<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 Dysosteosclerosis and explain in detail? [/INST] Dysosteosclerosis (DSS), also known as autosomal recessive dysosteosclerosis or X-linked recessive dysosteosclerosis, is a rare osteoclast-poor form of osteosclerosis that is presented during infancy and early childhood, characterized by progressive osteosclerosis and platyspondyly.  Platyspondyly and other skeletal abnormalities are radiographic features of the disease which distinguish DSS from other osteosclerotic disorders. Patients usually experience neurological and psychological deterioration, therefore patients are commonly associated with delayed milestones.
The cause of DSS is unclear. Different genetic mutations are observed in patients, therefore it is suggested that the cause is genetically heterogeneous. Genetic mutations responsible include, but are not limited to, TCIRG1, TNFRSF11A , and SLC29A3. It is congenital and inherited as an autosomal recessive disorder, however, an X-linked recessive inheritance is outlined in some families. There is no cure for DSS. Supportive care includes orthopaedic care. Symptomatic treatment involves the reduction in calcium intake in diet. Less than 30 cases of DSS have been reported in literature to date.

Symptoms and Signs
The main signs and symptoms of DSS includes:
Skeletal abnormalities: platyspondyly, sclerosis
Physical abnormalities: short stature, macrocephaly
Neurological abnormalities: delayed development, mental retardation

Skeletal abnormalities
In general, patients with DSS develop osteopenia and bone fragility. DSS also affects specific areas of the human skeleton, such as the spine, skull, pelvis, and limbs.
The most common sign of DSS is platyspondyly, which is the flattening of vertebral bodies of the axial skeleton, present in 80-99% of individuals with DSS. Other spinal abnormalities associated with DSS include widened intervertebral disks, small, dense vertebral bodies, irregular vertebral endplates, hypoplastic vertebral bodies, and pronounced vertebral anterior notches.More than 80% of patients also reported abnormalities of the skull. Common symptoms include craniofacial hyperostosis, which is the excessive growth of bone in the skull and face. Skull base sclerosis, periorbital sclerosis, hypoplastic mandibular condyle, and absent paranasal or frontal sinuses are present in rare cases.It is also reported that individuals may also have pelvic abnormalities. This includes the development of narrow iliac wings, as well as widened femoral necks. However, incidence of both symptoms are rare in patients with DSS, occurring in less than 30% of cases.The occurrence of DSS also leads to deformities of the limbs. 80% of patients reported with abnormalities of the metaphysis such as metaphyseal flaring, radiolucent metaphyses, abnormal metaphyseal trabeculation, which is abnormal trabecula patterns in the metaphyseal region, and epimetaphyseal sclerosis. Other limbic abnormalities include progressive bowing of long bones, which is present in rare cases.

Physical abnormalities
In general, patients appear to be short statured. In addition, as a result of sclerosis of the frontal and parietal region of the calvarium, macrocephaly and square shaped heads are reported in more than 80% of patients.Abnormal skin conditions of red-violet macular mottled skins over the entire body are occasionally observed in patients. However it is unclear whether this clinical feature is relevant to diagnosis of DSS.

Neurological abnormalities
Visual problems are often found in people with DSS. Patients experience optic atrophy due to progressive cranial nerve compression, which may lead to nystagmus or even blindness in severe cases.Other neurological abnormalities include intellectual disability, speech and psychological deterioration. Convulsions and status epilepticus are also present in patients, however the mechanisms for the development of these features are unknown. Patients also experience cranial nerve damage resulting from progressive cranial pressure.

Pathogenesis
DSS is classified as an autosomal recessive disease(OMIM 224300), but it is also identified as an X-linked recessive inheritance in certain families. The total number of genes that are responsible for causing the disease and the correlation between genotype and phenotype remains unclear. Multiple gene mutations were identified in different patients via whole genome sequencing, therefore it is presumed that DSS is genetically heterogeneous.

TCIRG1 mutation
The TCIRG1 gene is present in chromosome locus 11q13, which encodes for the a3 subunit of vacuolar H+ ATPase (V-ATPase) that is unique to osteoclasts. The a3 subunit is responsible in anchoring the vacuolar proton pump to the ruffled membrane of osteoclasts. The V-ATPase is important in mediating the transport of hydrogen ions into the resorption lacunae, which is a pit on the bone surface enclosed by the osteoclast for bone resorption. The accumulation of ions in the lacuna facilitates the decomposition of hydroxyapatite crystals by creating an acidic environment, resulting in bone resorption.

Mutation of the gene results in osteoclast-rich osteopetrosis due to poor translation and altered structure of proton pump structure, which is normally involved in large amounts of osteoclast activity leading to absorption of bone tissue. Mutation of TCIRG1 gene may arise from deletion or gene splicing defects, leading to frame-shifts of the nucleotides of the gene.TCIRG1 mutations illustrate the heterogeneity of DSS through a case study where DSS occurred due to a frameshift mutation, in conjunction with a mutation at an intron located in the gene in one of the alleles of chromosome 11 resulting in a splice site mutation. Despite a frameshift mutation altering the C-terminal of the proton pump, due to increased remnant expression of the wild type transcript, it only resulted in intermediate autosomal recessive DSS due to the partial retainment of vacuolar proton pump function.

TNFRSF11A mutation
The TNFRSF11A gene is present in chromosome locus 18q21.33, which encodes for the receptor activator of NF-κB (RANK). RANK is expressed in immature osteoclasts, which facilitates osteoclasts maturation upon binding of RANK ligand (RANKL). Binding of RANK ligand mediates the RANK/RANKL/OPG signalling pathway. The pathway mediates osteoclast differentiation and activation by promoting differentiation of precursors into multinucleated osteoclasts, and activating osteoclasts, thereby contributing to bone resorption and remodelling. Health conditions related to genetic changes in TNFRSF11A includes osteopetrosis, osteolysis, and Pagets disease of bone.Multiple reports of gene mutations exists underlining the mutation of the exons and introns leading to aberrant splicing. There are five variants to the TNFRSF11A gene which produces five unique protein iso-forms. The effects of alternative splicing on each variants are unclear. However, it is suggested that such changes lead to different expression patterns of the gene in both space and time. Some mutant splicing variants would undergo nonsense-mediated mRNA decay (NMD), while others would not be subjected to NMD, and instead produce a truncated isoform of the RANK protein. The mutated protein has structural defects hence hinders normal function in the signalling pathway, contributing to development of the disease.

SLC29A3 mutation
The SLC29A3 gene is present in chromosome locus10q22.1, which encodes for the equilibrative nucleoside transporter 3 (ENT3), a nucleoside transporter that is present in membranes of mitochondria and lysosomes. ENT3 is responsible for the trafficking of nucleoside, free purines and pyrimidines into the mitochondria and out of lysosomes. Mutations in the gene is often accompanied by histiocytosis-lymphadenopathy plus syndrome, which is characterised by the accumulation of histiocytes leading to lymphadenopathy and other symptoms.Insertion in the coding region was reported in a patient but no records were found in any genetic databanks. Missense mutation was reported to be present in multiple patients and ranked disease-causing by MutationTaster. This insertion mutation is located in the loop within transmembrane helices 1 and 2, while the missense mutations is located in the loop within transmembrane helix 6, 9, and 11.Mutation leads to impaired ENT3 transportation activity, accumulation of nucleotides and nucleoside in lysosomes. As osteoclasts express the SLC29A3 gene, mutation results in incapacitated differentiated osteoclasts ability in demineralising calcium phosphate crystal surfaces, disrupted osteoclastic differentiation, and diminished osteoclast counts. The reduced osteoclast differentiation and activity results in decreased demineralisation and reabsorption of bone structures.

Radiographic features
Whilst some symptoms of DSS can be visually identified, many key symptoms of DSS cannot be identified as such. Therefore, radiographic techniques are required to reach a correct diagnosis for DSS.

Abnormal features of the axial skeleton
Skull
In the skull, sclerosis is predominantly observed in the cranial vault and skull base. Other symptoms displayed in the skull include dental anomalies such as abnormal dentition, hypodontia and impaired tooth calcification; intracranial calcifications, which is the calcification of the brain parenchyma; narrow optic canal and other cranial foramina.

Abnormal features of the appendicular skeleton
Chest
The ribs are sclerotic, truncated, expanded, and featureless. Sclerosis is also present in the sternum, clavicles and scapulae. Pectus carinatum, a chest deformity, is also characteristic of the disease.

Long bones
Sclerosis of epiphyses, diaphyses, and metaphyses with increased radiolucency are key characteristics of the disease. In addition, mottled metaphyseal sclerosis and widening are also present in patients. Development of irregular patchy sclerosis along the bone can also be identified, as well as metaphyseal flaring evolve towards Erlenmeyer flask deformity with nonuniform patches of sclerosis, which are especially prevalent in older patients.The metadiaphyses, a portmanteau of the metaphysis and diaphysis, are bulbous and expanded with bowing and relative radiolucency </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 Polycoria and explain in detail? [/INST] Polycoria is a pathological condition of the eye characterized by more than one pupillary opening in the iris. It may be congenital or result from a disease affecting the iris. It results in decreased function of iris and pupil, affecting the physical eye and visualization.
In the early history of China, double pupils were seen as a sign that a child would become a great king or sage.

