cell adenomas or a more specific adenoma that, however, remains non-secretive.
Any type of pituitary adenocarcinoma listed in the table below may cause compressive symptoms due to local expansion in addition to the systemic effects of secreted hormones listed in the pathology column.
Null cell adenomas by definition do not secrete hormones, but they commonly cause compressive effects on the pituitary stalk (stalk effect). This leads to decreased levels of dopamine from the hypothalamus reaching the anterior pituitary gland. Dopamine exerts an inhibitory effect on prolactin secretion. With the absence of this inhibitory effect, prolactin levels increase and are often increased in null cell adenomas. This leads to symptoms of hypogonadism.

Pituitary incidentalomas
Pituitary incidentalomas are pituitary tumors that are characterized as an incidental finding. They are often discovered by computed tomography (CT) or magnetic resonance imaging (MRI), performed in the evaluation of unrelated medical conditions such as suspected head trauma, in cancer staging or in the evaluation  of nonspecific symptoms such as dizziness and headache. It is not uncommon for them to be discovered at autopsy. In a meta-analysis, adenomas were found in an average of 16.7% in postmortem studies, with most being  microadenomas (<10mm); macrodenomas accounted for only 0.16% to 0.2% of the decedents. While non-secreting, noninvasive pituitary microadenomas are generally considered to be literally as well as clinically benign, there are to date scant studies of low quality to support this assertion.It has been recommended in the current Clinical Practice Guidelines (2011)  by the Endocrine Society - a professional, international medical organization in the field of endocrinology and metabolism – that all patients with pituitary incidentalomas undergo a complete medical history and physical examination, laboratory evaluations to screen for hormone hypersecretion and for hypopituitarism. If the lesion is in close proximity to the optic nerves or optic chiasm, a visual field examination should be performed. For those with incidentalomas which do not require surgical removal, follow up clinical assessments and  neuroimaging should be performed as well follow-up visual field examinations for incidentalomas that abut or compress the optic nerve and chiasm and follow-up endocrine testing for macroincidentalomas.

Ectopic pituitary adenoma
An ectopic (occurring in an abnormal place) pituitary adenoma is a rare type of tumor which occurs outside of the sella turcica, most often in the sphenoid sinus, suprasellar region, nasopharynx and the cavernous sinuses.

Metastases to the pituitary gland
Carcinomas that metastasize into the pituitary gland are uncommon and typically seen in the elderly, with lung and breast cancers being the most prevalent, In breast cancer patients, metastases to the pituitary gland occur in approximately 6-8% of cases.Symptomatic pituitary metastases account for only 7% of reported cases. In those who are symptomatic Diabetes insipidus often occurs with rates approximately 29–71%. Other commonly reported symptoms include anterior pituitary dysfunction, visual field defects, headache/pain, and ophthalmoplegia.

Treatment
Treatment options depend on the type of tumor and on its size:

Prolactinomas are most often treated with cabergoline or bromocriptine (both dopamine agonists), which decrease tumor size as well as alleviates symptoms, followed by serial imaging to detect any increase in size. Treatment, where the tumor is large, can be with radiation therapy, proton therapy or surgery, and patients generally respond 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 Persistent vegetative state and can you explain it in depth? [/INST] A persistent vegetative state (PVS) or post-coma unresponsiveness (PCU) is a disorder of consciousness in which patients with severe brain damage are in a state of partial arousal rather than true awareness. After four weeks in a vegetative state (VS), the patient is classified as being in a persistent vegetative state. This diagnosis is classified as a permanent vegetative state some months (three in the US and six in the UK) after a non-traumatic brain injury or one year after a traumatic injury. The term unresponsive wakefulness syndrome may be alternatively used, as "vegetative state" has some negative connotations among the public.

Definition
There are several definitions that vary by technical versus laymans usage. There are different legal implications in different countries.

Medical definition
Per the British Royal College of Physicians of London, a persistent vegetative state is "a wakeful unconscious state that lasts longer than a few weeks is referred to as a persistent (or continuing) vegetative state".

"Vegetative state"
The vegetative state is a chronic or long-term condition. This condition differs from a coma: a coma is a state that lacks both awareness and wakefulness. Patients in a vegetative state may have awoken from a coma, but still have not regained awareness. In the vegetative state patients can open their eyelids occasionally and demonstrate sleep-wake cycles, but completely lack cognitive function. The vegetative state is also called a "coma vigil". The chances of regaining awareness diminish considerably as the time spent in the vegetative state increases.

"Persistent vegetative state"
Persistent vegetative state is the standard usage (except in the UK) for a medical diagnosis, made after numerous neurological and other tests, that due to extensive and irreversible brain damage a patient is highly unlikely ever to achieve higher functions above a vegetative state. This diagnosis does not mean that a doctor has diagnosed improvement as impossible, but does open the possibility, in the US, for a judicial request to end life support. Informal guidelines hold that this diagnosis can be made after four weeks in a vegetative state. US caselaw has shown that successful petitions for termination have been made after a diagnosis of a persistent vegetative state, although in some cases, such as that of Terri Schiavo, such rulings have generated widespread controversy.
In the UK, the term is discouraged in favor of two more precisely defined terms that have been strongly recommended by the Royal College of Physicians (RCP).  These guidelines recommend using a continuous vegetative state for patients in a vegetative state for more than four weeks.  A medical determination of a permanent vegetative state can be made if, after exhaustive testing and a customary 12 months of observation, a medical diagnosis is made that it is impossible by any informed medical expectations that the mental condition will ever improve. Hence, a "continuous vegetative state" in the UK may remain the diagnosis in cases that would be called "persistent" in the US or elsewhere.
While the actual testing criteria for a diagnosis of "permanent" in the UK are quite similar to the criteria for a diagnosis of "persistent" in the US, the semantic difference imparts in the UK a legal presumption that is commonly used in court applications for ending life support.  The UK diagnosis is generally only made after 12 months of observing a static vegetative state. A diagnosis of a persistent vegetative state in the US usually still requires a petitioner to prove in court that recovery is impossible by informed medical opinion, while in the UK the "permanent" diagnosis already gives the petitioner this presumption and may make the legal process less time-consuming.In common usage, the "permanent" and "persistent" definitions are sometimes conflated and used interchangeably. However, the acronym "PVS" is intended to define a "persistent vegetative state", without necessarily the connotations of permanence, and is used as such throughout this article. Bryan Jennett, who originally coined the term "persistent vegetative state", has now recommended using the UK division between continuous and permanent in his book The Vegetative State, arguing that "the persistent component of this term ... may seem to suggest irreversibility".The Australian National Health and Medical Research Council has suggested "post coma unresponsiveness" as an alternative term for "vegetative state" in general.

