<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Hyponatremia and explain in detail? [/INST] Hyponatremia is a low sodium concentration in the blood. It is generally defined as a sodium concentration of less than 135 mmol/L (135 mEq/L), with severe hyponatremia being below 120 mEq/L. Symptoms can be absent, mild or severe. Mild symptoms include a decreased ability to think, headaches, nausea, and poor balance. Severe symptoms include confusion, seizures, and coma.The causes of hyponatremia are typically classified by a persons body fluid status into low volume, normal volume, or high volume. Low volume hyponatremia can occur from diarrhea, vomiting, diuretics, and sweating. Normal volume hyponatremia is divided into cases with dilute urine and concentrated urine. Cases in which the urine is dilute include adrenal insufficiency, hypothyroidism, and drinking too much water or too much beer. Cases in which the urine is concentrated include syndrome of inappropriate antidiuretic hormone secretion (SIADH). High volume hyponatremia can occur from heart failure, liver failure, and kidney failure. Conditions that can lead to falsely low sodium measurements include high blood protein levels such as in multiple myeloma, high blood fat levels, and high blood sugar.Treatment is based on the underlying cause. Correcting hyponatremia too quickly can lead to complications. Rapid partial correction with 3% normal saline is only recommended in those with significant symptoms and occasionally those in whom the condition was of rapid onset. Low volume hyponatremia is typically treated with intravenous normal saline. SIADH is typically treated by correcting the underlying cause and with fluid restriction while high volume hyponatremia is typically treated with both fluid restriction and a diet low in salt. Correction should generally be gradual in those in whom the low levels have been present for more than two days.Hyponatremia is the most common type of electrolyte imbalance, and is often found in older adults. It occurs in about 20% of those admitted to hospital and 10% of people during or after an endurance sporting event. Among those in hospital, hyponatremia is associated with an increased risk of death. The economic costs of hyponatremia are estimated at $2.6 billion per annum in the United States.

Signs and symptoms
Signs and symptoms of hyponatremia include nausea and vomiting, headache, short-term memory loss, confusion, lethargy, fatigue, loss of appetite, irritability, muscle weakness, spasms or cramps, seizures, and decreased consciousness or coma. Lower levels of plasma sodium are associated with more severe symptoms. However, mild hyponatremia (plasma sodium levels at 131–135 mmol/L) may be associated with complications and subtle symptoms (for example, increased falls, altered posture and gait, reduced attention, impaired cognition, and possibly higher rates of death).Neurological symptoms typically occur with very low levels of plasma sodium (usually <115 mmol/L). When sodium levels in the blood become very low, water enters the brain cells and causes them to swell (cerebral edema). This results in increased pressure in the skull and causes hyponatremic encephalopathy. As pressure increases in the skull, herniation of the brain can occur, which is a squeezing of the brain across the internal structures of the skull. This can lead to headache, nausea, vomiting, confusion, seizures, brain stem compression and respiratory arrest, and non-cardiogenic accumulation of fluid in the lungs. This is usually fatal if not immediately treated.
Symptom severity depends on how fast and how severe the drop in blood sodium level is. A gradual drop, even to very low levels, may be tolerated well if it occurs over several days or weeks, because of neuronal adaptation. The presence of underlying neurological disease such as a seizure disorder or non-neurological metabolic abnormalities, also affects the severity of neurologic symptoms.
Chronic hyponatremia can lead to such complications as neurological impairments. These neurological impairments most often affect gait (walking) and attention, and can lead to increased reaction time and falls. Hyponatremia, by interfering with bone metabolism, has been linked with a doubled risk of osteoporosis and an increased risk of bone fracture.

Causes
The specific causes of hyponatremia are generally divided into those with low tonicity (lower than normal concentration of solutes), without low tonicity, and falsely low sodiums. Those with low tonicity are then grouped by whether the person has high fluid volume, normal fluid volume, or low fluid volume. Too little sodium in the diet alone is very rarely the cause of hyponatremia.

High volume
Both sodium and water content increase: Increase in sodium content leads to hypervolemia and water content to hyponatremia.

Cirrhosis of the liver
Congestive heart failure
Nephrotic syndrome in the kidneys
Excessive drinking of fluids

Normal volume
There is volume expansion in the body, no edema, but hyponatremia occurs
SIADH (and its many causes)
Hypothyroidism
Not enough ACTH
Beer potomania
Normal physiologic change of pregnancy
Reset osmostat

Low volume
Hypovolemia (extracellular volume loss) is due to total body sodium loss.  Hyponatremia is caused by a relatively smaller loss in total body water.
Any cause of hypovolemia such as prolonged vomiting, decreased oral intake, severe diarrhea
Diuretic use (due to the diuretic causing a volume depleted state and thence ADH release, and not a direct result of diuretic-induced urine sodium loss)
Addisons disease and congenital adrenal hyperplasia in which the adrenal glands do not produce enough steroid hormones (combined glucocorticoid and mineralocorticoid deficiency)
Pancreatitis
Prolonged exercise and sweating, combined with drinking water without electrolytes is the cause of exercise-associated hyponatremia (EAH). It is common in marathon runners and participants of other endurance events.
The use of MDMA (ecstasy) can result in hyponatremia.

Medication
Antipsychotics have been reported to cause hyponatremia in a review of medical articles from 1946 to 2016.Available evidence suggests that all classes of psychotropics, i.e., antidepressants, antipsychotics, mood stabilizers, and sedative/hypnotics can lead to hyponatremia. Age is a significant factor for drug induced hyponatremia.

Other causes
Miscellaneous causes that are not included under the above classification scheme include the following:

False or pseudo hyponatremia is caused by a false lab measurement of sodium due to massive increases in blood triglyceride levels or extreme elevation of immunoglobulins as may occur in multiple myeloma.
Hyponatremia with elevated tonicity can occur with high blood sugar, causing an shift of excess free water into the serum.

Pathophysiology
The causes of and treatments for hyponatremia can only be understood by having a grasp of the size of the body fluid compartments and subcompartments and their regulation; how under normal circumstances the body is able to maintain the sodium concentration within a narrow range (homeostasis of body fluid osmolality); conditions can cause that feedback system to malfunction (pathophysiology); and the consequences of the malfunction of that system on the size and solute concentration of the fluid compartments.

Normal homeostasis
There is a hypothalamic-kidney feedback system which normally maintains the concentration of the serum sodium within a narrow range. This system operates as follows: in some of the cells of the hypothalamus, there are osmoreceptors which respond to an elevated serum sodium in body fluids by signalling the posterior pituitary gland to secrete antidiuretic hormone (ADH) (vasopressin). ADH then enters the bloodstream and signals the kidney to bring back sufficient solute-free water from the fluid in the kidney tubules to dilute the serum sodium back to normal, and this turns off the osmoreceptors in the hypothalamus. Also, thirst is stimulated. Normally, when mild hyponatremia begins to occur, that is, the serum sodium begins to fall below 135 mEq/L, there is no secretion of ADH, and the kidney stops returning water to the body from the kidney tubule. Also, no thirst is experienced. These two act in concert to raise the serum sodium to the normal range.

Hyponatremia
Hyponatremia occurs 1) when the hypothalamic-kidney feedback loop is overwhelmed by increased fluid intake, 2) the feedback loop malfunctions such that ADH is always "turned on", 3) the receptors in the kidney are always "open" regardless of there being no signal from ADH to be open; or 4) there is an increased ADH even though there is no normal stimulus (elevated serum sodium) for ADH to be increased.
Hyponatremia occurs in one of two ways: either the osmoreceptor-aquaporin feedback loop is overwhelmed, or it is interrupted. If it is interrupted, it is either related or not related to ADH. If the feedback system is overwhelmed, this is water intoxication with maximally dilute urine and is caused by 1) pathological water drinking (psychogenic polydipsia), 2) beer potomania, 3) overzealous intravenous solute free water infusion, or 4) infantile water intoxication. "Impairment of urine diluting ability related to ADH" occurs in nine situations: 1) arterial volume depletion 2) hemodynamically mediated, 3) congestive heart failure, 4) cirrhosis, 5) nephrosis, 6) spinal cord disease, 7) Addisons disease, 8) cerebral salt wasting, and 9) syndrome of inappropriate antidiuretic hormone secretion (SIADH).
If the feed-back system is normal, but an impairment of urine diluting ability unrelated to ADH occurs, this is 1) oliguric kidney failure, 2) tubular interstitial kidney disease, 3) diuretics, or 4) nephrogenic syndrome of antidiuresis.Sodium is the primary positively charged ion outside of the cell and cannot cross from the interstitial space into the cell. This is because charged sodium ions attract around them up to 25 water molecules, thereby creating a large polar structure too large to pass through the cell membrane: "channels" or "pumps" are required.
Cell swelling also produces activation of volume-regulated anion channels which is related to the release of taurine and glutamate from astrocytes.