Epidemiology
Polycoria is extremely rare, and other conditions are frequently mistaken for it. Polycoria is often congenital, however not diagnosed until adulthood. The general cause of polycoria is unknown, but there are some other eye conditions that are in association with polycoria. These include (although not often) polar cataracts, glaucoma, abnormally long eyelashes, abnormal eye development, and poor vision.There have been cases diagnosed from age 3 to adulthood. The prevalence of true polycoria is minimal. The two kinds of polycoria are true polycoria and false pseudopolycoria.
There are no known or proposed trends in the occurrences of polycoria based on geographical location, age, gender, or season.

True polycoria
In cases of true polycoria, there is an extra pupil that tends to be reactive to light and medication. To be considered true polycoria the extra pupil and the principal pupil must dilate and contract simultaneously with triggers such as light and administered drugs. The extraneous pupil is c. 2.5mm away from the principal pupil. In cases of true polycoria there is an intact sphincter muscle, which contracts and dilates the pupils. In an eye without polycoria, the sphincter muscle is a part of the iris that functions to constrict and dilate the pupil. A patient with true polycoria experiences handicapped vision as well as stimulation of the retina in response to bright lights.It is said that the term "true polycoria" is overused, and used correctly when addressing congenital deformations of the iris. Often "true polycoria" is used when it in fact is a case of pseudopolycoria.

Pseudopolycoria
Although less rare than true polycoria, pseudopolycoria is still very uncommon. In cases of pseudopolycoria there is a "passive constriction" that differentiates the extra pupil from the true pupil during constriction and dilation. The extra pupil in pseudopolycoria is different than the extra pupil in true polycoria because it shows defects that are independent of the sphincter muscles. Pseudopolycoria is often associated with Seckel syndrome, posterior polymorphous dystrophy, and juvenile glaucoma.Pseudopolycoria consists of splitting of the iris that are not contingent with the sphincter muscles at the root of the iris.

Symptoms and diagnosis
When a patient is diagnosed with polycoria, the signs and symptoms shown are associated with ocular and adnexal growth abnormalities. The iris and the pupil become less effective. Signs can be present as a child; however, the patient may be diagnosed later in their life. This condition results in abnormal eye development affecting both eyes or just one.Upon gross examination the patient will typically have excessively long eyelashes. The iris becomes hypoplastic, making abnormally shaped pupils with prominent crypts. The crypts are little squiggly lines that radiate out around the pupil; with this condition, thick round or oval openings can be seen.On diagnosis, signs lead to symptoms where there is more than one set of iris muscles, which controls the amount of light being brought into the eye. When the iris becomes deformed, it will disarrange the control of light coming in leading to blurred vision and finding it hard to visually focus. Polar cataracts will also be present in this condition where a round, opaque malformation of distorted lens fibers is located in the central posterior part of the lens showing disformality. Blindness may also be caused due to damage of the optic nerve from glaucoma.

Treatment
Polycoria has been linked to hereditary genetics, and also associated with polar cataracts, glaucoma, and retinal detachment. Not all cases are treated for this iris abnormality, but when cases are treated the only treatment is surgical procedure and life-long ocular monitoring that is highly recommended. Considerations for surgery are surgical correction, intraocular surgery, and/or reapproximation, as if it was being treated for glaucoma or retinal detachment. Children under the age of 3, who do not seek surgical surgery, have responded well with miotic drops that contained mydriatic/cycloplegic, allowing the separate eye sphincters to dilate and constrict together. This allows improved  balance of uncorrected visual acuity. A 1-mm limbal incisions would be made, a spatula is inserted through the side to elevate the two pupils (avoiding contact with the lens), and the iris tissue would be cut using viscoelastic material. Finally, the limbal incisions were closed with stromal hydration, and intracameral cefuroxime is applied.

Surgical technique
There have been cases where there are various techniques for surgical procedures and can be performed on children and adults. One of the techniques for repair is by using a double armed polypropylene suture, where the suture is left externally on the sclera with a knot buried in the scleral flap. This technique allows posterior fixation of intraocular lens implants in the absence of capsular support. Another technique for surgery is called pupilloplasty, where the patient would be placed under retrobulbar anesthesia with the pupils being dilated with 1% tropicamide.

Prognosis
Postoperative care
Hypertonic saline solution used as eye drops may be used to reduce the corneal edema, the use of anti-glaucomatous topicals to help improve corneal edema, and aqueous suppressants that are accompanied by miotics, include topical beta blockers, alpha antagonists, and carbonic anhydrase inhibitors. Antibiotics and steroid drops for 4 weeks post surgery.

Complications and benefits
Complications of surgical procedures are possible suture erosion through the sclera, conjunctiva, or both. Minor intraocular inflammation during and after surgery. Improved distant and near visual acuity, little defects surrounding sphincter muscles, and normal pupillary margins.

Prevention
There are no known preventive measures for polycoria, however genetic testing may be able to reveal genetic patterns of the disorder. Conditions such as reduced corneal thickness, are observed in people with cases of polycoria, as well as keratoconus (keratoconus is a corneal disease has the possibility of leading to blindness and/or astigmatism) </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 Entomophthoramycosis 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 Alpha-1 antitrypsin deficiency and explain in detail? [/INST] Alpha-1 antitrypsin deficiency (A1AD or AATD) is a genetic disorder that may result in lung disease or liver disease. Onset of lung problems is typically between 20 and 50 years of age. This may result in shortness of breath, wheezing, or an increased risk of lung infections. Complications may include chronic obstructive pulmonary disease (COPD), cirrhosis, neonatal jaundice, or panniculitis.A1AD is due to a mutation in the SERPINA1 gene that results in not enough alpha-1 antitrypsin (A1AT). Risk factors for lung disease include tobacco smoking and environmental dust. The underlying mechanism involves unblocked neutrophil elastase and buildup of abnormal A1AT in the liver. It is autosomal co-dominant, meaning that one defective allele tends to result in milder disease than two defective alleles. The diagnosis is suspected based on symptoms and confirmed by blood tests or genetic tests.Treatment of lung disease may include bronchodilators, inhaled steroids, and, when infections occur, antibiotics. Intravenous infusions of the A1AT protein or in severe disease lung transplantation may also be recommended. In those with severe liver disease liver transplantation may be an option. Avoiding smoking is recommended. Vaccination for influenza, pneumococcus, and hepatitis is also recommended. Life expectancy among those who smoke is 50 years while among those who do not smoke it is almost normal.The condition affects about 1 in 2,500 people of European descent. Severe deficiency occurs in about 1 in 5,000. In Asians it is uncommon. About 3% of people with COPD are believed to have the condition. Alpha-1 antitrypsin deficiency was first described in the 1960s.

Signs and symptoms
Individuals with A1AD may develop chronic obstructive pulmonary disease (emphysema) during their thirties or forties even without a history of smoking, though smoking greatly increases the risk. Symptoms may include shortness of breath (on exertion and later at rest), wheezing, and sputum production. Symptoms may resemble recurrent respiratory infections or asthma.A1AD may cause several manifestations associated with liver disease, which include impaired liver function and cirrhosis. In newborns, alpha-1 antitrypsin deficiency can result in early onset jaundice followed by prolonged jaundice. Between 3% and 5% of children with ZZ mutations develop life-threatening liver disease, including liver failure. A1AD is a leading reason for liver transplantation in newborns. In newborns and children, A1AD may cause jaundice, poor feeding, poor weight gain, hepatomegaly and splenomegaly.

Apart from COPD and chronic liver disease, α1-antitrypsin deficiency has been associated with necrotizing panniculitis (a skin condition) and with granulomatosis with polyangiitis in which inflammation of the blood vessels may affect a number of organs but predominantly the lungs and the kidneys.

Genetics
Serpin peptidase inhibitor, clade A, member 1 (SERPINA1) is the gene that encodes the protein alpha-1 antitrypsin.  SERPINA1 has been localized to chromosome 14q32.  Over 75 mutations of the SERPINA1 gene have been identified, many with clinically significant effects. The most common cause of severe deficiency, PiZ, is a single base-pair substitution leading to a glutamic acid to lysine mutation at position 342 (dbSNP: rs28929474), while PiS is caused by a glutamic acid to valine mutation at position 264 (dbSNP: rs17580). Other rarer forms have been described.

