<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Visual impairment and explain in detail? [/INST] Visual impairment, also known as vision impairment, is a medical definition primarily measured based on an individuals better eye visual acuity; in the absence of treatment such as correctable eyewear, assistive devices, and medical treatment– visual impairment may cause the individual difficulties with normal daily tasks including reading and walking. Low vision is a functional definition of visual impairment that is chronic, uncorrectable with treatment or correctable lenses, and impacts daily living. As such low vision can be used as a disability metric and varies based on an individuals experience, environmental demands, accommodations, and access to services. The American Academy of Ophthalmology defines visual impairment as the best-corrected visual acuity of less than 20/40 in the better eye, and the World Health Organization defines it as a presenting acuity of less than 6/12 in the better eye. The term blindness is used for complete or nearly complete vision loss. In addition to the various permanent conditions, fleeting temporary vision impairment, amaurosis fugax, may occur, and may indicate serious medical problems.
The most common causes of visual impairment globally are uncorrected refractive errors (43%), cataracts (33%), and glaucoma (2%). Refractive errors include near-sightedness, far-sightedness, presbyopia, and astigmatism. Cataracts are the most common cause of blindness. Other disorders that may cause visual problems include age-related macular degeneration, diabetic retinopathy, corneal clouding, childhood blindness, and a number of infections. Visual impairment can also be caused by problems in the brain due to stroke, premature birth, or trauma, among others. These cases are known as cortical visual impairment. Screening for vision problems in children may improve future vision and educational achievement. Screening adults without symptoms is of uncertain benefit. Diagnosis is by an eye exam.The World Health Organization (WHO) estimates that 80% of visual impairment is either preventable or curable with treatment. This includes cataracts, the infections river blindness and trachoma, glaucoma, diabetic retinopathy, uncorrected refractive errors, and some cases of childhood blindness. Many people with significant visual impairment benefit from vision rehabilitation, changes in their environment, and assistive devices.As of 2015 there were 940 million people with some degree of vision loss. 246 million had low vision and 39 million were blind. The majority of people with poor vision are in the developing world and are over the age of 50 years. Rates of visual impairment have decreased since the 1990s. Visual impairments have considerable economic costs both directly due to the cost of treatment and indirectly due to decreased ability to work.

Classification
In 2010, the WHO definition for visual impairment was changed and now follows the ICD-11. The previous definition which used "best corrected visual acuity" was changed to "presenting visual acuity". This change was made as newer studies showed that best-corrected vision overlooks a larger proportion of the population who has visual impairment due to uncorrected refractive errors, and/or lack of access to medical or surgical treatment.Distance vision impairment:

Category 0: No or mild visual impairment –presenting visual acuity better than 6/18
Category 1: Moderate visual impairment –presenting visual acuity worse than 6/18 and better than 6/60
Category 2: Severe visual impairment –presenting visual acuity worse than 6/60 and better than 3/60
Category 3: Blindness –presenting visual acuity worse than 3/60 and better than 1/60
Category 4: Blindness—presenting visual acuity worse than 1/60 with light perception
Category 5: Blindness—irreversible blindness with no light perceptionNear vision impairment:

Near visual acuity worse than N6 or M.08 at 40 cm.

United Kingdom
Severely sight impaired

Defined as having central visual acuity of less than 3/60 with normal fields of vision, or gross visual field restriction.
Unable to see at 3 metres (10 ft) what the normally sighted person sees at 60 metres (200 ft).Sight impaired

Able to see at 3 metres (10 ft), but not at 6 metres (20 ft), what the normally sighted person sees at 60 metres (200 ft)
Less severe visual impairment is not captured by registration data, and its prevalence is difficult to quantifyLow vision

A visual acuity of less than 6/18 but greater than 3/60.
Not eligible to drive and may have difficulty recognising faces across a street, watching television, or choosing clean, unstained, co-ordinated clothing.In the UK, the Certificate of Vision Impairment (CVI) is used to certify patients as severely sight impaired or sight impaired. The accompanying guidance for clinical staff states: "The National Assistance Act 1948 states that a person can be certified as severely sight impaired if they are so blind as to be unable to perform any work for which eye sight is essential". Certification is based on whether a person can do any work for which eyesight is essential, not just one particular job (such as their job before becoming blind).In practice, the definition depends on individuals visual acuity and the extent to which their field of vision is restricted. The Department of Health identifies three groups of people who may be classified as severely visually impaired.
Those below 3/60 (equivalent to 20/400 in US notation) Snellen (most people below 3/60 are severely sight impaired).
Those better than 3/60 but below 6/60 Snellen (people who have a very contracted field of vision only).
Those 6/60 Snellen or above (people in this group who have a contracted field of vision especially if the contraction is in the lower part of the field).The Department of Health also state that a person is more likely to be classified as severely visually impaired if their eyesight has failed recently or if they are an older individual, both groups being perceived as less able to adapt to their vision loss.

United States
In the United States, any person with vision that cannot be corrected to better than 20/200 in the best eye, or who has 20 degrees (diameter) or less of visual field remaining, is considered legally blind or eligible for disability classification and possible inclusion in certain government sponsored programs.
In the United States, the terms partially sighted, low vision, legally blind and totally blind are used by schools, colleges, and other educational institutions to describe students with visual impairments. They are defined as follows:

Partially sighted indicates some type of visual problem, with a need of person to receive special education in some cases.
Low vision generally refers to a severe visual impairment, not necessarily limited to distance vision. Low vision applies to all individuals with sight who are unable to read the newspaper at a normal viewing distance, even with the aid of eyeglasses or contact lenses. They use a combination of vision and other senses to learn, although they may require adaptations in lighting or the size of print, and, sometimes, braille.
Legally blind indicates that a person has less than 20/200 vision in the better eye after best correction (contact lenses or glasses), or a field of vision of less than 20 degrees in the better eye.
Totally blind students learn via braille or other non-visual media.In 1934, the American Medical Association adopted the following definition of blindness:

Central visual acuity of 20/200 or less in the better eye with corrective glasses or central visual acuity of more than 20/200 if there is a visual field defect in which the peripheral field is contracted to such an extent that the widest diameter of the visual field subtends an angular distance no greater than 20 degrees in the better eye.
The United States Congress included this definition as part of the Aid to the Blind program in the Social Security Act passed in 1935. In 1972, the Aid to the Blind program and two others combined under Title XVI of the Social Security Act to form the Supplemental Security Income program which states:

An individual shall be considered to be blind for purposes of this title if he has central visual acuity of 20/200 or less in the better eye with the use of a correcting lens. An eye which is accompanied by a limitation in the fields of vision such that the widest diameter of the visual field subtends an angle no greater than 20 degrees shall be considered for purposes of the first sentence of this subsection as having a central visual acuity of 20/200 or less. An individual shall also be considered to be blind for purposes of this title if he is blind as defined under a State plan approved under title X or XVI as in effect for October 1972 and received aid under such plan (on the basis of blindness) for December 1973, so long as he is continuously blind as so defined.

Temporary vision impairment
Vision impairment for a few seconds, or minutes, may occur due to any of a variety of causes, some serious and requiring medical attention.

Health effects
General functioning
Visual impairments may take many forms and be of varying degrees. Visual acuity alone is not always a good predictor of an individuals function. Someone with relatively good acuity (e.g., 20/40) can have difficulty with daily functioning, while someone with worse acuity (e.g., 20/200) may function reasonably well if they have low visual demands. It is also important to note that best-corrected visual acuity differs from presenting visual acuity; a person with a "normal" best corrected acuity can have "poor" presenting acuity (e.g. individual who has uncorrected refractive error). Thus, measuring an individuals general functioning depends on ones situational and contextual factors, as well as access to treatment.The American Medical Association has estimated that the loss of one eye equals 25% impairment of the visual system and 24% impairment of the whole person; total loss of vision in both eyes is considered to be 100% visual impairment and 85% impairment of the whole person.Some people who fall into this category can use their considerable residual vision – their remaining sight – to complete daily tasks without relying on alternative methods. The role of a low vision specialist (optometrist or ophthalmologist) is to maximize the functional level of a patients vision by optical or non-optical means. Primarily, this is by use of magnification in the form of telescopic systems for distance vision and optical or electronic magnification for near tasks.
People with significantly reduced acuity may benefit from training conducted by individuals trained in the provision of technical aids. Low vision rehabilitation professionals, some of whom are connected to an agency for the blind, can provide advice on lighting and contrast to maximize remaining vision. These professionals also have access to non-visual aids, and can instruct patients in their uses.

Mobility
Older adults with visual impairment are at an increased risk of physical inactivity, slower gait speeds, and fear of falls.Physical activity is a useful predictor of overall well-being, and routine physical activity reduces the risk of developing chronic diseases and disability. Older adults with visual impairment (including glaucoma, age-related macular degeneration, and diabetic retinopathy) have decreased physical activity as measured with self-reports and accelerometers. The US National Health and Nutrition Examination Survey (NHANES) showed that people with corrected visual acuity of less than 20/40 spent significantly less time in moderate to vigorous physical activity. Age-related macular degeneration is also associated with a 50% decrease in physical activity–however physical activity is protective against age-related macular degeneration progression.In terms of mobility, those with visual impairment have a slower gait speed than those without visual impairment; however, the rate of decline remains proportional with increasing age in both groups. Additionally, the visually impaired also have greater difficulty walking a quarter mile (400 m) and walking up stairs, as compared to those with normal vision.

Cognitive
Older adults with vision loss are at an increased risk of memory loss, cognitive impairment, and cognitive decline.

