<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 Autoimmune hypophysitis and explain in detail? [/INST] Autoimmune hypophysitis is defined as inflammation of the pituitary gland due to autoimmunity.

Signs and symptoms
Autoimmune hypophysitis can lead to deficiencies in one or more pituitary hormones, causing central diabetes insipidus if the posterior pituitary gland is affected as well as central adrenal insufficiency and central hypothyroidism if the anterior pituitary gland is affected. The symptoms depend on what part of the pituitary is affected. Lymphocytic adenohypophysitis (LAH) occurs when the anterior pituitary cells are affected by autoimmune inflammation resulting in either no symptoms, adrenal insufficiency (if the ACTH producing cells are affected), hypothyroidism (if the TSH producing cells are damaged), or hypogonadism (if the LH and/or FSH producing cells are involved). In some cases, the presence of inflammation within the pituitary gland leads to interruption of dopamine flow from the hypothalamus into the pituitary causing high levels of the hormone prolactin and, often as a consequence, milk production from the breasts (in older girls and women).  Lymphocytic Infundibuloneurohypophysitis (LINH) occurs when the posterior pituitary is affected resulting in diabetes insipidus. Both LAH and LINH may also lead to symptoms of an intracranial mass such as headache or disturbance of vision, i.e. bitemporal hemianopia. The pituitary produces multiple hormones relating to various metabolic functions. Sufficiently low production of certain pituitary hormones can be fatal resulting in the failure of the thyroid or adrenal glands.
Common symptoms include nausea, vomiting, fatigue, loss of libido, amenorrhea, and dizziness. It is estimated that, typically, it takes from 12 to 40 years for autoimmune destruction to present symptoms. However, there have been cases of isolated attacks as a result of drug reactions (i.e., use of blocking antibody ipilimumab) or idiopathic events that have presented symptoms which may disappear after relatively short term treatment (i.e., 1 year on corticoids or other immune suppressants). However, more rapid development of the disorder is the rule when it occurs during, or shortly after, pregnancy (even after miscarriage or abortion). Indeed, autoimmune hypophysitis occurs more commonly during and shortly after pregnancy than at any other time.

Antibodies
80% of patients with pituitary antibodies also have antibodies to thyroid gland or its hormones. Likewise, 20% of autoimmune thyroid patients also have pituitary antibodies.  It follows that a subset of thyroid patients may have a disease related to autoimmune hypophysitis.  Recent research has focused on a defect at the CTLA-4 gene which, coupled with other factors, may result in autoimmunity primarily focusing on certain endocrine glands including the pituitary and thyroid.

Cause
Diagnosis
Lymphocytic hypophysitis continues to be a diagnosis of exclusion, and histopathology with tissue biopsy is needed for a definitive diagnosis.[3] However, clinical, laboratory data, and imaging can all help with the diagnosis.[8] First and foremost, patients present with symptoms of hypopituitarism and must undergo pituitary hormone function evaluation. Biopsy is the only means of accurate diagnosis as no autoantigen has been discovered.  Biopsy of the pituitary gland is not easily performed with safety as it sits under the brain, however, a test does exist to detect antibodies to the pituitary without biopsy: autoantibodies to M(r) 49,000 pituitary cytosolic protein may represent markers for an immunological process affecting the pituitary gland. Tests for normal pituitary gland hormone production tend to be expensive and in some cases difficult to administer. In addition, certain hormone levels vary largely throughout the day and in response to metabolic factors, making abnormal levels difficult to calibrate—further hampering diagnosis. Assessment for other autoimmune and inflammatory diseases should also be performed by obtaining complete blood count, complete metabolic panel, c-reactive protein, erythrocyte sedimentation rate, antinuclear antibody, and lupus antibodies at the very least. Gadolinium-enhanced MRI of the pituitary is the imagining of choice as well, and it is important to distinguish lymphocytic hypophysitis from a pituitary adenoma.

Treatment
Inflammation resolves usually after several months of glucocorticoid treatment For those that show no improvement with corticosteroids or have relapsed after treatment with corticosteroids, immunosuppressive medications such as methotrexate, azathioprine, and cyclosporine can be used as well. There have also been some cases where dopamine agonists such as cabergoline/bromocriptine have also been successfully used in those with hyperprolactinemia due to pituitary inflammation </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 Autoimmune pancreatitis and explain in detail? [/INST] Autoimmune Pancreatitis (AIP) is an increasingly recognized  type of chronic pancreatitis that can be difficult to distinguish from pancreatic carcinoma but which responds to treatment with corticosteroids, particularly prednisone. Although autoimmune pancreatitis is quite rare, it constitutes an important clinical problem for both patients and their clinicians: the disease commonly presents itself as a tumorous mass which is diagnostically indistinguishable from pancreatic cancer, a disease that is much more common in addition to being very dangerous. Hence, some patients undergo pancreatic surgery, which is associated to substantial  mortality and morbidity, out of the fear by patients and clinicians to undertreat a malignancy. However, surgery is not a good treatment for this condition as AIP responds well to immunosuppressive treatment. There are two categories of AIP: Type 1 and Type 2, each with distinct clinical profiles.
Type 1 AIP is now regarded as a manifestation of IgG4-related disease, and those affected have tended to be older and to have a high relapse rate. Type 1 is associated with pancreatitis, Sjogren syndrome, Primary sclerosing cholangitis and Inflammatory bowel disease.  Patients with Type 2 AIP do not experience relapse, tend to be younger and not associated with systemic disease. AIP occurring in association with an autoimmune disorder has been referred to as "secondary" or "syndromic" AIP. AIP does not affect long-term survival.

Signs and symptoms
Autoimmune pancreatitis may cause a variety of symptoms and signs, which include pancreatic and biliary (bile duct) manifestations, as well as systemic effects of the disease. Two-thirds of patients present with either painless jaundice due to bile duct obstruction or a "mass" in the head of the pancreas, mimicking carcinoma. As such, a thorough evaluation to rule out cancer is important in cases of suspected AIP.Type 1 AIP typically presents in a 60–70-year-old male with painless jaundice. In some cases, imaging reveals a mass in the pancreas or diffuse pancreatic enlargement. Narrowing in the pancreatic duct called strictures may occur.  Rarely, Type 1 AIP presents with acute pancreatitis. Type 1 AIP presents with manifestations of autoimmune disease (IgG4 related) in at least half of cases.  The most common form of systemic involvement is cholangitis, which occurs in up to 80 percent of cases of Type 1 AIP. Additional manifestations include inflammation in the salivary glands (chronic sclerosing sialadenitis), in the lungs resulting in scarring (pulmonary fibrosis) and nodules, scarring within the chest cavity (mediastinal fibrosis) or in the anatomic space behind the abdomen (retroperitoneal fibrosis) and inflammation in the kidneys (tubulointerstitial nephritis).AIP is characterized by the following features:

Scleral Icterus (yellow eyes), jaundice (yellow skin) which is usually painless, usually without acute attacks of pancreatitis.
Relatively mild symptoms, such as minimal weight loss or nausea.
Increased serum levels of gamma globulins, immunoglobulin G (IgG) or IgG4.
The presence of serum autoantibodies such as anti-nuclear antibody (ANA), anti-lactoferrin antibody, anti-carbonic anhydrase II antibody, and rheumatoid factor (RF).
Contrast-enhanced CT demonstrates a diffusely enlarged (sausage-shaped) pancreas.
Diffuse irregular narrowing of the main pancreatic duct, and stenosis of the intrapancreatic bile duct on endoscopic retrograde cholangiopancreatography (ERCP).
Rare pancreatic calcification or cyst formation.
Marked responsiveness to treatment with corticosteroids.

Histopathology
Histopathologic examination of the pancreas reveals a characteristic lymphoplasmacytic infiltrate of CD4- or CD8-positive lymphocytes and IgG4-positive plasma cells, and exhibits interstitial fibrosis and acinar cell atrophy in later stages. At the initial stages, typically, there is a cuff of lymphoplasma cells surrounding the ducts but also more diffuse infiltration in the lobular parenchyma.  However, localization and the degree of duct wall infiltration are variable.  Whereas histopathologic examination remains the primary method for differentiation of AIP from acute and chronic pancreatitis, lymphoma, and cancer.  By Fine Needle Aspiration (FNA) the diagnosis can be made if adequate tissue is obtained. In such cases, lymphoplasmacytic infiltration of the lobules are the key finding. Rarely, granulomatous reaction could be observed. It has been proposed that a cytologic smear primarily composed of acini rich in  chronic inflammatory cells (lymphocytes, plasma cells), with rare ductal epithelial cells lacking atypia, favors the diagnosis of AIP.  The sensitivity and the specificity of these criteria for differentiating AIP from neoplasia are unknown. In cases of systemic manifestation of AIP, the pathologic features are similar in other organs.Although the exact mechanism explaining the clinical manifestations of autoimmune pancreatitis remain for an important part obscure, most professionals would agree that the development of IgG4 antibodies, recognizing an epitiope on the membrane of pancreatic ancinar cells is an important factor in the pathophysiology of the disease. These antibodies are postulated to provoke an immune response against these ancinar cells resulting in pancreatic inflammation and destruction. Knowing the auto-antigens involved would allow early diagnosis of the disease, its differentiation from a diagnosis of pancreatic cancer, and potentially even prevention, but unfortunately these remain obscure. An earlier publication suggested that the human ubiquitin-protein ligase E3 component n-recognin 2 (UBR2) was an important antigen  but follow up studies suggested this finding is likely to be an artifact. Hence improved diagnosis, understanding and treatment of autoimmune pancreatitis awaits the identification of the auto-antigens involved.

