<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 Ventricular aneurysm and can you explain it in depth? [/INST] Ventricular aneurysms are one of the many complications that may occur after a heart attack. The word aneurysm refers to a bulge or pocketing of the wall or lining of a vessel commonly occurring in the blood vessels at the base of the septum, or within the aorta. In the heart, they usually arise from a patch of weakened tissue in a ventricular wall, which swells into a bubble filled with blood. This, in turn, may block the passageways leading out of the heart, leading to severely constricted blood flow to the body. Ventricular aneurysms can be fatal. They are usually non-rupturing because they are lined by scar tissue.
A left ventricular aneurysm can be associated with ST elevation.

Signs and symptoms
Ventricular aneurysms usually grow at a very slow pace, but can still pose problems. Usually, this type of aneurysm grows in the left ventricle. This bubble has the potential to block blood flow to the rest of the body, and thus limit the patients stamina. In other cases, a similarly developed pseudoaneurysm ("false aneurysm") may burst, sometimes resulting in the death of the patient. Also, blood clots may form on the inside of ventricular aneurysms, and form embolisms. If such a clot escapes from the aneurysm, it will be moved in the circulation throughout the body. If it gets stuck inside a blood vessel, it may cause ischemia in a limb, a painful condition that can lead to reduced movement and tissue death in the limb. Alternatively, if a clot blocks a vessel going to the brain, it can cause a stroke. In certain cases, ventricular aneurysms cause ventricular failure or arrythmia. At this stage, treatment is necessary.

Causes
Ventricular aneurysms are usually complications resulting from a heart attack. When the heart muscle (cardiac muscle) partially dies during a heart attack, a layer of muscle may survive, and, being severely weakened, start to become an aneurysm. Blood may flow into the surrounding dead muscle and inflate the weakened flap of muscle into a bubble. It may also be congenital.

Diagnosis
When a person visits the hospital or doctor with other symptoms, especially with a history of heart problems, they will normally be required to undergo an electrocardiogram, which monitors electrical activity within the heart and shows abnormalities when a cardiac aneurysm is present. It can also appear as a bulge on a chest x-ray, and a more accurate diagnosis will then be made using an echocardiogram, which uses ultrasound to photograph the heart and how it functions while it beats.

Differential diagnosis
It should also not be confused with a pseudoaneurysm, coronary artery aneurysm or a myocardial rupture (which involves a hole in the wall, not just a bulge.)

Cardiac Diverticulum
Cardiac diverticulum or ventricular diverticulum is defined as a congenital malformation of the fibrous or muscular part of the heart which is only visible during chest x-rays or during an echocardiogram reading. This should not be confused with ventricular diverticulum, as the latter is a sub type derived from the latter in congenital cases. it is usually asymptomatic and is only detected using imaging. Fibrous diverticulum is characterised by a calcification if present at the tip ( apex) or a thrombi that may detaches to form an emboli. Muscular diverticulum is characterised by appendix forming at the ether of the ventricles. it is a rare anomaly and can be diagnosed prenatal. Diagnosis is usually done by a chest X-ray and silhouette is viewed around the heart. Echocardiogram reading present a similar picture to ventricular aneurysms on the ST segment. Management is dependent on the situation presented and the severity of the case. Usually, surgical resection is advised but in prenatal cases, due to combination with other cardiac abnormalities, especially in latter trimesters, but pericardiocentesis is useful technique to reduce pleural effusion or/ and secondary disorders.

Treatment
Some people live with this type of aneurysm for many years without any specific treatment. Treatment is limited to surgery (ventricular reduction) for this defect of the heart. However, surgery is not required in most cases but, limiting the patients physical activity levels to lower the risk of making the aneurysm bigger is advised. Also, ACE Inhibitors seem to prevent Left Ventricular remodeling and aneurysm formation.Blood thinning agents may be given to help reduce the likelihood of blood thickening and clots forming, along with the use of drugs to correct the irregular rhythm of the heart (seen on the electrocardiogram)

See also
Coronary artery aneurysm

References
Further reading
Graber, J.D.; Oakley, C.M.; Pickering, B.N.; Goodwin, J.F.; Raphael, M.J.; Steiner, R.E. (1972). "Ventricular aneurysm. An appraisal of diagnosis and surgical treatment". British Heart Journal </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 Dissecting cellulitis of the scalp 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 Ligamentous laxity and can you explain it in depth? [/INST] Ligamentous laxity, or ligament laxity, means loose ligaments. Ligamentous laxity is a cause of chronic body pain characterized by loose ligaments. When this condition affects joints in the entire body, it is called generalized joint hypermobility, which occurs in about ten percent of the population, and may be genetic. Loose ligaments can appear in a variety of ways and levels of severity. It also does not always affect the entire body. One could have loose ligaments of the feet, but not of the arms.
Someone with ligamentous laxity, by definition, has loose ligaments. Unlike other, more pervasive diseases, the diagnosis does not require the presence of loose tendons, muscles or blood vessels, hyperlax skin or other connective tissue problems. In heritable connective tissue disorders associated with joint hypermobility (such as Marfan syndrome and Ehlers–Danlos syndrome types I–III, VII, and XI), the joint laxity usually is apparent before adulthood. However, age of onset and extent of joint laxity are variable in Marfan syndrome, and joint laxity may be confined to the hands alone, as in Ehlers–Danlos syndrome type I. In addition, ligamentous laxity may appear in conjunction with physical co-ordination conditions such as dyspraxia.

Presentation
While ligamentous laxity may be genetic and affect an individual from a very early age, it can also be the result of an injury. Injuries, especially those involving the joints, invariably damage ligaments either by stretching them abnormally or even tearing them.
Loose or lax ligaments in turn are not capable of supporting joints as effectively as healthy ones, making the affected individual prone to further injury as well as compensation for the weakness using other parts of the body. Affected individuals may improve over time and lose some of their juvenile hyperlaxity as they age. Individuals over age 40 often have recurrent joint problems and almost always have chronic pain. Back patients with ligamentous laxity in the area of the spine may also experience osteoarthritis and disc degeneration.
In the case of extreme laxity, or hypermobility, affected individuals often have a decreased ability to sense joint position, which can contribute to joint damage. The resulting poor limb positions can lead to the acceleration of degenerative joint conditions. Many hypermobility patients have osteoarthritis, disorders involving nerve compression, chondromalacia patellae, excessive anterior mandibular movement, mitral valve prolapse, uterine prolapse and varicose veins.

Symptoms
Arthralgia, or symptoms such as frequent sprained ankles, shoulder dislocations, knee effusions and back problems are common among individuals with ligamentous laxity. Affected individuals are also prone to bone dislocation, and those with a sedentary job often report back pain. In addition, people may experience referred pain, that is, pain in an area of the body away from the injured or otherwise affected site.
Individuals with extremely lax, or hypermobile joints, can be identified by their ability to bend their elbows, knees or hips past a position of neutrality. They may also be able to easily touch their hands flat to the floor while bending forward from the waist. The ability to touch the thumb to the forearm is also common.
Referred pain is created by ligamentous laxity around a joint, but is felt at some distance from the injury. (Pain will not only occur at the site of the injury and loose ligaments, but may also be referred to other parts of the body.) These painful points that refer pain elsewhere are called trigger points, and will be dealt with later. Abnormal joint movement also creates many "protective actions" by adjacent tissues. Muscles will contract in spasm in an attempt to pull the joint back to the correct location or stabilize it to protect it from further damage.
When this occurs in the back, orthopedic surgeons will often try to reduce vertebral instability by fusing the vertebrae with bone and/or metal fixation.

Feet
Those who have loose ligaments in the legs and feet may appear to have flat feet. While their feet have an arch when not supporting weight, when stood upon, the arch will flatten. This is because the loose ligaments cannot support the arch in the way that they should. This can make walking and standing painful and tiring.
Pain will usually occur in the feet and lower legs, but can also spread to the back due to abnormal standing and walking habits. Wearing shoes that have good arch support can help minimize the discomfort. The underlying problem, however, is not solved by wearing shoes with arch supports, or worsened by wearing shoes without arch support </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 Thoracic insufficiency syndrome 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 Noma (disease) and can you explain it in depth? [/INST] Noma (also known as necrotizing ulcerative stomatitis, gangrenous stomatitis, or cancrum oris) is a rapidly progressive and often fatal infection of the mouth and face. This disease predominantly affects children between the ages of two and six years old in the least developed countries around the world.

Signs and symptoms
The mucous membranes of the mouth develop ulcers, followed by rapid, painful tissue degeneration and necrosis of the tissues of the bones in the face.

Causes
The underlying causes for this disease are primarily poor sanitation and malnutrition. Although the causative organisms are common in many environments, this disease nearly exclusively affects extremely impoverished and malnourished children in tropical regions.Noma is often reported as a sequela to acute necrotizing ulcerative gingivitis. Fusobacterium necrophorum and Prevotella intermedia are important bacterial pathogens in this disease process, interacting with one or more other bacterial organisms (such as Treponema denticola, Treponema vincentii, Porphyromonas gingivalis, Tannerella forsythia, Staphylococcus aureus, and certain species of nonhemolytic Streptococcus) </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 Lymphangitis carcinomatosa 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 Pleural thickening 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 Acheiropodia 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 Parasystole and can you explain it in depth? [/INST] Parasystole is a kind of arrhythmia caused by the presence and function of a secondary pacemaker in the heart, which works in parallel with the SA node. Parasystolic pacemakers are protected from depolarization by the SA node by some kind of entrance block </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 Phocomelia and can you explain it in depth? [/INST] Phocomelia is a condition that involves malformations of human arms and legs. Although many factors can cause phocomelia, the prominent roots come from the use of the drug thalidomide and from genetic inheritance.
Occurrence in an individual results in various abnormalities to the face, limbs, ears, nose, vessels and many other underdevelopments. Although operations may improve some abnormalities, many are not surgically treatable due to the lack of nerves and other related structures.
The term is from Ancient Greek φώκη phōkē, "seal (animal)" + -o- interfix + μέλος melos, "limb" + English suffix -ia). Phocomelia is an extremely rare congenital disorder involving malformation of the limbs (dysmelia). Étienne Geoffroy Saint-Hilaire coined the term in 1836.