Diagnosis
The history, physical exam, and laboratory testing are required to determine the underlying cause of hyponatremia. A blood test demonstrating a serum sodium less than 135 mmol/L is diagnostic for hyponatremia. The history and physical exam are necessary to help determine if the person is hypovolemic, euvolemic, or hypervolemic, which has important implications in determining the underlying cause. An assessment is also made to determine if the person is experiencing symptoms from their hyponatremia. These include assessments of alertness, concentration, and orientation.

False hyponatremia
False hyponatremia, also known as spurious, pseudo, hypertonic, or artifactual hyponatremia is when the lab tests read low sodium levels but there is no hypotonicity. In hypertonic hyponatremia, resorption of water by molecules such as glucose (hyperglycemia or diabetes) or mannitol (hypertonic infusion) occurs. In isotonic hyponatremia a measurement error due to high blood triglyceride level (most common) or paraproteinemia occurs. It occurs when using techniques that measure the amount of sodium in a specified volume of serum/plasma, or that dilute the sample before analysis.

True hyponatremia
True hyponatremia, also known as hypotonic hyponatremia, is the most common type. It is often simply referred to as "hyponatremia."  Hypotonic hyponatremia is categorized in 3 ways based on the persons blood volume status. Each category represents a different underlying reason for the increase in ADH that led to the water retention and thence hyponatremia:

High volume hyponatremia, wherein there is decreased effective circulating volume (less blood flowing in the body) even though total body volume is increased (by the presence of edema or swelling, especially in the ankles). The decreased effective circulating volume stimulates the release of anti-diuretic hormone (ADH), which in turn leads to water retention. Hypervolemic hyponatremia is most commonly the result of congestive heart failure, liver failure, or kidney disease.
Normal volume hyponatremia, wherein the increase in ADH is secondary to either physiologic but excessive ADH release (as occurs with nausea or severe pain) or inappropriate and non-physiologic secretion of ADH, that is, syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH).  Often categorized under euvolemic is hyponatremia due to inadequate urine solute (not enough chemicals or electrolytes to produce urine) as occurs in beer potomania or "tea and toast" hyponatremia, hyponatremia due to hypothyroidism or central adrenal insufficiency, and those rare instances of hyponatremia that are truly secondary to excess water intake.
Low volume hyponatremia, wherein ADH secretion is stimulated by or associated with volume depletion (not enough water in the body) due to decreased effective circulating volume.

Acute versus chronic
Chronic hyponatremia is when sodium levels drop gradually over several days or weeks and symptoms and complications are typically moderate. Chronic hyponatremia is often called asymptomatic hyponatremia in clinical settings because it is thought to have no symptoms; however, emerging data suggests that "asymptomatic" hyponatremia is not actually asymptomatic.Acute hyponatremia is when sodium levels drop rapidly, resulting in potentially dangerous effects, such as rapid brain swelling, which can result in coma and death.

Treatment
The treatment of hyponatremia depends on  the underlying cause. How quickly treatment is required depends on a persons symptoms. Fluids are typically the cornerstone of initial management. In those with severe disease an increase in sodium of about 5 mmol/L over one to four hours is recommended. A rapid rise in serum sodium is anticipated in certain groups when the cause of the hyponatremia is addressed thus warranting closer monitoring in order to avoid overly rapid correction of the blood sodium concentration. These groups include persons who have hypovolemic hyponatremia and receive intravenous fluids (thus correcting their hypovolemia), persons with adrenal insufficiency who receive hydrocortisone, persons in whom a medication causing increased ADH release has been stopped, and persons who have hyponatremia due to decreased salt and/or solute intake in their diet who are treated with a higher solute diet. If large volumes of dilute urine are seen, this can be a warning sign that overcorrection is imminent in these individuals.Sodium deficit = (140 – serum sodium) x total body waterTotal body water = kilograms of body weight x 0.6

FluidsOptions include:
Mild and asymptomatic hyponatremia is treated with adequate solute intake (including salt and protein) and fluid restriction starting at 500 millilitres per day (mL/d) of water with adjustments based on serum sodium levels. Long-term fluid restriction of 1,200–1,800 mL/d may maintain the person in a symptom-free state.
Moderate and/or symptomatic hyponatremia is treated by raising the serum sodium level by 0.5 to 1 mmol per liter per hour for a total of 8 mmol per liter during the first day with the use of furosemide and replacing sodium and potassium losses with 0.9% saline.
Severe hyponatremia or severe symptoms (confusion, convulsions, or coma): consider hypertonic saline (3%) 1–2 mL/kg IV in 3–4 h. Hypertonic saline may  lead to a rapid dilute diuresis and fall in the serum sodium. It should not be used in those with an expanded extracellular fluid volume.

Electrolyte abnormalities
In persons with hyponatremia due to low blood volume (hypovolemia) from diuretics with simultaneous low blood potassium levels, correction of the low potassium level can assist with correction of hyponatremia.

Medications
American and European guidelines come to different conclusions regarding the use of medications. In the United States they are recommended in those with SIADH, cirrhosis, or heart failure who fail limiting fluid intake. In Europe they are not generally recommended.There is tentative evidence that vasopressin receptor antagonists (vaptans), such as conivaptan, may be slightly more effective than fluid restriction in those with high volume or normal volume hyponatremia. They should not be used in people with low volume. They may also be used in people with chronic hyponatremia due to SIADH that is insufficiently responsive to fluid restriction and/or sodium tablets.Demeclocycline, while sometimes used for SIADH, has significant side effects including potential kidney problems and sun sensitivity. In many people it has no benefit while in others it can result in overcorrection and high blood sodium levels.Daily use of urea by mouth, while not commonly used due to the taste, has tentative evidence in SIADH. However, it is not available in many areas of the world.

Precautions
Raising the serum sodium concentration too rapidly may cause osmotic demyelination syndrome. Rapid correction of sodium levels can also lead to central pontine myelinolysis (CPM). It is recommended not to raise the serum sodium by more than 10 mEq/L/day.

Epidemiology
Hyponatremia is the most commonly seen water–electrolyte imbalance. The disorder is more frequent in females, the elderly, and in people who are hospitalized. The number of cases of hyponatremia depends largely on the population. In hospital it affects about 15–20% of people; however, only 3–5% of people who are hospitalized have a sodium level less than 130 mmol/L. Hyponatremia has been reported in up to 30% of the elderly in nursing homes and is also present in approximately 30% of people who are depressed on selective serotonin reuptake inhibitors.People who have hyponatremia who require hospitalisation have a longer length of stay (with associated increased costs) and also have a higher likelihood of requiring readmission. This is particularly the case in men and in the elderly.

References
Further reading
Sandy Craig; Erik D Schraga; Francisco Talavera; Howard A Bessen; John D Halamka (2010-04-13). "Hyponatremia in Emergency Medicine" </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Bitlis and explain in detail? [/INST] Bitlis (Armenian: Բաղեշ Baghesh/Paghesh; Kurdish: Bidlîs; Ottoman Turkish: بتليس) is a city in southeastern Turkey and the capital of Bitlis Province. The city is located at an elevation of 1,545 metres, 15 km from Lake Van, in the steep-sided valley of the Bitlis River, a tributary of the Tigris. The local economy is mainly based on agricultural products which include fruits, grain and tobacco. Industry is fairly limited, and deals mainly with leatherworking, manufacture of tobacco products as well as weaving and dyeing of coarse cloth. Bitlis is connected to other urban centres by road, including Tatvan on Lake Van, 25 km to the northeast, and the cities of Muş (Mush), 100 km northwest, and Diyarbakır, 200 km to the west. The climate of Bitlis can be harsh, with long winters and heavy snowfalls. Summers are hot, and often humid. Since the local elections of March 2019, the Mayor of Bitlis is Nesrullah Tanğlay.

