<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Eye and can you explain it in depth? [/INST] Eyes are organs of the visual system. They provide living organisms with vision, the ability to receive and process visual detail, as well as enabling several photo response functions that are independent of vision. Eyes detect light and convert it into electro-chemical impulses in neurons (neurones). In higher organisms, the eye is a complex optical system which collects light from the surrounding environment, regulates its intensity through a diaphragm, focuses it through an adjustable assembly of lenses to form an image, converts this image into a set of electrical signals, and transmits these signals to the brain through complex neural pathways that connect the eye via the optic nerve to the visual cortex and other areas of the brain. Eyes with resolving power have come in ten fundamentally different forms, and 96% of animal species possess a complex optical system. Image-resolving eyes are present in molluscs, chordates and arthropods.The most simple eyes, pit eyes, are eye-spots which may be set into a pit to reduce the angle of light that enters and affects the eye-spot, to allow the organism to deduce the angle of incoming light. From more complex eyes, retinal photosensitive ganglion cells send signals along the retinohypothalamic tract to the suprachiasmatic nuclei to effect circadian adjustment and to the pretectal area to control the pupillary light reflex.

Overview
Complex eyes distinguish shapes and colours. The visual fields of many organisms, especially predators, involve large areas of binocular vision for depth perception. In other organisms, particularly prey animals, eyes are located to maximise the field of view, such as in rabbits and horses, which have monocular vision.
The first proto-eyes evolved among animals 600 million years ago about the time of the Cambrian explosion. The last common ancestor of animals possessed the biochemical toolkit necessary for vision, and more advanced eyes have evolved in 96% of animal species in six of the ~35 main phyla. In most vertebrates and some molluscs, the eye allows light to enter and project onto a light-sensitive layer of cells known as the retina. The cone cells (for colour) and the rod cells (for low-light contrasts) in the retina detect and convert light into neural signals which are transmitted to the brain via the optic nerve to produce vision. Such eyes are typically spheroid, filled with the transparent gel-like vitreous humour, possess a focusing lens, and often an iris. Muscles around the iris change the size of the pupil, regulating the amount of light that enters the eye and reducing aberrations when there is enough light. The eyes of most cephalopods, fish, amphibians and snakes have fixed lens shapes, and focusing is achieved by telescoping the lens in a similar manner to that of a camera.The compound eyes of the arthropods are composed of many simple facets which, depending on anatomical detail, may give either a single pixelated image or multiple images per eye. Each sensor has its own lens and photosensitive cell(s). Some eyes have up to 28,000 such sensors arranged hexagonally, which can give a full 360° field of vision. Compound eyes are very sensitive to motion. Some arthropods, including many Strepsiptera, have compound eyes of only a few facets, each with a retina capable of creating an image. With each eye producing a different image, a fused, high-resolution image is produced in the brain.

Possessing detailed hyperspectral colour vision, the Mantis shrimp has the worlds most complex colour vision system. Trilobites, now extinct, had unique compound eyes. Clear calcite crystals formed the lenses of their eyes. They differ in this from most other arthropods, which have soft eyes. The number of lenses in such an eye varied widely; some trilobites had only one while others had thousands of lenses per eye.
In contrast to compound eyes, simple eyes have a single lens. Jumping spiders have one pair of large simple eyes with a narrow field of view, augmented by an array of smaller eyes for peripheral vision. Some insect larvae, like caterpillars, have a type of simple eye (stemmata) which usually provides only a rough image, but (as in sawfly larvae) can possess resolving powers of 4 degrees of arc, be polarization-sensitive, and capable of increasing its absolute sensitivity at night by a factor of 1,000 or more. Ocelli, some of the simplest eyes, are found in animals such as some of the snails. They have photosensitive cells but no lens or other means of projecting an image onto those cells. They can distinguish between light and dark but no more, enabling them to avoid direct sunlight.
In organisms dwelling near deep-sea vents, compound eyes are adapted to see the infra-red light produced by the hot vents; enabling the creatures to avoid being boiled alive.

Types
There are ten different eye layouts—indeed every technological method of capturing an optical image commonly used by human beings, with the exceptions of zoom and Fresnel lenses, occur in nature. Eye types can be categorised into "simple eyes", with one concave photoreceptive surface, and "compound eyes", which comprise a number of individual lenses laid out on a convex surface. Note that "simple" does not imply a reduced level of complexity or acuity. Indeed, any eye type can be adapted for almost any behaviour or environment. The only limitations specific to eye types are that of resolution—the physics of compound eyes prevents them from achieving a resolution better than 1°. Also, superposition eyes can achieve greater sensitivity than apposition eyes, so are better suited to dark-dwelling creatures. Eyes also fall into two groups on the basis of their photoreceptors cellular construction, with the photoreceptor cells either being cilliated (as in the vertebrates) or rhabdomeric. These two groups are not monophyletic; the cnidaria also possess cilliated cells,
 and some gastropods, as well as some annelids possess both.Some organisms have photosensitive cells that do nothing but detect whether the surroundings are light or dark, which is sufficient for the entrainment of circadian rhythms. These are not considered eyes because they lack enough structure to be considered an organ, and do not produce an image.

Non-compound eyes
Simple eyes are rather ubiquitous, and lens-bearing eyes have evolved at least seven times in vertebrates, cephalopods, annelids, crustaceans and cubozoa.

Pit eyes
Pit eyes, also known as stemma, are eye-spots which may be set into a pit to reduce the angles of light that enters and affects the eye-spot, to allow the organism to deduce the angle of incoming light. Found in about 85% of phyla, these basic forms were probably the precursors to more advanced types of "simple eyes". They are small, comprising up to about 100 cells covering about 100 µm. The directionality can be improved by reducing the size of the aperture, by incorporating a reflective layer behind the receptor cells, or by filling the pit with a refractile material.Pit vipers have developed pits that function as eyes by sensing thermal infra-red radiation, in addition to their optical wavelength eyes like those of other vertebrates (see infrared sensing in snakes). However, pit organs are fitted with receptors rather different from photoreceptors, namely a specific transient receptor potential channel (TRP channels) called TRPV1. The main difference is that photoreceptors are G-protein coupled receptors but TRP are ion channels.

Spherical lens eye
The resolution of pit eyes can be greatly improved by incorporating a material with a higher refractive index to form a lens, which may greatly reduce the blur radius encountered—hence increasing the resolution obtainable. The most basic form, seen in some gastropods and annelids, consists of a lens of one refractive index. A far sharper image can be obtained using materials with a high refractive index, decreasing to the edges; this decreases the focal length and thus allows a sharp image to form on the retina. This also allows a larger aperture for a given sharpness of image, allowing more light to enter the lens; and a flatter lens, reducing spherical aberration. Such a non-homogeneous lens is necessary for the focal length to drop from about 4 times the lens radius, to 2.5 radii.Heterogeneous eyes have evolved at least nine times: four or more times in gastropods, once in the copepods, once in the annelids, once in the cephalopods, and once in the chitons, which have aragonite lenses. No extant aquatic organisms possess homogeneous lenses; presumably the evolutionary pressure for a heterogeneous lens is great enough for this stage to be quickly "outgrown".This eye creates an image that is sharp enough that motion of the eye can cause significant blurring. To minimise the effect of eye motion while the animal moves, most such eyes have stabilising eye muscles.The ocelli of insects bear a simple lens, but their focal point usually lies behind the retina; consequently, those cant form a sharp image. Ocelli (pit-type eyes of arthropods) blur the image across the whole retina, and are consequently excellent at responding to rapid changes in light intensity across the whole visual field; this fast response is further accelerated by the large nerve bundles which rush the information to the brain. Focusing the image would also cause the suns image to be focused on a few receptors, with the possibility of damage under the intense light; shielding the receptors would block out some light and thus reduce their sensitivity.
This fast response has led to suggestions that the ocelli of insects are used mainly in flight, because they can be used to detect sudden changes in which way is up (because light, especially UV light which is absorbed by vegetation, usually comes from above).

Multiple lenses
Some marine organisms bear more than one lens; for instance the copepod Pontella has three. The outer has a parabolic surface, countering the effects of spherical aberration while allowing a sharp image to be formed. Another copepod, Copilia, has two lenses in each eye, arranged like those in a telescope. Such arrangements are rare and poorly understood, but represent an alternative construction.
Multiple lenses are seen in some hunters such as eagles and jumping spiders, which have a refractive cornea: these have a negative lens, enlarging the observed image by up to 50% over the receptor cells, thus increasing their optical resolution.

Refractive cornea
In the eyes of most mammals, birds, reptiles, and most other terrestrial vertebrates (along with spiders and some insect larvae) the vitreous fluid has a higher refractive index than the air. In general, the lens is not spherical. Spherical lenses produce spherical aberration. In refractive corneas, the lens tissue is corrected with inhomogeneous lens material (see Luneburg lens), or with an aspheric shape. Flattening the lens has a disadvantage; the quality of vision is diminished away from the main line of focus. Thus, animals that have evolved with a wide field-of-view often have eyes that make use of an inhomogeneous lens.As mentioned above, a refractive cornea is only useful out of water. In water, there is little difference in refractive index between the vitreous fluid and the surrounding water. Hence creatures that have returned to the water—penguins and seals, for example—lose their highly curved cornea and return to lens-based vision. An alternative solution, borne by some divers, is to have a very strongly focusing cornea.

Reflector eyes
An alternative to a lens is to line the inside of the eye with "mirrors", and reflect the image to focus at a central point. The nature of these eyes means that if one were to peer into the pupil of an eye, one would see the same image that the organism would see, reflected back out.Many small organisms such as rotifers, copepods and flatworms use such organs, but these are too small to produce usable images. Some larger organisms, such as scallops, also use reflector eyes. The scallop Pecten has up to 100 millimetre-scale reflector eyes fringing the edge of its shell. It detects moving objects as they pass successive lenses.There is at least one vertebrate, the spookfish, whose eyes include reflective optics for focusing of light. Each of the two eyes of a spookfish collects light from both above and below; the light coming from above is focused by a lens, while that coming from below, by a curved mirror composed of many layers of small reflective plates made of guanine crystals.