Signs and symptoms
The symptoms of phocomelia syndrome are undeveloped limbs and absent pelvic bones; however, various abnormalities can occur to the limbs and bones. Usually the upper limbs are not fully formed and sections of the "hands and arms may be missing." Short arm bones, fused fingers, and missing thumbs will often occur. Sometimes hands or fingers will be present but limp due to having no bones or being loosely attached. Legs and feet are also affected similarly to the arms and hands. Individuals with phocomelia will often lack thigh bones, and the hands or feet may be abnormally small or appear as stumps due to their close "attachment to the body."According to National Organization for Rare Disorders (NORD), individuals carrying phocomelia syndrome will generally show symptoms of growth retardation previous to and after birth. The syndrome can also cause severe mental deficiencies in infants. Infants born with phocomelia will normally have a petite head with "sparse hair" that may appear "silvery-blonde." Hemangioma, the abnormal buildup of blood vessels, will possibly develop around the facial area at birth and the eyes may be set widely apart, a condition known as orbital hypertelorism. The pigment of the eyes will be a bluish white. Phocomelia can also cause: an undeveloped nose with slender nostrils, disfigured ears, irregularly petite jaws (a condition known as micrognathia), and a cleft lip with cleft palate. According to NORD, severe symptoms of phocomelia include:
A fissure of the skull and a projecting brain known as (encephalocele)
An accumulation of spinal fluid under the skull also known as hydrocephalus; causing vomiting and migraines
An abnormally shaped uterus (bicornuate)
Inability to clot blood efficiently due to a low amount of platelets running through the blood
Malformations in the kidney and heart
Shortened neck
Abnormalities in the urethra

Thalidomide syndrome symptoms
When an individual is born with phocomelia due to drugs or pharmaceuticals, it is known as thalidomide syndrome. The symptoms of thalidomide syndrome are defined by absent or shortened limbs; causing flipper hands and feet. According to Anthony J Perri III, and Sylvia Hsu they can additionally receive:
Palsy disorder of the face
Ear and eye abnormalities; resulting in limited/complete loss of hearing or sight
Gastrointestinal and genitourinary tract disorders
Ingrown genitalia
Undeveloped/missing lungs
Distorted digestive tract, heart, kidney
disorders to the limbsThe infants that were exposed to thalidomide during development phases had a 40% chance of survival. The McMredie-McBride hypothesis explains that the limbs of the infants become malformed as a result of the thalidomide harming the neural tissue—simply because the neural tissue has such a large impact on formation and development of the limbs.

Causes
Thalidomide
Thalidomide was released onto the market in 1958 in West Germany under the name Contergan. Primarily prescribed as a sedative or hypnotic, thalidomide also claimed to cure "anxiety, insomnia, gastritis, and tension". Afterwards it was used against nausea and to alleviate morning sickness in pregnant women. Thalidomide became an over-the-counter drug in Germany around 1960, i.e. it could be bought without a prescription. Shortly after the drug was sold, in Germany between 5,000 and 7,000 infants were born with phocomelia. Only 40% of these children survived.Research also proves that although phocomelia did exist through the 1940s and 1950s cases of severe phocomelia multiplied in the 1960s when thalidomide was released in Germany; the direct cause was traced to thalidomide. The statistic was given that "50 percent of the mothers with deformed children had taken thalidomide during the first trimester of pregnancy." Throughout Europe, Australia and the United States 10,000 cases were reported of infants with phocomelia; only 50% of the 10,000 survived. Thalidomide became effectively linked to death or severe disabilities among babies. Those subjected to thalidomide while in the womb experienced limb deficiencies in that the long limbs either were not developed or presented themselves as stumps. Other effects included deformed eyes, hearts, alimentary and urinary tracts, blindness and deafness.

Genetic inheritance
According to National Organization for Rare Disorders (NORD): when phocomelia is transmitted [in its familial genetic form] it is seen as an autosomal recessive trait and the mutation is linked to chromosome 8.A study of Roberts Syndrome, a genetic disorder showing similar symptoms to phocomelia, has shed light on the possible causes. An individual afflicted with Roberts Syndrome will have chromosome copies that do not connect at the centromeres, making them unable to line up accordingly. As a result, the newly made cells contain an excess or reduced number of chromosomes. In both Roberts Syndrome and phocomelia the cells cease to develop, or die, preventing proper development of the limbs, eyes, brain, palate, or other structures.

Treatment
Prosthesis is a synthetic alternative for missing limbs, teeth, and various other body parts. Advances in prosthetic limbs have increased greatly during the twentieth century. The use of new materials such as modern plastics, complex procedures and better pigments have created lighter in weight and more realistic looking artificial limbs. With the advancement of myoelectric prosthetic limbs, patients are able to move their limbs without the use of cords or other devices. The myoelectric limbs can detect electric signals from the nervous system and muscles. They were first used on adults, but now they are being fitted to children.Patients that receive a loss of limbs due to phocomelia are typically treated with prosthetics. Infants at the age of six months are recommended to have a prosthetic mitten fitted; enabling them to get used to the prosthesis. A hook will be added when the child reaches the age of two years. Eventually the patient may receive a myoelectric prosthetic limb. Patients are treated in this way due to the lack of understanding at a young age and the absence of necessary tissues and bones to hold the prosthetic limb.

Notable cases
Mat Fraser was born with phocomelia due to his mother taking thalidomide while she was pregnant. He is known as the drummer of rock bands including Fear of Sex, The Reasonable Strollers, Joyride, The Grateful Dub, and Living in Texas. He is also an actor and performing artist.
Alison Lapper was born with phocomelia. She is arm deficient and has shortened bones and legs. Lapper graduated from Brighton University in 1994, established herself as a visual artist, and in 2000 gave birth to a son, Parys. Lapper produces cards and calendars for The Mouth and Foot Painters Association. She does not wear prosthetic limbs.
Ronan Tynan was born with phocomelia. He became a track and field athlete, competing in the 1984 and 1988 Summer Paralympics. Tynan went on to a career as a physician, and later, a singer.
Ame Barnbrook was born without arms and only the lower half of her left leg, and three toes </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 Nephrocalcinosis and can you explain it in depth? [/INST] Nephrocalcinosis, once known as Albrights calcinosis after Fuller Albright, is a term originally used to describe deposition of calcium salts in the renal parenchyma due to hyperparathyroidism. The term nephrocalcinosis is used to describe the deposition of both calcium oxalate and calcium phosphate. It may cause acute kidney injury. It is now more commonly used to describe diffuse, fine, renal parenchymal calcification in radiology. It is caused by multiple different conditions and is determined progressive kidney dysfunction.  These outlines eventually come together to form a dense mass. During its early stages, nephrocalcinosis is visible on x-ray, and appears as a fine granular mottling over the renal outlines. It is most commonly seen as an incidental finding with medullary sponge kidney on an abdominal x-ray.
It may be severe enough to cause (as well as be caused by) renal tubular acidosis or even end stage kidney disease, due to disruption of the kidney tissue by the deposited calcium.

Signs and symptoms
Though this condition is usually asymptomatic, if symptoms are present they are usually related to the causative process, (e.g. hypercalcemia). Some of the symptoms that can happen are blood in the urine, fever and chills, nausea and vomiting, severe pain in the belly area, flanks of the back, groin, or testicles.
These include renal colic, polyuria and polydipsia:
Renal colic is usually caused by pre-existing nephrolithiasis, as may occur in patients with chronic hypercalciuria. Less commonly, it can result from calcified bodies moving into the calyceal system.
Nocturia, polyuria, and polydipsia from reduced urinary concentrating capacity (i.e. nephrogenic diabetes insipidus) as can be seen in hypercalcemia, medullary nephrocalcinosis of any cause, or in children with Bartter syndrome in whom essential tubular salt reabsorption is compromised.There are several causes of nephrocalcinosis that are typically acute and present only with kidney failure. These include tumor lysis syndrome, acute phosphate nephropathy, and occasional cases of enteric hyperoxaluria.

Cause
Nephrocalcinosis is connected with conditions that cause hypercalcemia, hyperphosphatemia, and the increased excretion of calcium, phosphate, and/or oxalate in the urine. A high urine pH can lead to  Nephrocalcinosis but only if it is accompanied by hypercalciuria and hypocitraturia, since having a normal urinary citrate usually inhibits the crystallization of calcium. In conjunction with Nephrocalcinosis, hypercalcemia and hypercalciuria the following can occur:
Primary hyperparathyroidism: Nephrocalcinosis is one of the most common symptoms of primary hyperparathyroidism.
Sarcoidosis: Nephrocalcinosis is one of the most common symptoms.
Vitamin D: This can cause nephrocalcinosis because of Vitamin D therapy because it increases the absorption of ingested calcium and bone resorption, resulting in hypercalcemia and hypercalciuria.