History
Ancient and medieval
The origin of the name Bitlis is not known. A popular folk etymology explanation, without historical basis, is that it is derived from "Lis/Batlis", the name of a general said to have built Bitlis castle by the order of Alexander the Great. To Armenians, it was known as Balalesa or Baghaghesh, and later Baghesh. According to one popular Armenian folk story, on a cold, wintry day a donkey left its stable and wandered down the valley below. The donkey died of the freezing temperatures and was only discovered in the spring, once the ice had melted; thus, it received the name Pagh Esh, or "Cold Donkey."Baghesh was one of the most important cities of the Kingdom of Armenias province of Aghdznik, and it served as the primary fortress of the provinces canton of Salnodzor. Some medieval Armenian writers, such as Anania Shirakatsi and Vardan Areveltsi, later mention it as a part of the canton of Bznunik. The fortress guarded the Baghesh Pass, which linked the southern reaches of the Armenian Plateau to northern Mesopotamia. The Arabs conquered Baghesh at the end of the seventh century and it eventually became the capital of the Zurārid emirs of Arzan. Because it was on an important trade route, it prospered greatly.
The next two centuries, however, marked a turbulent period in the towns history. After Bugha al-Kabirs destructive 852-855 campaign in Armenia, the Shaybanid emirs wrested control of Baghesh from the Zurārids; thereafter, in the first quarter of the tenth century, it was taken by the Kaysite emirs of Manzikert. In his 929-30 campaign against the Kaysites, the Byzantine general John Curcuas was able to capture and annex Baghesh. Following the devastation of the Arab emirs in the second half of the tenth century, a great number of Kurds settled in Baghesh and at the end of the tenth century, the city fell into the hands of the Kurdish Marwanid dynasty after breaking from Buyid rule. At the end of the eleventh century, with the collapse of Byzantine power after the Battle of Manzikert, Bitlis fell under the control of Togan Arslan, a subject of the Shah Arman (Also called Ahlatshah) dynasty based in Akhlat after brief Dilmachoglu rule. It was also ruled by Ayyubid (1207–1231), Khwarezm Shahs (shortly rule in 1230), Sultanate of Rûm (1231–1243) and Ilkhanate (1243–1335).

Emirate
Bitlis was a Kurdish emirate from the 13th to the 19th century. Though often subordinate to a succession of larger powers that ruled the Van region, it always maintained a measure of independence. In the 14th century its emirs, the Kurdish Rusaki family, were vassals of the Karakoyunlu and the emirates territory also consisted of several smaller emirates: Ahlat, Mush, and Hinis. The emir of Bitlis submitted to Timur in 1394, but later helped the re-establishment of Karakoyunlu control in the region. After the collapse of the Karakoyunlu state, the Bitlis emirate disintegrated. However, in the 1470s it took the Aq Qoyunlu (White Sheep Turkomans) three successive sieges to capture Bitlis and in 1494/95 the Ruzaki recaptured the town. Armenians formed a large part of the citys population. A number of monasteries were permitted to be built by the Kurdish emirs and during the fifteenth century, Biltis flourished as a center for Armenian manuscript production.
Bitlis was forced to accept a Persian governor during the invasion of the Safavid Shah Ismail, but sided with the Ottoman forces as they approached the region. Its emir, Sheref, later changed his allegiance to the Persians. An Ottoman army besieged Bitlis for three months in 1531/32, but was forced to retire. Sheref was killed in battle in 1533 and his son and successor submitted to the Ottoman Empire. Mush and Hınıs were removed from the Bitlis emirate, becoming separate sanjaks but still with Ruzaki beys. A Jesuit mission was established in Bitlis in 1685. The Ruzakid Kurdish dynasty in Bitlis lasted until 1849, when an Ottoman governor evicted its last emir, Sheref Bey, who was taken to Constantinople as a prisoner. After this, Bitlis was governed by a Turkish pasha and formed the capital of a vilayet bearing its name.

Modern
In 1814 the population of Bitlis town was said to be 12,000 people - one half Muslim, the other half was constituted by Christian Armenians. By 1838 its population was said to be between 15,000 and 18,000 - two thirds Muslim, one third Armenian, and a small minority of Assyrians. In 1898 Lynch considered the population to be close to 30,000, comprising 10,000 Armenians, 300 [As]syrians, and the rest Muslim Kurds (both Alevis and Sunnis included). The Armenians had five schools for boys and three for girls. One third of the population of Bitlis was ethnic Armenian prior to World War I (1914, whereas the majority of the population was Kurdish Muslim (Alevi as well as Sunni Muslims). In 1915, during the Armenian genocide, Turks and Kurds, led by Jevdet Bey Pasha, massacred some 15,000 Armenians in Bitlis.In February 1916, as part of the Caucasus Campaign, Imperial Russian forces launched an offensive to capture Mush and Bitlis. Mush fell on February 16. At Bitlis, the Turkish positions were in a strong location on the outskirts of the town and could not be outflanked because of the narrowness of the valley. On the night of March 2–3, during a blizzard, the Russian 8th Caucasian Rifles advanced silently and, after several hours of hand-to-hand fighting, took the Turkish positions with 1,000 prisoners. The Turks then abandoned Bitlis, retreating towards Siirt. The Russian forces and intelligence officers found evidence of the massacres of Christians by the Kurdish and Turkish radicals in 1915.
In August 1916 the Turkish Second Army started an offensive against the Russian front in eastern Turkey. On August 2, the Ottoman 16th Corps, together with strong Kurdish irregulars support, attacked Bitlis and Mush. Fearing encirclement General Nazarbekov, the Russian commander, abandoned Bitlis on August 5. When Mush also fell, he decided to abandon Tatvan and the whole Mush valley and retreat to Ahlat. Around 18 August, the Russians having been reinforced, were able to counter-attack. By September the Turkish offensive was stalled and then turned. Nazarbekov advanced as the Turkish forces withdrew from Tatvan and Mush, but he did not have the available forces to hold Bitlis as winter approached. The Russian February Revolution in the spring of 1917 prevented any further Russian gains.

Description
Bitlis preserves more medieval and traditional architecture than any other town in eastern Turkey. They are of a high quality and are mostly constructed from locally quarried light-brown stone, sometimes called Ahlat stone.
The town contains a large number of late-medieval Islamic buildings in the form of mosques, madrassas, and tombs. Also commercial buildings such as "Hans Caravanserais. Commissioned mostly by its local Kurdish rulers, the architectural style of these buildings is very conservative and similar to much earlier Seljuq-period structures. Important monuments include the 12th-century Ulu Mosque with its 15th-century minaret, and the Gokmeydani Medresesi and Sherefiye Mosque from the sixteenth century. Until 1915 there were five Armenian monasteries and several churches in Bitlis – only a 19th-century Armenian church survives, now used as a warehouse.Bitlis is also notable for its many old houses. These are built of cut stone and are often large and impressive structures. Most have two stories, but three stories are also found. Ground floors were generally intended for storage and stables, with the residential quarters on the upper floors. Ground floor rooms have few windows, upper floors are well lit. Roofs are flat and covered with beaten clay.  Unlike traditional houses in nearby Erzurum or Van, Bitlis houses do not have bay windows and balconies.

Gallery
Demographics
According to Encyclopædia Britannica Eleventh Edition from 1911, the town had 35 thousand people with 12 thousand Armenians, the rest being Kurdish.

Climate
Bitlis has a dry-summer humid continental climate according to the (Köppen climate classification: Dsa, or Trewartha climate classification: Dca). Bitlis has hot, dry summers and cold, very snowy winters.

Economy
Historically, Bitlis produced wheat, which the British, in 1920, described as being "particularly excellent." However, poor trade routes in the area during the early 20th century meant that the wheat was mainly produced and used by locals. During this time, the British stated that the people of Bitlis were unable to use all of the wheat they produced, and most was "left to rot in the underground storehouses."

Notable individuals
Badh ibn Dustak (died 991), Kurdish tribal leader
Arakel Paghishetsi (1380-1454) Armenian musician, hymnologist
Hovhannes Paghishetsi (1678-1741) 49th Armenian patriarch of Constantinople
Vardan Paghishetsi (???-1705) Armenian chronographer
Vardan Paghishetsi (16th century) Armenian medieval illuminatorThe city was the home of the sixteenth century Kurdish historian, Sherefxan Bedlisi (also: Sharaf al-Din Bitlisi), author of the Sharafnameh, and who was also an appointed prince of the Persian and later Ottoman Empires.
Hosam al-Din Ali Bitlisi was a Kurdish Sufi author. He was the father of the noted historian Idris Bitlisi.
Ottoman administrator and Kurdish religious scholar and author Idris-i Bitlisi is claimed to have been born in Bitlis also.  He was instrumental in conquest, Ottomanization and administration of Ottoman lands from Urfa, Mardin to Egypt.
Said Nursi (Nurs, Bitlis, 1877) notable Kurdish Sunni Muslim Theologian. Writer of the Risale-i-Nur collection used as the foundation of movements such as the Nurcu in Turkey and the Gulenist movement founded by Fetullah Gulen.
Fuat Sezgin (Bitlis, 1924), a prominent Historian of Science, Orientalist was born in Bitlis. He is the author and editor of numerous publications. His 13-volume work Geschichte des Arabischen Schrifttums (1967-2000) is the cornerstone reference on the history of science and technology in the Islamic world </s>


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Melanotic neuroectodermal tumor of infancy and explain in detail? [/INST] Melanotic neuroectodermal tumor of infancy is a very rare oral cavity tumor that is seen in patients usually at or around birth. It must be removed to be cured. Definitions:  A rare, biphasic, neuroblastic, and pigmented epithelial neoplasm of craniofacial sites, usually involving the oral cavity or gums.

