<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Coats disease and explain in detail? [/INST] Coats disease is a rare congenital, nonhereditary eye disorder, causing full or partial blindness, characterized by abnormal development of blood vessels behind the retina. Coats disease can also fall under glaucoma.
It can have a similar presentation to that of retinoblastoma.

Signs and symptoms
The most common sign at presentation is leukocoria (abnormal white reflection of the retina). Symptoms typically begin as blurred vision, usually pronounced when one eye is closed (due to the unilateral nature of the disease).  Often the unaffected eye will compensate for the loss of vision in the other eye; however, this results in some loss of depth perception and parallax.  Deterioration of sight may begin in either the central or peripheral vision. Deterioration is likely to begin in the upper part of the vision field as this corresponds with the bottom of the eye where blood usually pools. Flashes of light, known as photopsia, and floaters are common symptoms. Persistent color patterns may also be perceived in the affected eye. Initially, these may be mistaken for psychological hallucinations, but are actually the result of both retinal detachment and foreign fluids mechanically interacting with the photoreceptors located on the retina.
One early warning sign of Coats disease is yellow-eye in flash photography. Just as the red-eye effect is caused by a reflection off blood vessels in the back of a normal eye, an eye affected by Coats will glow yellow in photographs as light reflects off cholesterol deposits. Children with yellow-eye in photographs are typically advised to immediately seek evaluation from an optometrist or ophthalmologist, who will assess and diagnose the condition and refer to a vitreo-retinal specialist.

Coats disease itself is painless. Pain may occur if fluid is unable to drain from the eye properly, causing the internal pressure to swell, resulting in painful glaucoma.

Presentation
Coats usually affects only one eye (unilateral) and occurs predominantly in young males 1/100,000, with the onset of symptoms generally appearing in the first decade of life. Peak age of onset is between 6–8 years of age, but onset can range from 5 months to 71 years.Coats disease results in a gradual loss of vision. Blood leaks from the abnormal vessels into the back of the eye, leaving behind cholesterol deposits and damaging the retina. Coats disease normally progresses slowly. At advanced stages, retinal detachment is likely to occur. Glaucoma, atrophy, and cataracts can also develop secondary to Coats disease. In some cases, removal of the eye may be necessary (enucleation).
Coats disease is a rare extramuscular manifestation of facioscapulohumeral muscular dystrophy (FSHD). A single study reported it in 1 percent of FSHD patients, most often those with FSHD type 1 (FSHD1) with large D4Z4 deletions.

Pathogenesis
Coats disease is thought to result from breakdown of the blood-retinal barrier in the endothelial cells, resulting in leakage of blood products containing cholesterol crystals and lipid-laden macrophages into the retina and subretinal space. Over time, the accumulation of this proteinaceous exudate thickens the retina, leading to massive, exudative retinal detachment.

Diagnosis
On funduscopic eye examination, the retinal vessels in early Coats disease appear tortuous and dilated, mainly confined to the peripheral and temporal portions of retina. In moderate to severe Coats disease, massive retinal detachment and hemorrhage from the abnormal vessels may be seen.

Imaging findings
Imaging studies such as ultrasonography (US), Computerized Tomography (CT) and Magnetic Resonance Imaging (MRI) can aid diagnosis. On ultrasound, Coats disease appears as a hyperechoic mass in the posterior vitreous without posterior acoustic shadowing; vitreous and subretinal hemorrhage may often be observed.On CT, the globe appears hyperdense compared to normal vitreous due to the proteinaceous exudate, which may obliterate the vitreous space in advanced disease. The anterior margin of the subretinal exudate enhances with contrast. Since the retina is fixed posteriorly at the optic disc, this enhancement has a V-shaped configuration.On MRI, the subretinal exudate shows high signal intensity on both T1- and T2-weighted images. The exudate may appear heterogeneous if hemorrhage or fibrosis is present. The subretinal space does not enhance with gadolinium contrast. Mild to moderate linear enhancement may be seen between the exudate and the remaining vitreous </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Adrenal crisis and explain in detail? [/INST] Adrenal crisis is a potentially life-threatening medical condition requiring immediate emergency treatment. It is a constellation of symptoms (caused by insufficient levels of the hormone cortisol) that indicate severe adrenal insufficiency </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Amusia and explain in detail? [/INST] Amusia is a musical disorder that appears mainly as a defect in processing pitch but also encompasses musical memory and recognition. Two main classifications of amusia exist: acquired amusia, which occurs as a result of brain damage, and congenital amusia, which results from a music-processing anomaly present since birth.
Studies have shown that congenital amusia is a deficit in fine-grained pitch discrimination and that 4% of the population has this disorder. Acquired amusia may take several forms. Patients with brain damage may experience the loss of ability to produce musical sounds while sparing speech, much like aphasics lose speech selectively but can sometimes still sing. Other forms of amusia may affect specific sub-processes of music processing. Current research has demonstrated dissociations between rhythm melody and emotional processing of music. Amusia may include impairment of any combination of these skill sets.

Signs and symptoms
Symptoms of amusia are generally categorized as receptive, clinical, or mixed. Symptoms of receptive amusia, sometimes referred to as "musical deafness" or "tone deafness", include the inability to recognize familiar melodies, the loss of ability to read musical notation, and the inability to detect wrong or out-of tune notes. Clinical, or expressive, symptoms include the loss of ability to sing, write musical notation, and/or play an instrument. A mixed disorder is a combination of expressive and receptive impairment.Clinical symptoms of acquired amusia are much more variable than those of congenital amusia and are determined by the location and nature of the lesion. Brain injuries may affect motor or expressive functioning, including the ability to sing, whistle, or hum a tune (oral-expressive amusia), the ability to play an instrument (instrumental amusia or musical apraxia), and the ability to write music (musical agraphia). Additionally, brain damage to the receptive dimension affects the faculty to discriminate tunes (receptive or sensorial amusia), the ability to read music (musical alessia), and the ability to identify songs that were familiar prior to the brain damage (amnesic amusia).Research suggests that patients with amusia also have difficulty when it comes to spatial processing. Amusics performed more quickly than normal individuals on a combined task of both spatial and musical processing tasks, which is most likely due to their deficit. Normal individuals experience interference due to their intact processing of both musical and spatial tasks, while amusics do not. Pitch processing normally depends on the cognitive mechanisms that are usually used to process spatial representations.Those with congenital amusia show impaired performance on discrimination, identification and imitation of sentences with intonational differences in pitch direction in their final word. This suggests that amusia can in subtle ways impair language processing.

Social and emotional
Amusic individuals have a remarkable sparing of emotional responses to music in the context of severe and lifelong deficits in processing music. Some individuals with amusia describe music as unpleasant. Others simply refer to it as noise and find it annoying. This can have social implications because amusics often try to avoid music, which in many social situations is not an option.In China and other countries where tonal languages are spoken, amusia may have a more pronounced social and emotional impact: difficulty in speaking and understanding the language. However, context clues are often strong enough to determine the correct meaning, similarly to how homophones can be understood.

Related diseases
Amusia has been classified as a learning disability that affects musical abilities. Research suggests that in congenital amusia, younger subjects can be taught tone differentiation techniques. This finding leads researchers to believe that amusia is related to dyslexia and other similar disorders. Research has been shown that amusia may be related to an increase in size of the cerebral cortex, which may be a result of a malformation in cortical development. Conditions such as dyslexia and epilepsy are due to a malformation in cortical development and also lead to an increase in cortical thickness, which leads researchers to believe that congenital amusia may be caused by the identical phenomenon in a different area of the brain.Amusia is also similar to aphasia in that they affect similar areas of the brain near the temporal lobe. Most cases of those with amusia do not show any symptoms of aphasia. However, a number of cases have shown that those who have aphasia can exhibit symptoms of amusia, especially in acquired aphasia. The two are not mutually exclusive and having one does not imply possession of the other. In acquired amusia, inability to perceive music correlates with an inability to perform other higher-level functions. In this case, as musical ability improves, so too do the higher cognitive functions which suggests that musical ability is closely related to these higher-level functions, such as memory and learning, mental flexibility, and semantic fluency.Amusia can also be related to aprosody, a disorder in which the persons speech is affected, becoming extremely monotonous. It has been found that both amusia and aprosody can arise from seizures occurring in the non-dominant hemisphere. They can also both arise from lesions to the brain, as can Brocas aphasia come about simultaneously with amusia from injury. There is a relation between musical abilities and the components of speech; however, it is not understood very well.