Medullary nephrocalcinosis
Medullary sponge kidney
Distal renal tubular acidosis
Hyperoxaluria
Renal papillary necrosisAnd other causes of hypercalcemia (and thus hypercalciuria)
Immobilization (leading to hypercalcemia and hypercalciuria)
Milk-alkali syndrome
Hypervitaminosis D
Multiple myeloma

Hypercalciuria without hypercalcemia
These conditions can cause nephrocalcinosis in association with hypercalciuria without hypercalcemia:
Distal renal tubular acidosis
Medullary sponge kidney
Neonatal nephrocalcinosis and loop diuretics
Inherited tubulopathies
Chronic hypokalemia
Beta thalassemia

Mechanism
Nephrocalcinosis is caused by an increase in the urinary excretion of calcium, phosphate, and/or oxalate. Nephrocalcinosis is closely associated with nephrolithiasis, and patients frequently present with both conditions, however there have been cases where one occurs without the other. Calcium oxalate and calcium phosphate crystals form when the concentration of the reactants exceeds the limit. The deposits are collected in the inner medullary interstitium in the basement membranes of the thin limbs of the loop of Henle. The calcium phosphate plaques can enlarge into the surrounding interstitial tissue, or even rupture into the tubule lumen and can promote calcium oxalate stone formation.

Diagnosis
Nephrocalcinosis is diagnosed for the most part by imaging techniques. The imagings used are ultrasound (US), abdominal plain film and CT imaging. Of the 3 techniques CT and US are the more preferred. Nephrocalcinosis is considered present if at least two radiologists make the diagnosis on US and/or CT. In some cases a renal biopsy is done instead if imaging is not enough to confirm nephrocalcinosis. Once the diagnosis is confirmed additional testing is needed to find the underlying cause because the underlying condition may require treatment for reasons independent of nephrocalcinosis. These additional tests will measure serum, electrolytes, calcium, and phosphate, and the urine pH. If no underlying cause can be found then urine collection should be done for 24 hours and measurements of the excretion of calcium, phosphate, oxalate, citrate, and creatinine are looked at.

Stages of nephrocalcinosis
Chemical or Molecular nephrocalcinosis: Defined as a measurable increase in intracellular calcium concentrations, however, it is not visible through X-ray or microscopically.
Microscopic nephrocalcinosis: Occurs when depositis are visible by light microscope by obtaining a tissue sample from a biopsy. However, this cannot be seen in an X-ray.
Macroscopic nephrocalcinosis: Occurs when calcification can be seen through X-ray imaging.

Treatment
Increasing fluid intake to yield a urine output of greater than 2 liters a day can be advantageous for all patients with nephrocalcinosis. Patients with hypercalciuria can reduce calcium excretion by restricting animal protein, limiting sodium intake to less than 100 meq a day and being lax of potassium intake. If changing ones diet alone does not result in a suitable reduction of hypercalciuria, a thiazide diuretic can be administered in patients who do not have hypercalcemia. Citrate can increase the solubility of calcium in urine and limit the development of nephrocalcinosis. Citrate is not given to patients who have urine pH equal to or greater than 7.

Prognosis
The prognosis of nephrocalcinosis is determined by the underlying cause </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Exotropia and can you explain it in depth? [/INST] Exotropia is a form of strabismus where the eyes are deviated outward. It is the opposite of esotropia and usually involves more severe axis deviation than exophoria. People with exotropia often experience crossed diplopia. Intermittent exotropia is a fairly common condition. "Sensory exotropia" occurs in the presence of poor vision in one eye. Infantile exotropia (sometimes called "congenital exotropia") is seen during the first year of life, and is less common than "essential exotropia" which usually becomes apparent several years later.
The brains ability to see three-dimensional objects depends on proper alignment of the eyes. When both eyes are properly aligned and aimed at the same target, the visual portion of the brain fuses the two forms from the two eyes into a single image. When one eye turns inward, outward, upward, or downward, two different pictures are sent to the brain. Thus, the brain can no longer fuse the two images coming from the two eyes.  This causes loss of depth perception and binocular vision. The term is from Greek exo meaning "outward" and trope meaning "a turning".

Signs and symptoms
The earliest sign of exotropia is usually a noticeable outward deviation of the eye. This sign may at first be intermittent, occurring when a child is daydreaming, not feeling well, or tired. It may also be more noticeable when the child looks at something in the distance. Squinting or frequent rubbing of the eyes is also common with exotropia. The child probably will not mention seeing double, i.e., double vision or diplopia. However, he or she may close one eye to compensate for the problem.  In children, the reason for not seeing double is that the brain may ignore the image it receives from the squinting eye.  This shutting down is known as Suppression.
Generally, exotropia progresses in frequency and duration. As the disorder progresses, the eyes start to turn out when looking at close objects as well as those in the distance. If left untreated, the eye may turn out continually, causing a loss of binocular vision or stereopsis.
In young children with any form of strabismus, the brain may learn to ignore the misaligned eyes image and see only the image from the best-seeing eye. This is called amblyopia, or lazy eye, and results in a loss of binocular vision, impairing depth perception. In adults who develop strabismus, double vision sometimes occurs because the brain has already been trained to receive images from both eyes and cannot ignore the image from the turned eye.
Additionally in adults who have had exotropia since childhood, the brain may adapt to using a "blind-spot", whereby it receives images from both eyes, but no full image from the deviating eye, thus avoiding double vision, and in fact, increasing peripheral vision on the side of the deviating eye.
According to a study published in the American Journal of Ophthalmology, over 90 percent of children with intermittent exotropia become nearsighted by the time they’re 20.

Causes
The causes of exotropia are not fully understood. Six muscles  control eye movement, four that move the eye up and down and two that move it left and right. All these muscles must be coordinated and working properly for the brain to see a single image. When one or more of these muscles does not work properly, some form of strabismus may occur. Strabismus is more common in children with disorders that affect the brain such as cerebral palsy, Down syndrome, hydrocephalus, and brain tumors. One study has found that children with exotropia are three times more likely to develop a psychiatric disorder in comparison with the general population.

Treatment
A comprehensive eye examination including an ocular motility (i.e., eye movement) evaluation and an evaluation of the internal ocular structures allows an eye doctor to accurately diagnose exotropia. Although glasses and/or patching therapy, exercises, or prisms may reduce or help control the outward-turning eye in some children, surgery is often required.
A common form of exotropia is known as "convergence insufficiency" that responds well to orthoptic vision therapy including exercises. This disorder is characterized by an inability of the eyes to work together when used for near viewing, such as reading. Instead of the eyes focusing together on the near object, one deviates outward.
Consecutive exotropia arises after an initial esotropia. Most often it results from surgical overcorrection of the initial esotropia. It can be addressed with further surgery or with vision therapy; vision therapy has shown promising results if the consecutive exotropia is intermittent, alternating, and of small magnitude. (Consecutive exotropia may however also spontaneously develop from esotropia, without surgery or botulinum toxin treatment.)
Because of the risks of surgery, and because about 35% of people require at least one more surgery, many people try vision therapy first. This consists of visual exercises. Although vision therapy is generally not covered by American health insurance companies, many large insurers such as Aetna have recently begun offering full or partial coverage in response to recent studies.
Strabismus surgery is sometimes recommended if the exotropia is present for more than half of each day or if the frequency is increasing over time. It is also indicated if a child has significant exotropia when reading or viewing near objects or if evidence shows that the eyes are losing their ability to work as a single unit (binocular vision). Finally, if there is a complaint of headaches, and no other cause for the headaches can be found, then these headaches could be because the child or adult is trying to control the exotropia.  If none of these criteria are met, surgery may be postponed pending simple observation with or without some form of eyeglass and/or patching therapy. In very mild cases, a chance exists that the exotropia will diminish with time </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Episodic ataxia and can you explain it in depth? [/INST] Episodic ataxia (EA) is an autosomal dominant disorder characterized by sporadic bouts of ataxia (severe discoordination) with or without myokymia (continuous muscle movement). There are seven types recognized but the majority are due to two recognized entities. Ataxia can be provoked by psychological stress or startle, or heavy exertion, including exercise. Symptoms can first appear in infancy. There are at least six loci for EA, of which 4 are known genes. Some patients with EA also have migraine or progressive cerebellar degenerative disorders, symptomatic of either familial hemiplegic migraine or spinocerebellar ataxia. Some patients respond to acetazolamide though others do not.

Signs and symptoms
Typically, episodic ataxia presents as bouts of ataxia induced by startle, stress, or exertion. Some patients also have continuous tremors of various motor groups, known as myokymia. Other patients have nystagmus, vertigo, tinnitus, diplopia or seizures.

Cause
The various symptoms of EA are caused by dysfunction of differing areas. Ataxia, the most common symptom, is due to misfiring of Purkinje cells in the cerebellum. This is either due to direct malfunction of these cells, such as in EA2, or improper regulation of these cells, such as in EA1. Seizures are likely due to altered firing of hippocampal neurons (KCNA1 null mice have seizures for this reason).

