<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Folliculitis and can you explain it in depth? [/INST] Folliculitis is the infection and inflammation of one or more hair follicles. The condition may occur anywhere on hair-covered skin. The rash may appear as pimples that come to white tips on the face, chest, back, arms, legs, buttocks, or head.Although acne can often involve superficial infection and inflammation of some hair follicles, the condition of those follicles is usually not called folliculitis, as that term is usually reserved for the separate set of disease entities comprising infected and inflamed hair follicles with causes other than acne.

Signs and symptoms
Rash (reddened skin area)
Itching skin
Pimples or pustules located around a hair or follicle; may be confused with chicken pox
May crust over
Typically occur on neck, armpit, or groin
May present as genital lesions
Spreading from leg to arm to body through improper treatment with antibiotics

Complications
This condition can develop into a more severe skin condition, such as cellulitis or abscess.

Causes
Most carbuncles, boils, and other cases of folliculitis are infected with Staphylococcus aureus.Folliculitis starts with the introduction of a skin pathogen to a hair follicle. Hair follicles can also be damaged by friction from clothing, an insect bite, blockage of the follicle, shaving, or braids that are very tight and close to the scalp. The damaged follicles are then infected by Staphylococcus spp. Folliculitis can affect people of all ages.Iron-deficiency anemia is sometimes associated with chronic cases.

Bacterial
Staphylococcus aureus folliculitis
Hot-tub folliculitis is caused by the bacterium Pseudomonas aeruginosa.  The folliculitis usually occurs after sitting in a hot tub that was not properly cleaned before use.  Symptoms are found around the body parts that sit in the hot tub - the legs, hips, chest, buttocks, and surrounding areas.  Symptoms are amplified around regions that were covered by wet clothing, such as bathing suits.
Sycosis vulgaris, sycosis barbae, or barbers itch is a staphylococcal infection of the hair follicles in the bearded area of the face, usually the upper lip. Shaving aggravates the condition.
Gram-negative folliculitis may appear after prolonged acne treatment with antibiotics.

Fungal
Tinea barbae is similar to barbers itch, but the infection is caused by the fungus T </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Urtica dioica and can you explain it in depth? [/INST] Urtica dioica, often known as common nettle, burn nettle, stinging nettle (although not all plants of this species sting) or nettle leaf, or just a nettle or stinger, is a herbaceous perennial flowering plant in the family Urticaceae. Originally native to Europe, much of temperate Asia and western North Africa, it is now found worldwide, including New Zealand and  North America. The species is divided into six subspecies, five of which have many hollow stinging hairs called trichomes on the leaves and stems, which act like hypodermic needles, injecting histamine and other chemicals that produce a stinging sensation upon contact ("contact urticaria", a form of contact dermatitis).The plant has a long history of use as a source for traditional medicine, food, tea, and textile raw material in ancient (such as Saxon) and modern societies.

Description
Urtica dioica is a dioecious, herbaceous, perennial plant, 3 to 7 feet (0.9 to 2 metres) tall in the summer and dying down to the ground in winter. It has widely spreading rhizomes and stolons, which are bright yellow, as are the roots. The soft, green leaves are 1 to 6 inches (30 to 200 mm) long and are borne oppositely on an erect, wiry, green stem. The leaves have a strongly serrated margin, a cordate base, and an acuminate tip with a terminal leaf tooth longer than adjacent laterals. It bears small, greenish or brownish, numerous flowers in dense axillary inflorescences.
The leaves and stems are very hairy with non-stinging hairs, and in most subspecies, also bear many stinging hairs (trichomes or spicules), whose tips come off when touched, transforming the hair into a needle that can inject several chemicals causing a painful sting or paresthesia, giving the species its common names: stinging nettle, burn-nettle, burn-weed, or burn-hazel.

Taxonomy
The taxonomy of Urtica species has been confused, and older sources are likely to use a variety of systematic names for these plants. Formerly, more species were recognised than are now accepted. However, at least six clear subspecies of U. dioica are described, some formerly classified as separate species:

U. dioica subsp. dioica (European stinging nettle), from Europe, Asia, and northern Africa, has stinging hairs.
U. dioica subsp. galeopsifolia (fen nettle or stingless nettle), from Europe, does not have stinging hairs.
U. dioica subsp. afghanica, from southwestern and central Asia, sometimes has stinging hairs or is sometimes hairless.
U. dioica subsp. gansuensis, from eastern Asia (China), has stinging hairs.
U. dioica subsp. gracilis (Ait.) Selander (American stinging nettle), from North America, has stinging hairs and is monoecious.
U. dioica subsp. holosericea (Nutt.) Thorne (hoary stinging nettle), from North America, has stinging hairs and is monoecious.Other species names formerly accepted as distinct by some authors but now regarded as synonyms of one or other subspecies include U. breweri, U. californica, U. cardiophylla, U. lyalli, U. major, U. procera, U. serra, U. strigosissima, U. trachycarpa, and U. viridis.

Etymology
Urtica is derived from a Latin word meaning sting.Dioica (δίοικος) is derived from Greek, meaning of two houses (having separate staminate and pistillate plants; dioecious).

Distribution and habitat
U. dioica is considered to be native to Europe, much of temperate Asia and western North Africa. It is abundant in northern Europe and much of Asia, usually found in the countryside. It is less widespread in southern Europe and north Africa, where it is restricted by its need for moist soil, but is still common. It has been introduced to many other parts of the world. In North America, it is widely distributed in Canada and the United States, where it is found in every province and state except for Hawaii, and also can be found in northernmost Mexico. It grows in abundance in the Pacific Northwest, especially in places where annual rainfall is high. The European subspecies has been introduced into Australia, North America and South America.In Europe, nettles have a strong association with human habitation and buildings. The presence of nettles may indicate the site of a long-abandoned building, and can also indicate soil fertility. Human and animal waste may be responsible for elevated levels of phosphate and nitrogen in the soil, providing an ideal environment for nettles.

Ecology
Nettles are the larval food plant for several species of butterflies, such as the peacock butterfly, comma (Polygonia c-album), and the small tortoiseshell. It is also eaten by the larvae of some moths including angle shades, buff ermine, dot moth, the flame, the gothic, grey chi, grey pug, lesser broad-bordered yellow underwing, mouse moth, setaceous Hebrew character, and small angle shades. The roots are sometimes eaten by the larva of the ghost moth (Hepialus humuli).
It is a known host to the pathogenic fungus Phoma herbarum.Stinging nettle is particularly found as an understory plant in wetter environments, but it is also found in meadows. Although nutritious, it is not widely eaten by either wildlife or livestock, presumably because of the sting. It spreads by abundant seeds and also by rhizomes, and is often able to survive and re-establish quickly after fire.

Cultivation
Field
Sowing and planting
Three cultivation techniques can be used for the stinging nettle: 1) direct sowing, 2) growing seedlings in nurseries with subsequent transplantation and 3) vegetative propagation via stolons or head cuttings.
Direct sowing: The seedbed should have a loose and fine structure, but should be reconsolidated using a packer roller imminently prior to sowing. Sowing time can be either in autumn or in spring. Seed density should be 6 kilograms/hectare with row spacing of 30 cm (12 in) and 42–50 cm in autumn and spring, respectively. The disadvantage of direct sowing is that it usually leads to incomplete plant coverage. This drawback can be mitigated by covering the seedbed with a transparent perforated foil in order to improve seed germination. Further, weed control can be problematic as the stinging nettle has a slow seedling development time.
Growing seedlings: For this technique pre-germinated seeds are sown between mid-/end-February and beginning of April and grown in nurseries. Seedlings are grown in tuffs with 3–5 plants/tuff and a seed density of 1.2–1.6 kg/1000 tuffs. A fastened germination is achieved by alternating high temperature during daytime (30 °C for 8 h) and lower temperature during nighttime (20 °C for 16 h). Before transplanting, the seedlings should be fertilized and acclimated to cold temperatures. Transplantation should start around Mid-April with row spacing of 42–50 cm (17–20 in) and plant spacing within rows of 25–30 cm.
Vegetative propagation: Stolons (with several buds) of 10 cm should be planted from mid-April in a depth of 5–7 cm (2–2+3⁄4 in). Head cuttings are grown in nurseries starting between mid-May and mid-June. Growing tips with two leaf pairs are cut from the mother plant and treated with root-growth inducing hormones. Transplantation can be delayed in comparison to the growing seedling technique.

Greenhouse
The stinging nettle can also be grown in controlled-environment agriculture systems, such as soil-less medium cultivations or aeroponics, which may achieve higher yields, standardize quality, and reduce harvesting costs and contamination.

Sting and treatment
Urtica dioica produces its inflammatory effect on skin (stinging, burning sensation often called "contact urticaria") both by impaling the skin via spicules – causing mechanical irritation – and by biochemical irritants, such as histamine, serotonin, and acetylcholine, among other chemicals. Anti-itch drugs, usually in the form of creams containing antihistamines or hydrocortisone, may provide relief from nettle dermatitis. The term, contact urticaria, has a wider use in dermatology, involving dermatitis caused by various skin irritants and pathogens.Docks, especially the broad-leaf dock (Rumex obtusifolius) often grow in similar environments to stinging nettles and are regarded as a folk remedy to counteract the sting of a nettle, although there is no evidence of any chemical effect. It may be that the act of rubbing a dock leaf against a nettle sting acts as a distracting counterstimulation, or that belief in the docks effect provides a placebo effect.

