<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 Ligneous conjunctivitis 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 Worth 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 Pelvic kidney 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 Gunshot wound and can you explain it in depth? [/INST] A gunshot wound (GSW) is a penetrating injury caused by a projectile (e.g. a bullet) from a gun (typically firearm or air gun). Damages may include bleeding, bone fractures, organ damage, wound infection, loss of the ability to move part of the body and, in more severe cases, death. Damage depends on the part of the body hit, the path the bullet follows through the body, and the type and speed of the bullet. Long-term complications can include lead poisoning and post-traumatic stress disorder (PTSD).Factors that determine rates of gun violence vary by country. These factors may include the illegal drug trade, easy access to firearms, substance misuse including alcohol, mental health problems, firearm laws, social attitudes, economic differences and occupations such as being a police officer. Where guns are more common, altercations more often end in death.Before management begins it should be verified the area is safe. This is followed by stopping major bleeding, then assessing and supporting the airway, breathing, and circulation. Firearm laws, particularly background checks and permit to purchase, decrease the risk of death from firearms. Safer firearm storage may decrease the risk of firearm-related deaths in children.In 2015, about a million gunshot wounds occurred from interpersonal violence. In 2016, firearms resulted in 251,000 deaths globally, up from 209,000 in 1990. Of these deaths 161,000 (64%) were the result of assault, 67,500 (27%) were the result of suicide, and 23,000 (9%) were accidents. In the United States, guns resulted in about 40,000 deaths in 2017. Firearm-related deaths are most common in males between the ages of 20 to 24 years. Economic costs due to gunshot wounds have been estimated at US$140 billion a year in the United States.

Signs and symptoms
Trauma from a gunshot wound varies widely based on the bullet, velocity, mass, entry point, trajectory, affected anatomy, and exit point. Gunshot wounds can be particularly devastating compared to other penetrating injuries because the trajectory and fragmentation of bullets can be unpredictable after entry. Moreover, gunshot wounds typically involve a large degree of nearby tissue disruption and destruction caused by the physical effects of the projectile correlated with the bullet velocity classification.The immediate damaging effect of a gunshot wound is typically severe bleeding with the potential for hypovolemic shock, a condition characterized by inadequate delivery of oxygen to vital organs. In the case of traumatic hypovolemic shock, this failure of adequate oxygen delivery is due to blood loss, as blood is the means of delivering oxygen to the bodys constituent parts. Devastating effects can result when a bullet strikes a vital organ such as the heart, lungs or liver, or damages a component of the central nervous system such as the spinal cord or brain.Common causes of death following gunshot injury include bleeding, low oxygen caused by pneumothorax, catastrophic injury to the heart and major blood vessels, and damage to the brain or central nervous system. Non-fatal gunshot wounds frequently have mild to severe long-lasting effects, typically some form of major disfigurement such as amputation because of a severe bone fracture and may cause permanent disability. A sudden blood gush may take effect immediately from a gunshot wound if a bullet directly damages larger blood vessels, especially arteries.

Pathophysiology
The degree of tissue disruption caused by a projectile is related to the cavitation the projectile creates as it passes through tissue. A bullet with sufficient energy will have a cavitation effect in addition to the penetrating track injury. As the bullet passes through the tissue, initially crushing then lacerating, the space left forms a cavity; this is called the permanent cavity. Higher-velocity bullets create a pressure wave that forces the tissues away, creating not only a permanent cavity the size of the caliber of the bullet but a temporary cavity or secondary cavity, which is often many times larger than the bullet itself. The temporary cavity is the radial stretching of tissue around the bullets wound track, which momentarily leaves an empty space caused by high pressures surrounding the projectile that accelerate material away from its path. The extent of cavitation, in turn, is related to the following characteristics of the projectile:

Kinetic energy: KE = 1/2mv2 (where m is mass and v is velocity). This helps to explain why wounds produced by projectiles of higher mass and/or higher velocity produce greater tissue disruption than projectiles of lower mass and velocity. The velocity of the bullet is a more important determinant of tissue injury. Although both mass and velocity contribute to the overall energy of the projectile, the energy is proportional to the mass while proportional to the square of its velocity. As a result, for constant velocity, if the mass is doubled, the energy is doubled; however, if the velocity of the bullet is doubled, the energy increases four times. The initial velocity of a bullet is largely dependent on the firearm. The US military commonly uses 5.56-mm bullets, which have a relatively low mass as compared with other bullets; however, the speed of these bullets is relatively fast. As a result, they produce a larger amount of kinetic energy, which is transmitted to the tissues of the target. The size of the temporary cavity is approximately proportional to the kinetic energy of the bullet and depends on the resistance of the tissue to stress. Muzzle energy, which is based on muzzle velocity, is often used for ease of comparison.
Yaw: Handgun bullets will generally travel in a relatively straight line or make one turn if a bone is hit. Upon travel through deeper tissue, high-energy rounds may become unstable as they decelerate, and may tumble (pitch and yaw) as the energy of the projectile is absorbed, causing stretching and tearing of the surrounding tissue.
Fragmentation: Most commonly, bullets do not fragment, and secondary damage from fragments of shattered bone is a more common complication than bullet fragments.