Pathophysiology
EA1: KCNA1
Type 1 episodic ataxia (EA1) is characterized by attacks of generalized ataxia induced by emotion or stress, with myokymia both during and between attacks. This disorder is also known as episodic ataxia with myokymia (EAM), hereditary paroxysmal ataxia with neuromyotonia and Isaacs-Mertens syndrome. Onset of EA1 occurs during early childhood to adolescence and persists throughout the patients life. Attacks last from seconds to minutes. Mutations of the gene KCNA1, which encodes the voltage-gated potassium channel KV1.1, are responsible for this subtype of episodic ataxia. KV1.1 is expressed heavily in basket cells and interneurons that form GABAergic synapses on Purkinje cells. The channels aid in the repolarization phase of action potentials, thus affecting inhibitory input into Purkinje cells and, thereby, all motor output from the cerebellum. EA1 is an example of a synaptopathy. There are currently 17 KV1.1 mutations associated with EA1, Table 1 and Figure 1. 15 of these mutations have been at least partly characterized in cell culture based electrophysiological assays wherein 14 of these 15 mutations have demonstrated drastic alterations in channel function. As described in Table 1, most of the known EA1 associated mutations result in a drastic decrease in the amount of current through KV1.1 channels. Furthermore, these channels tend to activate at more positive potentials and slower rates, demonstrated by positive shifts in their V½ values and slower τ activation time constants, respectively. Some of these mutations, moreover, produce channels that deactivate at faster rates (deactivation τ), which would also result in decreased current through these channels. While these biophysical changes in channel properties likely underlie some of the decrease in current observed in experiments, many mutations also seem to result in misfolded or otherwise mistrafficked channels, which is likely to be the major cause of dysfunction and disease pathogenesis. It is assumed, though not yet proven, that decrease in KV1.1 mediated current leads to prolonged action potentials in interneurons and basket cells. As these channels are important in the regulation of Purkinje cell activity, it is likely that this results increased and aberrant inhibitory input into Purkinje cells and, thus, disrupted Purkinje cell firing and cerebellum output.

EA2: CACNA1A
Type 2 episodic ataxia (EA2) is characterized by acetazolamide-responsive attacks of ataxia with or without migraine. Patients with EA2 may also present with progressive cerebellar atrophy, nystagmus, vertigo, visual disturbances and dysarthria. These symptoms last from hours to days, in contrast with EA1, which lasts from seconds to minutes. Attacks can be accompanied by increased heart rate and blood pressure, moderate to severe shaking, and stuttering. Like EA1, attacks can be precipitated by exercise, emotional stress/agitation, physical stress, or heat (overheated body temperature) but also by coffee and alcohol. EA2 is caused by mutations in CACNA1A, which encodes the P/Q-type voltage-gated calcium channel CaV2.1, and is also the gene responsible for causing spinocerebellar ataxia type-6 and familial hemiplegic migraine type-1. EA2 is also referred to as episodic ataxia with nystagmus, hereditary paroxysmal cerebellopathy, familial paroxysmal ataxia and acetazolamide-responsive hereditary paroxysmal cerebellar ataxia (AHPCA). There are currently 19 mutations associated with EA2, though only 3 have been characterized electrophysiologically, table 2 and figure 2. Of these, all result in decreased current through these channels. It is assumed that the other mutations, especially the splicing and frameshift mutations, also result in a drastic decrease in CaV2.1 currents, though this may not be the case for all mutations. CACNA1A is heavily expressed in Purkinje cells of the cerebellum where it is involved in coupling action potentials with neurotransmitter release. Thus, decrease in Ca2+ entry through CaV2.1 channels is expected to result in decreased output from Purkinje cells, even though they will fire at an appropriate rate. The tottering mouse is a widely used model to study EA2, as it developed a spontaneous homologous mutation in Cacna1a in the early 1960s. Alternatively, some CACNA1A mutations, such as those seen in familial hemiplegic migraine type-1, result in increased Ca2+ entry and, thereby, aberrant transmitter release. This can also result in excitotoxicity, as may occur in some cases of spinocerebellar ataxia type-6.

EA3: 1q42
Episodic ataxia type-3 (EA3) is similar to EA1 but often also presents with tinnitus and vertigo. Patients typically present with bouts of ataxia lasting less than 30 minutes and occurring once or twice daily. During attacks, they also have vertigo, nausea, vomiting, tinnitus and diplopia. These attacks are sometimes accompanied by headaches and precipitated by stress, fatigue, movement and arousal after sleep. Attacks generally begin in early childhood and last throughout the patients lifetime. Acetazolamide administration has proved successful in some patients. As EA3 is extremely rare, there is currently no known causative gene. The locus for this disorder has been mapped to the long arm of chromosome 1 (1q42).

EA4
Also known as periodic vestibulocerebellar ataxia, type-4 episodic ataxia (EA4) is an extremely rare form of episodic ataxia differentiated from other forms by onset in the third to sixth generation of life, defective smooth pursuit and gaze-evoked nystagmus. Patients also present with vertigo and ataxia. There are only two known families with EA4, both located in North Carolina. The locus for EA4 is unknown.

EA5: CACNB4
There are two known families with type-5 episodic ataxia (EA5).These patients can present with an overlapping phenotype of ataxia and seizures similar to juvenile myoclonic epilepsy.
In fact, juvenile myoclonic epilepsy and EA5 are allelic and produce proteins with similar dysfunction.Patients with pure EA5 present with recurrent episodes of ataxia with vertigo.
Between attacks they have nystagmus and dysarthria. These patients are responsive to acetazolamide.
Both juvenile myoclonic epilepsy and EA5 are a result of mutations in CACNB4, a gene that encodes the calcium channel β4 subunit. This subunit coassembles with α-subunits and produces channels that slowly inactivate after opening.EA5 patients have a cysteine to phenylalanine mutation at position 104.Thus results in channels with 30% greater current than wild-type.
As this subunit is expressed in the cerebellum, it is assumed that such increased current results in neuronal hyperexcitability
Coding and noncoding variation of the human calcium-channel beta4-subunit gene CACNB4 in patients with idiopathic generalized epilepsy and episodic ataxia.

EA6: SLC1A3
Type-6 episodic ataxia (EA6) is a rare form of episodic ataxia, identified initially in a 10-year-old boy who first presented with 30 minute bouts of decreased muscle tone during infancy. He required "balance therapy" as a young child to aid in walking and has a number of ataxic attacks, each separated by months to years. These attacks were precipitated by fever. He has cerebellar atrophy and subclinical seizures </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 Mouth ulcer and can you explain it in depth? [/INST] A mouth ulcer (aphtha) is an ulcer that occurs on the mucous membrane of the oral cavity. Mouth ulcers are very common, occurring in association with many diseases and by many different mechanisms, but usually there is no serious underlying cause. Rarely, a mouth ulcer that does not heal may be a sign of oral cancer. These ulcers may form individually or multiple ulcers may appear at once (i.e., a "crop" of ulcers). Once formed, an ulcer may be maintained by inflammation and/or secondary infection.

The two most common causes of oral ulceration are local trauma (e.g. rubbing from a sharp edge on a broken filling or braces, biting ones lip, etc.) and aphthous stomatitis ("canker sores"), a condition characterized by recurrent formation of oral ulcers for largely unknown reasons. Mouth ulcers often cause pain and discomfort and may alter the persons choice of food while healing occurs (e.g. avoiding acidic, sugary, salty or spicy foods and beverages).

Definition
An ulcer (; from Latin ulcus, "ulcer, sore") is a break in the skin or mucous membrane with loss of surface tissue and the disintegration and necrosis of epithelial tissue. A mucosal ulcer is an ulcer which specifically occurs on a mucous membrane.
An ulcer is a tissue defect which has penetrated the epithelial-connective tissue border, with its base at a deep level in the submucosa, or even within muscle or periosteum. An ulcer is a deeper breach of epithelium compared to an erosion or excoriation, and involves damage to both epithelium and lamina propria.An erosion is a superficial breach of the epithelium, with little damage to the underlying lamina propria. A mucosal erosion is an erosion which specifically occurs on a mucous membrane. Only the superficial epithelial cells of the epidermis or of the mucosa are lost, and the lesion can reach the depth of the basement membrane. Erosions heal without scar formation.Excoriation is a term sometimes used to describe a breach of the epithelium which is deeper than an erosion but shallower than an ulcer. This type of lesion is tangential to the rete pegs and shows punctiform (small pinhead spots) bleeding, caused by exposed capillary loops.

