<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 Breast and explain in detail? [/INST] The breast is one of two prominences located on the upper ventral region of a primates torso. Both females and males develop breasts from the same embryological tissues.
In females, it serves as the mammary gland, which produces and secretes milk to feed infants. Subcutaneous fat covers and envelops a network of ducts that converge on the nipple, and these tissues give the breast its size and shape. At the ends of the ducts are lobules, or clusters of alveoli, where milk is produced and stored in response to hormonal signals. During pregnancy, the breast responds to a complex interaction of hormones, including estrogens, progesterone, and prolactin, that mediate the completion of its development, namely lobuloalveolar maturation, in preparation of lactation and breastfeeding.
Humans are the only animals with permanent breasts. At puberty, estrogens, in conjunction with growth hormone, cause permanent breast growth in female humans. This happens only to a much lesser extent in other primates—breast development in other primates generally only occurs with pregnancy. Along with their major function in providing nutrition for infants, female breasts have social and sexual characteristics. Breasts have been featured in ancient and modern sculpture, art, and photography. They can figure prominently in the perception of a womans body and sexual attractiveness. A number of cultures associate breasts with sexuality and tend to regard bare breasts in public as immodest or indecent. Breasts, especially the nipples, are an erogenous zone.

Etymology and terminology
The English word breast derives from the Old English word brēost (breast, bosom) from Proto-Germanic *breustam (breast), from the Proto-Indo-European base bhreus– (to swell, to sprout). The breast spelling conforms to the Scottish and North English dialectal pronunciations. The Merriam-Webster Dictionary states that "Middle English brest, [comes] from Old English brēost; akin to Old High German brust..., Old Irish brú [belly], [and] Russian bryukho"; the first known usage of the term was before the 12th century.A large number of colloquial terms for breasts are used in English, ranging from fairly polite terms to vulgar or slang. Some vulgar slang expressions may be considered to be derogatory or sexist to women.

Evolutionary development
Humans are the only mammals whose breasts become permanently enlarged after sexual maturity (known in humans as puberty). The reason for this evolutionary change was unknown. Several hypotheses have been put forward:
A link has been proposed to processes for synthesizing the endogenous steroid hormone precursor dehydroepiandrosterone which takes place in fat rich  regions  of the body like the buttocks and breasts. These contributed to human brain development and played a part in increasing brain size.  Breast enlargement may for this purpose may have occurred as early as Homo ergaster (1.7-1.4 MYA). Other breast formation hypotheses may have then taken over as principal drivers.It has been suggested by zoologists Avishag and Amotz Zahavi  that the size of the human  breasts can be explained by the handicap theory of sexual dimorphism. This would see the explanation for larger breasts as them being  an honest display of the womens health and ability to grow and carry them in her life. Prospective mates can then evaluate the genes of a potential mate for their ability to sustain her health even with the additional energy demanding burden she is carrying.The zoologist Desmond Morris describes a sociobiological approach in his popular science book The Naked Ape. He suggests, by making comparisons with the other primates, that breasts evolved to replace swelling buttocks as a sex signal, of ovulation. He notes how humans have, relatively speaking, large penises as well as large breasts. Furthermore, early humans adopted bipedalism and face-to-face coitus. He therefore suggested enlarged sexual signals helped maintain the bond between a mated male and female even though they performed different duties and therefore were separated for lengths of time.The study The Evolution of the Human Breast (2001) proposed that the rounded shape of a womans breast evolved to prevent the sucking infant offspring from suffocating while feeding at the teat; that is, because of the human infants small jaw, which did not project from the face to reach the nipple, he or she might block the nostrils against the mothers breast if it were of a flatter form (cf. common chimpanzee). Theoretically, as the human jaw receded into the face, the womans body compensated with round breasts.Ashley Montague (1965) proposed that breasts came about as an  adaptation for infant feeding for a different reason as early human ancestors adopted bipedalism and the loss of body hair.  Human upright stance meant  infants must be carried at the hip or shoulder instead of on the back as in the apes. This gives the infant less opportunity to find the nipple or the  purchase to cling on to the mothers body hair.  The mobility of the nipple on a large breast  in most human females gives the infant more ability to find grasp it and feed.Other suggestions include simply that permanent breasts attracted mates, that "pendulous" breasts gave infants something to cling to, or that permanent breasts shared the function of a camels hump, to store fat as an energy reserve.

Anatomy
In women, the breasts overlie the pectoralis major muscles and extend on average from the level of the second rib to the level of the sixth rib in the front of the rib cage; thus, the breasts cover much of the chest area and the chest walls. At the front of the chest, the breast tissue can extend from the clavicle (collarbone) to the middle of the sternum (breastbone). At the sides of the chest, the breast tissue can extend into the axilla (armpit), and can reach as far to the back as the latissimus dorsi muscle, extending from the lower back to the humerus bone (the bone of the upper arm). As a mammary gland, the breast is composed of differing layers of tissue, predominantly two types: adipose tissue; and glandular tissue, which affects the lactation functions of the breasts.: 115 Morphologically the breast is tear-shaped. The superficial tissue layer (superficial fascia) is separated from the skin by 0.5–2.5 cm of subcutaneous fat (adipose tissue). The suspensory Coopers ligaments are fibrous-tissue prolongations that radiate from the superficial fascia to the skin envelope. The female adult breast contains 14–18 irregular lactiferous lobes that converge at the nipple. The 2.0–4.5 mm milk ducts are immediately surrounded with dense connective tissue that support the glands. Milk exits the breast through the nipple, which is surrounded by a pigmented area of skin called the areola. The size of the areola can vary widely among women. The areola contains modified sweat glands known as Montgomerys glands. These glands secrete oily fluid that lubricate and protect the nipple during breastfeeding. Volatile compounds in these secretions may also serve as an olfactory stimulus for the newborns appetite.The dimensions and weight of the breast vary widely among women. A small-to-medium-sized breast weighs 500 grams (1.1 pounds) or less, and a large breast can weigh approximately 750 to 1,000 grams (1.7 to 2.2 pounds) or more. The tissue composition ratios of the breast also vary among women. Some womens breasts have a higher proportion of glandular tissue than of adipose or connective tissues. The fat-to-connective-tissue ratio determines the density or firmness of the breast. During a womans life, her breasts change size, shape, and weight due to hormonal changes during puberty, the menstrual cycle, pregnancy, breastfeeding, and menopause.

Glandular structure
The breast is an apocrine gland that produces the milk used to feed an infant. The nipple of the breast is surrounded by the areola (nipple-areola complex). The areola has many sebaceous glands, and the skin color varies from pink to dark brown. The basic units of the breast are the terminal duct lobular units (TDLUs), which produce the fatty breast milk. They give the breast its offspring-feeding functions as a mammary gland. They are distributed throughout the body of the breast. Approximately two-thirds of the lactiferous tissue is within 30 mm of the base of the nipple. The terminal lactiferous ducts drain the milk from TDLUs into 4–18 lactiferous ducts, which drain to the nipple. The milk-glands-to-fat ratio is 2:1 in a lactating woman, and 1:1 in a non-lactating woman. In addition to the milk glands, the breast is also composed of connective tissues (collagen, elastin), white fat, and the suspensory Coopers ligaments. Sensation in the breast is provided by the peripheral nervous system innervation by means of the front (anterior) and side (lateral) cutaneous branches of the fourth-, fifth-, and sixth intercostal nerves. The T-4 nerve (Thoracic spinal nerve 4), which innervates the dermatomic area, supplies sensation to the nipple-areola complex.

Lymphatic drainage
Approximately 75% of the lymph from the breast travels to the axillary lymph nodes on the same side of the body, whilst 25% of the lymph travels to the parasternal nodes (beside the sternum bone).: 116  A small amount of remaining lymph travels to the other breast and to the abdominal lymph nodes. The subareolar region has a lymphatic plexus known as the "subareolar plexus of Sappey". The axillary lymph nodes include the pectoral (chest), subscapular (under the scapula), and humeral (humerus-bone area) lymph-node groups, which drain to the central axillary lymph nodes and to the apical axillary lymph nodes. The lymphatic drainage of the breasts is especially relevant to oncology because breast cancer is common to the mammary gland, and cancer cells can metastasize (break away) from a tumour and be dispersed to other parts of the body by means of the lymphatic system.

Shape, texture, and support
The morphologic variations in the size, shape, volume, tissue density, pectoral locale, and spacing of the breasts determine their natural shape, appearance, and position on a womans chest. Breast size and other characteristics do not predict the fat-to-milk-gland ratio or the potential for the woman to nurse an infant. The size and the shape of the breasts are influenced by normal-life hormonal changes (thelarche, menstruation, pregnancy, menopause) and medical conditions (e.g. virginal breast hypertrophy). The shape of the breasts is naturally determined by the support of the suspensory Coopers ligaments, the underlying muscle and bone structures of the chest, and by the skin envelope. The suspensory ligaments sustain the breast from the clavicle (collarbone) and the clavico-pectoral fascia (collarbone and chest) by traversing and encompassing the fat and milk-gland tissues. The breast is positioned, affixed to, and supported upon the chest wall, while its shape is established and maintained by the skin envelope. In most women, one breast is slightly larger than the other. More obvious and persistent asymmetry in breast size occurs in up to 25% of women.While it is a common belief that breastfeeding causes breasts to sag, researchers have found that a womans breasts sag due to four key factors: cigarette smoking, number of pregnancies, gravity, and weight loss or gain.The base of each breast is attached to the chest by the deep fascia over the pectoralis major muscles. The space between the breast and the pectoralis major muscle, called retromammary space, gives mobility to the breast.
The chest (thoracic cavity) progressively slopes outwards from the thoracic inlet (atop the breastbone) and above to the lowest ribs that support the breasts. The inframammary fold, where the lower portion of the breast meets the chest, is an anatomic feature created by the adherence of the breast skin and the underlying connective tissues of the chest; the IMF is the lower-most extent of the anatomic breast. Normal breast tissue typically has a texture that feels nodular or granular, to an extent that varies considerably from woman to woman.