Diagnosis
Criteria
Most recently the fourteenth Congress of the International Association of Pancreatology developed the International Consensus Diagnostic Criteria (ICDC) for AIP. The ICDC emphasizes five cardinal features of AIP which includes the imaging appearance of pancreatic parenchyma and the pancreatic duct, serum IgG4 level, other organ involvement with IgG4-related disease, pancreatic histology and response to steroid therapy.In 2002, the Japanese Pancreas Society proposed the following diagnostic criteria for autoimmune pancreatitis:
I. Pancreatic imaging studies show diffuse narrowing of the main pancreatic duct with irregular wall (more than 1/3 of length of the entire pancreas).
II. Laboratory data demonstrate abnormally elevated levels of serum gamma globulin and/or IgG, or the presence of autoantibodies.
III. Histopathologic examination of the pancreas shows fibrotic changes with lymphocyte and plasma cell infiltrate.For diagnosis, criterion I (pancreatic imaging) must be present with criterion II (laboratory data) and/or III (histopathologic findings).Mayo Clinic has come up with five diagnostic criteria  called HISORt criteria which stands for histology, imaging, serology, other organ involvement, and response to steroid therapy.

Radiologic features
Computed tomography (CT) findings in AIP include a diffusely enlarged hypodense pancreas or a focal mass that may be mistaken for a pancreatic malignancy.  A low-density, capsule-like rim on CT (possibly corresponding to an inflammatory process involving peripancreatic tissues) is thought to be an additional characteristic feature (thus the mnemonic: sausage-shaped). Magnetic resonance imaging (MRI) reveals a diffusely decreased signal intensity and delayed enhancement on dynamic scanning.  The characteristic ERCP finding is segmental or diffuse irregular narrowing of the main pancreatic duct, usually accompanied by an extrinsic-appearing stricture of the distal bile duct. Changes in the extrapancreatic bile duct similar to those of primary sclerosing cholangitis (PSC) have been reported.The role of endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) in the diagnosis of AIP is not well described, and EUS findings have been described in only a small number of patients.  In one study, EUS revealed a diffusely swollen and hypoechoic pancreas in 8 of the 14 (57%) patients, and a solitary, focal, irregular mass was observed in 6 (46%) patients.  Whereas EUS-FNA is sensitive and specific for the diagnosis of pancreatic malignancy, its role in the diagnosis of AIP remains unclear.

Treatment
AIP often completely resolves with steroid treatment.  The failure to differentiate AIP from malignancy may lead to unnecessary pancreatic resection, and the characteristic lymphoplasmacytic infiltrate of AIP has been found in up to 23% of patients undergoing pancreatic resection for suspected malignancy who are ultimately found to have benign disease.  In this subset of patients, a trial of steroid therapy may have prevented a Whipple procedure or complete pancreatectomy for a benign disease which responds well to medical therapy. "This benign disease resembles pancreatic carcinoma both clinically and radiographically. The diagnosis of autoimmune pancreatitis is challenging to make </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 Cyclopes and explain in detail? [/INST] In Greek mythology and later Roman mythology, the Cyclopes ( sy-KLOH-peez; Greek: Κύκλωπες, Kýklōpes, "Circle-eyes" or "Round-eyes"; singular Cyclops  SY-klops; Κύκλωψ, Kýklōps) are giant one-eyed creatures. Three groups of Cyclopes can be distinguished. In Hesiods Theogony, the Cyclopes are the three brothers Brontes, Steropes, and Arges, who made for Zeus his weapon the thunderbolt. In Homers Odyssey, they are an uncivilized group of shepherds, the brethren of Polyphemus encountered by Odysseus. Cyclopes were also famous as the builders of the Cyclopean walls of Mycenae and Tiryns.
In Cyclops, the fifth-century BC play by Euripides, a chorus of satyrs offers comic relief based on the encounter of Odysseus and Polyphemus. The third-century BC poet Callimachus makes the Hesiodic Cyclopes the assistants of smith-god Hephaestus; as does Virgil in the Latin epic Aeneid, where he seems to equate the Hesiodic and Homeric Cyclopes.
From at least the fifth century BC, Cyclopes have been associated with the island of Sicily and the volcanic Aeolian Islands.

Kinds
Three groups of Cyclopes can be distinguished: the Hesiodic, the Homeric and the wall-builders. In Hesiods Theogony, the Cyclopes are the three brothers: Brontes, Steropes, and Arges, sons of Uranus and Gaia, who made for Zeus his characteristic weapon, the thunderbolt. In Homers Odyssey, the Cyclopes are an uncivilized group of shepherds, one of whom, Polyphemus, the son of Poseidon, is encountered by Odysseus. Cyclopes were also said to have been the builders of the Cyclopean walls of Mycenae and Tiryns. A scholiast, quoting the fifth-century BC historian Hellanicus, tells us that, in addition to the Hesiodic Cyclopes (whom the scholiast describes as "the gods themselves"), and the Homeric Cyclopes, there was a third group of Cyclopes: the builders of the walls of Mycenae.

Hesiodic Cyclopes
Hesiod, in the Theogony (c. 700 BC), described three Cyclopes: Brontes, Steropes, and Arges, who were the sons of Uranus (Sky) and Gaia (Earth), and the brothers of the Titans and Hundred-Handers, and who had a single eye set in the middle of their foreheads. They made for Zeus his all-powerful thunderbolt, and in so doing, the Cyclopes played a key role in the Greek succession myth, which told how the Titan Cronus overthrew his father Uranus, and how in turn Zeus overthrew Cronus and his fellow Titans, and how Zeus was eventually established as the final and permanent ruler of the cosmos. The names that Hesiod gives them: Arges (Bright), Brontes (Thunder), and Steropes (Lightning), reflect their fundamental role as thunderbolt makers. As early as the late seventh-century BC, the Cyclopes could be used by the Spartan poet Tyrtaeus to epitomize extraordinary size and strength.According to the accounts of Hesiod and mythographer Apollodorus, the Cyclopes had been imprisoned by their father Uranus. Zeus later freed the Cyclopes, and they repaid him by giving him the thunderbolt. The Cyclopes provided for Hesiod, and other theogony-writers, a convenient source of heavenly weaponry, since the smith-god Hephaestus—who would eventually take over that role—had not yet been born. According to Apollodorus, the Cyclopes also provided Poseidon with his trident and Hades with his cap of invisibility, and the gods used these weapons to defeat the Titans.
Although the primordial Cyclopes of the Theogony were presumably immortal (as were their brothers the Titans), the sixth-century BC Hesiodic Catalogue of Women, has them being killed by Apollo. Later sources tell us why: Apollos son Asclepius had been killed by Zeus thunderbolt, and Apollo killed the Cyclopes, the makers of the thunderbolt, in revenge. According to a scholiast on Euripides Alcestis, the fifth-century BC mythographer Pherecydes supplied the same motive, but said that Apollo, rather than killing the Cyclopes, killed their sons (one of whom he named Aortes) instead. No other source mentions any offspring of the Cyclopes. A Pindar fragment suggests that Zeus himself killed the Cyclopes to prevent them from making thunderbolts for anyone else.The Cyclopes prowess as craftsmen is stressed by Hesiod who says "strength and force and contrivances were in their works." Being such skilled craftsmen of great size and strength, later poets, beginning with the third-century BC poet Callimachus, imagine these Cyclopes, the primordial makers of Zeus thunderbolt, becoming the assistants of the smith-god Hephaestus, at his forge in Sicily, underneath Mount Etna, or perhaps the nearby Aeolian Islands. In his Hymn to Artemis, Callimachus has the Cyclopes on the Aeolian island of Lipari, working "at the anvils of Hephaestus", make the bows and arrows used by Apollo and Artemis. The first-century BC Latin poet Virgil, in his epic Aeneid, has the Cyclopes: "Brontes and Steropes and bare-limbed Pyracmon" toil under the direction of Vulcan (Hephaestus), in caves underneath Mount Etna and the Aeolian islands. Virgil describes the Cyclopes, in Vulcans smithy forging iron, making a thunderbolt, a chariot for Mars, and Pallass Aegis, with Vulcan interrupting their work to command the Cyclopes to fashion arms for Aeneas. The later Latin poet Ovid also has the Hesiodic Cyclopes Brontes and Steropes (along with a third Cyclops named Acmonides), work at forges in Sicilian caves.According to a Hellenistic astral myth, the Cyclopes were the builders of the first altar. The myth was a catasterism, which explained how the constellation the Altar (Ara) came to be in the heavens. According to the myth, the Cyclopes built an altar upon which Zeus and the other gods swore alliance before their war with the Titans. After their victory, "the gods placed the altar in the sky in commemoration", and thus began the practice, according to the myth, of men swearing oaths upon altars "as a guarantee of their good faith".According to the second-century geographer Pausanias, there was a sanctuary called the "altar of the Cyclopes" on the Isthmus of Corinth at a place sacred to Poseidon, where sacrifices were offered to the Cyclopes. There is no evidence for any other cult associated with the Cyclopes. According to a version of the story in the Iliad scholia (found nowhere else), when Zeus swallowed Metis, she was pregnant with Athena by the Cyclops Brontes.Although described by Hesiod as "having very violent hearts" (ὑπέρβιον ἦτορ ἔχοντας), and while their extraordinary size and strength would have made them capable of great violence, there is no indication of the Hesiodic Cyclopes having behaved in any other way than as dutiful servants of the gods.Walter Burkert suggests that groups or societies of lesser gods, like the Hesiodic Cyclopes, "mirror real cult associations (thiasoi) ... It may be surmised that smith guilds lie behind Cabeiri, Idaian Dactyloi, Telchines, and Cyclopes."