Uses
Culinary
U. dioica has a flavour similar to spinach when cooked. Young plants were harvested by Native Americans and used as a cooked plant in spring when other food plants were scarce. Soaking stinging nettles in water or cooking removes the stinging chemicals from the plant, which allows them to be handled and eaten without injury. After the stinging nettle enters its flowering and seed-setting stages, the leaves develop gritty particles called cystoliths, which can irritate the kidneys and urinary tract.: 106–107   Cystoliths are made of calcium carbonate, and will not dissolve when boiled.  Leaves harvested post-flowering must have their cystoliths broken down by acid, as in the fermentation process. In its peak season, nettle contains up to 25% protein, dry weight, which is high for a leafy green vegetable. The leaves are also dried and may then be used to make a herbal tea, as can also be done with the nettles flowers.
Nettles can be used in a variety of recipes, such as polenta, pesto, and purée. Nettle soup is a common use of the plant, particularly in Northern and Eastern Europe.
Nettles are sometimes used in cheesemaking, such as for Cornish Yarg and as a flavouring in varieties of Gouda.Nettles are used in Montenegro, Serbia and Bosnia and Hercegovina as part of the dough filling for the börek pastry. The top baby leaves are selected and simmered, and then mixed with other ingredients such as herbs and rice, before being used as a filling between dough layers. Similarly, in Greece the tender leaves are often used, after simmering, as a filling for hortopita, which is similar to spanakopita, but with wild greens rather than spinach for filling.Young nettles can also be used to make an alcoholic drink.

Competitive eating
In the UK, an annual World Nettle Eating Championship draws thousands of people to Dorset, where competitors attempt to eat as much of the raw plant as possible. Competitors are given 60 cm (24 in) stalks of the plant, from which they strip the leaves and eat them. Whoever strips and eats the most stinging nettle leaves in a fixed time is the winner. The competition dates back to 1986, when two neighbouring farmers attempted to settle a dispute about which had the worst infestation of nettles, and one of them said, "Ill eat any nettle of yours thats longer than mine."

Traditional medicine
As Old English stiðe, nettle is one of the nine plants invoked in the pagan Anglo-Saxon Nine Herbs Charm, recorded in 10th century traditional medicine. Nettle was believed to be a galactagogue – a substance that promotes lactation. Urtication, or flogging with nettles is the process of deliberately applying stinging nettles to the skin to provoke inflammation. An agent thus used was considered to be a rubefacient (something that causes redness), used as a folk remedy for treating rheumatism.

Chastisement
In indigenous justice systems in Ecuador, urtication was used as punishment for severe crimes in 2010. The sentenced perpetrator of a crime was flogged with stinging nettle, in public, naked, whilst being showered with freezing cold water.

Textiles and fibre
Nettle stems contain a bast fibre that has been traditionally used for the same purposes as linen and is produced by a similar retting process. Unlike cotton, nettles grow easily without pesticides. The fibres are coarser, however.Historically, nettles have been used to make clothing for almost 3,000 years, as ancient nettle textiles from the Bronze Age have been found in Denmark. It is widely believed that German Army uniforms were almost all made from nettle during World War I due to a potential shortage of cotton, although there is little evidence to support this. More recently, companies in Austria, Germany, and Italy have started to produce commercial nettle textiles.The fibre content in nettle shows a high variability and reaches from below 1% to 17%. Under middle-European conditions, stems yield typically between 45 and 55 dt / ha (decitons per hectare), which is comparable to flax stem yield. Due to the variable fibre content, the fibre yields vary between 0.2 and 7 dt / ha, but the yields are normally in the range between 2 and 4 dt / ha. Fibre varieties are normally cloning varieties and therefore planted from vegetative propagated plantlets. Direct seeding is possible, but leads to great heterogeneity in maturity.Nettles may be used as a dye-stuff, producing yellow from the roots, or yellowish green from the leaves.

Feed
Nutrient contents
Fresh leaves contain approximately 82.4% water, 17.6% dry matter, 5.5% protein, 0.7 to 3.3% fat, and 7.1% carbohydrates. Mature leaves contain about 40% α- linolenic acid, a valuable omega-3 acid. For exact fatty acid contents see Table 1. Seeds contain much more fatty acid than leaves.
Minerals (Ca, K, Mg, P, Si, S, Cl) and trace elements (Ti, 80 ppm, Mn, Cu, Fe) contents depend mostly on the soil and the season.Carotenoids can be found primarily in the leaves, where different forms of lutein, xanthophyll and carotene are present (Table 2). Some carotenes are precursors of vitamin A (retinol), their retinol equivalents RE or retinol activity equivalents per g dry weight are 1.33 for mature leaves and 0.9 for young leaves. Nettle contains much less carotenes and retinol than carrots, which contain 8.35 RE per g fresh weight. Depending on the batch and the leave and stem content, nettle contains only traces of zeaxanthin or between 20–60 mg/kg of dry matter. Nettle contains ascorbic acid (vitamin C), riboflavin (vitamin B2), pantothenic acid, vitamin K1 and tocopherols (vitamin E). The highest vitamin contents can be found in the leaves.

Poultry: Egg yolk colouring in laying hens
In laying hens, nettle can be used as an egg yolk colorant instead of artificial pigments or other natural pigments (derived from marigold for yellow). Nettle has high carotenoid contents, especially lutein, β-carotene and zeaxanthin, of which lutein and zeaxanthin act as yellow pigments. Feeding as little as 6.25 g dry nettle per kg feed is as effective as the synthetic pigments to colour the egg yolk. Feeding nettle has no detrimental effect on the performance of the laying hens or on the general quality of eggs.

Ruminants
Ruminants avoid fresh stinging nettles; however, if the nettles are wilted or dry, voluntary intake can be high.

Use in agriculture / horticulture
In the European Union and United Kingdom, nettle extract can be used as a insecticide, fungicide, and acaricide under Basic Substance regulations. As an insecticide nettle extract can be used for the control of codling moth, diamondback moth, and spider mites. As a fungicide, it can be used for the control of Pythium root rot, powdery mildew, early blight, late blight, Septoria blight, Alternaria leaf spot, and grey mould.

Gardening
Nettles have a number of other uses in the vegetable garden, including the potential for encouraging beneficial insects. Since nettles prefer to grow in phosphorus-rich and nitrogen rich soils that have recently been disturbed (and thus aerated), the growth of nettles is an indicator that an area has high fertility (especially phosphate and nitrate), and thus is an indicator to gardeners as to the quality of the soil.Nettles contain nitrogenous compounds, so are used as a compost activator or can be used to make a liquid fertilizer, which although low in phosphate, is useful in supplying magnesium, sulphur, and iron. They are also one of the few plants that can tolerate, and flourish in, soils rich in poultry droppings.
The stinging nettle is the red admiral caterpillars primary host plant and can attract migrating red admiral butterflies to a garden. U. dioica can be a troubling weed, and mowing can increase plant density. Regular and persistent tilling will greatly reduce its numbers, and the use of herbicides such as 2,4-D and glyphosate are effective control measures.

Culture
In Great Britain and Ireland, U. dioica and the annual nettle Urtica urens are the only common stinging plants and have found a place in several figures of speech in the English language. Shakespeares Hotspur urges that "out of this nettle, danger, we pluck this flower, safety" (Henry IV, Part 1, Act II Scene 3). The figure of speech "to grasp the nettle" probably originated from Aesops fable "The Boy and the Nettle". In Seán OCaseys Juno and the Paycock, one of the characters quotes Aesop "Gently touch a nettle and itll sting you for your pains/Grasp it as a lad of mettle and soft as silk remains". The metaphor may refer to the fact that if a nettle plant is grasped firmly rather than brushed against, it does not sting so readily, because the hairs are crushed down flat and do not penetrate the skin so easily.In the German language, the idiom sich in die Nesseln setzen, or to sit in nettles, means to get into trouble.
In Hungarian, the idiom csalánba nem üt a mennykő, the lightning bolt does not strike into nettles, alludes to the belief that bad people escape trouble or the devil looks after his own. The same idiom exists in the Serbian language – неће гром у коприве. In Dutch, a netelige situatie means a predicament. In French, the idiom faut pas pousser mémé dans les orties (do not push granny into the nettles) means that we should be careful not to abuse a situation. The name urticaria for hives comes from the Latin name of nettle (Urtica, from urere, to burn).
The English word nettled, meaning irritated or angry, is derived from nettle.There is a common idea in Great Britain that the nettle was introduced by the Romans. The idea was mentioned by William Camden in his book Britannia of 1586. However, in 2011, an early Bronze Age burial cist on Whitehorse Hill, Dartmoor, Devon was excavated. The cist dated from between 1730 and 1600 BC. It contained various high value beads as well as fragments of a sash made from nettle fibre. It is possible that the sash was traded from mainland Europe, but perhaps more probable that it was locally made.