Diagnosis
The diagnosis of amusia requires multiple investigative tools all described in the Montreal Protocol for Identification of Amusia. This protocol has at its center the Montreal Battery of Evaluation of Amusia (MBEA), which involves a series of tests that evaluate the use of musical characteristics known to contribute to the memory and perception of conventional music, but the protocol also allow for the ruling out of other conditions that can explain the clinical signs observed. The battery comprises six subtests which assess the ability to discriminate pitch contour, musical scales, pitch intervals, rhythm, meter, and memory. An individual is considered amusic if they perform two standard deviations below the mean obtained by musically competent controls.This musical pitch disorder represents a phenotype that serves to identify the associated neuro-genetic factors. Both MRI-based brain structural analyses and electroencephalography (EEG) are common methods employed to uncover brain anomalies associated with amusia (See Neuroanatomy). Additionally, voxel-based morphometry (VBM) is used to detect anatomical differences between the MRIs of amusic brains and musically intact brains, specifically with respect increased and/or decreased amounts of white and grey matter.

Classifications
There are two general classifications of amusia: congenital amusia and acquired amusia.

Congenital amusia
Congenital amusia, commonly known as tone deafness, refers to a musical disability that cannot be explained by prior brain lesion, hearing loss, cognitive defects, or lack of environmental stimulation, and it affects about 4% of the population. Individuals with congenital amusia seem to lack the musical predispositions with which most people are born. They are unable to recognize or hum familiar tunes even if they have normal audiometry and above-average intellectual and memory skills. Also, they do not show sensitivity to dissonant chords in a melodic context, which, as discussed earlier, is one of the musical predispositions exhibited by infants. The hallmark of congenital amusia is a deficit in fine-grained pitch discrimination, and this deficit is most apparent when congenital amusics are asked to pick out a wrong note in a given melody. If the distance between two successive pitches is small, congenital amusics are not able to detect a pitch change. As a result of this defect in pitch perception, a lifelong musical impairment may emerge due to a failure to internalize musical scales. A lack of fine-grained pitch discrimination makes it extremely difficult for amusics to enjoy and appreciate music, which consists largely of small pitch changes.Tone-deaf people seem to be disabled only when it comes to music as they can fully interpret the prosody or intonation of human speech. Tone deafness has a strong negative correlation with belonging to societies with tonal languages. This could be evidence that the ability to reproduce and distinguish between notes may be a learned skill; conversely, it may suggest that the genetic predisposition towards accurate pitch discrimination may influence the linguistic development of a population towards tonality. A correlation between allele frequencies and linguistic typological features has been recently discovered, supporting the latter hypothesis.Tone deafness is also associated with other musical-specific impairments such as the inability to keep time with music (beat deafness, or the lack of rhythm), or the inability to remember or recognize a song. These disabilities can appear separately, but some research shows that they are more likely to appear in tone-deaf people. Experienced musicians, such as W. A. Mathieu, have addressed tone deafness in adults as correctable with training.

Acquired amusia
Acquired amusia is a musical disability that shares the same characteristics as congenital amusia, but rather than being inherited, it is the result of brain damage. It is also more common than congenital amusia. While it has been suggested that music is processed by music-specific neural networks in the brain, this view has been broadened to show that music processing also encompasses generic cognitive functions, such as memory, attention, and executive processes. A study was published in 2009 which investigated the neural and cognitive mechanisms that underlie acquired amusia and contribute to its recovery. The study was performed on 53 stroke patients with a left or right hemisphere middle cerebral artery (MCA) infarction one week, three months, and six months after the stroke occurred. Amusic subjects were identified one week following their stroke, and over the course of the study, amusics and non-amusics were compared in both brain lesion location and their performances on neuropsychological tests.Results showed that there was no significant difference in the distribution of left and right hemisphere lesions between amusic and non-amusic groups, but that the amusic group had a significantly higher number of lesions to the frontal lobe and auditory cortex. Temporal lobe lesions were also observed in patients with amusia. Amusia is a common occurrence following an ischemic MCA stroke, as evidenced by the 60% of patients who were found to be amusic at the one-week post-stroke stage. While significant recovery takes place over time, amusia can persist for long periods of time. Test results suggest that acquired amusia and its recovery in the post-stroke stage are associated with a variety of cognitive functions, particularly attention, executive functioning and working memory.

Neuroanatomy
Neurologically intact individuals appear to be born musical. Even before they are able to talk, infants show remarkable musical abilities that are similar to those of adults in that they are sensitive to musical scales and a regular tempo. Also, infants are able to differentiate between consonant and dissonant intervals. These perceptual skills indicate that music-specific predispositions exist.Prolonged exposure to music develops and refines these skills. Extensive musical training does not seem to be necessary in the processing of chords and keys. The development of musical competence most likely depends on the encoding of pitch along musical scales and maintaining a regular pulse, both of which are key components in the structure of music and aid in perception, memory, and performance. Also, the encoding of pitch and temporal regularity are both likely to be specialized for music processing. Pitch perception is absolutely crucial to processing music. The use of scales and the organization of scale tones around a central tone (called the tonic) assign particular importance to notes in the scale and cause non-scale notes to sound out of place. This enables the listener to ascertain when a wrong note is played. However, in individuals with amusia, this ability is either compromised or lost entirely.Music-specific neural networks exist in the brain for a variety of music-related tasks. It has been shown that Brocas area is involved in the processing of musical syntax. Furthermore, brain damage can disrupt an individuals ability to tell the difference between tonal and atonal music and detect the presence of wrong notes, but can preserve the individuals ability to assess the distance between pitches and the direction of the pitch. The opposite scenario can also occur, in which the individual loses pitch discrimination capabilities, but can sense and appreciate the tonal context of the work. Distinct neural networks also exist for music memories, singing, and music recognition. Neural networks for music recognition are particularly intriguing. A patient can undergo brain damage that renders them unable to recognize familiar melodies that are presented without words. However, the patient maintains the ability to recognize spoken lyrics or words, familiar voices, and environmental sounds. The reverse case is also possible, in which the patient cannot recognize spoken words, but can still recognize familiar melodies. These situations overturn previous claims that speech recognition and music recognition share a single processing system. Instead, it is clear that there are at least two distinct processing modules: one for speech and one for music.Many research studies of individuals with amusia show that a number of cortical regions appear to be involved in processing music. Some report that the primary auditory cortex, secondary auditory cortex, and limbic system are responsible for this faculty, while more recent studies suggest that lesions in other cortical areas, abnormalities in cortical thickness, and deficiency in neural connectivity and brain plasticity may contribute to amusia. While various causes of amusia exist, some general findings that provide insight to the brain mechanisms involved in music processing are discussed below.

Pitch relations
Studies suggest that the analysis of pitch is primarily controlled by the right temporal region of the brain. The right secondary auditory cortex processes pitch change and manipulation of fine tunes; specifically, this region distinguishes the multiple pitches that characterize melodic tunes as contour (pitch direction) and interval (frequency ratio between successive notes) information. The right superior temporal gyrus recruits and evaluates contour information, while both right and left temporal regions recruit and evaluate interval information. In addition, the right anterolateral part of Heschls gyrus (primary auditory cortex) is also concerned with processing pitch information.

Temporal relations
The brain analyzes the temporal (rhythmic) components of music in two ways: (1) it segments the ongoing sequences of music into temporal events based on duration, and (2) it groups those temporal events to understand the underlying beat to music. Studies on rhythmic discrimination reveal that the right temporal auditory cortex is responsible for temporal segmenting, and the left temporal auditory cortex is responsible for temporal grouping. Other studies suggest the participation of motor cortical areas in rhythm perception and production. Therefore, a lack of involvement and networking between bilateral temporal cortices and neural motor centers may contribute to both congenital and acquired amusia.

Memory
Memory is required in order to process and integrate both melodic and rhythmic aspects of music. Studies suggest that there is a rich interconnection between the right temporal gyrus and frontal cortical areas for working memory in music appreciation. This connection between the temporal and frontal regions of the brain is extremely important since these regions play critical roles in music processing. Changes in the temporal areas of the amusic brain are most likely associated with deficits in pitch perception and other musical characteristics, while changes in the frontal areas are potentially related to deficits in cognitive processing aspects, such as memory, that are needed for musical discrimination tasks. Memory is also concerned with the recognition and internal representation of tunes, which help to identify familiar songs and confer the ability to sing tunes in ones head. The activation of the superior temporal region and left inferior temporal and frontal areas is responsible for the recognition of familiar songs, and the right auditory cortex (a perceptual mechanism) is involved in the internal representation of tunes. These findings suggest that any abnormalities and/or injuries to these regions of the brain could facilitate amusia.