Pathophysiology
A1AT is a glycoprotein mainly produced in the liver by hepatocytes, and, in some quantity, by enterocytes, monocytes, and macrophages. In a healthy lung, it functions as an inhibitor against neutrophil elastase, a neutral serine protease that controls lung elastolytic activity which stimulates mucus secretion and CXCL8 release from epithelial cells that perpetuate the inflammatory state. With A1AT deficiency, neutrophil elastase can disrupt elastin and components of the alveolar wall of the lung that may lead to emphysema, and hypersecretion of mucus can develop chronic bronchitis. Both conditions are the makeup of chronic obstructive pulmonary disease (COPD).Normal blood levels of alpha-1 antitrypsin may vary with analytical method but are typically around 1.0-2.7 g/L.  In individuals with PiSS, PiMZ and PiSZ genotypes, blood levels of A1AT are reduced to between 40 and 60% of normal levels; this is usually sufficient to protect the lungs from the effects of elastase in people who do not smoke. However, in individuals with the PiZZ genotype, A1AT levels are less than 15% of normal, and they are likely to develop panlobular emphysema at a young age. Cigarette smoke is especially harmful to individuals with A1AD. In addition to increasing the inflammatory reaction in the airways, cigarette smoke directly inactivates alpha-1 antitrypsin by oxidizing essential methionine residues to sulfoxide forms, decreasing the enzyme activity by a factor of 2,000.With A1AT deficiency, the pathogenesis of the lung disease is different from that of the liver disease, which is caused by the accumulation of abnormal A1AT proteins in the liver, resulting in liver damage. As such, lung disease and liver disease of A1AT deficiency appear unrelated, and the presence of one does not appear to predict the presence of the other. Between 10 and 15% of people with the PiZZ genotype will develop liver fibrosis or liver cirrhosis, because the A1AT is not secreted properly and therefore accumulates in the liver. The mutant Z form of A1AT protein undergoes inefficient protein folding (a physical process where a protein chain achieves its final conformation). 85 percent of the mutant Z form are unable to be secreted and remain in the hepatocyte.  Nearly all liver disease caused by A1AT is due to the PiZZ genotype, although other genotypes involving different combinations of mutated alleles (compound heterozygotes) may also result in liver disease. A liver biopsy in such cases will reveal PAS-positive, diastase-resistant inclusions within hepatocytes. Unlike glycogen and other mucins which are diastase sensitive (i.e., diastase treatment disables PAS staining), A1AT deficient hepatocytes will stain with PAS even after diastase treatment - a state thus referred to as "diastase resistant". The accumulation of these inclusions or globules is the main cause of liver injury in A1AT deficiency. However, not all individuals with PiZZ genotype develop liver disease (incomplete penetrance), despite the presence of accumulated mutated protein in the liver. Therefore, additional factors (environmental, genetic, etc.) likely influence whether liver disease develops.

Diagnosis
The gold standard of diagnosis for A1AD consists of blood tests to determine the phenotype of the AAT protein or genotype analysis of DNA. Liver biopsy is the gold standard for determining the extent of hepatic fibrosis and assessing for the presence of cirrhosis.A1AT deficiency remains undiagnosed in many patients. Patients are usually labeled as having COPD without an underlying cause. It is estimated that about 1% of all COPD patients actually have an A1AT deficiency. Testing is recommended in those with COPD, unexplained liver disease, unexplained bronchiectasis, granulomatosis with polyangiitis or necrotizing panniculitis. American guidelines recommend that all people with COPD are tested, whereas British guidelines recommend this only in people who develop COPD at a young age with a limited smoking history or with a family history. The initial test performed is serum A1AT level. A low level of A1AT confirms the diagnosis and further assessment with A1AT protein phenotyping and A1AT genotyping should be carried out subsequently.As protein electrophoresis does not completely distinguish between A1AT and other minor proteins at the alpha-1 position (agarose gel), antitrypsin can be more directly and specifically measured using a nephelometric or immunoturbidimetric method. Thus, protein electrophoresis is useful for screening and identifying individuals likely to have a deficiency. A1AT is further analyzed by isoelectric focusing (IEF) in the pH range 4.5-5.5, where the protein migrates in a gel according to its isoelectric point or charge in a pH gradient.
Normal A1AT is termed M, as it migrates toward the center of such an IEF gel. Other variants are less functional and are termed A-L and N-Z, dependent on whether they run proximal or distal to the M band. The presence of deviant bands on IEF can signify the presence of alpha-1 antitrypsin deficiency. Since the number of identified mutations has exceeded the number of letters in the alphabet, subscripts have been added to most recent discoveries in this area, as in the Pittsburgh mutation described above. As every person has two copies of the A1AT gene, a heterozygote with two different copies of the gene may have two different bands showing on electrofocusing, although a heterozygote with one null mutant that abolishes expression of the gene will only show one band. In blood test results, the IEF results are notated as, e.g., PiMM, where Pi stands for protease inhibitor and "MM" is the banding pattern of that person.Other detection methods include use of enzyme-linked-immuno-sorbent-assays in vitro and radial immunodiffusion.
Alpha-1 antitrypsin levels in the blood depend on the genotype. Some mutant forms fail to fold properly and are, thus, targeted for destruction in the proteasome, whereas others have a tendency to polymerize, thereafter being retained in the endoplasmic reticulum. The serum levels of some of the common genotypes are:
PiMM: 100% (normal)
PiMS: 80% of normal serum level of A1AT
PiSS: 60% of normal serum level of A1AT
PiMZ: 60% of normal serum level of A1AT
PiSZ: 40% of normal serum level of A1AT
PiZZ: 10–15% (severe alpha-1 antitrypsin deficiency)

Treatment
Treatment of lung disease may include bronchodilators, inhaled steroids, and, when infections occur, antibiotics. Intravenous infusions of the A1AT protein or in severe disease lung transplantation may also be recommended. In those with severe liver disease liver transplantation may be an option. Avoiding smoking and getting vaccinated for influenza, pneumococcus, and hepatitis is also recommended.People with lung disease due to A1AD may receive intravenous infusions of alpha-1 antitrypsin, derived from donated human plasma. This augmentation therapy is thought to arrest the course of the disease and halt any further damage to the lungs. Long-term studies of the effectiveness of A1AT replacement therapy are not available. It is currently recommended that patients begin augmentation therapy only after the onset of emphysema symptoms. As of 2015 there were four IV augmentation therapy manufacturers in the United States, Canada, and several European countries. IV therapies are the standard mode of augmentation therapy delivery.Liver disease due to A1AD does not include any specific treatment, beyond routine care for chronic liver disease </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 Taurodontism and explain in detail? [/INST] Taurodontism is defined as the enlargement of pulp chambers with the furcation area being displaced toward the apex of the root. It cannot be diagnosed clinically and requires radiographic visualization since the crown of a taurodontic tooth appears normal and its distinguishing features are present below the alveolar margin. Taurodontism can present in deciduous or permanent dentition, unilaterally or bilaterally, but is most common in the permanent molar teeth of humans. The underlying mechanism of taurodontism is the failure or late invagination of Hertwigs epithelial root sheath, which leads an apical shift of the root furcation.

Classification
The term was coined by Sir Arthur Keith. It comes from the Latin taurus meaning "bull" and the Greek ὀδούς (odous), genitive singular ὀδόντος (odontos) meaning "tooth", to indicate the similarity of these teeth to those of hoofed/ungulates, or cud-chewing animals.Radiographic characteristics of taurodontism include:

lack of pulp chamber constriction at the cementoenamel junction (CEJ);
an enlarged pulp chamber that appears rectangular in shape; and
displacement of the pulp chamber floor toward the root apex, shortening the roots and root canals.Earlier classification systems considered only the apical displacement of the pulp chamber floor; whereas, later systems additionally consider the position of the pulp chamber in relation to the cemento-enamel junction and alveolar margin.

Shaw 1928
One of the first attempts to classify taurodontism was made by C.J.Shaw. He used the apical displacement of the pulp chamber floor to classify taurodontism into four distinct categories: cynodont (normal), hypotaurodont, hypertaurodont, and mesotaurodont.

Shifman & Chanannel 1978
Later, Shifman & Chanannel quantified the degree of taurodontism based on a mathematical formula relating the anatomical landmarks as shown in the figure above </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 Sinus pericranii and explain in detail? [/INST] Sinus pericranii (SP) is a rare disorder characterized by a congenital (or occasionally, acquired) epicranial venous malformation of the scalp </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 Inhalant and explain in detail? [/INST] Inhalants are a broad range of household and industrial chemicals whose volatile vapors or pressurized gases can be concentrated and breathed in via the nose or mouth to produce intoxication, in a manner not intended by the manufacturer. They are inhaled at room temperature through volatilization (in the case of gasoline or acetone) or from a pressurized container (e.g., nitrous oxide or butane), and do not include drugs that are sniffed after burning or heating. For example, amyl nitrite (poppers), nitrous oxide and toluene – a solvent widely used in contact cement, permanent markers, and certain types of glue – are considered inhalants, but smoking tobacco, cannabis, and crack are not, even though these drugs are inhaled as smoke or vapor.While a few inhalants are prescribed by medical professionals and used for medical purposes, as in the case of inhaled anesthetics and nitrous oxide (an anxiolytic and pain relief agent prescribed by dentists), this article focuses on inhalant use of household and industrial propellants, glues, fuels, and other products in a manner not intended by the manufacturer, to produce intoxication or other psychoactive effects. These products are used as recreational drugs for their intoxicating effect. According to a 1995 report by the National Institute on Drug Abuse, the most serious inhalant use occurs among homeless children and teenagers who "... live on the streets completely without family ties." Inhalants are the only substance used more by younger teenagers than by older teenagers. Inhalant users inhale vapor or aerosol propellant gases using plastic bags held over the mouth or by breathing from a solvent-soaked rag or an open container. The practices are known colloquially as "sniffing", "huffing" or "bagging".
The effects of inhalants range from an alcohol-like intoxication and intense euphoria to vivid hallucinations, depending on the substance and the dose. Some inhalant users are injured due to the harmful effects of the solvents or gases or due to other chemicals used in the products that they are inhaling. As with any recreational drug, users can be injured due to dangerous behavior while they are intoxicated, such as driving under the influence. In some cases, users have died from hypoxia (lack of oxygen), pneumonia, heart failure or arrest, or aspiration of vomit. Brain damage is typically seen with chronic long-term use of solvents as opposed to short-term exposure.Even though many inhalants are legal, there have been legal actions taken in some jurisdictions to limit access by minors. While solvent glue is normally a legal product, a Scottish court has ruled that supplying glue to children is illegal if the store knows the children intend to inhale the glue. In the US, thirty-eight of 50 states have enacted laws making various inhalants unavailable to those under the age of 18 or making inhalant use illegal.