Social and psychological
Studies demonstrate an association between older adults with visual impairment and a poor mental health; discrimination was identified as one of the causes of this association. Older adults with visual impairment have a 1.5-fold risk of reporting perceived discrimination and of these individuals, there was a 2-fold risk of loneliness and 4-fold risk of reporting a lower quality of life. Among adults with visual impairment, the prevalence of moderate loneliness is 28.7% (18.2% in general population) and prevalence of severe loneliness is 19.7% (2.7% in general population). The risk of depression and anxiety are also increased in the visually impaired; 32.2% report depressive symptoms (12.01% in general population), and 15.61% report anxiety symptoms (10.69% in general population).The subjects making the most use of rehabilitation instruments, who lived alone, and preserved their own mobility and occupation were the least depressed, with the lowest risk of suicide and the highest level of social integration.
Those with worsening sight and the prognosis of eventual blindness are at comparatively high risk of suicide and thus may be in need of supportive services. Many studies have demonstrated how rapid acceptance of the serious visual impairment has led to a better, more productive compliance with rehabilitation programs. Moreover, psychological distress has been reported to be at its highest when sight loss is not complete, but the prognosis is unfavorable. Therefore, early intervention is imperative for enabling successful psychological adjustment.

Associated conditions
Blindness can occur in combination with such conditions as intellectual disability, autism spectrum disorders, cerebral palsy, hearing impairments, and epilepsy. Blindness in combination with hearing loss is known as deafblindness.
It has been estimated that over half of completely blind people have non-24-hour sleep–wake disorder, a condition in which a persons circadian rhythm, normally slightly longer than 24 hours, is not entrained (synchronized) to the light–dark cycle.

Cause
The most common causes of visual impairment globally in 2010 were:

Refractive error (42%)
Cataract  (33%)
Glaucoma (2%)
Age-related macular degeneration (1%)
Corneal opacification (1%)
Diabetic retinopathy (1%)
Childhood blindness
Trachoma (1%)
Undetermined (18%)The most common causes of blindness worldwide in 2010 were:

Cataracts (51%)
Glaucoma (8%)
Age-related macular degeneration (5%)
Corneal opacification (4%)
Childhood blindness (4%)
Refractive errors (3%)
Trachoma (3%)
Diabetic retinopathy (1%)
Undetermined (21%)About 90% of people who are visually impaired live in the developing world. Age-related macular degeneration, glaucoma, and diabetic retinopathy are the leading causes of blindness in the developed world.Among working-age adults who are newly blind in England and Wales the most common causes in 2010 were:
Hereditary retinal disorders (20.2%)
Diabetic retinopathy (14.4%)
Optic atrophy (14.1%)
Glaucoma (5.9%)
Congenital abnormalities (5.1%)
Disorders of the visual cortex (4.1%)
Cerebrovascular disease (3.2%)
Degeneration of the macula and posterior pole (3.0%)
Myopia (2.8%)
Corneal disorders (2.6%)
Malignant neoplasms of the brain and nervous system (1.5%)
Retinal detachment (1.4%)

Cataracts
Cataracts are the greying or opacity of the crystalline lens, which can be caused in children by intrauterine infections, metabolic disorders, and genetically transmitted syndromes. Cataracts are the leading cause of child and adult blindness that doubles in prevalence with every ten years after the age of 40. Consequently, today cataracts are more common among adults than in children. That is, people face higher chances of developing cataracts as they age. Nonetheless, cataracts tend to have a greater financial and emotional toll upon children as they must undergo expensive diagnosis, long term rehabilitation, and visual assistance. Also, according to the Saudi Journal for Health Sciences, sometimes patients experience irreversible amblyopia after pediatric cataract surgery because the cataracts prevented the normal maturation of vision prior to operation. Despite the great progress in treatment, cataracts remain a global problem in both economically developed and developing countries. At present, with the variant outcomes as well as the unequal access to cataract surgery, the best way to reduce the risk of developing cataracts is to avoid smoking and extensive exposure to sun light (i.e. UV-B rays).

Glaucoma
Glaucoma is an eye disease often characterized by increased pressure within the eye or intraocular pressure (IOP). Glaucoma causes visual field loss as well as severs the optic nerve. Early diagnosis and treatment of glaucoma in patients is imperative because glaucoma is triggered by non-specific levels of IOP. Also, another challenge in accurately diagnosing glaucoma is that the disease has four causes: 1) inflammatory ocular hypertension syndrome (IOHS); 2) severe uveitic angle closure; 3) corticosteroid-induced; and 4) a heterogonous mechanism associated with structural change and chronic inflammation. In addition, often pediatric glaucoma differs greatly in cause and management from the glaucoma developed by adults. Currently, the best sign of pediatric glaucoma is an IOP of 21 mm Hg or greater present within a child. One of the most common causes of pediatric glaucoma is cataract removal surgery, which leads to an incidence rate of about 12.2% among infants and 58.7% among 10-year-olds.

Infections
Childhood blindness can be caused by conditions related to pregnancy, such as congenital rubella syndrome and retinopathy of prematurity. Leprosy and onchocerciasis each blind approximately 1 million individuals in the developing world.
The number of individuals blind from trachoma has decreased in the past 10 years from 6 million to 1.3 million, putting it in seventh place on the list of causes of blindness worldwide.
Central corneal ulceration is also a significant cause of monocular blindness worldwide, accounting for an estimated 850,000 cases of corneal blindness every year in the Indian subcontinent alone. As a result, corneal scarring from all causes is now the fourth greatest cause of global blindness.

Injuries
Eye injuries, most often occurring in people under 30, are the leading cause of monocular blindness (vision loss in one eye) throughout the United States. Injuries and cataracts affect the eye itself, while abnormalities such as optic nerve hypoplasia affect the nerve bundle that sends signals from the eye to the back of the brain, which can lead to decreased visual acuity.
Cortical blindness results from injuries to the occipital lobe of the brain that prevent the brain from correctly receiving or interpreting signals from the optic nerve. Symptoms of cortical blindness vary greatly across individuals and may be more severe in periods of exhaustion or stress. It is common for people with cortical blindness to have poorer vision later in the day.
Blinding has been used as an act of vengeance and torture in some instances, to deprive a person of a major sense by which they can navigate or interact within the world, act fully independently, and be aware of events surrounding them. An example from the classical realm is Oedipus, who gouges out his own eyes after realizing that he fulfilled the awful prophecy spoken of him. Having crushed the Bulgarians, the Byzantine Emperor Basil II blinded as many as 15,000 prisoners taken in the battle, before releasing them. Contemporary examples include the addition of methods such as acid throwing as a form of disfigurement.

Genetic defects
People with albinism often have vision loss to the extent that many are legally blind, though few of them actually cannot see. Leber congenital amaurosis can cause total blindness or severe sight loss from birth or early childhood. Retinitis pigmentosa is characterized by decreased peripheral vision and trouble seeing at night.
Advances in mapping of the human genome have identified other genetic causes of low vision or blindness. Two such examples are Bardet–Biedl syndrome .

Poisoning
Rarely, blindness is caused by the intake of certain chemicals. A well-known example is methanol, which is only mildly toxic and minimally intoxicating, and breaks down into the substances formaldehyde and formic acid which in turn can cause blindness, an array of other health complications, and death. When competing with ethanol for metabolism, ethanol is metabolized first, and the onset of toxicity is delayed. Methanol is commonly found in methylated spirits, denatured ethyl alcohol, to avoid paying taxes on selling ethanol intended for human consumption. Methylated spirits are sometimes used by alcoholics as a desperate and cheap substitute for regular ethanol alcoholic beverages.

Other
Amblyopia: is a category of vision loss or visual impairment that is caused by factors unrelated to refractive errors or coexisting ocular diseases. Amblyopia is the condition when a childs visual systems fail to mature normally because the child either has been born premature, measles, congenital rubella syndrome, vitamin A deficiency, or meningitis. If left untreated during childhood, amblyopia is currently incurable in adulthood because surgical treatment effectiveness changes as a child matures. Consequently, amblyopia is the worlds leading cause of child monocular vision loss, which is the damage or loss of vision in one eye. In the best case scenario, which is very rare, properly treated amblyopia patients can regain 20/40 acuity.
Corneal opacification
Degenerative myopia
Diabetic retinopathy: is one of the manifestation microvascular complications of diabetes, which is characterized by blindness or reduced acuity. That is, diabetic retinopathy describes the retinal and vitreous hemorrhages or retinal capillary blockage caused by the increase of A1C, which a measurement of blood glucose or sugar level. In fact, as A1C increases, people tend to be at greater risk of developing diabetic retinopathy than developing other microvascular complications associated with diabetes (e.g. chronic hyperglycemia, diabetic neuropathy, and diabetic nephropathy). Despite the fact that only 8% of adults 40 years and older experience vision-threatening diabetic retinopathy (e.g. nonproliferative diabetic retinopathy or NPDR and proliferative diabetic retinopathy or PDR), this eye disease accounted for 17% of cases of blindness in 2002.
Retinitis pigmentosa
Retinopathy of prematurity: The most common cause of blindness in infants worldwide. In its most severe form, ROP causes retinal detachment, with attendant visual loss. Treatment is aimed mainly at prevention, via laser or Avastin therapy.
Stargardts disease
Uveitis: is a group of 30 intraocular inflammatory diseases caused by infections, systemic diseases, organ-specific autoimmune processes, cancer or trauma. That is, uveitis refers to a complex category of ocular diseases that can cause blindness if either left untreated or improperly diagnosed. The current challenge of accurately diagnosing uveitis is that often the cause of a specific ocular inflammation is either unknown or multi-layered. Consequently, about 3–10% of those with uveitis in developed countries, and about 25% of those with uveitis in the developing countries, become blind from incorrect diagnosis and from ineffectual prescription of drugs, antibiotics or steroids. In addition, uveitis is a diverse category of eye diseases that are subdivided as granulomatous (or tumorous) or non-granulomatous anterior, intermediate, posterior or pan uveitis. In other words, uveitis diseases tend to be classified by their anatomic location in the eye (e.g. uveal tract, retina, or lens), as well as can create complication that can cause cataracts, glaucoma, retinal damage, age-related macular degeneration or diabetic retinopathy.
Xerophthalmia, often due to vitamin A deficiency, is estimated to affect 5 million children each year; 500,000 develop active corneal involvement, and half of these go blind.