Other regions of the brain possibly linked to amusia
Lesions in (or the absence of) associations between the right temporal lobe and inferior frontal lobe. In nine of ten tone-deaf people, the superior arcuate fasciculus in the right hemisphere could not be detected, suggesting a disconnection between the posterior superior temporal gyrus and the posterior inferior frontal gyrus. Researchers suggested the posterior superior temporal gyrus was the origin of the disorder.
Cortical thickness and reduced white matter – in a recent study, voxel-based morphometry, an imaging technique used to explore structural differences in the brain, revealed a decrease in white matter concentration in the right inferior frontal gyrus of amusic individuals as compared to controls. Lack of extensive exposure to music could be a contributing factor to this white matter reduction. For example, amusic individuals may be less inclined to listen to music than others, which could ultimately cause reduced myelination of connections to the frontal areas of the brain.
Involvement of the parahippocampal gyrus (responsible for the emotional reaction to music)

Treatment
Currently, no forms of treatment have proven effective in treating amusia. One study has shown tone differentiation techniques to have some success; however, future research on treatment of this disorder will be necessary to verify this technique as an appropriate treatment.

History
In 1825, F. Gall mentioned a "musical organ" in a specific region of the human brain that could be spared or disrupted after a traumatic event resulting in brain damage. In 1865, Jean-Baptiste Bouillaud described the first series of cases that involved the loss of music abilities that were due to brain injury. In 1878, Grant Allen was the first to describe in the medical literature what would later be termed congenital amusia, calling it "note-deafness". Later, during the late nineteenth century, several influential neurologists studied language in an attempt to construct a theory of cognition. While not studied as thoroughly as language, music and visual processing were also studied. In 1888–1890, August Knoblauch produced a cognitive model for music processing and termed it amusia. This model for music processing was the earliest produced.While the possibility that certain individuals may be born with musical deficits is not a new notion, the first documented case of congenital amusia was published only in 2002. The study was conducted with a female volunteer, referred to as Monica, who declared herself to be musically impaired in response to an advertisement in the newspaper. Monica had no psychiatric or neurological history, nor did she have any hearing loss. MRI scans showed no abnormalities. Monica also scored above average on a standard intelligence test, and her working memory was evaluated and found to be normal. However, Monica had a lifelong inability to recognize or perceive music, which had persisted even after involvement with music through church choir and band during her childhood and teenage years. Monica said that she does not enjoy listening to music because, to her, it sounded like noise and evoked a stressful response.
In order to determine if Monicas disorder was amusia, she was subjected to the MBEA series of tests. One of the tests dealt with Monicas difficulties in discriminating pitch variations in sequential notes. In this test, a pair of melodies was played, and Monica was asked if the second melody in the pair contained a wrong note. Monicas score on this test was well below the average score generated by the control group. Further tests showed that Monica struggled with recognizing highly familiar melodies, but that she had no problems in recognizing the voices of well-known speakers. Thus, it was concluded that Monicas deficit seemed limited to music. A later study showed that not only do amusics experience difficulty in discriminating variations in pitch, but they also exhibit deficits in perceiving patterns in pitch.This finding led to another test that was designed to assess the presence of a deficiency in pitch perception. In this test, Monica heard a sequence of five piano tones of constant pitch followed by a comparison sequence of five piano tones in which the fourth tone could be the same pitch as the other notes in the sequence or a completely different pitch altogether. Monica was asked to respond "yes" if she detected a pitch change on the fourth tone or respond "no" if she could not detect a pitch change. Results showed that Monica could barely detect a pitch change as large as two semitones (whole tone), or half steps. While this pitch-processing deficit is extremely severe, it does not seem to include speech intonation. This is because pitch variations in speech are very coarse compared with those used in music. In conclusion, Monicas learning disability arose from a basic problem in pitch discrimination, which is viewed as the origin of congenital amusia.

Research
Over the past decade, much has been discovered about amusia. However, there remains a great deal more to learn. While a method of treatment for people with amusia has not been defined, tone differentiation techniques have been used on amusic patients with some success. It was found with this research that children reacted positively to these tone differentiation techniques, while adults found the training annoying. However, further research in this direction would aid in determining if this would be a viable treatment option for people with amusia. Additional research can also serve to indicate which processing component in the brain is essential for normal music development. Also, it would be extremely beneficial to investigate musical learning in relation to amusia since this could provide valuable insights into other forms of learning disabilities such as dysphasia and dyslexia.

Notable cases
In fiction
Horatio Hornblower
Grace from Home on the Range
James Fraser from Outlander by Diana Gabaldon
Rodrigo from Mozart in the Jungle

See also
Absolute pitch, the human ability to name a musical note when played or sung (less common than relative pitch)
Auditory agnosia
Cognitive neuroscience of music
Color blindness
Musical aptitude
Music-specific disorders
Relative pitch, the human ability to accurately distinguish pitch intervals (more common than absolute pitch)
Synesthesia
Tonal memory

References
Further reading
Kazez D (1985). "The myth of tone deafness" </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Polyhydramnios and explain in detail? [/INST] Polyhydramnios is a medical condition describing an excess of amniotic fluid in the amniotic sac. It is seen in about 1% of pregnancies.  It is typically diagnosed when the amniotic fluid index (AFI) is greater than 24 cm.
There are two clinical varieties of polyhydramnios: chronic polyhydramnios where excess amniotic fluid accumulates gradually, and acute polyhydramnios where excess amniotic fluid collects rapidly.
The opposite to polyhydramnios is oligohydramnios, not enough amniotic fluid.

Presentation
Associated conditions
Fetuses with polyhydramnios are at risk for a number of other problems including cord prolapse, placental abruption, premature birth and perinatal death. At delivery the baby should be checked for congenital abnormalities.

Causes
In most cases, the exact cause cannot be identified. A single case may have one or more causes, including intrauterine infection (TORCH), rh-isoimmunisation, or chorioangioma of the placenta. In a multiple gestation pregnancy, the cause of polyhydramnios usually is twin-to-twin transfusion syndrome. Maternal causes include cardiac problems, kidney problems, and maternal diabetes mellitus, which causes fetal hyperglycemia and resulting polyuria (fetal urine is a major source of amniotic fluid).
A recent study distinguishes between mild and severe polyhydramnios and showed that Apgar score of less than 7, perinatal death and structural malformations only occurred in women with severe polyhydramnios.
In another study, all patients with polyhydramnios, that had a sonographically normal fetus, showed no chromosomal anomalies.(M/C for polyhydramnio is fetal anomalies Williams Obstetrics, 24th Edition – Cunningham,  Leveno, Bloom et al. Table 11–2)
but these anomalies include:

gastrointestinal abnormalities such as esophageal atresia and duodenal atresia (causing inability to swallow amniotic fluid), anencephaly, facial cleft, neck masses, tracheoesophageal fistula, and diaphragmatic hernias. An annular pancreas causing obstruction may also be the cause.
Bochdaleks hernia, in which the pleuro-peritoneal membranes (especially the left) will fail to develop and seal the pericardio-peritoneal canals </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Paraneoplastic pemphigus and explain in detail? [/INST] Paraneoplastic pemphigus (PNP)  is an autoimmune disorder stemming from an underlying tumor. It is hypothesized that antigens associated with the tumor trigger an immune response resulting in blistering of the skin and mucous membranes.
While patients with malignant and benign tumors are both at risk, malignancy is associated with high mortality rates (near 90%). Current treatment focuses on general wound healing and administering corticosteroids, which has not demonstrated a high success rate. Recent research developments aim to treat the underlying tumor in order to alleviate the symptoms of PNP.

Signs and symptoms
While the presence of lesions is the denominator among patients with PNP, the characteristics of the lesions differ. The five clinical presentations of lesions associated with PNP include:

"Pemphigus-like": Flaccid blister (discrete), crusts over the raw exuding skin lesions
"Pemphigoid-like": Tense blister(s) on brick red erythema
"Erythema multiforme-like": Severe polymorphic skin and/or mucous membrane lesions
"Graft-vs.-host disease-like": Widespread lichenoid eruption with severe mucous membrane involvement
"Lichen planus-like": Small red flat-topped scaly papulesIt is most common that mucous membrane lesions of the oral cavity are presented first. They can involve the oropharynx, nasopharynx, tongue, and vermilion (red portion) of the lips. They are also known to develop in the conjunctiva of the eye, anogenital (perineum) region, and esophagus. Cutaneous lesions tend to follow the onset of mucosal lesions. The blisters often erupt in waves, usually affecting the upper trunk, head, neck, and proximal extremities. Pemphigoid-like lesions are seen more often on the extremities. Lichenoid lesions are more common among children, presenting on the trunk and limbs, ranging from small red scaly papules to extensive violet to brown papules extending to the face and neck. Within the spectrum of lichenoid presentations are wounds that have features of erythema multiforme and graft-vs.-host disease. Scaly lesions on the palms of the hand and soles of the feet have been noted to coincide with the lichenoid lesions. Lesions of varying morphology may present simultaneously and transform from one type to another as the disease progresses.