See also
Nettles in folklore

References
Further reading
Elliott, C. (1997). "Rash Encounters". Horticulture </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Ornithine aminotransferase deficiency and can you explain it in depth? [/INST] Ornithine aminotransferase deficiency (also known as gyrate atrophy of the choroid and retina) is an inborn error of ornithine metabolism, caused by decreased activity of the enzyme ornithine aminotransferase.  Biochemically, it can be detected by elevated levels of ornithine in the blood.  Clinically, it presents initially with poor night vision, which slowly progresses to total blindness.  It is believed to be inherited in an autosomal recessive manner.  Approximately 200 known cases have been reported in the literature.  The incidence is highest in Finland, estimated at 1:50,000.Research suggests there can be some adverse effect on muscles and also the brain. The cause of this is somewhat unclear but may relate to very low levels of creatine often found in this population.
Treatment may include vitamin B6, lysine or dramatic dietary change to minimise arginine from patients diet. Research has indicated that these treatments may be somewhat effective in lowering ornithine blood concentration levels in some patients, either in combination or individually.  Vitamin B6 has been found to be very effective in a small proportion of patients.

Presentation
Quite often, the presenting symptom of ornithine aminotransferase (OAT) deficiency is myopia which progresses to night blindness.  The onset of myopia is often in early childhood.  Ophthalmological findings in affected individuals include constricted visual fields, posterior subcapsular cataracts (can begin in late teens), elevated dark adaptation thresholds and decreased or absent electroretinographic responses </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Valsalva retinopathy and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Nelsons syndrome and can you explain it in depth? [/INST] Nelsons syndrome is a disorder that occurs in about one in four patients who have had both adrenal glands removed to treat Cushings disease. In patients with pre-existing adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas, loss of adrenal feedback following bilateral adrenalectomy can trigger the rapid growth of the tumor, leading to visual symptoms (e.g. bitemporal hemianopsia) and hyperpigmentation. The severity of the disease is dependent upon the effect of ACTH release on the skin, pituitary hormone loss from mass compression, as well as invasion into surrounding structures around the pituitary gland.The first case of Nelsons syndrome was reported in 1958 by Dr. Don Nelson. Within the past ten to twenty years, improvements have been made with identification and care for patients with Cushings disease. Techniques such as pituitary radiation therapy, ACTH assay, transsphenoidal pituitary surgery, higher resolution MRIs, and sampling of the inferior petrosal sinus have allowed physicians to pursue routes for Cushings syndrome therapy prior to consideration of bilateral adrenalectomy.Nelsons syndrome is also referred to as post adrenalectomy syndrome, a possible result of adrenalectomy performed for Cushings disease.

Symptoms and signs
The common symptoms include:
hyper-pigmentation of the skin
visual disturbances
headaches
abnormally high levels of beta-MSH and ACTH
abnormal enlargements of the pituitary gland,
interruption of menstrual cycles in women

Cause
Common causes include bilateral adrenalectomy for the treatment of Cushings disease, and hypopituitarism. The onset of the disease can occur up to 24 years after a bilateral adrenalectomy has been performed, with an average of up to 15 years after. A preventative measure that can be utilized is prophylactic radiotherapy when a bilateral adrenalectomy is being performed in order to prevent Nelsons syndrome from manifesting. Screening can also be done with the help of an MRI in order to visualize the pituitary for tumors. If tumors are not present then an MRI should be performed at intervals. Hyper-pigmentation and fasting ACTH levels within plasma above 154 pmol/L are predictive of Nelsons syndrome after an adrenalectomy. Risk factors include being younger in age and pregnancy.

Mechanism
After a bilateral adrenalectomy is performed cortisol levels are no longer normal. This increases CRH production because it is not suppressed within the hypothalamus anymore. The increased CRH levels promote the growth of the tumor. Mutations with genes and with the glucocorticoid receptor can affect the tumor as well. Furthermore, differences between Nelson syndrome and Cushings disease have been studied. Particularly Nelsons syndrome differs from Cushings disease due to the following: secretions from the tumors, replacement of glucocorticoids, and injury to the hypothalamus due to radiation therapy utilized on the patient. The pathophysiology of Nelsons syndrome is not understood very well. Corticotrophinomas are generated from corticotroph cells. Expression of functional CRH and vasopressin V3 receptors increase in number. Additionally, there are two isoforms of glucocorticoid receptors. Heterozygosity loss in the glucocorticoid receptor can occur in the tumors present from Nelsons syndrome. Overall, not all patients that have had a total bilateral adrenalectomy develop Nelsons syndrome, which makes the mechanism harder to understand for such a rare disease. It is not clear whether the adrenalectomy or reduced cortisol secretion causes aggressive tumor growth.

Diagnosis
Common diagnostic techniques include:
MRIs
CAT scans
blood samples.Blood samples are assessed for the absence or presence of aldosterone and cortisol. Physical examinations are also useful in patients in order to examine vision, skin pigmentation, how the body replaces steroids, and the cranial nerves. Recent advancements in high-resolution MRIs allow for adenomas to be detected during the early stages of Nelson syndrome. Physical examination including height, weight, vital signs, blood pressure, eye examination, thyroid examination, abdominal examination, neurological examination, skin examination and pubertal staging needs to be assessed. Through blood pressure and pulse readings can indicate hypothyroidism and adrenal insufficiency. Hyper-pigmentation, hyporeflexia, and loss of vision can also indicate Nelsons syndrome when assessed together. Specifically for a child who might have Nelsons syndrome, the patient should be questioned about the symptoms of the disease, and well as symptoms of other diseases to narrow down which disease the patient presents with. The patient should be questioned about how often and to what degree headaches, visual disturbances, and symptoms associated with pituitary malfunction occur. Additionally, adrenal steroid replacement should be assessed.

Treatment
Common treatments for Nelsons syndrome include radiation or surgical procedure. Radiation allows for the limitation of the growth of the pituitary gland and the adenomas. If the adenomas start to affect the surrounding structures of the brain, then a micro-surgical technique can be adapted in order to remove the adenomas in a transsphenoidal (bone at base of the skull) process. Death may result with development of a locally aggressive pituitary tumor </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Retinal dysplasia and can you explain it in depth? [/INST] Retinal dysplasia is an eye disease affecting the retina of animals and, less commonly, humans.  It is usually a nonprogressive disease and can be caused by viral infections, drugs, vitamin A deficiency, or genetic defects.  Retinal dysplasia is characterized by folds or rosettes (round clumps) of the retinal tissue.

Retinal dysplasia in dogs
Most cases of retinal dysplasia in dogs are hereditary.  It can involve one or both retinas.  Retinal dysplasia can be focal, multifocal, geographic, or accompanied by retinal detachment </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is 5α-Reductase 2 deficiency and can you explain it in depth? [/INST] 5α-Reductase 2 deficiency (5αR2D) is an autosomal recessive condition caused by a mutation in SRD5A2, a gene encoding the enzyme 5α-reductase type 2 (5αR2). The condition is rare, affects only genetic males, and has a broad spectrum of presentations, most apparent in the genitalia where a male is born with an underdeveloped penis that might develop to various extents in puberty and hence be raised as female up to a certain age.
5αR2 is expressed in specific tissues and catalyzes the transformation of testosterone (T) to 5α-dihydrotestosterone (DHT). DHT plays a key role in the process of sexual differentiation in the external genitalia and prostate during development of the male fetus. 5αR2D is a result of impaired 5αR2 activity resulting in decreased DHT levels. This defect results in a spectrum of phenotypes including overt genital ambiguity, female appearing genitalia, hypospadias, and isolated micropenis. Affected males still develop typical masculine features at puberty (deep voice, facial hair, muscle bulk) since most aspects of pubertal virilization are driven by testosterone, not DHT.
Management of this condition in the context of sex assignment is a challenging and controversial area. Diagnostic availability, local laws, parental anxiety all play roles in treatment decisions.
The investigation of 5αR2D as a disease has played a key role in the biochemical characterization of the SRD5A2 gene, the 5αR2 enzyme, and DHT in male sexual differentiation.

Presentation
Mutations in the SRD5A2 gene can result in a 46,XY disorder of sex development (46,XY DSD) called 5α-reductase 2 deficiency (5αR2D). The mutations are inherited in an autosomal recessive pattern can be either homozygous or, less frequently, compound heterozygous loss-of-function. Affected males exhibit a broad spectrum of presentation including atypical genitalia (ranging from female appearing to undervirilized male), hypospadias, and isolated micropenis. The internal reproductive structures (vasa deferentia, seminal vesicles, epididymides and ejaculatory ducts) are normal but testes are usually undescended and prostate hypoplasia is common. Males with the same mutations in SRD5A2 can have different phenotypes suggesting additional factors that are involved in clinical presentation. Females with the same mutations in SRD5A2 as affected males (as seen in siblings) are unaffected and have normal female phenotypes and reproductive function.Virilization of genitalia with voice deepening, development of muscle mass occur at puberty in affected males and height is not impaired. Gynecomastia is uncommon and bone density is normal in contrast to 46,XY DSD from other causes such as partial androgen insensitivity syndrome and 17β-hydroxysteroid dehydrogenase 3 deficiency. Hair on the face and body is reduced and male pattern baldness does not occur.