Development
The breasts are principally composed of adipose, glandular, and connective tissues. Because these tissues have hormone receptors, their sizes and volumes fluctuate according to the hormonal changes particular to thelarche (sprouting of breasts), menstruation (egg production), pregnancy (reproduction), lactation (feeding of offspring), and menopause (end of menstruation).

Puberty
The morphological structure of the human breast is identical in males and females until puberty. For pubescent girls in thelarche (the breast-development stage), the female sex hormones (principally estrogens) in conjunction with growth hormone promote the sprouting, growth, and development of the breasts. During this time, the mammary glands grow in size and volume and begin resting on the chest. These development stages of secondary sex characteristics (breasts, pubic hair, etc.) are illustrated in the five-stage Tanner Scale.During thelarche the developing breasts are sometimes of unequal size, and usually the left breast is slightly larger. This condition of asymmetry is transitory and statistically normal in female physical and sexual development. Medical conditions can cause overdevelopment (e.g., virginal breast hypertrophy, macromastia) or underdevelopment (e.g., tuberous breast deformity, micromastia) in girls and women.
Approximately two years after the onset of puberty (a girls first menstrual cycle), estrogen and growth hormone stimulate the development and growth of the glandular fat and suspensory tissues that compose the breast. This continues for approximately four years until the final shape of the breast (size, volume, density) is established at about the age of 21. Mammoplasia (breast enlargement) in girls begins at puberty, unlike all other primates in which breasts enlarge only during lactation.

Changes during the menstrual cycle
During the menstrual cycle, the breasts are enlarged by premenstrual water retention and temporary growth.

Pregnancy and breastfeeding
The breasts reach full maturity only when a womans first pregnancy occurs.  Changes to the breasts are among the first signs of pregnancy. The breasts become larger, the nipple-areola complex becomes larger and darker, the Montgomerys glands enlarge, and veins sometimes become more visible. Breast tenderness during pregnancy is common, especially during the first trimester. By mid-pregnancy, the breast is physiologically capable of lactation and some women can express colostrum, a form of breast milk.Pregnancy causes elevated levels of the hormone prolactin, which has a key role in the production of milk. However, milk production is blocked by the hormones progesterone and estrogen until after delivery, when progesterone and estrogen levels plummet.

Menopause
At menopause, breast atrophy occurs. The breasts can decrease in size when the levels of circulating estrogen decline. The adipose tissue and milk glands also begin to wither. The breasts can also become enlarged from adverse side effects of combined oral contraceptive pills. The size of the breasts can also increase and decrease in response to weight fluctuations. Physical changes to the breasts are often recorded in the stretch marks of the skin envelope; they can serve as historical indicators of the increments and the decrements of the size and volume of a womans breasts throughout the course of her life.

Breastfeeding
The primary function of the breasts, as mammary glands, is the nourishing of an infant with breast milk. Milk is produced in milk-secreting cells in the alveoli. When the breasts are stimulated by the suckling of her baby, the mothers brain secretes oxytocin. High levels of oxytocin trigger the contraction of muscle cells surrounding the alveoli, causing milk to flow along the ducts that connect the alveoli to the nipple.Full-term newborns have an instinct and a need to suck on a nipple, and breastfed babies nurse for both nutrition and for comfort.  Breast milk provides all necessary nutrients for the first six months of life, and then remains an important source of nutrition, alongside solid foods, until at least one or two years of age.

Clinical significance
The breast is susceptible to numerous benign and malignant conditions. The most frequent benign conditions are puerperal mastitis, fibrocystic breast changes and mastalgia.
Lactation unrelated to pregnancy is known as galactorrhea. It can be caused by certain drugs (such as antipsychotic medications), extreme physical stress, or endocrine disorders. Lactation in newborns is caused by hormones from the mother that crossed into the babys bloodstream during pregnancy.

Breast cancer
Breast cancer is the most common cause of cancer death among women and it is one of the leading causes of death among women. Factors that appear to be implicated in decreasing the risk of breast cancer are regular breast examinations by health care professionals, regular mammograms, self-examination of breasts, healthy diet, and exercise to decrease excess body fat, and breastfeeding.

Male breasts
Both females and males develop breasts from the same embryological tissues. Normally, males produce lower levels of estrogens and higher levels of androgens, namely testosterone, which suppress the effects of estrogens in developing excessive breast tissue.
In boys and men, abnormal breast development is manifested as gynecomastia, the consequence of a biochemical imbalance between the normal levels of estrogen and testosterone in the male body. Around 70% of boys temporarily develop breast tissue during adolescence.
The condition usually resolves by itself within two years. When male lactation occurs, it is considered a symptom of a disorder of the pituitary gland.

Plastic surgery
Plastic surgery can be performed to augment or reduce the size of breasts, or reconstruct the breast in cases of deformative disease, such as breast cancer. Breast augmentation and breast lift (mastopexy) procedures are done only for cosmetic reasons, whereas breast reduction is sometimes medically indicated.
In cases where a womans breasts are severely asymmetrical, surgery can be performed to either enlarge the smaller breast, reduce the size of the larger breast, or both.Breast augmentation surgery generally does not interfere with future ability to breastfeed. Breast reduction surgery more frequently leads to decreased sensation in the nipple-areola complex, and to low milk supply in women who choose to breastfeed. Implants can interfere with mammography (breast x-rays images).

Society and culture
General
In Christian iconography, some works of art depict women with their breasts in their hands or on a platter, signifying that they died as a martyr by having their breasts severed; one example of this is Saint Agatha of Sicily.

Femen is a feminist activist group which uses topless protests as part of their campaigns against sex tourism religious institutions, sexism, and homophobia. Femen activists have been regularly detained by police in response to their protests.There is a long history of female breasts being used by comedians as a subject for comedy fodder (e.g., British comic Benny Hills burlesque/slapstick routines).

Art history
In European pre-historic societies, sculptures of female figures with pronounced or highly exaggerated breasts were common. A typical example is the so-called Venus of Willendorf, one of many Paleolithic Venus figurines with ample hips and bosom. Artifacts such as bowls, rock carvings and sacred statues with breasts have been recorded from 15,000 BC up to late antiquity all across Europe, North Africa and the Middle East.
Many female deities representing love and fertility were associated with breasts and breast milk. Figures of the Phoenician goddess Astarte were represented as pillars studded with breasts. Isis, an Egyptian goddess who represented, among many other things, ideal motherhood, was often portrayed as suckling pharaohs, thereby confirming their divine status as rulers. Even certain male deities representing regeneration and fertility were occasionally depicted with breast-like appendices, such as the river god Hapy who was considered to be responsible for the annual overflowing of the Nile.
Female breasts were also prominent in Minoan art in the form of the famous Snake Goddess statuettes, and a few other pieces, though most female breasts are covered. In Ancient Greece there were several cults worshipping the "Kourotrophos", the suckling mother, represented by goddesses such as Gaia, Hera and Artemis. The worship of deities symbolized by the female breast in Greece became less common during the first millennium. The popular adoration of female goddesses decreased significantly during the rise of the Greek city states, a legacy which was passed on to the later Roman Empire.During the middle of the first millennium BC, Greek culture experienced a gradual change in the perception of female breasts. Women in art were covered in clothing from the neck down, including female goddesses like Athena, the patron of Athens who represented heroic endeavor. There were exceptions: Aphrodite, the goddess of love, was more frequently portrayed fully nude, though in postures that were intended to portray shyness or modesty, a portrayal that has been compared to modern pin ups by historian Marilyn Yalom. Although nude men were depicted standing upright, most depictions of female nudity in Greek art occurred "usually with drapery near at hand and with a forward-bending, self-protecting posture". A popular legend at the time was of the Amazons, a tribe of fierce female warriors who socialized with men only for procreation and even removed one breast to become better warriors (the idea being that the right breast would interfere with the operation of a bow and arrow). The legend was a popular motif in art during Greek and Roman antiquity and served as an antithetical cautionary tale.

Body image
Many women regard their breasts as important to their sexual attractiveness, as a sign of femininity that is important to their sense of self. A woman with smaller breasts may regard her breasts as less attractive.

Clothing
Because breasts are mostly fatty tissue, their shape can—within limits—be molded by clothing, such as foundation garments. Bras are commonly worn by about 90% of Western women, and are often worn for support. The social norm in most Western cultures is to cover breasts in public, though the extent of coverage varies depending on the social context. Some religions ascribe a special status to the female breast, either in formal teachings or through symbolism. Islam forbids free women from exposing their breasts in public.
Many cultures, including Western cultures in North America, associate breasts with sexuality and tend to regard bare breasts as immodest or indecent. In some cultures, like the Himba in northern Namibia, bare-breasted women are normal. In some African cultures, for example, the thigh is regarded as highly sexualised and never exposed in public, but breast exposure is not taboo. In a few Western countries and regions female toplessness at a beach is acceptable, although it may not be acceptable in the town center.Social attitudes and laws regarding breastfeeding in public vary widely. In many countries, breastfeeding in public is common, legally protected, and generally not regarded as an issue. However, even though the practice may be legal or socially accepted, some mothers may nevertheless be reluctant to expose a breast in public to breastfeed due to actual or potential objections by other people, negative comments, or harassment. It is estimated that around 63% of mothers across the world have publicly breast-fed. Bare-breasted women are legal and culturally acceptable at public beaches in Australia and much of Europe. Filmmaker Lina Esco made a film entitled Free the Nipple, which is about "...laws against female toplessness or restrictions on images of female, but not male, nipples", which Esco states is an example of sexism in society.