Homeric Cyclopes
In an episode of Homers Odyssey (c. 700 BC), the hero Odysseus encounters the Cyclops Polyphemus, the son of Poseidon, a one-eyed man-eating giant who lives with his fellow Cyclopes in a distant land. The relationship between these Cyclopes and Hesiods Cyclopes is unclear. Homer described a very different group of Cyclopes, than the skilled and subservient craftsman of Hesiod. Homers Cyclopes live in the "world of men" rather than among the gods, as they presumably do in the Theogony. The Homeric Cyclopes are presented as uncivilized shepherds, who live in caves, savages with no regard for Zeus. They have no knowledge of agriculture, ships or craft. They live apart and lack any laws.The fifth-century BC playwright Euripides also told the story of Odysseus encounter with Polyphemus in his satyr play Cyclops. Euripides Cyclopes, like Homers, are uncultured cave-dwelling shepherds. They have no agriculture, no wine, and live on milk, cheese and the meat of sheep. They live solitary lives, and have no government. They are inhospitable to strangers, slaughtering and eating all who come to their land. While Homer does not say if the other Cyclopes are like Polyphemus in their appearance and parentage, Euripides makes it explicit, calling the Cyclopes "Poseidons one-eyed sons". And while Homer is vague as to their location, Euripides locates the land of the Cyclopes on the island of Sicily near Mount Etna.Like Euripides, Virgil has the Cyclopes of Polyphemus live on Sicily near Etna. For Virgil apparently, these Homeric Cyclopes are members of the same race of Cyclopes as Hesiods Brontes and Steropes, who live nearby.

Cyclopean wall-builders
Cyclopes were also said to have been the builders of the so-called Cyclopean walls of Mycenae, Tiryns, and Argos. Although they can be seen as being distinct, the Cyclopean wall-builders share several features with the Hesiodic Cyclopes: both groups are craftsmen of supernatural skill, possessing enormous strength, who lived in primordial times. These builder Cyclopes were apparently used to explain the construction of the stupendous walls at Mycenae and Tiryns, composed of massive stones that seemed too large and heavy to have been moved by ordinary men.These master builders were famous in antiquity from at least the fifth century BC onwards. The poet Pindar has Heracles driving the cattle of Geryon through the "Cyclopean portal" of the Tirynian king Eurystheus. The mythographer Pherecydes says that Perseus brought the Cyclopes with him from Seriphos to Argos, presumably to build the walls of Mycenae. Proetus, the mythical king of ancient Argos, was said to have brought a group of seven Cyclopes from Lycia to build the walls of Tiryns.The late fifth and early fourth-century BC comic poet Nicophon wrote a play called either Cheirogastores or Encheirogastores (Hands-to-Mouth), which is thought to have been about these Cyclopean wall-builders. Ancient lexicographers explained the title as meaning "those who feed themselves by manual labour", and, according to Eustathius of Thessalonica, the word was used to describe the Cyclopean wall-builders, while "hands-to-mouth" was one of the three kinds of Cyclopes distinguished by scholia to Aelius Aristides. Similarly,  possibly deriving from Nicophons comedy, the first-century Greek geographer Strabo says these Cyclopes were called "Bellyhands" (gasterocheiras) because they earned their food by working with their hands.The first-century natural philosopher Pliny the Elder, in his Natural History, reported a tradition, attributed to Aristotle, that the Cyclopes were the inventors of masonry towers. In the same work Pliny also mentions the Cyclopes, as being among those credited with being the first to work with iron, as well as bronze. In addition to walls, other monuments were attributed to the Cyclopes. For example, Pausanias says that at Argos there was "a head of Medusa made of stone, which is said to be another of the works of the Cyclopes".

Principal sources
Hesiod
According to the Theogony of Hesiod, Uranus (Sky) mated with Gaia (Earth) and produced eighteen children. First came the twelve Titans, next came the three one-eyed Cyclopes:

Then [Gaia] bore the Cyclopes, who have very violent hearts, Brontes (Thunder) and Steropes (Lightning) and strong-spirited Arges (Bright), those who gave thunder to Zeus and fashioned the thunderbolt. These were like the gods in other regards, but only one eye was set in the middle of their foreheads; and they were called Cyclopes (Circle-eyed) by name, since a single circle-shaped eye was set in their foreheads. Strength and force and contrivances were in their works.
Following the Cyclopes, Gaia next gave birth to three more monstrous brothers, the Hecatoncheires, or Hundred-Handed Giants. Uranus hated his monstrous children, and as soon as each was born, he imprisoned them underground, somewhere deep inside Gaia. Eventually Uranus son, the Titan Cronus, castrated Uranus, becoming the new ruler of the cosmos, but he did not release his brothers, the Cyclopes and the Hecatoncheires, from their imprisonment in Tartarus.For this failing, Gaia foretold that Cronus would eventually be overthrown by one of his children, as he had overthrown his own father.  To prevent this, as each of his children were born, Cronus swallowed them whole; as gods they were not killed, but imprisoned within his belly.  His wife, Rhea, sought her mothers advice to avoid losing all of her children in this way, and Gaia advised her to give Cronus a stone wrapped in swaddling clothes.  In this way, Zeus was spared the fate of his elder siblings, and was hidden away by his mother.  When he was grown, Zeus forced his father to vomit up his siblings, who rebelled against the Titans.  Zeus released the Cyclopes and Hecatoncheires, who became his allies.  While the Hundred-Handed Giants fought alongside Zeus and his siblings, the Cyclopes gave Zeus his great weapon, the thunderbolt, with the aid of which he was eventually able to overthrow the Titans, establishing himself as the ruler of the cosmos.

Homer
In Book 9 of the Odyssey, Odysseus describes to his hosts the Phaeacians his encounter with the Cyclops Polyphemus. Having just left the land of the Lotus-eaters, Odysseus says "Thence we sailed on, grieved at heart, and we came to the land of the Cyclopes".
Homer had already (Book 6) described the Cyclopes as "men overweening in pride who plundered [their neighbors the Phaeacians] continually", driving the Phaeacians from their home. In Book 9, Homer gives a more detailed description of the Cyclopes as:

an overweening and lawless folk, who, trusting in the immortal gods, plant nothing with their hands nor plough; but all these things spring up for them without sowing or ploughing, wheat, and barley, and vines, which bear the rich clusters of wine, and the rain of Zeus gives them increase. Neither assemblies for council have they, nor appointed laws, but they dwell on the peaks of lofty mountains in hollow caves, and each one is lawgiver to his children and his wives, and they reck nothing one of another.
According to Homer, the Cyclopes have no ships, nor ship-wrights, nor other craftsman, and know nothing of agriculture. They have no regard for Zeus or the other gods, for the Cyclopes hold themselves to be "better far than they".Homer says that "godlike" Polyphemus, the son of Poseidon and the nymph Thoosa, the daughter of Phorcys, is the "greatest among all the Cyclopes". Homer describes Polyphemus as a shepherd who:

mingled not with others, but lived apart, with his heart set on lawlessness. For he was fashioned a wondrous monster, and was not like a man that lives by bread, but like a wooded peak of lofty mountains, which stands out to view alone, apart from the rest, ... [and as] a savage man that knew naught of justice or of law.
Although Homer does not say explicitly that Polyphemus is one-eyed, for the account of his blinding to make sense he must be. If Homer meant for the other Cyclopes to be assumed (as they usually are) to be like Polyphemus, then they too will be one-eyed sons of Poseidon; however Homer says nothing explicit about either the parentage or appearance of the other Cyclopes.