Diagnosis
Classification
Gunshot wounds are classified according to the speed of the projectile using the Gustilo open fracture classification:

Low-velocity: Less than 1,100 ft/s (340 m/s)Low velocity wounds are typical of small caliber handguns and display wound patterns like Gustilo Anderson Type 1 or 2 wounds

Medium-velocity: Between 1,200 ft/s (340 m/s) and 2,000 ft/s (610 m/s)These are more typical of shotgun blasts or higher caliber handguns like magnums. The risk of infection from these types of wounds can vary depending on the type and pattern of bullets fired as well as the distance from the firearm.

High-velocity: Between 2,000 ft/s (610 m/s) and 3,500 ft/s (1,100 m/s)Usually caused by powerful assault or hunting rifles and usually display wound pattern similar to Gustilo Anderson Type 3 wounds. The risk of infection is especially high due to the large area of injury and destroyed tissue.Bullets from handguns are sometimes less than 1,000 ft/s (300 m/s) but with modern pistol loads, they usually are slightly above 1,000 ft/s (300 m/s), while bullets from most modern rifles exceed 2,500 ft/s (760 m/s). One recently developed class of firearm projectiles is the hyper-velocity bullet, such cartridges are usually either wildcats made for achieving such high speed or purpose-built factory ammunition with the same goal in mind. Examples of hyper velocity cartridges include the .220 Swift, .17 Remington and .17 Mach IV cartridges. The US military commonly uses 5.56mm bullets, which have a relatively low mass as compared with other bullets (40-62 grains); however, the speed of these bullets is relatively fast (Approximately 2,800 ft/s (850 m/s), placing them in the high velocity category). As a result, they produce a larger amount of kinetic energy, which is transmitted to the tissues of the target. However, one must remember that high kinetic energy does not necessarily equate to high stopping power, as incapacitation usually results from remote wounding effects such as bleeding, rather than raw energy transfer. High energy does indeed result in more tissue disruption, which plays a role in incapacitation, but other factors such as wound size and shot placement play as big of, if not a bigger role in stopping power and thus, effectiveness. Muzzle velocity does not consider the effect of aerodynamic drag on the flight of the bullet for the sake of ease of comparison.

Prevention
Medical organizations in the United States recommend a criminal background check being held before a person buys a gun and that a person who has convictions for crimes of violence should not be permitted to buy a gun. Safe storage of firearms is recommended, as well as better mental health care and removal of guns from those at risk of suicide. In an effort to prevent mass shootings greater regulations on guns that can rapidly fire many bullets is recommended.

Management
Initial assessment for a gunshot wound is approached in the same way as other acute trauma using the advanced trauma life support (ATLS) protocol. These include:

A) Airway - Assess and protect airway and potentially the cervical spine
B) Breathing - Maintain adequate ventilation and oxygenation
C) Circulation - Assess for and control bleeding to maintain organ perfusion including focused assessment with sonography for trauma (FAST)
D) Disability - Perform basic neurological exam including Glasgow Coma Scale (GCS)
E) Exposure - Expose entire body and search for any missed injuries, entry points, and exit points while maintaining body temperatureDepending on the extent of injury, management can range from urgent surgical intervention to observation. As such, any history from the scene such as gun type, shots fired, shot direction and distance, blood loss on scene, and pre-hospital vitals signs can be very helpful in directing management. Unstable people with signs of bleeding that cannot be controlled during the initial evaluation require immediate surgical exploration in the operating room. Otherwise, management protocols are generally dictated by anatomic entry point and anticipated trajectory.

Neck
A gunshot wound to the neck can be particularly dangerous because of the high number of vital anatomical structures contained within a small space. The neck contains the larynx, trachea, pharynx, esophagus, vasculature (carotid, subclavian, and vertebral arteries; jugular, brachiocephalic, and vertebral veins; thyroid vessels), and nervous system anatomy (spinal cord, cranial nerves, peripheral nerves, sympathetic chain, brachial plexus). Gunshots to the neck can thus cause severe bleeding, airway compromise, and nervous system injury.Initial assessment of a gunshot wound to the neck involves non-probing inspection of whether the injury is a penetrating neck injury (PNI), classified by violation of the platysma muscle. If the platysma is intact, the wound is considered superficial and only requires local wound care. If the injury is a PNI, surgery should be consulted immediately while the case is being managed. Of note, wounds should not be explored on the field or in the emergency department given the risk of exacerbating the wound.
Due to the advances in diagnostic imaging, management of PNI has been shifting from a "zone-based" approach, which uses anatomical site of injury to guide decisions, to a "no-zone" approach which uses a symptom-based algorithm. The no-zone approach uses a hard signs and imaging system to guide next steps. Hard signs include airway compromise, unresponsive shock, diminished pulses, uncontrolled bleeding, expanding hematoma, bruits/thrill, air bubbling from wound or extensive subcutaneous air, stridor/hoarseness, neurological deficits. If any hard signs are present, immediate surgical exploration and repair is pursued alongside airway and bleeding control. If there are no hard signs, the person receives a multi-detector CT angiography for better diagnosis. A directed angiography or endoscopy may be warranted in a high-risk trajectory for the gunshot. A positive finding on CT leads to operative exploration. If negative, the person may be observed with local wound care.