Signs and symptoms
Most patients present with a very rapidly growing mass that often gives a bluish appearance in the mouth. This is because the pigmentation in the cells appears blue through the overlying epithelium (mucosa). By imaging studies, there is usually a large expansive radiolucent (clear) mass without well defined borders. Calcifications within the mass may be seen. More than 70% involve the maxilla (usually maxillary anterior alveolar ridge), while the mandible and skull are affected less often. There is often an elevated vanilmandelic acid level.

Pathogenesis
It is considered to be a developmental anomaly, and thus is congenital in presentation. It is thought to be derived from neural crest, which is one of the embryologic tissue types. The reason for this postulation is based on the expression of melanotransferrin (melanoma-specific peptide that may play role in iron metabolism).

Diagnosis
Macroscopic
Usually there is a smooth, firm mass, with mottled white-gray to blue-black cut surfaces. The overall size ranges from 1–10 cm with a mean size 3.5 cm.

Microscopic
The tumor is usually very well circumscribed but not encapsulated. There are two cell types present (biphasic), arranged in alveolar or tubular configurations. There are centrally located, small, darkly staining cells comprising the majority of cells. These cells have a fibrillary cytoplasm surrounding round nuclei with coarse and heavy nuclear chromatin. These cells are surrounded by much larger polygonal cells that have open nuclear chromatin and abundant opaque cytoplasm that has granular melanin pigment. There is usually no hemorrhage, necrosis or increased mitoses.

Immunohistochemistry
The lesional cells will show cross reactivity with several different families of immunohistochemistry markers (polyphenotypic), including neural, melanocytic, and epithelial.

Large tumor cells: Keratin, vimentin, HMB-45, NSE, CD57
Small tumor cells: Synaptophysin, GFAP, NSE, CD57
There is usually a variable expression of EMA and S100 protein.

Differential diagnoses
It is important in this age group to exclude other tumors that can have a similar appearance, such as rhabdomyosarcoma, lymphoma, Ewing sarcoma (primitive neuroectodermal tumor), or even a melanoma (although they are very very rare in infants).

Management
Even though there is often a very dramatic and rapidly enlarging, destructive tumor, there is usually a benign clinical course after complete local excision (usually by partial maxillectomy) with clear or free surgical margins. In rare cases, chemotherapy may be used for recurrent or residual tumors </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Video game addiction and explain in detail? [/INST] Video game addiction (VGA), also known as  gaming disorder or internet gaming disorder, is generally defined as the problematic, compulsive use of video games that results in significant impairment to an individuals ability to function in various life domains over a prolonged period of time. This and associated concepts have been the subject of considerable research, debate, and discussion among experts in several disciplines and has generated controversy within the medical, scientific, and gaming communities. Such disorders can be diagnosed when an individual engages in gaming activities at the cost of fulfilling daily responsibilities or pursuing other interests without regard for the negative consequences. As defined by the ICD-11, the main criterion for this disorder is a lack of self control over gaming.The World Health Organization included gaming disorder in the 11th revision of its International Classification of Diseases (ICD). The American Psychiatric Association (APA), while stating there is insufficient evidence for the inclusion of Internet gaming disorder in the Diagnostic and Statistical Manual of Mental Disorders in 2013, considered it worthy of further study.Controversy around the diagnosis includes whether the disorder is a separate clinical entity or a manifestation of underlying psychiatric disorders. Research has approached the question from a variety of viewpoints, with no universally standardized or agreed definitions, leading to difficulties in developing evidence-based recommendations.

Definition and diagnosis
In its report, the Council on Science and Public Health to the American Medical Association (AMA) used this two-hour-per-day limit to define "gaming overuse", citing the American Academy of Pediatrics guideline of no more than one to two hours per day of "screen time". However, the ESA document cited in the Council report does not contain the two-hour-per-day data.

American Psychiatric Association
While the American Psychiatric Association (APA) does not recognise video game addiction as a disorder, in light of existing evidence, the organisation included video game addiction as a "condition requiring further study" in the DSM-5 as Internet gaming disorder. Video game addiction is a broader concept than internet gaming addiction, but most video game addiction is associated with internet gaming. APA suggests, like Khan, the effects (or symptoms) of video game addiction may be similar to those of other proposed psychological addictions.  Video game addiction may be an impulse control disorder, similar to compulsive gambling The APA explains why Internet Gaming Disorder has been proposed as a disorder:This decision was based upon the large number of studies of this condition and the severity of its consequences. ... Because of the distinguishing features and increased risks of clinically significant problems associated with gaming in particular, the Workgroup recommended the inclusion of only internet gaming disorder in Section 3 of the DSM-5.
Some players become more concerned with their interactions in the game than in their broader lives. Players may play many hours per day, neglect personal hygiene, gain or lose significant weight, disrupt sleep patterns resulting in sleep deprivation, play at work, avoid phone calls from friends, or lie about how much time they spend playing video games.The APA has developed nine criteria for characterising the proposed Internet Gaming Disorder:
Pre-occupation. Do you spend a lot of time thinking about games even when you are not playing, or planning when you can play next?
Withdrawal. Do you feel restless, irritable, moody, angry, anxious or sad when attempting to cut down or stop gaming, or when you are unable to play?
Tolerance. Do you feel the need to play for increasing amounts of time, play more exciting games, or use more powerful equipment to get the same amount of excitement you used to get?
Reduce/stop. Do you feel that you should play less, but are unable to cut back on the amount of time you spend playing games?
Give up other activities. Do you lose interest in or reduce participation in other recreational activities due to gaming?
Continue despite problems. Do you continue to play games even though you are aware of negative consequences, such as not getting enough sleep, being late to school/work, spending too much money, having arguments with others, or neglecting important duties?
Deceive/cover up. Do you lie to family, friends or others about how much you game, or try to keep your family or friends from knowing how much you game?
Escape adverse moods. Do you game to escape from or forget about personal problems, or to relieve uncomfortable feelings such as guilt, anxiety, helplessness or depression?
Risk/lose relationships/opportunities. Do you risk or lose significant relationships, or job, educational or career opportunities because of gaming?One of the most commonly used instruments for the measurement of addiction, the PVP Questionnaire (Problem Video Game Playing Questionnaire, Tejeiro & Moran, 2002), was presented as a quantitative measure, not as a diagnostic tool.
According to Griffiths, "all addictions (whether chemical or behavioral) are essentially about constant rewards and reinforcement". He proposes that addiction has six components: salience, mood modification, tolerance, withdrawal, conflict, and relapse. But the APAs nine criteria for diagnosing Internet Gaming Disorder were made by taking point of departure in eight different diagnostic/measuring tools proposed in other studies. Thus, the APAs criteria attempt to condense the scientific work on diagnosing Internet Gaming Disorder.

World Health Organization
The World Health Organization (WHO) had proposed and later included "gaming disorder" in the 11th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-11), released in June 2018, which was approved by the World Health Assembly in May 2019. The use and enforcement of ICD-11 is expected to start on 1 January 2022.

Screening tools
The first psychometric test to assess IGD was the Internet Gaming Disorder Test (IGD-20). This test includes 20 questions designed to assess the extent of problems caused by disordered gaming and the degree of symptoms experienced by gamers. The test was first published in a journal article published in the PLoS ONE journal on 14 October 2014.
The Internet Gaming Disorder Scale–Short-Form (IGDS9-SF) is a short psychometric test to assess video game addiction according to the American Psychiatric Association framework for IGD. Recent review studies suggest that the IGDS9-SF presents with robust empirical and clinical evidence and is an effective tool to assess IGD. Moreover, the scale was adapted in several languages as Spanish, Chinese, Czech, German, and many more.
On 3 June 2019, a screening tool for Gaming Disorder, specifically as defined by the World Health Organization, called the "Gaming Disorder Test" was published in a journal article.