Euripides
The Hesiodic Cyclopes: makers of Zeus thunderbolts, the Homeric Cyclopes: brothers of Polyphemus, and the Cyclopean wall-builders, all figure in the plays of the fifth-century BC playwright Euripides. In his  play Alcestis, where we are told that the Cyclopes who forged Zeus thunderbolts, were killed by Apollo. The prologue of that play has Apollo explain:

House of Admetus! In you I brought myself to taste the bread of menial servitude, god though I am. Zeus was the cause: he killed my son Asclepius, striking him in the chest with the lightning bolt, and in anger at this I slew the Cyclopes who forged Zeus’s fire. As my punishment for this Zeus compelled me to be a serf in the house of a mortal.
Euripides satyr play Cyclops tells the story of Odysseus encounter with the Cyclops Polyphemus, famously told in Homers Odyssey. It takes place on the island of Sicily near the volcano Mount Etna where, according to the play, "Poseidon’s one-eyed sons, the man-slaying Cyclopes, dwell in their remote caves." Euripides describes the land where Polyphemus brothers live, as having no "walls and city battlements", and a place where "no men dwell". The Cyclopes have no rulers and no government, "they are solitaries: no one is anyone’s subject." They grow no crops, living only "on milk and cheese and the flesh of sheep." They have no wine, "hence the land they dwell in knows no dancing". They show no respect for the important Greek value of Xenia ("guest friendship). When Odysseus asks if they are pious and hospitable toward strangers (φιλόξενοι δὲ χὤσιοι περὶ ξένους), he is told: "most delicious, they maintain, is the flesh of strangers ... everyone who has come here has been slaughtered."Several of Euripides plays also make reference to the Cyclopean wall-builders.  Euripides calls their walls "heaven-high" (οὐράνια), describes "the Cyclopean foundations" of Mycenae as "fitted snug with red plumbline and mason’s hammer", and calls  Mycenae "O hearth built by the Cyclopes". He calls Argos "the city built by the Cyclopes", refers to "the temples the Cyclopes built" and describes the "fortress of Perseus" as "the work of Cyclopean hands".

Callimachus
For the third-century BC poet Callimachus, the Hesiodic Cyclopes Brontes, Steropes and Arges, become assistants at the forge of the smith-god Hephaestus. Callimachus has the Cyclopes make Artemis bow, arrows and quiver, just as they had (apparently) made those of Apollo. Callimachus locates the Cyclopes on the island of Lipari, the largest of the Aeolian Islands in the Tyrrhenian Sea off the northern coast of Sicily, where Artemis finds them "at the anvils of Hephaestus" making a horse-trough for Poseidon:

And the nymphs were affrighted when they saw the terrible monsters like unto the crags of Ossa: all had single eyes beneath their brows, like a shield of fourfold hide for size, glaring terribly from under; and when they heard the din of the anvil echoing loudly, and the great blast of the bellows and the heavy groaning of the Cyclopes themselves. For Aetna cried aloud, and Trinacia cried, the seat of the Sicanians, cried too their neighbour Italy, and Cyrnos therewithal uttered a mighty noise, when they lifted their hammers above their shoulders and smote with rhythmic swing the bronze glowing from the furnace or iron, labouring greatly. Wherefore the daughters of Oceanus could not untroubled look upon them face to face nor endure the din in their ears. No shame to them! on those not even the daughters of the Blessed look without shuddering, though long past childhood’s years. But when any of the maidens doth disobedience to her mother, the mother calls the Cyclopes to her child—Arges or Steropes; and from within the house comes Hermes, stained with burnt ashes. And straightway he plays bogey to the child and she runs into her mother’s lap, with her hands upon her eyes. But thou, Maiden, even earlier, while yet but three years old, when Leto came bearing thee in her arms at the bidding of Hephaestus that he might give thee handsel and Brontes set thee on his stout knees—thou didst pluck the shaggy hair of his great breast and tear it out by force. And even unto this day the mid part of his breast remains hairless, even as when mange settles on a man’s temples and eats away the hair.
And Artemis asks:

Cyclopes, for me too fashion ye a Cydonian bow and arrows and a hollow casket for my shafts; for I also am a child of Leto, even as Apollo. And if I with my bow shall slay some wild creature or monstrous beast, that shall the Cyclopes eat.

Virgil
The first-century BC Roman poet Virgil seems to combine the Cyclopes of Hesiod with those of Homer, having them live alongside each other in the same part of Sicily. In his Latin epic Aeneid, Virgil has the hero Aeneas follow in the footsteps of Odysseus, the hero of Homers Odyssey.  Approaching Sicily and Mount Etna, in Book 3 of the Aeneid, Aeneas manages to survive the dangerous Charybdis, and at sundown comes to the land of the Cyclopes, while "near at hand Aetna thunders". The Cyclopes are described as being "in shape and size like Polyphemus ... a hundred other monstrous Cyclopes [who] dwell all along these curved shores and roam the high mountains." After narrowly escaping from Polyphemus, Aeneas tells how, responding to the Cyclops "mighty roar":

the race of the Cyclopes, roused from the woods and high mountains, rush to the harbour and throng the shores. We see them, standing impotent with glaring eye, the Aetnean brotherhood, their heads towering to the sky, a grim conclave: even as when on a mountaintop lofty oaks or cone-clad cypresses stand in mass, a high forest of Jove or grove of Diana.
Later, in Book 8 of the same poem, Virgil has the Hesiodic Cyclopes Brontes and Steropes, along with a third Cyclopes which he names Pyracmon, work in an extensive network of caverns stretching from Mount Etna to the Aeolian Islands. As the assistants of the smith-god Vulcan, they forge various items for the gods: thunderbolts for Jupiter, a chariot for Mars, and armor for Minerva:

In the vast cave the Cyclopes were forging iron—Brontes and Steropes and bare-limbed Pyracmon. They had a thunderbolt, which their hands had shaped, like the many that the Father hurls down from all over heaven upon earth, in part already polished, while part remained unfinished. Three shafts of twisted hail they had added to it, three of watery cloud, three of ruddy flame and the winged South Wind; now they were blending into the work terrifying flashes, noise, and fear, and wrath with pursuing flames. Elsewhere they were hurrying on for Mars a chariot and flying wheels, with which he stirs upmen and cities; and eagerly with golden scales of serpents were burnishing the awful aegis, armour of wrathful Pallas, the interwoven snakes, and on the breast of the goddess the Gorgon herself, with neck severed and eyes revolving.

Apollodorus
The mythographer Apollodorus, gives an account of the Hesiodic Cyclopes similar to that of Hesiods, but with some differences, and additional details. According to Apollodorus, the Cyclopes were born after the Hundred-Handers, but before the Titans (unlike Hesiod who makes the Titans the eldest and the Hundred-Handers the youngest).Uranus bound the Hundred-Handers and the Cyclopes, and cast them all into Tartarus, "a gloomy place in Hades as far distant from earth as earth is distant from the sky." But the Titans are, apparently, allowed to remain free (unlike in Hesiod). When the Titans overthrew Uranus, they freed the Hundred-Handers and Cyclopes (unlike in Hesiod, where they apparently remained imprisoned), and made Cronus their sovereign. But Cronus once again bound the six brothers, and reimprisoned them in Tartarus.As in Hesiods account, Rhea saved Zeus from being swallowed by Cronus, and Zeus was eventually able to free his siblings, and together they waged war against the Titans. According to Apollodorus, in the tenth year of that war, Zeus learned from Gaia, that he would be victorious if he had the Hundred-Handers and the Cyclopes as allies. So Zeus slew their warder Campe (a detail not found in Hesiod) and released them, and in addition to giving Zeus his thunderbolt (as in Hesiod), the Cyclopes also gave Poseidon his trident, and Hades a helmet (presumably the same cap of invisibility which Athena borrowed in the Iliad), and "with these weapons the gods overcame the Titans".Apollodorus also mentions a tomb of Geraestus, "the Cyclops" at Athens upon which, in the time of king Aegeus, the Athenians sacrificed the daughters of Hyacinth.

Nonnus
Dionysiaca, composed in the 4th or 5th century BC, is the longest surviving poem from antiquity – 20,426 lines.  It is written by the poet Nonnus in the Homeric dialect, and its main subject is the life of Dionysus. It describes a war that occurred between Dionysus troops and those of the Indian king Deriades. In book 28 of the Dionysiaca the Cyclopes join with Dionysian troops, and they prove to be great warriors and crush most of the Indian kings troops.