Diagnosis
It is important that people be examined by someone specializing in low vision care prior to other rehabilitation training to rule out potential medical or surgical correction for the problem and to establish a careful baseline refraction and prescription of both normal and low vision glasses and optical aids. Only a doctor is qualified to evaluate visual functioning of a compromised visual system effectively. The American Medical Association provides an approach to evaluating visual loss as it affects an individuals ability to perform activities of daily living.Screening adults who have no symptoms is of uncertain benefit.

Prevention
The World Health Organization estimates that 80% of visual loss is either preventable or curable with treatment. This includes cataracts, onchocerciasis, trachoma, glaucoma, diabetic retinopathy, uncorrected refractive errors, and some cases of childhood blindness. The Center for Disease Control and Prevention estimates that half of blindness in the United States is preventable.

Management
Mobility
Many people with serious visual impairments can travel independently, using a wide range of tools and techniques. Orientation and mobility specialists are professionals who are specifically trained to teach people with visual impairments how to travel safely, confidently, and independently in the home and the community. These professionals can also help blind people to practice travelling on specific routes which they may use often, such as the route from ones house to a convenience store. Becoming familiar with an environment or route can make it much easier for a blind person to navigate successfully.
Tools such as the white cane with a red tip – the international symbol of blindness – may also be used to improve mobility. A long cane is used to extend the users range of touch sensation. It is usually swung in a low sweeping motion, across the intended path of travel, to detect obstacles. However, techniques for cane travel can vary depending on the user and/or the situation. Some visually impaired persons do not carry these kinds of canes, opting instead for the shorter, lighter identification (ID) cane. Still others require a support cane. The choice depends on the individuals vision, motivation, and other factors.
A small number of people employ guide dogs to assist in mobility. These dogs are trained to navigate around various obstacles, and to indicate when it becomes necessary to go up or down a step. However, the helpfulness of guide dogs is limited by the inability of dogs to understand complex directions. The human half of the guide dog team does the directing, based upon skills acquired through previous mobility training. In this sense, the handler might be likened to an aircrafts navigator, who must know how to get from one place to another, and the dog to the pilot, who gets them there safely.
GPS devices can also be used as a mobility aid. Such software can assist blind people with orientation and navigation, but it is not a replacement for traditional mobility tools such as white canes and guide dogs.
Some blind people are skilled at echolocating silent objects simply by producing mouth clicks and listening to the returning echoes. It has been shown that blind echolocation experts use what is normally the "visual" part of their brain to process the echoes.Government actions are sometimes taken to make public places more accessible to blind people. Public transportation is freely available to blind people in many cities. Tactile paving and audible traffic signals can make it easier and safer for visually impaired pedestrians to cross streets. In addition to making rules about who can and cannot use a cane, some governments mandate the right-of-way be given to users of white canes or guide dogs.

Reading and magnification
Most visually impaired people who are not totally blind read print, either of a regular size or enlarged by magnification devices. Many also read large-print, which is easier for them to read without such devices. A variety of magnifying glasses, some handheld, and some on desktops, can make reading easier for them.
Others read braille (or the infrequently used Moon type), or rely on talking books and readers or reading machines, which convert printed text to speech or braille. They use computers with special hardware such as scanners and refreshable braille displays as well as software written specifically for the blind, such as optical character recognition applications and screen readers.
Some people access these materials through agencies for the blind, such as the National Library Service for the Blind and Physically Handicapped in the United States, the National Library for the Blind or the RNIB in the United Kingdom.
Closed-circuit televisions, equipment that enlarges and contrasts textual items, are a more high-tech alternative to traditional magnification devices.
There are also over 100 radio reading services throughout the world that provide people with vision impairments with readings from periodicals over the radio. The International Association of Audio Information Services provides links to all of these organizations.

Computers and mobile technology
Access technology such as screen readers, screen magnifiers and refreshable braille displays enable the blind to use mainstream computer applications and mobile phones. The availability of assistive technology is increasing, accompanied by concerted efforts to ensure the accessibility of information technology to all potential users, including the blind. Later versions of Microsoft Windows include an Accessibility Wizard & Magnifier for those with partial vision, and Microsoft Narrator, a simple screen reader. Linux distributions (as live CDs) for the blind include Vinux and Adriane Knoppix, the latter developed in part by Adriane Knopper who has a visual impairment.  macOS and iOS  also come with a built-in screen reader called VoiceOver, while Google TalkBack is built in to most Android devices.
The movement towards greater web accessibility is opening a far wider number of websites to adaptive technology, making the web a more inviting place for visually impaired surfers.
Experimental approaches in sensory substitution are beginning to provide access to arbitrary live views from a camera.
Modified visual output that includes large print and/or clear simple graphics can be of benefit to users with some residual vision.

Other aids and techniques
Blind people may use talking equipment such as thermometers, watches, clocks, scales, calculators, and compasses. They may also enlarge or mark dials on devices such as ovens and thermostats to make them usable. Other techniques used by blind people to assist them in daily activities include:

Adaptations of coins and banknotes so that the value can be determined by touch. For example:
In some currencies, such as the euro, the pound sterling and the Indian rupee, the size of a note increases with its value.
On US coins, pennies and dimes, and nickels and quarters are similar in size. The larger denominations (dimes and quarters) have ridges along the sides (historically used to prevent the "shaving" of precious metals from the coins), which can now be used for identification.
Some currencies banknotes have a tactile feature to indicate denomination. For example, the Canadian currency tactile feature is a system of raised dots in one corner, based on braille cells but not standard braille.
It is also possible to fold notes in different ways to assist recognition.
Labeling and tagging clothing and other personal items
Placing different types of food at different positions on a dinner plate
Marking controls of household appliancesMost people, once they have been visually impaired for long enough, devise their own adaptive strategies in all areas of personal and professional management.
For the blind, there are books in braille, audio-books, and text-to-speech computer programs, machines and e-book readers. Low vision people can make use of these tools as well as large-print reading materials and e-book readers that provide large font sizes.
Computers are important tools of integration for the visually impaired person. They allow, using standard or specific programs, screen magnification and conversion of text into sound or touch (braille line), and are useful for all levels of visual impairment. OCR scanners can, in conjunction with text-to-speech software, read the contents of books and documents aloud via computer. Vendors also build closed-circuit televisions that electronically magnify paper, and even change its contrast and color, for visually impaired users. For more information, consult assistive technology.
In adults with low vision there is no conclusive evidence supporting one form of reading aid over another. In several studies stand-mounted devices allowed faster reading than hand-held or portable optical aids. While electronic aids may allow faster reading for individuals with low vision, portability, ease of use, and affordability must be considered for people.Children with low vision sometimes have reading delays, but do benefit from phonics-based beginning reading instruction methods. Engaging phonics instruction is multisensory, highly motivating, and hands-on. Typically students are first taught the most frequent sounds of the alphabet letters, especially the so-called short vowel sounds, then taught to blend sounds together with three-letter consonant-vowel-consonant words such as cat, red, sit, hot, sun. Hands-on (or kinesthetically appealing) VERY enlarged print materials such as those found in "The Big Collection of Phonics Flipbooks" by Lynn Gordon (Scholastic, 2010) are helpful for teaching word families and blending skills to beginning readers with low vision. Beginning reading instructional materials should focus primarily on the lower-case letters, not the capital letters (even though they are larger) because reading text requires familiarity (mostly) with lower-case letters. Phonics-based beginning reading should also be supplemented with phonemic awareness lessons, writing opportunities, and many read-alouds (literature read to children daily) to stimulate motivation, vocabulary development, concept development, and comprehension skill development. Many children with low vision can be successfully included in regular education environments. Parents may need to be vigilant to ensure that the school provides the teacher and students with appropriate low vision resources, for example technology in the classroom, classroom aide time, modified educational materials, and consultation assistance with low vision experts.

Epidemiology
The WHO estimates that in 2012 there were 285 million visually impaired people in the world, of which 246 million had low vision and 39 million were blind.Of those who are blind 90% live in the developing world. Worldwide for each blind person, an average of 3.4 people have low vision, with country and regional variation ranging from 2.4 to 5.5.By age: Visual impairment is unequally distributed across age groups. More than 82% of all people who are blind are 50 years of age and older, although they represent only 19% of the worlds population. Due to the expected number of years lived in blindness (blind years), childhood blindness remains a significant problem, with an estimated 1.4 million blind children below age 15.
By gender: Available studies consistently indicate that in every region of the world, and at all ages, females have a significantly higher risk of being visually impaired than males.By geography: Visual impairment is not distributed uniformly throughout the world. More than 90% of the worlds visually impaired live in developing countries.Since the estimates of the 1990s, new data based on the 2002 global population show a reduction in the number of people who are blind or visually impaired, and those who are blind from the effects of infectious diseases, but an increase in the number of people who are blind from conditions related to longer life spans.In 1987, it was estimated that 598,000 people in the United States met the legal definition of blindness. Of this number, 58% were over the age of 65. In 1994–1995, 1.3 million Americans reported legal blindness.

Society and culture
Legal definition
To determine which people qualify for special assistance because of their visual disabilities, various governments have specific definitions for legal blindness. In North America and most of Europe, legal blindness is defined as visual acuity (vision) of 20/200 (6/60) or less in the better eye with best correction possible. This means that a legally blind individual would have to stand 20 feet (6.1 m) from an object to see it—with corrective lenses—with the same degree of clarity as a normally sighted person could from 200 feet (61 m). In many areas, people with average acuity who nonetheless have a visual field of less than 20 degrees (the norm being 180 degrees) are also classified as being legally blind.
Approximately fifteen percent of those deemed legally blind, by any measure, have no light or form perception. The rest have some vision, from light perception alone to relatively good acuity. Low vision is sometimes used to describe visual acuities from 20/70 to 20/200.