Classification
Inhalants can be classified by the intended function. Most inhalant drugs that are used non-medically are ingredients in household or industrial chemical products that are not intended to be concentrated and inhaled. A small number of recreational inhalant drugs are pharmaceutical products that are used illicitly.

Product category
Another way to categorize inhalants is by their product category. There are three main product categories: solvents; gases; and medical drugs which are used illicitly.

Solvents
A wide range of volatile solvents intended for household or industrial use are inhaled as recreational drugs. This includes petroleum products (gasoline and kerosene), toluene (used in paint thinner, permanent markers, contact cement and model glue), and acetone (used in nail polish remover). These solvents vaporize at room temperature. Ethanol (the alcohol which is normally drunk) is sometimes inhaled, but this cannot be done at room temperature. The ethanol must be converted from liquid into gaseous state (vapor) or aerosol (mist), in some cases using a nebulizer, a machine that agitates the liquid into an aerosol. The sale of nebulizers for inhaling ethanol was banned in some US states due to safety concerns.

Gases
A number of gases intended for household or industrial use are inhaled as recreational drugs. This includes chlorofluorocarbons used in aerosols and propellants (e.g., aerosol hair spray, aerosol deodorant). A gas used as a propellant in whipped cream aerosol containers, nitrous oxide, is used as a recreational drug. Pressurized canisters of propane and butane gas, both of which are intended for use as fuels, are used as inhalants.

Medical anesthetics
Several medical anesthetics are used as recreational drugs, including diethyl ether (a drug that is no longer used medically, due to its high flammability and the development of safer alternatives) and nitrous oxide, which is widely used in the 2010s by dentists as an anti-anxiety drug during dental procedures. Diethyl ether has a long history of use as a recreational drug. The effects of ether intoxication are similar to those of alcohol intoxication, but more potent. Also, due to NMDA antagonism, the user may experience all the psychedelic effects present in classical dissociatives such as ketamine in forms of thought loops and the feeling of the mind being disconnected from ones body. Nitrous oxide is a dental anesthetic that is used as a recreational drug, either by users who have access to medical-grade gas canisters (e.g., dental hygienists or dentists) or by using the gas contained in whipped cream aerosol containers. Nitrous oxide inhalation can cause pain relief, depersonalisation, derealisation, dizziness, euphoria, and some sound distortion.

Classification by effect
It is also possible to classify inhalants by the effect they have on the body. Some solvents act as depressants, causing users to feel relaxed or drowsy while others act as stimulants. Many inhalants act primarily as asphyxiant gases, with their primary effect due to oxygen deprivation. Nitrous oxide can be categorized as a dissociative drug, as it can cause visual and auditory hallucinations. Other agents may have more direct effects at receptors, as inhalants exhibit a variety of mechanisms of action. The mechanisms of action of many non-medical inhalants have not been well elucidated. Anesthetic gases used for surgery, such as nitrous oxide or enflurane, are believed to induce anesthesia primarily by acting as NMDA receptor antagonists, open-channel blockers that bind to the inside of the calcium channels on the outer surface of the neuron, and provide high levels of NMDA receptor blockade for a short period of time.
This makes inhaled anesthetic gases different from other NMDA antagonists, such as ketamine, which bind to a regulatory site on the NMDA-sensitive calcium transporter complex and provide slightly lower levels of NMDA blockade, but for a longer and much more predictable duration. This makes a deeper level of anesthesia achievable more easily using anesthetic gases but can also make them more dangerous than other drugs used for this purpose.

Chemical structure
Inhalants can also be classified by chemical structure. Classes include:

Administration and effects
Inhalant users inhale vapors or aerosol propellant gases using plastic bags held over the mouth or by breathing from an open container of solvents, such as gasoline or paint thinner. Nitrous oxide gases from whipped cream aerosol cans, aerosol hairspray or non-stick frying spray are sprayed into plastic bags. Some nitrous oxide users spray the gas into balloons. When inhaling non-stick cooking spray or other aerosol products, some users may filter the aerosolized particles out with a rag. Some gases, such as propane and butane gases, are inhaled directly from the canister. Once these solvents or gases are inhaled, the extensive capillary surface of the lungs rapidly absorb the solvent or gas, and blood levels peak rapidly. The intoxication effects occur so quickly that the effects of inhalation can resemble the intensity of effects produced by intravenous injection of other psychoactive drugs.Ethanol is also inhaled, either by vaporizing it by pouring it over dry ice in a narrow container and inhaling with a straw or by pouring alcohol in a corked bottle with a pipe, and then using a bicycle pump to make a spray. Alcohol can be vaporized using a simple container and open-flame heater. Medical devices such as asthma nebulizers and inhalers were also reported as means of application. The practice gained popularity in 2004, with the marketing of the device dubbed AWOL (Alcohol without liquid), a play on the military term AWOL (Absent Without Leave). AWOL, created by British businessman Dominic Simler, was first introduced in Asia and Europe, and then in the United States in August 2004. AWOL was used by nightclubs, at gatherings and parties, and it garnered attraction as a novelty, as people enjoyed passing it around in a group. AWOL uses a nebulizer, a machine that agitates the liquid into an aerosol. AWOLs official website states that "AWOL and AWOL 1 are powered by Electrical Air Compressors while AWOL 2 and AWOL 3 are powered by electrical oxygen generators", which refer to a couple of mechanisms used by the nebulizer drug delivery device for inhalation. Although the AWOL machine is marketed as having no downsides, such as the lack of calories or hangovers, Amanda Shaffer of Slate describes these claims as "dubious at best". Although inhaled alcohol does reduce the caloric content, the savings are minimal. After expressed safety and health concerns, sale or use of AWOL machines was banned in a number of American states.The effects of solvent intoxication can vary widely depending on the dose and what type of solvent or gas is inhaled. A person who has inhaled a small amount of rubber cement or paint thinner vapor may be impaired in a manner resembling alcohol inebriation. A person who has inhaled a larger quantity of solvents or gases, or a stronger chemical, may experience stronger effects such as distortion in perceptions of time and space, hallucinations, and emotional disturbances. The effects of inhalant use are also modified by the combined use of inhalants and alcohol or other drugs.
In the short term, many users experience headaches, nausea and vomiting, slurred speech, loss of motor coordination, and wheezing. A characteristic "glue sniffers rash" around the nose and mouth is sometimes seen after prolonged use. An odor of paint or solvents on clothes, skin, and breath is sometimes a sign of inhalant abuse, and paint or solvent residues can sometimes emerge in sweat.According to NIH, even a single session of inhalant use "can disrupt heart rhythms and lower oxygen levels", which can lead to death. "Regular abuse can result in serious harm to the brain, heart, kidneys, and liver."

Dangers and health problems
Statistics on deaths caused by heavy inhalant use are difficult to determine. It may be severely under-reported because death is often attributed to a discrete event such as a stroke or a heart attack, even if the event happened because of inhalant use. Inhalant use was mentioned on 144 death certificates in Texas during the period 1988–1998 and was reported in 39 deaths in Virginia between 1987 and 1996 from acute voluntary exposure to used inhalants.

General risks
Regardless of which inhalant is used, inhaling vapors or gases can lead to injury or death. One major risk is hypoxia (lack of oxygen), which can occur due to inhaling fumes from a plastic bag, or from using proper inhalation mask equipment (e.g., a medical mask for nitrous oxide) but not adding oxygen or room air. Another danger is freezing the throat. When a gas that was stored under high pressure is released, it cools abruptly and can cause frostbite if it is inhaled directly from the container. This can occur, for example, with inhaling nitrous oxide. When nitrous oxide is used as an automotive power adder, its cooling effect is used to make the fuel-air charge denser. In a person, this effect is potentially lethal. Many inhalants are volatile organic chemicals and can catch fire or explode, especially when combined with smoking. As with many other drugs, users may also injure themselves due to loss of coordination or impaired judgment, especially if they attempt to operate machinery.
Solvents have many potential risks in common, including pneumonia, cardiac failure or arrest, and aspiration of vomit. The inhaling of some solvents can cause hearing loss, limb spasms, and damage to the central nervous system and brain. Serious but potentially reversible effects include liver and kidney damage and blood-oxygen depletion. Death from inhalants is generally caused by a very high concentration of fumes. Deliberately inhaling solvents from an attached paper or plastic bag or in a closed area greatly increases the chances of suffocation. Brain damage is typically seen with chronic long-term use as opposed to short-term exposure. Parkinsonism (see: Signs and symptoms of Parkinsons disease) has been associated with huffing.