Compound eyes
A compound eye may consist of thousands of individual photoreceptor units or ommatidia (ommatidium, singular). The image perceived is a combination of inputs from the numerous ommatidia (individual "eye units"), which are located on a convex surface, thus pointing in slightly different directions. Compared with simple eyes, compound eyes possess a very large view angle, and can detect fast movement and, in some cases, the polarisation of light. Because the individual lenses are so small, the effects of diffraction impose a limit on the possible resolution that can be obtained (assuming that they do not function as phased arrays). This can only be countered by increasing lens size and number. To see with a resolution comparable to our simple eyes, humans would require very large compound eyes, around 11 metres (36 ft) in radius.Compound eyes fall into two groups: apposition eyes, which form multiple inverted images, and superposition eyes, which form a single erect image. Compound eyes are common in arthropods, annelids and some bivalved molluscs. Compound eyes in arthropods grow at their margins by the addition of new ommatidia.

Apposition eyes
Apposition eyes are the most common form of eyes and are presumably the ancestral form of compound eyes. They are found in all arthropod groups, although they may have evolved more than once within this phylum. Some annelids and bivalves also have apposition eyes. They are also possessed by Limulus, the horseshoe crab, and there are suggestions that other chelicerates developed their simple eyes by reduction from a compound starting point. (Some caterpillars appear to have evolved compound eyes from simple eyes in the opposite fashion.)
Apposition eyes work by gathering a number of images, one from each eye, and combining them in the brain, with each eye typically contributing a single point of information. The typical apposition eye has a lens focusing light from one direction on the rhabdom, while light from other directions is absorbed by the dark wall of the ommatidium.

Superposition eyes
The second type is named the superposition eye. The superposition eye is divided into three types:

refracting,
reflecting and
parabolic superpositionThe refracting superposition eye has a gap between the lens and the rhabdom, and no side wall. Each lens takes light at an angle to its axis and reflects it to the same angle on the other side. The result is an image at half the radius of the eye, which is where the tips of the rhabdoms are. This type of compound eye, for which a minimal size exists below which effective superposition cannot occur, is normally found in nocturnal insects, because it can create images up to 1000 times brighter than equivalent apposition eyes, though at the cost of reduced resolution. In the parabolic superposition compound eye type, seen in arthropods such as mayflies, the parabolic surfaces of the inside of each facet focus light from a reflector to a sensor array. Long-bodied decapod crustaceans such as shrimp, prawns, crayfish and lobsters are alone in having reflecting superposition eyes, which also have a transparent gap but use corner mirrors instead of lenses.

Parabolic superposition
This eye type functions by refracting light, then using a parabolic mirror to focus the image; it combines features of superposition and apposition eyes.

Other
Another kind of compound eye, found in males of Order Strepsiptera, employs a series of simple eyes—eyes having one opening that provides light for an entire image-forming retina. Several of these eyelets together form the strepsipteran compound eye, which is similar to the schizochroal compound eyes of some trilobites. Because each eyelet is a simple eye, it produces an inverted image; those images are combined in the brain to form one unified image. Because the aperture of an eyelet is larger than the facets of a compound eye, this arrangement allows vision under low light levels.Good fliers such as flies or honey bees, or prey-catching insects such as praying mantis or dragonflies, have specialised zones of ommatidia organised into a fovea area which gives acute vision. In the acute zone, the eyes are flattened and the facets larger. The flattening allows more ommatidia to receive light from a spot and therefore higher resolution. The black spot that can be seen on the compound eyes of such insects, which always seems to look directly at the observer, is called a pseudopupil. This occurs because the ommatidia which one observes "head-on" (along their optical axes) absorb the incident light, while those to one side reflect it.There are some exceptions from the types mentioned above. Some insects have a so-called single lens compound eye, a transitional type which is something between a superposition type of the multi-lens compound eye and the single lens eye found in animals with simple eyes. Then there is the mysid shrimp, Dioptromysis paucispinosa. The shrimp has an eye of the refracting superposition type, in the rear behind this in each eye there is a single large facet that is three times in diameter the others in the eye and behind this is an enlarged crystalline cone. This projects an upright image on a specialised retina. The resulting eye is a mixture of a simple eye within a compound eye.
Another version is a compound eye often referred to as "pseudofaceted", as seen in Scutigera. This type of eye consists of a cluster of numerous ommatidia on each side of the head, organised in a way that resembles a true compound eye.
The body of Ophiocoma wendtii, a type of brittle star, is covered with ommatidia, turning its whole skin into a compound eye. The same is true of many chitons. The tube feet of sea urchins contain photoreceptor proteins, which together act as a compound eye; they lack screening pigments, but can detect the directionality of light by the shadow cast by its opaque body.

Nutrients
The ciliary body is triangular in horizontal section and is coated by a double layer, the ciliary epithelium. The inner layer is transparent and covers the vitreous body, and is continuous from the neural tissue of the retina. The outer layer is highly pigmented, continuous with the retinal pigment epithelium, and constitutes the cells of the dilator muscle.
The vitreous is the transparent, colourless, gelatinous mass that fills the space between the lens of the eye and the retina lining the back of the eye. It is produced by certain retinal cells. It is of rather similar composition to the cornea, but contains very few cells (mostly phagocytes which remove unwanted cellular debris in the visual field, as well as the hyalocytes of Balazs of the surface of the vitreous, which reprocess the hyaluronic acid), no blood vessels, and 98–99% of its volume is water (as opposed to 75% in the cornea) with salts, sugars, vitrosin (a type of collagen), a network of collagen type II fibres with the mucopolysaccharide hyaluronic acid, and also a wide array of proteins in micro amounts. Amazingly, with so little solid matter, it tautly holds the eye.

Evolution
Photoreception is phylogenetically very old, with various theories of phylogenesis. The common origin (monophyly) of all animal eyes is now widely accepted as fact. This is based upon the shared genetic features of all eyes; that is, all modern eyes, varied as they are, have their origins in a proto-eye believed to have evolved some 650-600 million years ago, and the PAX6 gene is considered a key factor in this. The majority of the advancements in early eyes are believed to have taken only a few million years to develop, since the first predator to gain true imaging would have touched off an "arms race" among all species that did not flee the photopic environment. Prey animals and competing predators alike would be at a distinct disadvantage without such capabilities and would be less likely to survive and reproduce. Hence multiple eye types and subtypes developed in parallel (except those of groups, such as the vertebrates, that were only forced into the photopic environment at a late stage).
Eyes in various animals show adaptation to their requirements. For example, the eye of a bird of prey has much greater visual acuity than a human eye, and in some cases can detect ultraviolet radiation. The different forms of eye in, for example, vertebrates and molluscs are examples of parallel evolution, despite their distant common ancestry. Phenotypic convergence of the geometry of cephalopod and most vertebrate eyes creates the impression that the vertebrate eye evolved from an imaging cephalopod eye, but this is not the case, as the reversed roles of their respective ciliary and rhabdomeric opsin classes and different lens crystallins show.The very earliest "eyes", called eye-spots, were simple patches of photoreceptor protein in unicellular animals. In multicellular beings, multicellular eyespots evolved, physically similar to the receptor patches for taste and smell. These eyespots could only sense ambient brightness: they could distinguish light and dark, but not the direction of the light source.Through gradual change, the eye-spots of species living in well-lit environments depressed into a shallow "cup" shape. The ability to slightly discriminate directional brightness was achieved by using the angle at which the light hit certain cells to identify the source. The pit deepened over time, the opening diminished in size, and the number of photoreceptor cells increased, forming an effective pinhole camera that was capable of dimly distinguishing shapes. However, the ancestors of modern hagfish, thought to be the protovertebrate, were evidently pushed to very deep, dark waters, where they were less vulnerable to sighted predators, and where it is advantageous to have a convex eye-spot, which gathers more light than a flat or concave one. This would have led to a somewhat different evolutionary trajectory for the vertebrate eye than for other animal eyes.
The thin overgrowth of transparent cells over the eyes aperture, originally formed to prevent damage to the eyespot, allowed the segregated contents of the eye chamber to specialise into a transparent humour that optimised colour filtering, blocked harmful radiation, improved the eyes refractive index, and allowed functionality outside of water. The transparent protective cells eventually split into two layers, with circulatory fluid in between that allowed wider viewing angles and greater imaging resolution, and the thickness of the transparent layer gradually increased, in most species with the transparent crystallin protein.The gap between tissue layers naturally formed a biconvex shape, an optimally ideal structure for a normal refractive index. Independently, a transparent layer and a nontransparent layer split forward from the lens: the cornea and iris. Separation of the forward layer again formed a humour, the aqueous humour. This increased refractive power and again eased circulatory problems. Formation of a nontransparent ring allowed more blood vessels, more circulation, and larger eye sizes.