Literature and art
Antiquity
The Moche people of ancient Peru depicted the blind in their ceramics.In Greek myth, Tiresias was a prophet famous for his clairvoyance. According to one myth, he was blinded by the gods as punishment for revealing their secrets, while another holds that he was blinded as punishment after he saw Athena naked while she was bathing. In the Odyssey, the one-eyed Cyclops Polyphemus captures Odysseus, who blinds Polyphemus to escape. In Norse mythology, Loki tricks the blind god Höðr into killing his brother Baldr, the god of happiness.
The New Testament contains numerous instances of Jesus performing miracles to heal the blind. According to the Gospels, Jesus healed the two blind men of Galilee, the blind man of Bethsaida, the blind man of Jericho and the man who was born blind.
The parable of the blind men and an elephant has crossed between many religious traditions and is part of Jain, Buddhist, Sufi and Hindu lore. In various versions of the tale, a group of blind men (or men in the dark) touch an elephant to learn what it is like. Each one feels a different part, but only one part, such as the side or the tusk. They then compare notes and learn that they are in complete disagreement.
"Three Blind Mice" is a medieval English nursery rhyme about three blind mice whose tails are cut off after chasing the farmers wife. The work is explicitly incongruous, ending with the comment Did you ever see such a sight in your life, As three blind mice?

Modern times
Poet John Milton, who went blind in mid-life, composed "On His Blindness", a sonnet about coping with blindness. The work posits that [those] who best Bear [God]s mild yoke, they serve him best.
The Dutch painter and engraver Rembrandt often depicted scenes from the apocryphal Book of Tobit, which tells the story of a blind patriarch who is healed by his son, Tobias, with the help of the archangel Raphael.Slaver-turned-abolitionist John Newton composed the hymn "Amazing Grace" about a wretch who "once was lost, but now am found, Was blind, but now I see." Blindness, in this sense, is used both metaphorically (to refer to someone who was ignorant but later became knowledgeable) and literally, as a reference to those healed in the Bible. In the later years of his life, Newton himself would go blind.
H. G. Wells story "The Country of the Blind" explores what would happen if a sighted man found himself trapped in a country of blind people to emphasise societys attitude to blind people by turning the situation on its head.
Bob Dylans anti-war song "Blowin in the Wind" twice alludes to metaphorical blindness: How many times can a man turn his head // and pretend that he just doesnt see... How many times must a man look up // Before he can see the sky?
Contemporary fiction contains numerous well-known blind characters. Some of these characters can see by means of devices, such as the Marvel Comics superhero Daredevil, who can see via his super-human hearing acuity, or Star Treks Geordi La Forge, who can see with the aid of a VISOR, a fictional device that transmits optical signals to his brain.

Sports
Blind and partially sighted people participate in sports, such as swimming, snow skiing and athletics. Some sports have been invented or adapted for the blind, such as goalball, association football, cricket, golf, tennis, bowling, and beep baseball. The worldwide authority on sports for the blind is the International Blind Sports Federation. People with vision impairments have participated in the Paralympic Games since the 1976 Toronto summer Paralympics.

Metaphorical uses
The word "blind" (adjective and verb) is often used to signify a lack of knowledge of something. For example, a blind date is a date in which the people involved have not previously met; a blind experiment is one in which information is kept from either the experimenter or the participant to mitigate the placebo effect or observer bias. The expression "blind leading the blind" refers to incapable people leading other incapable people. Being blind to something means not understanding or being aware of it. A "blind spot" is an area where someone cannot see: for example, where a car driver cannot see because parts of his cars bodywork are in the way; metaphorically, a topic on which an individual is unaware of their own biases, and therefore of the resulting distortions of their own judgements (see Bias blind spot).

Research
A 2008 study tested the effect of using gene therapy to help restore the sight of patients with a rare form of inherited blindness, known as Lebers congenital amaurosis or LCA. Lebers Congenital Amaurosis damages the light receptors in the retina and usually begins affecting sight in early childhood, with worsening vision until complete blindness around the age of 30. The study used a common cold virus to deliver a normal version of the gene called RPE65 directly into the eyes of affected patients. All three patients, aged 19, 22 and 25, responded well to the treatment and reported improved vision following the procedure.
Two experimental treatments for retinal problems include a cybernetic replacement and transplant of fetal retinal cells.There is no high-quality evidence on the effect of assistive technologies on educational outcomes and quality of life in children with low vision as of 2015, nor is there evidence on magnifying reading aids in children </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Meconium aspiration syndrome and explain in detail? [/INST] Meconium aspiration syndrome (MAS) also known as neonatal aspiration of meconium is a medical condition affecting newborn infants. It describes the spectrum of disorders and pathophysiology of newborns born in meconium-stained amniotic fluid (MSAF) and have meconium within their lungs. Therefore, MAS has a wide range of severity depending on what conditions and complications develop after parturition. Furthermore, the pathophysiology of MAS is multifactorial and extremely complex which is why it is the leading cause of morbidity and mortality in term infants.The word meconium is derived from the Greek word mēkōnion meaning juice from the opium poppy as the sedative effects it had on the foetus were observed by Aristotle.Meconium is a sticky dark-green substance which contains gastrointestinal secretions, amniotic fluid, bile acids, bile, blood, mucus, cholesterol, pancreatic secretions, lanugo, vernix caseosa and cellular debris. Meconium accumulates in the foetal gastrointestinal tract throughout the third trimester of pregnancy and it is the first intestinal discharge released within the first 48 hours after birth. Notably, since meconium and the whole content of the gastrointestinal tract is located extracorporeally, its constituents are hidden and normally not recognised by the foetal immune system.For the meconium within the amniotic fluid to successfully cause MAS, it has to enter the respiratory system during the period when the fluid-filled lungs transition into an air-filled organ capable of gas exchange.

Causes
The main theories of meconium passage into amniotic fluid are caused by fetal maturity or from foetal stress as a result of hypoxia or infection. Other factors that promote the passage of meconium in utero include placental insufficiency, maternal hypertension, pre-eclampsia and maternal drug use of tobacco and cocaine. However, the exact mechanism for meconium passage into the amniotic fluid is not completely understood and it may be a combination of several factors.

Meconium passage as a result of foetal distress
There may be an important association between foetal distress and hypoxia with MSAF. It is believed that foetal distress develops into foetal hypoxia causing the foetus to defecate meconium resulting in MSAF and then perhaps MAS. Other stressors which causes foetal distress, and therefore meconium passage, includes when umbilical vein oxygen saturation is below 30%.Foetal hypoxic stress during parturition can stimulate colonic activity, by enhancing intestinal peristalsis and relaxing the anal sphincter, which results in the passage of meconium. Then, because of intrauterine gasping or from the first few breaths after delivery, MAS may develop. Furthermore, aspiration of thick meconium leads to obstruction of airways resulting in a more severe hypoxia.The association between foetal distress and meconium passage is not a definite cause-effect relationship as over 3⁄4 of infants with MSAF are vigorous at birth and do not have any distress or hypoxia. Additionally, foetal distress occurs frequently without the passage of meconium as well.

Meconium passage as a result of foetal maturity
Although meconium is present in the gastrointestinal tract early in development, MSAF rarely occurs before 34 weeks gestation.Peristalsis of the foetal intestines is present as early as 8 weeks gestation and the anal sphincter develops at about 20–22 weeks. The early control mechanisms of the anal sphincter are not well understood, however there is evidence that the foetus does defecate routinely into the amniotic cavity even in the absence of distress. The presence of fetal intestinal enzymes have been found in the amniotic fluid of women who are as early as 14–22 weeks pregnant. Thus, suggesting there is free passage of the intestinal contents into the amniotic fluid.Motilin is found in higher concentrations in post-term than pre-term foetal gastrointestinal tracts. Similarly, intestinal parasympathetic innervation and myelination also increases in later gestations. Therefore, the increased incidence of MAS in post-term pregnancies may reflect the maturation and development of the peristalsis within the gastrointestinal tract in the newborn.

Pathophysiology
As MAS describes a spectrum of disorders of newborns born through MSAF, without any congenital respiratory disorders or other underlying pathology, there are numerous hypothesised mechanisms and causes for the onset of this syndrome. Long-term consequences may arise from these disorders, for example, infants that develop MAS have higher rates of developing neurodevelopmental defects due to poor respiration.

Airway obstruction
In the first 15 minutes of meconium aspiration, there is obstruction of larger airways which causes increased lung resistance, decreased lung compliance, acute hypoxemia, hypercapnia, atelectasis and respiratory acidosis. After 60 minutes of exposure, the meconium travels further down into the smaller airways. Once within the terminal bronchioles and alveoli, the meconium triggers inflammation, pulmonary edema, vasoconstriction, bronchoconstriction, collapse of airways and inactivation of surfactant.

Foetal hypoxia
The lung areas which do not or only partially participate in ventilation, because of obstruction and/or destruction, will become hypoxic and an inflammatory response may consequently occur. Partial obstruction will lead to air trapping and hyperinflation of certain lung areas and pneumothorax may follow. Chronic hypoxia will lead to an increase in pulmonary vascular smooth muscle tone and persistent pulmonary hypertension causing respiratory and circulatory failure.