Transformations of Polyphemus
Depictions of the Cyclops Polyphemus have differed radically, depending on the literary genres in which he has appeared, and have given him an individual existence independent of the Homeric herdsman encountered by Odysseus. In the epic he was a man-eating monster dwelling in an unspecified land. Some centuries later, a dithyramb by Philoxenus of Cythera, followed by several episodes by the Greek pastoral poets, created of him a comedic and generally unsuccessful lover of the water nymph Galatea. In the course of these he woos his love to the accompaniment of either a cithara or the pan-pipes. Such episodes take place on the island of Sicily, and it was here that the Latin poet Ovid also set the tragic love story of Polyphemus and Galatea recounted in the Metamorphoses. Still later tradition made him the eventually successful husband of Galatea and the ancestor of the Celtic and Illyrian races.

Location
From at least the fifth-century BC onwards, Cyclopes have been associated with the island of Sicily, or the volcanic Aeolian islands just off Sicilys north coast. The fifth-century BC historian Thucydides says that the "earliest inhabitants" of Sicily were reputed to be the Cyclopes and Laestrygones (another group of man-eating giants encountered by Odysseus in Homers Odyssey). Thucydides also reports the local belief that Hephaestus (along with his Cyclopean assistants?) had his forge on the Aeolian island of Vulcano.Euripides locates Odysseus Cyclopes on the island of Sicily, near the volcano Mount Etna, and in the same play addresses Hephaestus as "lord of Aetna". The poet Callimachus locates the Cyclopes forge on the island of Lipari, the largest of the Aeolians. Virgil associates both the Hesiodic and the Homeric Cyclopes with Sicily. He has the thunderbolt makers: "Brontes and Steropes and bare-limbed Pyracmon", work in vast caverns extending underground from Mount Etna to the island of Vulcano, while the Cyclops brethren of Polyphemus live on Sicily where "near at hand Aetna thunders".As Thucydides notes, in the case of Hephaestus forge on Vulcano, locating the Cyclopes forge underneath active volcanoes provided an explanation for the fire and smoke often seen rising from them.

Etymology
For the ancient Greeks the name "Cyclopes" meant "Circle-eyes" or "Round-eyes", derived from the Greek kúklos ("circle") and ops ("eye"). This meaning can be seen as early as Hesiods Theogony  (8th–7th century BC), which explains that the Cyclopes were called that "since a single circle-shaped eye was set in their foreheads". Adalbert Kuhn, expanding on Hesiods etymology, proposed a connection between the first element kúklos (which can also mean "wheel") and the "wheel of the sun", producing the meaning "wheel (of the sun)-eyes". Other etymologies have been proposed which derive the second element of the name from the Greek klops ("thief") producing the meanings "wheel-thief" or "cattle-thief". Although Walter Burkert has described Hesiods etymology as "not too attractive", Hesiods explanation still finds acceptance by modern scholars.

Possible origins
A possible origin for one-eyed Cyclopes was advanced by the palaeontologist Othenio Abel in 1914. Abel proposed that fossil skulls of Pleistocene dwarf elephants, commonly found in coastal caves of Italy and Greece, may have given rise to the Polyphemus story. Abel suggested that the large, central nasal cavity (for the trunk) in the skull might have been interpreted as a large single eye-socket.Cyclopia, a rare birth defect, can result in foetuses which have a single eye. Although the possibility has been raised of a link between this deformity and the myth of the one-eyed Cyclopes, in such cases, the eye is below the nose—rather than above as in ancient Greek depictions.As noted above, Walter Burkert sees the possibility of the Hesiodic Cyclopes having ancient smith guilds as their basis.

See also
Polyphemus § Possible origins, for stories of other cyclopian giants similar to the story of Polyphemus encounter with Odysseus
List of one-eyed creatures in mythology and fiction

Notes
References
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Euripides, Cyclops in Euripides: Cyclops, Alcestis, Medea, edited and translated by David Kovacs, Loeb Classical Library No. 12, Cambridge, Massachusetts, Harvard University Press, 2001. ISBN 978-0-674-99560-4. Online version at Harvard University Press.
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West, M </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 Colpocephaly and explain in detail? [/INST] Colpocephaly is a cephalic disorder involving the disproportionate enlargement of the occipital horns of the lateral ventricles and is usually diagnosed early after birth due to seizures. It is a nonspecific finding and is associated with multiple neurological syndromes, including agenesis of the corpus callosum, Chiari malformation, lissencephaly, and microcephaly. Although the exact cause of colpocephaly is not known yet, it is commonly believed to occur as a result of neuronal migration disorders during early brain development, intrauterine disturbances, perinatal injuries, and other central nervous system disorders.  Individuals with colpocephaly have various degrees of motor disabilities, visual defects, spasticity, and moderate to severe intellectual disability.
No specific treatment for colpocephaly exists, but patients may undergo certain treatments to improve their motor function or intellectual disability.

Symptoms
There are various symptoms of colpocephaly and patients can experience effects ranging from mild to severe. Some patients do not show most of the symptoms related to colpocephaly, such as psychomotor abnormalilities and agenesis of the corpus callosum. In some cases, signs appear later on in life and a significant number of children only develop minor disabilities.
The following list includes common symptoms of colpocephaly.
partial or complete agenesis of the corpus callosum
intellectual disability
motor abnormalities
visual defects such as, crossing of the eyes, missing visual fields, and optic nerve hypoplasia
spasticity
seizures
cerebral palsyIntracranial abnormalities include:

Microcephaly
Agenesis of the corpus callosum
Meningomyelocele
Lissencephaly
Periventricular leukomalacia (PVL)
Enlargement of the cisterna magna
Cerebellar hypoplasia

Causes
There is no known definitive single mechanism that causes colpocephaly. However, researchers believe there are many possible causes of colpocephaly. It is a common symptom of other neurological disorders in newborns, can be caused as a result of shunt treatment of hydrocephalus, developmental disorders in premature infants, due to intrauterine disturbances during pregnancy, genetic disorders, underdevelopment or lack of white matter in the cerebrum, and exposure of the mother and the developing fetus to medications, infections, radiation, or toxic substances.  Also, it is usually more common in premature infants than in full-term infants, especially in babies born with hypoxia or lung immaturity.
Some of the central nervous system disorders which are associated with colpocephaly are as follows:
polymicrogyria
Periventricular leukomalacia (PVL)
intraventricular hemorrhage
Hydrocephalus
schizencephaly
microgyria
microcephaly
Pierre-Robin syndrome
NeurofibromatosisOften colpocephaly occurs as a result of hydrocephalus. Hydrocephalus  is the accumulation of cerebrospinal fluid (CSF) in the ventricles or in the subarachnoid space over the brain. The increased pressure due to this condition dilates occipital horns causing colpocephaly.
The most generally accepted theory is that of neuronal migration disorders occurring during the second to fifth months of fetal life. Neuronal migration disorders are caused by abnormal migration, proliferation, and organization of neurons during early brain development. During the seventh week of gestation, neurons start proliferating in the germinal matrix which is located in the subependymal layer of the walls of the lateral ventricles. During the eighth week of gestation, the neurons then start migrating from the germinal zone to cortex along specialized radial glial fibers. Next, neurons organize themselves into layers and form synaptic contacts with other neurons present in the cortex. Under normal conditions, the neurons forming a germinal layer around ventricles migrate to the surface of the brain and form the cerebral cortex and basal ganglia. If this process is abnormal or disturbed it could result in the enlargement of the occipital horns of the lateral ventricles. Common prenatal disturbances that have been shown to disturb the neuronal migration process include the following:
continuation of oral contraceptives
exposure to alcohol
intrauterine malnutrition
intrauterine infections such as toxoplasmosis
maternal drug ingestion during early pregnancy such as corticosteroids, salbutamol, and theophyllineResearchers also believe that these factors can cause destruction of neural elements that have previously been normally formed.It is suggested that the underdevelopment or lack of white matter in the developing fetus could be a cause of colpocephaly. The partial or complete absence of white matter, also known as agenesis of the corpus callosum results in anatomic malformations that can lead to colpocephaly. This starts to occur around the middle of the second month to the fifth month of pregnancy. The lateral ventricles are formed as large cavities of the telencephalic vesicle. The size of the ventricles are decreased in normal development after the formation of the Foramen of Magendie, which decompresses the ventricular cavities. Myelination of the ventricular walls and association fibers of the corpus callosum and the calcarine fissure helps shape the occipital horns. In cases where this developmental process is interrupted, occipital horns are disproportionately enlarged.Colpocephaly has been associated with chromosomal abnormalities such as trisomy 8 mosaic and trisomy 9 mosaic. A few reports of genetically transmitted colpocephaly are also found in literature. Some of these are of two siblings, monozygotic twins, and non-identical twins. The authors suggest a genetic origin with an autosomal or X-linked recessive inheritance rather than resulting from early prenatal disturbances.