Relationship to life requirements
Eyes are generally adapted to the environment and life requirements of the organism which bears them. For instance, the distribution of photoreceptors tends to match the area in which the highest acuity is required, with horizon-scanning organisms, such as those that live on the African plains, having a horizontal line of high-density ganglia, while tree-dwelling creatures which require good all-round vision tend to have a symmetrical distribution of ganglia, with acuity decreasing outwards from the centre.
Of course, for most eye types, it is impossible to diverge from a spherical form, so only the density of optical receptors can be altered. In organisms with compound eyes, it is the number of ommatidia rather than ganglia that reflects the region of highest data acquisition.: 23–24  Optical superposition eyes are constrained to a spherical shape, but other forms of compound eyes may deform to a shape where more ommatidia are aligned to, say, the horizon, without altering the size or density of individual ommatidia. Eyes of horizon-scanning organisms have stalks so they can be easily aligned to the horizon when this is inclined, for example, if the animal is on a slope.An extension of this concept is that the eyes of predators typically have a zone of very acute vision at their centre, to assist in the identification of prey. In deep water organisms, it may not be the centre of the eye that is enlarged. The hyperiid amphipods are deep water animals that feed on organisms above them. Their eyes are almost divided into two, with the upper region thought to be involved in detecting the silhouettes of potential prey—or predators—against the faint light of the sky above. Accordingly, deeper water hyperiids, where the light against which the silhouettes must be compared is dimmer, have larger "upper-eyes", and may lose the lower portion of their eyes altogether. In the giant Antarctic isopod Glyptonotus a small ventral compound eye is physically completely separated from the much larger dorsal compound eye. Depth perception can be enhanced by having eyes which are enlarged in one direction; distorting the eye slightly allows the distance to the object to be estimated with a high degree of accuracy.Acuity is higher among male organisms that mate in mid-air, as they need to be able to spot and assess potential mates against a very large backdrop. On the other hand, the eyes of organisms which operate in low light levels, such as around dawn and dusk or in deep water, tend to be larger to increase the amount of light that can be captured.It is not only the shape of the eye that may be affected by lifestyle. Eyes can be the most visible parts of organisms, and this can act as a pressure on organisms to have more transparent eyes at the cost of function.Eyes may be mounted on stalks to provide better all-round vision, by lifting them above an organisms carapace; this also allows them to track predators or prey without moving the head.

Physiology
Visual acuity
Visual acuity, or resolving power, is "the ability to distinguish fine detail" and is the property of cone cells. It is often measured in cycles per degree (CPD), which measures an angular resolution, or how much an eye can differentiate one object from another in terms of visual angles. Resolution in CPD can be measured by bar charts of different numbers of white/black stripe cycles. For example, if each pattern is 1.75 cm wide and is placed at 1 m distance from the eye, it will subtend an angle of 1 degree, so the number of white/black bar pairs on the pattern will be a measure of the cycles per degree of that pattern. The highest such number that the eye can resolve as stripes, or distinguish from a grey block, is then the measurement of visual acuity of the eye.
For a human eye with excellent acuity, the maximum theoretical resolution is 50 CPD (1.2 arcminute per line pair, or a 0.35 mm line pair, at 1 m). A rat can resolve only about 1 to 2 CPD. A horse has higher acuity through most of the visual field of its eyes than a human has, but does not match the high acuity of the human eyes central fovea region.Spherical aberration limits the resolution of a 7 mm pupil to about 3 arcminutes per line pair. At a pupil diameter of 3 mm, the spherical aberration is greatly reduced, resulting in an improved resolution of approximately 1.7 arcminutes per line pair. A resolution of 2 arcminutes per line pair, equivalent to a 1 arcminute gap in an optotype, corresponds to 20/20 (normal vision) in humans.
However, in the compound eye, the resolution is related to the size of individual ommatidia and the distance between neighbouring ommatidia. Physically these cannot be reduced in size to achieve the acuity seen with single lensed eyes as in mammals. Compound eyes have a much lower acuity than vertebrate eyes.

Colour perception
"Colour vision is the faculty of the organism to distinguish lights of different spectral qualities." All organisms are restricted to a small range of electromagnetic spectrum; this varies from creature to creature, but is mainly between wavelengths of 400 and 700 nm.
This is a rather small section of the electromagnetic spectrum, probably reflecting the submarine evolution of the organ: water blocks out all but two small windows of the EM spectrum, and there has been no evolutionary pressure among land animals to broaden this range.The most sensitive pigment, rhodopsin, has a peak response at 500 nm. Small changes to the genes coding for this protein can tweak the peak response by a few nm; pigments in the lens can also filter incoming light, changing the peak response. Many organisms are unable to discriminate between colours, seeing instead in shades of grey; colour vision necessitates a range of pigment cells which are primarily sensitive to smaller ranges of the spectrum. In primates, geckos, and other organisms, these take the form of cone cells, from which the more sensitive rod cells evolved. Even if organisms are physically capable of discriminating different colours, this does not necessarily mean that they can perceive the different colours; only with behavioural tests can this be deduced.Most organisms with colour vision can detect ultraviolet light. This high energy light can be damaging to receptor cells. With a few exceptions (snakes, placental mammals), most organisms avoid these effects by having absorbent oil droplets around their cone cells. The alternative, developed by organisms that had lost these oil droplets in the course of evolution, is to make the lens impervious to UV light—this precludes the possibility of any UV light being detected, as it does not even reach the retina.

Rods and cones
The retina contains two major types of light-sensitive photoreceptor cells used for vision: the rods and the cones.
Rods cannot distinguish colours, but are responsible for low-light (scotopic) monochrome (black-and-white) vision; they work well in dim light as they contain a pigment, rhodopsin (visual purple), which is sensitive at low light intensity, but saturates at higher (photopic) intensities. Rods are distributed throughout the retina but there are none at the fovea and none at the blind spot. Rod density is greater in the peripheral retina than in the central retina.
Cones are responsible for colour vision. They require brighter light to function than rods require. In humans, there are three types of cones, maximally sensitive to long-wavelength, medium-wavelength, and short-wavelength light (often referred to as red, green, and blue, respectively, though the sensitivity peaks are not actually at these colours). The colour seen is the combined effect of stimuli to, and responses from, these three types of cone cells. Cones are mostly concentrated in and near the fovea. Only a few are present at the sides of the retina. Objects are seen most sharply in focus when their images fall on the fovea, as when one looks at an object directly. Cone cells and rods are connected through intermediate cells in the retina to nerve fibres of the optic nerve. When rods and cones are stimulated by light, they connect through adjoining cells within the retina to send an electrical signal to the optic nerve fibres. The optic nerves send off impulses through these fibres to the brain.

Pigmentation
The pigment molecules used in the eye are various, but can be used to define the evolutionary distance between different groups, and can also be an aid in determining which are closely related—although problems of convergence do exist.Opsins are the pigments involved in photoreception. Other pigments, such as melanin, are used to shield the photoreceptor cells from light leaking in from the sides.
The opsin protein group evolved long before the last common ancestor of animals, and has continued to diversify since.There are two types of opsin involved in vision; c-opsins, which are associated with ciliary-type photoreceptor cells, and r-opsins, associated with rhabdomeric photoreceptor cells. The eyes of vertebrates usually contain ciliary cells with c-opsins, and (bilaterian) invertebrates have rhabdomeric cells in the eye with r-opsins. However, some ganglion cells of vertebrates express r-opsins, suggesting that their ancestors used this pigment in vision, and that remnants survive in the eyes. Likewise, c-opsins have been found to be expressed in the brain of some invertebrates. They may have been expressed in ciliary cells of larval eyes, which were subsequently resorbed into the brain on metamorphosis to the adult form. C-opsins are also found in some derived bilaterian-invertebrate eyes, such as the pallial eyes of the bivalve molluscs; however, the lateral eyes (which were presumably the ancestral type for this group, if eyes evolved once there) always use r-opsins. Cnidaria, which are an outgroup to the taxa mentioned above, express c-opsins—but r-opsins are yet to be found in this group </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Hyperparathyroidism and can you explain it in depth? [/INST] Hyperparathyroidism is an increase in parathyroid hormone (PTH) levels in the blood. This occurs from a disorder either within the parathyroid glands (primary hyperparathyroidism) or as response to external stimuli (secondary hyperparathyroidism). Symptoms of hyperparathyroidism are caused by inappropriately normal or elevated blood calcium leaving the bones and flowing into the blood stream in response to increased production of parathyroid hormone. In healthy people, when blood calcium levels are high, parathyroid hormone levels should be low.  With long-standing hyperparathyroidism, the most common symptom is kidney stones. Other symptoms may include bone pain, weakness, depression, confusion, and increased urination. Both primary and secondary may result in osteoporosis (weakening of the bones).In 80% of cases, primary hyperparathyroidism is due to a single benign tumor known as a parathyroid adenoma. Most of the remainder are due to several of these adenomas. Very rarely it may be due to parathyroid cancer. Secondary hyperparathyroidism typically occurs due to vitamin D deficiency, chronic kidney disease, or other causes of low blood calcium. The diagnosis of primary hyperparathyroidism is made by finding elevated calcium and PTH in the blood.Primary hyperparathyroidism may only be cured by removing the adenoma or overactive parathyroid glands. In those without symptoms, mildly increased blood calcium levels, normal kidneys, and normal bone density monitoring may be all that is required. The medication cinacalcet may also be used to decrease PTH levels in those unable to have surgery although it is not a cure. In those with very high blood calcium levels, treatment may include large amounts of intravenous normal saline. Low vitamin D should be corrected in those with secondary hyperparathyroidism but low Vitamin D pre-surgery is controversial for those with primary hyperparathyroidism. Low vitamin D levels should be corrected post-parathyroidectomy.Primary hyperparathyroidism is the most common type. In the developed world, between one and four per thousand people are affected. It occurs three times more often in women than men and is often diagnosed between the ages of 50 and 60 but is not uncommon before then. The disease was first described in the 1700s. In the late 1800s, it was determined to be related to the parathyroid. Surgery as a treatment was first carried out in 1925.