Infection
Microorganisms, most commonly Gram-negative rods, and endotoxins are found in samples of MSAF at a higher rate than in clear amniotic fluid, for example 46.9% of patients with MSAF also had endotoxins present. A microbial invasion of the amniotic cavity (MIAC) is more common in patients with MSAF and this could ultimately lead to an intra-amniotic inflammatory response. MIAC is associated with high concentrations of cytokines (such as IL-6), chemokines (such as IL-8 and monocyte chemoattractant protein-1), complement, phospholipase A2 and matrix-degrading enzymes. Therefore, these aforementioned mediators within the amniotic fluid during MIAC and intra-amniotic infection could, when aspirated in utero, induce lung inflammation within the foetus.

Pulmonary inflammation
Meconium has a complex chemical composition, so it is difficult to identify a single agent responsible for the several diseases that arise. As meconium is stored inside the intestines, and is partly unexposed to the immune system, when it becomes aspirated the innate immune system recognises as a foreign and dangerous substance. The immune system, which is present at birth, responds within minutes with a low specificity and no memory in order to try to eliminate microbes. Meconium perhaps leads to chemical pneumonitis as it is a potent activator of inflammatory mediators which include cytokines, complement, prostaglandins and reactive oxygen species.Meconium is a source of pro-inflammatory cytokines, including tumour necrosis factor (TNF) and interleukins (IL-1, IL-6, IL-8), and mediators produced by neutrophils, macrophages and epithelial cells that may injure the lung tissue directly or indirectly. For example, proteolytic enzymes are released from neutrophilic granules and these may damage the lung membrane and surfactant proteins. Additionally, activated leukocytes and cytokines generate reactive nitrogen and oxygen species which have cytotoxic effects. Oxidative stress results in vasoconstriction, bronchoconstriction, platelet aggregation and accelerated cellular apoptosis. Recently, it has been hypothesised that meconium is a potent activator of toll-like receptor (TLRs) and complement, key mediators in inflammation, and may thus contribute to the inflammatory response in MAS.Meconium contains high amounts of phospholipase A2 (PLA2), a potent proinflammatory enzyme, which may directly (or through the stimulation of arachidonic acid) lead to surfactant dysfunction, lung epithelium destruction, tissue necrosis and an increase in apoptosis. Meconium can also activate the coagulation cascade, production of platelet-activating factor (PAF) and other vasoactive substances that may lead to destruction of capillary endothelium and basement membranes. Injury to the alveolocapillary membrane results in leakage of liquid, plasma proteins, and cells into the interstitium and alveolar spaces.

Surfactant inactivation
Surfactant is synthesised by type II alveolar cells and is made of a complex of phospholipids, proteins and saccharides. It functions to lower surface tension (to allow for lung expansion during inspiration), stabilise alveoli at the end of expiration (to prevent alveolar collapse) and prevents lung oedema. Surfactant also contributes to lung protection and defence as it is also an anti-inflammatory agent. Surfactant enhances the removal of inhaled particles and senescent cells away from the alveolar structure.The extent of surfactant inhibition depends on both the concentration of surfactant and meconium. If the surfactant concentration is low, even very highly diluted meconium can inhibit surfactant function whereas, in high surfactant concentrations, the effects of meconium are limited. Meconium may impact surfactant mechanisms by preventing surfactant from spreading over the alveolar surface, decreasing the concentration of surfactant proteins (SP-A and SP-B), and by changing the viscosity and structure of surfactant. Several morphological changes occur after meconium exposure, the most notable being the detachment of airway epithelium from stroma and the shedding of epithelial cells into the airway. These indicate a direct detrimental effect on lung alveolar cells because of the introduction of meconium into the lungs.

Persistent Pulmonary Hypertension
Persistent pulmonary hypertension (PPHN) is the failure of the foetal circulation to adapt to extra-uterine conditions after birth. PPHN is associated with various respiratory diseases, including MAS (as 15-20% of infants with MAS develop PPHN), but also pneumonia and sepsis. A combination of hypoxia, pulmonary vasoconstriction and ventilation/perfusion mismatch can trigger PPHN, depending on the concentration of meconium within the respiratory tract. PPHN in newborns is the leading cause of death in MAS.

Apoptosis
Apoptosis is an important mechanism in the clearance of injured cells and in tissue repair, however too much apoptosis may cause harm, such as acute lung injury. Meconium induces apoptosis and DNA cleavage of lung airway epithelial cells, this is detected by the presence of fragmented DNA within the airways and in alveolar epithelial nuclei. Meconium induces an inflammatory reaction within the lungs as there is an increase of autophagocytic cells and levels of caspase 3 after exposure. After 8 hours of meconium exposure, in rabbit foetuses, the total amount of apoptotic cells is 54%. Therefore, the majority of meconium-induced lung damage may be due to the apoptosis of lung epithelium.

Diagnosis
Respiratory distress in an infant born through the darkly coloured MSAF as well as meconium obstructing the airways is usually sufficient enough to diagnose MAS. Additionally, newborns with MAS can have other types of respiratory distress such as tachypnea and hypercapnia. Sometimes it is hard to diagnose MAS as it can be confused with other diseases that also cause respiratory distress, such as pneumonia. Additionally, X-rays and lung ultrasounds can be quick, easy and cheap imaging techniques to diagnose lung diseases like MAS.

Prevention
In general, the incidence of MAS has been significantly reduced over the past two decades as the number of post-term deliveries has minimized.

Prevention during pregnancy
Prevention during pregnancy may include amnioinfusion and antibiotics but the effectiveness of these treatments are questionable.

Prevention during parturition
As previously mentioned, oropharyngeal and nasopharyngeal suctioning is not an ideal preventative treatment for both vigorous and depressed (not breathing) infants.

Treatment
Most infants born through MSAF do not require any treatments (other than routine postnatal care) as they show no signs of respiratory distress, as only approximately 5% of infants born through MSAF develop MAS. However, infants which do develop MAS need to be admitted to a neonatal unit where they will be closely observed and provided any treatments needed. Observations include monitoring heart rate, respiratory rate, oxygen saturation and blood glucose (to detect worsening respiratory acidosis or the development of hypoglycemia). In general, treatment of MAS is more supportive in nature.

Assisted ventilation techniques
To clear the airways of meconium, tracheal suctioning can be used however, the efficacy of this method is in question and it can cause harm.In cases of MAS, there is a need for supplemental oxygen for at least 12 hours in order to maintain oxygen saturation of haemoglobin at 92% or more. The severity of respiratory distress can vary significantly between newborns with MAS, as some require minimal or no supplemental oxygen requirement and, in severe cases, mechanical ventilation may be needed. The desired oxygen saturation is between 90 and 95% and PaO2 may be as high as 90mmHg. In cases where there is thick meconium deep within the lungs, mechanical ventilation may be required. In extreme cases, extracorporeal membrane oxygenation (ECMO) may be utilised in infants who fail to respond to ventilation therapy. While on ECMO, the body can have time to absorb the meconium and for all the associated disorders to resolve. There has been an excellent response to this treatment, as the survival rate of MAS while on ECMO is more than 94%.Ventilation of infants with MAS can be challenging and, as MAS can affect each individual differently, ventilation administration may need to be customised. Some newborns with MAS can have homogenous lung changes and others can have inconsistent and patchy changes to their lungs. It is common for sedation and muscle relaxants to be used to optimise ventilation and minimise the risk of pneumothorax associated with dyssynchronous breathing.

Inhaled nitric oxide
Inhaled nitric oxide (iNO) acts on vascular smooth muscle causing selective pulmonary vasodilation. This is ideal in the treatment of PPHN as it causes vasodilation within ventilated areas of the lung thus, decreasing the ventilation-perfusion mismatch and thereby, improves oxygenation. Treatment utilising iNO decreases the need for ECMO and mortality in newborns with hypoxic respiratory failure and PPHN as a result of MAS. However, approximately 30-50% of infants with PPHN do not respond to iNO therapy.

Antiinflammatories
As inflammation is such a huge issue in MAS, treatment has consisted of anti-inflammatories.

Glucocorticoids
Glucocorticoids have a strong anti-inflammatory activity and works to reduce the migration and activation of neutrophils, eosinophils, mononuclear cells, and other cells. They reduce the migration of neutrophils into the lungs ergo, decreasing their adherence to the endothelium. Thus, there is a reduction in the action of mediators released from these cells and therefore, a reduced inflammatory response.Glucocorticoids also possess a genomic mechanism of action in which, once bound to a glucocorticoid receptor, the activated complex moves into the nucleus and inhibits transcription of mRNA. Ultimately, effecting whether various proteins get produced or not. Inhibiting the transcription of nuclear factor (NF-κB) and protein activator (AP-1) attenuates the expression of pro-inflammatory cytokines (IL-1, IL-6, IL-8 and TNF etc.), enzymes (PLA2, COX-2, iNOs etc.) and other biologically active substances. The anti-inflammatory effect of glucocorticoids is also demonstrated by enhancing the activity of lipocortines which inhibit the activity of PLA2 and therefore, decrease the production of arachidonic acid and mediators of lipoxygenase and cyclooxygenase pathways.Anti-inflammatories need to be administered as quickly as possible as the effect of these drugs can diminish even just an hour after meconium aspiration. For example, early administration of dexamethasone significantly enhanced gas exchange, reduced ventilatory pressures, decreased the number of neutrophils in the bronchoalveolar area, reduced oedema formation and oxidative lung injury. However, glucocorticoids may increase the risk of infection and this risk increases with the dose and duration of glucocorticoid treatment. Other issues can arise, such as aggravation of diabetes mellitus, osteoporosis, skin atrophy and growth retardation in children.