Lack of legal clarity
Unlike brain death, permanent vegetative state (PVS) is recognized by  statute law as death in only a very few legal systems. In the US, courts have required petitions before termination of life support that demonstrate that any recovery of cognitive functions above a vegetative state is assessed as impossible by authoritative medical opinion.  In England, Wales and Scotland, the legal precedent for withdrawal of clinically assisted nutrition and hydration in cases of patients in a PVS was set in 1993 in the case of Tony Bland, who sustained catastrophic anoxic brain injury in the 1989 Hillsborough disaster.  An application to the Court of Protection is no longer required before nutrition and hydration can be withdrawn or withheld from PVS (or minimally conscious – MCS) patients.This legal grey area has led to vocal advocates that those in PVS should be allowed to die. Others are equally determined that, if recovery is at all possible, care should continue. The existence of a small number of diagnosed PVS cases that have eventually resulted in improvement makes defining recovery as "impossible" particularly difficult in a legal sense.  This legal and ethical issue raises questions about autonomy, quality of life, appropriate use of resources, the wishes of family members, and professional responsibilities.

Signs and symptoms
Most PVS patients are unresponsive to external stimuli and their conditions are associated with different levels of consciousness. Some level of consciousness means a person can still respond, in varying degrees, to stimulation. A person in a coma, however, cannot. In addition, PVS patients often open their eyes in response to feeding, which has to be done by others; they are capable of swallowing, whereas patients in a coma subsist with their eyes closed.Cerebral cortical function (e.g. communication, thinking, purposeful movement, etc.) is lost while brainstem functions (e.g. breathing, maintaining circulation and hemodynamic stability, etc.) are preserved.  Non-cognitive upper brainstem functions such as eye-opening, occasional vocalizations (e.g. crying, laughing), maintaining normal sleep patterns, and spontaneous non-purposeful movements often remain intact.
PVS patients eyes might be in a relatively fixed position, or track moving objects, or move in a disconjugate (i.e., completely unsynchronized) manner. They may experience sleep-wake cycles, or be in a state of chronic wakefulness. They may exhibit some behaviors that can be construed as arising from partial consciousness, such as grinding their teeth, swallowing, smiling, shedding tears, grunting, moaning, or screaming without any apparent external stimulus.
Individuals in PVS are seldom on any life-sustaining equipment other than a feeding tube because the brainstem, the center of vegetative functions (such as heart rate and rhythm, respiration, and gastrointestinal activity) is relatively intact.

Recovery
Many people emerge spontaneously from a vegetative state within a few weeks. The chances of recovery depend on the extent of injury to the brain and the patients age – younger patients having a better chance of recovery than older patients. A 1994 report found that of those who were in a vegetative state a month after a trauma, 54% had regained consciousness by a year after the trauma, whereas 28% had died and 18% were still in the vegetative state. For non-traumatic injuries such as strokes, only 14% had recovered consciousness at one year, 47% had died, and 39% were still vegetative. Patients who were vegetative six months after the initial event were much less likely to have recovered consciousness a year after the event than in the case of those who were simply reported vegetative at one month. A New Scientist article from 2000 gives a pair of graphs showing changes of patient status during the first 12 months after head injury and after incidents depriving the brain of oxygen.  After a year, the chances that a PVS patient will regain consciousness are very low and most patients who do recover consciousness experience significant disability. The longer a patient is in a PVS, the more severe the resulting disabilities are likely to be. Rehabilitation can contribute to recovery, but many patients never progress to the point of being able to take care of themselves.
The medical literature also includes case reports of the recovery of a small number of patients following the removal of assisted respiration with cold oxygen.  The researchers found that in many nursing homes and hospitals unheated oxygen is given to non-responsive patients via tracheal intubation. This bypasses the warming of the upper respiratory tract and causes a chilling of aortic blood and chilling of the brain which the authors believe may contribute to the persons nonresponsive state. The researchers describe a small number of cases in which removal of the chilled oxygen was followed by recovery from the PVS and recommend either warming of oxygen with a heated nebulizer or removal of the assisted oxygen if it is no longer needed. The authors further recommend additional research to determine if this chilling effect may either delay recovery or even may contribute to brain damage.
There are two dimensions of recovery from a persistent vegetative state: recovery of consciousness and recovery of function. Recovery of consciousness can be verified by reliable evidence of awareness of self and the environment, consistent voluntary behavioral responses to visual and auditory stimuli, and interaction with others. Recovery of function is characterized by communication, the ability to learn and to perform adaptive tasks, mobility, self-care, and participation in recreational or vocational activities. Recovery of consciousness may occur without functional recovery, but functional recovery cannot occur without recovery of consciousness.

Causes
There are three main causes of PVS (persistent vegetative state):

Acute traumatic brain injury
Non-traumatic: neurodegenerative disorder or metabolic disorder of the brain
Severe congenital abnormality of the central nervous systemPotential causes of PVS are:
Bacterial, viral, or fungal infection, including meningitis
Increased intracranial pressure, such as a tumor or abscess
Vascular pressure which causes intracranial hemorrhaging or stroke
Hypoxic ischemic injury (hypotension, cardiac arrest, arrhythmia, near-drowning)
Toxins such as uremia, ethanol, atropine, opiates, lead, dimethylmercury, endrin, parathion, and colloidal silver
Physical trauma: Concussion, contusion, etc.
Seizure, both nonconvulsive status epilepticus and postconvulsive state (postictal state)
Electrolyte imbalance, which involves hyponatremia, hypernatremia, hypomagnesemia, hypoglycemia, hyperglycemia, hypercalcemia, and hypocalcemia
Postinfectious: Acute disseminated encephalomyelitis (ADEM)
Endocrine disorders such as adrenal insufficiency and thyroid disorders
Degenerative and metabolic diseases including urea cycle disorders, Reye syndrome, and mitochondrial disease
Systemic infection and sepsis
Hepatic encephalopathyIn addition, these authors claim that doctors sometimes use the mnemonic device AEIOU-TIPS to recall portions of the differential diagnosis: Alcohol ingestion and acidosis, Epilepsy and encephalopathy, Infection, Opiates, Uremia, Trauma, Insulin overdose or inflammatory disorders, Poisoning and psychogenic causes, and Shock.