Sexual characteristic
In some cultures, breasts play a role in human sexual activity. In Western culture, breasts have a "...hallowed sexual status, arguably more fetishized than either sexs genitalia". Breasts and especially the nipples are among the various human erogenous zones. They are sensitive to the touch as they have many nerve endings; and it is common to press or massage them with hands or orally before or during sexual activity. During sexual arousal, breast size increases, venous patterns across the breasts become more visible, and nipples harden. Compared to other primates, human breasts are proportionately large throughout adult females lives. Some writers have suggested that they may have evolved as a visual signal of sexual maturity and fertility.Many people regard bare female breasts to be aesthetically pleasing or erotic, and they can elicit heightened sexual desires in men in many cultures. In the ancient Indian work the Kama Sutra, light scratching of the breasts with nails and biting with teeth are considered erotic. Some people show a sexual interest in female breasts distinct from that of the person, which may be regarded as a breast fetish. A number of Western fashions include clothing which accentuate the breasts, such as the use of push-up bras and decollete (plunging neckline) gowns and blouses which show cleavage. While U.S. culture prefers breasts that are youthful and upright, some cultures venerate women with drooping breasts, indicating mothering and the wisdom of experience.Research conducted at the Victoria University of Wellington showed that breasts are often the first thing men look at, and for a longer time than other body parts. The writers of the study had initially speculated that the reason for this is due to endocrinology with larger breasts indicating higher levels of estrogen and a sign of greater fertility, but the researchers said that "Men may be looking more often at the breasts because they are simply aesthetically pleasing, regardless of the size."Some women report achieving an orgasm from nipple stimulation, but this is rare. Research suggests that the orgasms are genital orgasms, and may also be directly linked to "the genital area of the brain". In these cases, it seems that sensation from the nipples travels to the same part of the brain as sensations from the vagina, clitoris and cervix. Nipple stimulation may trigger uterine contractions, which then produce a sensation in the genital area of the brain.

Anthropomorphic geography
There are many mountains named after the breast because they resemble it in appearance and so are objects of religious and ancestral veneration as a fertility symbol and of well-being. In Asia, there was "Breast Mountain", which had a cave where the Buddhist monk Bodhidharma (Da Mo) spent much time in meditation. Other such breast mountains are Mount Elgon on the Uganda–Kenya border; Beinn Chìochan and the Maiden Paps in Scotland; the Bundok ng Susong Dalaga (Maidens breast mountains) in Talim Island, Philippines, the twin hills known as the Paps of Anu (Dá Chích Anann or the breasts of Anu), near Killarney in Ireland; the 2,086 m high Tetica de Bacares or La Tetica in the Sierra de Los Filabres, Spain; Khao Nom Sao in Thailand, Cerro Las Tetas in Puerto Rico; and the Breasts of Aphrodite in Mykonos, among many others. In the United States, the Teton Range is named after the French word for nipple.

See also
Medicine portal
 Human sexuality portal
Udder

References
Bibliography
Hollander, Anne (1993). Seeing through clothes. Berkeley: University of California Press. ISBN 978-0-520-08231-1.
Morris, Desmond The Naked Ape: a zoologists study of the human animal Bantam Books, Canada. 1967
Yalom, Marilyn (1998). A history of the breast </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 Acute exacerbation of chronic obstructive pulmonary disease and explain in detail? [/INST] An acute exacerbation of chronic obstructive pulmonary disease, or acute exacerbations of chronic bronchitis (AECB), is a sudden worsening of chronic obstructive pulmonary disease (COPD) symptoms including shortness of breath, quantity and color of phlegm that typically lasts for several days.
It may be triggered by an infection with bacteria or viruses or by environmental pollutants. Typically, infections cause 75% or more of the exacerbations; bacteria can roughly be found in 25% of cases, viruses in another 25%, and both viruses and bacteria in another 25%. Airway inflammation is increased during the exacerbation resulting in increased hyperinflation, reduced expiratory air flow and decreased gas exchange.Exacerbations can be classified as mild, moderate, and severe. As COPD progresses, exacerbations tend to become more frequent, the average being about three episodes per year.

Signs and symptoms
An acute exacerbation of COPD is associated with increased frequency and severity of coughing. It is often accompanied by worsened chest congestion and discomfort. Shortness of breath and wheezing are present in many cases. Exacerbations may be accompanied by increased amount of cough and sputum productions, and a change in appearance of sputum. An abrupt worsening in COPD symptoms may cause rupture of the airways in the lungs, which in turn may cause a spontaneous pneumothorax.In infection, there is often weakness, fever and chills. If due to a bacterial infection, the sputum may be slightly streaked with blood and coloured yellow or green.

Causes
As the lungs tend to be vulnerable organs due to their exposure to harmful particles in the air, several things can cause an acute exacerbation of COPD:

Respiratory infection, being responsible for approximately half of COPD exacerbations. Approximately half of these are due to viral infections and another half appears to be caused by bacterial infections. Common bacterial pathogens of acute exacerbations include Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis. Less common bacterial pathogens include Chlamydia pneumoniae and MRSA. Pathogens seen more frequently in patients with impaired lung function (FEV<35% of predicted) include Haemophilus parainfluenzae (after repeated use of antibiotics), Mycoplasma pneumoniae and gram-negative,  opportunistic pathogens like Pseudomonas aeruginosa and Klebsiella pneumoniae.
Allergens, e.g., pollens, wood or cigarette smoke, pollution
Toxins, including a variety of different chemicals
Air pollution
Failing to follow a drug therapy program, e.g. improper use of an inhalerIn one-third of all COPD exacerbation cases, the cause cannot be identified.

Diagnosis
The diagnostic criteria for acute exacerbation of COPD generally include a production of sputum that is purulent and may be thicker than usual, but without evidence of pneumonia (which involves mainly the alveoli rather than the bronchi). Also, diagnostic criteria may include an increase in frequency and severity of coughing, as well as increased shortness of breath.A chest X-ray is usually performed on people with fever and, especially, hemoptysis (blood in the sputum), to rule out pneumonia and get information on the severity of the exacerbation. Hemoptysis may also indicate other, potentially fatal, medical conditions.A history of exposure to potential causes and evaluation of symptoms may help in revealing the cause the exacerbation, which helps in choosing the best treatment. A sputum culture can specify which strain is causing a bacterial AECB. An early morning sample is preferred.E-nose showed the ability to smell the cause of the exacerbation.The definition of a COPD exacerbation is commonly described as "lost in translation", meaning that there is no universally accepted standard with regard to defining an acute exacerbation of COPD. Many organizations consider it a priority to create such a standard, as it would be a major step forward in the diagnosis and quality of treatment of COPD.

Prevention
Acute exacerbations can be partially prevented. Some infections can be prevented by vaccination against pathogens such as influenza and Streptococcus pneumoniae. Regular medication use can prevent some COPD exacerbations; long acting beta-adrenoceptor agonists (LABAs), long-acting anticholinergics, inhaled corticosteroids and low-dose theophylline have all been shown to reduce the frequency of  COPD exacerbations. Other methods of prevention include:

Smoking cessation and avoiding dust, passive smoking, and other inhaled irritants
Yearly influenza and 5-year pneumococcal vaccinations
Regular exercise, appropriate rest, and healthy nutrition
Avoiding people currently infected with e.g. cold and influenza
Maintaining good fluid intake and humidifying the home, in order to help reduce the formation of thick sputum and chest congestion.

Treatment
Based on the severity different treatments may be used. Mild exacerbations are treated with short acting bronchodilators (SABDs). Moderate exacerbations are treated with SABDs together with antibiotics or oral corticosteroids, or both. Severe exacerbations need hospital treatment, and the prognosis is poor.

Oxygen
Oxygen therapy should be initiated if there is significantly low blood oxygen. High flow oxygen may be harmful in those with an acute exacerbation of COPD. In the prehospital environment those given high flow O2 rather than titrating their O2 saturations to 88% to 92% had worse outcomes. Antibiotics and steroids appear useful in mild to severe disease.

Medications
Inhaled bronchodilators open up the airways in the lungs. These include salbutamol and terbutaline (both β2-adrenergic agonists), and ipratropium (an anticholinergic). Medication can be administered via inhaler or nebuliser. There is no evidence to prefer a nebuliser over an inhaler.
Antibiotics are used if a bacterial infection is the suspected cause.  However, antibiotics will not treat exacerbations caused by viruses. Viral infections will usually be cured with time with the aid of proper rest and care. Still, other medications may be needed to control symptoms. Lipid-soluble antibiotics such as macrolides, tetracyclines, and fluoroquinolones penetrate the lung tissue well. Macrolides are more active against Streptococcus pneumoniae than the tetracyclines and the older fluoroquinolones. Within the macrolides, newer ones are more active against Haemophilus influenzae than the older erythromycin. Regimens should generally be given for five days. Choice of antibiotics is also dependent on the severity of the symptoms:
"Simple" COPD is generally where a person 65 years or less, has fewer than four exacerbations per year, has minimal or moderate impairment in respiratory function and no comorbid disease. In patients with "simple" COPD, therapy should be targeted towards Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, and possibly pathogens of atypical pneumonia. The first-line treatment is a beta-lactam antibiotic such as amoxicillin. The choice will depend on resistance patterns. In patients with penicillin allergy, doxycycline or trimethoprim are preferred.
More complicated bronchitis may be when the patient is more than 65 years old, has four or more exacerbations per year, has an FEV1/FVC ratio of less than 50% on spirometry, has failed to respond to previous antibiotic treatment, and/or has comorbidity. In these cases, treatment should be aimed at Gram-negative bacteria and the possibility of high antibiotic resistance should be considered. Sputum culture results are of great value in determining antibiotic resistance. First-line treatment is cefuroxime or co-amoxiclav. Third-line treatment, as well as treatment in penicillin-allergic patients, is a fluoroquinolone such as ciprofloxacin. An agent active against Streptococcus pneumoniae may have to be added.
Corticosteroids such as prednisolone reduce inflammation in the airways. According to a 2018 systematic review, a shorter, five-day course of systemic corticosteroids is likely comparable to longer (10–14 day) therapy for treatment of COPD exacerbation (Odds ratio (OR) 0.72, 95% confidence interval (CI) 0.36 to 1.46).
Theophylline is generally not recommended.There should also be a "care plan" in case of future exacerbations </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 Progressive retinal atrophy and explain in detail? [/INST] Progressive retinal atrophy (PRA) is a group of genetic diseases seen in certain breeds of dogs and, more rarely, cats.  Similar to retinitis pigmentosa in humans, it is characterized by the bilateral degeneration of the retina, causing progressive vision loss culminating in blindness.  The condition in nearly all breeds is inherited as an autosomal recessive trait, with the exception of the Siberian Husky (inherited as an X chromosome linked trait) and the Bullmastiff (inherited as an autosomal dominant trait).  There is no treatment.