Chest
Important anatomy in the chest includes the chest wall, ribs, spine, spinal cord, intercostal neurovascular bundles, lungs, bronchi, heart, aorta, major vessels, esophagus, thoracic duct, and diaphragm. Gunshots to the chest can thus cause severe bleeding (hemothorax), respiratory compromise (pneumothorax, hemothorax, pulmonary contusion, tracheobronchial injury), cardiac injury (pericardial tamponade), esophageal injury, and nervous system injury.Initial workup as outlined in the Workup section is particularly important with gunshot wounds to the chest because of the high risk for direct injury to the lungs, heart, and major vessels. Important notes for the initial workup specific for chest injuries are as follows. In people with pericardial tamponade or tension pneumothorax, the chest should be evacuated or decompressed if possible prior to attempting tracheal intubation because the positive pressure ventilation can cause hypotention or cardiovascular collapse. Those with signs of a tension pneumothorax (asymmetric breathing, unstable blood flow, respiratory distress) should immediately receive a chest tube (> French 36) or needle decompression if chest tube placement is delayed. FAST exam should include extended views into the chest to evaluate for hemopericardium, pneumothorax, hemothorax, and peritoneal fluid.Those with cardiac tamponade, uncontrolled bleeding, or a persistent air leak from a chest tube all require surgery. Cardiac tamponade can be identified on FAST exam. Blood loss warranting surgery is 1–1.5 L of immediate chest tube drainage or ongoing bleeding of 200-300 mL/hr. Persistent air leak is suggestive of tracheobronchial injury which will not heal without surgical intervention. Depending on the severity of the persons condition and if cardiac arrest is recent or imminent, the person may require surgical intervention in the emergency department, otherwise known as an emergency department thoracotomy (EDT).However, not all gunshot to the chest require surgery. Asymptomatic people with a normal chest X-ray can be observed with a repeat exam and imaging after 6 hours to ensure no delayed development of pneumothorax or hemothorax. If a person only has a pneumothorax or hemothorax, a chest tube is usually sufficient for management unless there is large volume bleeding or persistent air leak as noted above. Additional imaging after initial chest X-ray and ultrasound can be useful in guiding next steps for stable people. Common imaging modalities include chest CT, formal echocardiography, angiography, esophagoscopy, esophagography, and bronchoscopy depending on the signs and symptoms.

Abdomen
Important anatomy in the abdomen includes the stomach, small bowel, colon, liver, spleen, pancreas, kidneys, spine, diaphragm, descending aorta, and other abdominal vessels and nerves. Gunshots to the abdomen can thus cause severe bleeding, release of bowel contents, peritonitis, organ rupture, respiratory compromise, and neurological deficits.
The most important initial evaluation of a gunshot wound to the abdomen is whether there is uncontrolled bleeding, inflammation of the peritoneum, or spillage of bowel contents. If any of these are present, the person should be transferred immediately to the operating room for laparotomy. If it is difficult to evaluate for those indications because the person is unresponsive or incomprehensible, it is up to the surgeons discretion whether to pursue laparotomy, exploratory laparoscopy, or alternative investigative tools.
Although all people with abdominal gunshot wounds were taken to the operating room in the past, practice has shifted in recent years with the advances in imaging to non-operative approaches in more stable people. If the persons vital signs are stable without indication for immediate surgery, imaging is done to determine the extent of injury. Ultrasound (FAST) and help identify intra-abdominal bleeding and X-rays can help determine bullet trajectory and fragmentation. However, the best and preferred mode of imaging is high-resolution multi-detector CT (MDCT) with IV, oral, and sometimes rectal contrast. Severity of injury found on imaging will determine whether the surgeon takes an operative or close observational approach.
Diagnostic peritoneal lavage (DPL) has become largely obsolete with the advances in MDCT, with use limited to centers without access to CT to guide requirement for urgent transfer for operation.