Signs and symptoms
In primary hyperparathyroidism, about 75% of people are "asymptomatic". While most primary patients are asymptomatic at the time of diagnosis, asymptomatic is poorly defined and represents only those without "obvious clinical sequalae" such as kidney stones, bone disease, or hypercalcemic crisis.  These "asymptomatic" patients may have other symptoms such as depression, anxiety, gastrointestinal distress, and neuromuscular problems that are not counted as symptoms.  The problem is often picked up incidentally during blood work for other reasons, and the test results show a higher amount of calcium in the blood than normal. Many people only have non-specific symptoms.Common manifestations of hypercalcemia include weakness and fatigue, depression, bone pain, muscle soreness (myalgias), decreased appetite, feelings of nausea and vomiting, constipation, pancreatitis, polyuria, polydipsia, cognitive impairment, kidney stones (), vertigo and osteopenia or osteoporosis. A history of acquired racquet nails (brachyonychia) may be indicative of bone resorption. Radiographically, hyperparathyroidism has a pathognomic finding of rugger jersey spine.  Parathyroid adenomas are very rarely detectable on clinical examination. Surgical removal of a parathyroid tumor eliminates the symptoms in most patients.In secondary hyperparathyroidism due to lack of Vitamin D absorption, the parathyroid gland is behaving normally; clinical problems are due to bone resorption and manifest as bone syndromes such as rickets, osteomalacia, and renal osteodystrophy.

Causes
Radiation exposure increases the risk of primary hyperparathyroidism. A number of genetic conditions including multiple endocrine neoplasia syndromes also increase the risk. Parathyroid adenomas have been linked with DDT although a causal link has not yet been established.

Mechanism
Normal parathyroid glands measure the ionized calcium (Ca2+) concentration in the blood and secrete parathyroid hormone accordingly; if the ionized calcium rises above normal, the secretion of PTH is decreased, whereas when the Ca2+ level falls, parathyroid hormone secretion is increased.Secondary hyperparathyroidism occurs if the calcium level is abnormally low. The normal glands respond by secreting parathyroid hormone at a persistently high rate. This typically occurs when the 1,25 dihydroxyvitamin D3 levels in the blood are low and  hypocalcemia is present. A lack of 1,25 dihydroxyvitamin D3 can result from a deficient dietary intake of vitamin D, or from a lack of exposure of the skin to sunlight, so the body cannot make its own vitamin D from cholesterol. The resulting hypovitaminosis D is usually due to a partial combination of both factors. Vitamin D3 (or cholecalciferol) is converted to 25-hydroxyvitamin D (or calcidiol) by the liver, from where it is transported via the circulation to the kidneys, and it is converted into the active hormone, 1,25 dihydroxyvitamin D3. Thus, a third cause of secondary hyperparathyroidism is chronic kidney disease. Here the ability to manufacture 1,25 dihydroxyvitamin D3 is compromised, resulting in hypocalcemia.

Diagnosis
The gold standard of diagnosis is the PTH immunoassay. Once an elevated PTH has been confirmed, the goal of diagnosis is to determine whether the hyperparathyroidism is primary or secondary in origin by obtaining a serum calcium level:

Tertiary hyperparathyroidism has a high PTH and high serum calcium.  It is differentiated from primary hyperparathyroidism by a history of chronic kidney failure and secondary hyperparathyroidism.Hyperparathyroidism can cause hyperchloremia and increase renal bicarbonate loss, which may result in a normal anion gap metabolic acidosis.

Differential diagnosis
Familial benign hypocalciuric hypercalcaemia can present with similar lab changes. In this condition, the calcium creatinine clearance ratio, however, is typically under 0.01.

Blood tests
Intact PTH
In primary hyperparathyroidism, parathyroid hormone (PTH) levels are either elevated or "inappropriately normal" in the presence of elevated calcium.  Typically, PTH levels vary greatly over time in the affected patient and (as with Ca and Ca++ levels) must be retested several times to see the pattern.  The currently accepted test for PTH is intact PTH, which detects only relatively intact and biologically active PTH molecules. Older tests often detected other, inactive fragments. Even intact PTH may be inaccurate in patients with kidney dysfunction. Intact pth blood tests may be falsely low if biotin has been ingested in the previous few days prior to the blood test.

Calcium levels
In cases of primary hyperparathyroidism or tertiary hyperparathyroidism, heightened PTH leads to increased serum calcium (hypercalcemia) due to:
increased bone resorption, allowing the flow of calcium from bone to blood
reduced kidney clearance of calcium
increased intestinal calcium absorption

Serum phosphate
In primary hyperparathyroidism, serum phosphate levels are abnormally low as a result of decreased reabsorption of phosphate in the kidney tubules. However, this is only present in about 50% of cases. This contrasts with secondary hyperparathyroidism, in which serum phosphate levels are generally elevated because of kidney disease.

Alkaline phosphatase
Alkaline phosphatase levels are usually elevated in hyperparathyroidism. In primary hyperparathyroidism, levels may remain within the normal range, but this is inappropriately normal given the increased levels of plasma calcium.

Nuclear medicine
A technetium sestamibi scan is a procedure in nuclear medicine that identifies hyperparathyroidism (or parathyroid adenoma). It is used by surgeons to locate ectopic parathyroid adenomas, most commonly found in the anterior mediastinum.

Classification
Primary
Primary hyperparathyroidism results from a hyperfunction of the parathyroid glands themselves. The oversecretion of PTH is due to a parathyroid adenoma, parathyroid hyperplasia, or rarely, a parathyroid carcinoma. This disease is often characterized by the quartet stones, bones, groans, and psychiatric overtones referring to the presence of kidney stones, hypercalcemia, constipation, and peptic ulcers, as well as depression, respectively.In a minority of cases, this occurs as part of a multiple endocrine neoplasia (MEN) syndrome, either type 1 (caused by a mutation in the gene MEN1) or type 2a (caused by a mutation in the gene RET), which is also associated with the adrenal tumor pheochromcytoma. Other mutations that have been linked to parathyroid neoplasia include mutations in the genes HRPT2  and CASR.Patients with bipolar disorder who are receiving long-term lithium treatment are at increased risk for hyperparathyroidism. Elevated calcium levels are found in 15% to 20% of patients who have been taking lithium long-term. However, only a few of these patients have significantly elevated levels of parathyroid hormone and clinical symptoms of hyperparathyroidism. Lithium-associated hyperparathyroidism is usually caused by a single parathyroid adenoma.

Secondary
Secondary hyperparathyroidism is due to physiological (i.e. appropriate) secretion of parathyroid hormone (PTH) by the parathyroid glands in response to hypocalcemia (low blood calcium levels). The most common causes are vitamin D deficiency (caused by lack of sunlight, diet or malabsorption) and chronic kidney failure.Lack of vitamin D leads to reduced calcium absorption by the intestine leading to hypocalcemia and increased parathyroid hormone secretion. This increases bone resorption.
In chronic kidney failure the problem is more specifically failure to convert vitamin D to its active form in the kidney. The bone disease in secondary hyperparathyroidism caused by kidney failure is termed renal osteodystrophy.

Tertiary
Tertiary hyperparathyroidism is seen in those with long-term secondary hyperparathyroidism, which eventually leads to hyperplasia of the parathyroid glands and a loss of response to serum calcium levels. This disorder is most often seen in patients with end-stage kidney disease and is an autonomous activity.

Treatment
Treatment depends on the type of hyperparathyroidism encountered.

Primary
People with primary hyperparathyroidism who are symptomatic benefit from parathyroidectomy—surgery to remove the parathyroid tumor (parathyroid adenoma). Indications for surgery are:
Symptomatic hyperparathyroidism
Asymptomatic hyperparathyroidism with any of the following:
24-hour urinary calcium > 400 mg (see footnote, below)
serum calcium > 1 mg/dl above upper limit of normal
Creatinine clearance > 30% below normal for patients age
Bone density > 2.5 standard deviations below peak (i.e., T-score of −2.5)
People age < 50A 2020 Cochrane systematic review compared the surgical procedures of minimally invasive parathyroidectomy and classically used bilateral neck exploration, however it did not find one approach to be superior to the other in either benefits or risks.Surgery can rarely result in hypoparathyroidism.

Secondary
In people with secondary hyperparathyroidism, the high PTH levels are an appropriate response to low calcium and treatment must be directed at the underlying cause of this (usually vitamin D deficiency or chronic kidney failure) </s>


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


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


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Klumpke paralysis and can you explain it in depth? [/INST] Klumpkes paralysis is a variety of partial palsy of the lower roots of the brachial plexus. The brachial plexus is a network of spinal nerves that originates in the back of the neck, extends through the axilla (armpit), and gives rise to nerves to the upper limb. The paralytic condition is named after Augusta Déjerine-Klumpke.

Signs and symptoms
Symptoms include intrinsic minus hand deformity, paralysis of intrinsic hand muscles, and C8/T1 Dermatome distribution numbness. Involvement of T1 may result in Horners syndrome, with ptosis, and miosis. Weakness or lack of ability to use specific muscles of the shoulder or arm. It can be contrasted to Erb-Duchennes palsy, which affects C5 and C6.

Cause
Klumpkes paralysis is a form of paralysis involving the muscles of the forearm and hand, resulting from a brachial plexus injury in which the eighth cervical (C8) and first thoracic (T1) nerves are injured either before or after they have joined to form the lower trunk. The subsequent paralysis affects, principally, the intrinsic muscles of the hand (notably the interossei, thenar and hypothenar muscles) and the flexors of the wrist and fingers (notably flexor carpi ulnaris and ulnar half of the flexor digitorum profundus). The classic presentation of Klumpkes palsy is the “claw hand” where the forearm is supinated, the wrist extended and the fingers flexed </s>


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


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Aspergillosis and can you explain it in depth? [/INST] Aspergillosis is a fungal infection of usually the lungs, caused by the genus Aspergillus, a common mould that is breathed in frequently from the air around, but does not usually affect most people. It generally occurs in people with lung diseases such as asthma, cystic fibrosis or tuberculosis, or those who have had a stem cell or organ transplant, and those who cannot fight infection because of medications they take such as steroids and some cancer treatments. Rarely, it can affect skin.Aspergillosis occurs in humans, birds and other animals. Aspergillosis occurs in chronic or acute forms which are clinically very distinct. Most cases of acute aspergillosis occur in people with severely compromised immune systems, e.g. those undergoing bone marrow transplantation. Chronic colonization or infection can cause complications in people with underlying respiratory illnesses, such as asthma, cystic fibrosis, sarcoidosis, tuberculosis, or chronic obstructive pulmonary disease. Most commonly, aspergillosis occurs in the form of chronic pulmonary aspergillosis (CPA), aspergilloma, or allergic bronchopulmonary aspergillosis (ABPA). Some forms are intertwined; for example ABPA and simple aspergilloma can progress to CPA.
Other, noninvasive manifestations include fungal sinusitis (both allergic in nature and with established fungal balls), otomycosis (ear infection), keratitis (eye infection), and onychomycosis (nail infection). In most instances, these are less severe, and curable with effective antifungal treatment.
The most frequently identified pathogens are Aspergillus fumigatus and Aspergillus flavus, ubiquitous organisms capable of living under extensive environmental stress. Most people are thought to inhale thousands of Aspergillus spores daily but without effect due to an efficient immune response. Taken together, the major chronic, invasive, and allergic forms of aspergillosis account for around 600,000 deaths annually worldwide.