Diagnosis
Despite converging agreement about the definition of persistent vegetative state, recent reports have raised concerns about the accuracy of diagnosis in some patients, and the extent to which, in a selection of cases, residual cognitive functions may remain undetected and patients are diagnosed as being in a persistent vegetative state. Objective assessment of residual cognitive function can be extremely difficult as motor responses may be minimal, inconsistent, and difficult to document in many patients, or may be undetectable in others because no cognitive output is possible. In recent years, a number of studies have demonstrated an important role for functional neuroimaging in the identification of residual cognitive function in persistent vegetative state; this technology is providing new insights into cerebral activity in patients with severe brain damage. Such studies, when successful, may be particularly useful where there is concern about the accuracy of the diagnosis and the possibility that residual cognitive function has remained undetected.

Diagnostic experiments
Researchers have begun to use functional neuroimaging studies to study implicit cognitive processing in patients with a clinical diagnosis of persistent vegetative state. Activations in response to sensory stimuli with positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and electrophysiological methods can provide information on the presence, degree, and location of any residual brain function. However, use of these techniques in people with severe brain damage is methodologically, clinically, and theoretically complex and needs careful quantitative analysis and interpretation.
For example, PET studies have shown the identification of residual cognitive function in persistent vegetative state. That is, an external stimulation, such as a painful stimulus, still activates "primary" sensory cortices in these patients but these areas are functionally disconnected from "higher order" associative areas needed for awareness. These results show that parts of the cortex are indeed still functioning in "vegetative" patients.In addition, other PET studies have revealed preserved and consistent responses in predicted regions of auditory cortex in response to intelligible speech stimuli. Moreover, a preliminary fMRI examination revealed partially intact responses to semantically ambiguous stimuli, which are known to tap higher aspects of speech comprehension.Furthermore, several studies have used PET to assess the central processing of noxious somatosensory stimuli in patients in PVS. Noxious somatosensory stimulation activated midbrain, contralateral thalamus, and primary somatosensory cortex in each and every PVS patient, even in the absence of detectable cortical evoked potentials. In conclusion, somatosensory stimulation of PVS patients, at intensities that elicited pain in controls, resulted in increased neuronal activity in primary somatosensory cortex, even if resting brain metabolism was severely impaired. However, this activation of primary cortex seems to be isolated and dissociated from higher-order associative cortices.Also, there is evidence of partially functional cerebral regions in catastrophically injured brains. To study five patients in PVS with different behavioral features, researchers employed PET, MRI and magnetoencephalographic (MEG) responses to sensory stimulation. In three of the five patients, co-registered PET/MRI correlate areas of relatively preserved brain metabolism with isolated fragments of behavior. Two patients had had anoxic injuries and demonstrated marked decreases in overall cerebral metabolism to 30–40% of normal. Two other patients with non-anoxic, multifocal brain injuries demonstrated several isolated brain regions with higher metabolic rates, that ranged up to 50–80% of normal. Nevertheless, their global metabolic rates remained <50% of normal. MEG recordings from three PVS patients provide clear evidence for the absence, abnormality or reduction of evoked responses. Despite major abnormalities, however, these data also provide evidence for localized residual activity at the cortical level. Each patient partially preserved restricted sensory representations, as evidenced by slow evoked magnetic fields and gamma band activity. In two patients, these activations correlate with isolated behavioral patterns and metabolic activity. Remaining active regions identified in the three PVS patients with behavioral fragments appear to consist of segregated corticothalamic networks that retain connectivity and partial functional integrity. A single patient who sustained severe injury to the tegmental mesencephalon and paramedian thalamus showed widely preserved cortical metabolism, and a global average metabolic rate of 65% of normal. The relatively high preservation of cortical metabolism in this patient defines the first functional correlate of clinical–pathological reports associating permanent unconsciousness with structural damage to these regions. The specific patterns of preserved metabolic activity identified in these patients reflect novel evidence of the modular nature of individual functional networks that underlie conscious brain function. The variations in cerebral metabolism in chronic PVS patients indicate that some cerebral regions can retain partial function in catastrophically injured brains.

Misdiagnoses
Statistical PVS misdiagnosis is common. An example study with 40 patients in the United Kingdom reported 43% of their patients classified as PVS were believed so and another 33% had recovered whilst the study was underway. Some PVS cases may actually be a misdiagnosis of patients being in an undiagnosed minimally conscious state. Since the exact diagnostic criteria of the minimally conscious state were only formulated in 2002, there may be chronic patients diagnosed as PVS before the secondary notion of the minimally conscious state became known.
Whether or not there is any conscious awareness with a patients vegetative state is a prominent issue.  Three completely different aspects of this should be distinguished. First, some patients can be conscious simply because they are misdiagnosed (see above). In fact, they are not in vegetative states. Second, sometimes a patient was correctly diagnosed but is then examined during the early stages of recovery. Third, perhaps some day the notion itself of vegetative states will change so to include elements of conscious awareness. Inability to disentangle these three example cases causes confusion. An example of such confusion is the response to an experiment using functional magnetic resonance imaging which revealed that a woman diagnosed with PVS was able to activate predictable portions of her brain in response to the testers requests that she imagine herself playing tennis or moving from room to room in her house. The brain activity in response to these instructions was indistinguishable from those of healthy patients.In 2010, Martin Monti and fellow researchers, working at the MRC Cognition and Brain Sciences Unit at the University of Cambridge, reported in an article in the New England Journal of Medicine that some patients in persistent vegetative states responded to verbal instructions by displaying different patterns of brain activity on fMRI scans. Five out of a total of 54 diagnosed patients were apparently able to respond when instructed to think about one of two different physical activities. One of these five was also able to "answer" yes or no questions, again by imagining one of these two activities. It is unclear, however, whether the fact that portions of the patients brains light up on fMRI could help these patients assume their own medical decision making.In November 2011, a publication in The Lancet presented bedside EEG apparatus and indicated that its signal could be used to detect awareness in three of 16 patients diagnosed in the vegetative state.