Types of PRA
In general, PRAs are characterised by initial loss of rod photoreceptor cell function followed by that of the cones and for this reason night blindness is the first significant clinical sign for most dogs affected with PRA. As other retinal disorders, PRA can be divided into either dysplastic disease, where the cells develop abnormally, and degenerative, where the cells develop normally but then degenerate during the dogs lifetime.Generalized PRA is the most common type and causes atrophy of all the neural retinal structures.  Central progressive retinal atrophy (CPRA) is a different disease from PRA involving the retinal pigment epithelium (RPE), and is also known as retinal pigment epithelial dystrophy (RPED).

Generalized PRA
Commonly affected breeds:
Akita - Symptoms at one to three years old and blindness at three to five years old.  Selective  breeding has greatly reduced the incidence of this disease in this breed.
Miniature longhaired Dachshund - Symptoms at six months old.
Papillon - Slowly progressive with blindness at seven to eight years old.
Tibetan Spaniel - Symptoms at three to five years old.
Tibetan Terrier - PRA3/RCD4 disease of middle age dogs.  http://www.ttca-online.org/html/Petersen-Jones_PRA_article.pdf
Samoyed - Symptoms by three to five years old.

Rod-cone dysplasia
This type of PRA has an early onset of severe vision loss.  It is caused by a defect in the gene for cGMP-phosphodiesterase, which leads to retinal levels of cyclic guanosine monophosphate ten times normal.

Rod-cone dysplasia type 1
Irish Setter - Rod cell response is nearly absent.  Night blindness by six to eight weeks old, often blind by one year old.
Sloughi - A DNA test can identify whether Sloughis have the mutated recessive gene. This has enabled breeders to breed away from PRA, and the disease is now rare in the breed.

Rod-cone dysplasia type 2
Collie - Rod cell response is nearly absent.  Night blindness by six weeks old, blind by one to two years old.

Rod-cone dysplasia type 3
Cardigan Welsh Corgi

Rod dysplasia
Norwegian Elkhound - Characterized by dysplasia of the rod cell unit and subsequent degeneration of the cone cell unit.  Rod cell response is nearly absent.  Night blindness by six months old, blind by three to five years old.  Rod dysplasia has now been bred out of this breed.

Early retinal degeneration
Norwegian Elkhound - Night blindness by six weeks old, blind by twelve to eighteen months old.

Photoreceptor dysplasia
This is caused by an abnormal development of both rod and cone cells.  Dogs are initially night blind and then progress to day blindness.

Miniature Schnauzer - Slowly progressive, not seen until two to five years old.
Belgian Shepherd Dog - Complete blindness by eight weeks old.

Cone degeneration
Alaskan Malamute - Temporary loss of vision in daylight (hemeralopia) at eight to ten weeks old.  There is a purely rod cell retina by four years old.

Cone-rod dystrophy
Glen of Imaal Terrier - CRD3 results in gradual blindness with onset around 4 years of age (often detectable as retinal thinning as early as 3 years of age). Caused by a mutation in gene ADAM9, the disease is analogous to CRD9 in humans. A genetic test is now available from Optigen, LLC, that will identify whether a dog is affected, a carrier (heterozygous), or clear.

Progressive rod-cone degeneration (PRCD)
This is a disease with normal rod and cone cell development but late onset degeneration of the rod cells that progresses to the cone cells.  It is inherited as an autosomal recessive trait and has been linked to the ninth canine chromosome.
Poodle - Night blindness by three to five years old, blind by five to seven years old.
English Cocker Spaniel - Occurs late in life, usually at four to eight years old.
American Cocker Spaniel - Night blindness by three to five years old, blind one to two years later.
Labrador Retriever - Night blindness by four to six years old, blind at six to eight years old.
Portuguese Water Dog
Chesapeake Bay Retriever
Australian Cattle Dog
American Eskimo Dog
Nova Scotia Duck Tolling Retriever

X-linked PRA
This condition is linked to the X chromosome.

Siberian Husky - Night blindness by two to four years old.
Samoyed - More severe disease than the Husky.

Dominant PRA
Bullmastiff - Inherited as an autosomal dominant trait due to a mutation in the gene for rhodopsin.

Feline PRA
Abyssinian - Two forms exist.  One is inherited as an autosomal dominant trait and has an early age onset.  The other is inherited as an autosomal recessive trait and has a middle age onset.
Early onset PRA has also been reported in the domestic shorthaired cat and Persian.  The Siamese also likely has a hereditary form of PRA.  Despite belief among breeders to the contrary, there is apparently no link between coat color in Persians and the development of PRA.

Central progressive retinal atrophy (CPRA)
CPRA is also known as retinal pigment epithelial dystrophy (RPED).  The cause of this condition is the loss of the retinal pigment epitheliums ability to effectively process the photoreceptor outer segment (POS) and subsequent accumulation of POS material in the RPE and loss of function.  The loss of function of the RPE leads to photoreceptor degeneration.  Vitamin E deficiency may play a role in the development of CPRA.  It is characterized by accumulation of pigment spots in the retina surrounded by retinal atrophy and a mottled appearance of the pigmented nontapetal fundus.  The pigmented spots eventually coalesce and fade as the atrophy of the retina increases.  It is an inherited condition (in the Labrador Retriever it is inherited as an autosomal dominant trait with variable penetrance).  CPRA occurs in older dogs.  Peripheral vision is retained for a long time.  Vision is better in low light and better for moving or distant objects.  Not all affected dogs go blind.  Secondary cataracts are common.

Commonly affected breeds
Labrador Retriever
Golden Retriever
Border Collie
Collie
Shetland Sheepdog
English Cocker Spaniel
English Springer Spaniel
Chesapeake Bay Retriever
Cavalier King Charles Spaniel
Briard - has an especially high frequency.It can also be found in the poodle varieties

Hereditary retinal dysplasia
There is another retinal disease in Briards known as hereditary retinal dysplasia.  These dogs are night blind from birth, and day vision varies.  Puppies affected often have nystagmus </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 Craniopagus twins and explain in detail? [/INST] Craniopagus twins are conjoined twins that are fused at the cranium. The union may occur on any portion of the cranium, but does not primarily involve either the face or the foramen magnum; their brains are usually separate, but they may share some brain tissue. Conjoined twins are genetically identical and always share the same sex. The thorax and abdomen are separate and each twin has its own umbilicus and umbilical cord.The condition is extremely rare, with an incidence of approximately 1 in 2.5 million live births. An estimated 50 craniopagus twins born around the world every year as of 2021, with only 15 twins surviving beyond the first 30 days of life. Relatively few craniopagus twins survive the perinatal period; approximately 40% of conjoined twins are stillborn and an additional 33% die within the immediate perinatal period, usually from organ abnormalities and failure.However, 25% of craniopagus twins survive and may be considered for a surgical separation; several such attempts occur yearly worldwide. Advances in neuroimaging, neuroanesthesia, and neurosurgery have proven that a successful outcome is possible. Among all conjoined twins, craniopagus twins account for a mere 2% to 6%.

Classification
The first classification system was developed by OConnell in 1976, where craniopagus twins were classified as total and partial. In the former, twins shared an "extensive surface area with widely connected cranial cavities", while in the latter, only a "limited, superficial surface area" was connected.In 2006, Stone and Goodrich came up with a more nuanced classification system, which is the "most commonly used" system. Partial CPT was defined as "lacking substantial shared dural venous sinuses", whereas total CPT "share a large portion of their dural venous sinuses and present with pronounced brain compression, which leads to distortion within the cranium".

Total
Total craniopagus twins share a large portion of dural venous sinuses and present with pronounced brain compression, leading to distortion within the cranium. Stone and Goodrich also defined two main subtypes, based on whether the long-axis angle between the twins was angular or vertical. The angular subtype has a higher rate of comorbidities than the vertical subtype.Vertical craniopagus calvaria is continuous and is further subdivided on the basis of intertwin axial facial rotation:

Type 1: both children face in the same general directional axis so that the angle between twins is less than 40 degrees. These twins show relatively symmetric superior bi-parietal or vertex compressional flattening.
Type 2: both children face opposite directions so that the deformity shows an axial rotation between 140 and 180 degrees.
Type 3: in this variety axial rotation is intermediate between the first two types with a rotation of being between 40 and 140.Another classification system divides total craniopagus twins into four categories:

Frontal: twins are facing each other with the axis of the bodies forming an acute angle
Temporoparietal: joined immediately above the external auditory meatus
Occipital: twins are connected in the occipital lobe causing the twins to face away from each other
Parietal: twins fuse at the vertex with the axis of the twins forming an obtuse angle; this leads to a situation where the twins share the most veins, lobes, and neural circuitry and thus is often described as one brain shared by two individuals
Having this kind of juncture means that there would be one common continuous cranium housing four cerebral hemispheres. An incomplete dural septum typically separates the flattened cerebral hemispheres. In total vertical craniopagus, the major cerebral arterial supply is usually confined to each respective twin and in some cases conjoined brain tissue may contain a larger artery. Within this category there are three smaller subdivisions that basically outline the different rotational symmetry of the junction.