Risk factors
The Internet can foster various addictions including addiction to gameplaying.Addictive playing of MMORPGs is associated with negative effects, whereas normal play is not.Younger people and men are more likely to experience a gaming disorder than older people and women respectively. Research shows that the average age of a gamer is 30 years old, and 32% of players are under 18.Adolescents are at a higher risk of sustaining video game disorder over time than adults. An international meta-analysis over 34 jurisdictions quantified the effect size of gender as small, with most effect in Asia, lesser in Europe and Africa, and null in North America, and further finding that economic factors, internet availability, social norms and addiction-related health factors mediate the effect of gender, with nations with a greater GDP per capita having less differences in video game addiction between genders.Comorbid psychiatric disorders act as both risk factors and consequences. Indeed, there is a strong association between video game addiction and anxiety, depression, ADHD, social phobia, and poor psycho-social support. ADHD and its symptoms, such as impulsivity and conduct problems, also increase risks of developing video game disorder. Although internet gaming disorder has a strong relationship with obsessive-compulsive disorder, it is not specific and internet gaming disorder is both phenomenologically and neurobiologically distinct, which indicates that internet gaming disorder is more characterized by impulsivity than compulsivity. Familial factors appear to play an important role, although not well understood.Some personality traits, such as high neuroticism, high impulsivity, and high aggressiveness are consistently significant predictors of internet gaming disorder, and combination of personality traits seem to play a pivotal role in the acquisition, maintenance and development of the disorder.

Mechanisms
Although there is much research since the 1980s on problematic online gaming use, the mechanisms are not well understood, due to inconsistent definitions used in studies.

Video game structure
Some theories focus on the presumed built-in reward systems of video games, such as compulsion loops, to explain their potentially addictive nature. The anticipation of such rewards can create a neurological reaction that releases dopamine the body, so that once the reward is obtained, the person will remember it as a pleasurable feeling. This has been found to be similar to the neurological reaction of other behavioral addictions such as substance abuse and gambling disorder.Mark Griffiths has proposed another reason online video games are potentially addictive is because they "can be played all day every day." The fact there is no end to the game can feel rewarding for some, and hence players are further engaged in the game.

Addiction circuits in the brain
Long-term internet video/mobile game playing affects brain regions responsible for reward, impulse control and sensory-motor coordination. Structural analyses shown modifications in the volume of the ventral striatum, possibly as result of changes in rewards, and video game addicts had faulty inhibitory control and reward mechanisms. Video game playing is associated with dopamine release similar in magnitude to that of drug abuse and gambling, and the presentation of gaming pictures activates brain regions similarly to drug pictures for drug addicts. Treatment studies which used fMRI to monitor the brain connectivity changes found a decrease in the activity of the regions associated with cravings. Although there are evidences that video game addiction may be supported by similar neural mechanisms underlying drug abuse, as video game and internet addictions reduce the sensitivity of the dopaminergic reward system, it is still premature to conclude that this addiction is equivalent to substance addictions, as the research is in its early stages. There is evidence of a dual processing model of digital technology addictions characterized by an imbalance between the reactive and the reflective reward systems. Other studies shown increased difficulties in decision making in specific contexts, such as risky situations but not in ambiguous situations, and an increased preference for short-term rewards. Although the number of neuroimaging studies on internet gaming disorder is rising, there are several methodological shortcomings, particularly in the inconsistency of psychometric assessments. Furthermore, the conclusions on reduced inhibition should be moderated, as only one study included a functional control, which then showed no difference in inhibition.A meta-analytic review of the research concluded the evidence suggests video game addiction arises out of other mental health problems, rather than causing them. Thus it is unclear whether video game addiction should be considered a unique diagnosis.

Management
As concern over video game addiction grows, the use of psychopharmacology, psychotherapy, twelve-step programs, and use of continuing developing treatment enhancements have been proposed to treat this disorder. Empirical studies indeed indicate that internet gaming disorder is associated with detrimental health-related outcomes. However, the clinical trials of potential treatments remain of low quality, except for cognitive-behavioral therapies, which shows efficacy to reduce gaming disorder and depressive symptoms but not total time spent. Although there is a scientific consensus that cognitive-behavioral therapy is preferable to pharmacological treatment, it remains difficult to make definitive statements about its benefits and efficiency due to methodological inconsistencies and lack of follow-up. Since efficacious treatments have not been well established, prevention of video gaming disorder is crucial. Some evidence suggest that up to 50% of people affected by the internet gaming disorder may recover naturally.Some countries, such as South Korea, China, the Netherlands, Canada, and the United States, have responded to the perceived threat of video game addiction by opening treatment centres.

China
China was the first country to treat "internet addiction" clinically in 2008. The Chinese government operates several clinics to treat those who overuse online games, chatting and web surfing. Treatment for the patients, most of whom have been forced to attend by parents or government officials, includes various forms of pain including shock therapy. In August 2009, Deng Sanshan was reportedly beaten to death in a correctional facility for video game and Web addiction.  Most of the addiction "boot camps" in China are actually extralegal militaristically managed centers, but have remained popular despite growing controversy over their practices.In 2019, China set up a curfew, banning minors from playing between certain hours. In 2021, China government published a new policy to force corporations to only serves underage teenagers on Friday, Saturday, and Sunday between 8 pm to 9 pm.

Netherlands
In June 2006, the Smith and Jones clinic in Amsterdam—which has now gone bankrupt—became the first treatment facility in Europe to offer a residential treatment program for compulsive gamers. Keith Bakker, founder and former head of the clinic, has stated that 90% of the young people who seek treatment for compulsive computer gaming are not addicted.

Canada
At a Computer Addiction Services center in Richmond, British Columbia, excessive gaming accounts for 80% of one youth counselors caseload.

United Kingdom
In 2018, the National Health Service announced its plans to open a treatment center, run by the Central and North West London NHS foundation trust, that will initially focus on gaming disorder, but is planned to expand to cover other internet-based addictions.  The specialist treatment center opened in 2019 for treating adolescents and young people aged 13–25 who are addicted to video games.

Outcomes
Physical health
The most frequent physical health-related outcome are alterations in physical functioning such as somatisation and sleep disturbances. Preliminary evidence suggest that internet gaming disorder and the induced sedentarity may contribute to a lack of physical exercise, even though the relationship is not causal.

Epidemiology
The prevalence of internet gaming disorder range from 0.7% to 25.5% worldwide, or 1.0% to 26.8% worldwide, and 3.5% to 17% in China, and is higher among males than females and among younger than older people, with geographical region being an insignificant contributor. The prevalence was found to be 5.06% among a high-school student population from Sri Lanka, suggesting an increasing trend in low- and middle-income countries as well. A longer time spent on video games predicts a tendency towards pathological gaming in the future. The studies, however, used various methodologies and definitions, which renders consensus difficult to achieve and may explain the wide range of prevalence.

Research
Debates on the classification
A meta-analytic review of pathological gaming studies concluded that about 3% of gamers may experience some symptoms of pathological gaming. The report noted problems in the field with defining and measuring pathological gaming and concluded that pathological gaming behaviors were more likely the product of underlying mental health problems rather than the inverse.Barnett and Coulson expressed concern that much of the debate on the issue of addiction may be a knee jerk response stimulated by poor understanding of games and game players. Such issues may lead both society and scholars to exaggerate the prevalence and nature of problematic gaming, and over-focus on games specifically, while ignoring underlying mental health issues. However, Problem gamblers have a higher chance for getting mental illness as well.Other scholars have cautioned that comparing the symptoms of problematic gaming with problematic gambling is flawed, and that such comparisons may introduce research artifacts and artificially inflate prevalence estimates. For instance, Richard Wood has observed that behaviors which are problematic in regards to gambling may not be as problematic when put into the context of other behaviors that are rewarding such as gaming. Similarly, Barnett and Coulson have cautioned that discussions of problematic gaming have moved forward prematurely without proper understanding of the symptoms, proper assessment and consequences.Rather than video gaming disorder being a subtype of gambling disorder, a majority of researchers support the idea of video game addiction being a part of a more comprehensive framework of impulse control disorders with "pathological technology use" with similar characteristics, including the pathological use of video games, internet, computers and other interactive medias. Although internet and video game addictions are generally considered different from gambling disorder and substance abuse, there is a growing body of evidence indicating they share common features, including behavioral and neural features. Indeed, it is suggested that while behavioral addiction may differ with drug addictions in magnitude, they share several characteristics, with Hellman et al. proposing that the concept of addiction should be de-medicalized.On the contrary, a literature review found that as the video game addiction develops, online gaming addicts spend increasing amounts of time not only playing but also preparing for and organizing their playing sessions, suggesting this addiction may be behavioral rather than a disorder of impulse control. There is recent evidence suggesting that internet gaming disorder can cause two distinct types of dysfunctions: cognitive and metacognitive.Griffiths has suggested that psycho-social dependence may revolve around the intermittent reinforcements in the game and the need to belong. Hagedorn & Young have suggested that social dependence may arise due to video games occurring online where players interact with others and the relationships "often become more important for gamers than real-life relationships".

