<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 Sunburn and explain in detail? [/INST] Sunburn is a form of radiation burn that affects living tissue, such as skin, that results from an overexposure to ultraviolet (UV) radiation, usually from the Sun. Common symptoms in humans and animals include: red or reddish skin that is hot to the touch or painful, general fatigue, and mild dizziness. Other symptoms include blistering, peeling skin, swelling, itching, and nausea. Excessive UV radiation is the leading cause of (primarily) non-malignant skin tumors, and in extreme cases can be life-threatening.  Sunburn is an inflammatory response in the tissue triggered by direct DNA damage by UV radiation. When the cells DNA is overly damaged by UV radiation, type I cell-death is triggered and the tissue is replaced.Sun protective measures including sunscreen and sun protective clothing are widely accepted to prevent sunburn and some types of skin cancer. Special populations, including children, are especially susceptible to sunburn and protective measures should be used to prevent damage.

Signs and symptoms
Typically, there is initial redness, followed by varying degrees of pain, proportional in severity to both the duration and intensity of exposure.
Other symptoms can include blistering, swelling (edema), itching  (pruritus), peeling skin, rash, nausea, fever, chills, and fainting (syncope). Also, a small amount of heat is given off from the burn, caused by the concentration of blood in the healing process, giving a warm feeling to the affected area. Sunburns may be classified as superficial, or partial thickness burns. Blistering is a sign of second degree sunburn.

Variations
Minor sunburns typically cause nothing more than slight redness and tenderness to the affected areas. In more serious cases, blistering can occur. Extreme sunburns can be painful to the point of debilitation and may require hospital care.

Duration
Sunburn can occur in less than 15 minutes, and in seconds when exposed to non-shielded welding arcs or other sources of intense ultraviolet light. Nevertheless, the inflicted harm is often not immediately obvious.
After the exposure, skin may turn red in as little as 30 minutes but most often takes 2 to 6 hours. Pain is usually strongest 6 to 48 hours after exposure. The burn continues to develop for 1 to 3 days, occasionally followed by peeling skin in 3 to 8 days. Some peeling and itching may continue for several weeks.

Skin cancer
Ultraviolet radiation causes sunburns and increases the risk of three types of skin cancer: melanoma, basal-cell carcinoma and squamous-cell carcinoma. Of greatest concern is that the melanoma risk increases in a dose-dependent manner with the number of a persons lifetime cumulative episodes of sunburn. It has been estimated that over 1/3 of melanomas in the United States and Australia could be prevented with regular sunscreen use.

Causes
Sunburn is caused by UV radiation from the sun, but "sunburn" may result from artificial sources, such as tanning lamps, welding arcs, or ultraviolet germicidal irradiation. It is a reaction of the body to direct DNA damage from UVB light. This damage is mainly the formation of a thymine dimer. The damage is recognized by the body, which then triggers several defense mechanisms, including DNA repair to revert the damage, apoptosis and peeling to remove irreparably damaged skin cells, and increased melanin production to prevent future damage.
Melanin readily absorbs UV wavelength light, acting as a photoprotectant. By preventing UV photons from disrupting chemical bonds, melanin inhibits both the direct alteration of DNA and the generation of free radicals, thus indirect DNA damage. However, human melanocytes contain over 2,000 genomic sites that are highly sensitive to UV, and such sites can be up to 170-fold more sensitive to UV induction of cyclobutane pyrimidine dimers than the average site  These sensitive sites often occur at biologically significant locations near genes.
Sunburn causes an inflammation process, including production of prostanoids and bradykinin. These chemical compounds increase sensitivity to heat by reducing the threshold of heat receptor (TRPV1) activation from 109 °F (43 °C) to 85 °F (29 °C). The pain may be caused by overproduction of a protein called CXCL5, which activates nerve fibers.Skin type determines the ease of sunburn. In general, people with lighter skin tone and limited capacity to develop a tan after UV radiation exposure have a greater risk of sunburn. The Fitzpatricks Skin phototypes classification describes the normal variations of skin responses to UV radiation. Persons with type I skin have the greatest capacity to sunburn and type VI have the least capacity to burn. However, all skin types can develop sunburn.Fitzpatricks skin phototypes:

Type 0: Albino
Type I: Pale white skin, burns easily, does not tan
Type II: White skin, burns easily, tans with difficulty
Type III: White skin, may burn but tans easily
Type IV: Light brown/olive skin, hardly burns, tans easily
Type V: Brown skin, usually does not burn, tans easily
Type VI: Black skin, very unlikely to burn, becomes darker with UV radiation exposureAge also affects how skin reacts to sun. Children younger than six and adults older than sixty are more sensitive to sunlight.There are certain genetic conditions, for example xeroderma pigmentosum, that increase a persons susceptibility to sunburn and subsequent skin cancers. These conditions involve defects in DNA repair mechanisms which in turn decreases the ability to repair DNA that has been damaged by UV radiation.

Medications
The risk of a sunburn can be increased by pharmaceutical products that sensitize users to UV radiation. Certain antibiotics, oral contraceptives, antidepressants, acne medications, and tranquillizers have this effect.

UV intensity
The UV Index indicates the risk of getting a sunburn at a given time and location. Contributing factors include:
The time of day. In most locations, the suns rays are strongest between approximately 10 am and 4 pm daylight saving time.
Cloud cover. UV is partially blocked by clouds; but even on an overcast day, a significant percentage of the suns damaging UV radiation can pass through clouds.
Proximity to reflective surfaces, such as water, sand, concrete, snow, and ice. All of these reflect the suns rays and can cause sunburns.
The season of the year. The position of the sun in late spring and early summer can cause a more-severe sunburn.
Altitude. At a higher altitude it is easier to become burnt, because there is less of the earths atmosphere to block the sunlight. UV exposure increases about 4% for every 1000 ft (305 m) gain in elevation.
Proximity to the equator (latitude). Between the polar and tropical regions, the closer to the equator, the more direct sunlight passes through the atmosphere over the course of a year. For example, the southern United States gets fifty percent more sunlight than the northern United States.
Because of variations in the intensity of UV radiation passing through the atmosphere, the risk of sunburn increases with proximity to the tropic latitudes, located between 23.5° north and south latitude. All else being equal (e.g., cloud cover, ozone layer, terrain, etc.), over the course of a full year, each location within the tropic or polar regions receives approximately the same amount of UV radiation. In the temperate zones between 23.5° and 66.5°, UV radiation varies substantially by latitude and season. The higher the latitude, the lower the intensity of the UV rays.  Intensity in the northern hemisphere is greatest during the months of May, June and July—and in the southern hemisphere, November, December and January. On a minute-by-minute basis, the amount of UV radiation is dependent on the angle of the sun. This is easily determined by the height ratio of any object to the size of its shadow (if the height is measured vertical to the earths gravitational field, the projected shadow is ideally measured on a flat, level surface; furthermore, for objects wider than skulls or poles, the height and length are best measured relative to the same occluding edge). The greatest risk is at solar noon, when shadows are at their minimum and the suns radiation passes most directly through the atmosphere. Regardless of ones latitude (assuming no other variables), equal shadow lengths mean equal amounts of UV radiation.
The skin and eyes are most sensitive to damage by UV at 265–275 nm wavelength, which is in the lower UVC band that is almost never encountered except from artificial sources like welding arcs. Most sunburn is caused by longer wavelengths, simply because those are more prevalent in sunlight at ground level.

Ozone depletion
In recent decades, the incidence and severity of sunburn have increased worldwide, partly because of chemical damage to the atmospheres ozone layer. Between the 1970s and the 2000s, average stratospheric ozone decreased by approximately 4%, contributing an approximate 4% increase to the average UV intensity at the earths surface. Ozone depletion and the seasonal "ozone hole" have led to much larger changes in some locations, especially in the southern hemisphere.

Tanning
Suntans, which naturally develop in some individuals as a protective mechanism against the sun, are viewed by most in the Western world as desirable. This has led to an overall increase in exposure to UV radiation from both the natural sun and tanning lamps. Suntans can provide a modest sun protection factor (SPF) of 3, meaning that tanned skin would tolerate up to three times the UV exposure as pale skin.Sunburns associated with indoor tanning can be severe.The World Health Organization, American Academy of Dermatology, and the Skin Cancer Foundation recommend avoiding artificial UV sources such as tanning beds, and do not recommend suntans as a form of sun protection.