Signs and symptoms
A fungus ball in the lungs may cause no symptoms and may be discovered only with a chest X-ray, or it may cause repeated coughing up of blood, chest pain, and occasionally severe, even fatal, bleeding. A rapidly invasive Aspergillus infection in the lungs often causes cough, fever, chest pain, and difficulty breathing.
Poorly controlled aspergillosis can disseminate through the blood to cause widespread organ damage. Symptoms include fever, chills, shock, delirium, seizures, and blood clots. The person may develop kidney failure, liver failure (causing jaundice), and breathing difficulties. Death can occur quickly.
Aspergillosis of the ear canal causes itching and occasionally pain. Fluid draining overnight from the ear may leave a stain on the pillow. Aspergillosis of the sinuses causes a feeling of congestion and sometimes pain or discharge. It can extend beyond the sinuses.In addition to the symptoms, an X-ray or computerised tomography (CT) scan of the infected area provides clues for making the diagnosis. Whenever possible, a doctor sends a sample of infected material to a laboratory to confirm identification of the fungus.

Cause
Aspergillosis is caused by Aspergillus, a common mold, which tends to affect people who already have a lung disease such as cystic fibrosis or asthma, or who cannot fight infection themselves. The most common causative species is Aspergillus fumigatus.

Risk factors
People who are immunocompromised — such as patients undergoing hematopoietic stem cell transplantation, chemotherapy for leukaemia, or AIDS — are at an increased risk for invasive aspergillosis infections. These people may have neutropenia or corticoid-induced immunosuppression as a result of medical treatments. Neutropenia is often caused by extremely cytotoxic medications such as cyclophosphamide. Cyclophosphamide interferes with cellular replication including that of white blood cells such as neutrophils. A decreased neutrophil count inhibits the ability of the body to mount immune responses against pathogens. Although tumor necrosis factor alpha (TNF-α) — a signaling molecule related to acute inflammation responses — is produced, the abnormally low number of neutrophils present in neutropenic patients leads to a depressed inflammatory response.
If the underlying neutropenia is not fixed, rapid and uncontrolled hyphal growth of the invasive fungi will occur and result in negative health outcomes. In addition to decreased neutrophil degranulation, the antiviral response against Flu and SARS-CoV-2 viruses, mediated by type I and type II interferon, is diminished jointly with the local antifungal immune response measured in the lungs of patients with IAPA (Influenza-Associated Pulmonary Aspergillosis) and CAPA (COVID-19-Associated Pulmonary Aspergillosis).

Diagnosis
On chest X-ray and CT, pulmonary aspergillosis classically manifests as a halo sign, and later, an air crescent sign.
In hematologic patients with invasive aspergillosis, the galactomannan test can make the diagnosis in a noninvasive way. False-positive Aspergillus galactomannan tests have been found in patients on intravenous treatment with some antibiotics or fluids containing gluconate or citric acid such as some transfusion platelets, parenteral nutrition, or PlasmaLyte.On microscopy, Aspergillus species are reliably demonstrated by silver stains, e.g., Gridley stain or Gomori methenamine-silver. These give the fungal walls a gray-black colour. The hyphae of Aspergillus species range in diameter from 2.5 to 4.5 μm. They have septate hyphae, but these are not always apparent, and in such cases they may be mistaken for Zygomycota. Aspergillus hyphae tend to have dichotomous branching that is progressive and primarily at acute angles of around 45°.

Prevention
Prevention of aspergillosis involves a reduction of mold exposure via environmental infection-control. Antifungal prophylaxis can be given to high-risk patients. Posaconazole is often given as prophylaxis in severely immunocompromised patients.

Screening
A systematic review has evaluated the diagnostic accuracy of polymerase chain reaction (PCR) tests in people with defective immune systems from medical treatment such as chemotherapy. Evidence suggests PCR tests have moderate diagnostic accuracy when used for screening for invasive aspergillosis in high risk groups. CT and MRI are vital to diagnosis, however it is always highly recommended to under go a biopsy of the area to confirm a diagnosis.

Treatment
The current medical treatments for aggressive invasive aspergillosis include voriconazole and liposomal amphotericin B in combination with surgical debridement.
For the less aggressive allergic bronchopulmonary aspergillosis, findings suggest the use of oral steroids for a prolonged period of time, preferably for 6–9 months in allergic aspergillosis of the lungs. Itraconazole is given with the steroids, as it is considered to have a "steroid-sparing" effect, causing the steroids to be more effective, allowing a lower dose.
Other drugs used, such as amphotericin B, caspofungin (in combination therapy only), flucytosine (in combination therapy only), or itraconazole,
are used to treat this fungal infection. However, a growing proportion of infections are resistant to the triazoles. A. fumigatus, the most commonly infecting species, is intrinsically resistant to fluconazole.

Epidemiology
Aspergillosis is thought to affect more than  14 million people worldwide, with allergic bronchopulmonary aspergillosis (ABPA, >4 million), severe asthma with fungal sensitization (>6.5 million), and chronic pulmonary aspergillosis (CPA, ~3 million) being considerably more prevalent than invasive aspergillosis (IA, >300,000). Other common conditions include Aspergillus bronchitis, Aspergillus rhinosinusitis (many millions), otitis externa, and  Aspergillus onychomycosis (10 million). Alterations in the composition and function of the lung microbiome and mycobiome have been associated with an increasing number of chronic pulmonary diseases such as COPD, cystic fibrosis, chronic rhinosinusitis and asthma.

Society and culture
During the COVID-19 pandemic 2020/21, COVID-19-associated pulmonary aspergillosis was reported in some people who had been admitted to hospital and received longterm steroid treatment.

Animals
While relatively rare in humans, aspergillosis is a common and dangerous infection in birds, particularly in pet parrots.  Mallards and other ducks are particularly susceptible, as they often resort to poor food sources during bad weather </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Metabolic disorder and can you explain it in depth? [/INST] A metabolic disorder is a disorder that negatively alters the bodys processing and distribution of macronutrients, such as proteins, fats, and carbohydrates. Metabolic disorders can happen when abnormal chemical reactions in the body alter the normal metabolic process. It can also be defined as inherited single gene anomaly, most of which are autosomal recessive.

Signs and symptoms
Some of the symptoms that can occur with metabolic disorders are lethargy, weight loss, jaundice and seizures. The symptoms expressed would vary with the type of metabolic disorder. There are four categories of symptoms: acute symptoms, late-onset acute symptoms, progressive general symptoms and permanent symptoms.

Causes
Inherited metabolic disorders are one cause of metabolic disorders, and occur when a defective gene causes an enzyme deficiency. These diseases, of which there are many subtypes, are known as inborn errors of metabolism. Metabolic diseases can also occur when the liver or pancreas do not function properly.

Types
The principal classes of metabolic disorders are:

Diagnosis
Metabolic disorders can be present at birth, and many can be identified by routine screening. If a metabolic disorder is not identified early, then it may be diagnosed later in life, when symptoms appear. Specific blood and DNA tests can be done to diagnose genetic metabolic disorders.The gut microbiota, which is a population of microbes that live in the human digestive system, also has an important part in metabolism and generally has a positive function for its host. In terms of pathophysiological/mechanism interactions, an abnormal gut microbiota can play a role in metabolic disorder related obesity.

Screening
Metabolic disorder screening can be done in newborns via blood, skin, or hearing tests.

Management
Metabolic disorders can be treatable by nutrition management, especially if detected early. It is important for dieticians to have knowledge of the genotype to create a treatment that will be more effective for the individual.

See also
Metabolic syndrome
Metabolic Myopathies
Lysosomal storage disease
Deficiency disease
Hypermetabolism

References
Further reading
Hoffmann, Georg F.; Zschocke, Johannes; Nyhan, William L. (21 November 2009). Inherited Metabolic Diseases: A Clinical Approach. Springer </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Weakness and can you explain it in depth? [/INST] Weakness is a symptom of a number of different conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, including muscular dystrophy and inflammatory myopathy. It occurs in neuromuscular junction disorders, such as myasthenia gravis.

Pathophysiology
Muscle cells work by detecting a flow of electrical impulses from the brain, which signals them to contract through the release of calcium by the sarcoplasmic reticulum. Fatigue (reduced ability to generate force) may occur due to the nerve, or within the muscle cells themselves. New research from scientists at Columbia University suggests that muscle fatigue is caused by calcium leaking out of the muscle cell. This makes less calcium available for the muscle cell. In addition, the Columbia researchers propose that an enzyme activated by this released calcium eats away at muscle fibers.Substrates within the muscle generally serve to power muscular contractions. They include molecules such as adenosine triphosphate (ATP), glycogen and creatine phosphate. ATP binds to the myosin head and causes the ratchetting that results in contraction according to the sliding filament model. Creatine phosphate stores energy so ATP can be rapidly regenerated within the muscle cells from adenosine diphosphate (ADP) and inorganic phosphate ions, allowing for sustained powerful contractions that last between 5–7 seconds. Glycogen is the intramuscular storage form of glucose, used to generate energy quickly once intramuscular creatine stores are exhausted, producing lactic acid as a metabolic byproduct. Contrary to common belief, lactic acid accumulation doesnt actually cause the burning sensation felt when people exhaust their oxygen and oxidative metabolism, but in actuality, lactic acid in presence of oxygen recycles to produce pyruvate in the liver, which is known as the Cori cycle.Substrates produce metabolic fatigue by being depleted during exercise, resulting in a lack of intracellular energy sources to fuel contractions. In essence, the muscle stops contracting because it lacks the energy to do so.