Extremities
The four main components of extremities are bones, vessels, nerves, and soft tissues. Gunshot wounds can thus cause severe bleeding, fractures, nerve deficits, and soft tissue damage. The Mangled Extremity Severity Score (MESS) is used to classify the severity of injury and evaluates for severity of skeletal and/or soft tissue injury, limb ischemia, shock, and age. Depending on the extent of injury, management can range from superficial wound care to limb amputation.
Vital sign stability and vascular assessment are the most important determinants of management in extremity injuries. As with other traumatic cases, those with uncontrolled bleeding require immediate surgical intervention. If surgical intervention is not readily available and direct pressure is insufficient to control bleeding, tourniquets or direct clamping of visible vessels may be used temporarily to slow active bleeding. People with hard signs of vascular injury also require immediate surgical intervention. Hard signs include active bleeding, expanding or pulsatile hematoma, bruit/thrill, absent distal pulses and signs of extremity ischemia.For stable people without hard signs of vascular injury, an injured extremity index (IEI) should be calculated by comparing the blood pressure in the injured limb compared to an uninjured limb in order to further evaluate for potential vascular injury. If the IEI or clinical signs are suggestive of vascular injury, the person may undergo surgery or receive further imaging including CT angiography or conventional arteriography.
In addition to vascular management, people must be evaluated for bone, soft tissue, and nerve injury. Plain films can be used for fractures alongside CTs for soft tissue assessment. Fractures must be debrided and stabilized, nerves repaired when possible, and soft tissue debrided and covered. This process can often require multiple procedures over time depending on the severity of injury.

Epidemiology
In 2015, about a million gunshot wounds occurred from interpersonal violence. Firearms, globally in 2016, resulted in 251,000 deaths up from 209,000 in 1990. Of these deaths 161,000 (64%) were the result of assault, 67,500 (27%) were the result of suicide, and 23,000 were accidents. Firearm related deaths are most common in males between the ages of 20 to 24 years.The countries with the greatest number of deaths from firearms are Brazil, United States, Mexico, Colombia, Venezuela, Guatemala and South Africa which make up just over half the total. In the United States in 2015 about half of the 44,000 people who died by suicide did so with a gun.As of 2016, the countries with the highest rates of gun violence per capita were El Salvador, Venezuela, and Guatemala with 40.3, 34.8, and 26.8 violent gun deaths per 100,000 people respectively. The countries with the lowest rates of were Singapore, Japan, and South Korea with 0.03, 0.04, and 0.05 violent gun deaths per 100,000 people respectively.

Canada
In 2016, about 893 people died due to gunshot wounds in Canada (2.1 per 100,000). About 80% were suicides, 12% were assaults, and 4% percent were an accident.

United States
In 2017, there were 39,773 deaths in the United States as a result gunshot wounds. Of these 60% were suicides, 37% were homicides, 1.4% were by law enforcement, 1.2% were accidents, and 0.9% were from an unknown cause. This is up from 37,200 deaths in 2016 due to a gunshot wound (10.6 per 100,000). With respect to those that pertain to interpersonal violence, it had the 31st highest rate in the world with 3.85 deaths per 100,000 people in 2016. The majority of all homicides and suicides are firearm-related, and the majority of firearm-related deaths are the result of murder and suicide. When sorted by GDP, however, the United States has a much higher violent gun death rate compared to other developed countries, with over 10 times the number of firearms assault deaths than the next four highest GDP countries combined. Gunshot violence is the third most costly cause of injury and the fourth most expensive form of hospitalization in the United States.

History
Until the 1880s, the standard practice for treating a gunshot wound called for physicians to insert their unsterilized fingers into the wound to probe and locate the path of the bullet. Standard surgical theory such as opening abdominal cavities to repair gunshot wounds, germ theory, and Joseph Listers technique for antiseptic surgery using diluted carbolic acid, had not yet been accepted as standard practice. For example, sixteen doctors attended to President James A </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 Radiation burn and can you explain it in depth? [/INST] A radiation burn is a damage to the skin or other biological tissue and organs as an effect of radiation. The radiation types of greatest concern are thermal radiation, radio frequency energy, ultraviolet light and ionizing radiation.
The most common type of radiation burn is a sunburn caused by UV radiation. High exposure to X-rays during diagnostic medical imaging or radiotherapy can also result in radiation burns. As the ionizing radiation interacts with cells within the body—damaging them—the body responds to this damage, typically resulting in erythema—that is, redness around the damaged area. Radiation burns are often discussed in the same context as radiation-induced cancer due to the ability of ionizing radiation to interact with and damage DNA, occasionally inducing a cell to become cancerous. Cavity magnetrons can be improperly used to create surface and internal burning. Depending on the photon energy, gamma radiation can cause deep gamma burns, with 60Co internal burns common. Beta burns tend to be shallow as beta particles are not able to penetrate deeply into a body; these burns can be similar to sunburn. Alpha particles can cause internal alpha burns if inhaled, with external damage (if any) being limited to minor erythema.
Radiation burns can also occur with high power radio transmitters at any frequency where the body absorbs radio frequency energy and converts it to heat. The U.S. Federal Communications Commission (FCC) considers 50 watts to be the lowest power above which radio stations must evaluate emission safety. Frequencies considered especially dangerous occur where the human body can become resonant, at 35 MHz, 70 MHz, 80-100 MHz, 400 MHz, and 1 GHz. Exposure to microwaves of too high intensity can cause microwave burns.