Partial
Stone and Goodrich define partial craniopagus twins as lacking substantial shared dural venous sinuses, with limited surface area involvement, with either intact crania or cranial defects. It is less common than total craniopagus twins.
In partial craniopagus twins, the unions are usually frontal and less commonly occipital and vertical. Angular frontal junctions occur when the two twins are joined at any part of the forehead. Occipital twins are joined at the occipital lobe in the back of the head and vertical are joined on the top of the head and usually face opposite directions. The junctional diameter is often smaller in partial forms and occasionally an incomplete layer of bone may be present between the twins.  Each child maintains independent calvarial convexities except at the common area of skull junction. The dura of both children may be intact or deficient and cortical gyri may interdigitate. Additionally, shared dural venous sinuses is usually absent, or, if it is present, negligible. These twins usually undergo successful separation and both twins may live to lead normal lives.

Gestation and embryology
The exact nature of how conjoined twins develop in utero remains unclear. Embryologists have traditionally attributed identical twinning as "splitting or fission" of either the inner cell mass of pleuripotential cells or early embryonic disc at 13–14 days of gestation just before the primitive streak. Some theorists suggested that conjoined twins develop as a result of the failed fusion of a single fertilized ovum. However a new hypothesis suggests that cranial fusion occurs between two separate embryos before the end of the 4th week of gestation. This can happen because the cranial neuropore is still open, which is responsible for the ultimate fusion and formation of the brain stem and central nervous system. Furthermore, this secondary fusion of embryonic discs could implicate that intact skin will not fuse to other intact skin, including the ectoderm of the embryo. This means that two embryonic discs could only unite in locations where the ectoderm is absent. Moreover, the fusion occurs from neural folds of two separate, dorsally oriented embryonic discs, and the union can occur only after the ectoderm is disrupted to allow the neural and surface ectodermal layers to separate from each other.
The union in craniopagus twins may happen at any portion of the calvarium. The juncture can involve either the entire diameter of the head or any portion of the head and can be positioned at a multitude of rotational angles. In fact, craniopagus twins are rarely found in a symmetrical union. Apart from this, the vertebral axes may have a straight line. Despite this, the angle of the vertebrae is the ultimate dictator in how the individuals heads actually face. The majority of twins face either the same way or the exact opposite direction.

Medical procedures
Diagnosis
Conjoined twins, including craniopagus twins, can be diagnosed using standard ultrasound procedures during a pregnancy. In part because treatment of conjoined twins varies largely, many parents make the decision to terminate pregnancy due to the prognosis and quality-of -life issues. If the parents choose to continue the pregnancy, mother and babies will be closely monitored. In almost all cases, a C-section delivery is planned, often two to three weeks before the due date.

Separation surgeries
After the twins are born, parents and doctors decide whether or not separation surgery is possible. The doctors also must consider the possibility of reconstructive surgery and the social and learning issues the twins may have to face after they are separated.
Due to advances in neuroimaging, neuroanesthesia, and neurosurgical techniques, successful separation operations have become more common. Physical traits like joined brain tissue, shared arteries and veins, as well as defects in the skull and dura mater complicate a separation operation.Neuroimaging especially plays an important role because it is imperative in surgical planning to understand the shared vascular anatomy—including the brain parenchyma, calvaria, and dura mater—because separating shared vessels can lead to thrombosis, air embolism, cerebral infarction, and hemorrhage. Technologies such as CT scans, MRIs, and angiography are used to map the shared vascular structures.

Cases
Emilie and Elisabeth Stoll were born on January 17, 1912. Their parents exhibited them until their death in July 1912. Their cause of death is unknown, but they were probably weakened by the stress of travelling and exhibition.
Rodney and Roger Brodie were born in Rock Island, Illinois, in 1951. In December 1952 a medical team led by neurosurgeon Oscar Sugar attempted to separate the 15-month old twins in a surgery that lasted 12 hours. During surgery, the doctors discovered that the twins shared the superior sagittal sinus, the canal that drains blood from the brain to the heart. This vessel was retained by Rodney Brodie. Both twins survived the surgery, although Roger did not regain consciousness and died 34 days later. Rodney recovered but suffered neurological damage; because his skull was never closed, he wore a helmet until his death at age 11. This was the first case where craniopagual twins were separated and one survived.
Lotti and Rosemarie Knaack, who were born in Germany in 1951, were separated at age 6, with Lotti dying in surgery. Rosemarie survived until 2008.
Lori and George Schappell, born in 1961, are believed to be the longest-surviving craniopagus twins still living.
Ladan and Laleh Bijani, who were born in Iran,  were separated in 2003 at age 29, only to die 90 minutes apart after surgery.
Ahmed and Mohamed Ibrahim, who were born in Egypt, were successfully separated in Dallas, Texas, in October 2001, when they were 28 months old.
Lea and Tabea Block, who were born in Germany in 2003, were separated in September 2004 at Johns Hopkins Hospital in Baltimore, Maryland. Tabea died of cardiac arrest an hour after separation.
Anastasia and Tatiana Dogaru were born in 2004 with the crown of Tatianas head joined to the back of Anastasias. Doctors determined in 2007 that they could not be separated.
Krista and Tatiana Hogan, born on October 25, 2006. After a series of tests doctors also determined these twins could also not be separated.
Joseph and Luka Banda from Zambia, born in 1997, were separated successfully the same year in South Africa by a team of surgeons led by Ben Carson.
Trishna and Krishna from Bangladesh born in December 2006, joined on the tops of their skulls and sharing a small amount of brain tissue. In 2009, they were separated in Melbourne, Australia.
Ganga and Jamuna Shreshta, born in Kathmandu, Nepal in 2000, were successfully separated by Dr. Chumpon Chan and his team from the Singapore General Hospital in 2001
Rital and Ritaj Gaboura of Sudan, were separated at 11 months old in 2011 at the Great Ormond Street Hospital in London. As of 2019 they lived in Ireland.
Jadon and Anias McDonald were separated at 13 months old in 2016 in a crowdfunded operation costing $2.5million (USD) at Montefiore Hospital in New York.
Maria Ysadora and Maria Ysabelle, born in July 2016, were successfully separated on October 27, 2018, after a five-step surgery in São Paulo, Brazil by a multidisciplinary team of neurosurgeons and plastic surgeons led by Helio Machado and James Tait Goodrich.
Safa and Marwa Bibi, born in Peshawar, Pakistan, on January 7, 2017, were separated in February 2019 during the third of three surgeries.
Erin and Abby Delaney, born on July 24, 2016 in North Carolina, were successfully separated by a team led by Dr. Jesse Taylor and Dr. Gregory Heuer at the Childrens Hospital of Philadelphia on June 6, 2017.
Jaga and Kalia, twins from Odisha, India, were separated successfully in September 2017 at All India Institutes of Medical Sciences in New Delhi and kept at SCB Medical College for monitoring. Kalia died on 25 November 2020 from cardiac arrest while Jaga continues to live.
Rabeya and Rukaya Islam, born in Pabna, Bangladesh in July 2016, were successfully separated after a 33-hour surgery in Dhaka, Bangladesh, by a medical team from a Hungarian nonprofit called the Action for Defenseless People Foundation led by renowned neurosurgeon András Csókay.
Two unnamed year-old twins conjoined at the back of their heads were separated successfully in a surgery performed by Dr. Mickey Gideon at the Soroka Medical Center in Beersheba, Israel, in September 2021.
Bernado and Arthur Lima, three-year-old twins from Roraima, Brazil, were separated by a team led by Owase Jeelani in a Rio de Janeiro hospital. Seven surgeries were needed, the last of which alone took 27 hours. The operation was particularly notable in that Jeelani received assistance from Great Ormond Street Hospital in London via the use of virtual reality, as well as the twins being the oldest craniopagus twins to be separated.

Tatiana and Krista
Throughout history, the fascination about craniopagus twins has continually increased as neurobiology and the field of neuroscience has become more interesting to the public.
In 2011, The New York Times Magazine covered a story of two craniopagus twin girls who share a brain and seem to show all different kinds of physiological and emotional responses due to their condition. Though Krista and Tatiana Hogan share a brain, the two girls showed distinct personalities and behavior. One example was when Krista started drinking her juice Tatiana felt it physically going through her body. In any other set of twins the natural conclusion about the two events would be that Kristas drinking and Tatianas reaction would be coincidental. But because Krista and Tatiana are connected at their heads, whatever the girls do they do it together. In this case, brain images revealed that there was an attenuated line stretching between the two brains and forming a "thalamic bridge", a bridge connecting the two thalami. Knowing that the thalamus acts as a major control panel within the body, it is believed that the girls share part of this control panel and so when one girl drinks the other one feels it. This along with many other cases, has advanced social media and neurological related research concerning this kind of link between craniopagus twins. Unfortunately, no controlled studies have been done because the twins are so young and their brains are still very malleable and plastic.
Although there is not an overwhelming amount of research surrounding how the union between craniopagus twins leads to different personality, cognitive and motor traits, there have been some studies exploring what it actually means to share a brain. In the case of Tatiana and Krista, it is possible that the twins shared some conscious thought. Studies of the thalamus’ role in the brain provide neurological data that help explain these behavioral observations that these two twins experience.
Thalamo-cortico-thalamic circuits are the looped neural pathways that connect the thalamus to the cerebral cortex, and then the cerebral cortex back to the thalamus. Because the thalamus is mainly responsible for relaying sensory messages from the body to the brain, it is possible that there is a lot of overlap between the twins’ sensory reception and the actual response it creates within the brain. One study examines this by studying the thalamus when it is at a persistent vegetative state that is when the patient is awake but not conscious. This study proved that the cortical activity on its own is not conscious and that all the activity between the loops of the thalamus, the cerebral cortex and the thalamus itself are all conscious actions. Another study of the thalamus reaffirms that the thalamus does not answer yes/no questions but instead acts as a mediator between different parts of the cerebral cortex and systemic sensory reception.These loops actually may account for the relationship between Tatiana and Krista </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 Carcinoma and explain in detail? [/INST] Carcinoma is a malignancy that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesodermal or ectodermal germ layer during embryogenesis.Carcinomas occur when the DNA of a cell is damaged or altered and the cell begins to grow uncontrollably and become malignant. It is from the Greek: καρκίνωμα, romanized: karkinoma, lit. sore, ulcer, cancer (itself derived from karkinos meaning crab).