Differential diagnosis
True vs. perceived weakness
True weakness (or neuromuscular) describes a condition where the force exerted by the muscles is less than would be expected, for example muscular dystrophy.
Perceived weakness (or non-neuromuscular) describes a condition where a person feels more effort than normal is required to exert a given amount of force but actual muscle strength is normal, for example chronic fatigue syndrome.In some conditions, such as myasthenia gravis, muscle strength is normal when resting, but true weakness occurs after the muscle has been subjected to exercise. This is also true for some cases of chronic fatigue syndrome, where objective post-exertion muscle weakness with delayed recovery time has been measured and is a feature of some of the published definitions.

Asthenia vs. myasthenia
Asthenia (Greek: ἀσθένεια, lit lack of strength but also disease) is a medical term referring to a condition in which the body lacks or has lost strength either as a whole or in any of its parts. It denotes symptoms of physical weakness and loss of strength. General asthenia occurs in many chronic wasting diseases (such as tuberculosis and cancer), sleep disorders or chronic disorders of the heart, lungs or kidneys, and is probably most marked in diseases of the adrenal gland. Asthenia may be limited to certain organs or systems of organs, as in asthenopia, characterized by ready fatiguability. Asthenia is also a side effect of some medications and treatments, such as Ritonavir (a protease inhibitor used in HIV treatment). Differentiating psychogenic (perceived) asthenia and true asthenia from myasthenia is often difficult, and in time apparent psychogenic asthenia accompanying many chronic disorders is seen to progress into a primary weakness.Myasthenia (my- from Greek μυο meaning "muscle" + -asthenia ἀσθένεια meaning "weakness"), or simply muscle weakness, is a lack of muscle strength. The causes are many and can be divided into conditions that have either true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, including muscular dystrophy and inflammatory myopathy. It occurs in neuromuscular diseases, such as myasthenia gravis.

Types
Muscle fatigue can be central, neuromuscular, or peripheral muscular. Central muscle fatigue manifests as an overall sense of energy deprivation, and peripheral muscle weakness manifests as a local, muscle-specific inability to do work. Neuromuscular fatigue can be either central or peripheral.

Central fatigue
The central fatigue is generally described in terms of a reduction in the neural drive or nerve-based motor command to working muscles that results in a decline in the force output.  It has been suggested that the reduced neural drive during exercise may be a protective mechanism to prevent organ failure if the work was continued at the same intensity. The exact mechanisms of central fatigue are unknown, though there has been considerable interest in the role of serotonergic pathways.

Neuromuscular fatigue
Nerves control the contraction of muscles by determining the number, sequence, and force of muscular contraction. When a nerve experiences synaptic fatigue it becomes unable to stimulate the muscle that it innervates. Most movements require a force far below what a muscle could potentially generate, and barring pathology, neuromuscular fatigue is seldom an issue.For extremely powerful contractions that are close to the upper limit of a muscles ability to generate force, neuromuscular fatigue can become a limiting factor in untrained individuals. In novice strength trainers, the muscles ability to generate force is most strongly limited by nerves ability to sustain a high-frequency signal. After an extended period of maximum contraction, the nerves signal reduces in frequency and the force generated by the contraction diminishes. There is no sensation of pain or discomfort, the muscle appears to simply stop listening and gradually cease to move, often lengthening. As there is insufficient stress on the muscles and tendons, there will often be no delayed onset muscle soreness following the workout.  Part of the process of strength training is increasing the nerves ability to generate sustained, high frequency signals which allow a muscle to contract with their greatest force </s>


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


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Allergic contact dermatitis and can you explain it in depth? [/INST] Allergic contact dermatitis (ACD) is a form of contact dermatitis that is the manifestation of an allergic response caused by contact with a substance; the other type being irritant contact dermatitis (ICD).
Although less common than ICD, ACD is accepted to be the most prevalent form of immunotoxicity found in humans. By its allergic nature, this form of contact dermatitis is a hypersensitive reaction that is atypical within the population. The mechanisms by which these reactions occur are complex, with many levels of fine control. Their immunology centres on the interaction of immunoregulatory cytokines and discrete subpopulations of T lymphocytes.

Signs and symptoms
The symptoms of allergic contact dermatitis are very similar to the ones caused by irritant contact dermatitis, which makes the first even harder to diagnose. The first sign of allergic contact dermatitis is the presence of the rash or skin lesion at the site of exposure. Depending on the type of allergen causing it, the rash can ooze, drain or crust and it can become raw, scaled or thickened. Also, it is possible that the skin lesion does not take the form of a rash but it may include papules, blisters, vesicles or even a simple red area. The main difference between the rash caused by allergic contact dermatitis and the one caused by irritant contact dermatitis is that the latter tends to be confined to the area where the trigger touched the skin, whereas in allergic contact dermatitis the rash is more likely to be more widespread on the skin.  Another characteristic of the allergic contact dermatitis rash is that it usually appears after a day or two after exposure to the allergen, unlike irritant contact dermatitis that appears immediately after the contact with the trigger.
Other symptoms may include itching, skin redness or inflammation, localized swelling and the area may become more tender or warmer. If left untreated, the skin may darken and become leathery and cracked. Pain can also be present. Dermatitis can occur anywhere on the skin, but is most common on the hands (22% of people), scattered across the body (18%), or on the face (17%).The rash and other symptoms typically occur 24 to 48 hours after the exposure; in some cases, the rash may persist for weeks.  Once an individual has developed a skin reaction to a certain substance it is most likely that they will have it for the rest of their life, and the symptoms will reappear when in contact with the allergen.

Cause
Common allergens implicated include the following:

Bacitracin – topical antibiotic found by itself, or as Polysporin or Triple Antibiotic
Balsam of Peru (Myroxylon pereirae) – used in food and drink for flavoring, in perfumes and toiletries for fragrance, and in medicine and pharmaceutical items for healing properties; derived from tree resin.  It may also be a component of artificial vanilla and/or cinnamon flavorings.
Chromium – used in the tanning of leather.  Also a component of uncured cement/mortar, facial cosmetics and some bar soaps.
Cobalt chloride – metal found in medical products; hair dye; antiperspirant; metal-plated objects such as snaps, buttons or tools; and in cobalt blue pigment
Colophony (Rosin) – rosin, sap or sawdust typically from spruce or fir trees
Formaldehyde – preservative with multiple uses, e.g., in paper products, paints, medications, household cleaners, cosmetic products, and fabric finishes.  Often released into products by the use of formaldehyde releasers such as imidazolidinyl urea, diazolidinyl urea, Quaternium-15, DMDM Hydantoin, and 2-bromo-2-nitropropane-1,3-diol.
Fragrance mix – group of the eight most common fragrance allergens found in foods, cosmetic products, insecticides, antiseptics, soaps, perfumes, and dental products
Gold (gold sodium thiosulfate) – precious metal and compound often found in jewelry and dental materials
Isothiazolinones – preservatives used in many personal care, household, and commercial products.
Mercaptobenzothiazole – in rubber products, notably shoes, gloves, and car tires.
Neomycin – topical antibiotic common in first aid creams and ointments, cosmetics, deodorant, soap, and pet food.  Found by itself, or in Neosporin or Triple Antibiotic
Nickel (nickel sulfate hexahydrate) – has been recognized as a significant cause of allergy.  This metal is frequently encountered in stainless steel cookware, jewelry and clasps or buttons on clothing. Current estimates gauge are that roughly 2.5 million US adults and 250,000 children suffer from nickel allergy, which costs an estimated $5.7 billion per year for treatment of symptoms. A significant portion of nickel allergy is preventable.
p-Phenylenediamine (PPD) - although its mainly used as a component of engineering polymers and composites like kevlar, it is also an ingredient in hair dyes which once sensitized to, becomes lifelong. One can develop active sensitization to products, including but not limited to black clothing, various inks, hair dye, dyed fur, dyed leather, and certain photographic products.
Photographic developers, especially those containing metol
Quaternium-15 – preservative in cosmetic products (self-tanners, shampoo, nail polish, sunscreen) and in industrial products (polishes, paints and waxes).
Sap from certain species of mangrove and agave
Soluble salts of platinum – see platinosis
Thiomersal – mercury compound used in local antiseptics and in vaccines
Topical anesthetics – such as pramoxine or diphenhydramine, after prolonged use
Topical steroid – see steroid allergy
Urushiol – oily coating from plants of Toxicodendron genus –  poison ivy, poison oak, and poison sumac. Also found in mango plants, mango skin, cashews, and smoke from burning urushiol-containing plants, which can cause skin as well as severe lung irritation.