Treatment
Currently no treatment for vegetative state exists that would satisfy the efficacy criteria of evidence-based medicine. Several methods have been proposed which can roughly be subdivided into four categories: pharmacological methods, surgery, physical therapy, and various stimulation techniques. Pharmacological therapy mainly uses activating substances such as tricyclic antidepressants or methylphenidate. Mixed results have been reported using dopaminergic drugs such as amantadine and bromocriptine and stimulants such as dextroamphetamine. Surgical methods such as deep brain stimulation are used less frequently due to the invasiveness of the procedures. Stimulation techniques include sensory stimulation, sensory regulation, music and musicokinetic therapy, social-tactile interaction, and cortical stimulation.

Zolpidem
There is limited evidence that the hypnotic drug zolpidem has an effect. The results of the few scientific studies that have been published so far on the effectiveness of zolpidem have been contradictory.

Epidemiology
In the United States, it is estimated that there may be between 15,000 and 40,000 patients who are in a persistent vegetative state, but due to poor nursing home records exact figures are hard to determine.

History
The syndrome was first described in 1940 by Ernst Kretschmer who called it apallic syndrome.  The term persistent vegetative state was coined in 1972 by Scottish spinal surgeon Bryan Jennett and American neurologist Fred Plum to describe a syndrome that seemed to have been made possible by medicines increased capacities to keep patients bodies alive.

Society and culture
Ethics and policy
An ongoing debate exists as to how much care, if any, patients in a persistent vegetative state should receive in health systems plagued by limited resources.  In a case before the New Jersey Superior Court, Betancourt v. Trinitas Hospital, a community hospital sought a ruling that dialysis and CPR for such a patient constitutes futile care.  An American bioethicist, Jacob M. Appel, argued that any money spent treating PVS patients would be better spent on other patients with a higher likelihood of recovery.
The patient died naturally prior to a decision in the case, resulting in the court finding the issue moot.
In 2010, British and Belgian researchers reported in an article in the New England Journal of Medicine that some patients in persistent vegetative states actually had enough consciousness to "answer" yes or no questions on fMRI scans. However, it is unclear whether the fact that portions of the patients brains light up on fMRI will help these patient assume their own medical decision making. Professor Geraint Rees, Director of the Institute of Cognitive Neuroscience at University College London, responded to the study by observing that, "As a clinician, it would be important to satisfy oneself that the individual that you are communicating with is competent to make those decisions. At the moment it is premature to conclude that the individual able to answer 5 out of 6 yes/no questions is fully conscious like you or I." In contrast, Jacob M </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 Roths spot 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 Hormone receptor positive breast tumor 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 Gunther disease and can you explain it in depth? [/INST] Gunther disease is a congenital form of erythropoietic porphyria. The word porphyria originated from the Greek word porphura. Porphura actually means "purple pigment", which, in suggestion, the color that the body fluid changes when a person has Gunthers disease. It is a rare, autosomal recessive metabolic disorder affecting heme, caused by deficiency of the enzyme uroporphyrinogen cosynthetase. It is extremely rare, with a prevalence estimated at 1 in 1,000,000 or less. There have been times that prior to birth of a fetus, Gunthers disease has been shown to lead to anemia. In milder cases patients have not presented any symptoms until they have reached adulthood. In Gunthers disease, porphyrins are accumulated in the teeth and bones and an increased amount are seen in the plasma, bone marrow, feces, red blood cells, and urine.

Symptoms and signs
Though expressivity is varied depending on the mutation responsible for decrease in enzyme function, severe cutaneous sensitivity is present in most cases of this Porphyria. An estimated 30–40% of cases are due to the C73R mutation, which decreases stability of the enzyme and results in <1% of its activity. Exposure to long-wave ultraviolet light causes the affected skin to thicken and produce vesicles that are prone to rupture and infection; these secondary infections, along with bone resorption, can lead to disfigurement of the sun-exposed face and extremities.
Enzyme dysfunction prevents the normal production of heme and hemolytic anemia is another common symptom, though a lack of hemolysis in this disease is possible. Porphyrins additionally accumulate in the bone and teeth, resulting in erythrodontia.
When unexpected attacks occur, abdominal pain, as well as vomiting and constipation commonly follow the attacks. Exposure to the sunlight can cause discomfort and result in blistering, consciousness of heat, and swelling and redness of the skin.

Complications
Photomutilation and transfusion-dependent anemia are common complications. Liver disease is also observed in some cases. It has been reported that early childhood-onset haematological manifestations is a poor prognosis factor.

Causes
Gunther disease is caused by mutations in the gene that encodes the enzyme uroporphyrinogen III synthase (UROS), located at human chromosome 10q25.2-q26.3. The disorder is inherited in an autosomal recessive manner. This means the defective gene is responsible for the disorder and is located on an autosome, and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder. When there is a homozygous mutation it causes a uroporphyrinogen III synthase and uroporphyrinogen cosynthase defect. When the enzyme uroporphyrinogen III synthase is reacting normally it results in the making of isomer III porphyrinogen, which is what is used to form heme. When isomer III porphyrinogen is not produced because of a poor production of uroporphyrinogen III synthase then isomer I porphyrinogen is made which will oxidize and give a reddish tint skin.