Diagnosis
Presentation
Colpocephaly is characterized by disproportionately large occipital horns of the lateral ventricles (also frontal and temporal ventricles in some cases). MRI and CT scans of patients demonstrate abnormally thick gray matter with thin poorly myelinated white matter. This happens as a result of partial or complete absence of the corpus callosum. Corpus callosum is the band of white matter connecting the two cerebral hemispheres. The corpus callosum plays an extremely important role in interhemispheric communication, thus lack of or absence of these neural fibers results in a number of disabilities.The lemon sign on CT scans of patients refers to the shape of the fetal skull when the frontal bones lose their normal convex contour and appear flattened or inwardly scalloped. This gives the skull a shape similar to that of a lemon. The sign is seen on transverse sonograms of the fetal cranium obtained at the level of the ventricles.
A special case is found in literature where lissencephaly, colpocephaly, and septal agenesis are all present together. The CT scans of the patient shows the ventricular system having a unique appearance of a crown of a king. This is referred to as the CROWN SIGN.

Prenatal
Diagnosing colpocephaly prenatally is difficult because in many cases signs start to appear after birth. Prenatal diagnosis is made by detecting enlargement of either or both occipital horns of the lateral ventricles. Usually prenatal ultrasounds dont show cephalic abnormalities and in cases that they do show abnormality is of low accuracy, making it difficult to diagnose colpocephaly. Often, abnormalities in prenatal ultrasounds can be misdiagnosed as hydrocephalus.

Postnatal
After birth, MR imaging can be done to look for cephalic abnormalities. This is the most commonly used method for diagnosing colpocephaly. Physicians look for abnormally large occipital horns of the lateral ventricles and diminished thickness of white matter. Spinal tapping is not a preferred method for diagnosis because newborn babies with colpocephaly or hydrocephaly have open fontanelles which makes it difficult to collect CSF. Also, colpocephaly is not associated with increased pressure.

Treatment
Colpocephaly is usually non-fatal. There has been relatively little research conducted to improve treatments for colpocephaly, and there is no known definitive treatment of colpocephaly yet. Specific treatment depends on associated symptoms and the degree of dysfunction. Anticonvulsant medications can be given to prevent seizure complications, and physical therapy is used to prevent contractures (shrinkage or shortening of muscles) in patients that have limited mobility. Patients can also undergo surgeries for stiff joints to improve motor function. The prognosis for individuals with colpocephaly depends on the severity of the associated conditions and the degree of abnormal brain development.A rare case of colpocephaly is described in literature which is associated with macrocephaly instead of microcephaly. Increased intracranial pressure was also found in the condition. Similar symptoms (absence of corpus callosum and increased head circumference) were noted as in the case of colpocephaly that is associated with microcephaly. A bi-ventricular peritoneal shunt was performed, which greatly improved the symptoms of the condition </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 Sleep apnea and explain in detail? [/INST] Sleep apnea, also spelled sleep apnoea, is a sleep disorder in which pauses in breathing or periods of shallow breathing during sleep occur more often than normal. Each pause can last for a few seconds to a few minutes and they happen many times a night. In the most common form, this follows loud snoring. There may be a choking or snorting sound as breathing resumes. Because the disorder disrupts normal sleep, those affected may experience sleepiness or feel tired during the day. In children, it may cause hyperactivity or problems in school.Sleep apnea may be either obstructive sleep apnea (OSA), in which breathing is interrupted by a blockage of air flow, central sleep apnea (CSA), in which regular unconscious breath simply stops, or a combination of the two. OSA is the most common form. OSA has four key contributors; these include a narrow, crowded, or collapsible upper airway, an ineffective pharyngeal dilator muscle function during sleep, airway narrowing during sleep and unstable control of breathing (high loop gain). It is often a chronic condition. Other risk factors include being overweight, a family history of the condition, allergies, and enlarged tonsils. Some people with sleep apnea are unaware they have the condition. In many cases it is first observed by a family member. Sleep apnea is often diagnosed with an overnight sleep study. For a diagnosis of sleep apnea, more than five episodes per hour must occur.In central sleep apnea (CSA), the basic neurological controls for breathing rate malfunction and fail to give the signal to inhale, causing the individual to miss one or more cycles of breathing. If the pause in breathing is long enough, the percentage of oxygen in the circulation will drop to a lower than normal level (hypoxaemia) and the concentration of carbon dioxide will build to a higher than normal level (hypercapnia). In turn, these conditions of hypoxia and hypercapnia will trigger additional effects on the body. Brain cells need constant oxygen to live, and if the level of blood oxygen goes low enough for long enough, brain damage and even death will occur.
A systemic disorder, sleep apnea is associated with a wide array of effects, including increased risk of car accidents, hypertension, cardiovascular disease, myocardial infarction, stroke, atrial fibrillation, insulin resistance, higher incidence of cancer, and neurodegeneration. The exact effects of the condition will depend on how severe the apnea is and on the individual characteristics of the person having the apnea.
Treatment may include lifestyle changes, mouthpieces, breathing devices, and surgery. Effective lifestyle changes may include avoiding alcohol, losing weight, stopping smoking, and sleeping on ones side. Breathing devices include the use of a CPAP machine. With proper use, CPAP improves outcomes. Evidence suggests that CPAP may improve sensitivity to insulin, blood pressure, and sleepiness. Long term compliance, however, is an issue with more than half of people not appropriately using the device. In 2017, only 15% of potential patients in developed countries used CPAP machines, while in developing countries well under 1% of potential patients used CPAP. Without treatment, sleep apnea may increase the risk of heart attack, stroke, diabetes, heart failure, irregular heartbeat, obesity, and motor vehicle collisions.Alzheimers disease and severe obstructive sleep apnea are connected because there is an increase in the protein beta-amyloid as well as white-matter damage.  These are the main indicators of Alzheimers, which in this case comes from the lack of proper rest or poorer sleep efficiency resulting in neurodegeneration.  Having sleep apnea in mid-life brings a higher likelihood of developing Alzheimers in older age, and if one has Alzheimers then one is also more likely to have sleep apnea. This is demonstrated by cases of sleep apnea even being misdiagnosed as dementia. With the use of treatment through CPAP, there is a reversible risk factor in terms of the amyloid proteins.  This usually restores brain structure and diminishes cognitive impairment.OSA is a common sleep disorder. A large analysis in 2019 of the estimated prevalence of OSA found that OSA affects 936 million—1 billion people between the ages of 30-69 globally, or roughly every 1 in 10 people, and up to 30% of the elderly. Sleep apnea is somewhat more common in men than women, roughly a 2:1 ratio of men to women, and in general more people are likely to have it with older age and obesity.

Signs and symptoms
People with sleep apnea have problems with excessive daytime sleepiness (EDS) and impaired alertness. OSA may increase risk for driving accidents and work-related accidents. If OSA is not treated, people are at increased risk of other health problems, such as diabetes.
Due to the disruption in daytime cognitive state, behavioral effects may be present. These can include moodiness, belligerence, as well as a decrease in attentiveness and energy. These effects may become intractable, leading to depression.There is evidence that the risk of diabetes among those with moderate or severe sleep apnea is higher. Finally, because there are many factors that could lead to some of the effects previously listed, some people are not aware that they have sleep apnea and are either misdiagnosed or ignore the symptoms altogether.

Risk factors
Sleep apnea can affect people regardless of sex, race, or age. However, risk factors include:
being male
obesity
age over 40
large neck circumference (greater than 16–17 inches)
enlarged tonsils or tongue
narrow upper jaw
nasal congestion
allergies
receding chin
gastroesophageal reflux
a family history of sleep apnea
smokingAlcohol, sedatives and tranquilizers may also promote sleep apnea by relaxing throat muscles. People who smoke tobacco have sleep apnea at three times the rate of people who have never done so.Central sleep apnea is more often associated with any of the following risk factors:

being male
an age above 65
having heart disorders such as atrial fibrillation or atrial septal defects such as PFO
strokeHigh blood pressure is very common in people with sleep apnea.

Mechanism
When breathing is paused, carbon dioxide builds up in the bloodstream. Chemoreceptors in the bloodstream note the high carbon dioxide levels. The brain is signaled to awaken the person, which clears the airway and allows breathing to resume. Breathing normally will restore oxygen levels and the person will fall asleep again. This carbon dioxide build-up may be due to the decrease of output of the brainstem regulating the chest wall or pharyngeal muscles, which causes the pharynx to collapse. People with sleep apnea experience reduced or no slow-wave sleep and spend less time in REM sleep.