Mechanism
ACD arises as a result of two essential stages: an induction phase, which primes and sensitizes the immune system for an allergic response, and an elicitation phase, in which this response is triggered. As it involves a cell-mediated allergic response, ACD is termed a Type IV delayed hypersensitivity reaction, making it an exception in the usage of the designation "allergic," which otherwise usually refers to type I hypersensitivity reactions.
Contact allergens are essentially soluble haptens (low in molecular weight) and, as such, have the physico-chemical properties that allow them to cross the stratum corneum of the skin. They can only cause their response as part of a complete antigen, involving their association with epidermal proteins forming hapten-protein conjugates. This, in turn, requires them to be protein-reactive.
The conjugate formed is then recognized as a foreign body by the Langerhans cells (LCs) (and in some cases other Dendritic cells (DCs)), which then internalize the protein; transport it via the lymphatic system to the regional lymph nodes; and present the antigen to T-lymphocytes. This process is controlled by cytokines and chemokines – with tumor necrosis factor alpha (TNF-α) and certain members of the interleukin family (1, 13 and 18) – and their action serves either to promote or to inhibit the mobilization and migration of these LCs. As the LCs are transported to the lymph nodes, they become differentiated and transform into DCs, which are immunostimulatory in nature.
Once within the lymph glands, the differentiated DCs present the allergenic epitope associated with the allergen to T lymphocytes. These T cells then divide and differentiate, clonally multiplying so that if the allergen is experienced again by the individual, these T cells will respond more quickly and more aggressively.
White et al. have suggested that there appears to be a threshold to the mechanisms of allergic sensitisation by ACD-associated allergens (1986). This is thought to be linked to the level at which the toxin induces the up-regulation of the required mandatory cytokines and chemokines. It has also been proposed that the vehicle in which the allergen reaches the skin could take some responsibility in the sensitisation of the epidermis by both assisting the percutaneous penetration and causing some form of trauma and mobilization of cytokines itself.

Memory response
Once an individual is sensitized to an allergen, future contacts with the allergen can trigger a reaction, commonly known as a memory response, in the original site of sensitization.  So for example if a person has an allergic contact dermatitis on the eyelids, say from use of makeup, touching the contact allergen with the fingers can trigger an allergic reaction on the eyelids.This is due to local skin memory T-cells, which remain in the original sensitization site.  In a similar fashion, cytotoxic T lymphocytes patrol an area of skin and play an important role in controlling both the reactivation of viruses (such as the "cold sore" virus) and in limiting its replication when reactivated.  Memory response, or "Retest Reactivity", usually takes 2 to 3 days after coming in contact with the allergen, and can persist for 2 to 4 weeks.

Diagnosis
Diagnosing allergic contact dermatitis is primarily based on physical exam and medical history. In some cases doctors can establish an accurate diagnosis based on the symptoms that the patient experiences and on the rashs appearance. In the case of a single episode of allergic contact dermatitis, this is all that is necessary.  Chronic and/or intermittent rashes which are not readily explained by history and physical exam often will benefit from further testing.

A patch test (contact delayed hypersensitivity allergy test) is a commonly used examination to determine the exact cause of an allergic contact dermatitis.  According to the American Academy of Allergy, Asthma, and Immunology, "patch testing is the gold standard for contact allergen identification".The patch test consists of applying small quantities of potential allergens to small patches and which are then placed on the skin. After two days, they are removed and if a skin reaction occurred to one of the substances applied, a raised bump will be noticeable underneath the patch.  The tests are again read at 72 or 96 hours after application.
Patch testing is used for patients who have chronic, recurring contact dermatitis. Other tests that may be used to diagnose contact dermatitis and rule out other potential causes of the symptoms include a skin biopsy and culture of the skin lesion.

Treatment
The clinical expression of the dermatitis can be mitigated by avoidance of the allergen.  Through compliance with avoidance measures, the immune system can become less stimulated.  The key to avoidance is proper evaluation and detection of the inciting allergen. However, once the immune system registers the allergen, the recognition is permanent.
The first step in treating the condition is appropriate recognition of the clinical problem, followed by identification of the culprit chemical and the source of that chemical. Corticosteroid creams should be used carefully and according to the prescribed directions because when overused over longer periods of time they can cause thinning of the skin. Also, in some instances such as poison ivy dermatitis calamine lotion and cool oatmeal baths may relieve itching.Usually, severe cases are treated with systemic corticosteroids which may be tapered gradually, with various dosing schedules ranging from a total of 12 – 20 days to prevent the recurrence of the rash (while the chemical allergen is still in the skin, up to 3 weeks, as well as a topical corticosteroid. Tacrolimus ointment or pimecrolimus cream can also be used additionally to the corticosteroid creams or instead of these. Oral antihistamines such as diphenhydramine or hydroxyzine may also be used in more severe cases to relieve the intense itching via sedation. Topical antihistamines are not advised as there might be a second skin reaction (treatment associated contact dermatitis) from the lotion itself.
The other symptoms caused by allergic contact dermatitis may be eased with cool compresses to stop the itching. It is vital for treatment success that the trigger be identified and avoided </s>


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


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is 3 and can you explain it in depth? [/INST] 3 (three) is a number, numeral and digit. It is the natural number following 2 and preceding 4, and is the smallest odd prime number and the only prime preceding a square number. It has religious or cultural significance in many societies.

Evolution of the Arabic digit
The use of three lines to denote the number 3 occurred in many writing systems, including some (like Roman and Chinese numerals) that are still in use. That was also the original representation of 3 in the Brahmic (Indian) numerical notation, its earliest forms aligned vertically.  However, during the Gupta Empire the sign was modified by the addition of a curve on each line. The Nāgarī script rotated the lines clockwise, so they appeared horizontally, and ended each line with a short downward stroke on the right. In cursive script, the three strokes were eventually connected to form a glyph resembling a ⟨3⟩ with an additional stroke at the bottom: ३.
The Indian digits spread to the Caliphate in the 9th century.  The bottom stroke was dropped around the 10th century in the western parts of the Caliphate, such as the Maghreb and Al-Andalus, when a distinct variant ("Western Arabic") of the digit symbols developed, including modern Western 3.  In contrast, the Eastern Arabs retained and enlarged that stroke, rotating the digit once more to yield the modern ("Eastern") Arabic digit "٣".In most modern Western typefaces, the digit 3, like the other decimal digits, has the height of a capital letter, and sits on the baseline.  In typefaces with text figures, on the other hand, the glyph usually has the height of a lowercase letter "x" and a descender: "". In some French text-figure typefaces, though, it has an ascender instead of a descender.

A common graphic variant of the digit three has a flat top, similar to the letter Ʒ (ezh). This form is sometimes used to prevent falsifying a 3 as an 8. It is found on UPC-A barcodes and standard 52-card decks.

Mathematics
3 is the second smallest prime number and the first odd prime number. It is the first unique prime, such that the period length value of 1 of the decimal expansion of its reciprocal, 0.333..., is unique. 3 is a twin prime with 5, and a cousin prime with 7, and the only known number

        n

    {\displaystyle n}
   such that

        n

    {\displaystyle n}
  ! - 1 and

        n

    {\displaystyle n}
  ! + 1 are prime, as well as the only prime number

        p

    {\displaystyle p}
   such that

        p

    {\displaystyle p}
   - 1 yields another prime number, 2. A triangle is made of three sides. It is the smallest non-self-intersecting polygon and the only polygon not to have proper diagonals. When doing quick estimates, 3 is a rough approximation of π, 3.1415..., and a very rough approximation of e, 2.71828...
3 is the first Mersenne prime, as well as the second Mersenne prime exponent and the second double Mersenne prime exponent, for 7 and 127, respectively. 3 is also the first of five known Fermat primes, which include 5, 17, 257, and 65537. It is the second Fibonacci prime (and the second Lucas prime), the second Sophie Germain prime, the third Harshad number in base 10, and the second factorial prime, as it is equal to 2! + 1.
3 is the second and only prime triangular number, and Gauss proved that every integer is the sum of at most 3 triangular numbers.
3 is the number of non-collinear points needed to determine a plane and a circle.
Three is the only prime which is one less than a perfect square. Any other number which is

          n

            2

    {\displaystyle n^{2}}
   − 1 for some integer

        n

    {\displaystyle n}
   is not prime, since it is (

        n

    {\displaystyle n}
   − 1)(

        n

    {\displaystyle n}
   + 1). This is true for 3 as well (with

        n

    {\displaystyle n}
   = 2), but in this case the smaller factor is 1. If

        n

    {\displaystyle n}
   is greater than 2, both

        n

    {\displaystyle n}
   − 1 and

        n

    {\displaystyle n}
   + 1 are greater than 1 so their product is not prime.
A natural number is divisible by three if the sum of its digits in base 10 is divisible by 3. For example, the number 21 is divisible by three (3 times 7) and the sum of its digits is 2 + 1 = 3. Because of this, the reverse of any number that is divisible by three (or indeed, any permutation of its digits) is also divisible by three. For instance, 1368 and its reverse 8631 are both divisible by three (and so are 1386, 3168, 3186, 3618, etc.). See also Divisibility rule. This works in base 10 and in any positional numeral system whose base divided by three leaves a remainder of one (bases 4, 7, 10, etc.).
Three of the five Platonic solids have triangular faces – the tetrahedron, the octahedron, and the icosahedron. Also, three of the five Platonic solids have vertices where three faces meet – the tetrahedron, the hexahedron (cube), and the dodecahedron. Furthermore, only three different types of polygons comprise the faces of the five Platonic solids – the triangle, the square, and the pentagon.
There are only three distinct 4×4 panmagic squares.
According to Pythagoras and the Pythagorean school, the number 3, which they called triad, is the noblest of all digits, as it is the only number to equal the sum of all the terms below it, and the only number whose sum with those below equals the product of them and itself.There are three finite convex uniform polytope groups in three dimensions, aside from the infinite families of prisms and antiprisms: the tetrahedral group, the octahedral group, and the icosahedral group. In dimensions

        n

    {\displaystyle n}
   ⩾ 5, there are only three regular polytopes: the

        n

    {\displaystyle n}
  -simplexes,

        n

    {\displaystyle n}
  -cubes, and

        n

    {\displaystyle n}
  -orthoplexes. In dimensions

        n

    {\displaystyle n}
   ⩾ 9, the only three uniform polytope families, aside from the numerous infinite proprismatic families, are the

            A

            n

    {\displaystyle \mathrm {A} _{n}}
   simplex,

            B

            n

    {\displaystyle \mathrm {B} _{n}}
   cubic, and

            D

            n

    {\displaystyle \mathrm {D} _{n}}
   demihypercubic families. For paracompact hyperbolic honeycombs, there are three groups in dimensions 6 and 9, or equivalently of ranks 7 and 10, with no other forms in higher dimensions. Of the final three groups, the largest and most important is

                T
                ¯

            9

    {\displaystyle {\bar {T}}_{9}}
  , that is associated with an important Kac–Moody Lie algebra

            E

            10

    {\displaystyle \mathrm {E} _{10}}
  .The trisection of the angle was one of the three famous problems of antiquity.