Causes
Ulcers and erosions can be the result of a spectrum of conditions including:

Those causing auto-immune epithelial damage, damage because of an immune defect (e.g., HIV, leukemia)
Infections (e.g. herpes viruses)
Nutritional disorders (e.g., vitamin deficiencies).
Chemicals such as SLS (a common ingredient in many toothpastes) have been linked to mouth ulcers, and have been recognized by public health agencies such as the NHS as a risk factor.
Injuries (e.g. biting of the lip, tongue, and cheek, hard foods can scrape the oral tissues, hot foods can cause burns)
Stress: When the body is stressed, the immune symptom may trigger mouth sores

Pathophysiology
The exact pathogenesis is dependent upon the cause.
Simple mechanisms which predispose the mouth to trauma and ulceration are xerostomia (dry mouth – as saliva usually lubricates the mucous membrane and controls bacterial levels) and epithelial atrophy (thinning, e.g., after radiotherapy), making the lining more fragile and easily breached.: 7  Stomatitis is a general term meaning inflammation within the mouth, and often may be associated with ulceration.Pathologically, the mouth represents a transition between the gastrointestinal tract and the skin, meaning that many gastrointestinal and cutaneous conditions can involve the mouth. Some conditions usually associated with the whole gastrointestinal tract may present only in the mouth, e.g., orofacial granulomatosis/oral Crohns disease.Similarly, cutaneous (skin) conditions can also involve the mouth and sometimes only the mouth, sparing the skin. The different environmental conditions (saliva, thinner mucosa, trauma from teeth and food), mean that some cutaneous disorders which produce characteristic lesions on the skin produce only non specific lesions in the mouth. The vesicles and bullae of blistering mucocutaneous disorders progress quickly to ulceration in the mouth, because of moisture and trauma from food and teeth. The high bacterial load in the mouth means that ulcers may become secondarily infected. Cytotoxic drugs administered during chemotherapy target cells with fast turnovers such as malignant cells. However, the epithelia of the mouth also has a high turnover rate and makes oral ulceration (mucositis) a common side effect of chemotherapy.Erosions, which involve the epithelial layer, are red in appearance since the underlying lamina propria shows through. When the full thickness of the epithelium is penetrated (ulceration), the lesion becomes covered with a fibrinous exudate and takes on a yellow-grey color. Because an ulcer is a breach of the normal lining, when seen in cross section, the lesion is a crater. A "halo" may be present, which is a reddening of the surrounding mucosa and is caused by inflammation. There may also be edema (swelling) around the ulcer. Chronic trauma may produce an ulcer with a keratotic (white, thickened mucosa) margin. Malignant lesions may ulcerate either because the tumor infiltrates the mucosa from adjacent tissues, or because the lesion originates within the mucosa itself, and the disorganized growth leads to a break in the normal architecture of the lining tissues. Repeat episodes of mouth ulcers can be indicative of an immunodeficiency, signaling low levels of immunoglobulin in the oral mucous membranes. Chemotherapy, HIV, and mononucleosis are all causes of immunodeficiency/immunosuppression with which oral ulcers may become a common manifestation. Autoimmunity is also a cause of oral ulceration. Mucous membrane pemphigoid, an autoimmune reaction to the epithelial basement membrane, causes desquamation/ulceration of the oral mucosa.
Numerous aphthous ulcers could be indicative of an inflammatory autoimmune disease called Behçets disease. This can later involve skin lesions and uveitis in the eyes. Vitamin C deficiency may lead to scurvy which impairs wound healing, which can contribute to ulcer formation. For a detailed discussion of the pathophysiology of aphthous stomatitis, see Aphthous stomatitis#Causes.

Diagnostic
Diagnosis of mouth ulcers usually consists of a medical history followed by an oral examination as well as examination of any other involved area. The following details may be pertinent: The duration that the lesion has been present, the location, the number of ulcers, the size, the color and whether it is hard to touch, bleeds or has a rolled edge. As a general rule, a mouth ulcer that does not heal within 2 or 3 weeks should be examined by a health care professional who is able to rule out oral cancer (e.g. a dentist, oral physician, oral surgeon, or maxillofacial surgeon).  If there have been previous ulcers that have healed, then this again makes cancer unlikely.
An ulcer that keeps forming on the same site and then healing may be caused by a nearby sharp surface, and ulcers that heal and then recur at different sites are likely to be RAS. Malignant ulcers are likely to be single in number, and conversely, multiple ulcers are very unlikely to be oral cancer. The size of the ulcers may be helpful in distinguishing the types of RAS, as can the location (minor RAS mainly occurs on non-keratinizing mucosa, major RAS occurs anywhere in the mouth or oropharynx). Induration, contact bleeding and rolled margins are features of a malignant ulcer. There may be nearby causative factor, e.g. a broken tooth with a sharp edge that is traumatizing the tissues. Otherwise, the person may be asked about problems elsewhere, e.g. ulceration of the genital mucous membranes, eye lesions or digestive problems, swollen glands in neck (lymphadenopathy) or a  general unwell feeling.The diagnosis comes mostly from the history and examination, but the following special investigations may be involved: blood tests (vitamin deficiency, anemia, leukemia, Epstein-Barr virus, HIV infection, diabetes) microbiological swabs (infection), or urinalysis (diabetes). A biopsy (minor procedure to cut out a small sample of the ulcer to look at under a microscope) with or without immunofluorescence may be required, to rule out cancer, but also if a systemic disease is suspected. Ulcers caused by local trauma are painful to touch and sore. They usually have an irregular border with erythematous margins and the base is yellow. As healing progresses, a keratotic (thickened, white mucosa) halo may occur.: 52

Differential diagnosis
Due to various factors (saliva, relative thinness of oromucosa, trauma from teeth, chewing, etc.), vesicles and bullae which form on the mucous membranes of the oral cavity tend to be fragile and quickly break down to leave ulcers.
Aphthous stomatitis and local trauma are very common causes of oral ulceration; the many other possible causes are all rare in comparison.

Traumatic ulceration
Most mouth ulcers that are not associated with recurrent aphthous stomatitis are caused by local trauma. The mucous membrane lining of the mouth is thinner than the skin, and easily damaged by mechanical, thermal (heat/cold), chemical, or electrical means, or by irradiation.

Mechanical
Common causes of oral ulceration include rubbing on sharp edges of teeth, fillings, crowns, false teeth (dentures), or braces (orthodontic appliances), or accidental biting caused by a lack of awareness of painful stimuli in the mouth (e.g., following local anesthetic used during dental treatment, which the person becomes aware of as the anesthetic wears off).Eating hard foods (e.g., potato chips) can damage the lining of the mouth. Some people cause damage inside their mouths themselves, either through an absentminded habit or as a type of deliberate self-harm (factitious ulceration). Examples include biting the cheek, tongue, or lips, or rubbing a fingernail, pen, or toothpick inside the mouth. Tearing (and subsequent ulceration) of the upper labial frenum may be a sign of child abuse (non-accidental injury).Iatrogenic ulceration can also occur during dental treatment, where incidental abrasions to the soft tissues of the mouth are common. Some dentists apply a protective layer of petroleum jelly to the lips before carrying out dental work to minimize this.The lingual frenum is also vulnerable to ulceration by repeated friction during oral sexual activity ("cunnilingus tongue"). Rarely, infants can ulcerate the tongue or lower lip with the teeth, termed Riga-Fede disease.

Thermal and electrical burn
Thermal burns usually result from placing hot food or beverages in the mouth. This may occur in those who eat or drink before a local anesthetic has worn off. The normal painful sensation is absent and a burn may occur. Microwave ovens sometimes produce food that is cold externally and very hot internally, and this has led to a rise in the frequency of intra-oral thermal burns. Thermal food burns are usually on the palate or posterior buccal mucosa, and appear as zones of erythema and ulceration with necrotic epithelium peripherally. Electrical burns more commonly affect the oral commissure (corner of the mouth). The lesions are usually initially painless, charred and yellow with little bleeding. Swelling then develops and by the fourth day following the burn the area becomes necrotic and the epithelium sloughs off.Electrical burns in the mouth are usually caused by chewing on live electrical wiring (an act that is relatively common among young children). Saliva acts as a conducting medium and an electrical arc flows between the electrical source and the tissues, causing extreme heat and possible tissue destruction.

Chemical injury
Caustic chemicals may cause ulceration of the oral mucosa if they are of strong-enough concentration and in contact for a sufficient length of time. The holding of medication in the mouth instead of swallowing it occurs mostly in children, those under psychiatric care, or simply because of a lack of understanding. Holding an aspirin tablet next to a painful tooth in an attempt to relieve pulpitis (toothache) is common, and leads to epithelial necrosis. Chewable aspirin tablets should be swallowed, with the residue quickly cleared from the mouth.Other caustic medications include eugenol and chlorpromazine. Hydrogen peroxide, used to treat gum disease, is also capable of causing epithelial necrosis at concentrations of 1–3%. Silver nitrate, sometimes used for pain relief from aphthous ulceration, acts as a chemical cauterant and destroys nerve endings, but the mucosal damage is increased. Phenol is used during dental treatment as a cavity sterilizing agent and cauterizing material, and it is also present in some over-the-counter agents intended to treat aphthous ulcerations. Mucosal necrosis has been reported to occur with concentrations of 0.5%. Other materials used in endodontics are also caustic, which is part of the reason why use of a rubber dam is now recommended.

Irradiation
As a result of radiotherapy to the mouth, radiation-induced stomatitis may develop, which can be associated with mucosal erosions and ulceration. If the salivary glands are irradiated, there may also be xerostomia (dry mouth), making the oral mucosa more vulnerable to frictional damage as the lubricating function of saliva is lost, and mucosal atrophy (thinning), which makes a breach of the epithelium more likely. Radiation to the bones of the jaws causes damage to osteocytes and impairs the blood supply. The affected hard tissues become hypovascular (reduced number of blood vessels), hypocellular (reduced number of cells), and hypoxic (low levels of oxygen). Osteoradionecrosis is the term for when such an area of irradiated bone does not heal from this damage. This usually occurs in the mandible, and causes chronic pain and surface ulceration, sometimes resulting in non-healing bone being exposed through a soft tissue defect. Prevention of osteradionecrosis is part of the reason why all teeth of questionable prognosis are removed before the start of a course of radiotherapy.