Types
Radiation dermatitis (also known as radiodermatitis) is a skin disease associated with prolonged exposure to ionizing radiation.: 131–2  Radiation dermatitis occurs to some degree in most patients receiving radiation therapy, with or without chemotherapy.There are three specific types of radiodermatitis: acute radiodermatitis, chronic radiodermatitis, and eosinophilic, polymorphic, and pruritic eruption associated with radiotherapy.: 39–40  Radiation therapy can also cause radiation cancer.: 40 With interventional fluoroscopy, because of the high skin doses that can be generated in the course of the intervention, some procedures have resulted in early (less than two months after exposure) and/or late (two months or more after exposure) skin reactions, including necrosis in some cases.: 773 Radiation dermatitis, in the form of intense erythema and vesiculation of the skin, may be observed in radiation ports.: 131 As many as 95% of patients treated with radiation therapy for cancer will experience a skin reaction. Some reactions are immediate, while others may be later (e.g., months after treatment).

Acute
Acute radiodermatitis occurs when an "erythema dose" of ionizing radiation is given to the skin, after which visible erythema appears up to 24 hours after.: 39   Radiation dermatitis generally manifests within a few weeks after the start of radiotherapy.: 143   Acute radiodermatitis, while presenting as red patches, may sometimes also present with desquamation or blistering.  Erythema may occur at a dose of 2 Gy radiation or greater.

Chronic
Chronic radiodermatitis occurs with chronic exposure to "sub-erythema" doses of ionizing radiation over a prolonged period, producing varying degrees of damage to the skin and its underlying parts after a variable latent period of several months to several decades.: 40   In the distant past this type of radiation reaction occurred most frequently in radiologists and radiographers who were constantly exposed to ionizing radiation, especially before the use of X-ray filters.: 40   Chronic radiodermatitis, squamous and
basal cell carcinomas may develop months to years after radiation exposure.: 130   Chronic radiodermatitis presents as atrophic indurated plaques, often whitish or yellowish, with telangiectasia, sometimes with hyperkeratosis.: 130

Other
Eosinophilic, polymorphic, and pruritic eruption associated with radiotherapy is a skin condition that occurs most often in women receiving cobalt radiotherapy for internal cancer.: 39–40 Radiation-induced erythema multiforme may occur when phenytoin is given prophylactically to neurosurgical patients who are receiving whole-brain therapy and systemic steroids.: 130

Delayed effects
Radiation acne is a cutaneous condition characterized by comedo-like papules occurring at sites of previous exposure to therapeutic ionizing radiation, skin lesions that begin to appear as the acute phase of radiation dermatitis begins to resolve.: 501 Radiation recall reactions occur months to years after radiation treatment, a reaction that follows recent administration of a chemotherapeutic agent and occurs with the prior radiation port, characterized by features of radiation dermatitis.  Restated, radiation recall dermatitis is an inflammatory skin reaction that occurs in a previously irradiated body part following drug administration.  There does not appear to be a minimum dose, nor an established radiotherapy dose relationship.

Alpha burns
"Alpha burns" are caused by alpha particles, which can cause extensive tissue damage if inhaled. Due to the keratin in the epidermal layer of the skin, external alpha burns are limited to only mild reddening of the outermost layer of skin.

Beta burns
"Beta burns"—caused by beta particles—are shallow surface burns, usually of skin and less often of lungs or gastrointestinal tract, caused by beta particles, typically from hot particles or dissolved radionuclides that came to direct contact with or close proximity to the body. They can appear similar to sunburn. Unlike gamma rays, beta emissions are stopped much more effectively by materials and therefore deposit all their energy in only a shallow layer of tissue, causing more intense but more localized damage. On cellular level, the changes in skin are similar to radiodermatitis.
High doses of radiation can cause rapid browning of skin, known as "nuclear tan".The dose is influenced by relatively low penetration of beta emissions through materials. The cornified keratine layer of epidermis has enough stopping power to absorb beta radiation with energies lower than 70 keV. Further protection is provided by clothing, especially shoes. The dose is further reduced by limited retention of radioactive particles on skin; a 1 millimeter particle is typically released in 2 hours, while a 50 micrometer particle usually does not adhere for more than 7 hours. Beta emissions are also severely attenuated by air; their range generally does not exceed 6 feet (1.8 m) and intensity rapidly diminishes with distance.The eye lens seems to be the most sensitive organ to beta radiation, even in doses far below maximum permissible dose. Safety goggles are recommended to attenuate strong beta.Beta burns can occur also to plants. An example of such damage is the Red Forest, a victim of the Chernobyl accident.
Careful washing of exposed body surface, removing the radioactive particles, may provide significant dose reduction. Exchanging or at least brushing off clothes also provides a degree of protection.
If the exposure to beta radiation is intense, the beta burns may first manifest in 24–48 hours by itching and/or burning sensation that last for one or two days, sometimes accompanied by hyperaemia. After 1–3 weeks burn symptoms appear; erythema, increased skin pigmentation (dark colored patches and raised areas), followed by epilation and skin lesions. Erythema occurs after 5–15 Gy, dry desquamation after 17 Gy, and bullous epidermitis after 72 Gy. Chronic radiation keratosis may develop after higher doses. Primary erythema lasting more than 72 hours is an indication of injury severe enough to cause chronic radiation dermatitis. Edema of dermal papillae, if present within 48 hours since the exposition, is followed by transepidermal necrosis. After higher doses, the malpighian layer cells die within 24 hours; lower doses may take 10–14 days to show dead cells. Inhalation of beta radioactive isotopes may cause beta burns of lungs and nasopharyngeal region, ingestion may lead to burns of gastrointestinal tract; the latter being a risk especially for grazing animals.