Inhibitors of phosphodiesterase
Phosphodiesterases (PDE) degrades cAMP and cGMP and, within the respiratory system of a newborn with MAS, various isoforms of PDE may be involved due to their pro-inflammatory and smooth muscle contractile activity. Therefore, non-selective and selective inhibitors of PDE could potentially be used in MAS therapy. However, the use of PDE inhibitors can cause cardiovascular side effects. Non-selective PDE inhibitors, such as methylxanthines, increase concentrations of cAMP and cGMP in the cells leading to bronchodilation and vasodilation. Additionally, methylxanthines decreases the concentrations of calcium, acetylcholine and monoamines, this controls the release of various mediators of inflammation and bronchoconstriction, including prostaglandins. Selective PDE inhibitors target one subtype of phosphodiesterase and in MAS the activities of PDE-3, PDE-4, PDE-5 and PDE-7 may become enhanced. For example, Milrinone (a selective PDE3 inhibitor) improved oxygenation and survival of neonates with MAS.

Inhibitors of cyclooxygenase
Arachidonic acid is metabolised, via cyclooxygenase (COX) and lipoxygenase, to various substances including prostaglandins and leukotrienes, which exhibit potent pro-inflammatory and vasoactive effects. By inhibiting COX, and more specifically COX-2, (either through selective or non-selective drugs) inflammation and oedema can be reduced. However, COX inhibitors may induce peptic ulcers and cause hyperkalemia and hypernatremia. Additionally, COX inhibitors have not shown any great response in the treatment of MAS.

Antibiotics
Meconium is typically sterile however, it can contain various cultures of bacteria so appropriate antibiotics may need to be prescribed.

Surfactant treatment
Lung lavage with diluted surfactant is a new treatment with potentially beneficial results depending on how early it is administered in newborns with MAS. This treatment shows promise as it has a significant effect on air leaks, pneumothorax, the need for ECMO and death. Early intervention and using it on newborns with mild MAS is more effective. However, there are risks as a large volume of fluid instillation to the lung of a newborn can be dangerous (particularly in cases of severe MAS with pulmonary hypertension) as it can exacerbate hypoxia and lead to mortality.

Previous treatments
Originally, it was believed that MAS developed as a result of the meconium being a physical blockage of the airways. Thus, to prevent newborns, who were born through MSAF, from developing MAS, suctioning of the oropharyngeal and nasopharyngeal area before delivery of the shoulders followed by tracheal aspiration was utilised for 20 years. This treatment was believed to be effective as it was reported to significantly decrease the incidence of MAS compared to those newborns born through MSAF who were not treated. This claim was later disproved and future studies concluded that oropharyngeal and nasopharyngeal suctioning, before delivery of the shoulders in infants born through MSAF, does not prevent MAS or its complications. In fact, it can cause more issues and damage (e.g. mucosal damage), thus it is not a recommended preventative treatment. Suctioning may not significantly reduce the incidence of MAS as meconium passage and aspiration may occur in-utero. Thereby making the suctioning redundant and useless as the meconium may already be deep within the lungs at the time of birth.Historically, amnioinfusion has been used when MSAF was present, which involves a transcervical infusion of fluid during labour. The idea was to dilute the thick meconium to reduce its potential pathophysiology and reduce cases of MAS, since MAS is more prevalent in cases of thick meconium. However, there are associated risks, such as umbilical cord prolapse and prolongation of labour </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Imperforate hymen and explain in detail? [/INST] An imperforate hymen is a congenital disorder where a hymen without an opening completely obstructs the vagina. It is caused by a failure of the hymen to perforate during fetal development. It is most often diagnosed in adolescent girls when menstrual blood accumulates in the vagina and sometimes also in the uterus. It is treated by surgical incision of the hymen.

Signs and symptoms
Affected newborns may present with acute urinary retention. In adolescent females, the most common symptoms of an imperforate hymen are cyclic pelvic pain and amenorrhea; other symptoms associated with hematocolpos include urinary retention, constipation, low back pain, nausea, and diarrhea. Other vaginal anomalies can have similar symptoms to an imperforate hymen. Vaginal atresia and a transverse vaginal septum require differentiation. A strong urge to defecate has been observed in a few women.

Complications
If untreated or unrecognized before puberty, an imperforate hymen can lead to peritonitis or endometriosis due to retrograde bleeding. Additionally, it can lead to mucometrocolpos (dilatation of the vaginal canal and uterus due to mucus buildup) or hematometrocolpos (dilatation due to buildup of menstrual fluid). Mucometrocolpos and hematocolpos can in turn cause urinary retention, constipation, and urinary tract infection.

Pathophysiology
An imperforate hymen is formed during fetal development when the sinovaginal bulbs fail to canalize with the rest of the vagina. Although some instances of familial occurrence have been reported, the conditions occurrence is mostly sporadic, and no genetic markers or mutations have been linked to its cause.

Diagnosis
An imperforate hymen is most often diagnosed in adolescent girls after the age of menarche with otherwise normal development. In adolescent girls of menarcheal age, the typical presentation of the condition is amennorhea and cyclic pelvic pain, indicative of hematocolpos secondary to vaginal obstruction. An imperforate hymen is usually visible on vaginal inspection as a bulging blue membrane. If hematocolpos is present, a mass is often palpable on abdominal or rectal examination. The diagnosis of an imperforate hymen is usually made based purely on the physical exam, although if necessary the diagnosis can be confirmed by transabdominal, transperineal or transrectal ultrasound.An imperforate hymen can also be diagnosed in newborn babies and it is occasionally detected on ultrasound scans of the foetus during pregnancy. In newborns the diagnosis is based on the findings of an abdominal or pelvic mass or a bulging hymen. Examination of the normal neonatal vagina usually reveals a track of mucus at the posterior commissure of the labia majora; an absence of mucus may indicate an imperforate hymen or another vaginal obstruction.A similar condition, cribriform hymen, is diagnosed when the hymen contains many minute openings.

Management
Before surgical intervention in adolescents, symptoms can be relieved by the combined oral contraceptive pill taken continuously to suppress the menstrual cycle or NSAIDs to relieve pain </s>


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Lipopolysaccharide and explain in detail? [/INST] Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer membrane of Gram-negative bacteria. Today, the term endotoxin is often used synonymously with LPS, although there are a few endotoxins (in the original sense of toxins that are inside the bacterial cell that are released when the cell disintegrates) that are not related to LPS, such as the so-called delta endotoxin proteins produced by Bacillus thuringiensis.Lipopolysaccharides can have substantial impacts on human health, primarily through interactions with the immune system. LPS is a potent activator of the immune system and pyrogen (agent that causes fever). In severe cases, LPS can play a role in causing septic shock. In lower levels and over a longer time period, there is evidence LPS may play an important and harmful role in autoimmunity, obesity, depression, and cellular senescence.

Discovery
The toxic activity of LPS was first discovered and termed endotoxin by Richard Friedrich Johannes Pfeiffer. He distinguished between exotoxins, toxins that are released by bacteria into the surrounding environment, and endotoxins, which are toxins "within" the bacterial cell and released only after destruction of the bacterial outer membrane. Subsequent work showed that release of LPS from gram negative microbes does not necessarily require the destruction of the bacterial cell wall, but rather, LPS is secreted as part of the normal physiological activity of membrane vesicle trafficking in the form of bacterial outer membrane vesicles (OMVs), which may also contain other virulence factors and proteins.

Functions in bacteria
LPS is a major component of the outer membrane of Gram-negative bacteria, contributing greatly to the structural integrity of the bacteria and protecting the membrane from certain kinds of chemical attack. LPS is the most abundant antigen on the cell surface of most Gram-negative bacteria, contributing up to 80% of the outer membrane of E. coli and Salmonella.  LPS increases the negative charge of the cell membrane and helps stabilize the overall membrane structure. It is of crucial importance to many Gram-negative bacteria, which die if the genes coding for it are mutated or removed. However, it appears that LPS is nonessential in at least some Gram-negative bacteria, such as Neisseria meningitidis, Moraxella catarrhalis, and Acinetobacter baumannii. It has also been implicated in non-pathogenic aspects of bacterial ecology, including surface adhesion, bacteriophage sensitivity, and interactions with predators such as amoebae. LPS is also required for the functioning of omptins, a class of bacterial protease.

Composition
Lipopolysaccharides are composed of three parts: The O antigen (or O polysaccharide), the Core oligosaccharide, and Lipid A.

O-antigen
The repetitive glycan polymer contained within an LPS is referred to as the O antigen, O polysaccharide, or O side-chain of the bacteria. The O antigen is attached to the core oligosaccharide, and comprises the outermost domain of the LPS molecule. The composition of the O chain varies from strain to strain; there are over 160 different O antigen structures produced by different E. coli strains. The presence or absence of O chains determines whether the LPS is considered "rough" or "smooth". Full-length O-chains would render the LPS smooth, whereas the absence or reduction of O-chains would make the LPS rough. Bacteria with rough LPS usually have more penetrable cell membranes to hydrophobic antibiotics, since a rough LPS is more hydrophobic. O antigen is exposed on the very outer surface of the bacterial cell, and, as a consequence, is a target for recognition by host antibodies.

Core
The core domain always contains an oligosaccharide component that attaches directly to lipid A and commonly contains sugars such as heptose and 3-Deoxy-D-manno-oct-2-ulosonic acid (also known as KDO, keto-deoxyoctulosonate).  The LPS cores of many bacteria also contain non-carbohydrate components, such as phosphate, amino acids, and ethanolamine substituents.

Lipid A
Lipid A is, in normal circumstances, a phosphorylated glucosamine disaccharide decorated with multiple fatty acids. These hydrophobic fatty acid chains anchor the LPS into the bacterial membrane, and the rest of the LPS projects from the cell surface. The lipid A domain is responsible for much of the toxicity of Gram-negative bacteria. When bacterial cells are lysed by the immune system, fragments of membrane containing lipid A are released into the circulation, causing fever, diarrhea, and possible fatal endotoxic shock (also called septic shock). The Lipid A moiety is a very conserved component of the LPS. However Lipid A structure varies among bacterial species. Lipid A structure largely defines the degree and nature of the overall host immune activation.