Aphthous stomatitis
Aphthous stomatitis (also termed recurrent aphthous stomatitis, RAS, and commonly called "canker sores") is a very common cause of oral ulceration. 10–25% of the general population have this non-contagious condition. Three types of aphthous stomatitis exists based on their appearance, namely minor, major and herpetiform major aphthous ulceration. Minor aphthous ulceration is the most common type, presenting with 1–6 small (2-4mm diameter), round/oval ulcers with a yellow-grey color and an erythematous (red) "halo". These ulcers heal with no permanent scarring in about 7–10 days. Ulcers recur at intervals of about 1–4 months. Major aphthous ulceration is less common than the minor type, but produces more severe lesions and symptoms. Major aphthous ulceration presents with larger (>1 cm diameter) ulcers that take much longer to heal (10–40 days) and may leave scarring. The minor and major subtypes of aphthous stomatitis usually produce lesions on the non-keratinized oral mucosa (i.e. the inside of the cheeks, lips, underneath the tongue and the floor of mouth), but less commonly major aphthous ulcers may occur in other parts of the mouth on keratinized mucosal surfaces. The least common type is herpetiform ulceration, so named because the condition resembles primary herpetic gingivostomatitis. Herpetiform ulcers begin as small blisters (vesicles) which break down into 2-3mm sized ulcers. Herpetiform ulcers appear in "crops" sometimes hundreds in number, which can coalesce to form larger areas of ulceration. This subtype may cause extreme pain, heals with scarring and may recur frequently.The exact cause of aphthous stomatitis is unknown, but there may be a genetic predisposition in some people. Other possible causes include hematinic deficiency (folate, vitamin B, iron), stopping smoking, stress, menstruation, trauma, food allergies or hypersensitivity to sodium lauryl sulphate (found in many brands of toothpaste). Aphthous stomatitis has no clinically detectable signs or symptoms outside the mouth, but the recurrent ulceration can cause much discomfort to those affected. Treatment is aimed at reducing the pain and swelling and speeding healing, and may involve systemic or topical steroids, analgesics (pain killers), antiseptics, anti-inflammatories or barrier pastes to protect the raw area(s).

Infection
Many infections can cause oral ulceration (see table). The most common are herpes simplex virus (herpes labialis, primary herpetic gingivostomatitis), varicella zoster (chicken pox, shingles), and coxsackie A virus (hand, foot and mouth disease). Human immunodeficiency virus (HIV) creates immunodeficiencies which allow opportunistic infections or neoplasms to proliferate. Bacterial processes leading to ulceration can be caused by  Mycobacterium tuberculosis (tuberculosis) and Treponema pallidum (syphilis).Opportunistic activity by combinations of otherwise normal bacterial flora, such as aerobic streptococci, Neisseria, Actinomyces, spirochetes, and Bacteroides species can prolong the ulcerative process. Fungal causes include Coccidioides immitis (valley fever), Cryptococcus neoformans (cryptococcosis), and Blastomyces dermatitidis ("North American Blastomycosis"). Entamoeba histolytica, a parasitic protozoan, is sometimes known to cause mouth ulcers through formation of cysts. Epstein-Barr virus-positive mucocutaneous ulcer is a rare form of the Epstein-Barr virus-associated lymphoproliferative diseases in which infiltrating, Epstein-Barr virus (i.e. EBV)-infected B cells cause solitary, well-circumscribed ulcers in mucous membranes and skin.

Drug-induced
Many drugs can cause mouth ulcers as a side effect. Common examples are alendronate (a bisphosphonate, commonly prescribed for osteoporosis), cytotoxic drugs (e.g. methotrexate, i.e. chemotherapy), non-steroidal anti-inflammatory drugs, nicorandil (may be prescribed for angina) and propylthiouracil (e.g. used for hyperthyroidism). Some recreational drugs can cause ulceration, e.g. cocaine.

Malignancy
Rarely, a persistent, non-healing mouth ulcer may be a cancerous lesion. Malignancies in the mouth are usually carcinomas, but lymphomas, sarcomas and others may also be possible. Either the tumor arises in the mouth, or it may grow to involve the mouth, e.g. from the maxillary sinus, salivary glands, nasal cavity or peri-oral skin. The most common type of oral cancer is squamous cell carcinoma. The main risk factors are long-term smoking and alcohol consumption (particularly when combined) and betel use.
Common sites of oral cancer are the lower lip, the floor of the mouth, and the sides, underside of the tongue and mandibular alveolar ridge, but it is possible to have a tumor anywhere in the mouth. Appearances vary greatly, but a typical malignant ulcer would be a persistent, expanding lesion that is totally red (erythroplasia) or speckled red and white (erythroleukoplakia). Malignant lesions also typically feel indurated (hardened) and attached to adjacent structures, with "rolled" margins or a punched out appearance and bleeds easily on gentle manipulation. If someone has an unexplained mouth ulcer persisting for more than 3 weeks this may indicate a need for a referral from the GDP or GP to hospital to exclude oral cancer.

Vesiculobullous diseases
Some of the viral infections mentioned above are also classified as vesiculobullous diseases. Other example vesiculobullous diseases include pemphigus vulgaris, mucous membrane pemphigoid, bullous pemphigoid, dermatitis herpetiformis, linear IgA disease, and epidermolysis bullosa.: 1, 22

Allergy
Rarely, allergic reactions of the mouth and lips may manifest as erosions; however, such reactions usually do not produce frank ulceration. An example of one common allergen is Balsam of Peru. If individuals allergic to this substance have oral exposure they may experience stomatitis and cheilitis (inflammation, rash, or painful erosion of the lips, oropharyngeal mucosa, or angles of their mouth).  Balsam of Peru is used in foods and drinks for flavoring, in perfumes and toiletries for fragrance, and in medicine and pharmaceutical items for healing properties.

Other causes
A wide range of other diseases may cause mouth ulcers. Hematological causes include anemia, hematinic deficiencies, neutropenia, hypereosinophilic syndrome, leukemia, myelodysplastic syndromes, other white cell dyscrasias, and gammopathies </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 Hospitalism and can you explain it in depth? [/INST] Hospitalism (or anaclitic depression in its sublethal form) was a pediatric diagnosis used in the 1930s to describe infants who wasted away while in a hospital. The symptoms could include decreased physical development and disruption of perceptual-motor skills and language. In the first half of the 20th century, hospitalism was discovered to be linked to social deprivation between an infant and its caregiver.  The term was used by the psychotherapist René Spitz in 1945, but the term can be traced back as early as 1897.It appears under adjustment disorders at F43.2, in the World Health Organizations classification of diseases, ICD-10.

History
In 1945, the psychoanalyst René Spitz published an article in which he explained how deprivation of social interactions can lead to a condition named "hospitalism" in infants. According to Spitz, young children who are cared for in institutions can suffer from severe impairment in their development because they are not provided with sufficient maternal care. Spitz did not coin the term "hospitalism," which can be traced back to the end of the 19th century. In 1897, Floyd M. Crandall published an article in the Archive of Pediatrics in which he used the term to describe a condition in institutionalized infants characterized by loss of weight, susceptibility to various diseases, and ultimately death. According to Crandall, this high mortality rate of institutionalized children under one-year-old was suspected to be caused by a lack of hygiene, food, air, exercise and personal contact.After rapid growth in welfare centres for infants at the beginning of the 20th century, hospitalism became a more public concern. One solution that was offered was the improvement of general hygiene to avoid the spread of infections. Breastfeeding became increasingly important since it was considered to provide sufficient nutrition and to improve the infants immune systems, which helped to reduce the mortality rate. The assumption that infants had no social competence or dependence on personal interactions had developed. Nurses began to replace the mothers role for institutionalized infants, and mothers were usually not allowed to visit their children more than once a week. This was supposed to minimize the risk of infections and was considered to be a solution to hospitalism. The pediatrician Meinhard von Pfaundler criticized this approach and argued that this rational and distant care would damage the infants’ physical and emotional well-being. He claimed that children needed more external stimulation than was provided in the environment of hospitals.In the early 1930s, researchers at the Vienna Psychological Institute started to concentrate on the development of infants. The so-called Viennese Baby Tests were created by Charlotte Bühler and could be used to assess the mental, social, and physical development of children. Katherine Wolf and Hildegard Durfee used these tests to conduct studies on infants in different institutions. They concluded that the environment influenced the development of children and that this was especially important for the development of social competence. According to them, infants needed to be in contact with their mothers to receive sufficient love and care for their development. In the 1940s, the idea that infections led to hospitalism was increasingly criticized, especially since hospitalized infants were often kept alone in small cubicles, without any contact with caregivers or external stimuli, to prevent cross-infections.In 1945, the psychoanalyst René Spitz redefined the term hospitalism by arguing that the mortality rate of infants was still high, despite the isolation in cubicles, because the lack of maternal care impaired their development. Spitz conducted research for his hypothesis by comparing infants in a foundling hospital in Mexico and in a prison nursery in New York with two control groups of children growing up with their families. With the help of Katherine Wolf, he assessed the development of the infants using the Viennese Baby Tests. Spitz concluded that the decline in development and the high susceptibility to diseases he discovered in institutionalized babies were not due to a lack of environmental stimuli, since the prison nursery infants actually had access to toys, but mostly due to emotional and social deprivation. According to Spitz, a stable and intimate mother-child relationship is critical for the healthy development of the child. In his short film, Grief: A Peril in Infancy, he demonstrated the consequences of hospitalism. This idea had a strong influence on other researchers, and in 1951, the British psychoanalyst John Bowlby published a report on homeless children in the USA. This report, which was titled Maternal Care and Mental Health, was commissioned by the WHO and supported his theory of maternal deprivation. According to Bowlby, a child needs to have a loving and continuous relationship with the mother to avoid permanent developmental damage and hospitalism.