Mechanism
5α-Reductase type 2 (5αR2) is an enzyme, encoded by the SRD5A2 gene, that is expressed in specific tissues in the male body from fetal development to adulthood. The enzyme catalyzes the transformation of testosterone (T) to 5α-dihydrotestosterone (DHT) intracellularly.  DHT is the most potent ligand to the androgen receptor (AR). Upon binding, the DHT-AR complex translocates from cytoplasm to the nucleus and activates the androgen receptor-regulated genes involved in processes that include male sexual differentiation.Some mutations in 5αR2 impair the synthesis of DHT resulting in 5αR2D. In the male fetus, T mediates Wolffian ductal differentiation while DHT mediates external genital and prostate differentiation. The fact that women with the same 5αR2 mutations as affected male siblings have normal female phenotypes and normal reproductive function supports the notion that 5αR2 does not play an important role in female biology. Most aspects of virilization in male puberty are driven by testosterone, which is why most affected males undergo virilization at that time.Though 5αR2D only affects a small number of people, study of this disorder revealed fundamental aspects of 5α-reductases (including cloning of the underlying genes), androgen action, the process of sexual differentiation, and the factors that influence normal sexual behavior.

Genetics
Two of three isozymes of 5αR can catalyze the transformation of T to DHT, but it is only 5αR2D that causes 46XY, DSD. 5αR2 is encoded by the gene SRD5A2 which is located on the short arm of chromosome 2 and contains five exons and four introns.  5αR2 consists of 254 amino acid residues with reported mutations at 67 of them with multiple different mutations at some residues.The first known mutation SRD5A2 was almost a complete deletion which was discovered from analysis of affected males in Papua New Guinean tribe. The majority of SRD5A2 mutations are missense mutations but small deletions, splice junction mutations, and gross deletions were also observed. Mutations result in a spectrum of activity effects ranging from destabilizing 5αR2 to complete loss of activity.SRD5A2 mutations are inherited in an autosomal recessive pattern. Homozygous defects are more common than compound heterozygous ones. A phenotype-genotype correlation is not known to exist for many of the most common mutations, and affected males with the same 5αR2 mutations have variable phenotypes suggesting other interacting genetic factors that determine phenotype.

Diagnosis
Diagnosis is usually made between birth and puberty. Pseudovaginal perineoscrotal hypospadias presenting with female appearing genitalia and pubertal virilization is the classical syndrome attributed to 5αR2D, but modern diagnostic methods can diagnose the deficiency shortly after birth and recognize the broad spectrum of presentation.The initial diagnosis of 46,XY DSD is indicated by overt genital abnormality. The objective clinical evaluation of dysmorphic features to diagnose 46,XY DSD for apparent female genitalia include: enlarged clitoris, posterior labial fusion, and inguinal/labial mass. For apparent male genitalia:  nonpalpable testes, micropenis, isolated perineal hypospadias, or mild hypospadias with undescended testis. Family history and prenatal history are also taken into account in evaluation. Karyotyping and SRY gene analysis on samples from peripheral leukocytes will exclude sex chromosome abnormalities. With the determination of an XY karyotype and normal SRY, the differential diagnosis of 46,XY DSD is made with endocrinological measurements of T/DHT ratios (which indicate 5αR2 activity) and precise anatomical imaging since 5αR2D can be difficult to distinguish from other causes of 46,XY DSD (e.g., partial androgen insensitivity syndrome and 17β- hydroxysteroid dehydrogenase type 3 enzyme deficiencies).The measurement of the serum DHT concentration is challenging since the concentrations are low and DHT has a high level of cross-reactivity. A high level of assay specificity is required to measure concentrations of DHT since serum T levels are generally 10 fold higher than DHT in young males.   Endocrinological tests for T/DHT ratios can be difficult to interpret since the normal ratio level varies according to age and severity of 5αR2 activity impairment. Affected young males of at least pubertal age with normal serum T levels demonstrate elevated T/DHT levels (normal T, lower than normal DHT).  Stimulation with human chorionic gonadotropin (hCG) (alternatively, testosterone enanthate) is required in prepubertal children (with stimulation and samples taken over several days) to increase serum testosterone levels for measurement. Interpreting T/DHT ratios in male newborns is especially challenging due to neonatal testosterone surge and higher than normal 5a-reductase type 1 activity. SRD5A2 gene analysis is recommended for diagnosis in newborns. Broadly, 5αR2D is diagnosed with T/DHT ratios greater than 18 while ratios greater than 30 have been observed in severely affected individuals. 5αR2D can also be indicated by low ratios of 5α- to 5ß- reduced steroids, as measured in urine measured via gas chromatography–mass spectrometry.Ultrasonography is the primary means for assessing internal reproductive organs for diagnosis while genitography and voiding cystourethrography are used to resolve structures such as urethral and vaginal tracts. The use of pelvic MRI for diagnostic imaging for 5αR2D remains controversial.

Management
One of the most clinically challenging and controversial topics with 46,XY DSD is the practice of "sex assignment" or "sex of rearing". This is especially so in 5αR2D, since most affected individuals have undervirilized genitalia at birth but virilize to varying degrees at puberty.  Historically most 5αR2D individuals have been "raised as females", but later reports show that over half of patients who underwent virilizing puberty adopted a male gender identity thus challenging historical practices.The goal of sex assignment/of rearing is to facilitate the greatest likelihood of a concordant gender identity in the patients adulthood. The factors that contribute to gender identity are complex and not easy to report but some factors that contribute include sex chromosomes, androgen exposure, psychosocial development, cultural expectations, family dynamics and social situation.Female sex of rearing in 5αR2D individuals involves surgical procedures such as childhood gonadectomy (to prevent virilization at puberty) and vaginoplasty. Life-long hormonal treatments as also required for the development and maintenance of female secondary sex characteristics. Male sex of rearing avoids lifelong hormonal treatments and allow for the potential of fertility.  Cryptorchidism and hypospadias must be addressed to prevent damage to the seminiferous tubules that are essential for spermatogenesis and fertility. Diagnosis in infancy is essential before any gender assignment or surgical intervention since patients should be considered males at birth.The intersection of the childs well-being, parental wishes, recommendations of the associated medical team and local laws makes decision making challenging in these cases. The necessity and ethics around consent and deception involved in administering such interventions has been seriously questioned.

Fertility
Spontaneous fertility in 5αR2D affected males is usually not possible (though has been observed) due to semen abnormalities that include reduced sperm counts, high semen viscosity and, in some cases, lack of primary spermatocytes. This supports the notion that DHT has an important role in spermatocyte differentiation. The broad spectrum of presentation is consistent with highly varying sperm counts among affected males. Testicular function may also be impaired by incomplete descent as well as the genetic mutation itself.Assisted reproduction methods involving sperm extraction and concentration for intrauterine insemination, intracytoplasmic sperm injection, and in vitro fertilization have all demonstrated successful outcomes.

Epidemiology
5αR2D is a rare condition, but has a worldwide distribution. A 2020 study identified 434 cases of 5αR2D across 44 countries including Turkey (23%), China (17%), Italy (9%), and Brazil (7%). The same study also found that genitalia virilization influenced sex assignment while gender change was influenced by cultural aspects across the countries. Molecular diagnosis resulted in favoring male sex assignment in affected newborns.Many SRD5A2 mutations come from areas with high coefficients of inbreeding, including the Dominican Republic (where people with the condition are called güevedoces – "testes at twelve"), and Papua New Guinea (where it is known as kwolu-aatmwol – suggesting a persons transformation "into a male thing"), and Turkey.In the Dominican Republic, güevedoces are regarded as a third gender and experience ambivalent gender socialisation. In adulthood, they most commonly self-identify as men, but are not necessarily completely treated as such by society. In the cases in Papua New Guinea, it has been said that the "girl" is shunned when he begins his natural transformation into a male body and socially assumes a male gender role.

History
An autosomal recessive disorder of sex development, described as pseudovaginal perineoscrotal hypospadias (PPSH), was discovered in males in 1961. The main feature of this syndrome was female appearing external genitalia with the presence of bilateral testes and male urogenital tracts in which the ejaculatory ducts terminate in a blind-ending vagina. This disorder was consistent with 5αR2D as the underlying cause as observed in animal models </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Björnstad syndrome and can you explain it in depth? [/INST] Björnstad syndrome is an autosomal recessive congenital condition involving pili torti, sensorineural deafness, and hair abnormalities. It was first characterized in 1965, in Oslo, by prof. Roar Theodor Bjørnstad after he observed an association between pili torti and hearing loss. The condition is extremely rare, with less than 50 cases documented in medical literature worldwide.Björnstad syndrome is caused by mutations of the BCS1L gene. The protein product of this gene is BCS1L, which plays an important role in oxidative phosphorylation. Mutated BCS1L increases production of reactive oxygen species, which may be the molecular cause of pili torti and hearing loss, both of which are associated with Björnstad syndrome. Pili torti is recognized in early childhood and is characterized by twisted hair shafts and brittle hair. The hearing loss usually becomes evident very early in life as well, often in the first year.

Signs and symptoms
The two major symptoms of Björnstad syndrome are pili torti and sensorineural hearing impairment. These two symptoms typically appear before the age of 2 and are present in 80-99% of individuals with Björnstad syndrome. Approximately 5-29% of individuals also experience intellectual disabilities and hypogonadism. Cases showing lack of hair pigmentation and anhidrosis have also been documented.Pili torti is a hair abnormality characterized by twisted hair shafts. In Björnstad syndrome patients, the hair usually appears dry, fragile, coarse, and is easily broken. In some patients, hair abnormalities only affect hair on the head, although cases affecting eyebrows, eyelashes, and hair on other parts of the body have been documented. Weakening of the hair associated with pili torti also causes alopecia in approximately 80% of patients.The severity of hearing loss associated with Björnstad syndrome varies. Some individuals are unable to hear sounds at certain frequencies, while others are completely deaf. Their hearing loss is caused by tissue damage of the inner ear.