In first degree beta burns the damage is largely limited to epidermis. Dry or wet desquamation occurs; dry scabs are formed, then heal rapidly, leaving a depigmented area surrounded with irregular area of increased pigmentation. The skin pigmentation returns to normal within several weeks.
Second degree beta burns lead to formation of blisters.
Third and fourth degree beta burns result in deeper, wet ulcerated lesions, which heal with routine medical care after covering themselves with dry scab. In case of heavy tissue damage, ulcerated necrotic dermatitis may occur. Pigmentation may return to normal within several months after wound healing.Lost hair begins regrowing in nine weeks and is completely restored in about half a year.The acute dose-dependent effects of beta radiation on skin are as follows:
According to other source:
As shown, the dose thresholds for symptoms vary by source and even individually. In practice, determining the exact dose tends to be difficult.
Similar effects apply to animals, with fur acting as additional factor for both increased particle retention and partial skin shielding. Unshorn thickly wooled sheep are well protected; while the epilation threshold for sheared sheep is between 23 and 47 Gy (2500–5000 rep) and the threshold for normally wooled face is 47–93 Gy (5000–10000 rep), for thickly wooled (33 mm hair length) sheep it is 93–140 Gy (10000–15000 rep). To produce skin lesions comparable with contagious pustular dermatitis, the estimated dose is between 465 and 1395 Gy.

Energy vs penetration depth
The effects depend on both the intensity and the energy of the radiation. Low-energy beta (sulfur-35, 170 keV) produces shallow ulcers with little damage to dermis, while cobalt-60 (310 keV), caesium-137 (550 keV), phosphorus-32 (1.71 MeV), strontium-90 (650 keV) and its daughter product yttrium-90 (2.3 MeV) damage deeper levels of the dermis and can result in chronic radiation dermatitis. Very high energies from electron beams from particle accelerators, reaching tens of megaelectronvolts, can be deeply penetrating. Conversely, megavolt-scale beams can deposit their energy deeper with less damage to the dermis; modern radiotherapy electron beam accelerators take advantage of this. At yet higher energies, above 16 MeV, the effect does not show significantly anymore, limiting the usefulness of higher energies for radiotherapy. As a convention, surface is defined as the topmost 0.5 mm of skin. High-energy beta emissions should be shielded with plastic instead of lead, as high-Z elements generate deeply penetrating gamma bremsstrahlung.
The electron energies from beta decay are not discrete but form a continuous spectrum with a cutoff at maximum energy. The rest of the energy of each decay is carried off by an antineutrino which does not significantly interact and therefore does not contribute to the dose. Most energies of beta emissions are at about a third of the maximum energy. Beta emissions have much lower energies than what is achievable from particle accelerators, no more than few megaelectronvolts.
The energy-depth-dose profile is a curve starting with a surface dose, ascending to the maximum dose in a certain depth dm (usually normalized as 100% dose), then descends slowly through depths of 90% dose (d90) and 80% dose (d80), then falls off linearly and relatively sharply though depth of 50% dose (d50). The extrapolation of this linear part of the curve to zero defines the maximum electron range, Rp. In practice, there is a long tail of weaker but deep dose, called "bremsstrahlung tail", attributable to bremsstrahlung. The penetration depth depends also on beam shape, narrower beam tend to have less penetration. In water, broad electron beams, as is the case in homogeneous surface contamination of skin, have d80 about E/3 cm and Rp about E/2 cm, where E is the beta particle energy in MeV.The penetration depth of lower-energy beta in water (and soft tissues) is about 2 mm/MeV. For a 2.3 MeV beta the maximum depth in water is 11 mm, for 1.1 MeV it is 4.6 mm. The depth where maximum of the energy is deposited is significantly lower.The energy and penetration depth of several isotopes is as follows:
For a wide beam, the depth-energy relation for dose ranges is as follows, for energies in megaelectronvolts and depths in millimeters. The dependence of surface dose and penetration depth on beam energy is clearly visible.

Causes
Radiation burns are caused by exposure to high levels of radiation. Levels high enough to cause burn are generally lethal if received as a whole-body dose, whereas they may be treatable if received as a shallow or local dose.