Classification
As of 2004, no simple and comprehensive classification system has been devised and accepted within the scientific community. Traditionally, however, malignancies have generally been classified into various types using a combination of criteria, including:The cell type from which they start; specifically:

Epithelial cells ⇨ carcinoma
Non-hematopoietic mesenchymal cells ⇨ sarcoma
Hematopoietic cells
Bone marrow-derived cells that normally mature in the bloodstream ⇨ leukemia
Bone marrow-derived cells that normally mature in the lymphatic system ⇨ lymphoma
Germ cells ⇨ germinomaOther criteria that play a role include:

The degree to which the malignant cells resemble their normal, untransformed counterparts
The appearance of the local tissue and stromal architecture
The anatomical location from which tumors arise
Genetic, epigenetic, and molecular features

Histological types
Adenocarcinoma
(adeno = gland) Refers to a carcinoma featuring microscopic glandular-related tissue cytology, tissue architecture, and/or gland-related molecular products, e.g., mucin.
Squamous cell carcinoma
Refers to a carcinoma with observable features and characteristics indicative of squamous differentiation (intercellular bridges, keratinization, squamous pearls).
Adenosquamous carcinoma
Refers to a mixed tumor containing both adenocarcinoma and squamous cell carcinoma, wherein each of these cell types comprise at least 10% of the tumor volume.
Anaplastic carcinoma
Refers to a heterogeneous group of high-grade carcinomas that feature cells lacking distinct histological or cytological evidence of any of the more specifically differentiated neoplasms. These tumors are referred to as anaplastic or undifferentiated carcinomas.
Large cell carcinoma
Composed of large, monotonous rounded or overtly polygonal-shaped cells with abundant cytoplasm.
Small cell carcinoma
Cells are usually round and are less than approximately 3 times the diameter of a resting lymphocyte and with little evident cytoplasm. Occasionally, small cell malignancies may themselves have significant components of slightly polygonal and/or spindle-shaped cells.There are a large number of rare subtypes of anaplastic, undifferentiated carcinoma. Some of the more well known include the lesions containing pseudo-sarcomatous components: spindle cell carcinoma (containing elongated cells resembling connective tissue cancers), giant cell carcinoma (containing huge, bizarre, multinucleated cells), and sarcomatoid carcinoma (mixtures of spindle and giant cell carcinoma). Pleomorphic carcinoma contains spindle cell and/or giant cell components, plus at least a 10% component of cells characteristic of more highly differentiated types (i.e. adenocarcinoma and/or squamous cell carcinoma). Very rarely, tumors may contain individual components resembling both carcinoma and true sarcoma, including carcinosarcoma and pulmonary blastoma. A history of cigarette smoking is the most common cause of large cell carcinoma.

Carcinoma of unknown primary site
The term carcinoma has also come to encompass malignant tumors composed of transformed cells whose origin or developmental lineage is unknown (see cancer of unknown primary origin; CUP), but that possess certain specific molecular, cellular, and histological characteristics typical of epithelial cells. This may include the production of one or more forms of cytokeratin or other intermediate filaments, intercellular bridge structures, keratin pearls, and/or tissue architectural motifs such as stratification or pseudo-stratification.

ICD-10 code
(8010-8045) Epithelial neoplasms, NOS
(8050-8080) Squamous cell neoplasms
(M8070/3) Squamous cell carcinoma, NOS
(8090-8110) Basal cell neoplasms
(M8090/3) Basal cell carcinoma, NOS
(8120-8130) Transitional cell carcinomas
(8140-8380) Adenocarcinomas
(M8140/3) Adenocarcinoma, NOS
(M8142/3) Linitis plastica
(M8155/3) Vipoma
(M8160/3) Cholangiocarcinoma
(M8170/3) Hepatocellular carcinoma, NOS
(M8200/3) Adenoid cystic carcinoma
(M8312/3) Renal cell carcinoma
(M8312/3) Grawitz tumor
(8390-8420) Adnexal and Skin appendage Neoplasms
(8430-8439) Mucoepidermoid Neoplasms
(8440-8490) Cystic, Mucinous and Serous Neoplasms
(8500-8540) Ductal, Lobular and Medullary Neoplasms
(8550-8559) Acinar cell neoplasms
(8560-8580) Complex epithelial neoplasms

Carcinoma In situ
The term carcinoma in situ (or CIS) is a term for cells that are significantly abnormal but not cancer. They are thus not typically carcinomas.

Pathogenesis
Cancer occurs when a single progenitor cell accumulates mutations and other changes in the DNA, histones, and other biochemical compounds that make up the cells genome. The cell genome controls the structure of the cells biochemical components, the biochemical reactions that occur within the cell, and the biological interactions of that cell with other cells. Certain combinations of mutations in the given progenitor cell ultimately result in that cell (also called a cancer stem cell) displaying a number of abnormal, malignant cellular properties that, when taken together, are considered characteristic of cancer, including:

the ability to continue to divide perpetually, producing an exponentially (or near-exponentially) increasing number of new malignant cancerous "daughter cells" (uncontrolled mitosis);
the ability to penetrate normal body surfaces and barriers, and to bore into or through nearby body structures and tissues (local invasiveness);
the ability to spread to other sites within the body (metastasize) by penetrating or entering into the lymphatic vessels (regional metastasis) and/or the blood vessels (distant metastasis).If this process of continuous growth, local invasion, and regional and distant metastasis is not halted via a combination of stimulation of immunological defenses and medical treatment interventions, the result is that the host has a continuously increasing burden of tumor cells throughout the body. Eventually, the tumor burden increasingly interferes with normal biochemical functions carried out by the hosts organs, and death ultimately ensues.
Carcinoma is but one form of cancer—one composed of cells that have developed the cytological appearance, histological architecture, or molecular characteristics of epithelial cells. A progenitor carcinoma stem cell can be formed from any of a number of oncogenic combinations of mutations in a totipotent cell, a multipotent cell, or a mature differentiated cell.

Invasion and metastasis
The hallmark of a malignant tumor is its tendency to invade and infiltrate local and adjacent structures and, eventually, spread from the site of its origin to non-adjacent regional and distant sites in the body, a process called metastasis. If unchecked, tumor growth and metastasis eventually creates a tumor burden so great that the host succumbs. Carcinoma metastasizes through both the lymph nodes and the blood.

Mutation
Whole genome sequencing has established the mutation frequency for whole human genomes. The mutation frequency in the whole genome between generations for humans (parent to child) is about 70 new mutations per generation.Carcinomas, however, have much higher mutation frequencies. The particular frequency depends on tissue type, whether a mis-match DNA repair deficiency is present, and exposure to DNA damaging agents such as components of tobacco smoke. Tuna and Amos have summarized the mutation frequencies per megabase (Mb) in some carcinomas, as shown in the table (along with the indicated frequencies of mutations per genome).

Cause of mutations
The likely major underlying cause of mutations in carcinomas is DNA damage. For example, in the case of lung cancer, DNA damage is caused by agents in exogenous genotoxic tobacco smoke (e.g. acrolein, formaldehyde, acrylonitrile, 1,3-butadiene, acetaldehyde, ethylene oxide and isoprene). Endogenous (metabolically caused) DNA damage is also very frequent, occurring on average more than 60,000 times a day in the genomes of human cells. Externally and endogenously caused damages may be converted into mutations by inaccurate translesion synthesis or inaccurate DNA repair (e.g. by non-homologous end joining).

High frequency
The high frequency of mutations in the total genome within carcinomas suggests that, often, an early carcinogenic alteration may be a deficiency in DNA repair. For instance, mutation rates substantially increase (sometimes by 100-fold) in cells defective in DNA mismatch repairA deficiency in DNA repair, itself, can allow DNA damages to accumulate, and error-prone translesion synthesis past some of those damages may give rise to mutations. In addition, faulty repair of these accumulated DNA damages may give rise to epigenetic alterations or epimutations. While a mutation or epimutation in a DNA repair gene, itself, would not confer a selective advantage, such a repair defect may be carried along as a passenger in a cell when the cell acquires an additional mutation/epimutation that does provide a proliferative advantage. Such cells, with both proliferative advantages and one or more DNA repair defects (causing a very high mutation rate), likely give rise to the high frequency of total genome mutations seen in carcinomas.

DNA repair
In somatic cells, deficiencies in DNA repair sometimes arise by mutations in DNA repair genes, but much more often are due to epigenetic reductions in expression of DNA repair genes. Thus, in a sequence of 113 colorectal carcinomas, only four had somatic missense mutations in the DNA repair gene MGMT, while the majority of these cancers had reduced MGMT protein expression due to methylation of the MGMT promoter region.