Controversy and alternative viewpoints
Common challenges involve the reliability of the methodology and validity of the results in some studies. Many rely on self-surveys from university students and also lack time frames making it difficult to study the impact, if any, of addiction on a long term scale. Other concerns also address the definition of addiction and how to measure it, questioning whether or not time is a proper unit to determine how addicted someone is to gaming. Daria Joanna Kuss and Mark D. Griffiths have argued the current scientific knowledge on internet gaming addiction is copious in scope and complexity. They state that instead, a simple framework should be provided to allow all current and future studies to be categorised, as internet gaming addiction lies on a continuum beginning with etiology and risk factors all the way through the development of "full-blown" addiction and ending with ramifications and potential treatment. In addition, they caution the deployment of the label "addiction" since it heavily denotes the use of substances or engagement in certain behaviors. Finally, the researcher promotes other researchers to assess the validity and reliability of existing measures instead of developing additional measurement instruments.Other challenges include the lack of context of the participants life and the negative portrayal of gaming addicts. Some state that gamers sometimes use video games to either escape from an uncomfortable environment or alleviate their already existing mental issues—both possibly important aspects in determining the psychological impact of gaming. Negative portrayal also deals with the lack of consistency in measuring addictive gaming. This leads to discussions that sometimes exaggerate the issue and create a misconception in some that they, themselves, may be addicted when they are not.The evidence of video game addiction to create withdrawal symptoms is very limited and thus debated, due to different definitions and low quality trials.The concept of video game disorder is itself being debated, with the overlap of its symptoms with other mental disorders, the unclear consensus on a definition and thresholds, and the lack of evidence raising doubts on whether or not this qualifies as a mental disorder of its own. Despite the lack of a unified definition, there is an emerging consensus among studies that Internet gaming disorder is mainly defined by three features: 1) withdrawal, 2) loss of control, and 3) conflict. Although the DSM-5 definition of video game disorder has a good fit to current methodological definitions used in trials and studies, there are still debates on the clinical pertinence.Michael Brody, M.D., head of the TV and Media Committee of the American Academy of Child and Adolescent Psychiatry, stated in a 2007 press release that "... there is not enough research on whether or not video games are addictive."  However, Brody also cautioned that for some children and adolescents, "... it displaces physical activity and time spent on studies, with friends, and even with family."A major issue concerns the lack of consistent measures and definitions and of acquisition of follow-up data. Furthermore, the study design quality has not greatly improved between the 2000s and 2017. For instance, most studies measured internet gaming behaviors in terms of frequency of use (total time spent), without considering the type of game (e.g., MMORPG), the social context (e.g., physically or virtually with friends), nor the motivations (e.g., competitive, achievement-oriented "grinding"). Although the amount of time spent was postulated by Johanssonn and Götestam in 2004 to lead to pathological behaviors, it is unclear whether the time spent is a cause or a consequence of pathological use. These criticisms, however, mostly pertain to Western research since there is more data of higher quality available in Asian regions, where the Internet gaming disorder is more prevalent.A survey conducted in 2019 of 214 scholars shown that 60.8% agreed that pathological video game use could be a mental health problems, whereas 30.4% were skeptical. However, only 49.7% agreed with the DSM-5 definition of Internet gaming disorder, and 56.5% to the definition of the World Health Organization. Most scholars were worried that WHOs and DSM-5s inclusion of Internet gaming disorder was "overpathologizing normal youth" and "precipitated moral panic over video games". This indicates a lack of consensus on the issue as of 2019.

History
Video game addiction has been studied since the 1980s, and has seen a significant increase in the number of empirical studies since then.The press has reported concerns over online gaming since at least 1994, when Wired mentioned a college student who was playing a MUD game for 12 hours a day instead of attending class.Press reports have noted that some Finnish Defence Forces conscripts were not mature enough to meet the demands of military life and were required to interrupt or postpone military service for a year. One reported source of the lack of needed social skills is overuse of computer games or the internet. Forbes termed this overuse "Web fixations" and stated they were responsible for 13 such interruptions or deferrals over the five years from 2000 to 2005.In an April 2008 article, The Daily Telegraph reported that surveys of 391 players of Asherons Call showed that three percent of respondents experienced agitation when they were unable to play, or missed sleep or meals to play. The article reports that University of Bolton lead researcher John Charlton said, "Our research supports the idea that people who are heavily involved in game playing may be nearer to autistic spectrum disorders than people who have no interest in gaming."On 6 March 2009, the Canadian Broadcasting Corporations (CBC) national news magazine program the fifth estate aired an hour-long report on video game addiction and the Brandon Crisp story, titled "Top Gun", subtitled "When a video gaming obsession turns to addiction and tragedy."In August 2010, Wired reported that a man in Hawaii, Craig Smallwood, sued the gaming company NCSoft for negligence and for not specifying that their game, Lineage II, was so addictive. He alleged he would not have begun playing if he was aware he would become addicted. Smallwood says he has played Lineage for 20,000 hours between 2004 and 2009.In 2013, a man from China observed his sons addiction to video games, and decided to take action. He hired online assassins to kill his sons virtual avatar every time he logged in. He hoped that being relentlessly killed would help his son lose interest in this destructive habit.

Inclusion in the ICD-11
In the draft versions leading to the final ICD-11 document, gaming disorder was included alongside gambling disorder under "Disorders Due to Addictive Behaviors". The addition defines as "a pattern of persistent or recurrent gaming behaviour (digital gaming or video-gaming)", defined by three criteria: the lack of control over playing video games, priority given to video games over other interests, and the inability to stop playing video games even after being affected by negative consequences. For gaming disorder to be diagnosed, the behavior pattern must be of sufficient severity to result in significant impairment in personal, family, social, educational, occupational or other important areas of functioning and would normally have been evident for at least 12 months. Research shows gaming disorders can be associated with anxiety, depression, loneliness, obesity, sleeping disorders, attention problems, and stress.Vladimir Poznyak, the coordinator for the WHO Department of Mental Health and Substance Abuse, defended the addition of gaming disorder, believing the backlash against the addition to be a moral panic as they chose a very narrow definition that encompasses only the most extreme cases of gaming disorder. He said evaluating a disorder for inclusion is nominally done without any external feedback "to avoid interference from commercial and other entities which may have vested interest in the outcome of the process". Dr. Poznyak asserted that several medical professionals consulting on the ICD-11 did believe gaming disorder to be real, and by including it in the ICD-11, there can now be earnest efforts to define its causes and symptoms betters and methods to deal with it, and now include the video game industry within the conversation to help reduce the effects of video games on public health.The addition of "gaming disorder" to the ICD-11 was criticized by gamers and the video game industry, while some researchers remained skeptical. Some of these researchers said the evidence remains weak and "there is a genuine risk of abuse of diagnoses." A group of 26 scholars wrote an open letter to the WHO, suggesting that the proposed diagnostic categories lacked scientific merit and were likely to do more harm than good. In counter-argument, a group of fifty academic researchers in behavioral science agreed that the evidence to support gaming disorder was weak, but it would be best that WHO identify gaming disorder in ICD-11 so that it could be considered a clinical and public health need.A report, prepared by mental health experts at Oxford University, Johns Hopkins University, Stockholm University and the University of Sydney, sponsored by The Association for UK Interactive Entertainment argues that while there may be potential addiction associated with video gaming, it is premature to consider it a disorder without further study, given the stigmatisation that surrounds video, and ask the WHO to use caution when finalising the ICD draft. This report was promoted by 22 video game industry trade organizations including the Entertainment Software Association of the United States and Interactive Software Federation of EuropeAs the final approval of the ICD-11 neared, several video game trade associations issued a statement requesting WHO to reconsider the addition of "gaming disorder", stating that, "The evidence for its inclusion remains highly contested and inconclusive". The Entertainment Software Association had meetings with the WHO during December 2018 to try to convince them to hold off including gaming disorder within ICD-11, with more planned meetings to follow.

Society and culture
Parental concerns
According to ABC News, parents have many concerns about their children playing video games, including concerns about age appropriateness, the amount of time spent playing games, physical health, and aggressive behaviour.