Causes
There are three conditions which determine the likelihood of hospitalism in a patient:
How healthy the person is before the admission into the hospital
How well the operation or appointment gets done
How the patient is taken care of after the operation or appointment, including the number of patients in the hospital in general and the hygiene of the hospitalThe most investigated causes which have been observed are those from infants and children in hospitals or nursery homes. The main cause of hospitalism in children and infants is the separation of the child from the mother. They experience a massive desperation and distress due to the isolation from their mother. An example is children or infants in a nursery home when they are only held in cribs, depriving them of the opportunity to interact with their environment and other people. This deprivation might happen since the nurse has to take care of multiple children at once. A lot of causes, as well as assumptions of causes, still have to get scientifically proved and investigated.

Symptoms
Symptoms of hospitalism are numerous. Symptoms are largely observable in behaviour, but a patients psychological or physical impairments are largely driven by the cause of their condition, and as such not all patients experience the same suite of problems. Physical impairments include physical underdevelopment, reduced motor speed, and increased risk of rapid-onset muscle atrophy. Patients commonly suffer from maladaptive or disruptive eating behaviour, which results in a general decrease in stamina. This has been linked to malnutrition, extreme weight loss, and food addiction. Patients tend to have a strong predisposition to marasmus, which increases mental and physical fragility, alongside an impairment of their immune system, leading them to be at higher risk for infections and viral diseases. Infants also experience a higher mortality rate. The psychological circumstances fit this image. Especially in children that stayed in orphanages for a long time and suffer from deprivation syndrome – the sensory withdrawal before adulthood resulting in physical and psychological damages – one can observe a reduction of activities due to a lack of motivation and suppression of feelings. Sleeplessness, loss of weight and apathy are additional symptoms of depression that can also play a role. Another effect of withdrawal of sensory desires in an early age are personality disorders as for example borderline and attachment and adjustment disorders that are especially seen in behavioral abnormalities.These abnormalities can consist of stereotypes – a motor restlessness that results in showing repetitive and consistent motor processes and spoken utterances that do not have any goal or function and occur in absolutely unfitting situations. Stereotypic movement might also result in self harm. Behavioral abnormalities can also hinder social relations effectively. Affected individuals tend to become apathetic and withdrawn. Antisocial behavior might manifest as lying or stealing. Disrupted social functions related to a lack of socialization and integration can lead to further isolation. Hygiene and appearance may also be negatively impacted.

Consequences and complication
The consequences of hospitalism can be detrimental for the people affected and reveal themselves in different ways. It is noteworthy that the symptoms can vary across different individuals, and several factors, such as age, play a significant role.Patients are also at higher risk for various mental disorders and anti-social behaviors:
anxiety disorders
depression
borderline-personality disorder
suicidal tendencies
apathy
low self-esteem
autoaggressive behaviour
attachment anxiety
adjustment and communication disorders
tendencies towards aggressive behaviour
lack of personal hygieneIndividuals suffering from hospitalism are also at risk for sensory perception problems:
altered or delayed pain perception
fear of touch
hypersensitivity   Other common consequences relate to cognitive disorders, such as:
learning disabilities
rarely memory lapses or even loss of long- or short-term memory
motor disorders such as monotonous and sterotyped movements (for example, banging the head against the wall) or a severely reduced ability to reactLong-term consequences, which is causally related to traumatic experiences, can be expressed in different ways. People showing signs of hospitalism might express an extreme aversion towards showing or accepting emotional or physical affection, effectively shutting themselves off from others </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 Pseudohypoaldosteronism 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 Ischial bursitis and can you explain it in depth? [/INST] Ischial bursitis (also known as weavers bottom) is inflammation of the synovial bursa located between gluteus maximus muscle and ischial tuberosity.

Signs and symptoms
Ischial bursitis causes pain down the posterior aspect of the upper thigh </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 Caffeine-induced anxiety disorder and can you explain it in depth? [/INST] Caffeine-induced anxiety disorder is a subclass of the DSM-5 diagnosis of substance/medication-induced anxiety disorder.Consumption of caffeine has long been linked to anxiety. The effects of caffeine and the symptoms of anxiety both increase activity within the sympathetic nervous system. Caffeine has been linked to the aggravation and maintenance of anxiety disorders, and the initiation of panic or anxiety attacks in those who are already predisposed to such phenomena. Caffeine usage surpassing 200 mg has been shown to increase the likelihood for anxiety and panic attacks in a population. Excessive amounts of caffeine can result in symptoms from general anxiety to obsessive-compulsive and phobic symptoms.

DSM-5 classification
Diagnostic criteria
Caffeine-induced anxiety disorder is a subclass of the DSM-5 diagnosis of substance/medication-induced anxiety disorder. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, or DSM-5, is the current authority for psychiatric diagnosis in the United States. Substance/medication-induced anxiety disorder falls under the category of anxiety disorders in the DSM-5, and not the category of substance-related and addictive disorders, even though the symptoms are due to the effects of a substance.Diagnosis according to the DSM-5 is dependent on various criteria. Patients must present symptoms of either panic attacks or anxiety. There must also be evidence that the panic or anxiety symptoms are a direct result of the use of the intoxicating substance. In caffeine-induced anxiety disorder, such symptoms would be due to the consumption of caffeine. The DSM-5 makes the distinction that the substance must be physiologically capable of leading to the anxiety and panic symptoms. This establishes the relationship between the abused chemical agent and the observed clinical effects. Caffeine has been proven to act as an antagonist on adenosine receptors, which acts as a stimulant and therefore fulfills this criteria. Symptoms must also not have a more likely clinical cause, such as another type of anxiety disorder, come before the ingestion of the intoxicating substance, or last for an extended amount of time after stopping the use of the substance. Diagnosis also requires that the panic attacks or anxiety due to the use of the intoxicating substance cause a certain amount of disturbance in the patient or lead to deficiency of varying types of daily performance.

Diagnostic features
In addition to the criteria above, it is important to recognize that the diagnostic criteria for substance/medication-induced anxiety disorder are not met if the symptoms of panic come before the intoxication by the substance. In caffeine-induced anxiety disorder, a diagnosis will not be made if symptoms of anxiety or panic precede the ingestion of caffeine. Also, if symptoms persist for more than one month after substance intoxication, the diagnosis cannot be made. Persistence and continuation of symptoms beyond the initial consumption of caffeine suggest an alternate diagnosis that would better explain the long-lasting symptoms. Anxiety symptoms caused by caffeine are often mistaken for serious mental disorders including bipolar disorder and schizophrenia, leaving patients medicated for the wrong issue. A caffeine-induced anxiety disorder diagnosis should be made, rather than a substance abuse or intoxication diagnosis, when symptoms of panic attacks or anxiety predominate.

Prevalence
Although exact rates of prevalence are not available, general population data shows a 0.002% prevalence over a year-long period and higher prevalence within clinical populations.

Caffeine
Caffeine is a methylxanthine, and is hydrophobic.
The structure of caffeine allows the molecule to pass freely through biological membranes including the blood-brain barrier. Absorption in the gastrointestinal tract reaches near completion at about 99% after only 45 minutes. Half-life of caffeine for most adults is between 2.5 and 4.5 hours when consumption is limited to less than 10 mg/kg. However, during neonatal development, half-life for the fetus is significantly longer and decreases exponentially after birth to reach a normal rate at about 6 months. Cytochrome P-450, a hemeprotein, acts in liver microsomes to metabolize caffeine into dimethylxanthines, monomethylxanthines, dimethyl uric acids, monomethyl uric acids, trimethylallantoin, dimethylallantoin, and derivatives of uracil. Most caffeine is metabolized by 3-methyl demethylation, forming the metabolite of paraxanthine. Many metabolites, in addition to caffeine, act within the body and are partly responsible for the physiological response to caffeine.

Mechanism of caffeine action
Caffeine acts in multiple ways within the brain and the rest of the body. However, due to the concentration of caffeine required, antagonism of adenosine receptors is the primary mode of action. The following mechanisms are ways in which caffeine may act within the body, but depending on necessary caffeine concentration and other factors may not be responsible for the clinical effects of the substance.

Mobilization of intracellular calcium
At very high concentrations of about 1–2 mM, caffeine lowers the excitability threshold in muscle cells, leading to prolonged contraction. The introduction of such high doses of caffeine allows calcium to enter the muscle cell through the plasma membrane and sarcoplasmic reticulum more readily. Influx of calcium through the membranes in muscle cells requires at least 250 μM of caffeine. Normally, other toxic effects of caffeine begin to occur in concentrations over 200 μM, however average consumption averages lead to concentrations less than 100 μM. This means that calcium influx and mobilization are most likely not the cause of caffeines effect on the central nervous system, and are therefore not the cause of caffeine-induced anxiety disorder.

Inhibition of phosphodiesterases
Methylxanthines such as caffeine inhibit the action of cyclic nucleotide phosphodiesterase, which normally acts to break down cAMP. Cyclic adenosine monophosphate, or cAMP, is a second messenger important in many cellular processes and is a critical factor in signal transduction. The inhibition of the phosphodiesterase would lead to a buildup of cAMP, increasing the activity of the second messenger throughout the cell. Though this mechanism is possible, it only occurs after levels of caffeine have reached a toxic level, and therefore it is unlikely to explain the mechanism of caffeine in the brain.