Female inhalant users who are pregnant may have adverse effects on the fetus, and the baby may be smaller when it is born and may need additional health care (similar to those seen with alcohol – fetal alcohol syndrome). There is some evidence of birth defects and disabilities in babies born to women who sniffed solvents such as gasoline.
In the short term, death from solvent use occurs most commonly from aspiration of vomit while unconscious or from a combination of respiratory depression and hypoxia, the second cause being especially a risk with heavier-than-air vapors such as butane or gasoline vapor. Deaths typically occur from complications related to excessive sedation and vomiting. Actual overdose from the drug does occur, however, and inhaled solvent use is statistically more likely to result in life-threatening respiratory depression than intravenous use of opioids such as heroin. Most deaths from solvent use could be prevented if individuals were resuscitated quickly when they stopped breathing and their airway cleared if they vomited. However, most inhalant use takes place when people inhale solvents by themselves or in groups of people who are intoxicated. Certain solvents are more hazardous than others, such as gasoline.
In contrast, a few inhalants like amyl nitrate and diethyl ether have medical applications and are not toxic in the same sense as solvents, though they can still be dangerous when used recreationally. Nitrous oxide is thought to be particularly non-toxic, though heavy long-term use can lead to a variety of serious health problems linked to destruction of vitamin B12 and folic acid.

Risks of specific agents
The hypoxic effect of inhalants can cause damage to many organ systems (particularly the brain, which has a very low tolerance for oxygen deprivation), but there can also be additional toxicity resulting from either the physical properties of the compound itself or additional ingredients present in a product. Organochlorine solvents are particularly hazardous; many of these are now restricted in developed countries due to their environmental impact.

Methylene chloride, after being metabolized, can cause carbon monoxide poisoning.
Gasoline sniffing can cause lead poisoning, in locations where leaded gas is not banned.
Ingestion of alkyl nitrites can cause methemoglobinemia, and by inhalation it has not been ruled out.
Carbon tetrachloride can cause significant damage to multiple systems, but its association with liver damage is so strong that it is used in animal models to induce liver injury.
Use of butane, propane, nitrous oxide and other inhalants can create a risk of freezing burns from contact with the extremely cold liquid (See aerosol burn). The risk of such contact is greatly increased by the impaired judgement and motor coordination brought on by inhalant intoxication.
Benzene use can cause bone marrow depression. It is also a known carcinogen.
Toluene can damage myelin.Toxicity may also result from the pharmacological properties of the drug; excess NMDA antagonism can completely block calcium influx into neurons and provoke cell death through apoptosis, although this is more likely to be a long-term result of chronic solvent use than a consequence of short-term use.

Sudden sniffing death syndrome
Sudden sniffing death syndrome is commonly known as SSDS.
Inhaling butane gas can cause drowsiness, unconsciousness, asphyxia, and cardiac arrhythmia. Butane is the most commonly misused volatile solvent in the UK and caused 52% of solvent-related deaths in 2000. When butane is sprayed directly into the throat, the jet of fluid can cool rapidly to −20 °C by adiabatic expansion, causing prolonged laryngospasm.Some inhalants can also indirectly cause sudden death by cardiac arrest, in a syndrome known as "sudden sniffing death". The anaesthetic gases present in the inhalants appear to sensitize the user to adrenaline and, in this state, a sudden surge of adrenaline (e.g., from a frightening hallucination or run-in with aggressors), may cause fatal cardiac arrhythmia.Furthermore, the inhalation of any gas that is capable of displacing oxygen in the lungs (especially gases heavier than oxygen) carries the risk of hypoxia as a result of the very mechanism by which breathing is triggered. Since reflexive breathing is prompted by elevated carbon dioxide levels (rather than diminished blood oxygen levels), breathing a concentrated, relatively inert gas (such as computer-duster tetrafluoroethane or nitrous oxide) that removes carbon dioxide from the blood without replacing it with oxygen will produce no outward signs of suffocation even when the brain is experiencing hypoxia. Once full symptoms of hypoxia appear, it may be too late to breathe without assistance, especially if the gas is heavy enough to lodge in the lungs for extended periods. Even completely inert gases, such as argon, can have this effect if oxygen is largely excluded.

Legal aspects
Solvent glue
Even though solvent glue is normally a legal product, there is a case where a court has ruled that supplying glue to children is illegal. Khaliq v HM Advocate was a Scottish criminal case decided by the High Court of Justiciary on appeal, in which it was decided that it was an offense at common law to supply glue-sniffing materials that were otherwise legal in the knowledge that they would be used recreationally by children. Two shopkeepers in Glasgow were arrested and charged with supplying to children "glue-sniffing kits" consisting of a quantity of petroleum-based glue in a plastic bag. They argued there was nothing illegal about the items that they had supplied. On appeal, the High Court took the view that, even though glue and plastic bags might be perfectly legal, everyday items, the two shopkeepers knew perfectly well that the children were going to use the articles as inhalants and the charge on the indictment should stand. When the case came to trial at Glasgow High Court the two were sentenced to three years imprisonment.
"Thirty-eight of 50 [US] states have enacted laws making various inhalants unavailable to those under the age of 18. Other states prohibit the sale of these items to anyone without recognition of purpose for the purchase. Some states mandate laws against using these products for purposes of getting high, while some states have laws about possessing certain inhalants. Nearly every state imposes fines and jail terms for violation of their specific laws.""Connecticut law bans the unauthorized manufacture or compounding, possession, control, sale, delivery, or administration of any "restricted substance". It defines restricted substances as... specific volatile substances if they are sold, compounded, possessed or controlled, or delivered or administered to another person for breathing, inhaling, sniffing, or drinking to induce a stimulant, depressant, or hallucinogenic effect. Violators can be fined up to $100." As well, 24 states "ban the use, possession, or sale or other distribution of inhalants... like glue and solvents.""Louisiana prohibits the sale, transfer, or possession of model glue and inhalable toluene substances to minors. In Ohio, it is illegal to inhale certain compounds for intoxication—a common, general prohibition other states have enacted.
Some states draw their prohibitions more narrowly... In Massachusetts, retailers must ask minors for identification before selling them glue or cement that contains a solvent that can release toxic vapors."

Propellant gases
"New Jersey... prohibits selling or offering to sell minors products containing chlorofluorocarbon that is used in refrigerant."

Poppers
The sale of alkyl nitrite-based poppers was banned in Canada in 2013. Although not considered a narcotic and not illegal to possess or use, they are considered a drug. Sales that are not authorized can now be punished with fines and prison. Since 2007, reformulated poppers containing isopropyl nitrite are sold in Europe because only isobutyl nitrite is prohibited. In France, the sale of products containing butyl nitrite, pentyl nitrite, or isomers thereof, has been prohibited since 1990 on grounds of danger to consumers. In 2007, the government extended this prohibition to all alkyl nitrites that were not authorized for sale as drugs. After litigation by sex shop owners, this extension was quashed by the Council of State on the grounds that the government had failed to justify such a blanket prohibition: according to the court, the risks cited, concerning rare accidents often following abnormal usage, rather justified compulsory warnings on the packaging.In the United Kingdom, poppers are widely available and frequently (legally) sold in gay clubs/bars, sex shops, drug paraphernalia head shops, over the Internet and on markets. It is illegal under Medicines Act 1968 to sell them advertised for human consumption, and to bypass this, they are usually sold as odorizers. In the U.S., originally marketed as a prescription drug in 1937, amyl nitrite remained so until 1960, when the Food and Drug Administration removed the prescription requirement due to its safety record. This requirement was reinstated in 1969, after observation of an increase in recreational use. Other alkyl nitrites were outlawed in the U.S. by Congress through the Anti-Drug Abuse Act of 1988. The law includes an exception for commercial purposes. The term commercial purpose is defined to mean any use other than for the production of consumer products containing volatile alkyl nitrites meant for inhaling or otherwise introducing volatile alkyl nitrites into the human body for euphoric or physical effects. The law came into effect in 1990. Visits to retail outlets selling these products reveal that some manufacturers have since reformulated their products to abide by the regulations, through the use of the legal cyclohexyl nitrite as the primary ingredient in their products, which are sold as video head cleaners, polish removers, or room odorants.