Governmental concerns
The first video game to attract political controversy was the 1978 arcade game Space Invaders. In 1981, a political bill called the Control of Space Invaders (and other Electronic Games) Bill was drafted by British Labour Party MP George Foulkes in an attempt to ban the game for its "addictive properties" and for causing "deviancy". The bill was debated and only narrowly defeated in parliament by 114 votes to 94 votes.In August 2005, the government of the Peoples Republic of China, where more than 20 million people play online games, introduced an online gaming restriction limiting playing time to three hours, after which the player would be expelled from whichever game they were playing. In 2006, it relaxed the rule so only citizens under the age of 18 would face the limitation. Reports indicate underage gamers found ways to circumvent the measure. In July 2007, the rule was relaxed yet again. Internet games operating in China must require users identify themselves by resident identity numbers. After three hours, players under 18 are prompted to stop and "do suitable physical exercise". If they continue, their in-game points are "slashed in half". After five hours, all their points are automatically erased.In 2008 in the United States (US), one of the five Federal Communications Commission (FCC) Commissioners, Deborah Taylor Tate, stated that online gaming addiction was "one of the top reasons for college drop-outs".  However, she did not mention a source for the statement nor identify its position in relation to other top reasons.In 2011, the South Korean government implemented a law, known as the Shutdown law or the Cinderella Law, which prohibits children under the age of 16 from playing online video games between the hours of 12:00 a.m. to 6:00 a.m. Later on, the law was amended and now children under the age of 16 can play after midnight if they have permission from their parents. In 2021, the South Korean government moved to abolish this law.A systematic review identified in 2017 three types of currently attempted governmental policies: 1) limiting the availability of video games (shutdown, fatigue system, parental controls),  2) reduce the risks and harm (warning messages), 3) provide addiction help services to gamers. Most of these policies were either not as efficient as intended or not yet evaluated for efficiency, which lead some researchers to prompt for a global public health approach to prevent the onset and progression of this disorder. Some researchers suggest that the video game industry should itself place preventive measures against video game addiction.

Deaths
There have been at least a few deaths caused directly by exhaustion from playing games for excessive periods of time.

China
In 2005, thirteen-year-old Zhang Xiaoyi committed suicide by jumping from the top of a 24-story tower block in his home province Tianjin. After previously having spent two straight days playing online role-playing games in an Internet cafe, Zhang had told his parents that he had "been poisoned by games and could no longer control himself". His parents sued Aomeisoft, the China-region publisher of the game World of Warcraft. The head of a software association said to gaming website Play.tm that same year: "In the hypothetical world created by such games, [players] become confident and gain satisfaction, which they cannot get in the real world."In 2007, a 26-year-old man identified only as "Zhang" died of a heart attack due to lack of physical activity following a seven-day gaming binge, while a 30-year-old man died in a Guangzhou Internet cafe after playing online games for three straight days.

South Korea
In 2005, 28-year old industrial repairman Seungseob Lee (Hangul: 이승섭) visited an Internet cafe in the city of Daegu and played StarCraft almost continuously for fifty hours </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Parinauds syndrome and explain in detail? [/INST] Parinauds syndrome is an inability to move the eyes up and down. It is caused by compression of the vertical gaze center at the rostral interstitial nucleus of medial longitudinal fasciculus (riMLF). The eyes lose the ability to move upward and down.
It is a group of abnormalities of eye movement and pupil dysfunction. It is caused by lesions of the upper brain stem and is named for Henri Parinaud (1844–1905), considered to be the father of French ophthalmology.

Signs and symptoms
Parinauds syndrome is a cluster of abnormalities of eye movement and pupil dysfunction, characterized by:

Paralysis of upwards gaze: Downward gaze is usually preserved. This vertical palsy is supranuclear, so dolls head maneuver should elevate the eyes, but eventually all upward gaze mechanisms fail.
Pseudo-Argyll Robertson pupils: Accommodative paresis ensues, and pupils become mid-dilated and show light-near dissociation.
Convergence-retraction nystagmus: Attempts at upward gaze often produce this phenomenon. On fast up-gaze, the eyes pull in and the globes retract. The easiest way to bring out this reaction is to ask the patient to follow down-going stripes on an optokinetic drum.
Eyelid retraction (Colliers sign)
Conjugate down gaze in the primary position: "setting-sun sign". Neurosurgeons see this sign most commonly in patients with failed hydrocephalus shunts.It is also commonly associated with bilateral papilledema. It has less commonly been associated with spasm of accommodation on attempted upward gaze, pseudoabducens palsy (also known as thalamic esotropia) or slower movements of the abducting eye than the adducting eye during horizontal saccades, see-saw nystagmus and associated ocular motility deficits including skew deviation, oculomotor nerve palsy, trochlear nerve palsy and internuclear ophthalmoplegia.

Causes
Parinauds syndrome results from injury, either direct or compressive, to the dorsal midbrain.  Specifically, compression or ischemic damage of the mesencephalic tectum, including the superior colliculus adjacent oculomotor (origin of cranial nerve III) and Edinger-Westphal nuclei, causing dysfunction to the motor function of the eye.
Classically, it has been associated with three major groups:

Young patients with brain tumors in the pineal gland or midbrain: pinealoma (intracranial germinomas) are the most common lesion producing this syndrome.
Women in their 20s-30s with multiple sclerosis
Older patients following stroke of the upper brainstemHowever, any other compression, ischemia or damage to this region can produce these phenomena: obstructive hydrocephalus, midbrain hemorrhage, cerebral arteriovenous malformation, trauma and brainstem toxoplasmosis infection. Neoplasms and giant aneurysms of the posterior fossa have also been associated with the midbrain syndrome.
Vertical supranuclear ophthalmoplegia has also been associated with metabolic disorders, such as Niemann-Pick disease, Wilsons disease, kernicterus, and barbiturate overdose.

Diagnosis
Diagnosis can be made via combination of physical exam, particularly deficits of the relevant cranial nerves. Confirmation can be made via imaging, such as CT scan or MRI.

Treatment
Treatment is primarily directed towards etiology of the dorsal midbrain syndrome. A thorough workup, including neuroimaging is essential to rule out anatomic lesions or other causes of this syndrome. Visually significant upgaze palsy can be relieved with bilateral inferior rectus recessions. Retraction nystagmus and convergence movement are usually improved with this procedure as well.

Prognosis
The eye findings of Parinauds syndrome generally improve slowly over months, especially with resolution of the causative factor; continued resolution after the first 3–6 months of onset is uncommon. However, rapid resolution after normalization of intracranial pressure following placement of a ventriculoperitoneal shunt has been reported.

References
Further reading
Aguilar-Rebolledo F, Zárate-Moysén A, Quintana-Roldán G (1998). "Parinauds syndrome in children". Rev. Invest </s>


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


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


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Twin-to-twin transfusion syndrome and explain in detail? [/INST] Twin-to-twin transfusion syndrome (TTTS), also known as feto-fetal transfusion syndrome (FFTS), twin oligohydramnios-polyhydramnios sequence (TOPS) and stuck twin syndrome, is a complication of monochorionic multiple pregnancies (the most common form of identical twin pregnancy) in which there is disproportionate blood supply between the fetuses. This leads to unequal levels of amniotic fluid between each fetus and usually leads to death of the undersupplied twin and, without treatment, usually death or a range of birth defects or disabilities for a surviving twin, such as underdeveloped, damaged or missing limbs, digits or organs (including the brain), especially cerebral palsy.The condition occurs when the vein–artery connections within the fetuses shared placenta allow the blood flow between each fetus to become progressively imbalanced. It usually develops between week 16 and 25 of pregnancy, during peak placental growth. The cause of the developmental effects on a surviving fetus may include necrotic embolisms from a dead fetus, low blood volume due to pooling in the dead fetus or velamentous cord insertion (insertion of the umbilical cord into the chorioamniotic membranes).The primary treatment of TTTS is fetoscopy and laser ablation of the interconnecting blood vessels to cut off the exchange of blood between the fetuses. This treatment is associated with an 85% survival rate of at least one fetus. Other treatments include periodic removal of amniotic fluid (serial amniocentesis), which is associated with a 66% survival rate of at least one fetus. Without treatment, there is an almost 100% mortality rate of one or all fetuses. Even with treatment, the condition is associated with premature birth and a risk of cerebral palsy in a surviving fetus.
Around 5–15% of identical twin fetuses will go on to develop TTTS. The condition was first described by German obstetrician Friedrich Schatz in 1875.