Diagnosis
Differential diagnosis
The differential diagnosis of sunburn includes other skin pathology induced by UV radiation including photoallergic reactions, phototoxic reactions to topical or systemic medications, and other dermatologic disorders that are aggravated by exposure to sunlight. Considerations for diagnosis include duration and intensity of UV exposure, use of topical or systemic medications, history of dermatologic disease, and nutritional status.

Phototoxic reactions: Non-immunological response to sunlight interacting with certain drugs and chemicals in the skin which resembles an exaggerated sunburn.  Common drugs that may cause a phototoxic reaction include amiodarone, dacarbazine, fluoroquinolones, 5-fluorouracil, furosemide, nalidixic acid, phenothiazines, psoralens, retinoids, sulfonamides, sulfonylureas, tetracyclines, thiazides, and vinblastine.
Photoallergic reactions: Uncommon immunological response to sunlight interacting with certain drugs and chemicals in the skin. When in excited state by UVR, these drugs and chemicals form free radicals that react to form functional antigens and induce a Type IV hypersensitivity reaction.  These drugs include 6-methylcoumarin, aminobenzoic acid and esters, chlorpromazine, promethazine, diclofenac, sulfonamides, and sulfonylureas. Unlike phototoxic reactions which resemble exaggerated sunburns, photoallergic reactions can cause intense itching and can lead to thickening of the skin.
Phytophotodermatitis: UV radiation induces inflammation of the skin after contact with certain plants (including limes, celery, and meadow grass). Causes pain, redness, and blistering of the skin in the distribution of plant exposure.
Polymorphic light eruption: Recurrent abnormal reaction to UVR. It can present in various ways including pink-to-red bumps, blisters, plaques and urticaria.
Solar urticaria: UVR-induced wheals that occurs within minutes of exposure and fades within hours.
Other skin diseases exacerbated by sunlight: Several dermatologic conditions can increase in severity with exposure to UVR. These include systemic lupus erythematosus (SLE), dermatomyositis, acne, atopic dermatitis, and rosacea.Additionally, since sunburn is a type of radiation burn, it can initially hide a severe exposure to radioactivity resulting in acute radiation syndrome or other radiation-induced illnesses, especially if the exposure occurred under sunny conditions. For instance, the difference between the erythema caused by sunburn and other radiation burns is not immediately obvious. Symptoms common to heat illness and the prodromic stage of acute radiation syndrome like nausea, vomiting, fever, weakness/fatigue, dizziness or seizure can add to further diagnostic confusion.

Prevention
The most effective way to prevent sunburn is to reduce the amount of UV radiation reaching the skin. The World Health Organization, American Academy of Dermatology, and Skin Cancer Foundation recommend the following measures to prevent excessive UV exposure and skin cancer:
Limiting sun exposure between the hours of 10 am and 4 pm, when UV rays are the strongest
Seeking shade when UV rays are most intense
Wearing sun-protective clothing including a wide brim hat, sunglasses, and tightly-woven, loose-fitting clothing
Using sunscreen
Avoiding tanning beds and artificial UV exposure

UV intensity
The strength of sunlight is published in many locations as a UV Index. Sunlight is generally strongest when the sun is close to the highest point in the sky. Due to time zones and daylight saving time, this is not necessarily at 12 noon, but often one to two hours later. Seeking shade including using umbrellas and canopies can reduce the amount of UV exposure, but does not block all UV rays. The WHO recommends following the shadow rule: "Watch your shadow – Short shadow, seek shade!"

Grapes
A 2022 study found that eating 60 grapes a day can stop you getting sunburn. Scientists found people who ate three-quarters of a punnet every day for two weeks were better protected against damage to the skin from ultraviolet light. Polyphenols found naturally in the fruits are thought to be responsible for the resistance.

Sunscreen
Commercial preparations are available that block UV light, known as sunscreens or sunblocks. They have a sun protection factor (SPF) rating, based on the sunblocks ability to suppress sunburn: The higher the SPF rating, the lower the amount of direct DNA damage. The stated protection factors are correct only if 2 mg of sunscreen is applied per square cm of exposed skin. This translates into about 28 mL (1 oz) to cover the whole body of an adult male, which is much more than many people use in practice. Sunscreens function as chemicals such as oxybenzone and dioxybenzone (organic sunscreens) or opaque materials such as zinc oxide or titanium oxide (inorganic sunscreens) that both mainly absorb UV radiation. Chemical and mineral sunscreens vary in the wavelengths of UV radiation blocked. Broad-spectrum sunscreens contain filters that protect against UVA radiation as well as UVB. Although UVA radiation does not primarily cause sunburn, it does contribute to skin aging and an increased risk of skin cancer.
Sunscreen is effective and thus recommended for preventing melanoma and squamous cell carcinoma. There is little evidence that it is effective in preventing basal cell carcinoma. Typical use of sunscreen does not usually result in vitamin D deficiency, but extensive usage may.

Recommendations
Research has shown that the best sunscreen protection is achieved by application 15 to 30 minutes before exposure, followed by one reapplication 15 to 30 minutes after exposure begins. Further reapplication is necessary only after activities such as swimming, sweating, and rubbing. This varies based on the indications and protection shown on the label—from as little as 80 minutes in water to a few hours, depending on the product selected. The American Academy of Dermatology recommends the following criteria in selecting a sunscreen:
Broad spectrum: protects against both UVA and UVB rays
SPF 30 or higher
Water resistant: sunscreens are classified as water resistant based on time, either 40 minutes, 80 minutes, or not water resistant

Eyes
The eyes are also sensitive to sun exposure at about the same UV wavelengths as skin; snow blindness is essentially sunburn of the cornea. Wrap-around sunglasses or the use by spectacle-wearers of glasses that block UV light reduce the harmful radiation. UV light has been implicated in the development of age-related macular degeneration,  pterygium and cataract.  Concentrated clusters of melanin, commonly known as freckles, are often found within the iris.
The tender skin of the eyelids can also become sunburned, and can be especially irritating.

Lips
The lips can become chapped (cheilitis) by sun exposure. Sunscreen on the lips does not have a pleasant taste and might be removed by saliva. Some lip balms (ChapSticks) have SPF ratings and contain sunscreens.

Feet
The skin of the feet is often tender and protected, so sudden prolonged exposure to UV radiation can be particularly painful and damaging to the top of the foot. Protective measures include sunscreen, socks, and swimwear or swimgear that covers the foot.

Diet
Dietary factors influence susceptibility to sunburn, recovery from sunburn, and risk of secondary complications from sunburn.  Several dietary antioxidants, including essential vitamins, have been shown to have some effectiveness for protecting against sunburn and skin damage associated with ultraviolet radiation, in both human and animal studies.  Supplementation with Vitamin C and Vitamin E was shown in one study to reduce the amount of sunburn after a controlled amount of UV exposure.
A review of scientific literature through 2007 found that beta carotene (Vitamin A) supplementation had a protective effect against sunburn, but that the effects were only evident in the long-term, with studies of supplementation for periods less than 10 weeks in duration failing to show any effects. There is also evidence that common foods may have some protective ability against sunburn if taken for a period before the exposure.

Protecting children
Babies and children are particularly susceptible to UV damage which increases their risk of both melanoma and non-melanoma skin cancers later in life. Children should not sunburn at any age and protective measures can ensure their future risk of skin cancer is reduced.
Infants 0–6 months: Children under 6mo generally have skin too sensitive for sunscreen and protective measures should focus on avoiding excessive UV exposure by using window mesh covers, wide brim hats, loose clothing that covers skin, and reducing UV exposure between the hours of 10am and 4pm.
Infants 6–12 months: Sunscreen can safely be used on infants this age. It is recommended to apply a broad-spectrum, water-resistant SPF 30+ sunscreen to exposed areas as well as avoid excessive UV exposure by using wide-brim hats and protective clothing.
Toddlers and Preschool-aged children: Apply a broad-spectrum, water-resistant SPF 30+ sunscreen to exposed areas, use wide-brim hats and sunglasses, avoid peak UV intensity hours of 10am-4pm and seek shade. Sun protective clothing with a SPF rating can also provide additional protection.