Diagnosis
When diagnosing Congenital Erythroipoetic Porphyria (Gunther Disease) one must exclude other forms of porphyria. These include Hepatoerythropoietic Porphyria and rare homozygous variants of Variegate Porphyria, Hereditary Coproporphyria, and STING-associated vasculopathy with onset in Infancy (SAVI). Mild variants may be present similarly to Porphyria Cutanea Tarda.There are four steps in establishing the diagnosis of any porphyria. First, a thorough history (particularly family history) and physical exam are performed with special attention paid to sun-exposed skin. Biochemical measurements of porphyrins and precursors in the urine, feces, and blood are necessary. Specialized labs are helpful in measuring activity of specific enzymes of the heme synthesis pathway and/or DNA and mutational analyses. In CEP, activity of uroporphyrinogen III synthase (the fourth enzyme in the heme biosynthetic pathway) will be markedly decreased.In congenital erythropoietic porphyria, urine aminolavulanic acid and porphobilinogen are typically normal. However, uroporphyrin and coproporphyrin tend to be markedly elevated and moderately elevated, respectively, in the urine more than in the feces. Additionally, fecal protoporphyrin is typically mildly elevated.In the red blood cells, uroporphyrin, coproporphyrin and protoporphyrin are all elevated, distinguishing this form of porphyria from the others. Finally, plasma analysis will demonstrate elevated uroporphyrin and coproporphyrin.Other nonspecific but helpful diagnostic clues are history of cutaneous photosensitivity, blistering, erosions, crusts and ulcerations leading to extensive scarring and deformation of the hands, loss of eyebrows, eyelashes with severe mutilation of cartilaginous structures like the nose, erythrodontia, and variable degree of hematologic involvement ranging from mild hemolytic anemia to intrauterine hydrops fetalis. Other early clues are red or violet staining of diapers.

Treatment
There are a multiple ways to treat Gunthers diseases, but one of the most crucial things that a person with this disease can do is limit themselves from sun exposure or eliminate sun exposure altogether. There are some sunscreens that have undesirable effects such as tropical sunscreens, but other sunscreens containing zinc oxide and titanium dioxide are shown to provide protection due to those light-reflective agents. To block the ultraviolet and visible light wavelengths and get the protection that patients with Gunthers disease require, physical barriers are needed </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 Nocardiosis and can you explain it in depth? [/INST] Nocardiosis is an infectious disease affecting either the lungs (pulmonary nocardiosis) or the whole body (systemic nocardiosis). It is due to infection by a bacterium of the genus Nocardia, most commonly Nocardia asteroides or Nocardia brasiliensis.
It is most common in adult males, especially those with a weakened immune system. In patients with brain nocardia infection, mortality exceeds 80%; in other forms, mortality is 50%, even with appropriate therapy.It is one of several conditions that have been called "the great imitator". Cutaneous nocardiosis commonly occurs in immunocompetent hosts and is caused in 80% of cases by Nocardia brasiliensis.

Signs and symptoms
Pulmonary infection

Produces a virulent form of pneumonia (progressive)
Night sweats, fever, cough, chest pain
Pulmonary nocardiosis is subacute in onset and refractory to treatment with standard antibiotics
Symptoms are more severe in immunocompromised individuals
Radiologic studies show multiple pulmonary infiltrates, with a tendency to central necrosisNeurological infection

Headache, lethargy, confusion, seizures, sudden onset of neurological deficit
CT scan shows cerebral abscess
Nocardial meningitis is difficult to diagnoseCardiac conditions

Nocardia has been highly linked to endocarditis as a main manifestation
In recorded cases, it has caused damage to heart valves whether natural or prostheticLymphocutaneous disease

Nocardial cellulitis is akin to erysipelas but is less acute
Nodular lymphangeitis mimics sporotrichosis with multiple nodules alongside a lymphatic pathway
Chronic subcutaneous infection is a rare complication and osteitis may ensue
May be misidentified and treated as a staph infection, specifically superficial skin infections
Cultures must incubate more than 48 hours to guarantee an accurate testOcular disease

Very rarely, nocardiae cause keratitis
Generally there is a history of ocular traumaDisseminated nocardiosis

Dissemination occurs through the spreading enzymes possessed by the bacteria
Disseminated infection can occur in very immunocompromised patients
It generally involves both lungs and brain
Fever, moderate or very high can be seen
Multiple cavitating pulmonary infiltrates develop
Cerebral abscesses arise later
Cutaneous lesions are very rarely seen
If untreated, the prognosis is poor for this form of disease

Causes
Normally found in soil, these organisms cause occasional sporadic disease in humans and animals throughout the world. Another well publicized find is that of Nocardia as part of the oral microflora. Nocardia spp. have been reported in the normal gingivae and periodontal pockets along with other species such as Actinomyces, Arthromyces and Streptomyces spp.The usual mode of transmission is inhalation of organisms suspended in dust. Another very common method is by traumatic introduction, especially in the jaw. This leads to the entrance of Nocardia into the blood stream and the propagation of its pathogenic effects. Transmission by direct inoculation through puncture wounds or abrasions is less common. Generally, nocardial infection requires some degree of immune suppression.A weakened immune system is a general indicator of a person who is more susceptible to nocardiosis, such as someone who already has a disease that weakens their immune system. Additionally, those with low T-cell counts or other complications involving T-cells can expect to have a higher chance of becoming infected. Besides those with weak immune systems, a local traumatic inoculation can cause nocardiosis, specifically the cutaneous, lymphocutaneous, and subcutaneous forms of the disease. There is no racial pattern in the risk of becoming infected with Nocardiosis.

Diagnosis
Diagnosis of nocardiosis can be made by a doctor using various techniques. These techniques include, but are not limited to: a chest x-ray to analyze the lungs, a bronchoscopy, a brain/lung/skin biopsy, or a sputum culture. However, diagnosis may be difficult. Nocardiae are gram positive, weakly acid-fast, branching rod-shaped bacteria and can be visualized by a modified Ziehl–Neelsen stain such as the Fite-Faraco method. In the clinical laboratory, routine cultures may be held for insufficient time to grow nocardiae, and referral to a reference laboratory may be needed for species identification. Pulmonary infiltration and pleural effusion are usually detected via x-ray.

Treatment
Nocardiosis requires at least 6 months of treatment, preferably with trimethoprim/sulfamethoxazole or high doses of sulfonamides. In patients who do not respond to sulfonamide treatment, other drugs, such as ampicillin, erythromycin, or minocycline, may be added.Treatment also includes surgical drainage of abscesses and excision of necrotic tissue. The acute phase requires complete bed rest; as the patient improves, activity can increase.A new combination drug therapy (sulfonamide, ceftriaxone, and amikacin) has also shown promise.