Cause
As a result of sharing a single placenta, the blood supplies of monochorionic twin fetuses can become connected, so that they share blood circulation: although each fetus uses its own portion of the placenta, the connecting blood vessels within the placenta allow blood to pass from one twin to the other. It is thought that most monochorionic placentae have these "shared connections" that cross the placenta, with the net flow volumes being equal between them. This state is sometimes referred to as "flow balance". When the placenta has deep vein–artery connection, this can cause blood flow to become unbalanced.Depending on the number, type and direction of the interconnecting blood vessels (anastomoses), blood can be transferred disproportionately from one twin (the "donor") to the other (the "recipient"), due to a state of "flow imbalance" imparted by new blood vessel growth across the placental "equator", the line that divides each babys proportion of the shared placenta. This state of transfusion causes the donor twin to have decreased blood volume, retarding the donors development and growth, and also decreased urinary output, leading to a lower than normal level of amniotic fluid (becoming oligohydramnios). The blood volume of the recipient twin is increased, which can strain the fetuss heart and eventually lead to heart failure, and also higher than normal urinary output, which can lead to excess amniotic fluid (becoming polyhydramnios). The demise of the fetus is typically a result of ischemia related to the lack of blood flow. The lack of blood flow causes bowel atresia, brain damage, and kidney failure.TTTS usually develops during the period of peak placental growth, starting in week 16 and proceeding through week 25; after this point, the placentas growth decelerates, essentially stopping just after week 30. While TTTS has occasionally been detected beyond this timepoint, it is thought that its occurrence beyond week 30 may be due to a placental embolism that upsets the flow balance of the shared connections between the babies. TTTS is potentially lethal to either or both twins, no matter when it is detected. However, when detected past week 25, emergency delivery may be considered to rescue the babies if the TTTS is severe.Other than requiring a monochorionic twin (or higher multiple) pregnancy, the underlying causes of TTTS are not known. It is not known to be hereditary or genetic.

Effects to the surviving fetus
The fetal demise of one of the twins during the second trimester of a monochorionic pregnancy can result in serious complications to the surviving fetus. Complications include gangrenous limbs, hands and feet, cerebral palsy and IQ deficits, constriction rings of limbs and digits, reduced digits, skin defects, brain cysts, hydranencephaly, multicystic encephalomalacia, microencephaly, renal agenesis and bowel atresia. There are three hypotheses explaining these complications.
Embolic Theory: The demise of the donor twin allows necrotic tissue, presumably thrombosis-plastin like material, to pass through the vasculature of the surviving twin via the placental vessels. The necrotic tissue embolizes the surviving twins mesenteric artery, resulting in bowel atresia, the renal artery, resulting in renal agenesis, or the peripheral arteries, resulting in limb ischemia and skin abnormalities.
Ischemic Theory: The demise of the donor twin creates a low-pressure state resulting in the shunting of blood into the low-resistance vascular system of the dead fetus. This state of low pressure acutely causes hypovolemia, resulting in ischemia and poor end-organ perfusion.
Placentation Theory: The incidence of velamentous cord insertion, an abnormal insertion of the umbilical cord into the placenta, is higher in TTTS. The exact mechanism of effect this has on fetal damage is unknown.

Diagnosis
Quintero stages
A staging system is commonly used to classify the severity of TTTS.Stage I: A small amount of amniotic fluid (oligohydramnios) is found around the donor twin and a large amount of amniotic fluid (polyhydramnios) is found around the recipient twin.
Stage II: In addition to the description above, the ultrasound is not able to identify the bladder in the donor twin.
Stage III: In addition to the characteristics of Stages I and II, there is abnormal blood flow in the umbilical cords of the twins.
Stage IV: In addition to all of the above findings, the recipient twin has swelling under the skin and appears to be experiencing heart failure (fetal hydrops).
Stage V: In addition to all of the above findings, one of the twins has died. This can happen to either twin. The risk to either the donor or the recipient is roughly equal & is quite high in Stage II or higher TTTS.
The Quintero staging does not provide information about prognosis, and other staging systems have been proposed.

Treatment
Various treatments exist for TTTS.

Non treatment
This is equivalent of zero intervention. It has been associated with almost 100% mortality rate of one or all fetuses. Exceptions to this include patients that are still in Stage 1 TTTS and are past 22 weeks gestation.

Adjustment of amniotic fluid
Serial amniocentesis
This procedure involves removal of amniotic fluid periodically throughout the pregnancy under the assumption that the extra fluid in the recipient twin can cause preterm labor, perinatal mortality, or tissue damage. In the case that the fluid does not reaccumulate, the reduction of amniotic fluid stabilizes the pregnancy. Otherwise, the treatment is repeated as necessary. There is no standard procedure for how much fluid is removed each time. There is a danger that if too much fluid is removed, the recipient twin could die. This procedure is associated with a 66% survival rate of at least one fetus, with a 15% risk of cerebral palsy, and average delivery occurring at 29 weeks gestation.

Septostomy, or iatrogenic disruption of the dividing membrane
This procedure involves the tearing of the dividing membrane between fetuses such that the amniotic fluid of both twins mixes, under the assumption that pressure is different in either amniotic sac and that its equilibration will ameliorate progression of the disease. It has not been proven that pressures are different in either amniotic sac. Use of this procedure can preclude use of other procedures as well as make difficult the monitoring of disease progression. In addition, tearing the dividing membrane has contributed to cord entanglement and demise of fetuses through physical complications.

Adjustment of blood supply
Laser therapy
This procedure involves endoscopic surgery using laser to interrupt the vessels that allow exchange of blood between fetuses under the assumption that the unequal sharing of blood through these vascular communications leads to unequal levels of amniotic fluid. Each fetus remains connected to its primary source of blood and nutrition, the placenta, through the umbilical cord. This procedure is conducted once, with the exception of all vessels not having been found. The use of endoscopic instruments allows for short recovery time. This procedure has been associated with 85% survival rate of at least one fetus, with a 6–7% risk of cerebral palsy and average delivery occurring at 32–33 weeks gestation.Twin anemia–polycythemia sequence (TAPS) may occur after laser surgery for TTTS (post-laser form). The spontaneous form of TAPS complicates approximately 3 to 5% of monochorionic twin pregnancies, whereas the post-laser form occurs in 2 to 13% of TTTS cases. The pathogenesis of TAPS is based on the presence of few, minuscule arterio-venous (AV) placental anastomoses (diameter <1mm) allowing a slow transfusion of blood from the donor to the recipient and leading gradually to highly discordant Hb levels.A 2014 review found that laser coagulation resulted in fewer fetal and perinatal deaths than amnioreduction and septostomy, and recommended its use for all states of TTTS.

Umbilical cord occlusion
This procedure involves the ligation or otherwise occlusion of the umbilical cord to interrupt the exchange of blood between the fetuses. The procedure is typically offered in cases where one of the fetuses is presumed moribund and endangering the life or health of the other twin through resultant hypotension. Use of this treatment has decreased as TTTS is identified and treated in earlier stages and with better outcomes. When used, it is associated with an 85% survival rate of the remaining fetuses with 5% risk of cerebral palsy and a 33–39 weeks of gestation at delivery.

Diet supplementation
Some doctors recommend complete bed rest for the mother coupled with massive intakes of protein as a therapy to try to counteract the syndrome. Research completed shows these nutritional supplements do work.Diet supplementation was associated with lower overall incidence of TTTS (20/52 versus 8/51, P = 0.02) and lower prevalence of TTTS at delivery (18/52 versus 6/51, P = 0.012) when compared with no supplementation. In the study, nutritional supplementation contained 250kcal, consisting of 6g of lipids, 40g of carbohydrates, 9g of protein, vitamins and minerals, consumed three times per day. Nutritional intervention also significantly prolonged the time between the diagnosis of TTTS and delivery (9.4 ± 3.7 weeks versus 4.6 ± 6.5 weeks; P = 0.014). The earlier nutritional regimen was introduced, the lesser chance of detecting TTTS ( P = 0.001). Although not statistically significant, dietary intervention was also associated with lower Quintero stage, fewer invasive treatments, and lower twin birth weight discordance.Diet supplementation appears to counter maternal metabolic abnormalities in monochorionic twin pregnancies and improve perinatal outcomes in TTTS when combined with the standard therapeutic options. Nutritional therapy appears to be most effective in mitigating cases that are caught in Quintero Stage I, little effect has been observed in those that are beyond Stage I.

Epidemiology
Based on recent (2005) US NCHS data, the rate of multiple births is now approximately 3.4% (4,138,349 total births, of which 139,816 were twins or higher-order multiple births). The majority of identical twins share a common (monochorionic) placenta, and of these approximately 15% go on to develop TTTS </s>