Artificial UV exposure
The WHO recommends that artificial UV exposure including tanning beds should be avoided as no safe dose has been established. When one is exposed to any artificial source of occupational UV, special protective clothing (for example, welding helmets/shields) should be worn </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 Swimmers itch and explain in detail? [/INST] Swimmers itch, cercarial dermatitis or schistosome dermatitis is a short-term allergic contact dermatitis occurring in the skin of humans that have been infected by water-borne schistosomes, a type of flatworm. It is common in freshwater, brackish and marine habitats worldwide. The incidence of this condition may be increasing, although this may be attributed to better monitoring and reporting. Nevertheless, the condition is considered to be an emerging infectious disease.The main symptom is itchy papules (raised skin) that commonly occur within 2 days of infection. Initially, wheals develop quickly, then turn into maculae in about half an hour. Within 10–12 hours these turn into very itchy papules that reach their worst by the second or third day. The papules disappear in 1–2 weeks but secondary effects from scratching can continue longer. The intense itching, which peaks after 48–72 hours, is associated with pain and swelling of the affected areas. People repeatedly exposed to cercariae develop heavier symptoms with faster onset.There are no permanent effects to people from this condition. Orally administered hydroxyzine, an antihistamine, is sometimes prescribed to treat swimmers itch and similar dermal allergic reactions. In addition, bathing in oatmeal, baking soda, or Epsom salts can also provide relief of symptoms.

Cause
Swimmers itch was known to exist as early as the 19th century, but it was not until 1928 that a biologist found that the dermatitis was caused by the larval stage of a group of flatworm parasites in the family Schistosomatidae. The genera most commonly associated with swimmers itch in humans are Trichobilharzia and Gigantobilharzia. It can also be caused by schistosome parasites of non-avian vertebrates, such as Schistosomatium douthitti, which infects snails and rodents. Other taxa reported to cause the reaction include Bilharziella polonica and Schistosoma bovis. In marine environments, especially along the coasts, swimmers itch can occur as well.These parasites use both freshwater snails and vertebrates as hosts in their parasitic life cycles as follows:

Once a schistosome egg is immersed in water, a short-lived, non-feeding, free-living stage known as the miracidium emerges. The miracidium uses cilia to follow chemical and physical cues thought to increase its chances of finding the first intermediate host in its life cycle, a freshwater snail.
After infecting a snail, it develops into a mother sporocyst, which in turn undergoes asexual reproduction, yielding large numbers of daughter sporocysts, which asexually produce another short-lived, free-living stage, the cercaria.
Cercariae use a tail-like appendage (often forked in genera causing swimmers itch) to swim to the surface of the water; and use various physical and chemical cues in order to locate the next and final (definitive) host in the life cycle, a bird. These larvae can accidentally come into contact with the skin of a swimmer. The cercaria penetrates the skin and dies in the skin immediately. The cercariae cannot infect humans, but they cause an inflammatory immune reaction. This reaction causes initially mildly itchy spots on the skin. Within hours, these spots become raised papules which are intensely itchy. Each papule corresponds to the penetration site of a single parasite.
After locating a bird, the parasite penetrates through the skin (usually the feet), dropping the forked tail in the process. Inside the circulatory system, the immature worms (schistosomula) develop into mature male and female worms, mate and migrate through the hosts circulatory system (or nervous system in case of T. regenti) to the final location (veins feeding the gastrointestinal tract) within the host body. There they lay eggs in the small veins in the intestinal mucosa from which they make their way into the lumen of the gut, and are dumped into the water when the bird defecates. One European species, Trichobilharzia regenti, instead infects the bird hosts nasal tissues and larvae hatch from the eggs directly in the tissue during drinking/feeding of the infected birds.

Risk factors
Humans usually become infected after swimming in slow-moving rivers, lakes or ponds. Some laboratory evidence indicates snails shed cercariae most intensely in the morning and on sunny days, and exposure to water in these conditions may therefore increase risk. Duration of swimming is correlated with increased risk of infection in Europe and North America, and shallow inshore waters may harbour higher densities of cercariae than open waters offshore </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 Periodic breathing 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 Anaplastic large-cell lymphoma and explain in detail? [/INST] Anaplastic large cell lymphoma (ALCL) refers to a group of non-Hodgkin lymphomas in which aberrant T cells proliferate uncontrollably. Considered as a single entity, ALCL is the most common type of peripheral lymphoma and represents ~10% of all peripheral lymphomas in children. The incidence of ALCL is estimated to be 0.25 cases per 100,000 people in the United States of America. There are four distinct types of anaplastic large cell lymphomas that on microscopic examination share certain key histopathological features and tumor marker proteins. However, the four types have very different clinical presentations, gene abnormalities, prognoses, and/or treatments.ALCL is defined based on microscopic histopathological examination of involved tissues which shows the presence of at least some ALCL-defining pleomorphic cells. These "hallmark" cells have abnormal kidney-shaped or horseshoe-shaped nuclei, prominent Golgi, and express the CD30 tumor marker protein on their surface membranes. In 2016, the World Health Organization (WHO) separated ALCL into four types: ALK-positive ALCL (also termed ALK+ ALCL), ALK-negative ALCL (ALK− ALCL), primary cutaneous ALCL (pcALCL), and breast implant-associated ALCL (BIA-ALCL). WHO defined BIA-ALCL as an ALCL type provisionally, i.e. subject to redefinition if future studies should support such a change.ALK-positive and ALK-negative ALCL are aggressive systemic lymphomas. They are differentiated based on their expression of an abnormal ALK protein made by a somatic recombination in the ALK gene. ALK, i.e. anaplastic lymphoma kinase, is a protein product of the ALK gene located on chromosome 2. In ALK-positive ALCL, a portion of the ALK gene has merged with another site on the same or different chromosome to form a chimeric gene consisting of part of the new site and part of the ALK gene coding for ALKs activity. This chimeric gene overproduces a fusion protein with excessive ALK activity. ALK is a serine/threonine-specific protein kinase that activities PI3K/AKT/mTOR, Ras-activated ERKs, Janus kinase-activated STAT proteins, and other cell signaling pathways as well as the expression of various genes by epigenetic mechanisms. Activations of these signaling pathways and genes may stimulate cell growth, proliferation, survival, and/or other behaviors that promote malignancy. ALK-negative ALCL, while not involving ALK translocations, has, in a variable percentage of cases, various translocations, rearrangements, and mutations that may contribute to its development.pcALCL and BIA-ALCL are far less aggressive lymphomas that tend to be localized to one or a very few sites. pcALCL presents as a single or, less commonly, multifocal skin papules or tumors that typically are limited to the dermis without infiltrating to the subcutaneous tissues or spreading to other sites. Its neoplastic cells may contain some gene translocations including, in very rare cases, ones with the ALK gene that are similar to those in ALK-positive ALCL. BIA-ALCL is caused by and develops around a breast implant. It typically presents many years after the surgical implantation as a deformation, textural change, and/or pain emanating in the area around implanted breast. In most cases, the disease is localized to the involved breast. BPI-ALCL is associated with occasional mutations in one or two genes but has not been reported to be associated with products of gene translocations or rearrangements.

ALK-positive anaplastic large cell lymphoma
Signs and symptoms
ALK-positive ALCL occurs mostly but not exclusively in children and young adults and is slightly more common in males. Most individuals present with stage III or IV (i.e. advanced) disease. They evidence systemic symptoms including B symptoms such as fever, night sweats, and weight loss in 75% of cases; lymph node enlargement (90%) including those in the mediastinum (36%); and lymphomatous lesions in the skin (26%), bone (14%), soft tissues (15%), lung (12%), and/or liver (8%). Tumor cells are found in the bone marrow in up to 40% of the cases when immunohistochemical analysis is performed. Involvement of the central nervous system or a leukemia-like circulation of malignant cells in the blood occurs only very rarely. Most patients, including up to 90% of young children and adolescents, have circulating autoantibodies directed against the ALK fusion protein expressed by their tumor cells.