Mechanism
Underlying cause
PNP is ultimately caused by the presence of a tumor. There is a strong association between the development of PNP and malignancy of the tumor. However, it is not uncommon for the tumor to be benign, as in the case of afflictions such as thymoma and Castlemans disease. Only one patient without a tumor has met the diagnostic criteria for PNP. However, they rapidly reached their demise and it is suggested they may have had an undiagnosed tumor.

Mechanism behind display of major symptoms
The underlying tumor causes circulating and tissue-bound antibodies to direct themselves against antigens in the plakin family, which are involved in the intracellular attachment structures in various levels of the skin/respiratory tract/membranes (keeping skin tissue together throughout the body). The number of target antigens varies on a case by case basis. The variability is likely what accounts for the different presentations of PNP. Through immunoprecipitation, target antigens have been found to include desmoglein-3, desmoglein-1, envoplakin, periplakin, desmoplakin 1, desmoplakin 2, and bullous pemphigoid antigen I.The precise mechanism for how tumors are able to induce autoantibodies toward the plakin proteins is unknown. Suggested theories include tumor production of plakin proteins which initiate an autoimmune response against them, and cross-reactivity of tumor antigens and epidermal antigens.Once the molecules that hold the various levels of the membranes together are attacked, they are unable to function properly, and the tissue breaks apart. This is manifested as the associated blistering and lesions of PNP.

Diagnosis
In order to diagnose paraneoplastic pemphigus, several tests may be performed. Initially, samples are obtained via skin biopsy for routine microscopy and direct immunofluorescence (DIF) testing. The skin sample needs to be obtained from an unaffected area adjacent to a lesion. Testing in more detail follows depending on the results from the DIF. Prompt diagnosis of PNP is crucial due to the high mortality rate of the disease.
Camisa and Helm revised the original criteria from Anhalt et al. into major and minor signs indicating PNP:Major:

Polymorphic mucocutaneous eruption
Concurrent internal tumor
Serum antibodies with a specific immunoprecipitation patternMinor:

Histologic evidence of acantholysis (loss of intercellular connections leading to breaking apart of the skin; lesion)
Direct immunofluorescence showing intercellular and basement membrane staining
Indirect immunofluorescence staining with rat bladder epithelium

Microscopy
Microscopy of the skin sample obtained from the biopsy is used to detect the presence of cleavage within the dermis, epidermal acantholysis (breaking apart of the skin), dyskeratotic keratinocytes and vacuolar changes in the layers of the skin, interfacial dermatitis, and epidermal exocytosis. Presentation of these characteristics suggests PNP.

Direct immunofluorescence testing
The presence of Immunoglobulin G, A, or M in the epidermis is normal.
Detection in other locations such as intercellular and areas below the epidermis (subepidermal), as well as along the dermoepidermal junction (area that joins the epidermis and dermis), suggests paraneoplastic pemphigus.

Follow-up tests for confirmation
Indirect immunofluorescence (IDIF)
Patients with high concentration of antibodies show intercellular, intraepidermal antibodies as well as along the dermoepidermal junction. Patients with low concentration of antibodies only present with them inside the cells (intercellular).If the results are negative, perform the additional assays regardless. Cases have been confirmed that reported with initial negative DIF and IDIF tests.

Assays
Immunoprecipitation, immunoblotting and enzyme-link immunosorbent assay (ELISA)
Poot et al. 2013 determined that immunoprecipitation for antibodies against envoplakin and periplakin or alpha2-macroglobulin-like–1 is the most sensitive test. However, alpha2-macroglobulin-like-1 can also be detected in patients with toxic epidermal necrosis.

Similar diseases with overlapping symptoms
Bullous Pemphigoid, Cicatricial Pemphigoid, Drug Eruptions. Epidermolysis Bullosa, Epidermolysis Bullosa Acquisita, Erythema Multiforme, Lichen Planus, pemphigus vulgaris, Stevens–Johnson syndrome and toxic epidermal necrolysis.PNP is most commonly mistaken for pemphigus vulgaris, due to the extreme similarities of the lesions that develop. However, the difference lies in the specificity of the autoreactive antibodies in each case.

Treatment
Wound healing
Initial treatment involves addressing any existing infections that may have occurred due to the broken state of the skin. Existing wounds are treated with warm compresses, non-adherent (non-stick) dressing, and topical antibiotic ointment. Immunosuppressive agents are administered in attempt to decrease blistering; this is not often effective. The first medication given aiming to heal the wounds are high dose corticosteroids. This is followed by steroid sparing agents  which may reduce steroid intake and therefore lessen the side effects. Skin lesions are more likely to respond to this line of treatment than mucosal lesions. However, a high level of caution is advised in patients with a confirmed malignancy, where immunosuppression is vital and dictates treatment options. If the initial therapy fails to control the symptoms of PNP, and the condition of the patient deteriorates, a more aggressive approach may be necessary.

Medication
Prednisone
Prednisone is an immunosuppressive agent which affects all of the organ systems. Effects on the cellular level include cell activation, replication, differentiation, and mobility. The overall goal is to decrease blistering (inhibition of immediate and delayed hypersensitivity) through decreasing the production of autoantibodies. In order to suppress the production of antibodies, higher doses must be administered. Lesser doses can be prescribed in order to achieve suppression of monocyte function.

Azathioprine
Azathioprine is a steroid-sparing agent used in combination with Prednisone. It functions by inhibiting RNA and DNA synthesis.

Ciclosporin
Ciclosporin is an immunosuppressive agent most often used in organ transplantation that has demonstrated to be effective with skin disorders. It functions by lessening production of autoantibodies and therefore diminishing the development of blisters and erosions. The mechanism of action is by inhibiting the production of T lymphocytes and lymphokines.

Cyclophosphamide
Cyclophosphamide is an immunomodulator used in combination with systemic steroids to remove bone marrow. This is followed by transplanting peripheral blood stem cells.

Prognosis
Quality of life/ Life expectancy
If the lesions are mild, the patient will be subject to a good deal of pain. If the lesions are severe, the overall quality of life is devastating. The impaired skin barrier function commonly leads to localized infection, which sepsis and death may follow. The pain from the oral and pharyngeal ulcers interfere with eating, which can compromise nutritional health.The general prognosis for PNP is poor. It is more hopeful if the tumor is benign, but in the case of malignant tumors, the mortality rate is roughly 90%. The two most commonly associated types of tumors are non-Hodgkin lymphoma and chronic lymphocytic lymphoma; nearly all of these patients die within two years of diagnosis. This is attributed to the effects of the tumor combined with the negative side effects of the medication administered to treat PNP.Roughly 1/3 of the deaths from PNP stem from pulmonary insufficiency which is brought about by the action of PNP on the respiratory mucosa. It manifests as dyspnea and progresses to bronchiolitis obliterans (non-reversible obstructive lung disease) via an unknown mechanism.

Risk Factors
As PNP is ultimately caused by the presence of a tumor, it is not contagious. There is no known way to predict who will become afflicted with it. Patients with cancer are therefore a group at risk. Although PNP has been known to affect all age groups, it is more likely to afflict middle-aged to older patients.

Recent research
The Development of ELISA testing for specific diagnosis of PNP was released in 2009. The research focuses on the specific determination of autoantibodies involved in the mechanism of PNP. Specifically, antibodies against envoplakin and periplakin were being investigated. Further use of ELISA testing on these antibodies confirmed the presence of anti-envoplakin and anti-periplakin autoantibodies in patients with PNP.Further research in 2013 outlined the various types of assays that could be used to determine which antibodies were involved in PNP. Demonstration of certain antibodies in the serum was named as the basis for diagnosis of PNP. This piece labeled PNP as a "multiorgan disease characterized by antibodies against plakins, desmogleins and the α2-macroglobulin-like-1 (A2ML1) protein, in association with an underlying neoplasm".A study concluded in 2009, summarized in 2010, surrounded the surgical removal of the associated tumor as a means to treat PNP </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Sandhoff disease and explain in detail? [/INST] Sandhoff disease is a lysosomal genetic, lipid storage disorder caused by the inherited deficiency to create functional beta-hexosaminidases A and B. These catabolic enzymes are needed to degrade the neuronal membrane components, ganglioside GM2, its derivative GA2, the glycolipid globoside in visceral tissues, and some oligosaccharides. Accumulation of these metabolites leads to a progressive destruction of the central nervous system and eventually to death. The rare autosomal recessive neurodegenerative disorder is clinically almost indistinguishable from Tay–Sachs disease, another genetic disorder that disrupts beta-hexosaminidases A and S. There are three subsets of Sandhoff disease based on when first symptoms appear: classic infantile, juvenile and adult late onset.