Complication
It is considered that OSA is a serious medical condition. Daytime fatigue and sleepiness, cardiovascular problems and eye problems are also be considered as a potential complications of OSA. OSA may also be a risk factor of COVID-19. It is found that people with OSA have a higher risk of developing severe complications of COVID-19.

Diagnosis
Despite this medical consensus, the variety of apneic events (e.g., hypopnea vs apnea, central vs obstructive), the variability of patients physiologies, and the inherent shortcomings and variability of equipment and methods, this field is subject to debate.
Within this context, the definition of an event depends on several factors (e.g., patients age) and account for this variability through a multi-criteria decision rule described in several, sometimes conflicting, guidelines.

Oximetry
Oximetry, which may be performed over one or several nights in a persons home, is a simpler, but less reliable alternative to a polysomnography. The test is recommended only when requested by a physician and should not be used to test those without symptoms. Home oximetry may be effective in guiding prescription for automatically self-adjusting continuous positive airway pressure.

Classification
There are three types of sleep apnea. OSA accounts for 84%, CSA for 0.9%, and 15% of cases are mixed.

Obstructive sleep apnea
Obstructive sleep apnea (OSA) is the most common category of sleep-disordered breathing. The muscle tone of the body ordinarily relaxes during sleep, and at the level of the throat, the human airway is composed of collapsible walls of soft tissue that can obstruct breathing. Mild occasional sleep apnea, such as many people experience during an upper respiratory infection, may not be significant, but chronic severe obstructive sleep apnea requires treatment to prevent low blood oxygen (hypoxemia), sleep deprivation, and other complications.
Individuals with low muscle-tone and soft tissue around the airway (e.g., because of obesity) and structural features that give rise to a narrowed airway are at high risk for obstructive sleep apnea. The elderly are more likely to have OSA than young people. Men are more likely to develop sleep apnea than women and children are, though it is not uncommon in the last two population groups.The risk of OSA rises with increasing body weight, active smoking and age. In addition, patients with diabetes or "borderline" diabetes have up to three times the risk of having OSA.
Common symptoms include loud snoring, restless sleep, and sleepiness during the daytime. Diagnostic tests include home oximetry or polysomnography in a sleep clinic.
Some treatments involve lifestyle changes, such as avoiding alcohol or muscle relaxants, losing weight, and quitting smoking. Many people benefit from sleeping at a 30-degree elevation of the upper body or higher, as if in a recliner. Doing so helps prevent the gravitational collapse of the airway. Lateral positions (sleeping on a side), as opposed to supine positions (sleeping on the back), are also recommended as a treatment for sleep apnea, largely because the gravitational component is smaller in the lateral position. Some people benefit from various kinds of oral appliances such as the Mandibular advancement splint to keep the airway open during sleep. Continuous positive airway pressure (CPAP) is the most effective treatment for severe obstructive sleep apnea, but oral appliances are considered a first-line approach equal to CPAP for mild to moderate sleep apnea, according to the AASM parameters of care. There are also surgical procedures to remove and tighten tissue and widen the airway.
Snoring is a common finding in people with this syndrome. Snoring is the turbulent sound of air moving through the back of the mouth, nose, and throat. Although not everyone who snores is experiencing difficulty breathing, snoring in combination with other risk factors has been found to be highly predictive of OSA. The loudness of the snoring is not indicative of the severity of obstruction, however. If the upper airways are tremendously obstructed, there may not be enough air movement to make much sound. Even the loudest snoring does not mean that an individual has sleep apnea syndrome. The sign that is most suggestive of sleep apneas occurs when snoring stops.
Up to 78% of genes associated with habitual snoring also increase the risk for OSA.Other indicators include (but are not limited to): hypersomnolence, obesity (BMI ≥ 30), large neck circumference—16 in (410 mm) in women, 17 in (430 mm) in men — enlarged tonsils and large tongue volume, micrognathia, morning headaches, irritability/mood-swings/depression, learning and/or memory difficulties, and sexual dysfunction.
The term "sleep-disordered breathing" is commonly used in the U.S. to describe the full range of breathing problems during sleep in which not enough air reaches the lungs (hypopnea and apnea). Sleep-disordered breathing is associated with an increased risk of cardiovascular disease, stroke, high blood pressure, arrhythmias, diabetes, and sleep deprived driving accidents. When high blood pressure is caused by OSA, it is distinctive in that, unlike most cases of high blood pressure (so-called essential hypertension), the readings do not drop significantly when the individual is sleeping. Stroke is associated with obstructive sleep apnea.Obstructive sleep apnea is associated with problems in daytime functioning, such as daytime sleepiness, motor vehicle crashes, psychological problems, decreased cognitive functioning, and reduced quality of life. Other associated problems include cerebrovascular diseases (hypertension, coronary artery disease, and stroke) and diabetes. These problems could be, at least in part, caused by risk factors of OSA.

Central sleep apnea
In pure central sleep apnea or Cheyne–Stokes respiration, the brains respiratory control centers are imbalanced during sleep. Blood levels of carbon dioxide, and the neurological feedback mechanism that monitors them, do not react quickly enough to maintain an even respiratory rate, with the entire system cycling between apnea and tachypnea, even during wakefulness. The sleeper stops breathing and then starts again. There is no effort made to breathe during the pause in breathing: there are no chest movements and no struggling. After the episode of apnea, breathing may be faster (tachypnea) for a period of time, a compensatory mechanism to blow off retained waste gases and absorb more oxygen.
While sleeping, a normal individual is "at rest" as far as cardiovascular workload is concerned. Breathing is regular in a healthy person during sleep, and oxygen levels and carbon dioxide levels in the bloodstream stay fairly constant. Any sudden drop in oxygen or excess of carbon dioxide (even if tiny) strongly stimulates the brains respiratory centers to breathe.
In any person, hypoxia and hypercapnia have certain common effects on the body. The heart rate will increase, unless there are such severe co-existing problems with the heart muscle itself or the autonomic nervous system that makes this compensatory increase impossible. The more translucent areas of the body will show a bluish or dusky cast from cyanosis, which is the change in hue that occurs owing to lack of oxygen in the blood ("turning blue"). Overdoses of drugs that are respiratory depressants (such as heroin, and other opiates) kill by damping the activity of the brains respiratory control centers. In central sleep apnea, the effects of sleep alone can remove the brains mandate for the body to breathe.

Normal Respiratory Drive: After exhalation, the blood level of oxygen decreases and that of carbon dioxide increases. Exchange of gases with a lungful of fresh air is necessary to replenish oxygen and rid the bloodstream of built-up carbon dioxide. Oxygen and carbon dioxide receptors in the blood stream (called chemoreceptors) send nerve impulses to the brain, which then signals reflex opening of the larynx (so that the opening between the vocal cords enlarges) and movements of the rib cage muscles and diaphragm. These muscles expand the thorax (chest cavity) so that a partial vacuum is made within the lungs and air rushes in to fill it.
Physiologic effects of central apnea: During central apneas, the central respiratory drive is absent, and the brain does not respond to changing blood levels of the respiratory gases. No breath is taken despite the normal signals to inhale. The immediate effects of central sleep apnea on the body depend on how long the failure to breathe endures. At worst, central sleep apnea may cause sudden death. Short of death, drops in blood oxygen may trigger seizures, even in the absence of epilepsy. In people with epilepsy, the hypoxia caused by apnea may trigger seizures that had previously been well controlled by medications. In other words, a seizure disorder may become unstable in the presence of sleep apnea. In adults with coronary artery disease, a severe drop in blood oxygen level can cause angina, arrhythmias, or heart attacks (myocardial infarction). Longstanding recurrent episodes of apnea, over months and years, may cause an increase in carbon dioxide levels that can change the pH of the blood enough to cause a respiratory acidosis.

Mixed apnea
Some people with sleep apnea have a combination of both types; its prevalence ranges from 0.56% to 18%. The condition is generally detected when obstructive sleep apnea is treated with CPAP and central sleep apnea emerges. The exact mechanism of the loss of central respiratory drive during sleep in OSA is unknown but is most likely related to incorrect settings of the CPAP treatment and other medical conditions the person has.

Management
The treatment of obstructive sleep apnea is different than that of central sleep apnea. Treatment often starts with behavioral therapy. Many people are told to avoid alcohol, sleeping pills, and other sedatives, which can relax throat muscles, contributing to the collapse of the airway at night.

Changing sleep position
More than half of people with obstructive sleep apnea have some degree of positional obstructive sleep apnea, meaning that it gets worse when they sleep on their backs.  Sleeping on their sides is an effective and cost-effective treatment for positional obstructive sleep apnea.