Prognosis
The prognosis of nocardiosis is highly variable </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 Limb body wall complex 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 Tremor and can you explain it in depth? [/INST] A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, face, head, vocal folds, trunk, and legs. Most tremors occur in the hands. In some people, a tremor is a symptom of another neurological disorder. A very common tremor is the teeth chattering, usually induced by cold temperatures or by fear.

Types
Tremor is most commonly classified by clinical features and cause or origin. Some of the better-known forms of tremor, with their symptoms, include the following:

Cerebellar tremor (also known as intention tremor) is a slow, broad tremor of the extremities that occurs at the end of a purposeful movement, such as trying to press a button or touching a finger to the tip of ones nose. Cerebellar tremor is caused by lesions in or damage to the cerebellum resulting from stroke, tumor, or disease such as multiple sclerosis or some inherited degenerative disorder.  It can also result from chronic alcoholism or overuse of some medicines. In classic cerebellar tremor, a lesion on one side of the brain produces a tremor in that same side of the body that worsens with directed movement. Cerebellar damage can also produce a "wing-beating" type of tremor called rubral or Holmes tremor — a combination of rest, action, and postural tremors. The tremor is often most prominent when the affected person is active or is maintaining a particular posture. Cerebellar tremor may be accompanied by other manifestations of ataxia, including dysarthria (speech problems), nystagmus (rapid, involuntary rolling of the eyes), gait problems and postural tremor of the trunk and neck. Titubation is tremor of the head and is of cerebellar origin.
Dystonic tremor occurs in individuals of all ages who are affected by dystonia, a movement disorder in which sustained involuntary muscle contractions cause twisting and repetitive motions or painful and abnormal postures or positions.  Dystonic tremor may affect any muscle in the body and is seen most often when the patient is in a certain position or moves a certain way.  The pattern of dystonic tremor may differ from essential tremor. Dystonic tremors occur irregularly and can often be relieved by complete rest. Touching the affected body part or muscle may reduce tremor severity (a geste antagoniste).  The tremor may be the initial sign of dystonia localized to a particular part of the body. The dystonic tremor has usually a frequency of about 7 Hz.
Essential tremor (sometimes inaccurately called benign essential tremor) is the most common of the more than 20 types of tremor.  Although the tremor may be mild and nonprogressive in some people, in others, the tremor is slowly progressive, starting on one side of the body but affecting both sides within 3 years. The hands are most often affected but the head, voice, tongue, legs, and trunk may also be involved.  Head tremor may be seen as a vertical or horizontal motion. Essential tremor may be accompanied by mild gait disturbance. Tremor frequency may decrease as the person ages, but the severity may increase, affecting the persons ability to perform certain tasks or activities of daily living.  Heightened emotion, stress, fever, physical exhaustion, or low blood sugar may trigger tremors or increase their severity.  Onset is most common after age 40, although symptoms can appear at any age.  It may occur in more than one family member. Children of a parent who has essential tremor have a 50 percent chance of inheriting the condition. Essential tremor is not associated with any known pathology. Its frequency is between 4 and 8 Hz.
Orthostatic tremor is characterized by fast (>12 Hz) rhythmic muscle contractions that occur in the legs and trunk immediately after standing up. Cramps are felt in the thighs and legs and the patient may shake uncontrollably when asked to stand in one spot.  No other clinical signs or symptoms are present and the shaking ceases when the patient sits or is lifted off the ground. The high frequency of the tremor often makes the tremor look like rippling of leg muscles while standing. Orthostatic tremor may also occur in patients who have essential tremor, and there might be an overlap between these categories of tremor.
Parkinsonian tremor is caused by damage to structures within the brain that control movement. This resting tremor, which can occur as an isolated symptom or be seen in other disorders, is often a precursor to Parkinsons disease (more than 25 percent of patients with Parkinsons disease have an associated action tremor). The tremor, which is classically seen as a "pill-rolling" action of the hands that may also affect the chin, lips, legs, and trunk, can be markedly increased by stress or emotion. Onset is generally after age 60. Movement starts in one limb or on one side of the body and usually progresses to include the other side. The tremors frequency is between 4 and 6 Hz.
Physiological tremor occurs in every normal individual and has no clinical significance. It is rarely visible and may be heightened by strong emotion (such as anxiety or fear), physical exhaustion, hypoglycemia, hyperthyroidism, heavy metal poisoning, stimulants, alcohol withdrawal or fever. It can be seen in all voluntary muscle groups and can be detected by extending the arms and placing a piece of paper on top of the hands. Enhanced physiological tremor is a strengthening of physiological tremor to more visible levels. It is generally not caused by a neurological disease but by reaction to certain drugs, alcohol withdrawal, or medical conditions including an overactive thyroid and hypoglycemia. It is usually reversible once the cause is corrected. This tremor classically has a frequency of about 10 Hz.
Psychogenic tremor (also called hysterical tremor and functional tremor) can occur at rest or during postural or kinetic movement. The characteristics of this kind of tremor may vary but generally include sudden onset and remission, increased incidence with stress, change in tremor direction or body part affected, and greatly decreased or disappearing tremor activity when the patient is distracted. Many patients with psychogenic tremor have a conversion disorder (see Posttraumatic stress disorder) or another psychiatric disease.
Rubral tremor is characterized by coarse slow tremor which is present at rest, at posture and with intention. This tremor is associated with conditions which affect the red nucleus in the midbrain, classically unusual strokes.
Neuropathic tremor may occur in patients with peripheral neuropathies, when the nerves that supply the bodys muscles are traumatized by injury, disease, abnormality in the central nervous system, or as the result of systemic illnesses. It is most commonly observed in patients with an immunoglobulin M paraproteinaemic neuropathy (IgMNP), but also in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). The tremor is predominantely exhibited as an action or postural tremor with a frequency of 3 to 10 Hz. Peripheral neuropathy can affect the whole body or certain areas, such as the hands, and may be progressive. Resulting sensory loss may be seen as a tremor or ataxia (inability to coordinate voluntary muscle movement) of the affected limbs and problems with gait and balance. Clinical characteristics may be similar to those seen in patients with essential tremor.Tremor can result from other conditions as well

Alcoholism, excessive alcohol consumption, or alcohol withdrawal can kill certain nerve cells, resulting in a tremor known as asterixis. Conversely, small amounts of alcohol may help to decrease familial and essential tremor, but the mechanism behind it is unknown. Alcohol potentiates GABAergic transmission and might act at the level of the inferior olive.
Tobacco withdrawal symptoms include tremor.
Most of the symptoms can also occur randomly when panicked.