Diagnosis
Carcinomas can be definitively diagnosed through biopsy, including fine-needle aspiration (FNA), core biopsy, or subtotal removal of single node,. Microscopic examination by a pathologist is then necessary to identify molecular, cellular, or tissue architectural characteristics of epithelial cells.

Types
Oral: Most oral cancers are squamous-cell carcinoma
Lung: Carcinoma comprises >98% of all lung cancers.
Breast: Nearly all breast cancers are ductal carcinoma.
Prostate: The most common form of carcinoma of the prostate is adenocarcinoma.
Colon and rectum: Nearly all malignancies of the colon and rectum are either adenocarcinoma or squamous cell carcinoma.
Pancreas: Pancreatic carcinoma is almost always of the adenocarcinoma type and is highly lethal.
Ovaries: One of the most deadly forms due to late detection.Some carcinomas are named for their or the putative cell of origin, (e.g.hepatocellular carcinoma, renal cell carcinoma).

Staging
Staging of carcinoma refers to the process of combining physical/clinical examination, pathological review of cells and tissues, surgical techniques, laboratory tests, and imaging studies in a logical fashion to obtain information about the size of the neoplasm and the extent of its invasion and metastasis.
Carcinomas are usually staged with Roman numerals </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 Lace bite 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 Wolfram-like syndrome and explain in detail? [/INST] Wolfram-like syndrome is a rare autosomal dominant genetic disorder which shares some of the features shown by those affected with the autosomal recessive Wolfram syndrome. It is a type of WFS1-related disorder.

Signs and symptoms
Individuals with this condition usually exhibit early-onset progressive hearing loss which starts around the age of 10 years old, early-onset optic atrophy which usually manifests in a persons mid teenage–late adulthood years of life, and adult-onset diabetes mellitus.Although rarely, psychiatric symptoms can also manifest in people with the condition, this group of symptoms consists of hallucinations, depression, anxiety, and sleep disorders.Psychosis and autism are sometimes seen as features of the disorder.Other symptoms include nephrocalcinosis, psychomotor delay, glaucoma, and megalocornea.

Complications
The psychiatric features that may appear in patients with this condition, particularly depression, can cause a patient to be live in a constantly miserable state of mind, which can lead some patients to develop suicidal tendencies and, which can ultimately lead to making the decision of commiting suicide.

Genetics
This condition is caused by mutations in the WFS1 gene, these mutations are inherited in an autosomal dominant manner, meaning that for a person to exhibit the symptoms of Wolfram-like syndrome, they must have at least one copy of the mutation that is responsible for the phenotype of the disorder, this mutation is usually inherited, but there are cases where the mutation is de novo, meaning that it wasnt inherited from either parent, but rather the result of a spontaneous error in cell division.This gene encodes a protein called wolframin, the mutations typically found in people with this condition cause the production of a protein that is either absent or has little to no function at all.Mutations in this gene are also associated with other disorders affecting vision or hearing, (aside from Wolfram syndrome) such as non-syndromic autosomal dominant deafness type 6., isolated autosomal dominant congenital cataract, etc.
In rare cases, a mutation in the CDK13 gene instead of the WFS1 gene is responsible for the disorder, this genetic mutation has only been described in 3 affected children belonging to a consanguineous Pakistani family who, in addition to the typical symptoms of the disorder, also had anomalies affecting the gastrointestinal tract, congenital heart defects, and clinodactyly.

Diagnosis
The following diagnostic methods can be used to diagnose Wolfram-like syndrome

Genetic mutation responsible for Wolfram-like syndrome
Genetic testingWhole exome sequencing
Whole genome sequencing
Gene sequencing focused on the WFS1 gene

Diabetes
Blood testsBlood sugar test at a random time
Fasting blood sugar test
A1C test
Oral glucose tolerance testing

Hearing loss
At-homeHearing loss screening mobile apps
Whisper test
In clinical settingAudiometer tests
Tuning fork test
Physical examination

Optic atrophy
OphthalmoscopyOptic disc examination, paleness strongly indicates optic atrophy
Visual acuity examination

Psychiatric symptoms
Depression
Use of the DSM-5 depression diagnosis criteria
Physical examination
Laboratory studies
Psychiatric evaluation

Anxiety
Use of the DSM-5 criteria for anxiety disorder
Psychological evaluation

Hallucinations (with or without delusions and/or disconnection from reality)
Hallucinations dont necessarily need to have an official clinical diagnosis (although one can be useful for treatment to be performed), but it can be used as a diagnostic method for other conditions such as psychosis or schizophrenia. Hallucinations can be auditory, visual, tactile, olfactory, or gustatory, and they involve a false perception of stimuli where there is none. The same (no necessary need for official clinical diagnosis but can be used as a diagnostic method for other conditions) goes for delusions, there are various types of delusions, including somatic, persecutory/paranoid, grandiose, etc. They involve a false, fixed, often irrational belief a person fully believes in and is hard to convince out of.

Treatment
There is no standard management method for Wolfram-like syndrome, however, the following treatment methods can be used to treat the symptoms Wolfram-like syndrome causes.

Diabetes
Insulin intake
Regular blood sugar monitoring
The use of metformin medication
Healthy eating habits
Regular physical activity

Hearing loss
Hearing aids
Cochlear implants
Surgical procedures

Vision loss
Optical aids
Surgical procedures
Medication

Psychiatric symptoms
Therapy (for depression, anxiety, etc.)
Use of medication (antidepressants, antipsychotics, etc.)

Prevalence
According to OMIM, around 15-20 cases from 4 affected families with Wolfram-like syndrome have been described in medical lirerature. All of the families studied were European, both by ancestry and by nacionality, the countries said families originated from were Denmark, the Netherlands, France, and Sweden, respectively.

History
The disorder was seemingly first described in 1940 by Samuelson et al, their patients were 4 members from a Swedish family with an apparently never-described-before combination of autosomal dominant sensorineural deafness and optic atrophy. Said family was later re-examined in 2011 by Rendtorff et al
In 2006, Eiberg et al. described 4 affected members from a 3-generation Danish family, said individuals showed a phenotype similar to that shown by patients with Wolfram syndrome, the pair of symptoms associated with the familys unique disorder was inherited following an autosomal dominant manner. All individuals had progressive hearing loss starting in childhood and optic atrophy with onset in either childhood or middle age. 3 out of the 4 individuals were found to have irregular glucose regulation, 1 had reduced glucose tolerance, another one was found to have diabetes which was previously undiagnosed, and yet another one of the patients was found to have decreased function of the pancreas beta cells. 1 out of the 4 individuals had a diagnosed anxiety disorder as well as a sleep disorder. Non-syndromic isolated congenital deafness was found in 2 other family members, although they were otherwise unaffected.The third case report was made by Valero et al in 2008, they described a 60-year old man and his 81-year-old mother from France. The both of them had noninsulin-dependent diabetes mellitus and childhood-onset hearing loss. Out of the 2 patients, the mother was the most affected, her phenotype consisted of additional features her son didnt suffer from including severe vision impairment, bilateral optic nerve atrophy. Even though both of them had hearing impairments, the son was the only one of the pair who wore a hearing aid, the mother didnt do so, and as a result she had very obvious difficulties comprehending speech.The fourth case report was made by Hogewind et al, their patients were 3 affected members of a 2-generation Dutch family (2 brothers and their mother). The three of them suffered from hearing loss ranging from moderate to severe and optic neuropathy but they didnt have any other symptoms, including the ones usually associated with both Wolfram syndrome and Wolfram-like syndrome (such as diabetes mellitus/insipidus or depression), but they did have red-green color deficiency </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 Ebullism and explain in detail? [/INST] Ebullism is the formation of gas bubbles in bodily fluids due to reduced environmental pressure, for example at high altitude.  It occurs because a system of liquid and gas at equilibrium will see a net conversion of liquid to gas as pressure lowers; for example, liquids reach their boiling point at lower temperatures when the pressure on them is lowered.

Symptoms
Symptoms of ebullism include bubbles in the membranes of the mouth and eyes, swelling of the skin, and bubbles in the blood. Blood circulation and breathing may be impaired or stopped. The brain tissue may be starved of oxygen because of blockage of arteries, and the lungs may swell and hemorrhage. Death results unless recompression is rapid enough to reduce the bubbles before tissue damage occurs.
In 1960, Joseph Kittinger experienced localised ebullism during a 31 kilometres (19 mi) ascent in a helium-driven gondola. His right-hand glove failed to pressurise and his hand expanded to roughly twice its normal volume  accompanied by disabling pain. His hand took about three hours to recover after his return to the ground.
Tissue samples from the remains of the crew of Space Shuttle STS-107 Columbia revealed evidence of ebullism. Given the level of tissue damage, the crew could not have regained consciousness even with re-pressurization.

Mechanism
In the atmospheric pressure present at sea level, water boils at 100 °C (212 °F) </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 Caplans syndrome and explain in detail? [/INST] Caplans syndrome (or Caplan disease or rheumatoid pneumoconiosis) is a combination of rheumatoid arthritis (RA) and pneumoconiosis that manifests as intrapulmonary nodules, which appear homogeneous and well-defined on chest X-ray.

Signs and symptoms
Caplan syndrome presents with cough and shortness of breath in conjunction with features of rheumatoid arthritis, such as painful joints and morning stiffness.
Examination should reveal tender, swollen metacarpophalangeal joints and rheumatoid nodules; auscultation of the chest may reveal diffuse crackles that do not disappear on coughing or taking a deep breath.
Caplan syndrome is a nodular condition of the lung occurring in dust-exposed persons with either a history of rheumatoid arthritis (RA) or who subsequently develop RA within the following 5–10 years. The nodules in the lung typically occur bilaterally and peripherally, on a background of simple coal workers pneumoconiosis. There are usually multiple nodules, varying in size from 0.5 to 5.0 cm. The nodules typically appear rapidly, often in only a few weeks. Nodules may grow, remain unchanged in size, resolve, or disappear and then reappear. They can cavitate, calcify, or develop air-fluid levels. Grossly, they can resemble a giant silicotic nodule. Histologically, they usually have a necrotic center surrounded by a zone of plasma cells and lymphocytes, and often with a peripheral inflammatory zone made of macrophages and neutrophils.