Medical imaging
Fluoroscopy may cause burns if performed repeatedly or for too long.Similarly, X-ray computed tomography and traditional projectional radiography have the potential to cause radiation burns if the exposure factors and exposure time are not appropriately controlled by the operator.
A study of radiation-induced skin injuries has been performed by the Food and Drug Administration (FDA) based on results from 1994, followed by an advisory to minimize further fluoroscopy-induced injuries. The problem of radiation injuries due to fluoroscopy has been further investigated in review articles in 2000, 2001, 2009 and 2010.

Radioactive fallout
Beta burns are frequently the result of exposure to radioactive fallout after nuclear explosions or nuclear accidents. Shortly after the explosion, the fission products have very high beta activity, with about two beta emissions per each gamma photon.
After the Trinity test, the fallout caused localized burns on the backs of cattle in the area downwind. The fallout had the appearance of small flaky dust particles. The cattle showed temporary burns, bleeding, and loss of hair. Dogs were also affected; in addition to localized burns on their backs, they also had burned paws, likely from the particles lodged between their toes as hoofed animals did not show problems with feet. About 350–600 cattle were affected by superficial burns and localized temporary loss of dorsal hair; the army later bought 75 most affected cows as the discolored regrown hair lowered their market value. The cows were shipped to Los Alamos and Oak Ridge, where they were observed. They healed, now sporting large patches of white fur; some looked as if they had been scalded.The fallout produced by the Castle Bravo test was unexpectedly strong. A white snow-like dust, nicknamed by the scientists "Bikini snow" and consisting of contaminated crushed calcined coral, fell for about 12 hours upon the Rongelap Atoll, depositing a layer of up to 2 cm. Residents developed beta burns, mostly on the backs of their necks and on their feet, and were resettled after three days. After 24–48 hours their skin was itching and burning; in a day or two the sensations subsided, to be followed after 2–3 weeks by epilation and ulcers. Darker-colored patches and raised areas appeared on their skin, blistering was uncommon. Ulcers formed dry scabs and healed. Deeper lesions, painful, weeping and ulcerated, formed on more contaminated residents; the majority healed with simple treatment. In general, the beta burns healed with some cutaneous scarring and depigmentation. Individuals who bathed and washed the fallout particles from their skin did not develop skin lesions. The fishing ship Daigo Fukuryu Maru was affected by the fallout as well; the crew suffered skin doses between 1.7 and 6.0 Gy, with beta burns manifesting as severe skin lesions, erythema, erosions, sometimes necrosis, and skin atrophy. Twenty-three U.S. radar servicemen of the 28-member weather station on Rongerik were affected, experiencing discrete 1–4 mm skin lesions which healed quickly, and ridging of fingernails several months later. Sixteen crew members of the aircraft carrier USS Bairoko received beta burns, and there was an increased cancer rate.During the Zebra test of the Operation Sandstone in 1948, three men had beta burns on their hands when removing sample collection filters from drones flying through the mushroom cloud; their estimated skin surface dose was 28 to 149 Gy, and their disfigured hands required skin grafts. A fourth man showed weaker burns after the earlier Yoke test.The Upshot–Knothole Harry test at the Frenchman Flat site released a large amount of fallout. A significant number of sheep died after grazing on contaminated areas. The AEC however had a policy to compensate farmers only for animals showing external beta burns, so many claims were denied. Other tests on the Nevada Test Site also caused fallout and corresponding beta burns to sheep, horses and cattle. During the Operation Upshot–Knothole, sheep as far as 50 miles (80 km) from the test site developed beta burns to their backs and nostrils.During underground nuclear testing in Nevada, several workers developed burns and skin ulcers, in part attributed to exposure to tritium.

Nuclear accidents
Beta burns were a serious medical issue for some victims of the Chernobyl disaster; from 115 patients treated in Moscow, 30% had burns covering 10–50% of body surface, 11% were affected on 50–100% of skin; the massive exposure was often caused by clothes drenched with radioactive water. Some firefighters developed beta burns of lungs and nasopharyngeal region after inhalation of massive amounts of radioactive smoke. Out of 28 deaths, 16 had skin injuries listed among the causes. The beta activity was extremely high, with beta/gamma ratio reaching 10–30 and beta energy high enough to damage basal layer of the skin, resulting in large area portals for infections, exacerbated by damage to bone marrow and weakened immune system. Some patients received skin dose of 400–500 Gy. The infections caused more than half of the acute deaths. Several died of fourth degree beta burns between 9–28 days after dose of 6–16 Gy </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 Pinguecula and can you explain it in depth? [/INST] A pinguecula is a common type of conjunctival stromal degeneration in the eye. It appears as an elevated yellow-white plaque in the bulbar conjunctiva near the limbus. Calcification may also seen occasionally.

Etiology
The exact etiology is unknown, but it may be associated with aging and excessive exposure to UV light.