Diagnosis
ALK-positive ALCL is diagnosed by histological and immunological examinations of involved tissues, typically lymph nodes. These tissues have lymphoma-like infiltrates that have variable numbers of ALCL "hallmark" cells, i.e. cells with kidney- or horseshoe-shaped nuclei that strongly express CD30 as detected by immunohistochemistry and an ALK fusion protein as detected by fluorescence in situ hybridization. These cells are scattered throughout the infiltrates. WHO classifies these infiltrates into 5 patterns: a Common Pattern consisting of large variably-shaped cells with large nuclei that typically contain multiple nucleoli (60–70% of cases); a Small Cell Pattern consisting of small to medium-sized neoplastic cells with clear cytoplasm and "hallmark" cells that are concentrated around small blood vessels (5–10% of cases); a Lymphohistiocytic Pattern consisting of small neoplastic cells along with abundant histiocytes (10% of cases); a Hodgkins-Like Pattern in which the architecture resembles the nodular sclerosis pattern of Hodgkin lymphoma (3% of cases); and a Composite Pattern consisting of two or more of the just described patterns (15% of cases). Detection of circulating autoantibody against ALK supports the diagnosis. Individuals with low levels of these autoantibodies are at an increase risk of relapsing after treatment.

Gene and molecular abnormalities
In 80–85% of cases, the ALK detected in ALK-positive ALCL is a NPM1-ALK fusion protein. It is made by a fusion of NPM1 gene, which makes nucleophosmin 1, located on the long or "q" arm of chromosome 5 at position 35 (notated as 5q35) with the ALK gene located on the short or "p" arm of chromosome 2 at position 23 (notated as 2p23) to form a chimeric gene notated as (2;5)(p23;q35). In 13% of cases ALK fuses with the TPM3 gene or in <1% of cases for each of the following genes: TFG, ATIC, CLTC, TPM4, MSN, RNF213 (also termed ALO17), MYH9, or TRAF1. All of these fusion proteins are considered to act like NPMI-ALK in possessing high ALK activity that promotes the development and progression ALK-positive ALCL by activating the cell signaling pathways cited in the Introduction. 15% Of individuals with ALK-positive ALCL also have point mutations in the NOTCH1 gene. While most of these abnormalities are thought to be detrimental not all are. For example, DUSP22 gene rearrangements are associated with favorable outcomes in ALK-positive (as well as ALK-negative) ALCL.

Treatment and prognosis
A recommended induction therapy for ALK-positive ALCL in individuals with lesions containing more than 10 percent CD30-positive cells consists of brentuximab vedotin (a drug consisting of an anti-CD30 antibody attached to a cell-killing agent, monomethyl auristatin E); two chemotherapy drugs, cyclophosphamide and the anthracycline, doxorubicin; and the  corticosteroid, prednisone. This regimen gave a progression-free survival rate of 48.2 months in one study and overall survival rates of 70–90% at five years in other studies. For >60 year old and medically unfit individuals of any age, the standard CHOP regimen (cyclophosphamide, doxorubicin, prednisone, and the chemotherapeutic agent, vincristine) is used. For younger, medically fit individuals, the chemotherapeutic agent etoposide is added to the CHOP regimen (CHOP plus etoposide is termed the "CHOEP" regimen). For patients with lesions that contain <10% CD30-positive neoplastic cells, brentuximab vedotin, which targets these cells, is not used. Rather, patients are treated with an anthracycline-based chemotherapy regimen. Patients >60 years or less medically fit are given cyclophosphamide, doxorubicin, vincristine, and prednisone while patients ≤60 years old are given CHOP plus etoposide or one of various other intensive chemotherapy regiments. The intensive chemotherapy regimens give 5 year overall survival rates of 70–93%. The role of radiation therapy for ALK-positive ALCL is unclear but has been used for patients who cannot tolerate or do not achieve complete responses to the drug regimens and to patients with organ-threatening or life-threatening tumorous infiltrates. The role of autologous or less preferably allogenic hematopoietic stem cell transplantation (transplantation using the individuals own bone marrow, i.e. autologous, or a donors, i.e. allogenic) after achieving a complete remission following induction therapy is also unclear. Individuals with relapsed or refractory disease are treated with brentuximab vedotin if they did not receive the drug previously or had not received it in the previous 6 months. A small study reported overall response rates, complete response rates, and disease-free survival rates at 24 months of 63%, 45%, and 54%, respectively, using this regimen. Those who attain a complete response on this drug and can tolerate it are than treated with bone marrow transplantation. Finally, patients who fail or relapse on these treatments are given salvage therapy regimens that have been used for relapsed or refractory aggressive B cell malignancies such as GDP (i.e. gemcitabine, dexamethasone, and cisplatin), DHAP, and ICE.Drugs that inhibit ALK activity such as crizotinib and alectinib have been successful in establishing complete and partial remissions in a limited number of patients with advanced, refractory ALK-positive ALCL. These and other drugs are undergoing clinical trials to determine there safety and effectiveness in treating ALK-positive ALCL. (Also see clinical trials that use ALK inhibitors in ALK-positive ALCL and clinical trials that use ALK inhibitors in ALK-positive cancers.)

ALK-negative anaplastic large cell lymphoma
Signs and symptoms
Unlike ALK-positive ALCL, ALK-negative ALCL tends to occur in older adults (median age at diagnosis: 55–60 years) and presents primarily with lymph node involvement; only 20% of patients with ALK-ALCL present with extra-nodal disease in sites such as the skin, bone, and soft tissues. Nonetheless, most individuals (~67%) present with advanced stage grade III or IV disease in which neoplastic infiltrates occur in multiple lymph node locations and/or extra-nodal sites. ALK autoantibodies are not found in this type of ALCL. The prognosis of ALK-negative ALCL is often quoted as being worse than that for ALK-positive ALCL but this may reflect the older age and advanced stage at which ALK-negative disease presents: studies comparing age- and grade-matched ALK-positive to ALK-negative ALCL patients show little differences in prognoses.

Diagnosis
The histology of ALK-negative ALCL, similar to ALK-positive ALCL, consist of "hallmark" cells that strongly express CD30. Unlike ALK-positive ALCL, however, ALK-negative ALC does not fall into different morphological patterns. The histological of this disease may overlap with and be difficult to distinguish from other CD30-positive T-cell lymphomas or the nodular sclerosis form of Hodgkin lymphoma. Cases in which ALK-negative ALCL is not distinguishable from the latter lymphomas are best diagnosed as peripheral T-cell lymphoma not otherwise specified (PTL, NOS). The histology of ALK-negative ALCL may also overlap with tumors of non–T-cell lineage such as various carcinomas. The differential diagnoses of ambiguous cases may be helped by examining the tumor cells for the expression of certain marker proteins. For example, expression of CD56, MUC1 (also termed EMA for epithelial membrane antigen), and clusterin and strong uniform expression of CD30 support the diagnosis of ALK-negative ALCL over PTL, NOS, while variable CD30 expression and extensive expression of T-cell receptor proteins favor PTCL-NOS over ALK-negative ALCL. Detection of certain gene abnormalities (see next section) may also help distinguishing these diseases.

Gene and molecular abnormalities
ALK-negative ALCL tumor cells show products made by chimeric genes: DUSP22-IRF4 (many of which are fused at particular site and termed DUSP22-FRA7H) in 30% of the cases; TP63-TBL1XR1 in 8% of cases; and NFKB2-ROS1, NCOR2-ROS1, NFKB2-TYK2, or PABPC4-TYK2 in rare cases. They also show mutations in the JAK1 and/or STAT3 genes in 18% of cases; the MSC gene in 15% of cases, and the NOTCH1 gene in 15% of cases. About 24% of cases have a truncated ERBB4 gene. DUSP22 gene rearrangements have been associated with favorable outcomes in ALK-negative ALCL while TP63 gene arrangements are often associated with a poorer prognosis in various cancers. ALK-negative ALCL cells overexpress overactive STAT3 in 47% of cases and JAK1 in many cases. Many of these gene abnormalities appear to contribute to the development of ALK-negative ALCL.