Genetics
Björnstad syndrome is caused by a mutation in the BCS1L gene (position 2pq35) and is inherited in an autosomal recessive pattern. BCS1L is a protein that adds Rieske Fe/S to complex III during oxidative phosphorylation of cellular respiration. Mutations of BCS1L gene prevents the protein product from aiding in complex III formation, which reduces oxidative phosphorylation and increases the production of reactive oxygen species.Two missense mutations linked to Björnstad syndrome have been documented, but several other variants are suspected to be pathogenic. The clinical severity of different BCS1L mutations may be caused by the varying production of reactive oxygen species. The symptoms of Björnstad syndrome may be attributed to a particular sensitivity of inner ear and hair tissues to reactive oxygen species, but more research is needed </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Herpetic gingivostomatitis and can you explain it in depth? [/INST] Gingivostomatitis is a combination of gingivitis and stomatitis, or an inflammation of the oral mucosa and gingiva. Herpetic gingivostomatitis is often the initial presentation during the first ("primary") herpes simplex infection. It is of greater severity than herpes labialis (cold sores) which is often the subsequent presentations. Primary herpetic gingivostomatitis is the most common viral infection of the mouth.Primary herpetic gingivostomatitis (PHGS) represents the clinically apparent pattern of primary herpes simplex virus (HSV) infection, since the vast majority of other primary infections are symptomless. PHGS is caused predominantly by HSV-1 and affects mainly children. Prodromal symptoms, such as fever, anorexia, irritability, malaise and headache, may occur in advance of disease. The disease presents as numerous pin-head vesicles, which rupture rapidly to form painful irregular ulcerations covered by yellow–grey membranes. Sub-mandibular lymphadenitis, halitosis and refusal to drink are usual concomitant findings.

Signs and symptoms
The symptoms can be mild or severe and may include:

Not able to chew or swallow
Sores on the inside of the cheeks or gums
Fever
General discomfort, uneasiness, or ill feeling
Very sore mouth with no desire to eat
Halitosis (bad breath)

Causes
Herpetic gingivostomatitis is an infection caused by the herpes simplex virus (HSV).  The HSV is a double-stranded DNA virus categorised into two types; HSV-1 and HSV-2.  HSV-1 is predominantly responsible for oral, facial and ocular infections whereas HSV-2 is responsible for most genital and cutaneous lower herpetic lesions.  Both HSV-1, and HSV-2 can be the cause of herpetic gingivostomatitis, although HSV-1 is the source of infection in around 90% of cases.Herpetic gingivostomatitis infections can present as acute or recurrent.  Acute infection refers to the first invasion of the virus, and recurrent is when reactivation of the latent virus occurs.  Acute herpetic gingivostomatitis primarily occurs in children, particularly of those under the age of six years old.On external surfaces the virus is short lived, however it is extremely contagious.  Most people acquire the virus via direct contact, it can enter the body by disrupting the integrity of skin, mucous membranes or enter via infected secretions such as saliva.  The virus replicates once it has penetrated the epithelial cell, then it travels to the corresponding nerve ganglion (i.e. trigeminal ganglion) via sensory nerves endings.  At the nerve ganglion the virus enters a latent phase and remains dormant until it is reactivated.  Reactivation can be spontaneous or stimulated by a number of factors such as: reinfection by direct effect of stimuli, immunosuppression, ultraviolet light, febrile illnesses and stress.

Risk factors
Age: Primary herpetic gingivostomatitis is common in children from 6 months to 5 years old.  This virus is also common in young adults aged around 20–25.Immune system: The prevalence and severity of the disease is dependent on the hosts immune response and the virulence of the virus.
Environment: As this virus is very contagious it has the potential to spread quickly in enclosed environments e.g. nurseries and orphanages.Epidemiology: Those living in developing countries are at a higher risk of HSV-1 infection. It has been reported that around a 1/3rd of children living in developing countries are HSV-1 positive by 5 years old and 70-80% of the population are infected by the age of adolescence.  In developed countries only 20% of children are infected at the age of 5 and there is no significant increase in disease prevalence until 20–40 years old where the percentage of infected individuals ranges from 40-60% Socio-economic status: Those with a lower income have a higher risk of HSV-1 infection at a younger age.Race: Studies have demonstrated that in the USA 35% of African Americans by the age of 5 have presented with the disease whereas only 18% of White Americans are affected.

Pathophysiology
Herpetic gingivostomatitis originates from a primary infection of HSV-1. The series of events that take place during this infection include replication of the herpes simplex virus, cell lysis and finally, destruction of the mucosal tissue.HSV-1 can very easily enter and replicate within epidermal and dermal cells through skin or mucosal surfaces which have abrasions. This results in numerous small vesicles or blisters of up to 1-2mm on the oral mucosa, erosions on the lips, eventual hemorrhagic crusting and even ulceration, covered by a yellowish-grey pseudomembrane, surrounded by an erythematous halo.As the virus continues to replicate and incolulate in great amounts, it can enter autonomic or sensory ganglia, where it travels within axons to reach ganglionic nerve bodies. HSV-1 most commonly infects the trigeminal ganglia, where it remains latent. If reactivated, it presents as herpes labialis, also known as cold sores.

Diagnosis
Histopathology
The histological appearance of a herpetic infection on the mucosa includes degeneration of stratified squamous epithelial cells, the loss of intercellular connections and inflammatory infiltrate around the capillaries of the dermis layer. An intact herpetic vesicle presents as an intraepithelial blister histologically. This vesicle is caused by rupture and distension of the virally epithelial cells by intracellular oedema and coalescence of disrupted cells.Rupturing of the infected cells cause a great number of viral particles to be released, rendering them the ability to affect adjacent epithelial cells and even the sensory axons of the trigeminal nerve. Histologically, these infected cells have an eosinophilic cytoplasm and large, pale vesicular nuclei, appearing swollen under the microscope. The cytoplasms of the infected cells fuse, collectively forming giant cells with many nuclei. The balloon cells and multi-nucleated giant cells can often be identified in smears taken from an intact vesicle or from one which has been recently ruptured.The lamina propria shows a variable inflammatory infiltrate, the density of which depends on the stage and severity of the disease, and inflammatory cells also extend into the epithelium.Cowdry type A bodies are intranuclear inclusion bodies visible under light microscopy. They show electron dense glycoproteins and viral capsids. Both Cowdry type A bodies can both be found in varicella zoster and herpetic gingivostomatitis, making it impossible to distinguish between both eosinophilic bodies. One way to distinguish between the herpes virus (and hence herpetic gingivostomatitis) and varicella virus is by direct immunohistochemistry using fluorescent antibodies.

Differential diagnosis
Diagnosis of HG is very much clinically based. Therefore, it is imperative to rule out other diseases that present similarly, bearing in mind the past medical history of the patient.
Some differential diagnoses to bear in mind when considering herpetic gingivostomatitis are:

Teething in infants:  A study mentioned that  "primary  tooth  eruption begins  at  about the  time that  infants  are  losing  maternal antibody protection  against  the  herpes  virus. Also, reports  on  teething  difficulties  have  recorded  symptoms  which  are  remarkably  consistent  with  primary oral  herpetic  infection  such as  fever,  irritability,  sleeplessness,  and difficulty  with eating." Another study highlighted that "younger infants  with  higher residual  levels  of  antibodies  would experience  milder infections  and  these  would be  more likely  to  go unrecognized  or  be  dismissed  as  teething  difficulty."
Herpangina: It is a disease that is caused by the Coxackie A virus rather than a herpes virus. In herpangina, ulcers are usually isolated to the soft palate and anterior pillar of the mouth. In herpetic gingivostomatitis, lesions can be found in these locations, but they are almost always accompanied by ulcerations on the gums, lips, tongue or buccal mucosa and/or by hyperemia, hypertrophy or hemorrhage of the gums.
Hand Foot and Mouth Disease: Similar to herpangina, hand foot and mouth disease occurs predominantly in children. It is caused by Coxsackie A and B virus, and lesions or blisters are found bilaterally on the hands, feet and mouth of the patient.
Oral candidiasis: Also known as thrush, herpetic gingivostomatitis can often be differentiated from these microorganism/bacterial causing white plaques on the palate, buccal mucosa, tongue, oropharynx etc.
Apthous stomatitis: They are commonly known as apthous ulcers, and are characterized by grey membranes and peripheral erythema. Lesions/ulcers for herpetic gingivostomatitis may also be found on the palate and keratinzied gingivae hence aphthous ulcers can be ruled out.
Stevens–Johnson syndrome: Stevens–Johnson syndrome is characterized by early symptoms of malaise and fever, and shortly after that erythema, purpura and plaques on the skin, which often progresses to epidermal necrosis and sloughing in extreme cases.
Infectious mononucleosis - Infectious Mononucleosis presents with a high fever and lymphadenopathy, which is may or may not be presented in the symptoms of herpetic gingivostomatitis.  However, upon closer oral examination, ulceration, petechiae and occasional gingivostomatitis may be spotted.
Behcets syndrome - It is an inflammatory disorder in which the presenting symptoms are recurrent aphthous ulcers, and severe cases may result in the patient having genital lesions, gastro-intestinal problems, and even arthritis.
Varicella - Small ulcers on the back of the oral cavity and vesicular lesions on the scalp and trunk are common for Varicella </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Segmental odontomaxillary dysplasia and can you explain it in depth? [/INST] Segmental odontomaxillary dysplasia is a painless, unilateral enlargement of the upper jaw.  The cause is unknown, and the disease affects the jaws, teeth, and adjacent soft tissue </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Tuberculoma and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Hypoplasminogenemia and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Progressive bulbar palsy and can you explain it in depth? [/INST] Progressive bulbar palsy (PBP) is a medical condition. It belongs to a group of disorders known as motor neuron diseases. PBP is a disease that attacks the nerves supplying the bulbar muscles. These disorders are characterized by the degeneration of motor neurons in the cerebral cortex, spinal cord, brain stem, and pyramidal tracts. This specifically involves the glossopharyngeal nerve (IX), vagus nerve (X), and hypoglossal nerve (XII).This disorder should not be confused with pseudobulbar palsy or progressive spinal muscular atrophy. The term infantile progressive bulbar palsy is used to describe progressive bulbar palsy in children. The ICD-11 lists progressive bulbar palsy as a variant of amyotrophic lateral sclerosis (ALS).