Antagonism of adenosine receptors
There are four well-known adenosine receptors found in the body, A1, A2A, A2B, and A3. The endogenous agonist for these receptors is adenosine, which is a purine nucleoside that is important for processes such as energy transfer in the form of adenosine triphosphate (ATP) and adenosine monophosphate (AMP) and signal transduction in the form of cyclic adenosine monophosphate (cAMP). A2B and A3 receptors require concentrations of caffeine that do not occur at normal physiological levels or with normal levels of caffeine consumption in order to be antagonized, and will therefore not be considered as a possible mechanism for caffeine-induced anxiety.Caffeine acts as an antagonist of adenosine A1 and A2A receptors. Adenosine is a normal neuromodulator that activates adenosine g-protein coupled receptors. The actions of A1 and A2A receptors oppose each other but are both inhibited by caffeine due to its function as an antagonist.A2A receptors are coupled to Gs proteins which activate adenylate cyclase and some voltage gated Ca2+ channels. A2A receptors are located in dopamine rich brain regions. A2A receptor mRNA was found in the same neurons as the dopamine receptor D2 within the dorsal striatum, nucleus accumbens and tuberculum olfactorium. A2A receptors are not found in neurons that express the dopamine receptor D1 receptors and Substance P. Within the striatum, part of the basal ganglia, activation of A2A receptors by adenosine increases GABA release, an inhibitory neurotransmitter. When caffeine binds to the receptor, less inhibitory neurotransmitter is released, supporting caffeines role as a central nervous system stimulant.A1 receptors are paired with the G-proteins of Gi-1, Gi-2, Gi-3, Go1, and Go2. The g-proteins of A1 receptors continue to inhibit adenylate cyclase, some voltage gated Ca2+ channels, and activate some K+ channels, and phospholipase C and D. A1 receptors are primarily located in the hippocampus, cerebral and cerebellar cortex, and particular thalamic nuclei. Adenosine acts on A1 receptors to decrease opening of N-type Ca2+ channels in some hippocampal neurons, and therefore decrease the rate of firing since Ca2+ is necessary for neurotransmitter release. Caffeines antagonistic action on the A1 receptor thus decreases the action of adenosine, allowing increased Ca2+ entry through N-type channels and higher rates of neurotransmitter release.

Other actions of caffeine
Though antagonism of adenosine receptors is the primary mechanism of caffeine, Introduction of the methylxanthine into the body also increases the rate of release and recycling of some monoamine neurotransmitters such as noradrenaline and dopamine. Caffeine also has an excitatory effect on mesocortical cholinergic neurons by acting as an antagonist on adenosine receptors that normally inhibit the neuron.

Genetics and variability of caffeine consumption
While many factors contribute to individual differences in a persons response to caffeine, such as environmental and demographic factors (i.e. age, drug use, circadian factors, etc.), genetics play an important role in individual variability. This inconsistency in responses to caffeine can take place either at the metabolic or at the drug-receptor level. The effects of genetic factors can occur either directly by changing acute or chronic reactions to the drug or indirectly by altering other psychological or physiological processes.Some of these processes include wakefulness, stimulation, and mood and cognition enhancement. Low doses can result in psychological effects of "mild euphoria, alertness, and enhanced cognitive performance"; higher doses produce physiological side effects of nausea, anxiety, trembling, and jitteriness.
There are individuals who are prone to caffeines anxiogenic effects whilst others are susceptible to its caffeine-induced sleep disturbances and insomnia. Studies with twins have shown that genetics influence individual differences in response to caffeine. Homozygous twins have been found to react in more consistent ways to the caffeine than heterozygous twins.

Behavioral effects
Caffeines widespread appeal is due primarily to its mild psychostimulant properties, which increase alertness and cognitive arousal and diminish fatigue. Caffeine also produces a wide range of other symptoms, including upregulation of the cardiovascular system, increased global cognitive processing, and improved physical functioning. Cardiovascular effects can range from increased heart rate and reactivity to severe cardiac arrhythmia. The cognitive effects of caffeine include increased performance in memory, attention, and text reading. The physical effects of caffeine include lowered sensations of pain, less perceived effort, and increased muscle strength and endurance. However, at doses above ~400 mg, both cognitive and physical performance begins to worsen and symptoms of anxiety increase. One study that explored ad lib caffeine consumption in 159 college students found that high consumers reported lower academic performance. The same study also concluded that moderate and high consumers combined reported significantly higher trait anxiety and depression scores when compared with abstainers. These anxiety symptoms include persisting insomnia, nervousness, and mood fluctuations.When undergoing stress, the body activates a system-wide response mechanism known as the HPA axis. This stress signal begins at the level of the hypothalamus in the brain and undergoes subsequent amplifications throughout the body. This system elevates levels of stress hormones in the blood, which results in the body shutting down secondary bodily processes and increasing alertness to better prepare for response to the perceived threat. Studies show that activation of this pathway is correlated with anxiety-like behaviors, including panic, post-traumatic stress, and generalized anxiety disorders, as well as depression. Rodent studies show that caffeine consumption in adolescence results in dysregulation of HPA axis function as well as central nervous system response, which impairs the bodys response to stressful stimuli.In cases of prolonged consumption of excess amounts of caffeine, studies show that individuals exhibit a reduced response to HPA axis activation by the hormone ACTH and a generalized increase in basal levels of stress hormone corticosterone. Researchers concluded that the sensitivity of adrenal glands to ACTH is diminished by caffeine consumption. People diagnosed with panic disorder show less HPA activity following stressful stimuli than their healthy control counterparts.

Susceptible populations
Caffeine has varying effects on anxiety across given populations. The populations most susceptible to caffeine-induced anxiety disorder include those already diagnosed with an anxiety disorder and adolescents. Adolescents, particularly, are at increased risk for developing anxiety disorders and anxiety-related symptoms. While few human studies have been done to investigate this connection, many rodent studies show a correlation between caffeine consumption in adolescence and increased anxiety. These studies showed that in adolescent rodents exposed to caffeine, functioning of serotonin systems was affected, leading to increased anxiety; anxiety-related behaviors were higher than in adult rats exposed to the same amount of caffeine; and reward seeking behaviors as well as mood fluctuations were increased as the rodents matured.

Long-term health effects
When consumed in moderation, caffeine can have many beneficial effects. However, over the course of several years, chronic caffeine consumption can produce various long-term health deficits in individuals. Among these, rodent studies have suggested caffeine intake may permanently alter the brains excitability </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 Pathological demand avoidance and can you explain it in depth? [/INST] Pathological demand avoidance (PDA) is a profile of autism spectrum disorder and a proposed sub-type. Characteristics ascribed to the condition include greater refusal to do what is asked of the person, even to activities the person would normally like, due to extreme levels of anxiety and lack of autonomy. Although PDA has its own traits that are separate from autism, they generally meet the diagnostic criteria by having significant impairments in social interaction and communication and presenting restricted and repetitive behaviors. Some notable differences in PDA compared to classic autism spectrum disorders are that individuals appear to be more sociable, have far better social skills and social understanding, tend to be more interested in people than objects, are more comfortable with pretend play, and tend to be more imaginative. It is not recognized by either the DSM-5 or the ICD-10 and is unlikely to be separated out now that the umbrella diagnosis of ASD has been adopted.
In 2011, it was suggested that these symptoms could represent the condition oppositional defiant disorder (ODD). Elizabeth ONions and others argue that unlike ASD, “children with PDA are said to use socially manipulative avoidance strategies”; and unlike ODD, they “resort to extreme, embarrassing or age-inappropriate behaviour”.The term was proposed in 1980 by the UK child psychologist Elizabeth Ann Newson.

Recognition
Pathological demand avoidance is not recognized by the DSM-5 or ICD-10, the two main classification systems for mental disorders. To be recognized, a sufficient amount of consensus and clinical history needs to be present, and as a newly proposed condition, PDA had not met the standard of evidence required at the time of recent revisions. However, DSM-5 also moved from sub-type classification to the use of ‘Autistic Spectrum Disorder’, which allows for the behavioural traits of different profiles to be described.
In 2011, the National Institute for Health and Care Excellence commented on the fact that PDA has been proposed as part of the autism spectrum but did not include further discussion within the guideline. NICE guidance also expects an ‘ASD’ diagnosis be accompanied by a diagnostic assessment, providing a profile of key strengths and difficulties. Demand Avoidance is listed as a ‘sign or symptom of ASD’ (Appendix 3).Christopher Gillberg wrote a commentary article in 2014 that reviewed recent research and stated, “Experienced clinicians throughout child psychiatry, child neurology and paediatrics testify to its existence and the very major problems encountered when it comes to intervention and treatment.”

Proposed diagnostic criteria
As of 2014 there are no recognized diagnostic criteria. Criteria proposed by Newson include:

Passive early history in the first year, avoiding ordinary demands and missing milestones
Continuing to avoid demands, panic attacks if demands are escalated
Surface sociability, but apparent lack of sense of social identity
Lability of mood and impulsivity
Comfortable in role play and pretending
Language delay, seemingly the result of passivity, often caught up quickly
Obsessive behavior
Neurological signs (awkwardness, similar to autism spectrum disorders)The underlying cause of this avoidance is said to be a high level of anxiety, usually from expectations of demands being placed on children, which can lead to a feeling of not being in control of a situation </s>


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<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 Bartons fracture and can you explain it in depth? [/INST]  </s>