Treatment and prognosis
The various treatments of ALK-negative ALCL generally follow those used for ALK-positive ALCL. However ALK-negative individuals more often present at an advanced stage of disease that requires intensive therapy. The aggressive treatments outline in the section on ALK-positive ALCL are used with the exception that patients with more favorable clinical and tumor tissue indicators as defined by having an International Prognostic Index score above 2 (particularly those who are under the age of 66) who obtain a complete remission after initial therapy are recommended for follow-up bone marrow transplantation. The International T-Cell Project reported on the treatment of 220 patients with ALK-negative ALCL; 15 received only supportive care, 168 were treated with anthracycline-containing chemotherapeutic regimens, 31 with anthracycline plus etoposide–containing chemotherapeutic regimens, 6 with other regimens; 16 with high-dose chemotherapy plus autologous stem cell bone marrow transplantation, and 4 with radiotherapy alone. Of the 205 patients that had more that supportive therapy, the overall and complete response rates were 77% and 63%, respectively. After a median follow-up of 52 months, the median progression free and overall survival times were 41 months and 55 months, respectively; 3- and 5-year progression-free rates were 52% and 43%, respectively; and 3- and 5-year overall survival rates were 60% and 49%, respectively. Chemotherapy treatments containing both anthracycline and etoposide were associated with superior overall survival rates (3- and 5-years of 76% and 69%, respectively) compared to chemotherapy treatment regiments containing an anthracycline but not etoposide (3- and 5-year overall survival rates of 56% and 44%, respectively). Progression-free survival rates with the latter two types of chemotherapy treatment regimens were not appreciably different.

Primary cutaneious anaplastic large cell lymphoma
Signs and symptoms
pcALCL is the second most common lymphoma in the category of Cutaneous T cell lymphoma cutaneous T cell lymphomas that includes lymphomatoid papulosis, various borderline CD30-positive cutaneous T cell lymphomas, and mycosis fungoides. The median age at diagnosis for pcALC is 61 years. The disease has a male predominance and appears to be more common in Caucasian populations. Individuals with pcALCL typically present with reddish masses that initially appear in the skin or, much less frequently, the lymph nodes or various organs. These masses are nodules or tumors that are often ulcerated, greater than 2 cm in diameter, and localized to a single site. In 20% of cases, however, they occur in multiple sites. In about 10% cases followed for many years, pcALCL presenting as skin lesions progresses to extracutaneous sites, mainly to regional draining lymph nodes. Over these same long periods, however, the diseases lesions partially regress in about 50% of cases but then relapse in about 40% of cases.

Diagnosis
pcALCL lesions exhibit large malignant T-cells or null cells (i.e. cells lacking many T-cell receptor proteins) with "Hallmark" cell features of anaplasia, pleomorphism, and kidney- and horse shaped-nuclei. These lesions are often limited to the dermis but can extend into the surrounding subcutaneous tissue and/or epidermis. Rarely, the lesions, termed pyrogenic variants, are rich in polymorphonuclear neutrophils. The neoplastic cells strongly express CD30 (100% of cases), CD2 (78%), CD4 (54–90% of cases), cytotoxicity marker proteins, and various other marker proteins that help distinguish it from other ALCL, cutaneous T-cell lymphomas, and cancers. While these cells typically are ALK-negative, they do express ALK-containing fusion proteins in rare cases. The latter cases have a relatively benign course compared to ALK-positive ALCL and are treated as variants of pcALCL rather than ALK-positive ALCL.

Gene and molecular abnormalities
Similar to ALK-negative ALCL, pcALCL have chromosomal rearrangements in their DUSP22 (20-30% of cases) and TP63 (5% of cases) genes and a mutation in the MSC (i.e. musculin) gene (6% of cases). Between 1993 and 2019, the Dutch registry had 6 (i.e. 2%) of 319 pcALCL cases that expressed ALK. Three of these cases were due to the NPM1-ALK chimeric gene that predominates in ALK-positive ALCL while the remaining three were due to TRAF1-ALK, ATIC-ALK, or TPM3-ALK chimeric genes. All 6 patients shared exactly the same breakpoint site in the ALK at exon 20 on the ALK gene.

Treatment and prognosis
Most pcALCL individuals present with isolated lesions that are effectively managed with radical surgical excision and/or radiation therapies; this approach is regarded as front-line therapy for localized  disease. However, individuals with extensive disease and/or multiple tissue involvement respond poorly to front line treatment. These as well as individuals who relapse after front-line therapy need further treatment. In one study of 65 patients with pcALCL, 95% treated with surgical excision achieved complete remission but 41% of them relapsed within 22 months while 64% of patients treated with surgery plus radiotherapy developed recurrent disease within 55 months. In another study of 135 patients with this disease, 39% had relapses limited to the skin, 15% developed extracutaneous disease, and 9% ultimately died from pcALCL. Individuals with refractory, recurrent, and/or extensive disease have been treated more aggressively. In various studies, 10 of 13 such patients responded within 4 weeks to treatment with the chemotherapeutic agent, methotrexate; 10 of 16 patients obtained complete remissions of their skin lesions when treated with the anti-CD30 monoclonal antibody, brentuximab verdotin, and 48 of 53 patients treated with the aggressive chemotherapeutic CHOP regimen had complete responses. However, most of these patients developed recurrent disease within four months. As currently recommended, brentuximab vedotin is use initially to treat widespread systemic disease; a single chemotherapeutic drug rather than aggressive combination chemotherapy with CHOP or similar regimens is used to treat patients not responding to brentuximab verdotin; aggressive chemotherapy regimens are used to treat widespread nodal and/of visceral disease and disease which failed on other regiments; and, although there is little data supporting this, employ allogeneic bone marrow transplantation for patients with multiple relapses that have progressed on systemic therapy. Recurrences, regardless of treatment type, are common. pcALCL has an estimated five-year failure-free survival rate of 55 percent. Nonetheless, the disease has a 10-year overall survival rate of 90%. Typically leg involvement portends a worse prognosis: it has a five-year disease-specific survival rate of 76 percent compared with 96 percent for disease in other locations. Involvement of local nodes alone in patients with skin lesions does not seem to portend an adverse prognosis.

Breast implant-associated anaplastic large cell lymphoma
Signs and symptoms
BIA-ALCL is a complication of silicon-filled and saline-filled breast implants which develops 9 years to 10 years (median times) after surgical implantation. First described in 1997, it is estimated that the prevalence of BIA-ACLC in individuals with implants that have a textured surface is 1 in 30,000 while the risk of it is 70-fold lower in individuals who have a smooth surface implant or have no implant at all (i.e. in patients that have another type of ALCL). These relations strongly suggest that BIA-ACLC develops primarily if not exclusively in patients with textured implants. In all cases, however, many researchers suspect that  BIA-ALCL is an under-recognized, misdiagnosed, and under-reported complication of breast implants. Two-thirds of individuals with BIA-ALCL present with swelling, discomfort, and/or (rarely) pain in the affected breast. This is due to the development of a tumor mass and/or swelling caused by an effusion (i.e. fluid) that accumulates between the breast implant surface and the fibrous capsule that has grown around it. The effusion fluid typically contains white blood cells, tumor cells, and high levels of protein. Besides or in addition to breast swelling, patients present with a breast mass in 30% present of cases, enlarged lymph nodes in the armpit or around the chest clavicle bones in 20% of cases, and/or in a small percentage of cases lesions in more distant tissues. Rarely, patients have presented with skin rash or itching on or around the involved breast. Using the Ann Arbor staging system, 83% of patients present with Stage 1 localized disease while the remaining 10, 0, and 7% of patients present with what is normally regarded as more aggressive Stage II, III, or IV diseases, respectively. Thus, about 17% of individuals present with a more aggressive disease that has spread from its original breast implant site to nearby lymph nodes, to areas outside of the capsule, or to more distal tissues.

Diagnosis
In most individuals with BIA-ALCL, the affected breast has a thickened capsule around the implant and effusion fluid between the capsule and implant. Neoplastic cells are located in and typically limited to the capsule and effusion. Histological examination of the capsules shows large anaplastic cells but cells with all the features of ALCL "hallmark" are often difficult to detect. In addition to these neoplastic cells, the capsule lesions contain, sometimes in a large excess that makes diagnosis difficult, a variety of non-malignant cells such as small lymphocytes, histiocytes, and granulocytes (the granulocytes are mostly eosinophils). The histology of palpable masses exhibit a different pathological picture: the tumor masses have multinodular areas that consist of necrosis or fibrous tissue interspaced with areas that consist of large neoplastic cells that have abundant cytoplasm and abnormally shaped nuclei within a fibrotic and chronic inflammatory cell background. Again, typical ALCL-defining "hallmark" cells may be difficult to find in these masses. The effusions show abundant, uniform-appearing, non-cohesive large cells with irregularly-shaped nuclei, prominent nucleoli and abundant cytoplasm. The histology and pathological features of diseased lymph nodes and tissues outside of the breast implant are indistinguishable from those seen in ALK-negative ALCL. The neoplastic cells in the capsules, effusions, and tissues strongly and uniformly express CD30, CD4 (75–84% of cases), EMA (48–90%), CD43 (86-95%), CD45 (44-74%), and in a far fewer percentage of cases various other marker proteins. These cells do not express ALK and often lack the characteristic surface marker proteins of T-cells. Identification of the status of these markers helps diagnose the disease.