Signs and symptoms
Prognosis for PBP patients is poor.  Progressive bulbar palsy symptoms can include progressive difficulty with talking and swallowing. Patients can also exhibit reduced gag reflexes, weak palatal movements, fasciculations, and weak movement of the facial muscles and tongue. In advanced cases of PBP, patients may be unable to protrude their tongue or manipulate food in their mouth.Patients with early cases of PBP have difficulty with pronunciations, particularly lateral consonants (linguals) and velars, and may show problems with drooling saliva. If the corticobulbar tract is affected a pseudobulbar affect with emotional changes may occur. Because PBP patients have such difficulty swallowing, food and saliva can be inhaled into the lungs. This can cause gagging and choking, and it increases the risk of pneumonia. Death, which is often from pneumonia, usually occurs 1 to 3 years after the start of the disorder.About twenty-five percent of patients with PBP eventually develop the widespread symptoms common to ALS.

Cause
The cause of PBP is unknown.  One form of PBP is found to occur within patients that have a CuZn-superoxide dismutase (SOD1) mutation. Progressive bulbar palsy patients that have this mutation are classified with FALS patients, Familial ALS (FALS) accounts for about 5%-10% of all ALS cases and is caused by genetic factors. Within these, about 20–25% are linked to the SOD1 mutation. It is not currently known if and how the decreased SOD1 activity contributes to Progressive Bulbar Palsy or FALS, and studies are being done in patients and transgenic mice to help further understand the impact of this gene on the disease.A case study was done on a 42-year-old woman who complained of muscle weakness 10 months prior to admission in the hospital. Upon neurological examination, the patient showed muscle atrophy, fasciculation in all limbs and decreased deep tendon reflexes. The patient’s older brother, father, and paternal uncle had previously all died of ALS or an ALS type syndrome. The patient developed progressive bulbar palsy, became dependent on a respirator, and had two episodes of cardiac arrest. The patient died from pneumonia two years after the onset of the disease. After studying the patient, it was found that the patient had a two base pair deletion in the 126th codon in exon 5 of the SOD1 gene. This mutation produced a frameshift mutation, which led to a stop codon at position 131. SOD1 activity was decreased by about 30%. The patient’s histological examination showed severe reduction in lower motor neurons. Upon further study, this case proved to be important because it demonstrated that SOD1 mutations might not effect steady neuropathological changes, and that environmental and genetic factors might affect the phenotype of the SOD1 mutations.

Treatment
PBP is aggressive and relentless, and there were no treatments for the disease as of 2005. However, early detection of PBP is the optimal scenario in which doctors can map out a plan for management of the disease. This typically involves symptomatic treatments that are frequently used in many lower motor disorders.

History
The disease was first recognized by the French neurologist Guillaume Duchenne in 1860 and termed, “labioglossolaryngeal paralysis”. In 1859, Wachsmuth changed the name to progressive bulbar palsy. In 1869, Charcot studied the involvement of the corticospinal tracts and with Joffroy, who noted the loss of the bulbar motor nuclei, discovered the similarities to amyotrophic lateral sclerosis (ALS). It was observed that a distinction from ALS was fatigue that predominated in muscles innervated by lower cranial nerve nuclei, rather than the upper motor neurons.

See also
Amyotrophic lateral sclerosis
Motor neuron disease

References
Bibliography
Lapiedra RC, Moreno Lopez LA, and Esparza Gomez GC. Progressive bulbar palsy: a case report diagnosed by lingual symptoms. J Oral Pathol Med. 31: 277-279. (2002)
Hughes TAT and Wiles CM. Neurogenic dysphagia: the role of the neurologist. J Neurol Neurosurg Psychiatry. 64:569-572. (1998)
Motor Neuron Disorders: Peripheral Nervous System Disorders. Merck Manual Professional section 16, chapter 223f. Merck Online Medical Library www.merck.com. (2005)
Collins, Joseph. Progressive Bulbar Palsy. ‘’The Treatment of Diseases of the Nervous System: A Manual for Practitioners’’. W. Wood and Company. (1900)
Swash M, and Desai J. Motor Neuron Disease: Classification and nomenclature. ALS and Other Motor Neuron Disorders. 1:105-112. (2000)
Kadekawa J et al. A clinicopathological study of a patient with familial amyotrophic lateral sclerosis associated with a two base pair deletion in the copper/zinc superoxide dismutase (SOD1) gene. Act Neuropathol </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Effects of cannabis and can you explain it in depth? [/INST] The effects of cannabis are caused by chemical compounds in the cannabis plant, including 113 different cannabinoids such as tetrahydrocannabinol (THC) and 120 terpenes, which allow its drug to have various psychological and physiological effects on the human body. Different plants of the genus Cannabis contain different and often unpredictable concentrations of THC and other cannabinoids and hundreds of other molecules that have a pharmacological effect, so that the final net effect cannot reliably be foreseen.
Acute effects while under the influence can sometimes include euphoria. Although some assert that cannabidiol (CBD), another cannabinoid found in cannabis in varying amounts, may alleviate the adverse effects of THC that some users experience, little is known about CBD effects on humans. Cannabinoid receptor antagonists have previously been tested as antidotes for cannabis intoxication with success, reducing or eliminating the physiological and psychological effects of intoxication. Some of these products are currently in development as cannabis antidotes.
In the United States, medical cannabis research is limited by federal restrictions. Smoking any substance could possibly carry similar risks as smoking tobacco due to carcinogens in all smoke, and the ultimate conclusions on these factors are disputed.Cannabis use disorder is defined as a medical diagnosis in the fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5).

Chemistry
Cannabinoids and cannabinoid receptors
The most prevalent psychoactive substances in cannabis are cannabinoids, particularly THC. Some varieties, having undergone careful selection and growing techniques, can yield as much as 34% THC. Another psychoactive cannabinoid present in Cannabis sativa is tetrahydrocannabivarin (THCV), but it is only found in small amounts and is a cannabinoid antagonist.There are similar compounds in cannabis that do not exhibit psychoactive response but are obligatory for functionality: cannabidiol (CBD), an isomer of THC; cannabivarin (CBV), an analog of cannabinol (CBN) with a different side chain, cannabidivarin (CBDV), an analog of CBD with a different side chain, and cannabinolic acid. CBD is believed to regulate the metabolism of THC by inactivating cytochrome P450 enzymes that metabolize drugs; one such mechanism is via generation of carbon monoxide (a pharmacologically active neurotransmitter) by upon metabolism of CBD. THC is converted rapidly to 11-hydroxy-THC, which is also pharmacologically active, so the euphoria outlasts measurable THC levels in blood.

Biochemical mechanisms in the brain
Cannabinoids usually contain a 1,1-di-methyl-pyran ring, a variedly derivatized aromatic ring and a variedly unsaturated cyclohexyl ring and their immediate chemical precursors, constituting a family of about 60 bi-cyclic and tri-cyclic compounds. Like most other neurological processes, the effects of cannabis on the brain follow the standard protocol of signal transduction, the electrochemical system of sending signals through neurons for a biological response. It is now understood that cannabinoid receptors appear in similar forms in most vertebrates and invertebrates and have a long evolutionary history of 500 million years. The binding of cannabinoids to cannabinoid receptors decrease adenylyl cyclase activity, inhibit calcium N channels, and disinhibit K+A channels. There are at least two types of cannabinoid receptors (CB1 and CB2).

Sustainability in the body
Most cannabinoids are lipophilic (fat soluble) compounds that are easily stored in fat, thus yielding a long elimination half-life relative to other recreational drugs. The THC molecule, and related compounds, are usually detectable in drug tests from 3 days up to 10 days according to Redwood Laboratories. Long-term users can produce positive tests for two to three months after ceasing cannabis use (see drug test).