Nitrous oxide
In the United States, possession of nitrous oxide is legal under federal law and is not subject to DEA purview. It is, however, regulated by the Food and Drug Administration under the Food Drug and Cosmetics Act; prosecution is possible under its "misbranding" clauses, prohibiting the sale or distribution of nitrous oxide for the purpose of human consumption as a recreational drug. Many states have laws regulating the possession, sale, and distribution of nitrous oxide. Such laws usually ban distribution to minors or limit the amount of nitrous oxide that may be sold without a special license. For example, in the state of California, possession for recreational use is prohibited and qualifies as a misdemeanor. In New Zealand, the Ministry of Health has warned that nitrous oxide is a prescription medicine, and its sale or possession without a prescription is an offense under the Medicines Act. This statement would seemingly prohibit all non-medicinal uses of the chemical, though it is implied that only recreational use will be legally targeted. In India, for general anesthesia purposes, nitrous oxide is available as Nitrous Oxide IP. Indias gas cylinder rules (1985) permit the transfer of gas from one cylinder to another for breathing purposes. Because Indias Food & Drug Authority (FDA-India) rules state that transferring a drug from one container to another (refilling) is equivalent to manufacturing, anyone found doing so must possess a drug manufacturing license.

Patterns of non-medical use
Inhalant drugs are often used by children, teenagers, incarcerated or institutionalized people, and impoverished people, because these solvents and gases are ingredients in hundreds of legally available, inexpensive products, such as deodorant sprays, hair spray, contact cement and aerosol air fresheners. However, most users tend to be "... adolescents (between the ages of 12 and 17)." In some countries, chronic, heavy inhalant use is concentrated in marginalized, impoverished communities. Young people who become used to heavy amounts of inhalants chronically are also more likely to be those who are isolated from their families and community. The article "Epidemiology of Inhalant Abuse: An International Perspective" notes that "[t]he most serious form of obsession with inhalant use probably occurs in countries other than the United States where young children live on the streets completely without family ties. These groups almost always use inhalants at very high levels (Leal et al. 1978). This isolation can make it harder to keep in touch with the sniffer and encourage him or her to stop sniffing."The article also states that "... high [inhalant use] rates among barrio Hispanics almost undoubtedly are related to the poverty, lack of opportunity, and social dysfunction that occur in barrios" and states that the "... same general tendency appears for Native-American youth" because "... Indian reservations are among the most disadvantaged environments in the United States; there are high rates of unemployment, little opportunity, and high rates of alcoholism and other health problems." There are a wide range of social problems associated with inhalant use, such as feelings of distress, anxiety and grief for the community; violence and damage to property; violent crime; stresses on the juvenile justice system; and stresses on youth agencies and support services.

Africa and Asia
Glue and gasoline (petrol) sniffing is also a problem in parts of Africa, especially with street children. In India and South Asia, three of the most widely used inhalants are the Dendrite brand and other forms of contact adhesives and rubber cement manufactured in Kolkata, and toluenes in paint thinners. Genkem is a brand of glue, which had become the generic name for all the glues used by glue-sniffing children in Africa before the manufacturer replaced n-hexane in its ingredients in 2000.The United Nations Office on Drugs and Crime has reported that glue sniffing is at the core of "street culture" in Nairobi, Kenya, and that the majority of street children in the city are habitual solvent users. Research conducted by Cottrell-Boyce for the African Journal of Drug and Alcohol Studies found that glue sniffing amongst Kenyan street children was primarily functional – dulling the senses against the hardship of life on the street – but it also provided a link to the support structure of the "street family" as a potent symbol of shared experience.Similar incidents of glue sniffing among destitute youth in the Philippines have also been reported, most commonly from groups of street children and teenagers collectively known as "Rugby" boys, which were named after a brand of toluene-laden contact cement. Other toluene-containing substances have also been used, most notably the Vulca Seal brand of roof sealants. Bostik Philippines, which currently owns the Rugby and Vulca Seal brands, has since responded to the issue by adding bitterants such as mustard oil to their Rugby line, as well as reformulating it by replacing toluene with xylene. Several other manufacturers have also followed suit.
Another very common inhalant is Erase-X, a correction fluid that contains toluene. It has become very common for school and college students to use it, because it is easily available in stationery shops in India. This fluid is also used by street and working children in Delhi.

Europe and North America
In the UK, marginalized youth use a number of inhalants, such as solvents and propellants. In Russia and Eastern Europe, gasoline sniffing became common on Russian ships following attempts to limit the supply of alcohol to ship crews in the 1980s. The documentary Children Underground depicts the huffing of a solvent called Aurolac (a product used in chroming) by Romanian homeless children. During the Interbellum the inhalation of ether (etheromania) was widespread in some regions of Poland, especially in Upper Silesia—tens of thousands of people were affected by this problem.In Canada, Native children in the isolated Northern Labrador community of Davis Inlet were the focus of national concern in 1993, when many were found to be sniffing gasoline. The Canadian and provincial Newfoundland and Labrador governments intervened on a number of occasions, sending many children away for treatment. Despite being moved to the new community of Natuashish in 2002, serious inhalant use problems have continued. Similar problems were reported in Sheshatshiu in 2000 and also in Pikangikum First Nation. In 2012, the issue once again made the news media in Canada. In Mexico, the inhaling of a mixture of gasoline and industrial solvents, known locally as "Activo" or "Chemo", has risen in popularity among the homeless and among the street children of Mexico City in recent years. The mixture is poured onto a handkerchief and inhaled while held in ones fist.
In the US, ether was used as a recreational drug during the 1930s Prohibition era, when alcohol was made illegal. Ether was either sniffed or drunk and, in some towns, replaced alcohol entirely. However, the risk of death from excessive sedation or overdose is greater than that with alcohol, and ether drinking is associated with damage to the stomach and gastrointestinal tract. Use of glue, paint and gasoline became more common after the 1950s. Model airplane glue-sniffing as problematic behavior among youth was first reported in 1959 and increased in the 1960s. Use of aerosol sprays became more common in the 1980s, as older propellants such as CFCs were phased out and replaced by more environmentally friendly compounds such as propane and butane. Most inhalant solvents and gases are not regulated under drug laws such as the United States Controlled Substances Act. However, many US states and Canadian cities have placed restrictions on the sale of some solvent-containing products to minors, particularly for products widely associated with sniffing, such as model cement. The practice of inhaling such substances is sometimes colloquially referred to as huffing, sniffing (or glue sniffing), dusting, or chroming.

Australia
Australia has long faced a petrol (gasoline) sniffing problem in isolated and impoverished aboriginal communities. Although some sources argue that sniffing was introduced by United States servicemen stationed in the nations Top End during World War II or through experimentation by 1940s-era Cobourg Peninsula sawmill workers, other sources claim that inhalant abuse (such as glue inhalation) emerged in Australia in the late 1960s. Chronic, heavy petrol sniffing appears to occur among remote, impoverished indigenous communities, where the ready accessibility of petrol has helped to make it a common addictive substance.
In Australia, petrol sniffing now occurs widely throughout remote Aboriginal communities in the Northern Territory, Western Australia, northern parts of South Australia, and Queensland. The number of people sniffing petrol goes up and down over time as young people experiment or sniff occasionally. "Boss", or chronic, sniffers may move in and out of communities; they are often responsible for encouraging young people to take it up.A 1983 survey of 4,165 secondary students in New South Wales showed that solvents and aerosols ranked just after analgesics (e.g., codeine pills) and alcohol for drugs that were inappropriately used. This 1983 study did not find any common usage patterns or social class factors. The causes of death for inhalant users in Australia included pneumonia, cardiac failure/arrest, aspiration of vomit, and burns. In 1985, there were 14 communities in Central Australia reporting young people sniffing. In July 1997, it was estimated that there were around 200 young people sniffing petrol across 10 communities in Central Australia. Approximately 40 were classified as chronic sniffers. There have been reports of young Aboriginal people sniffing petrol in the urban areas around Darwin and Alice Springs.
In 2005, the Government of Australia and BP Australia began the usage of opal fuel in remote areas prone to petrol sniffing. Opal is a non-sniffable fuel (which is much less likely to cause a high) and has made a difference in some indigenous communities.

In popular culture
Music and musical culture
One of the early musical references to inhalant use occurs in the 1974 Elton John song "The Bitch Is Back", in the line "I get high in the evening sniffing pots of glue." Inhalant use, especially glue-sniffing, is widely associated with the late-1970s punk youth subculture in the UK and North America. Raymond Cochrane and Douglas Carroll claim that when glue sniffing became widespread in the late 1970s, it was "adopted by punks because public [negative] perceptions of sniffing fitted in with their self-image" as rebels against societal values. While punks at first used inhalants "experimentally and as a cheap high, adult disgust and hostility [to the practice] encouraged punks to use glue sniffing as a way of shocking society." As well, using inhalants was a way of expressing their anti-corporatist DIY (do it yourself) credo; by using inexpensive household products as inhalants, punks did not have to purchase industrially manufactured liquor or beer.