Gene and molecular abnormalities
No chromosome translocations, chimeric genes, or fusion proteins have been described in BIA-ALCL although the neoplastic cells in the disease have been described to have gene copy number variations involving gains in gene copies on the p arm of chromosome 19 and losses of gene copies in the p arms of chromosome 10 and 1. The neoplastic cells in BIA-ALCL show mutations of the STAT3 gene in 64% of cases and reports of mutations in JAK1, JAK3, DNMT3A, and TP53 genes. The development of BIA-ALCL, it has often been suggested, may be at least in part a T-cell-induced, inflammation-driven cancer response to the implant.

Treatment and prognosis
The treatment regimens for BIA-ALCL recommended by 1) a multidisciplinary expert review panel, 2) the National Comprehensive Cancer Network, and 3) the French National Cancer Institute (Agence Nationale de Sécurité du Médicament [ANSM]) are very similar, commonly used, and summarized here. BIA-ALCL staging is done to identify patients with BIA-ALCL confined to the implant, capsule, and effusion from more disseminated disease. The staging preferably employs the TMN system designed to stage solid tumors. This is based on historical data suggesting that BIA-ALCL progresses locally like solid tumors rather than liquid tumors such as other lymphomas </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 Whooping cough and explain in detail? [/INST] Whooping cough, also known as pertussis or the 100-day cough, is a highly contagious bacterial disease. Initial symptoms are usually similar to those of the common cold with a runny nose, fever, and mild cough, but these are followed by two or three months of severe coughing fits. Following a fit of coughing, a high-pitched whoop sound or gasp may occur as the person breathes in. The violent coughing may last for 10 or more weeks, hence the phrase "100-day cough". A person may cough so hard that they vomit, break ribs, or become very tired from the effort. Children less than one year old may have little or no cough and instead have periods where they cannot breathe. The time between infection and the onset of symptoms is usually seven to ten days. Disease may occur in those who have been vaccinated, but symptoms are typically milder.Pertussis is caused by the bacterium Bordetella pertussis. It is spread easily through the coughs and sneezes of an infected person. People are infectious from the start of symptoms until about three weeks into the coughing fits. Those treated with antibiotics are no longer infectious after five days. Diagnosis is by collecting a sample from the back of the nose and throat. This sample can then be tested by either culture or by polymerase chain reaction.Prevention is mainly by vaccination with the pertussis vaccine. Initial immunization is recommended between six and eight weeks of age, with four doses to be given in the first two years of life. Protection from pertussis decreases over time, so additional doses of vaccine are often recommended for older children and adults. Vaccination during pregnancy is highly effective at protecting the infant from pertussis during their vulnerable early months of life, and is recommended in many countries. Antibiotics may be used to prevent the disease in those who have been exposed and are at risk of severe disease. In those with the disease, antibiotics are useful if started within three weeks of the initial symptoms, but otherwise have little effect in most people. In pregnant women and children less than one year old, antibiotics are recommended within six weeks of symptom onset. Antibiotics used include erythromycin, azithromycin, clarithromycin, or trimethoprim/sulfamethoxazole. Evidence to support interventions for the cough, other than antibiotics, is poor. About 50% of infected children less than a year old require hospitalization and nearly 0.5% (1 in 200) die.An estimated 16.3 million people worldwide were infected in 2015. Most cases occur in the developing world, and people of all ages may be affected. In 2015, pertussis resulted in 58,700 deaths – down from 138,000 deaths in 1990. Outbreaks of the disease were first described in the 16th century. The bacterium that causes the infection was discovered in 1906. The pertussis vaccine became available in the 1940s.

Signs and symptoms
The classic symptoms of pertussis are a paroxysmal cough, inspiratory whoop, and fainting, or vomiting after coughing. The cough from pertussis has been documented to cause subconjunctival hemorrhages, rib fractures, urinary incontinence, hernias, and vertebral artery dissection. Violent coughing can cause the pleura to rupture, leading to a pneumothorax. Vomiting after a coughing spell or an inspiratory whooping sound on coughing, almost doubles the likelihood that the illness is pertussis. The absence of a paroxysmal cough or posttussive emesis, though, makes it almost half as likely.The illness usually starts with mild respiratory symptoms include mild coughing, sneezing, or a runny nose (known as the catarrhal stage). After one or two weeks, the coughing classically develops into uncontrollable fits, sometimes followed by a high-pitched "whoop" sound, as the person tries to inhale. About 50% of children and adults "whoop" at some point in diagnosed pertussis cases during the paroxysmal stage.
This stage usually lasts two to eight weeks, or sometimes longer. A gradual transition then occurs to the convalescent stage, which usually lasts one to four weeks. This stage is marked by a decrease in paroxysms of coughing, although paroxysms may occur with subsequent respiratory infection for many months after the onset of pertussis.Symptoms of pertussis can be variable, especially between immunized and non-immunized people. Those that are immunized can present with a more mild infection; they may only have the paroxysmal cough for a couple of weeks, and it may lack the "whooping" characteristic. Although immunized people have a milder form of the infection, they can spread the disease to others who are not immune.

Incubation period
The time between exposure and the development of symptoms is on average 7–14 days (range 6–20 days), rarely as long as 42 days.

Cause
Pertussis is caused by the bacterium Bordetella pertussis. It is an airborne disease (through droplets) that spreads easily through the coughs and sneezes of an infected person.

Spread from animals
Uncertainties have existed of B. pertussis and whooping cough as a zoonotic disease since around 1910, but in the 1930s knowledge was gained that the bacteria lost their virulent power when repeatedly spread on agar media. This explained the difficulties to reproduce results from different studies as the pre-inoculating handlings of the bacteria were not standardized among scientists.Today it is established that at least some primate species are highly susceptible to B. pertussis and develop clinical whooping cough in high incidence when exposed to low inoculation doses. The bacteria may be present in wild animal populations, but this is not confirmed by laboratory diagnosis, although whooping cough is known among wild gorillas. Several zoos also have a long-standing custom of vaccinating their primates against whooping cough.

Mechanism
After the bacteria are inhaled, they initially adhere to the ciliated epithelium in the nasopharynx. Surface proteins of B. pertussis, including filamentous hemaglutinin and pertactin, mediate attachment to the epithelium. The bacteria then multiply. In infants, who experience more severe disease, the bacteria spread down to the lungs.The bacteria secretes a number of toxins. Tracheal cytotoxin, a fragment of peptidoglycan, kills ciliated epithelial cells and thereby inhibits the mucociliary elevator by which mucus and debris are removed. TCT may contribute to the cough characteristic of pertussis. The cough may also be caused by a yet-to-be identified "cough toxin". Pertussis toxin causes lymphocytosis by an unknown mechanism. The elevated number of white blood cells leads to pulmonary hypertension, a major cause of death by pertussis. In infants who develop encephalopathy, cerebral hemorrhage and cortical atrophy occur, likely due to hypoxia.

Diagnosis
Based on symptoms
A physicians overall impression is most effective in initially making the diagnosis. Single factors are much less useful. In adults with a cough of less than 8 weeks, vomiting after coughing or a "whoop" is supportive. If there are no bouts of coughing or there is a fever the diagnosis is unlikely. In children who have a cough of less than 4 weeks vomiting after coughing is somewhat supportive but not definitive.

Lab tests
Methods used in laboratory diagnosis include culturing of nasopharyngeal swabs on a nutrient medium (Bordet–Gengou medium), polymerase chain reaction (PCR), direct fluorescent antibody (DFA), and serological methods (e.g. complement fixation test). The bacteria can be recovered from the person only during the first three weeks of illness, rendering culturing and DFA useless after this period, although PCR may have some limited usefulness for an additional three weeks.
Serology may be used for adults and adolescents who have already been infected for several weeks to determine whether antibody against pertussis toxin or another virulence factor of B. pertussis is present at high levels in the blood of the person.