Toxicities
When cannabis is smoked, blood levels of THC peak rapidly after a few minutes and then decline, although the psychotropic effects persist for longer. Edible forms of cannabis often contain several hundred milligrams of THC, much more than the 32mg of a typical cannabis cigarette. The rise of edible cannabis products has been responsible for a large increase of poisoning of children and young people: in American states which have legalized cannabis, emergency room admissions of such cases have typically doubled. Symptoms in children can include lethargy, sedation and seizure.Cannabis is suspected of being a potential contributory factor or direct cause of sudden death, due to the strain it can place on the cardiovascular system, or because of cannabinoid hyperemesis syndrome.

Related to cannabinoids
THC, the principal psychoactive constituent of the cannabis plant, has an extremely low toxicity and the amount that can enter the body through the consumption of cannabis plants poses no threat of death. In dogs, the minimum lethal dose of THC is over 3000 mg/kg. Edible forms of cannabis often contain several hundred milligrams of THC per dose, much more than the 32mg of a typical cannabis cigarette
According to the Merck Index, the LD50 of THC (the dose which causes the death of 50% of individuals) is 1270 mg/kg for male rats and 730 mg/kg for female rats from oral consumption in sesame oil, and 42 mg/kg for rats from inhalation.It is important though to note that cannabinoids and other molecules present in cannabis can alter the metabolism of other drugs, especially due to competition for clearing metabolic pathways such as cytochromes CYP450, thus leading to drug toxicities by medications that the person consuming cannabis may be taking.

Related to smoking
A 2007 study found that while tobacco and cannabis smoke are quite similar, cannabis smoke contained higher amounts of ammonia, hydrogen cyanide, and nitrogen oxides, but lower levels of carcinogenic polycyclic aromatic hydrocarbons (PAHs). This study found that directly inhaled cannabis smoke contained as much as 20 times as much ammonia and 5 times as much hydrogen cyanide as tobacco smoke and compared the properties of both mainstream and sidestream (smoke emitted from a smouldering joint or cone) smoke. Mainstream cannabis smoke was found to contain higher concentrations of selected polycyclic aromatic hydrocarbons (PAHs) than sidestream tobacco smoke. However, other studies have found much lower disparities in ammonia and hydrogen cyanide between cannabis and tobacco, and that some other constituents (such as polonium-210, lead, arsenic, nicotine, and tobacco-specific nitrosamines) are either lower or non-existent in cannabis smoke. A 2021 longitudinal study conducted among populations of HIV-positive and HIV-negative adults found that smoke-related carcinogenic toxicants and biomarkers detected in tobacco smokers were also detected in exclusive marijuana smokers, including carbon monoxide (CO), polycyclic aromatic hydrocarbons (PAHs), aldehydes (such as acrolein), acrylonitrile and acrylamide metabolites, but exposures are lower compared with tobacco or dual smokers. Increased levels of acrolein exposure by tobacco smoking but not exclusive marijuana smoking were detected both in HIV-positive and HIV-negative adults, and contribute to increased diagnoses of cardiovascular diseases and respiratory diseases among tobacco smokers.Cannabis smoke contains thousands of organic and inorganic chemical compounds. This tar is chemically similar to that found in tobacco smoke or cigars. Over fifty known carcinogens have been identified in cannabis smoke. These include nitrosamines, reactive aldehydes, and polycylic hydrocarbons, including benz[a]pyrene.  Marijuana smoke was listed as a cancer agent in California in 2009.  A study by the British Lung Foundation published in 2012 identifies cannabis smoke as a carcinogen and also finds awareness of the danger is low compared with the high awareness of the dangers of smoking tobacco particularly among younger users. Other observations include possible increased risk from each cigarette; lack of research on the effect of cannabis smoke alone; low rate of addiction compared to tobacco; and episodic nature of cannabis use compared to steady frequent smoking of tobacco. Professor David Nutt, a UK drug expert, points out that the study cited by the British Lung Foundation has been accused of both "false reasoning" and "incorrect methodology". Further, he notes that other studies have failed to connect cannabis with lung cancer, and accuses the BLF of "scaremongering over cannabis".

Short-term effects
When smoked, the short-term effects of cannabis manifest within seconds and are fully apparent within a few minutes, typically lasting for 1–3 hours, varying by the person and the strain of cannabis. After oral ingestion of cannabis, the onset of effect is delayed relative to smoking, taking 30 minutes to 2 hours, but the duration is prolonged due to continued slow absorption. The duration of noticeable effects has been observed to diminish after prolonged, repeated use and the development of increased tolerance to cannabinoids.

Psychological effects
The psychoactive effects of cannabis, known as a "high", are subjective and vary among persons and the method of use.
When THC enters the blood stream and reaches the brain, it binds to cannabinoid receptors. The endogenous ligand of these receptors is anandamide, the effects of which THC emulates. This agonism of the cannabinoid receptors results in changes in the levels of various neurotransmitters, especially dopamine and norepinephrine; neurotransmitters which are closely associated with the acute effects of cannabis ingestion, such as euphoria and anxiety.
Some effects may include a general alteration of conscious perception, euphoria, feelings of well-being, relaxation or stress reduction, increased appreciation of the arts, including humor and music (especially discerning its various components/instruments), joviality, metacognition and introspection, enhanced recollection (episodic memory), increased sensuality, increased awareness of sensation, increased libido, and creativity. Abstract or philosophical thinking, disruption of linear memory and paranoia or anxiety are also typical. Anxiety is the most commonly reported negative side effect of smoking marijuana. Between 20 and 30 percent of recreational users experience intense anxiety and/or panic attacks after smoking cannabis; however, some report anxiety only after not smoking cannabis for a prolonged period of time. Inexperience and use in an unfamiliar environment are major contributing factors to this anxiety. Cannabidiol (CBD), another cannabinoid found in cannabis in varying amounts, has been shown to ameliorate the adverse effects of THC, including anxiety, that some consumers experience.Cannabis produces many other subjective effects, including an increased enjoyment of food taste and aroma, and marked distortions in the perception of time (where experiencing a "rush" of ideas can create the subjective impression of much time passing). At higher doses, effects can include altered body image, auditory and/or visual illusions, pseudohallucinations, and ataxia from selective impairment of polysynaptic reflexes. In some cases, cannabis can lead to acute psychosis and dissociative states such as depersonalization and derealization.Furthermore, even in those with no family history of psychosis, the administration of pure THC in clinical settings has been demonstrated to elicit transient psychotic symptoms. Any episode of acute psychosis that accompanies cannabis use usually abates after six hours, but in rare instances, heavy users may find the symptoms continuing for many days. If the episode is accompanied by aggression or sedation, physical restraint may be necessary.While psychoactive drugs are typically categorized as stimulants, depressants, or hallucinogens, cannabis exhibits a mix of all of these effects, perhaps leaning more towards hallucinogenic or psychedelic properties, though with other effects quite pronounced. THC is considered the primary active component of the cannabis plant. Scientific studies have suggested that other cannabinoids like CBD may also play a significant role in its psychoactive effects.

Somatic effects
Some of the short-term physical effects of cannabis use include increased heart rate, dry mouth, reddening of the eyes (congestion of the conjunctival blood vessels), a reduction in intra-ocular pressure, muscle relaxation and a sensation of cold or hot hands and feet and / or flushed face.Electroencephalography or EEG shows somewhat more persistent alpha waves of slightly lower frequency than usual. Cannabinoids produce a "marked depression of motor activity" via activation of neuronal cannabinoid receptors belonging to the CB1 subtype.

Duration
Peak levels of cannabis-associated intoxication occur approximately 20 minutes after smoking it and last for several hours.

Smoked
The total short-term duration of cannabis use when smoked depends on the potency, method of smoking – e.g. whether pure or in conjunction with tobacco – and how much is smoked. Peak levels of intoxication typically last an average of three to four hours.

Oral
When taken orally (in the form of capsules, food, or drink), the psychoactive effects take longer to manifest and generally last longer, typically lasting for an average of four to six hours after consumption. Oral ingestion use eliminates the need to inhale toxic combustion products created by smoking and therefore negates the risk of respiratory harm associated with cannabis smoking.

Effects on driving
While several studies have shown increased risk associated with cannabis use by drivers, other studies have not found increased risk. Cannabis usage has been shown in some studies to have a negative effect on driving ability.
The British Medical Journal indicated that "drivers who consume cannabis within three hours of driving are nearly twice as likely to cause a vehicle collision as those who are not under the influence of drugs or alcohol".In Cannabis and driving: a review of the literature and commentary, the United Kingdoms Department for Transport reviewed data on cannabis and driving, finding although impaired, "subjects under cannabis treatment appear to perceive that they are indeed impaired. Where they can compensate, they do". In a review of driving simulator studies, researchers note that "even in those who learn to compensate for a drugs impairing effects, substantial impairment in performance can still be observed under conditions of general task performance (i.e. when no contingencies are present to maintain compensated performance)."A 2012 meta-analysis found that acute cannabis use increased the risk of an automobile crash. An extensive 2013 review of 66 studies regarding crash risk and drug use found that cannabis was associated with minor, but not statistically significant increased odds of injury or fatal accident.In the largest and most precisely controlled study of its kind carried out by the U.S. Department of Transportations National Highway Traffic Safety Administration, it was found that other "studies that measure the presence of THC in the drivers blood or oral fluid, rather than relying on self-report tend to have much lower (or no) elevated crash risk estimates. Likewise better controlled studies have found lower (or no) elevated crash risk estimates". The study found that "after adjusting for age, gender, race and alcohol use, drivers who tested positive for marijuana  were no more likely to crash than those who had not used any drugs or alcohol prior to driving".A 2018 study indicated that the number of fatal crashes involving marijuana after the recreational marijuana legalization or decriminalization increased in Colorado, Washington, and Massachusetts.