Continuous positive airway pressure
For moderate to severe sleep apnea, the most common treatment is the use of a continuous positive airway pressure (CPAP) or automatic positive airway pressure (APAP) device. These splint the persons airway open during sleep by means of pressurized air. The person typically wears a plastic facial mask, which is connected by a flexible tube to a small bedside CPAP machine.Although CPAP therapy is effective in reducing apneas and less expensive than other treatments, some people find it uncomfortable. Some complain of feeling trapped, having chest discomfort, and skin or nose irritation. Other side effects may include dry mouth, dry nose, nosebleeds, sore lips and gums.Whether or not it decreases the risk of death or heart disease is controversial with some reviews finding benefit and others not. This variation across studies might be driven by low rates of compliance—analyses of those who use CPAP for at least four hours a night suggests a decrease in cardiovascular events.

Weight loss
Excess body weight is thought to be an important cause of sleep apnea. People who are overweight have more tissues in the back of their throat which can restrict the airway, especially when sleeping. In weight loss studies of overweight individuals, those who lose weight show reduced apnea frequencies and improved apnoea–hypopnoea index (AHI). Weight loss effective enough to relieve obesity hypoventilation syndrome (OHS) must be 25–30% of body weight. For some obese people, it can be difficult to achieve and maintain this result without bariatric surgery.

Rapid palatal expansion
In children, orthodontic treatment to expand the volume of the nasal airway, such as nonsurgical rapid palatal expansion is common. The procedure has been found to significantly decrease the AHI and lead to long-term resolution of clinical symptoms.Since the palatal suture is fused in adults, regular RPE using tooth-borne expanders cannot be performed. Mini-implant assisted rapid palatal expansion (MARPE) has been recently developed as a non-surgical option for the transverse expansion of the maxilla in adults. This method increases the volume of the nasal cavity and nasopharynx, leading to increased airflow and reduced respiratory arousals during sleep. Changes are permanent with minimal complications.
Palatal expansion is a unique treatment in that it is minimally invasive, has lasting changes and requires minimal patient compliance for treatment success.

Surgery
Several surgical procedures (sleep surgery) are used to treat sleep apnea, although they are normally a third line of treatment for those who reject or are not helped by CPAP treatment or dental appliances. Surgical treatment for obstructive sleep apnea needs to be individualized to address all anatomical areas of obstruction.

Nasal obstruction
Often, correction of the nasal passages needs to be performed in addition to correction of the oropharynx passage. Septoplasty and turbinate surgery may improve the nasal airway, but has been found to be ineffective at reducing respiratory arousals during sleep.

Pharyngeal obstruction
Tonsillectomy and uvulopalatopharyngoplasty (UPPP or UP3) are available to address pharyngeal obstruction.

The "Pillar" device is a treatment for snoring and obstructive sleep apnea; it is thin, narrow strips of polyester. Three strips are inserted into the roof of the mouth (the soft palate) using a modified syringe and local anesthetic, in order to stiffen the soft palate. This procedure addresses one of the most common causes of snoring and sleep apnea — vibration or collapse of the soft palate. It was approved by the FDA for snoring in 2002 and for obstructive sleep apnea in 2004. A 2013 meta-analysis found that "the Pillar implant has a moderate effect on snoring and mild-to-moderate obstructive sleep apnea" and that more studies with high level of evidence were needed to arrive at a definite conclusion; it also found that the polyester strips work their way out of the soft palate in about 10% of the people in whom they are implanted.

Hypopharyngeal or base of tongue obstruction
Base-of-tongue advancement by means of advancing the genial tubercle of the mandible, tongue suspension, or hyoid suspension (aka hyoid myotomy and suspension or hyoid advancement) may help with the lower pharynx.
Other surgery options may attempt to shrink or stiffen excess tissue in the mouth or throat, procedures done at either a doctors office or a hospital. Small shots or other treatments, sometimes in a series, are used for shrinkage, while the insertion of a small piece of stiff plastic is used in the case of surgery whose goal is to stiffen tissues.

Multi-level surgery
Maxillomandibular advancement (MMA) is considered the most effective surgery for people with sleep apnea, because it increases the posterior airway space (PAS). However, health professionals are often unsure as to who should be referred for surgery and when to do so: some factors in referral may include failed use of CPAP or device use; anatomy which favors rather than impedes surgery; or significant craniofacial abnormalities which hinder device use.

Potential complications
Several inpatient and outpatient procedures use sedation. Many drugs and agents used during surgery to relieve pain and to depress consciousness remain in the body at low amounts for hours or even days afterwards. In an individual with either central, obstructive or mixed sleep apnea, these low doses may be enough to cause life-threatening irregularities in breathing or collapses in a patients airways. Use of analgesics and sedatives in these patients postoperatively should therefore be minimized or avoided.
Surgery on the mouth and throat, as well as dental surgery and procedures, can result in postoperative swelling of the lining of the mouth and other areas that affect the airway. Even when the surgical procedure is designed to improve the airway, such as tonsillectomy and adenoidectomy or tongue reduction, swelling may negate some of the effects in the immediate postoperative period. Once the swelling resolves and the palate becomes tightened by postoperative scarring, however, the full benefit of the surgery may be noticed.
A person with sleep apnea undergoing any medical treatment must make sure their doctor and anesthetist are informed about the sleep apnea. Alternative and emergency procedures may be necessary to maintain the airway of sleep apnea patients.

Other
Neurostimulation
Diaphragm pacing, which involves the rhythmic application of electrical impulses to the diaphragm, has been used to treat central sleep apnea.In April 2014, the U.S. Food and Drug Administration granted pre-market approval for use of an upper airway stimulation system in people who cannot use a continuous positive airway pressure device. The Inspire Upper Airway Stimulation system senses respiration and applies mild electrical stimulation during inspiration, which pushes the tongue slightly forward to open the airway.

Medications
There is currently insufficient evidence to recommend any medication for OSA. This may result in part because people with sleep apnea have tended to be treated as a single group in clinical trials. Identifying specific physiological factors underlying sleep apnea makes it possible to test drugs specific to those causal factors: airway narrowing, impaired muscle activity, low arousal threshold for waking, and unstable breathing control.
Those who experience low waking thresholds may benefit from eszopiclone, a sedative typically used to treat insomnia. The  antidepressant desipramine may stimulate upper airway muscles and lessen pharyngeal collapsibility in people who have limited muscle function in their airways.There is limited evidence for medication, but 2012 AASM guidelines suggested that acetazolamide "may be considered" for the treatment of central sleep apnea; zolpidem and triazolam may also be considered for the treatment of central sleep apnea, but "only if the patient does not have underlying risk factors for respiratory depression".
Low doses of oxygen are also used as a treatment for hypoxia but are discouraged due to side effects.

Oral appliances
An oral appliance, often referred to as a mandibular advancement splint, is a custom-made mouthpiece that shifts the lower jaw forward and opens the bite slightly, opening up the airway. These devices can be fabricated by a general dentist. Oral appliance therapy (OAT) is usually successful in patients with mild to moderate obstructive sleep apnea. While CPAP is more effective for sleep apnea than oral appliances, oral appliances do improve sleepiness and quality of life and are often better tolerated than CPAP.

Nasal EPAP
Nasal EPAP is a bandage-like device placed over the nostrils that uses a persons own breathing to create positive airway pressure to prevent obstructed breathing.

Oral pressure therapy
Oral pressure therapy uses a device that creates a vacuum in the mouth, pulling the soft palate tissue forward. It has been found useful in about 25 to 37% of people.

Prognosis
Death could occur from untreated OSA due to lack of oxygen to the body.There is increasing evidence that sleep apnea may lead to liver function impairment, particularly fatty liver diseases (see steatosis).It has been revealed that people with OSA show tissue loss in brain regions that help store memory, thus linking OSA with memory loss. Using magnetic resonance imaging (MRI), the scientists discovered that people with sleep apnea have mammillary bodies that are about 20% smaller, particularly on the left side. One of the key investigators hypothesized that repeated drops in oxygen lead to the brain injury.The immediate effects of central sleep apnea on the body depend on how long the failure to breathe endures. At worst, central sleep apnea may cause sudden death. Short of death, drops in blood oxygen may trigger seizures, even in the absence of epilepsy. In people with epilepsy, the hypoxia caused by apnea may trigger seizures that had previously been well controlled by medications. In other words, a seizure disorder may become unstable in the presence of sleep apnea. In adults with coronary artery disease, a severe drop in blood oxygen level can cause angina, arrhythmias, or heart attacks (myocardial infarction). Longstanding recurrent episodes of apnea, over months and years, may cause an increase in carbon dioxide levels that can change the pH of the blood enough to cause a respiratory acidosis.

Epidemiology
The Wisconsin Sleep Cohort Study estimated in 1993 that roughly one in every 15 Americans was affected by at least moderate sleep apnea. It also estimated that in middle-age as many as 9% of women and 24% of men were affected, undiagnosed and untreated.The costs of untreated sleep apnea reach further than just health issues. It is estimated that in the U.S., the average untreated sleep apnea patients annual health care costs $1,336 more than an individual without sleep apnea </s>