<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 Iodine deficiency and explain in detail? [/INST] Iodine deficiency is a lack of the trace element iodine, an essential nutrient in the diet. It may result in metabolic problems such as goiter, sometimes as an endemic goiter as well as congenital iodine deficiency syndrome due to untreated congenital hypothyroidism, which results in developmental delays and other health problems. Iodine deficiency is an important global health issue, especially for fertile and pregnant women. It is also a preventable cause of intellectual disability.
Iodine is an essential dietary mineral for neurodevelopment among children. The thyroid hormones thyroxine and triiodothyronine contain iodine. In areas where there is little iodine in the diet, typically remote inland areas where no marine foods are eaten, iodine deficiency is common. It is also common in mountainous regions of the world where food is grown in iodine-poor soil.
Prevention includes adding small amounts of iodine to table salt, a product known as iodized salt. Iodine compounds have also been added to other foodstuffs, such as flour, water and milk, in areas of deficiency. Seafood is also a well known source of iodine.In the U.S., the use of iodine has decreased over concerns of overdoses since mid-20th century, and the iodine antagonists bromine, perchlorate and fluoride have become more ubiquitous. In particular, around 1980 the practice of using potassium iodate as dough conditioner in bread and baked goods was gradually replaced by the use of other conditioning agents such as bromide.Iodine deficiency resulting in goiter occurs in 187 million people globally as of 2010 (2.7% of the population). It resulted in 2700 deaths in 2013, up from 2100 deaths in 1990.

Signs and symptoms
Goiter
A low amount of thyroxine (one of the two thyroid hormones) in the blood, due to lack of dietary iodine to make it, gives rise to high levels of thyroid stimulating hormone (TSH), which stimulates the thyroid gland to increase many biochemical processes; the cellular growth and proliferation can result in the characteristic swelling or hyperplasia of the thyroid gland, or goiter. In mild iodine deficiency, levels of triiodothyronine (T3) may be elevated in the presence of low levels of levothyroxine, as the body converts more of the levothyroxine to triiodothyronine as a compensation. Some such patients may have a goiter, without an elevated TSH. The introduction of iodized salt since the early 1900s has eliminated this condition in many affluent countries; however, in Australia, New Zealand, and several European countries, iodine deficiency is a significant public health problem. It is more common in developing countries. Public health initiatives to lower the risk of cardiovascular disease have resulted in lower discretionary salt use at the table. Additionally, there is a trend towards consuming more processed foods in western countries. The noniodized salt used in these foods means that people are less likely to obtain iodine from adding salt during cooking.
Goiter is said to be endemic when the prevalence in a population is > 5%, and in most cases goiter can be treated with iodine supplementation. If goiter is untreated for around five years, however, iodine supplementation or thyroxine treatment may not reduce the size of the thyroid gland because the thyroid is permanently damaged.

Congenital iodine deficiency syndrome
Congenital iodine deficiency syndrome, previously known as cretinism, is a condition associated with iodine deficiency and goiter, commonly characterised by mental deficiency, deafness, squint, disorders of stance and gait and stunted growth due to hypothyroidism. Paracelsus was the first to point out the relation between goitrous parents and their mentally disabled children.As a result of restricted diet, isolation, intermarriage, etc., as well as low iodine content in their food, children often had peculiar stunted bodies and retarded mental faculties, a condition later known to be associated with thyroid hormone deficiency. Diderot, in his 1754 Encyclopédie, described these patients as "crétins". In French, the term "crétin des Alpes" also became current, since the condition was observed in remote valleys of the Alps in particular. The word cretin appeared in English in 1779.
While reporting recent progress towards overcoming iodine-deficiency disorders worldwide, The Lancet noted: "According to World Health Organization, in 2007, nearly 2 billion individuals had insufficient iodine intake, a third being of school age." A conclusion was made that the single most preventable cause of intellectual disability is that of iodine deficiency.

Fibrocystic breast changes
There is preliminary evidence that iodine deficiency enhances the sensitivity of breast tissue to estrogen. In rats treated with estradiol, iodine deficiency has been shown to lead to changes similar to benign breast changes that are reversible by increased iodine in the diet. In a few studies, iodine supplementation had beneficial effects (such as reducing the presence of breast cyst, fibrous tissue plaques and breast pain) in women with fibrocystic breast changes.Protective effects of iodine on breast cancer have been postulated from epidemiologic evidence and described in animal models. In view of the antiproliferative properties of iodine in breast tissue, molecular iodine supplementation has been suggested as an adjuvant in breast cancer therapy.

Risk factors
Following is a list of potential risk factors that may lead to iodine deficiency:
Low dietary iodine
Selenium deficiency
Pregnancy
Exposure to radiation
Increased intake/plasma levels of goitrogens, such as calcium
Sex (higher occurrence in women)
Smoking tobacco
Alcohol (reduced prevalence in users)
Oral contraceptives (reduced prevalence in users)
Perchlorates
Thiocyanates
Age (for different types of iodine deficiency at different ages)

Pathophysiology
Iodine accounts for 65% of the molecular weight of T4 and 59% of T3.  There is a total of 15–20 mg of iodine in the human body, primarily concentrated in thyroid tissue and hormones. Thirty percent of iodine is distributed in other tissues, including the mammary glands, eyes, gastric mucosa, choroid plexus, arterial walls, the cervix, and salivary glands. In the cells of these tissues, iodide enters directly by sodium-iodide symporter (NIS).