One history of the punk subculture argues that "substance abuse was often referred to in the music and did become synonymous with the genre, glue-sniffing especially" because the youths "faith in the future had died and that the youth just didnt care anymore" due to the "awareness of the threat of nuclear war and a pervasive sense of doom." In a BBC interview with a person who was a punk in the late 1970s, they said that "there was a real fear of imminent nuclear war—people were sniffing glue knowing that it could kill them, but they didnt care because they believed that very soon everybody would be dead anyway."
A number of 1970s punk rock and 1980s hardcore punk songs refer to inhalant use. The Ramones, an influential early US punk band, referred to inhalant use in several of their songs. The song "Now I Wanna Sniff Some Glue" describes adolescent boredom, and the song "Carbona not Glue" states, "My brain is stuck from shooting glue." An influential punk fanzine about the subculture and music took its name (Sniffin Glue) from the Ramones song. The 1980s punk band The Dead Milkmen wrote a song, "Life is Shit" from their album Beelzebubba, about two friends hallucinating after sniffing glue. Punk-band-turned-hip-hop group the Beastie Boys penned a song "Hold it Now – Hit It", which includes the line "cause Im beer drinkin, breath stinkin, sniffing glue." Their song "Shake Your Rump" includes the lines, "Should I have another sip no skip it/In the back of the ride and bust with the whippits". Pop punk band Sum 41 wrote a song, "Fat Lip", which refers to a character who does not "make sense from all the gas you be huffing..." The song Lança-perfume, written and performed by Brazilian pop star Rita Lee, became a national hit in 1980. The song is about chloroethane and its widespread recreational sale and use during the rise of Brazils carnivals.
Inhalants are referred to by bands from other genres, including several grunge bands—an early 1990s genre that was influenced by punk rock. The 1990s grunge band Nirvana, which was influenced by punk music, penned a song, "Dumb", in which Kurt Cobain sings "my heart is broke / But I have some glue/help me inhale / And mend it with you". L7, an all-female grunge band, penned a song titled "Scrap" about a skinhead who inhales spray-paint fumes until his mind "starts to gel". Also in the 1990s, the Britpop band Suede had a UK hit with their song "Animal Nitrate" whose title is a thinly veiled reference to amyl nitrite. The Beck song "Fume" from his "Fresh Meat and Old Slabs" release is about inhaling nitrous oxide. Another Beck song, "Cold Ass Fashion", contains the line "O.G. – Original Gluesniffer!" Primuss 1998 song "Lacquer Head" is about adolescents who use inhalants to get high. Hip hop performer Eminem wrote a song, "Bad Meets Evil", which refers to breathing "... ether in three lethal amounts." The Brian Jonestown Massacre, a retro-rock band from the 1990s, has a song "Hyperventilation", which is about sniffing model-airplane cement. Frank Zappas song "Teenage Wind" from 1981 has a reference to glue sniffing: "Nothing left to do but get out the ol glue; Parents, parents; Sniff it good now..."

Films
A number of films have depicted or referred to the use of solvent inhalants. In the 1980 comedy film Airplane!, the character of McCroskey (Lloyd Bridges) refers to his inhalant use when he states, "I picked the wrong week to quit sniffing glue." In the 1996 film Citizen Ruth, the character Ruth (Laura Dern), a homeless drifter, is depicted inhaling patio sealant from a paper bag in an alleyway. In the tragicomedy Love Liza, the main character, played by Philip Seymour Hoffman, plays a man who takes up building remote-controlled airplanes as a hobby to give him an excuse to sniff the fuel in the wake of his wifes suicide.
Harmony Korines 1997 Gummo depicts adolescent boys inhaling contact cement for a high. Edet Belzbergs 2001 documentary Children Underground chronicles the lives of Romanian street children addicted to inhaling paint. In The Basketball Diaries, a group of boys is huffing carbona cleaning liquid at 3 minutes and 27 seconds into the movie; further on, a boy is reading a diary describing the experience of sniffing the cleaning liquid.
In the David Lynch film Blue Velvet, the bizarre and manipulative character played by Dennis Hopper uses a mask to inhale amyl nitrite. In Little Shop of Horrors, Steve Martins character dies from nitrous oxide inhalation. The 1999 independent film Boys Dont Cry depicts two young low-income women inhaling aerosol computer cleaner (compressed gas) for a buzz. In The Cider House Rules, Michael Caines character is addicted to inhaling ether vapors.
In Thirteen, the main character, a teen, uses a can of aerosol computer cleaner to get high. In the action movie Shooter, an ex-serviceman on the run from the law (Mark Wahlberg) inhales nitrous oxide gas from a number of Whip-It! whipped cream canisters until he becomes unconscious. The South African film The Wooden Camera also depicts the use of inhalants by one of the main characters, a homeless teen, and their use in terms of socio-economic stratification. The title characters in Samson and Delilah sniff petrol; in Samsons case, possibly causing brain damage.
In the 2004 film Taxi, Queen Latifah and Jimmy Fallon are trapped in a room with a burst tank containing nitrous oxide. Queen Latifahs character curses at Fallon while they both laugh hysterically. Fallons character asks if it is possible to die from nitrous oxide, to which Queen Latifahs character responds with "Its laughing gas, stupid!" Neither of them had any side effects other than their voices becoming much deeper while in the room.
In the French horror film Them, (2006) a French couple living in Romania are pursued by a gang of street children who break into their home at night. Olivia Bonamys character is later tortured and forced to inhale aurolac from a silver-colored bag. During a flashback scene in the 2001 film Hannibal, Hannibal Lecter gets Mason Verger high on amyl nitrite poppers, then convinces Verger to cut off his own face and feed it to his dogs.

Books
The science fiction story "Waterspider" by Philip K. Dick (first published in January 1964 in If magazine) contains a scene in which characters from the future are discussing the culture of the early 1950s. One character says: "You mean he sniffed what they called airplane dope? He was a glue-sniffer?", to which another character replies: "Hardly. That was a mania among adolescents and did not become widespread in fact until a decade later. No, I am speaking about imbibing alcohol."The book Fear and Loathing in Las Vegas describes how the two main characters inhale diethyl ether and amyl nitrite.

Television
In the comedy series Newman and Baddiel in Pieces, Rob Newmans inhaling gas from a foghorn was a running joke in the series. One episode of the Jeremy Kyle Show featured a woman with a 20-year butane gas addiction. In the series Its Always Sunny in Philadelphia, Charlie Kelly has an addiction to huffing glue. Additionally, season nine episode 8 shows Dennis, Mac, and Dee getting a can of gasoline to use as a solvent, but instead end up taking turns huffing from the canister.
A 2008 episode of the reality show Intervention (season 5, episode 9) featured Allison, who was addicted to huffing computer duster for the short-lived, psychoactive effects. Allison has since achieved a small but significant cult following among bloggers and YouTube users. Several remixes of scenes from Allisons episode can be found online. Since 2009, Allison has worked with drug and alcohol treatment centers in Los Angeles County. In the third episode of season 5 of American Dad!, titled "Home Adrone", Roger asks an airline stewardess to bring him industrial adhesive and a plastic bag. In the seventh episode of the fourteenth season of South Park, Towelie, an anthropomorphic towel, develops an addiction to inhaling computer duster. In the show Squidbilles, the main character Early Cuyler is often seen inhaling gas or other substances.

See also
Inhaler or puffer, a medical device used for delivering medication into the body via the lungs (often used in the treatment of asthma)
Khaliq v HM Advocate, a Scottish criminal case in which the court ruled that it is an offense to supply materials that were used for sniffing
Mt Theo Program, a successful petrol-sniffing prevention program run by the indigenous Warlpiri community in Central Australia
Jenkem, a purported inhalant and hallucinogen supposedly created from fermented human waste
List of medical inhalants

References
Notes

Further reading
Burk, Isabel (2001). Inhalant Prevention Resource Guide (PDF). VA Dpt Ed (2nd ed.). The Health Network.
Chier, Ruth (2003) [1997]. Danger: Inhalants. The Drug Awareness Library. Powerkids Press. pp. 24 </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 Cortical visual impairment and explain in detail? [/INST] Cortical visual impairment (CVI) is a form of visual impairment that is caused by a brain problem rather than an eye problem. (The latter is sometimes termed "ocular visual impairment" when discussed in contrast to cortical visual impairment.) Some people have both CVI and a form of ocular visual impairment.
CVI is also sometimes known as cortical blindness, although most people with CVI are not totally blind.  The term neurological visual impairment (NVI) covers both CVI and total cortical blindness. Delayed visual maturation, another form of NVI, is similar to CVI, except the childs visual difficulties resolve in a few months.  Though the vision of a person with CVI may change, it rarely if ever becomes totally normal.
The major causes of CVI are as follows: asphyxia, hypoxia (a lack of sufficient oxygen in the bodys blood cells), or ischemia (not enough blood supply to the brain), all of which may occur during the birth process; developmental brain defects; head injury; hydrocephalus (when the cerebrospinal fluid does not circulate properly around the brain, and collects in the head, putting pressure on the brain); a stroke involving the occipital lobe; and infections of the central nervous system, such as meningitis and encephalitis.