Causes
Caplan syndrome occurs only in patients with both RA and pneumoconiosis related to mining dust (coal, asbestos, silica). The condition occurs in miners (especially those working in anthracite coal-mines), asbestosis, silicosis and other pneumoconioses </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 Flat feet and explain in detail? [/INST] Flat feet (also called pes planus or fallen arches) is a postural deformity in which the arches of the foot collapse, with the entire sole of the foot coming into complete or near-complete contact with the ground. Sometimes children are born with flat feet (congenital).
There is a functional relationship between the structure of the arch of the foot and the biomechanics of the lower leg. The arch provides an elastic, springy connection between the forefoot and the hind foot so that a majority of the forces incurred during weight bearing on the foot can be dissipated before the force reaches the long bones of the leg and thigh.In pes planus, the head of the talus bone is displaced medially and distal from the navicular bone. As a result, the Plantar calcaneonavicular ligament (spring ligament) and the tendon of the tibialis posterior muscle are stretched to the extent that the individual with pes planus loses the function of the medial longitudinal arch (MLA). If the MLA is absent or nonfunctional in both the seated and standing positions, the individual has "rigid" flatfoot. If the MLA is present and functional while the individual is sitting or standing up on their toes, but this arch disappears when assuming a foot-flat stance, the individual has "supple" flatfoot. This latter condition is often treated with arch supports. However, a recent randomized controlled trial found no evidence for the efficacy of treatment of flat feet in children either from expensive prescribed orthotics (i.e., shoe inserts) or less expensive over-the-counter orthotics.
Three studies (see citations below in Military performance section) of military recruits have shown no evidence of increased injury, or foot problems, due to flat feet, in a population of people who reach military service age without prior foot problems. However, these studies cannot be used to judge possible future damage from this condition when diagnosed at younger ages. They also cannot be applied to persons whose flat feet are associated with foot symptoms, or certain symptoms in other parts of the body (such as the leg or back) possibly referable to the foot.

Children
Studies have shown flat feet are a common occurrence in children and adolescents. The human arch develops in infancy and early childhood as part of normal muscle, tendon, ligament and bone growth.  Flat arches in children usually become high arches as the child progresses through adolescence and into adulthood. Children with flat feet are at a higher risk of developing knee, hip, and back pain. A 2007 randomized controlled trial found no evidence for the efficacy of treatment of flat feet in children either from expensive prescribed orthotics (i.e. shoe inserts) or less expensive over-the-counter orthotics. As a symptom itself, flat feet usually accompany genetic musculoskeletal conditions such as dyspraxia, ligamentous laxity or hypermobility.

Diagnosis
Since children are unlikely to suspect or identify flat feet on their own, it is important for adult caregivers to check on this themselves. Besides visual inspection of feet and of the treadwear pattern on shoe soles, caregivers should notice when a childs gait is abnormal or the child seems to be in pain from walking. Children who complain about calf muscle pains, arch pain, or any other pains around the foot area may be developing or have developed flat feet.

Treatment
Training of the feet, utilizing foot gymnastics and going barefoot on varying terrain, can facilitate the formation of arches during childhood, with a developed arch occurring for most by the age of four to six years. Ligament laxity is also among the factors known to be associated with flat feet. One medical study in India with a large sample size of children who had grown up wearing shoes and others going barefoot found that the longitudinal arches of the bare-footers were generally strongest and highest as a group, and that flat feet were less common in children who had grown up wearing sandals or slippers than among those who had worn closed-toe shoes. Focusing on the influence of footwear on the prevalence of pes planus, the cross-sectional study performed on children noted that wearing shoes throughout early childhood can be detrimental to the development of a normal or a high medial longitudinal arch. The vulnerability for flat foot among shoe-wearing children increases if the child has an associated ligament laxity condition. The results of the study suggest that children be encouraged to play barefooted on various surfaces of terrain and that slippers and sandals are less harmful compared to closed-toe shoes. It appeared that closed-toe shoes greatly inhibited the development of the arch of the foot more so than slippers or sandals. This conclusion may be a result of the notion that intrinsic muscle activity of the arch is required to prevent slippers and sandals from falling off the childs foot. In children with few symptoms orthotics are not recommended.

Adults
Flat feet can also develop as an adult ("adult acquired flatfoot") due to injury, illness, unusual or prolonged stress to the foot, faulty biomechanics, or as part of the normal aging process.  This is most common in women over 40 years of age. Known risk factors include obesity, hypertension and diabetes. Flat feet can also occur in pregnant women as a result of temporary changes, due to increased elastin (elasticity) during pregnancy.  However, if developed by adulthood, flat feet generally remain flat permanently.

If a youth or adult appears flatfooted while standing in a full weight bearing position, but an arch appears when the person plantarflexes, or pulls the toes back with the rest of the foot flat on the floor, this condition is called flexible flatfoot.  This is not a true collapsed arch, as the medial longitudinal arch is still present and the windlass mechanism still operates; this presentation is actually due to excessive pronation of the foot (rolling inwards), although the term flat foot is still applicable as it is a somewhat generic term.  Muscular training of the feet is helpful and will often result in increased arch height regardless of age.

Pathophysiology
Research has shown that tendon specimens from people who have adult-acquired flat feet show evidence of increased activity of proteolytic enzymes. These enzymes can break down the constituents of the involved tendons and cause the foot arch to fall. In the future, these enzymes may become targets for new drug therapies.

Diagnosis
Many medical professionals can diagnose a flat foot by examining the patient standing or just looking at them. On going up onto tip toe the deformity will correct when this is a flexible flat foot in a child with lax joints. Such correction is not seen in adults with a rigid flat foot.
An easy and traditional home diagnosis is the "wet footprint" test, performed by wetting the feet in water and then standing on a smooth, level surface such as smooth concrete or thin cardboard or heavy paper. Usually, the more the sole of the foot that makes contact (leaves a footprint), the flatter the foot.  In more extreme cases, known as a kinked flatfoot, the entire inner edge of the footprint may actually bulge outward, where in a normal to high arch this part of the sole of the foot does not make contact with the ground at all.
On plain radiography, flat feet can be diagnosed and graded by several measures, the most important in adults being the talonavicular coverage angle, the calcaneal pitch, and the talar-1st metatarsal angle (Mearys angle). The talonavicular coverage angle is abnormally laterally rotated in flat feet. It is normally up to 7 degrees laterally rotated, so a greater rotation indicates flat feet. Radiographies generally need to be taken on weightbearing feet in order to detect misalignment.

Treatment
Most flexible flat feet are asymptomatic, and do not cause pain. In these cases, there is usually no cause for concern. Flat feet were formerly a physical-health reason for service-rejection in many militaries. However, three military studies on asymptomatic adults (see section below), suggest that persons with asymptomatic flat feet are at least as tolerant of foot stress as the population with various grades of arch.
In a study performed to analyze the activation of the tibialis posterior muscle in adults with pes planus, it was noted that the tendon of this muscle may be dysfunctional and lead to disabling weightbearing symptoms associated with acquired flat foot deformity. The results of the study indicated that while barefoot, subjects activated additional lower-leg muscles to complete an exercise that resisted foot adduction. However, when the same subjects performed the exercise while wearing arch supporting orthotics and shoes, the tibialis posterior was selectively activated. Such discoveries suggest that the use of shoes with properly fitting, arch-supporting orthotics will enhance selective activation of the tibialis posterior muscle thus, acting as an adequate treatment for the undesirable symptoms of pes planus.Rigid flatfoot, a condition where the sole of the foot is rigidly flat even when a person is not standing, often indicates a significant problem in the bones of the affected feet, and can cause pain in about a quarter of those affected.  Other flatfoot-related conditions, such as various forms of tarsal coalition (two or more bones in the midfoot or hindfoot abnormally joined) or an accessory navicular (extra bone on the inner side of the foot) should be treated promptly, usually by the very early teen years, before a childs bone structure firms up permanently as a young adult.  Both tarsal coalition and an accessory navicular can be confirmed by X-ray.  Rheumatoid arthritis can destroy tendons in the foot (or both feet) which can cause this condition, and untreated can result in deformity and early onset of osteoarthritis of the joint. Such a condition can cause severe pain and considerably reduced ability to walk, even with orthoses.  Ankle fusion is usually recommended.Treatment of flat feet may also be appropriate if there is associated foot or lower leg pain, or if the condition affects the knees or the lower back. Treatment may include foot gymnastics or other exercises as recommended by a podiatrist or physical therapist. In cases of severe flat feet, orthoses should be used through a gradual process to lessen discomfort.  Over several weeks, slightly more material is added to the orthosis to raise the arch.  These small changes allow the foot structure to adjust gradually, as well as giving the patient time to acclimatise to the sensation of wearing orthoses.  In some cases, surgery can provide lasting relief, and even create an arch where none existed before; it should be considered a last resort, as it is usually very time-consuming and costly. A minimally-invasive surgical intervention involving a small implant is also available. The implant is inserted into the sinus tarsi and prevents the calcaneus and talus from sliding relative to each other. This prevents the sinus tarsi from collapsing and thus prevents the external symptom of the fallen arch from occurring.

Athletic performance
The effects of flat feet fall under two categories, which are asymptomatic and symptomatic. Individuals with rigid flat feet tend to exhibit symptoms such as foot and knee tendinitis, and are recommended to consider surgical options when managing symptoms </s>