Symptoms and signs
Sandhoff disease symptoms are clinically indeterminable from Tay–Sachs disease. The classic infantile form of the disease has the most severe symptoms and is incredibly hard to diagnose at this early age.  The first signs of symptoms begin before 6 months of age and the parents’ notice when the child begins regressing in their development.  If the children had the ability to sit up by themselves or crawl they will lose this ability.  This is caused by a slow deterioration of the muscles in the child’s body from the buildup of GM2 gangliosides.  Since the body is unable to create the enzymes it needs within the central nervous system, it is unable to attach to these gangliosides to break them apart and make them non-toxic.  With this buildup there are several symptoms that begin to appear such as muscle/motor weakness, sharp reaction to loud noises, blindness, deafness, inability to react to stimulants, respiratory problems and infections, mental retardation, seizures, cherry red spots in the retina, enlarged liver and spleen (hepatosplenomegaly), pneumonia, or bronchopneumonia.The other two forms of Sandhoff disease have similar symptoms but to a lesser extent.  Adult and juvenile forms of Sandhoff disease are more rare than the infantile form. In these cases victims suffer cognitive impairment (retardation) and a loss of muscle coordination that impairs and eventually destroys their ability to walk; the characteristic red spots in the retina also develop. The adult form of the disease, however, is sometimes milder, and may only lead to muscle weakness that impairs walking or the ability to get out of bed.

Causes
Two parents carrying a mutated gene and passing it on to their offspring cause the disease.  Even with both parents carrying the disease in their genome, there is only a 25% chance that they will have a child containing the genetic coding for the disease (see figure right).Each form of the disease is caused by the differences in the various mutations of the genome, in particular the codons on the 14 exons in the HEX B gene located within chromosome 5 (see figure bottom), leading to the differences in severities of the symptoms.  The difference in the codons has the consequence of inhibiting two enzymes located in the lysosomes of the neurons of the central nervous system. Lysosomes contain various enzymes to break down byproducts and toxins to ensure they do not accumulate enough to interfere with the function of the central nervous system.Using restriction enzymes, it was discovered that a mutation on chromosome 5 particularly within the C1214T allele caused the adult onset form of Sandhoff Disease. For the patient showing symptoms of the infantile or juvenile form they have a mutation on exon I207V from their father, and a 16 base pair deletion from their mother which can be located on as many as five exons, exons 1–5.

Mutations and polymorphism
Articles regarding Sandhoff disease frequencies among distinct groups of people contain discrepancies from one another. More than 25 mutations have been reported other than novel mutations.One article says that Sandhoff disease is found commonly in individuals with a non-Jewish descent.Others say that it is more commonly in:

the Creole population of northern Argentina
the indigenous Métis in Saskatchewan
Christian Maronite communities from CyprusDiscovery of several mutations in Ashkenazi Jews may reflect ascertainment bias rather than a high population frequency, because Ashkenazi Jews were the targeted population in a mass screening program for Tay-Sachs disease. Several rare SD mutations were discovered as researchers resolved cases of enzyme deficiency among suspected TSD carriers, but no cases of the disease itself have been reported.However, since it is an autosomal recessive disease, it is likely found in any ethnic group passing from generation to generation through carriers without being expressed in their offspring. Even though the family may not have a history of Sandhoff disease, it is possible for two individuals to have a child with the disease. Since Sandhoff disease was only discovered in 1968, there are years the disease has gone undetected because of misdiagnoses.

Pathophysiology
Biallelic pathogenic variants in the HEXB gene cause Sandhoff disease. The gene provides instructions for making a protein crucial to the enzymes beta-hexosaminidase A and beta-hexosaminidase B, which function in nerve cells to break down fatty substances, complex sugars, and molecules that are linked to sugars. In particular, beta-hexosaminidase A breaks down a fatty compound called GM2 ganglioside. Mutations in the HEXB gene disrupt the activity of these enzymes, preventing the breakdown of GM2 ganglioside and other molecules.As a result, progressive damage caused by the resulting buildup of GM2 ganglioside leads to the destruction of nerve cells, causing the signs and symptoms associated with Sandhoff disease.

Diagnosis
Sandhoff disease can be detected through the following procedures (before it is apparent through physical examination): a biopsy removing a sample of tissue from the liver, genetic testing, molecular analysis of cells and tissues (to determine the presence of a genetic metabolic disorder), enzyme assay, and occasionally a urinalysis to determine if the above-noted compounds are abnormally stored within the body. For a child to suffer from this disease, both parents must be carriers, and both must transmit the mutation to the child. Thus, even in the case where both parents have the mutation, there is only a 25 percent chance their child will inherit the condition. Frequently, parents are given the opportunity to have a DNA screening if they are at high risk, to determine their carrier status before they have children. However, it is also highly recommended to undergo testing even for those parents who do not have a family history of Sandhoff disease. Over 95% of the families that have children with Sandhoff disease had no known prior family history of the condition, as the mutation in the HEXB gene does not cause clinical symptoms when only one copy is present, and often passed undetected from one generation to the next Naturally, if an individual carries the mutation, he or she has a risk of transmitting it to the unborn child. Genetic counseling is recommended for those who have the mutation.It is possible for parents who are about to have a child or had a child with Sandhoff Disease can have a PGD or PEGD.  PEGD is pre-embryonic genetic diagnosis for the parents that would not benefit from a pre-implantation genetic diagnosis because of their religion or negative attitude for the discarding of embryos.  PEGD sequences the genome of the embryo to be produced by two parents if they were to conceive a child.  If the family has a history of Sandhoff disease it is recommended they have their genome sequenced to ensure they are not carriers or to sequence the genome of their child.

Types
There are three types of Sandhoff disease: classic infantile, juvenile, and adult late onset. Each form is classified by the severity of the symptoms as well as the age at which the patient shows these symptoms.
Classic infantile form of the disease is classified by the development of symptoms anywhere from 2 months to 9 months of age. It is the most common and most severe of all of the forms and will lead to death before the patient reaches the age of three. Infants with this disorder typically appear normal until the age of 3 to 6 months, when development slows and muscles used for movement weaken. Affected infants lose motor skills such as turning over, sitting, and crawling. As the disease progresses, infants develop seizures, vision and hearing loss, dementia, and paralysis. An eye abnormality called a cherry-red spot, which can be identified with an eye examination, is characteristic of this disorder. Some infants with Sandhoff disease may have enlarged organs (organomegaly) or bone abnormalities. Children with the severe form of this disorder usually live only into early childhood.
The juvenile form of the disease shows symptoms starting at age 3 ranging to age 10 and, although the child usually dies by the time they are 15, it is possible for them to live longer if they are under constant care. Symptoms include autism, ataxia, motor skills regression, spacticity, and learning disorders.
Adult onset form of the disease is classified by its occurrence in older individuals and has an effect on the motor function of these individuals. It is not yet known if Sandhoff disease will cause these individuals to have a decrease in their life span.Juvenile and adult onset forms of Sandhoff disease are very rare. Signs and symptoms can begin in childhood, adolescence, or adulthood and are usually milder than those seen with the infantile form of Sandhoff disease. As in the infantile form, mental abilities and coordination are affected. Characteristic features include muscle weakness, loss of muscle coordination (ataxia) and other problems with movement, speech problems, and mental illness. These signs and symptoms vary widely among people with late-onset forms of Sandhoff disease.