Cardiovascular effects
Short-term (one to two hours) effects on the cardiovascular system can include increased heart rate, dilation of blood vessels, and fluctuations in blood pressure.  There are medical reports of occasional heart attacks or myocardial infarction, stroke and other cardiovascular side effects.  Marijuanas cardiovascular effects are not associated with serious health problems for most young, healthy users. Researchers reported in the International Journal of Cardiology, "Marijuana use by older people, particularly those with some degree of coronary artery or cerebrovascular disease, poses greater risks due to the resulting increase in catecholamines, cardiac workload, and carboxyhemoglobin levels, and concurrent episodes of profound postural hypotension. Indeed, marijuana may be a much more common cause of myocardial infarction than is generally recognized. In day-to-day practice, a history of marijuana use is often not sought by many practitioners, and even when sought, the patients response is not always truthful".A 2013 analysis of 3,886 myocardial infarction survivors over an 18-year period showed "no statistically significant association between marijuana use and mortality".A 2008 study by the National Institutes of Health Biomedical Research Centre in Baltimore found that heavy, chronic smoking of marijuana (138 joints per week) changed blood proteins associated with heart disease and stroke.A 2000 study by researchers at Bostons Beth Israel Deaconess Medical Center, Massachusetts General Hospital and Harvard School of Public Health found that a middle age persons risk of heart attack rises nearly fivefold in the first hour after smoking marijuana, "roughly the same risk seen within an hour of sexual activity".Cannabis arteritis is a very rare peripheral vascular disease similar to Buergers disease. There were about 50 confirmed cases from 1960 to 2008, all of which occurred in Europe.

Combination with other drugs
A confounding factor in cannabis research is the prevalent usage of other recreational drugs, especially alcohol and nicotine. Such complications demonstrate the need for studies on cannabis that have stronger controls, and investigations into alleged symptoms of cannabis use that may also be caused by tobacco. Some critics question whether agencies doing the research make an honest effort to present an accurate, unbiased summary of the evidence, or whether they "cherry-pick" their data to please funding sources which may include the tobacco industry or governments dependent on cigarette tax revenue; others caution that the raw data, and not the final conclusions, are what should be examined.The Australian National Household Survey of 2001 showed that cannabis in Australia is rarely used without other drugs. 95% of cannabis users also drank alcohol; 26% took amphetamines; 19% took ecstasy and only 2.7% reported not having used any other drug with cannabis. While research has been undertaken on the combined effects of alcohol and cannabis on performing certain tasks, little research has been conducted on the reasons why this combination is so popular. Evidence from a controlled experimental study undertaken by Lukas and Orozco suggests that alcohol causes THC to be absorbed more rapidly into the blood plasma of the user. Data from the Australian National Survey of Mental Health and Wellbeing found that three-quarters of recent cannabis users reported using alcohol when cannabis was not available, this suggests that the two are substitutes.

Memory and learning
Studies on cannabis and memory are hindered by small sample sizes, confounding drug use, and other factors. The strongest evidence regarding cannabis and memory focuses on its temporary negative effects on short-term and working memory.In a 2001 study looking at neuropsychological performance in long-term cannabis users, researchers found "some cognitive deficits appear detectable at least 7 days after heavy cannabis use but appear reversible and related to recent cannabis exposure rather than irreversible and related to cumulative lifetime use". On his studies regarding cannabis use, lead researcher and Harvard professor Harrison Pope said he found marijuana is not dangerous over the long term, but there are short-term effects. From neuropsychological tests, Pope found that chronic cannabis users showed difficulties, with verbal memory in particular, for "at least a week or two" after they stopped smoking. Within 28 days, memory problems vanished and the subjects "were no longer distinguishable from the comparison group".
Researchers from the University of California, San Diego School of Medicine failed to show substantial, systemic neurological effects from long-term recreational use of cannabis. Their findings were published in the July 2003 issue of the Journal of the International Neuropsychological Society. The research team, headed by Dr Igor Grant, found that cannabis use did affect perception, but did not cause permanent brain damage. Researchers looked at data from 15 previously published controlled studies involving 704 long-term cannabis users and 484 nonusers. The results showed long-term cannabis use was only marginally harmful on the memory and learning. Other functions such as reaction time, attention, language, reasoning ability, perceptual and motor skills were unaffected. The observed effects on memory and learning, they said, showed long-term cannabis use caused "selective memory defects", but that the impact was "of a very small magnitude".  A study at Johns Hopkins University School of Medicine showed that very heavy use of marijuana is associated with decrements in neurocognitive performance even after 28 days of abstinence.

Appetite
The feeling of increased appetite following the use of cannabis has been documented for hundreds of years, and is known colloquially as "the munchies" in the English-speaking world. Clinical studies and survey data have found that cannabis increases food enjoyment and interest in food. A 2015 study suggests that cannabis triggers uncharacteristic behaviour in POMC neurons, which are usually associated with decreasing hunger.Endogenous cannabinoids ("endocannabinoids") were discovered in cows milk and soft cheeses. Endocannabinoids are also found in human breast milk. It is widely accepted that the neonatal survival of many species "is largely dependent upon their suckling behavior, or appetite for breast milk" and recent research has identified the endogenous cannabinoid system to be the first neural system to display complete control over milk ingestion and neonatal survival. It is possible that "cannabinoid receptors in our body interact with the cannabinoids in milk to stimulate a suckling response in newborns so as to prevent growth failure".

Pathogens and microtoxins
Most microorganisms found in cannabis only affect plants and not humans, but some microorganisms, especially those that proliferate when the herb is not correctly dried and stored, can be harmful to humans. Some users may store marijuana in an airtight bag or jar in a refrigerator to prevent fungal and bacterial growth.

Fungi
The fungi Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, Aspergillus parasiticus, Aspergillus tamarii, Aspergillus sulphureus, Aspergillus repens, Mucor hiemalis (not a human pathogen), Penicillium chrysogenum, Penicillium italicum and Rhizopus nigricans have been found in moldy cannabis. Aspergillus mold species can infect the lungs via smoking or handling of infected cannabis and cause opportunistic and sometimes deadly aspergillosis. Some of the microorganisms found create aflatoxins, which are toxic and carcinogenic. Researchers suggest that moldy cannabis should thus be discarded to avoid these serious risks.Mold is also found in smoke from mold-infected cannabis, and the lungs and nasal passages are a major means of contracting fungal infections. Levitz and Diamond (1991) suggested baking marijuana in home ovens at 150 °C [302 °F], for five minutes before smoking. Oven treatment killed conidia of A. fumigatus, A. flavus and A. niger, and did not degrade the active component of marijuana, tetrahydrocannabinol (THC)."

Bacteria
Cannabis contaminated with Salmonella muenchen was positively correlated with dozens of cases of salmonellosis in 1981. "Thermophilic actinomycetes" were also found in cannabis.

Long-term effects
Exposure to marijuana may have biologically based physical, mental, behavioral, and social health consequences and is "associated with diseases of the liver (particularly with co-existing hepatitis C), lungs, heart, eyesight, and vasculature" according to a 2013 literature review by Gordon and colleagues. The association with these diseases has only been reported in cases where people have smoked cannabis. The authors cautioned that "evidence is needed, and further research should be considered, to prove causal associations of marijuana with many physical health conditions".Cannabis use disorder is defined in the fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) as a condition requiring treatment. Several drugs have been investigated in an attempt to ameliorate the symptoms of stopping cannabis use. Such drugs include bupropion, divalproex, nefazodone, lofexidine, and dronabinol. Of these, dronabinol (a trade name for THC) has proven the most effective. The drugs buspirone and rimonabant have shown some success in helping maintain cannabis abstinence.There is evidence that long-term use of cannabis increases the risk of psychosis, regardless of confounding factors, and particularly for people who have genetic risk factors. A 2019 meta-analysis found that 34% of people with cannabis-induced psychosis transitioned to schizophrenia. This was found to be comparatively higher than hallucinogens (26%) and amphetamines (22%).Long-term cannabis users are at risk for developing cannabinoid hyperemesis syndrome (CHS), characterized by recurrent bouts of intense vomiting. The mechanism behind CHS is poorly understood and is contrary to the antiemetic properties of cannabis and cannabinoids. Of those who went to the emergency department (ED) with recurrent vomiting in one institution in the United States from 2005 to 2010, about 6% had the condition.

Effects in pregnancy
Cannabis consumption in pregnancy might be associated with restrictions in growth of the fetus, miscarriage, and cognitive deficits in offspring based on animal studies, although there is limited evidence for this in humans at this time. A 2012 systematic review found although it was difficult to draw firm conclusions, there was some evidence that prenatal exposure to cannabis was associated with "deficits in language, attention, areas of cognitive performance, and delinquent behavior in adolescence" </s>


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