Numeral systems
There is some evidence to suggest that early man may have used counting systems which consisted of "One, Two, Three" and thereafter "Many" to describe counting limits. Early peoples had a word to describe the quantities of one, two, and three but any quantity beyond was simply denoted as "Many". This is most likely based on the prevalence of this phenomenon among people in such disparate regions as the deep Amazon and Borneo jungles, where western civilizations explorers have historical records of their first encounters with these indigenous people.

List of basic calculations
Science
The Roman numeral III stands for giant star in the Yerkes spectral classification scheme.
Three is the atomic number of lithium.
Three is the ASCII code of "End of Text".
Three is the number of dimensions that humans can perceive. Humans perceive the universe to have three spatial dimensions, but some theories, such as string theory, suggest there are more.
Three is the number of elementary fermion generations according to the Standard Model of particle physics.
The triangle, a polygon with three edges and three vertices, is the most stable physical shape. For this reason it is widely utilized in construction, engineering and design.
The ability of the human eye to distinguish colors is based upon the varying sensitivity of different cells in the retina to light of different wavelengths. Humans being trichromatic, the retina contains three types of color receptor cells, or cones.
There are three primary colors in the additive and subtractive models.

Protoscience
In European alchemy, the three primes (Latin: tria prima) were salt (), sulfur () and mercury ().
The three doshas (weaknesses) and their antidotes are the basis of Ayurvedic medicine in India.

Pseudoscience
Three is the symbolic representation for Mu, Augustus Le Plongeons and James Churchwards lost continent.
In Pythagorean numerology the number 3 is the digit that represents the communication. It encourages the expansion of creativity, sociability between people and movement. For Pythagoras, the number 3 was a perfect number, representing harmony, perfection, and divine proportion.

Philosophy
Philosophers such as Aquinas, Kant, Hegel, C. S. Peirce, and Karl Popper have made threefold divisions, or trichotomies, which have been important in their work.
Hegels dialectic of Thesis + Antithesis = Synthesis creates three-ness from two-ness.

Religion
Many world religions contain triple deities or concepts of trinity, including:

The Hindu Trimurti
The Hindu Tridevi
The Three Jewels of Buddhism
The Three Pure Ones of Taoism
The Christian Holy Trinity
The Triple Goddess of Wicca

Christianity
The threefold office of Christ is a Christian doctrine which states that Christ performs the functions of prophet, priest, and king.
The ministry of Jesus lasted approximately three years.
During the Agony in the Garden, Christ asked three times for the cup to be taken from him.
Jesus rose from the dead on the third day after his death.
The devil tempted Jesus three times.
Saint Peter thrice denied Jesus and thrice affirmed his faith in Jesus.
The Magi – wise men who were astronomers/astrologers from Persia – gave Jesus three gifts.
There are three Synoptic Gospels and three epistles of John.
Paul the Apostle went blind for three days after his conversion to Christianity.

Judaism
Noah had three sons: Ham, Shem and Japheth
The Three Patriarchs: Abraham, Isaac and Jacob
The prophet Balaam beat his donkey three times.
The prophet Jonah spent three days and nights in the belly of a large fish
Three divisions of the Written Torah: Torah (Five Books of Moses), Neviim (Prophets), Ketuvim (Writings)
Three divisions of the Jewish people: Kohen, Levite, Yisrael
Three daily prayers: Shacharit, Mincha, Maariv
Three Shabbat meals
Shabbat ends when three stars are visible in the night sky
Three Pilgrimage Festivals: Passover, Shavuot, Sukkot
Three matzos on the Passover Seder table
The Three Weeks, a period of mourning bridging the fast days of Seventeenth of Tammuz and Tisha BAv
Three cardinal sins for which a Jew must die rather than transgress: idolatry, murder, sexual immorality
Upsherin, a Jewish boys first haircut at age 3
A Beth din is composed of three members
Potential converts are traditionally turned away three times to test their sincerity
In the Jewish mystical tradition of the Kabbalah, it is believed that the soul consists of three parts, with the highest being neshamah ("breath"), the middle being ruach ("wind" or "spirit") and the lowest being nefesh ("repose"). Sometimes the two elements of Chayah ("life" or "animal") and Yechidah ("unit") are additionally mentioned.
In the Kabbalah, the Tree of Life (Hebrew: Etz ha-Chayim, עץ החיים) refers to a latter 3-pillar diagrammatic representation of its central mystical symbol, known as the 10 Sephirot.

Islam
The three core principles in Shia tradition: Tawhid (Oneness of God), Nabuwwa (Concept of Prophethood), Imama (Concept of Imam)

Buddhism
The Triple Bodhi (ways to understand the end of birth) are Budhu, Pasebudhu, and Mahaarahath.
The Three Jewels, the three things that Buddhists take refuge in.

Shinto
The Imperial Regalia of Japan of the sword, mirror, and jewel.

Daoism
The Three Treasures (Chinese: 三寶; pinyin: sānbǎo; Wade–Giles: san-pao), the basic virtues in Taoism.
The Three Dantians
Three Lines of a Trigram
Three Sovereigns: Heaven Fu Xi (Hand – Head – 3º Eye), Humanity Shen Nong (Unit 69), Hell Nüwa (Foot – Abdomen – Umbiculus).

Hinduism
The Trimurti: Brahma the Creator, Vishnu the Preserver, and Shiva the Destroyer.
The three Gunas found in Samkhya school of Hindu philosophy.
The three paths to salvation in the Bhagavad Gita named Karma Yoga, Bhakti Yoga and Jnana Yoga.

Zoroastrianism
The three virtues of Humata, Hukhta and Huvarshta (Good Thoughts, Good Words and Good Deeds) are a basic tenet in Zoroastrianism.

Norse mythology
Three is a very significant number in Norse mythology, along with its powers 9 and 27.

Prior to Ragnarök, there will be three hard winters without an intervening summer, the Fimbulwinter.
Odin endured three hardships upon the World Tree in his quest for the runes: he hanged himself, wounded himself with a spear, and suffered from hunger and thirst.
Bor had three sons, Odin, Vili, and Vé.

Other religions
The Wiccan Rule of Three.
The Triple Goddess: Maiden, Mother, Crone; the three fates.
The sons of Cronus: Zeus, Poseidon, and Hades.
The Slavic god Triglav has three heads.

Esoteric tradition
The Theosophical Society has three conditions of membership.
Gurdjieffs Three Centers and the Law of Three.
Liber AL vel Legis, the central scripture of the religion of Thelema, consists of three chapters, corresponding to three divine narrators respectively: Nuit, Hadit and Ra-Hoor-Khuit.
The Triple Greatness of Hermes Trismegistus is an important theme in Hermeticism.

As a lucky or unlucky number
Three (三, formal writing: 叁, pinyin sān, Cantonese: saam1) is considered a good number in Chinese culture because it sounds like the word "alive" (生 pinyin shēng, Cantonese: saang1), compared to four (四, pinyin: sì, Cantonese: sei1), which sounds like the word "death" (死 pinyin sǐ, Cantonese: sei2).
Counting to three is common in situations where a group of people wish to perform an action in synchrony: Now, on the count of three, everybody pull! Assuming the counter is proceeding at a uniform rate, the first two counts are necessary to establish the rate, and the count of "three" is predicted based on the timing of the "one" and "two" before it. Three is likely used instead of some other number because it requires the minimal amount counts while setting a rate.
There is another superstition that it is unlucky to take a third light, that is, to be the third person to light a cigarette from the same match or lighter. This superstition is sometimes asserted to have originated among soldiers in the trenches of the First World War when a sniper might see the first light, take aim on the second and fire on the third.The phrase "Third times the charm" refers to the superstition that after two failures in any endeavor, a third attempt is more likely to succeed. This is also sometimes seen in reverse, as in "third man [to do something, presumably forbidden] gets caught".Luck, especially bad luck, is often said to "come in threes".

Sports
In American and Canadian football, a field goal is worth three points.
In association football:
For purposes of league standings, since the mid-1990s almost all leagues have awarded three points for a win.
A team that wins three trophies in a season is said to have won a treble.
A player who scores three goals in a match is said to have scored a hat-trick.
In baseball:
A batter strikes out upon the third strike in any single batting appearance.
Each teams half of an inning ends once the defense has recorded three outs (unless the home team has a walk-off hit in the ninth inning or any extra inning).
In scorekeeping, "3" denotes the first baseman.
In basketball:
Three points are awarded for a basket made from behind a designated arc on the floor.
The "3 position" is the small forward.
In bowling, three strikes bowled consecutively is known as a "turkey".
In cricket, a bowler who is credited with dismissals of batsmen on three consecutive deliveries has achieved a "hat-trick".
In Gaelic games (Gaelic football for men and women, hurling, and camogie), three points are awarded for a goal, scored when the ball passes underneath the crossbar and between the goal posts.
In ice hockey:
Scoring three goals is called a "hat trick" (usually not hyphenated in North America).
A team will typically have three forwards on the ice at any given time.
In professional wrestling, a pin is when one holds the opponents shoulders against the mat for a count of three.
In rugby union:
A successful penalty kick for goal or drop goal is worth three points.
In the French variation of the bonus points system, a team receives a bonus point in the league standings if it wins a match while scoring at least three more tries than its opponent.
The starting tighthead prop wears the jersey number 3.
In rugby league:
One of the two starting centres wears the jersey number 3 </s>