Lipooligosaccharides
The "rough form" of LPS has a lower molecular weight due to the absence of the O polysaccharide. In its place is   a short oligosaccharide: this form is known as Lipooligosaccharide (LOS), and is a glycolipid found in the outer membrane of some types of Gram-negative bacteria, such as Neisseria spp. and Haemophilus spp.  LOS plays a central role in maintaining the integrity and functionality of the outer membrane of the Gram negative cell envelope. LOS play an important role in the pathogenesis of certain bacterial infections because they are capable of acting as immunostimulators and immunomodulators. Furthermore, LOS molecules are responsible for the ability of some bacterial strains to display molecular mimicry and antigenic diversity, aiding in the evasion of host immune defenses and thus contributing to the virulence of these bacterial strains. In the case of Neisseria meningitidis, the lipid A portion of the molecule has a symmetrical structure and the inner core is composed of 3-deoxy-D-manno-2-octulosonic acid (KDO) and heptose (Hep) moieties. The outer core oligosaccharide chain varies depending on the bacterial strain.

LPS detoxification
A highly conserved host enzyme called acyloxyacyl hydrolase (AOAH) may detoxify LPS when it enters, or is produced in, animal tissues. It may also convert LPS in the intestine into an LPS inhibitor. Neutrophils, macrophages and dendritic cells produce this lipase, which inactivates LPS by removing the two secondary acyl chains from lipid A to produce tetraacyl LPS.  If mice are given LPS parenterally, those that lack AOAH develop high titers of non-specific antibodies, develop prolonged hepatomegaly, and experience prolonged endotoxin tolerance. LPS inactivation may be required for animals to restore homeostasis after parenteral LPS exposure.  Although mice have many other mechanisms for inhibiting LPS signaling, none is able to prevent these changes in animals that lack AOAH.
Dephosphorylation of LPS by intestinal alkaline phosphatase can reduce the severity of Salmonella tryphimurium and Clostridioides difficile infection restoring normal gut microbiota. Alkaline phosphatase prevents intestinal inflammation (and
"leaky gut") from bacteria by dephosphorylating the Lipid A portion of LPS.

Biosynthesis and transport
Biological effects on hosts infected with Gram-negative bacteria
Immune response
LPS acts as the prototypical endotoxin because it binds the CD14/TLR4/MD2 receptor complex in many cell types, but especially in monocytes, dendritic cells, macrophages and B cells, which promotes the secretion of pro-inflammatory cytokines, nitric oxide, and eicosanoids. Bruce Beutler was awarded a portion of the 2011 Nobel Prize in Physiology or Medicine for his work demonstrating that TLR4 is the LPS receptor.As part of the cellular stress response, superoxide is one of the major reactive oxygen species induced by LPS in various cell types that express TLR (toll-like receptor). LPS is also an exogenous pyrogen (fever-inducing substance).LPS function has been under experimental research for several years due to its role in activating many transcription factors. LPS also produces many types of mediators involved in septic shock. Humans are much more sensitive to LPS than other animals (e.g., mice). A dose of 1 µg/kg induces shock in humans, but mice will tolerate a dose up to a thousand times higher. This may relate to differences in the level of circulating natural antibodies between the two species.
Said et al. showed that LPS causes an IL-10-dependent inhibition of CD4 T-cell expansion and function by up-regulating PD-1 levels on monocytes which leads to IL-10 production by monocytes after binding of PD-1 by PD-L1.Endotoxins are in large part responsible for the dramatic clinical manifestations of infections with pathogenic Gram-negative bacteria, such as Neisseria meningitidis, the pathogens that causes meningococcal disease, including meningococcemia, Waterhouse–Friderichsen syndrome, and meningitis.
Portions of the LPS from several bacterial strains have been shown to be chemically similar to human host cell surface molecules; the ability of some bacteria to present molecules on their surface which are chemically identical or similar to the surface molecules of some types of host cells is termed molecular mimicry.  For example, in Neisseria meningitidis L2,3,5,7,9, the terminal tetrasaccharide portion of the oligosaccharide (lacto-N-neotetraose) is the same tetrasaccharide as that found in paragloboside, a precursor for ABH glycolipid antigens found on human erythrocytes. In another example, the terminal trisaccharide portion (lactotriaose) of the oligosaccharide from pathogenic Neisseria spp. LOS is also found in lactoneoseries glycosphingolipids from human cells.  Most meningococci from groups B and C, as well as gonococci, have been shown to have this trisaccharide as part of their LOS structure.  The presence of these human cell surface mimics may, in addition to acting as a camouflage from the immune system, play a role in the abolishment of immune tolerance when infecting hosts with certain human leukocyte antigen (HLA) genotypes, such as HLA-B35.LPS can be sensed directly by hematopoietic stem cells (HSCs) through the bonding with TLR4, causing them to proliferate in reaction to a systemic infection.  This response activate the TLR4-TRIF-ROS-p38 signaling within the HSCs and through a sustained TLR4 activation can cause a proliferative stress, leading to impair their competitive repopulating ability.  Infection in mice using S. typhimurium showed similar results, validating the experimental model also in vivo.

Effect of variability on immune response
O-antigens (the outer carbohydrates) are the most variable portion of the LPS molecule, imparting the antigenic specificity. In contrast, lipid A is the most conserved part. However, lipid A composition also may vary (e.g., in number and nature of acyl chains even within or between genera). Some of these variations may impart antagonistic properties to these LPS. For example, Rhodobacter sphaeroides diphosphoryl lipid A (RsDPLA) is a potent antagonist of LPS in human cells, but is an agonist in hamster and equine cells.It has been speculated that conical Lipid A (e.g., from E. coli) are more agonistic, less conical lipid A like those of Porphyromonas gingivalis may activate a different signal (TLR2 instead of TLR4), and completely cylindrical lipid A like that of Rhodobacter sphaeroides is antagonistic to TLRs. In general, LPS gene clusters are highly variable between different strains, subspecies, species of bacterial pathogens of plants and animals.Normal human blood serum contains anti-LOS antibodies that are bactericidal and patients that have infections caused by serotypically distinct strains possess anti-LOS antibodies that differ in their specificity compared with normal serum. These differences in humoral immune response to different LOS types can be attributed to the structure of the LOS molecule, primarily within the structure of the oligosaccharide portion of the LOS molecule.
In Neisseria gonorrhoeae it has been demonstrated that the antigenicity of LOS molecules can change during an infection due to the ability of these bacteria to synthesize more than one type of LOS, a characteristic known as phase variation. Additionally, Neisseria gonorrhoeae, as well as Neisseria meningitidis and Haemophilus influenzae, are capable of further modifying their LOS in vitro, for example through sialylation (modification with sialic acid residues), and as a result are able to increase their resistance to complement-mediated killing  or even down-regulate complement activation or evade the effects of bactericidal antibodies. Sialylation may also contribute to hindered neutrophil attachment and phagocytosis by immune system cells as well as a reduced oxidative burst. Haemophilus somnus, a pathogen of cattle, has also been shown to display LOS phase variation, a characteristic which may help in the evasion of bovine host immune defenses.
Taken together, these observations suggest that variations in bacterial surface molecules such as LOS can help the pathogen evade both the humoral (antibody and complement-mediated) and the cell-mediated (killing by neutrophils, for example) host immune defenses.

Non-canonical pathways of LPS recognition
Recently, it was shown that in addition to TLR4 mediated pathways, certain members of the family of the transient receptor potential ion channels recognize LPS. LPS-mediated activation of TRPA1 was shown in mice and Drosophila melanogaster flies. At higher concentrations, LPS activates other members of the sensory TRP channel family as well, such as TRPV1, TRPM3 and to some extent TRPM8.
LPS is recognized by TRPV4 on epithelial cells. TRPV4 activation by LPS was necessary and sufficient to induce nitric oxide production with a bactericidal effect.

Health effects
In general the health effects of LPS are due to its abilities as a potent activator and modulator of the immune system, especially its inducement of inflammation.

Endotoxemia
The presence of endotoxins in the blood is called endotoxemia. High level of endotoxemia can lead to septic shock, while lower concentration of endotoxins in the bloodstream is called metabolic endotoxemia. Endotoxemia is associated with obesity, diet, cardiovascular diseases, and diabetes, while also host genetics might have an effect.Moreover, endotoxemia of intestinal origin, especially, at the host-pathogen interface, is considered to be an important factor in the development of alcoholic hepatitis,  which is likely to develop on the basis of the small bowel bacterial overgrowth syndrome and an increased intestinal permeability.Lipid A may cause uncontrolled activation of mammalian immune systems with production of inflammatory mediators that may lead to septic shock. This inflammatory reaction is mediated by Toll-like receptor 4 which is responsible for immune system cell activation. Damage to the endothelial layer of blood vessels caused by these inflammatory mediators can lead to capillary leak syndrome, dilation of blood vessels and a decrease in cardiac function and can lead to septic shock. Pronounced complement activation can also be observed later in the course as the bacteria multiply in the blood. High bacterial proliferation triggering destructive endothelial damage can also lead to disseminated intravascular coagulation (DIC) with loss of function of certain internal organs such as the kidneys, adrenal glands and lungs due to compromised blood supply. The skin can show the effects of vascular damage often coupled with depletion of coagulation factors in the form of petechiae, purpura and ecchymoses. The limbs can also be affected, sometimes with devastating consequences such as the development of gangrene, requiring subsequent amputation. Loss of function of the adrenal glands can cause adrenal insufficiency and additional hemorrhage into the adrenals causes Waterhouse-Friderichsen syndrome, both of which can be life-threatening.
It has also been reported that gonococcal LOS can cause damage to human fallopian tubes.