Differential diagnosis
A similar, milder disease is caused by B. parapertussis.

Prevention
The primary method of prevention for pertussis is vaccination. Evidence is insufficient to determine the effectiveness of antibiotics in those who have been exposed, but are without symptoms. Preventive antibiotics, however, are still frequently used in those who have been exposed and are at high risk of severe disease (such as infants).

Vaccine
Pertussis vaccines are effective at preventing illness and are recommended for routine use by the World Health Organization and the United States Centers for Disease Control and Prevention. The vaccine saved an estimated half a million lives in 2002.The multicomponent acellular pertussis vaccine is 71–85% effective, with greater effectiveness against more severe strains. However, despite widespread vaccination, pertussis has persisted in vaccinated populations and is today "one of the most common vaccine-preventable diseases in Western countries". The 21st-century resurgences in pertussis infections is attributed to a combination of waning immunity and bacterial mutations that elude vaccines.Immunization does not confer lifelong immunity; a 2011 CDC study indicated that protection may only last three to six years. This covers childhood, which is the time of greatest exposure and greatest risk of death from pertussis.An effect of widespread immunization on society has been the shift of reported infections from children aged 1–9 years to infants, adolescents, and adults, with adolescents and adults acting as reservoirs for B. pertussis and infecting infants who have had fewer than three doses of vaccine.Infection induces incomplete natural immunity that wanes over time. A 2005 study said estimates of the duration of infection-acquired immunity range from 7 to 20 years and the different results could be the result of differences in levels of circulating B. pertussis, surveillance systems, and case definitions used. The study said protective immunity after vaccination wanes after 4–12 years. One study suggested that the availability of vaccine exemptions increases the number of pertussis cases.Some studies have suggested that while acellular pertussis vaccines are effective at preventing the disease, they have a limited impact on infection and transmission, meaning that vaccinated people could spread pertussis even though they may have only mild symptoms or none at all. Pertussis infection in these persons may be asymptomatic, or present as illness ranging from a mild cough to classic pertussis with persistent cough (i.e., lasting more than 7 days). Even though the disease may be milder in older persons, those who are infected may transmit the disease to other susceptible persons, including unimmunized or incompletely immunized infants. Older persons are often found to have the first case in a household with multiple pertussis cases, and are often the source of infection for children.

Treatment
The antibiotics erythromycin, clarithromycin, or azithromycin are typically the recommended treatment. Newer macrolides are frequently recommended due to lower rates of side effects. Trimethoprim-sulfamethoxazole (TMP/SMX) may be used in those with allergies to first-line agents or in infants who have a risk of pyloric stenosis from macrolides.A reasonable guideline is to treat people age >1 year within 3 weeks of cough onset and infants age <1 year and pregnant women within 6 weeks of cough onset. If the person is diagnosed late, antibiotics will not alter the course of the illness, and even without antibiotics, they should no longer be spreading pertussis. When used early, antibiotics decrease the duration of infectiousness, and thus prevent spread. Short-term antibiotics (azithromycin for 3–5 days) are as effective as long-term treatment (erythromycin 10–14 days) in eliminating B. pertussis with fewer and less severe side effects.People with pertussis are most infectious during the first two weeks following the onset of symptoms.Effective treatments of the cough associated with this condition have not been developed. The use of over the counter cough medications is discouraged and has not been found helpful.

Prognosis
While most healthy older children and adults fully recover, infection in newborns is particularly severe. Pertussis is fatal in an estimated 0.5% of US infants under one year of age. First-year infants are also more likely to develop complications, such as: apneas (31%), pneumonia (12%), seizures (0.6%) and encephalopathy (0.15%). This may be due to the ability of the bacterium to suppress the immune system.

Epidemiology
Worldwide, whooping cough affects around 16 million people yearly. One estimate for 2013 stated it resulted in about 61,000 deaths – down from 138,000 deaths in 1990. Another estimated 195,000 child deaths yearly from the disease worldwide. This is despite generally high coverage with the DTP and DTaP vaccines. Pertussis is one of the leading causes of vaccine-preventable deaths worldwide. About 90% of all cases occur in developing countries.Before vaccines, an average of 178,171 cases was reported in the U.S., with peaks reported every two to five years; more than 93% of reported cases occurred in children under 10 years of age. The actual incidence was likely much higher. After vaccinations were introduced in the 1940s, pertussis incidence fell dramatically to approximately 1,000 by 1976. Incidence rates have increased since 1980. In 2015, 20,762 people were reported to have been infected in the United States.Pertussis is the only vaccine-preventable disease that is associated with increasing deaths in the U.S. The number of deaths increased from four in 1996 to 17 in 2001, almost all of which were infants under one year. In Canada, the number of pertussis infections has varied between 2,000 and 10,000 reported cases each year over the last ten years, and it is the most common vaccine-preventable illness in Toronto.In 2009 Australia reported an average of 10,000 cases a year, and the number of cases had increased. In the U.S. pertussis in adults has increased significantly since about 2004.In 2017, India had a reported 23,766 reported pertussis cases, making it one of the highest reported number of cases of the year. Other countries, such as Germany, had reported 16,183 cases, while Australia and China had a reported number of 12,114 and 10,390 pertussis cases.

US outbreaks
In 2010, 10 babies in California died and health authorities declared an epidemic with 5,978 confirmed, probable and suspected cases. They found that doctors had failed to correctly diagnose the babies condition during several visits. Statistical analysis identified significant overlap in communities with a cluster of nonmedical child exemptions and cases. The number of exemptions varied widely among communities, but tended to be highly clustered. In some schools, more than 75 % of parents filed for vaccination exemptions. The data suggest vaccine refusal based on nonmedical reasons and personal belief exacerbated the outbreak. Other factors included reduced duration of immunity following the acellular vaccine and most vaccinated adults and older children not receiving a booster shot.In April and May 2012, pertussis was declared to be at epidemic levels in Washington, with 3,308 cases. In December 2012 Vermont declared an epidemic of 522 cases. Wisconsin had the highest incidence rate, with 3,877 cases, although it did not make an official epidemic declaration.

History
Discovery
B. pertussis was discovered in 1906 by Jules Bordet and Octave Gengou, who also developed the first serology and vaccine. Efforts to develop an inactivated whole-cell vaccine began soon after B. pertussis was cultured that year. In the 1920s, Louis W. Sauer developed a weak vaccine for whooping cough at Evanston Hospital (Evanston, IL). In 1925 Danish physician Thorvald Madsen was the first to test a whole-cell vaccine on a wide scale. Madsen used the vaccine to control outbreaks in the Faroe Islands in the North Sea.

Vaccine
In 1932 an outbreak of whooping cough hit Atlanta, Georgia, prompting pediatrician Leila Denmark to begin her study of the disease </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 Spondylolysis and explain in detail? [/INST] Spondylolysis is a defect or stress fracture in the pars interarticularis of the vertebral arch. The vast majority of cases occur in the lower lumbar vertebrae (L5), but spondylolysis may also occur in the cervical vertebrae.

Signs and symptoms
In majority of cases, spondylolysis presents asymptomatically which can make diagnosis both difficult and incidental. When a patient does present with symptoms, there are general signs and symptoms a clinician will look for:

Clinical signs:Pain on completion of the stork test (placed in hyperextension and rotation)
Excessive lordotic posture
Unilateral tenderness on palpation
Visible on diagnostic imaging (Scottie dog fracture)
Symptoms:Unilateral low back pain
Pain that radiates into the buttocks or legs
Onset of pain can be acute or gradual
Pain that can restrict daily activities
Pain that worsens after strenuous activity
Pain aggravated with lumbar hyperextension
Difficulty in movement in spinal cord

Cause
The cause of spondylolysis remains unknown, however many factors are thought to contribute to its development. The condition is present in up to 6% of the population, majority of which usually present asymptomatically. Research supports that there are hereditary and acquired risk factors that can make one more susceptible to the defect. The disorder is generally more prevalent in males compared to females, and tends to occur earlier in males due to their involvement in more strenuous activities at a younger age. In a young athlete, the spine is still growing which means there are many ossification centers, leaving points of weakness in the spine. This leaves young athletes at increased risk, particularly when involved in repetitive hyperextension and rotation across the lumbar spine. Spondylolysis is a common cause of low back pain in preadolescents and adolescent athletes, as it accounts for about 50% of all low back pain. It is believed that both repetitive trauma and an inherent genetic weakness can make an individual more susceptible to spondylolysis.