Treatment
Currently Sandhoff disease does not have any standard treatment and does not have a cure. However, a person suffering from the disease needs proper nutrition, hydration, and maintenance of clear airways. To reduce some symptoms that may occur with Sandhoff disease, the patient may take anticonvulsants to manage seizures or medications to treat respiratory infections, and consume a precise diet consisting of puree foods due to difficulties swallowing. Infants with the disease usually die by the age of 3 due to respiratory infections. The patient must be under constant surveillance because they can suffer from aspiration or lack the ability to change from the passageway to their lungs versus their stomach and their spit travels to the lungs causing bronchopneumonia.  The patient also lacks the ability to cough and therefore must undergo a treatment to shake up their body to remove the mucus from the lining of their lungs.  Medication is also given to patients to lessen their symptoms including seizures.Currently the government is testing several treatments including N-butyl-deoxynojirimycin in mice, as well as stem cell treatment in humans and other medical treatments recruiting test patients </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Amalgam tattoo and explain in detail? [/INST] Amalgam tattoo is a grey, blue or black area of discoloration on the mucous membranes of the mouth, typically on the gums of the lower jaw </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Shell shock and explain in detail? [/INST] Shell shock is a term coined in World War I by the British psychologist Charles Samuel Myers to describe the type of post-traumatic stress disorder (PTSD) many soldiers were afflicted with during the war (before PTSD was termed). It is a reaction to the intensity of the bombardment and fighting that produced a helplessness appearing variously as panic and being scared, flight, or an inability to reason, sleep, walk or talk.During the war, the concept of shell shock was ill-defined. Cases of "shell shock" could be interpreted as either a physical or psychological injury, or as a lack of moral fibre. The term shell shock is still used by the United States’ Department of Veterans Affairs to describe certain parts of PTSD, but mostly it has entered into memory, and it is often identified as the signature injury of the war.
In World War II and thereafter, diagnosis of "shell shock" was replaced by that of combat stress reaction, a similar but not identical response to the trauma of warfare and bombardment.

Origin
During the early stages of World War I in 1914, soldiers from the British Expeditionary Force began to report medical symptoms after combat, including tinnitus, amnesia, headaches, dizziness, tremors, and hypersensitivity to noise. While these symptoms resembled those that would be expected after a physical wound to the brain, many of those reporting sick showed no signs of head wounds. By December 1914 as many as 10% of British officers and 4% of enlisted men were experiencing "nervous and mental shock".The term "shell shock" was coined during the Battle of Loos to reflect an assumed link between the symptoms and the effects of explosions from artillery shells. The term was first published in 1915 in an article in The Lancet by Charles Myers. Some 60–80% of shell shock cases displayed acute neurasthenia, while 10% displayed what would now be termed symptoms of conversion disorder, including mutism and fugue.The number of shell shock cases grew during 1915 and 1916 but it remained poorly understood medically and psychologically. Some physicians held the view that it was a result of hidden physical damage to the brain, with the shock waves from bursting shells creating a cerebral lesion that caused the symptoms and could potentially prove fatal. Another explanation was that shell shock resulted from poisoning by the carbon monoxide formed by explosions.At the same time, an alternative view developed describing shell shock as an emotional, rather than a physical, injury. Evidence for this point of view was provided by the fact that an increasing proportion of men with shell shock symptoms had not been exposed to artillery fire. Since the symptoms appeared in men who had no proximity to an exploding shell, the physical explanation was clearly unsatisfactory.In spite of this evidence, the British Army continued to try to differentiate those whose symptoms followed explosive exposure from others. In 1915 the British Army in France was instructed that:

Shell-shock and shell concussion cases should have the letter W prefixed to the report of the casualty, if it was due to the enemy; in that case the patient would be entitled to rank as wounded and to wear on his arm a wound stripe.  If, however, the mans breakdown did not follow a shell explosion, it was not thought to be due to the enemy, and he was to [be] labelled Shell-shock or S (for sickness) and was not entitled to a wound stripe or a pension.
However, it often proved difficult to identify which cases were which, as the information on whether a casualty had been close to a shell explosion or not was rarely provided.

Management
Acute
At first, shell-shock casualties were rapidly evacuated from the front line – in part because of fear of their unpredictable behaviour. As the size of the British Expeditionary Force increased, and manpower became in shorter supply, the number of shell shock cases became a growing problem for the military authorities. At the Battle of the Somme in 1916, as many as 40% of casualties were shell-shocked, resulting in concern about an epidemic of psychiatric casualties, which could not be afforded in either military or financial terms.Among the consequences of this were an increasing official preference for the psychological interpretation of shell shock, and a deliberate attempt to avoid the medicalisation of shell shock. If men were uninjured it was easier to return them to the front to continue fighting. Another consequence was an increasing amount of time and effort devoted to understanding and treating shell shock symptoms. Soldiers who returned with shell shock generally could not remember much because their brain would shut out all the traumatic memories.
By the Battle of Passchendaele in 1917, the British Army had developed methods to reduce shell shock. A man who began to show shell-shock symptoms was best given a few days rest by his local medical officer. Col. Rogers, Regimental Medical Officer,  4th Battalion Black Watch wrote:

You must send your commotional cases down the line.  But when you get these emotional cases, unless they are very bad, if you have a hold of the men and they know you and you know them (and there is a good deal more in the man knowing you than in you knowing the man) … you are able to explain to him that there is really nothing wrong with him, give him a rest at the aid post if necessary and a day or two’s sleep, go up with him to the front line, and, when there, see him often, sit down beside him and talk to him about the war and look through his periscope and let the man see you are taking an interest in him.
If symptoms persisted after a few weeks at a local Casualty Clearing Station, which would normally be close enough to the front line to hear artillery fire, a casualty might be evacuated to one of four dedicated psychiatric centres which had been set up further behind the lines, and were labelled as "NYDN – Not Yet Diagnosed Nervous" pending further investigation by medical specialists.
Although the Battle of Passchendaele generally became a byword for horror, the number of cases of shell shock were relatively few. 5,346 shell shock cases reached the Casualty Clearing Station, or roughly 1% of the British forces engaged. 3,963 (or just under 75%) of these men returned to active service without being referred to a hospital for specialist treatment. The number of shell shock cases reduced throughout the battle, and the epidemic of illness was ended.During 1917, "shell shock" was entirely banned as a diagnosis in the British Army, and mentions of it were censored, even in medical journals.

Chronic treatment
The treatment of chronic shell shock varied widely according to the details of the symptoms, the views of the doctors involved, and other factors including the rank and class of the patient.
There were so many officers and men with shell shock that 19 British military hospitals were wholly devoted to the treatment of cases. Ten years after the war, 65,000 veterans of the war were still receiving treatment for it in Britain. In France it was possible to visit aged shell shock victims in hospital in 1960.

Physical causes
2015 research by Johns Hopkins University has found that the brain tissue of combat veterans who have been exposed to improvised explosive devices (IEDs) exhibit a pattern of injury in the areas responsible for decision making, memory and reasoning.  This evidence has led the researchers to conclude that shell shock may not only be a psychological disorder, since the symptoms exhibited by affected individuals from the First World War are very similar to these injuries. Immense pressure changes are involved in shell shock. Even mild changes in air pressure from weather have been linked to changes in behavior.There is also evidence to suggest that the type of warfare faced by soldiers would affect the probability of shell shock symptoms developing. First-hand reports from medical doctors at the time note that rates of such conditions decreased once the war was mobilized again during the 1918 German offensive, following the 1916–1917 period where the highest rates of shell shock can be found.  This could suggest that it was trench warfare, and the experience of siege warfare specifically, that led to the development of these symptoms.

Cowardice
Some men with shell shock were put on trial, and even executed, for military crimes including desertion and cowardice.  While it was recognised that the stresses of war could cause men to break down, a lasting episode was likely to be seen as symptomatic of an underlying lack of character. For instance, in his testimony to the post-war Royal Commission examining shell shock, Lord Gort said that shell shock was a weakness and was not found in "good" units. The continued pressure to avoid medical recognition of shell shock meant that it was not, in itself, considered an admissible defence. Although some doctors or medics did take procedure to try to cure soldiers shell shock, it was first done in a brutal way. Doctors would provide electric shock to soldiers in hopes that it would shock them back to their normal, heroic, pre-war self. After almost a year of giving one of his patients electric shocks, putting cigarettes on his tongue, hot plates at the back of his throat, etc., a British clinician, Lewis Yealland, said to his patient, "You will not leave this room until you are talking as well as you ever did... You must behave as the hero I expected you to be."Executions of soldiers in the British Army were not commonplace. While there were 240,000 Courts Martial and 3080 death sentences handed down, in only 346 cases was the sentence carried out. 266 British soldiers were executed for "Desertion", 18 for "Cowardice", 7 for "Quitting a post without authority", 5 for "Disobedience to a lawful command" and 2 for "Casting away arms".  On 7 November 2006, the government of the United Kingdom gave them all a posthumous conditional pardon.