Signs and symptoms
It is seen as a yellow-white deposit on the conjunctiva adjacent to the limbus (the junction between the cornea and sclera). (It is to be distinguished clinically from a pterygium, which is a wedge shaped area of fibrosis that may grow onto the cornea.) A pinguecula usually does not cause any symptoms. It is most common in tropical climates and there is a direct correlation with UV exposure.
Histologically, there is degeneration of the collagen fibers of the conjunctival stroma with thinning of the overlying epithelium and occasionally calcification. Actinic exposure of the thin conjunctival tissue is thought to cause fibroblasts to produce more elastin fibers, which are more twisted than normal elastin fibers and may lead to the degradation of the collagen fibers. Alternatively, it has been postulated that the sub-epithelial collagen fibers undergo degradation and assume the qualities of elastic tissue while fragmenting and twisting in a different configuration from their normal state.It is thought that the high reflectivity of the solid white scleral tissue underlying the conjunctival tissue may result in additional UV exposure to the back side of the tissue. The side of the nose also reflects sunlight on to the conjunctiva. As a result, pingueculae tend to occur more often on the nasal side of the eye.  While most pingueculae are found in people over the age of 40, they are not uncommon in 20- and 30-year-old adults who spend significant time in the sun.
The surface of the conjunctival tissue overlying a pinguecula interferes with the normal spreading of the tear film. The tear ferning test reveals abnormalities of the mucous component of the tear film, making it useful as a predictor of a persons tolerance of hydrophilic soft contact lenses </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 Coats disease and can you explain it in depth? [/INST] Coats disease is a rare congenital, nonhereditary eye disorder, causing full or partial blindness, characterized by abnormal development of blood vessels behind the retina. Coats disease can also fall under glaucoma.
It can have a similar presentation to that of retinoblastoma.

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

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

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

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

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

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


<s> [INST] <<SYS>> You are a 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 Adrenal crisis and can you explain it in depth? [/INST] Adrenal crisis is a potentially life-threatening medical condition requiring immediate emergency treatment. It is a constellation of symptoms (caused by insufficient levels of the hormone cortisol) that indicate severe adrenal insufficiency </s>


<s> [INST] <<SYS>> You are a 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 Amusia and can you explain it in depth? [/INST] Amusia is a musical disorder that appears mainly as a defect in processing pitch but also encompasses musical memory and recognition. Two main classifications of amusia exist: acquired amusia, which occurs as a result of brain damage, and congenital amusia, which results from a music-processing anomaly present since birth.
Studies have shown that congenital amusia is a deficit in fine-grained pitch discrimination and that 4% of the population has this disorder. Acquired amusia may take several forms. Patients with brain damage may experience the loss of ability to produce musical sounds while sparing speech, much like aphasics lose speech selectively but can sometimes still sing. Other forms of amusia may affect specific sub-processes of music processing. Current research has demonstrated dissociations between rhythm melody and emotional processing of music. Amusia may include impairment of any combination of these skill sets.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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


<s> [INST] <<SYS>> You are a 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 Polyhydramnios and can you explain it in depth? [/INST] Polyhydramnios is a medical condition describing an excess of amniotic fluid in the amniotic sac. It is seen in about 1% of pregnancies.  It is typically diagnosed when the amniotic fluid index (AFI) is greater than 24 cm.
There are two clinical varieties of polyhydramnios: chronic polyhydramnios where excess amniotic fluid accumulates gradually, and acute polyhydramnios where excess amniotic fluid collects rapidly.
The opposite to polyhydramnios is oligohydramnios, not enough amniotic fluid.

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

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

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


<s> [INST] <<SYS>> You are a 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 Paraneoplastic pemphigus and can you explain it in depth? [/INST] Paraneoplastic pemphigus (PNP)  is an autoimmune disorder stemming from an underlying tumor. It is hypothesized that antigens associated with the tumor trigger an immune response resulting in blistering of the skin and mucous membranes.
While patients with malignant and benign tumors are both at risk, malignancy is associated with high mortality rates (near 90%). Current treatment focuses on general wound healing and administering corticosteroids, which has not demonstrated a high success rate. Recent research developments aim to treat the underlying tumor in order to alleviate the symptoms of PNP.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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


<s> [INST] <<SYS>> You are a 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 Sandhoff disease and can you explain it in depth? [/INST] Sandhoff disease is a lysosomal genetic, lipid storage disorder caused by the inherited deficiency to create functional beta-hexosaminidases A and B. These catabolic enzymes are needed to degrade the neuronal membrane components, ganglioside GM2, its derivative GA2, the glycolipid globoside in visceral tissues, and some oligosaccharides. Accumulation of these metabolites leads to a progressive destruction of the central nervous system and eventually to death. The rare autosomal recessive neurodegenerative disorder is clinically almost indistinguishable from Tay–Sachs disease, another genetic disorder that disrupts beta-hexosaminidases A and S. There are three subsets of Sandhoff disease based on when first symptoms appear: classic infantile, juvenile and adult late onset.

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

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

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

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

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

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

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

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


<s> [INST] <<SYS>> You are a 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 Amalgam tattoo and can you explain it in depth? [/INST] Amalgam tattoo is a grey, blue or black area of discoloration on the mucous membranes of the mouth, typically on the gums of the lower jaw </s>