Auto-immune disease
The molecular mimicry of some LOS molecules is thought to cause autoimmune-based host responses, such as flareups of multiple sclerosis.  Other examples of bacterial mimicry of host structures via LOS are found with the bacteria Helicobacter pylori and Campylobacter jejuni, organisms which cause gastrointestinal disease in humans, and Haemophilus ducreyi which causes chancroid. Certain C. jejuni LPS serotypes (attributed to certain tetra- and pentasaccharide moieties of the core oligosaccharide) have also been implicated with Guillain–Barré syndrome and a variant of Guillain–Barré called Miller-Fisher syndrome.

Link to obesity
Epidemiological studies have shown that increased endotoxin load, which can be a result of increased populations of endotoxin-producing bacteria in the intestinal tract, is associated with certain obesity-related patient groups. Other studies have shown that purified endotoxin from Escherichia coli can induce obesity and insulin-resistance when injected into germ-free mouse models. A more recent study has uncovered a potentially contributing role for Enterobacter cloacae B29 toward obesity and insulin resistance in a human patient </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Thrombocytopenia and explain in detail? [/INST] Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in 20% of medical patients and a third of surgical patients.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. Values outside this range do not necessarily indicate disease. One common definition of thrombocytopenia requiring emergency treatment is a platelet count below 50,000 per microliter. Thrombocytopenia can be contrasted with the conditions associated with an abnormally high level of platelets in the blood: thrombocythemia (when the cause is unknown), and thrombocytosis (when the cause is known).

Signs and symptoms
Thrombocytopenia usually has no symptoms and is picked up on a routine complete blood count. Some individuals with thrombocytopenia may experience external bleeding such as nosebleeds, or bleeding gums. Some women may have heavier or longer periods or breakthrough bleeding. Bruising, particularly purpura in the forearms and petechiae in the feet, legs, and mucous membranes, may be caused by spontaneous bleeding under the skin.Eliciting a full medical history is vital to ensure the low platelet count is not secondary to another disorder. Ensuring that the other blood cell types, such as red blood cells and white blood cells are not also suppressed, is also important.
Painless, round, and pinpoint (1 to 3 mm in diameter) petechiae usually appear and fade, and sometimes group to form ecchymoses. Larger than petechiae, ecchymoses are purple, blue, or yellow-green areas of skin that vary in size and shape. They can occur anywhere on the body.A person with this disease may also complain of malaise, fatigue, and general weakness (with or without accompanying blood loss). Acquired thrombocytopenia may be associated with the use of certain drugs. Inspection typically reveals evidence of bleeding (petechiae or ecchymoses), along with slow, continuous bleeding from any injuries or wounds. Adults may have large, blood-filled bullae in the mouth. If the persons platelet count is between 30,000 and 50,000/mm3, bruising with minor trauma may be expected; if it is between 15,000 and 30,000/mm3, spontaneous bruising will be seen (mostly on the arms and legs).

Causes
Thrombocytopenia can be inherited or acquired.

Decreased production
Abnormally low platelet production may be caused by:
Dehydration, Vitamin B12 or folic acid deficiency
Leukemia, myelodysplastic syndrome, or aplastic anemia
Decreased production of thrombopoietin by the liver in liver failure
Sepsis, systemic viral or bacterial infection
Leptospirosis
Hereditary syndromesACTN1-related thrombocytopenia
Amegakaryocytic thrombocytopenia with radio-ulnar synostosis
ANKRD26 related thrombocytopenia
Autosomal dominant thrombocytopenia
Bernard–Soulier syndrome (associated with giant platelet disorder)
Congenital amegakaryocytic thrombocytopenia
Congenital amegakaryocytic thrombocytopenia and radioulnar synostosis
CYCS-related thrombocytopenia
Epstein syndrome (associated with giant platelet disorder)
ETV6 related thrombocytopenia
Fanconi anemia
Filaminopathies A
FYB related thrombocytopenia
Glanzmanns thrombasthenia
GNE myopathy with congenital thrombocytopenia
Gray platelet syndrome (associated with giant platelet disorder)
Harris platelet syndrome (associated with giant platelet disorder)
Macrothrombocytopenia and hearing loss
May–Hegglin anomaly (associated with giant platelet disorder)
MYH9-related disease (associated with giant platelet disorder)
PRKACG-related thrombocytopenia
Paris-Trousseau thrombocytopenia/Jacobsen syndrome
Sebastian syndrome
SLFN14-related thrombocytopenia
Stormorken syndrome
TRPM7-related thrombocytopenia
Thrombocytopenia absent radius syndrome
Tropomyosin 4-related thrombocytopenia
TUBB1-related thrombocytopenia
Upshaw–Schulman syndrome
Wiskott–Aldrich syndrome
X-linked thrombocytopenia
X-linked thrombocytopenia with thalassemia

Increased destruction
Abnormally high rates of platelet destruction may be due to immune or nonimmune conditions, including:
Immune thrombocytopenic purpura
Thrombotic thrombocytopenic purpura
Hemolytic–uremic syndrome
Disseminated intravascular coagulation
Paroxysmal nocturnal hemoglobinuria
Antiphospholipid syndrome
Systemic lupus erythematosus
Post-transfusion purpura
Neonatal alloimmune thrombocytopenia
Hypersplenism
Dengue fever
Gauchers disease
Zika virus

Medication-induced
These medications can induce thrombocytopenia through direct myelosuppression:
Valproic acid
Methotrexate
Carboplatin
Interferon
Isotretinoin
Panobinostat
H2 blockers and proton-pump inhibitors

Other causes
Lab error, possibly due to the anticoagulant EDTA in CBC specimen tubes; a citrated platelet count is a useful follow-up study
Snakebite
Niacin toxicity
Lyme disease
Thrombocytapheresis (also called plateletpheresis)
Niemann–Pick disease

Diagnosis
Laboratory tests for thrombocytopenia might include full blood count, liver enzymes, kidney function, vitamin B12 levels, folic acid levels, erythrocyte sedimentation rate, and peripheral blood smear. If the cause for the low platelet count remains unclear, a bone marrow biopsy is usually recommended to differentiate cases of decreased platelet production from cases of peripheral platelet destruction.Thrombocytopenia in hospitalized alcoholics may be caused by spleen enlargement, folate deficiency, and most frequently, the direct toxic effect of alcohol on production, survival time, and function of platelets. Platelet count begins to rise after 2 to 5 days abstinence from alcohol. The condition is generally benign, and clinically significant hemorrhage is rare.In severe thrombocytopenia, a bone marrow study can determine the number, size, and maturity of the megakaryocytes. This information may identify ineffective platelet production as the cause of thrombocytopenia and rule out a malignant disease process at the same time.

Treatment
Treatment is guided by the severity and specific cause of the disease. Treatment focuses on eliminating the underlying problem, whether that means discontinuing drugs suspected to cause it or treating underlying sepsis.  Diagnosis and treatment of serious thrombocytopenia is usually directed by a hematologist. Corticosteroids may be used to increase platelet production. Lithium carbonate or folate may also be used to stimulate platelet production in the bone marrow.

Platelet transfusions
Platelet transfusions may be suggested for people who have a low platelet count due to thrombocytopenia.

Thrombotic thrombocytopenic purpura
Treatment of thrombotic thrombocytopenic purpura (TTP) is a medical emergency, since the associated hemolytic anemia and platelet activation can lead to kidney failure and changes in the level of consciousness.  Treatment of TTP was revolutionized in the 1980s with the application of plasmapheresis.  According to the Furlan-Tsai hypothesis, this treatment works by removing antibodies against the von Willebrand factor-cleaving protease ADAMTS-13. The plasmapheresis procedure also adds active ADAMTS-13 protease proteins to the patient, restoring a normal level of von Willebrand factor multimers.  Patients with persistent antibodies against ADAMTS-13 do not always manifest TTP, and these antibodies alone are not sufficient to explain how plasmapheresis treats TTP.

Immune thrombocytopenic purpura
Many cases of immune thrombocytopenic purpura (ITP) also known as idiopathic thrombocytopenic purpura, can be left untreated, and spontaneous remission (especially in children) is not uncommon. However, counts under 50,000 are usually monitored with regular blood tests, and those with counts under 10,000 are usually treated, as the risk of serious spontaneous bleeding is high with such low platelet counts. Any patient experiencing severe bleeding symptoms is also usually treated. The threshold for treating ITP has decreased since the 1990s; hematologists recognize that patients rarely spontaneously bleed with platelet counts greater than 10,000, although exceptions to this observation have been documented.Thrombopoetin analogues have been tested extensively for the treatment of ITP.  These agents had previously shown promise, but had been found to stimulate antibodies against endogenous thrombopoietin or lead to thrombosis. Romiplostim (trade name Nplate, formerly AMG 531) was found to be safe and effective for the treatment of ITP in refractory patients, especially those who relapsed following splenectomy.

Heparin-induced thrombocytopenia
Discontinuation of heparin is critical in a case of heparin-induced thrombocytopenia (HIT). Beyond that, however, clinicians generally treat to avoid thrombosis. Treatment may include a direct thrombin inhibitor, such as lepirudin or argatroban. Other blood thinners sometimes used in this setting include bivalirudin and fondaparinux. Platelet transfusions are not routinely used to treat HIT because thrombosis, not bleeding, is the primary problem. Warfarin is not recommended until platelets have normalized.

Congenital amegakaryocytic thrombocytopenia
Bone marrow/stem cell transplants are the only known cures for this genetic disease. Frequent platelet transfusions are required to keep the patient from bleeding to death before the transplant can be performed, although this is not always the case.

Human induced pluripotent stem cell-derived platelets
Human induced pluripotent stem cell-derived platelets is a technology currently being researched by the private sector, in association with the Biomedical Advanced Research and Development Authority  and the U.S. Department of Health and Human Services, that would create platelets outside the human body.

Neonatal thrombocytopenia
Thrombocytopenia affects a few newborns, and its prevalence in neonatal intensive care units  is high. Normally, it is mild and resolves without consequences </s>