Causes
Tremor can be a symptom associated with disorders in those  parts of the brain that control muscles throughout the body or in particular areas, such as the hands. Neurological disorders or conditions that can produce tremor include multiple sclerosis, stroke, traumatic brain injury, chronic kidney disease and a number of  neurodegenerative diseases that damage or destroy parts of the brainstem or the cerebellum,  Parkinsons disease being the one most often associated with tremor. Lesions of the Guillain-Mollaret triangle (also called myoclonic triangle or dentato-rubro-olivary pathway) impair the predictions performed by the cerebellum, causing repetitive muscle discharges by triggering oscillatory activity in the central nervous system. Other causes include the use of drugs (such as amphetamines, cocaine, caffeine, corticosteroids, SSRIs) or alcohol, mercury poisoning, or the withdrawal of drugs such as alcohol or benzodiazepine. Tremors can also be seen in infants with phenylketonuria (PKU), overactive thyroid or liver failure. Tremors can be an indication of hypoglycemia, along with palpitations, sweating and anxiety.
Tremor can also be caused by lack of sleep, lack of vitamins, or increased stress. Deficiencies of magnesium and thiamine have also been known to cause tremor or shaking, which resolves when the deficiency is corrected. Tremors in animals can also be caused by some spider bites, e.g. the redback spider of Australia.

Diagnosis
During a physical exam, a doctor can determine whether the tremor occurs primarily during action or at rest. The doctor will also check for tremor symmetry, any sensory loss, weakness or muscle atrophy, or decreased reflexes. A detailed family history may indicate if the tremor is inherited. Blood or urine tests can detect thyroid malfunction, other metabolic causes, and abnormal levels of certain chemicals that can cause tremor. These tests may also help to identify contributing causes, such as drug interaction, chronic alcoholism, or another condition or disease. Diagnostic imaging using CT or MRI imaging may help determine if the tremor is the result of a structural defect or degeneration of the brain.The doctor will perform a neurological examination to assess nerve function and motor and sensory skills. The tests are designed to determine any functional limitations, such as difficulty with handwriting or the ability to hold a utensil or cup. The patient may be asked to place a finger on the tip of her or his nose, draw a spiral, or perform other tasks or exercises.The doctor may order an electromyogram to diagnose muscle or nerve problems. This test measures involuntary muscle activity and muscle response to nerve stimulation. The selection of the sensors used is important. In addition to studies of muscle activity, tremor can be assessed with accuracy using accelerometers .

Categories
The degree of tremor should be assessed in four positions. The tremor can then be classified by which position most accentuates the tremor:

Treatment
There is no cure for most tremors. The appropriate treatment depends on accurate diagnosis of the cause. Some tremors respond to treatment of the underlying condition. For example, in some cases of psychogenic tremor, treating the patients underlying psychological problem may cause the tremor to disappear. A few medications can help relieve symptoms temporarily.

Medications
Medications remain the basis of therapy in many cases. Symptomatic drug therapy is available for several forms of tremor:
Parkinsonian tremor drug treatment involves L-DOPA or dopamine-like drugs such as pergolide, bromocriptine and ropinirole; They can be dangerous, however, as they may cause symptoms such as tardive dyskinesia, akathisia, clonus, and in rare instances tardive (late developing) psychosis. Other drugs used to lessen parkinsonian tremor include amantadine and anticholinergic drugs like benztropine
Essential tremor may be treated with beta blockers (such as propranolol and nadolol) or  primidone, an anticonvulsant
Cerebellar tremor symptoms may decrease with the application of alcohol (ethanol) or benzodiazepine medications, both of which carry some risk of dependence or addiction
Rubral tremor patients may receive some relief using L-DOPA or anticholinergic drugs. Surgery may be helpful
Dystonic tremor may respond to diazepam, anticholinergic drugs, and intramuscular injections of botulinum toxin. Botulinum toxin is also prescribed to treat voice and head tremors and several movement disorders
Primary orthostatic tremor sometimes is treated with a combination of diazepam and primidone. Gabapentin provides relief in some cases
Enhanced physiological tremor is usually reversible once the cause is corrected. If symptomatic treatment is needed, beta blockers can be used

Lifestyle
Eliminating tremor "triggers" such as caffeine and other stimulants from the diet is often recommended.
Essential tremor may benefit from slight doses of ethanol, but the potential negative consequences of regular ethanol intake need to be taken into account. Beta blockers have been used as an alternative to alcohol in sports such as competitive dart playing and carry less potential for addiction.Physical therapy and occupational therapy may help to reduce tremor and improve coordination and muscle control for some patients. A physical therapist or occupational therapist will evaluate the patient for tremor positioning, muscle control, muscle strength, and functional skills. Teaching the patient to brace the affected limb during the tremor or to hold an affected arm close to the body is sometimes useful in gaining motion control. Coordination and balancing exercises may help some patients. Some occupational therapists recommend the use of weights, splints, other adaptive equipment, and special plates and utensils for eating.