Committee of Enquiry report
The British government produced a Report of the War Office Committee of Enquiry into "Shell-Shock" which was published in 1922. Recommendations from this included:

In forward areas
No soldier should be allowed to think that loss of nervous or mental control provides an honourable avenue of escape from the battlefield, and every endeavour should be made to prevent slight cases leaving the battalion or divisional area, where treatment should be confined to provision of rest and comfort for those who need it and to heartening them for return to the front line.
In neurological centres
When cases are sufficiently severe to necessitate more scientific and elaborate treatment they should be sent to special Neurological Centres as near the front as possible, to be under the care of an expert in nervous disorders.  No such case should, however, be so labelled on evacuation as to fix the idea of nervous breakdown in the patient’s mind.
In base hospitals
When evacuation to the base hospital is necessary, cases should be treated in a separate hospital or separate sections of a hospital, and not with the ordinary sick and wounded patients.  Only in exceptional circumstances should cases be sent to the United Kingdom, as, for instance, men likely to be unfit for further service of any kind with the forces in the field.  This policy should be widely known throughout the Force.
Forms of treatment
The establishment of an atmosphere of cure is the basis of all successful treatment, the personality of the physician is, therefore, of the greatest importance.  While recognising that each individual case of war neurosis must be treated on its merits, the Committee are of opinion that good results will be obtained in the majority by the simplest forms of psycho-therapy, i.e., explanation, persuasion and suggestion, aided by such physical methods as baths, electricity and massage.  Rest of mind and body is essential in all cases.The committee are of opinion that the production of hypnoidal state and deep hypnotic sleep, while beneficial as a means of conveying suggestions or eliciting forgotten experiences are useful in selected cases, but in the majority they are unnecessary and may even aggravate the symptoms for a time.
They do not recommend psycho-analysis in the Freudian sense.In the state of convalescence, re-education and suitable occupation of an interesting nature are of great importance.  If the patient is unfit for further military service, it is considered that every endeavour should be made to obtain for him suitable employment on his return to active life.
Return to the fighting line
Soldiers should not be returned to the fighting line under the following conditions:(1) If the symptoms of neurosis are of such a character that the soldier cannot be treated overseas with a view to subsequent useful employment.
(2) If the breakdown is of such severity as to necessitate a long period of rest and treatment in the United Kingdom.
(3) If the disability is anxiety neurosis of a severe type.
(4) If the disability is a mental breakdown or psychosis requiring treatment in a mental hospital.
It is, however, considered that many of such cases could, after recovery, be usefully employed in some form of auxiliary military duty.
Part of the concern was that many British veterans were receiving pensions and had long-term disabilities.

By 1939, some 120,000 British ex-servicemen had received final awards for primary psychiatric disability or were still drawing pensions – about 15% of all pensioned disabilities – and another 44,000 or so … were getting pensions for ‘soldier’s heart’ or Effort Syndrome.  There is, though, much that statistics do not show, because in terms of psychiatric effects, pensioners were just the tip of a huge iceberg.
War correspondent Philip Gibbs wrote:

Something was wrong.  They put on civilian clothes again and looked to their mothers and wives very much like the young men who had gone to business in the peaceful days before August 1914.  But they had not come back the same men.  Something had altered in them.  They were subject to sudden moods, and queer tempers, fits of profound depression alternating with a restless desire for pleasure.  Many were easily moved to passion where they lost control of themselves, many were bitter in their speech, violent in opinion, frightening.
One British writer between the wars wrote:

There should be no excuse given for the establishment of a belief that a functional nervous disability constitutes a right to compensation.  This is hard saying.  It may seem cruel that those whose sufferings are real, whose illness has been brought on by enemy action and very likely in the course of patriotic service, should be treated with such apparent callousness.  But there can be no doubt that in an overwhelming proportion of cases, these patients succumb to ‘shock’ because they get something out of it.  To give them this reward is not ultimately a benefit to them because it encourages the weaker tendencies in their character.  The nation cannot call on its citizens for courage and sacrifice and, at the same time, state by implication that an unconscious cowardice or an unconscious dishonesty will be rewarded.

Development of psychiatry
At the beginning of World War II, the term "shell shock" was banned by the British Army, though the phrase "postconcussional syndrome" was used to describe similar traumatic responses.

Society and culture
Shell shock has had a profound impact in British culture and the popular memory of World War I. At the time, war writers like the poets Siegfried Sassoon and Wilfred Owen dealt with shell shock in their work. Sassoon and Owen spent time at Craiglockhart War Hospital, which treated shell shock casualties. Author Pat Barker explored the causes and effects of shell shock in her Regeneration Trilogy, basing many of her characters on real historical figures and drawing on the writings of the first world war poets and the army doctor W. H. R. Rivers.

Modern cases of shell shock
Although the term "shell shocked" is typically used in discussion of WWI to describe early forms of PTSD, its high-impact explosives-related nature provides modern applications as well. During their deployment in Iraq and Afghanistan, approximately 380,000 U.S. troops, about 19% of those deployed, were estimated to have sustained brain injuries from explosive weapons and devices. This prompted the U.S. Defense Advanced Research Projects Agency (DARPA) to open up a $10 million study of the blast effects on the human brain. The study revealed that, while the brain remains initially intact immediately after low level blast effects, the chronic inflammation afterwards is what ultimately leads to many cases of shell shock and PTSD.

See also
Combat stress reaction

References
Sources
Coulthart, Ross. The Lost Diggers, Sydney: HarperCollins Publishers, 2012. ISBN 978-0732294618
Jones, E, Fear, N and Wessely, S. "Shell Shock and Mild Traumatic Brain Injury:  A Historical Review". Am J Psychiatry 2007; 164:1641–1645
Hochschild, Adam. To End all Wars – a story of loyalty and rebellion, 1914–1918 Mariner Books, Houghton, Mifflin Harcourt, Boston & New York, 2011. ISBN 978-0547750316
Horrocks, J. (2018). The limits of endurance: Shell shock and dissent in World War one. The Journal of New Zealand Studies, (NS27). https://doi.org/10.26686/jnzs.v0ins27.5175
Leese, Peter. Shell Shock. Traumatic Neurosis and the British Soldiers of the First World War, Palgrave Macmillan, 2014. ISBN 978-1137453372.
MacLeod, A. D. (2004). "Shell shock, Gordon Holmes and the Great War". Journal of the Royal Society of Medicine. 97 (2): 86–89 </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Bakers itch and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is List of autoimmune diseases and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Acute monocytic leukemia and explain in detail? [/INST] Acute monocytic leukemia (AMoL, or AML-M5) is a type of acute myeloid leukemia. In AML-M5 >80% of the leukemic cells are of monocytic lineage. This cancer is characterized by a dominance of monocytes in the bone marrow. There is an overproduction of monocytes that the body does not need in the periphery. These overproduced monocytes interfere with normal immune cell production which causes many health complications for the infected individual.

Causes
The pathology of AML involves abnormal proliferation and differentiation of a population of myeloid stem cells. Genetic mutations are identified in the majority of cases. A common genetic mutation identified in these cases are characterized as chromosomal translocations where information from one chromosome is exchanged to a non-homologous chromosome creating an unusual rearrangement of chromosomes. This translocation is often abbreviated as t(#of one chromosome involved, #of other chromosome involved). M5 is associated with characteristic chromosomal abnormalities, often involving chromosome 11, such as t(9;11), affecting the MLL (KMTA2) locus at 11q23; however MLL translocations are also found in other leukemia subtypes. The t(8;16) translocation in AMoL is associated with hemophagocytosis. These translocations yield the formation of chimeric proteins (RUNX1-RUNX1T1 and PML-RARA, respectively) which disrupt normal myeloid precursor development.
Secondary leukaemia, which may include AML-M5, has been associated with exposure to epipodophyllotoxins, such as etoposide.Many cases of AML-M5 are seen to have enhanced phosphorylation of the STAT3 protein due to increased induction of cytokines thus increasing cell proliferation and survival. Finally, genetic mutations involved in epigenetic regulation are associated with this leukemia, as they have downstream effects on cell differentiation and proliferation. Excessive cytokine release could be a byproduct of skewed epigenetic regulation.

Diagnosis
In order to fulfill World Health Organization (WHO) criteria for AML-5, a patient must have greater than 20% blasts in the bone marrow, and of these, greater than 80% must be of the monocytic lineage </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Primitive neuroectodermal tumor and explain in detail? [/INST] Primitive neuroectodermal tumor is a malignant (cancerous) neural crest tumor </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Cocaine intoxication and explain in detail? [/INST] Cocaine intoxication refers to the subjective, desired and adverse effects of cocaine on the mind and behavior of users. Both self-induced and involuntary cocaine intoxication have medical and legal implications (even in absence of relevant adverse effects).
Adverse effects can develop over time due to repeated use and so become chronic conditions. However, even a one-time intake of the substance can result in severe acute intoxication.
Recurrent cocaine use and dependence to the drug  inevitably leads to the reduction of the desired effects perceived by the users,  while the occurrence of adverse effects of intoxication increase. The last can sometimes be completely reversed without bearing consequences but they can also potentially kill the users (e.g., in cases of untreated or non-manageable overdoses).