Risk factors
Sports involving repetitive or forceful hyperextension of the spine, especially when combined with rotation are the main mechanism of injury for spondylolysis. The stress fracture of the pars interarticularis occurs on the side opposite to activity. For instance, for a right-handed player, the fracture occurs on the left side of the vertebrae.Spondylolysis has a higher occurrence in the following activities:
Baseball
Military service
Tennis
Diving
Cheerleading
Gymnastics
Gridiron Football
Association Football
Wrestling
Weightlifting
Roller Derby
Cricket
Pole Vault
Rugby
Volleyball
Gym
Ultimate Frisbee (especially during impact from laying out)
Ballet
Muay ThaiAlthough this condition can be caused by repetitive trauma to the lumbar spine in strenuous sports, other risk factors can also predispose individuals to spondylolysis. Males are more commonly affected by spondylolysis than females. In one study looking at youth athletes, it was found that the mean age of individuals with spondylolisthesis was 20 years of age. Spondylolysis also runs in families suggesting a hereditary component such as a predisposition to weaker vertebrae.

Pathophysiology
Spondylolysis is a bony defect or fracture within the pars interarticularis of the vertebral arch in the spinal column. The vast majority of spondylolysis occur in the lumbar vertebrae, however it can also be seen in cervical vertebrae. The lumbar vertebra consist of a body, pedicle, lamina, pars interarticularis, transverse process, spinous process and superior and inferior articular facets, which form joints that link the vertebrae together. When examining the vertebra, the pars interarticularis is the bony segment between the superior and inferior articular facet joints located anterior to the lamina and posterior to the pedicle. Separation of the pars interarticularis occurs when spondylolysis is present in the spinal column.Spondylolysis is typically caused by a stress fracture of the bone, and is especially common in adolescents who over-train in activities. The pars interarticularis is vulnerable to fracture during spinal hyperextension, especially when combined with rotation, or when experiencing a force during a landing. This stress fracture most commonly occurs where the concave lumbar spine transitions to the convex sacrum (L5-S1). A significant number of individuals with spondylolysis will develop spondylolisthesis, which is true for 50-81% of this population.

Diagnosis
There are several imaging techniques used to diagnose spondylolysis. Common imaging techniques include X-ray, MRI, Bone Scintigraphy (Bone Scan), and Computed Tomography (CT Scan).

X-Ray
X-rays (electromagnetic radiation) are projected through the body to produce an image of its internal structures. The radiation is more attenuated (absorbed) by the denser tissues of the body (i.e. bone) than the softer tissues (i.e. muscles, organs, etc) creating a picture composed of shades of grey ranging from white to black. A vertebra with a fracture or defect of the pars interarticularis will have a dark mark through this region of bone. Since this is difficult to see on the AP (anterior posterior) x-ray view an oblique x-ray of the lumbar spine can usually identify the spondylolysis. If inconclusive a further CT scan can produce a 3-dimensional images to more clearly show the defect although the exam increases the patients radiation dose by at least an order of magnitude than plain x-rays.

Bone scintigraphy
Also known as a bone scan, bone scintigraphy involves the injection of a small amount of radioactive tracer into the bloodstream. This tracer decays and emits radioactive energy which can be detected by a special camera. The camera produces a black and white image where areas shown as dark black indicate bone damage of some kind. If there is a black spot in the lumbar vertebrae (e.g. L5) this indicates damage and potentially spondylolysis. If this test is positive, a CT scan is usually ordered to confirm spondylolysis.

Computed tomography
Commonly known as a CT Scan or CAT scan, this form of imaging is very similar to x-ray technology but produces many more images than an x-ray does. The multiple images produce cross-sectional views not possible with an x-ray. This allows a physician or radiologist to examine the images from many more angles than an x-ray allows. For this reason the CT scan is much more accurate in detecting spondylolysis than an x-ray. Bone scintigraphy combined with CT scan is considered the gold standard which means that it is best at detecting spondylolysis.

MRI
MRI is a newer technique used to diagnose spondylolysis and is favorable for a few reasons. The MRI is much more accurate than the x-ray and also does not use radiation. The MRI uses powerful magnets and radio frequencies to produce very detailed images of many different densities of tissue including bone and soft tissues.

Treatment
Conservative management
Treatment for spondylolysis ranges from bracing, activity restriction, extension exercises, flexion exercises and deep abdominal strengthening, that is administered through physical therapy. The duration of physical therapy a patient receives varies upon the severity of spondylolysis, however typically ranges from three to six months. The goal of physical therapy is to minimize movement at the unstable defect of the pars interarticularis. Once a patient completes physical therapy, and displays no symptoms or inflammation in the lower back, they are cleared to continue with daily or athletic activities. However, a patient may need to maintain a variety of rehabilitation techniques after physical therapy to prevent the recurrence of spondylolysis.

Deep abdominal co-contraction exercises
The aim of deep abdominal co-contraction exercises is to train muscles surrounding the lumbar spine which provide stability of the spine. Spondylolysis results in a spinal instability and disrupts patterns of co-recruitment between muscle synergies. Specifically, local muscles that attach directly to the spine are affected. The lumbar multifidus and transversus abdominis  play a direct role in stabilizing the lumbar spine. Instead the local muscles in individuals with spondylolysis are vulnerable to dysfunction, which results in abnormal spinal stability causing chronic low back pain. To compensate, the large torque producing global muscles are used to stabilize the spine.In one study, patients are taught to train the co-contraction of deep abdominal muscles and lumbar multifidus in static postures, functional tasks and aerobic activities. This technique was shown to reduce pain and functional disability when compared to other conservative treatments. These results also had a long- term effect in reducing levels of pain and functional disability. This is because motor programming eventually became automatic, and conscious control was no longer needed to contract the deep abdominal muscles during activities.

Activity restriction
Activity restriction of spondylolysis is advised for a short period of time once the patient becomes symptomatic, followed by a guided physical therapy program. Once spondylolysis has been diagnosed, treatment often consists of a short rest period of two to three days, followed by a physical therapy program. There should be restriction of heavy lifting, excessive bending, twisting and avoidance of any work, recreational activities or participation in sport that causes stress to the lumbar spine. Activity restriction can help eliminate and control a patients symptoms so they are able to resume their normal activities. Activity restriction is most commonly used in conjunction with other rehabilitation techniques including bracing.

Bracing
Acute spondylolysis is most commonly treated through the use of an antilordotic brace (Boston brace) to control and limit spinal movement, and reduce stress on the injured spinal segment. Bracing immobilizes the spine in a flexed position for a short period to allow healing of the bony defect in the pars interarticularis. An antilordotic brace commonly utilizes a plastic component that is contoured to closely fit the body. Antilordotic bracing subsequently reduces the athlete’s symptoms by decreasing the amount of stress on the low back, and allows a prompt return to sport for athletes. Typically, bracing is utilized for 6–12 weeks.In order for a brace to be effective, it must be worn every day for the required amount of time. Patients are given a brace schedule determined by their physical therapist that explains the amount of time the brace must be worn daily. A braces effectiveness increases with adherence to the bracing schedule. Patients that do not follow their bracing schedule are more likely to have their symptoms progress. Research has demonstrated that when braces are used as prescribed with full compliance, they are successful at preventing spondylolysis progression.

Surgery
Most patients with spondylolysis do not require surgery but, if the symptoms are not relieved with non-surgical treatments, or when the condition progresses to high grade spondylolisthesis, then patients may require surgery. There are two main types of surgery for this condition:
Spinal fusion: This procedure is recommended when a set of vertebrae becomes loose or unstable. The surgeon joins two or more bones (vertebrae) together through the use of metal rods, screws, and bone grafts. The bone grafts complete their fusion in 4–8 months following the surgery, securing the spine in the correct position. The procedure is also used to treat spinal instability, fractures in the lumbar spine and, severe degenerative disc disease. The process is relatively non-invasive, performed through small incisions and has a high success rate.
Laminectomy: Often performed when spinal stenosis occurs in conjunction with spondylolysis. The procedure surgically removes part or all of the lamina from the bony ring of the vertebra to reduce the pressure on the spinal cord </s>