Surgery
Surgical intervention such as thalamotomy and deep brain stimulation may ease certain tremors. These surgeries are usually performed only when the tremor is severe and does not respond to drugs. Response can be excellent.Thalamotomy, involving the creation of lesions in the brain region called the thalamus, is quite effective in treating patients with essential, cerebellar, or Parkinsonian tremor. This in-hospital procedure is performed under local anesthesia, with the patient awake. After the patients head is secured in a metal frame, the surgeon maps the patients brain to locate the thalamus. A small hole is drilled through the skull and a temperature-controlled electrode is inserted into the thalamus. A low-frequency current is passed through the electrode to activate the tremor and to confirm proper placement. Once the site has been confirmed, the electrode is heated to create a temporary lesion. Testing is done to examine speech, language, coordination, and tremor activation, if any. If no problems occur, the probe is again heated to create a 3-mm permanent lesion. The probe, when cooled to body temperature, is withdrawn and the skull hole is covered. The lesion causes the tremor to permanently disappear without disrupting sensory or motor control.
Deep brain stimulation (DBS) uses implantable electrodes to send high-frequency electrical signals to the thalamus. The electrodes are implanted as described above. The patient uses a hand-held magnet to turn on and turn off a pulse generator that is surgically implanted under the skin. The electrical stimulation temporarily disables the tremor and can be "reversed", if necessary, by turning off the implanted electrode. Batteries in the generator last about 5 years and can be replaced surgically. DBS is currently used to treat parkinsonian tremor and essential tremor. It is also applied successfully for other rare causes of tremor.
The most common side effects of tremor surgery include dysarthria (problems with motor control of speech), temporary or permanent cognitive impairment (including visual and learning difficulties), and problems with balance.

Biomechanical loading
As well as medication, rehabilitation programmes and surgical interventions, the application of biomechanical loading on tremor movement has been shown to be a technique that is able to suppress the effects of tremor on the human body. It has been established in the literature  that most of the different types of tremor respond to biomechanical loading. In particular, it has been clinically tested that the increase of damping or inertia in the upper limb leads to a reduction of the tremorous motion. Biomechanical loading relies on an external device that either passively or actively acts mechanically in parallel to the upper limb to counteract tremor movement. This phenomenon gives rise to the possibility of an orthotic management of tremor.Starting from this principle, the development of upper-limb non-invasive ambulatory robotic exoskeletons is presented as a promising solution for patients who cannot benefit from medication to suppress the tremor. In this area robotic exoskeletons have emerged, in the form of orthoses, to provide motor assistance and functional compensation to disabled people. An orthosis is a wearable device that acts in parallel to the affected limb. In the case of tremor management, the orthosis must apply a damping or inertial load to a selected set of limb articulations.Recently, some studies demonstrated that exoskeletons could achieve a consistent 40% of tremor power reduction for all users, being able to attain a reduction ratio in the order of 80% tremor power in specific joints of users with severe tremor. In addition, the users reported that the exoskeleton did not affect their voluntary motion. These results indicate the feasibility of tremor suppression through biomechanical loading.
The main drawbacks of this mechanical management of tremor are (1) the resulting bulky solutions, (2) the inefficiency in transmitting loads from the exoskeleton to the human musculo-skeletal system and (3) technological limitations in terms of actuator technologies. In this regard, current trends in this field are focused on the evaluation of the concept of biomechanical loading of tremor through selective Functional Electrical Stimulation (FES) based on a (Brain-to-Computer Interaction) BCI-driven detection of involuntary (tremor) motor activity.

See also
Cerebral Palsy
Fasciculation  ("at rest" muscle twitches; usually benign).
Fibrillation
Restless Leg Syndrome
Shivering
Chronic solvent-induced encephalopathy
Neurology

References
External links

"NINDS Tremor Information Page". National Institute of Neurological Disorders and Stroke. July 20, 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 Zellweger syndrome and can you explain it in depth? [/INST] Zellweger syndrome is a rare congenital disorder characterized by the reduction or absence of functional peroxisomes in the cells of an individual. It is one of a family of disorders called Zellweger spectrum disorders which are leukodystrophies. Zellweger syndrome is named after Hans Zellweger (1909–1990), a Swiss-American pediatrician, a professor of pediatrics and genetics at the University of Iowa who researched this disorder.

Signs and symptoms
Zellweger syndrome is one of three peroxisome biogenesis disorders which belong to the Zellweger spectrum of peroxisome biogenesis disorders (PBD-ZSD). The other two disorders are neonatal adrenoleukodystrophy (NALD), and infantile Refsum disease (IRD). Although all have a similar molecular basis for disease, Zellweger syndrome is the most severe of these three disorders.Zellweger syndrome is associated with impaired neuronal migration, neuronal positioning, and brain development. In addition, individuals with Zellweger syndrome can show a reduction in central nervous system (CNS) myelin (particularly cerebral), which is referred to as hypomyelination. Myelin is critical for normal CNS functions, and in this regard, serves to insulate nerve fibers in the brain. Patients can also show postdevelopmental sensorineuronal degeneration that leads to a progressive loss of hearing and vision.Zellweger syndrome can also affect the function of many other organ systems. Patients can show craniofacial abnormalities (such as a high forehead, hypoplastic supraorbital ridges, epicanthal folds, midface hypoplasia, and a large fontanel), hepatomegaly (enlarged liver), chondrodysplasia punctata (punctate calcification of the cartilage in specific regions of the body), eye abnormalities, and renal cysts. Newborns may present with profound hypotonia (low muscle tone), seizures, apnea, and an inability to eat.

Cause
Zellweger syndrome is an autosomal recessive disorder caused by mutations in genes that encode peroxins, proteins required for the normal assembly of peroxisomes. Most commonly, patients have mutations in the PEX1, PEX2, PEX3, PEX5, PEX6, PEX10, PEX12, PEX13, PEX14, PEX16, PEX19, or PEX26 genes. In almost all cases, patients have mutations that inactivate or greatly reduce the activity of both the maternal and paternal copies of one these aforementioned PEX genes.As a result of impaired peroxisome function, an individuals tissues and cells can accumulate very long chain fatty acids (VLCFA) and branched chain fatty acids (BCFA) that are normally degraded in peroxisomes. The accumulation of these lipids can impair the normal function of multiple organ systems, as discussed above </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 Carnitine-acylcarnitine translocase deficiency and can you explain it in depth? [/INST] Carnitine-acylcarnitine translocase deficiency is a rare, autosomal recessive metabolic disorder that prevents the body from converting long-chain fatty acids into energy, particularly during periods without food. Carnitine, a natural substance acquired mostly through the diet, is used by cells to process fats and produce energy. People with this disorder have a faulty enzyme that prevents long-chain fatty acids from being transported into the innermost part of the mitochondria for processing.

Presentation
The signs of carnitine-acylcarnitine translocase deficiency usually begin within the first few hours of life </s>