Signs and symptoms
Cocaine increases alertness, feelings of well-being, euphoria, energy, sociability, and sexuality. The former are some of the desired effects of cocaine intoxication. Not having the normal use of mental faculties by reason of the introduction of cocaine is defined drug intoxication by the laws in America, Europe, and most of the rest of the World, and it is a serious crime in specific contexts (e.g., in drug-impaired driving).Mild adverse effects include anxiety, increased temperature, paranoia, restlessness, and teeth grinding.  With prolonged use, the drug can cause chronic complications like insomnia, weight loss, anorexia, persistent tachycardia, heart failure, kidney failure, hallucinations, and paranoid delusions.Depression with suicidal ideation may develop in heavy users. Finally, a loss of vesicular monoamine transporters, neurofilament proteins, and other morphological changes appear to indicate a long-term damage to dopamine neurons. Chronic intranasal usage can degrade the cartilage separating the nostrils (the nasal septum), which can eventually lead to its complete disappearance.Studies have shown that cocaine usage during pregnancy triggers premature labor and may lead to abruptio placentae.In cases of severe acute intoxication, potentially lethal adverse effects include prolonged episodes of arrhythmia (i.e., a group of abnormal heart rhythms that also include tachycardia), heavy hypoglycemia, tremors, convulsions, hyperthermia (i.e., markedly increased core temperature), untreated uremia, myocardial infarction, stroke, and sudden cardiac arrest.

Overdose
Cocaine can be snorted, swallowed, injected, or smoked. Most deaths due to cocaine are accidental but may also be the result of body packing or stuffing with rupture in the gastrointestinal tract. Use of cocaine causes abnormally fast heart rhythms and a marked elevation of blood pressure (hypertension), which can be life-threatening. This can lead to death from acute myocardial infarction, acute respiratory failure (i.e., hypoxemia, with or without hypercapnia), stroke, cerebral hemorrhage, and sudden cardiac arrest. Cocaine overdose may result in hyperthermia as stimulation and increased muscular activity cause greater heat production. Heat loss is also inhibited by the cocaine-induced vasoconstriction. Cocaine and/or associated hyperthermia may cause muscle cell destruction (rhabdomyolysis) and myoglobinuria resulting in kidney failure. Individuals with cocaine overdose should be transported immediately to the nearest emergency department, preferably by ambulance in case cardiac arrest occurs en route. According to the National Institute on Drug Abuse, approximately 14,600 deaths occurred in the US in 2017 due to an overdose where cocaine was somehow involved in any capacity, defined or undefined. Because of the increase in heart rate, cocaine users can be prone to elevated body temperatures, tremors, chest pains, and subject to nausea and vomiting. Some psychological symptoms due to an overdose include paranoia, delirium, anxiety as well as panicked feelings. Some signs of an overdose of cocaine are difficulty breathing, loss of urine control, bluish color of the skin, loss of awareness or surroundings, and high blood pressure. Although not as common, death can be caused from an over intoxication of cocaine. Most severe overdoses occur when users combine cocaine with other substances like alcohol or heroin, which increase the effects and heighten the chances of having a dangerous overdose. Treating an overdose can be done by bringing back blood flow to the heart, and restoring the body with oxygen rich blood, especially for the brain to reduce the risk of stroke. Cocaine overdoses have fluctuated over the years. From 2006 to 2010 there has been a decline in the number of reported cases. Though, from 2010 to 2015 there has been an increase in the reported cases involving over cocaine Intoxication. Males appear to have a much higher chance of overdosing than females. The ratio of male to female cocaine overdoses is 3:1.

Withdrawal
Cocaine withdrawal is not as severe as the withdrawal from other substances. For example, substances like alcohol and benzodiazepines can involve severe physical withdrawal symptoms while cocaine results in mostly psychological symptoms. Physiological changes caused by cocaine withdrawal include vivid and unpleasant dreams, insomnia, hypersomnia, anger, increased appetite, weight gain, psychomotor retardation, agitation, depression, and anxiety.  According to a study done by Gawin and Kleber in 1986, there are three phases in the withdrawal process. They observed the behavior of 30 cocaine-dependent individuals. Phase one, the crash, is characterized by acute dysphoria, irritability and anxiety, increased desire for sleep, exhaustion, increased appetite, decreased craving to use. Phase two, withdrawal, is characterized by increasing craving to use, poor concentration, some irritability and some lethargy, which persisted for up to 10 weeks. Lastly, phase three is characterized by the intermittent craving to use in the context of external cues. Cocaine and its metabolites are eliminated from the body by 3 days.  There are not any FDA-approved medications that specifically help treat cocaine withdrawal, however, there are some useful medications that could possibly help individuals overcome their addiction. One example is propranolol. Propranolol is a beta blocker that has been approved to treat hypertension, angina, anxiety, and other related psychological problems. Buprenorphine and naltrexone are two substances that act as an effective treatment in the earlier stages of withdrawal.

Pathophysiology
Cocaine pharmacodynamics involve multiple complex mechanisms. Although it has a short half-life (~ 1 hour), cocaine metabolites, which rise in concentrations several hours after cocaine ingestion, persist in circulation for up to 24 hours, and may cause delayed or recurrent coronary vasoconstriction. This drug binds and blocks monoamine (dopamine, epinephrine, norepinephrine, and serotonin) re-uptake transporters with equal affinity. Monoamines accumulate in the synaptic cleft resulting in enhanced and prolonged sympathetic effects. Cocaines acute effect in the central nervous system is to raise the amount of dopamine and serotonin in the nucleus accumbens (the pleasure center in the brain). When this effect ceases due to metabolism of cocaine, depletion of associated neurotransmitters, and receptor down-regulation (tachyphylaxis), the cocaine user may experience dysphoria, or a "crash" after the initial high. The principal actions of cocaine on the cardiovascular system are from alpha- and beta-1-adrenoceptor stimulation resulting in increased heart rate, systemic arterial pressure, and myocardial contractility, which are major determinants of myocardial oxygen demand. Cocaine and its metabolites may cause arterial vasoconstriction hours after use. Epicardial coronary arteries are especially vulnerable to these effects, leading to decreased myocardial oxygen supply. Cocaine-induced platelet activation and thrombus formation is another deleterious effect, caused by alpha-adrenergic- and adenosine diphosphate-mediated increase in platelet aggregation. Plasminogen activator inhibitor is also increased following cocaine use, thereby promoting thrombosis. Cocaine acts like a class I antiarrhythmic agent by blocking sodium and potassium channels, in a similar way of local anesthetics such as lidocaine, and interferes with action potential propagation. This Vaughn-Williams class IC effect increases the risk of conduction disturbance and tachyarrhythmias. Adding to its complex toxicity, cocaine targets muscarinic acetylcholine, N-methyl-D-aspartate (NMDA), sigma, and kappa-opioid receptors.

Management
There is no specific antidote for cocaine. Emergency treatment of cocaine-associated high body temperature consists of giving a benzodiazepine and physical cooling. Immediate administration of aspirin is required for patients reporting cocaine-associated chest pain. Cooling is best accomplished with tepid water misting and cooling with a fan. Antipyretics (e.g., paracetamol) have no effect in lowering high temperature because cocaine is an muscarinic receptor agonist.
The chest pain, high blood pressure, and increased heart rate caused by cocaine may be also treated with benzodiazepines. Multiple and escalating dose of benzodiazepines may be necessary to achieve effect, which increases risk of over-sedation and respiratory depression. A review of cocaine cardiovascular toxicity found benzodiazepines may not always reliably lower heart rate and blood pressure.
Lidocaine and intravenous lipid emulsion have been successfully used for serious ventricular tachyarrhythmias in several case reports.
People who are agitated are best treated with benzodiazepines, though antipsychotics such as haloperidol and olanzapine may also be useful. The alpha-2 agonist dexmedetomidine may also be useful for agitation, but effects on heart rate and blood pressure are variable based on several studies and case reports.

Vasodilators
Nitric-oxide mediated vasodilators, such as nitroglycerin and nitroprusside, are effective at lowering blood pressure and reversing coronary arterial vasoconstriction, but not heart rate </s>