Visual and Behavioural Characteristics
Visual and Behavioural Characteristics of CVI are individual and may include several (but not necessarily all) of the following:

The person with CVI may exhibit what at first appears to be frequent variable changes in vision. However, it is the environment that impacts their visual function rather than their neurology or capacity for vision at that moment. A persons change in visual function when processing visual information in a complex environment, or trying to process a certain complex or unfamiliar visual target likely accounts for what looks like their visual ability changing from one day to the next, or from minute to minute. Feeling tired or unwell may also compound this challenge. For some people with CVI the complexity of the environment, including variables like the complexity and familiarity of the visual input, or processing various forms of secondary sensory input (for instance, sound or touch) may cause them to have difficulty using their vision to their full potential. The amount of sensory input an individual can tolerate without impacting function significantly may change throughout development and person to person. Managing fatigue may reduce fluctuations but does not eliminate them, however utilizing breaks and being well rested may help to increase resilience during these times. Addressing these changes may mean adapting strategies that work for the individual person. For example, When undertaking critical activities, people with CVI should be prepared for their vision to fluctuate, by taking precautions such as always carrying a white cane, if they use one, even if they dont always use it to the fullest. Another example is having very large print available, just in case its needed (For example, consider the consequences of losing vision while giving a public speech). Other potential adaptations to improve visual function in higher environmental complexity may include strategies like clearing away excess clutter from a work spaces, or providing a plain background to view objects against, reducing noise levels, or other methods of monitoring and adapting for environmental complexity.
One eye may perform significantly worse than the other, and depth perception can be very limited (although not necessarily zero).
The field of view may be severely limited.  The best vision might be in the centre (like tunnel vision) but more often it is at some other point, and it is difficult to tell what the person is really looking at.  Note that if the person also has a common ocular visual impairment such as nystagmus then this can also affect which part(s) of the visual field are best. (Sometimes there exists a certain gaze direction which minimises the nystagmus, called a "null point.")
Even though the field of view may be very narrow indeed, it is often possible for the person to detect and track movement.  Movement is handled by the V5 part of the visual cortex, which may have escaped the damage.  Sometimes a moving object can be seen better than a stationary one; at other times the person can sense movement but cannot identify what is moving. (This can be annoying if the movement is prolonged, and to escape the annoyance the person may have to either gaze right at the movement or else obscure it.)  Sometimes it is possible for a person with CVI to see things while moving their gaze around that they didnt detect when stationary.  However, movement that is too fast can be hard to track; some people find that fast-moving objects "disappear."  Materials with reflective properties, which can simulate movement, may be easier for a person with CVI to see. However, too many reflections can be confusing (see cognitive overload).
Some objects may be easier to see than others.  For example, the person may have difficulty recognising faces or facial expressions but have fewer problems with written materials.  This is presumably due to the different way that the brain processes different things.
Colour and contrast are important.  The brains colour processing is distributed in such a way that it is more difficult to damage, so people with CVI usually retain full perception of colour.  This can be used to advantage by colour-coding objects that might be hard to identify otherwise.  Sometimes yellow and red objects are easier to see, as long as this does not result in poor contrast between the object and the background.
People with CVI strongly prefer a simplified view.  When dealing with text, for example, the person might prefer to see only a small amount of it at once.  People with CVI frequently hold text close to their eyes, both to make the text appear larger and to minimise the amount they must look at. This also ensures that important things such as letters are not completely hidden behind any scotomas (small defects in parts of the functioning visual field),  and reduces the chances of getting lost in the text.  However, the simplification of the view should not be done in such a way that it requires too rapid a movement to navigate around a large document, since too much motion can cause other problems (see above).
In viewing an array of objects, people with CVI can more easily see them if they only have to look at one or two at a time. People with CVI also see familiar objects more easily than new ones.  Placing objects against a plain background also makes them easier for the person with CVI to see.
For the same reason (simplified view), the person may also dislike crowded rooms and other situations where their functioning is dependent on making sense of a lot of visual clutter.
Visual processing can take a lot of effort.  Often the person has to make a conscious choice about how to divide mental effort between making sense of visual data and performing other tasks.  For some people, maintaining eye contact is difficult, which can create problems in Western culture (for example, bonding can be difficult for some parents who have an infant with CVI, and lack of contact in an older child can cause others to regard him or her with suspicion).
It can also be difficult for some people with CVI to look at an object and reach for it at the same time.  Looking and reaching are sometimes accomplished as two separate acts: look, then look away and reach.
People with CVI can sometimes benefit from a form of blindsight, which manifests itself as a kind of awareness of ones surroundings that cannot consciously be explained (for example, the person correctly guesses what they should do in order to avoid an obstacle but does not actually see that obstacle).  However, this cannot be relied on to work all the time.  In contrast, some people with CVI exhibit spatial difficulties and may have trouble moving about in their environment.
Approximately one third of people with CVI have some photophobia.  It can take longer than usual to adjust to large changes in light level, and flash photography can be painful.  On the other hand, CVI can also in some cases cause a desire to gaze compulsively at light sources, including such things as candle flames and fluorescent overhead lights. The use of good task lighting (especially low-temperature lamps which can be placed at very close range) is often beneficial.
Although people (with or without CVI) generally assume that they see things as they really are, in reality the brain may be doing a certain amount of guessing and "filling in", which is why people sometimes think they see things that turn out on closer inspection not to be what they seemed. This can occur more frequently when a person has CVI. Hence, a person with CVI can look at an optical illusion or abstract picture and perceive something that is significantly different from what a person without CVI will perceive.The presence of CVI does not necessarily mean that the persons brain is damaged in any other way, but it can often be accompanied by other neurological problems, the most common being epilepsy.

Diagnosis
Diagnosing CVI is difficult. A diagnosis is usually made when visual performance is poor but it is not possible to explain this from an eye examination. Before CVI was widely known among professionals, some would conclude that the patient was faking their problems or had for some reason engaged in self-deception. However, there are now testing techniques that do not depend on the patients words and actions, such as fMRI scanning, or the use of electrodes to detect responses to stimuli in both the retina and the brain. These can be used to verify that the problem is indeed due to a malfunction of the visual cortex and/or the posterior visual pathway.

See also
Cortical blindness

References
Further reading
Tallent, Aubri & Tallent, Andrei (2012). Little Bear Sees: How Children with Cortical Visual Impairment Can Learn to See. Little Bear Sees Publishing, of Wyatt-MacKenzie. p. 156. ISBN 978-1936214822. OCLC 1936214822.
Roman-Lantzy, Christine (2019). Cortical Visual Impairment: Advanced Principles. New York: AFB Press. ISBN 978-1616480073. OCLC 1055566701.
Roman-Lantzy, Christine (2017). Cortical Visual Impairment: An Approach to Assessment and Intervention 2nd Ed. New York: AFB Press. ISBN 978-0891286882.
Dutton GN, Lueck, AH (2015). Vision and the Brain: Understanding Cerebral Visual Impairment in Children. New York: AFB Press. ISBN 978-0891286394. OCLC 904801331.
Dutton, Gordon N (2006). "Cerebral Visual Impairment: Working within and around the Limitations of Vision" </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 Idiopathic guttate hypomelanosis 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 Fetal-maternal haemorrhage and explain in detail? [/INST] Fetal-maternal haemorrhage is the loss of fetal blood cells into the maternal circulation. It takes place in normal pregnancies as well as when there are obstetric or trauma related complications to pregnancy.
Normally the maternal circulation and the fetal circulation are kept from direct contact with each other, with gas and nutrient exchange taking place across a membrane in the placenta made of two layers, the syncytiotrophoblast and the cytotrophoblast </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 Emanuel syndrome and explain in detail? [/INST] Emanuel syndrome, also known as derivative 22 syndrome, or der(22) syndrome, is a rare disorder associated with multiple congenital anomalies, including profound intellectual disability, preauricular skin tags or pits, and conotruncal heart defects. It can occur in offspring of carriers of the constitutional chromosomal translocation t(11;22)(q23;q11), owing to a 3:1 meiotic malsegregation event resulting in partial trisomy of chromosomes 11 and 22. An unbalanced translocation between chromosomes 11 and 22 is described as Emanuel syndrome. It was first described in 1980 by American medical researchers Beverly S. Emanuel and Elaine H. Zackai, and a consortium of European scientists the same year.

Sign and symptoms
Infants with Emanuel syndrome have weak muscle tone (hypotonia) and fail to gain weight and grow at the expected rate (failure to thrive). Their development is significantly delayed, and most affected individuals have severe to profound intellectual disability. Other features of Emanuel syndrome include an unusually small head (microcephaly), distinctive facial features, and a small lower jaw (micrognathia). Ear abnormalities are common, including small holes in the skin just in front of the ears (preauricular pits, or sinuses). About half of all affected infants are born with an opening in the roof of the mouth (cleft palate) or a high arched palate. Males with Emanuel syndrome often have genital abnormalities. Additional signs of this condition can include heart defects and absent or unusually small (hypoplastic) kidneys; these problems can be life-threatening in infancy or childhood.

Causes
Emanuel syndrome is an inherited chromosome abnormality. It is caused by the presence of extra genetic material from chromosome 11 and chromosome 22 in each cell. In addition to the usual 46 chromosomes, people with Emanuel syndrome have an extra (supernumerary) chromosome consisting of a piece of chromosome 11 attached to a piece of chromosome 22. The extra chromosome is known as a derivative 22, or der(22), chromosome.

Genetics
People with Emanuel syndrome typically inherit the der(22) chromosome from an unaffected parent. The parent carries a chromosomal rearrangement between chromosomes 11 and 22 called a balanced translocation. No genetic material is gained or lost in a balanced translocation, so these chromosomal changes usually do not cause any health problems. As this translocation is passed to the next generation, it can become unbalanced </s>