Venturi S, Guidi A, Venturi M (1996). "[Extrathyroid iodine deficiency disorders: what is the real iodine requirement?]"". Le Basi Razionali della Terapia. 16: 267–275.
Pellerin P (1961). "La tecnique dautoradiographie anatomique a la temperature de lazote liquide". Path Biol. 232 (9): 233–252.

Diagnosis
The diagnostic workup of a suspected iodine deficiency includes signs and symptoms as well as possible risk factors mentioned above. A 24-hour urine iodine collection is a useful medical test, as approximately 90% of ingested iodine is excreted in the urine. For the standardized 24-hour test, a 50 mg iodine load is given first, and 90% of this load is expected to be recovered in the urine of the following 24 hours. Recovery of less than 90% is taken to mean high retention, that is, iodine deficiency. The recovery may, however, be well less than 90% during pregnancy, and an intake of goitrogens can alter the test results.If a 24-hour urine collection is not practical, a random urine iodine-to-creatinine ratio can alternatively be used. However, the 24-hour test is found to be more reliable.A general idea of whether a deficiency exists can be determined through a functional iodine test in the form of an iodine skin test. In this test, the skin is painted with an iodine solution: if the iodine patch disappears quickly, this is taken as a sign of iodine deficiency. However, no accepted norms exist on the expected time interval for the patch to disappear, and in persons with dark skin color the disappearance of the patch may be difficult to assess. If a urine test is taken shortly after, the results may be altered due to the iodine absorbed previously in a skin test.

Treatment
Iodine deficiency is treated by ingestion of iodine salts, such as found in food supplements. Mild cases may be treated by using iodized salt in daily food consumption, or drinking more milk, or eating egg yolks, and saltwater fish.  For a salt and/or animal product restricted diet, sea vegetables (kelp, hijiki, dulse, nori (found in sushi)) may be incorporated regularly into a diet as a good source of iodine.The recommended daily intake of iodine for adult women is 150–300 µg for maintenance of normal thyroid function; for men, it is somewhat less at 150 µg.Nonetheless, there is a lack of evidence on iodine fortification in foods, beverages, condiments, or seasonings other than salt in preventing goiter or improving physical development. On the other hand, such a measure may increase iodine concentration in urine.However, too high iodine intake, for example due to overdosage of iodine supplements, can have toxic side effects. It can lead to hyperthyroidism and consequently high blood levels of thyroid hormones (hyperthyroxinemia). In case of extremely high single-dose iodine intake, typically a short-term suppression of thyroid function (Plummer effect and Wolff–Chaikoff effect) occurs. Persons with pre-existing thyroid disease, elderly persons, fetuses and neonates, and patients with other risk factors are at a higher risk of experiencing iodine-induced thyroid abnormalities. In particular, in persons with goiter due to iodine deficiency or with altered thyroid function, a form of hyperthyroidism called Jod-Basedow phenomenon can be triggered even at small or single iodine dosages, for example as a side effect of administration of iodine-containing contrast agents. In some cases, excessive iodine contributes to a risk of autoimmune thyroid diseases (Hashimotos thyroiditis and Graves disease).
Different experts in nutrition advise different amounts of iodine supplementation.  Supplementation is typically in a product which contains roughly half iodine and half iodide (a popular product used and sold for decades is “Iodoral®” which contains 5 mg of Iodine and 7.5 mg of Iodide).
On low side there is Kara Fitzgerald recommending less than 1,100 mcg per day (except when treating some medical conditions), she considers long term dosage of 40,000 mcg per day “excessive”.  In the middle we have Dr. Alan Gaby who considers a “moderately high dose” to be 3,000 to 6,000 mcg per day.   On the higher end we have Dr. David Brownstein, Dr. Jorge Flechas, Dr. Guy Abraham, Dr. Alan Roby and Dr. Jonathan Wright who recommend 6,000 mcg to 50,000 mcg per day.

Prognosis
With iodine supplementation, goiters caused by iodine deficiency decrease in size in very young children and pregnant women. Generally, however, long-standing goiters caused by iodine deficiency respond with only small amounts of shrinkage after iodine supplementation, and patients are at risk for developing hyperthyroidism.Being pregnant while iodine-deficient additionally carries the risk of causing congenital iodine deficiency syndrome in the newborn. This disease can only be managed by lifelong administration of thyroxine (T4).

Epidemiology
Iodine deficiency resulting in goiter occurs in 187 million people globally as of 2010 (2.7% of the population). Certain areas of the world, due to natural deficiency and unavailability of iodine, are severely affected by iodine deficiency, which affects approximately two billion people worldwide. It is particularly common in the Western Pacific, South-East Asia and Africa. Among other nations affected by iodine deficiency, China and Kazakhstan have begun taking action, while Russia has not. Successful campaigns for the adoption of the use of iodized salt require education of salt producers and sellers and a communication campaign directed at the public. The cost of adding iodine to salt is negligible—"Only a few cents a ton."Iodine deficiency has largely been confined to the developing world for several generations, but reductions in salt consumption and changes in dairy processing practices eliminating the use of iodine-based disinfectants have led to increasing prevalence of the condition in Australia and New Zealand in recent years.  A proposal to mandate the use of iodized salt in most commercial breadmaking was adopted in Australia in October 2009. In a study of the United Kingdom published in 2011, almost 70% of test subjects were found to be iodine deficient. The studys authors suggested an investigation regarding "evidence-based recommendations for iodine supplementation".Micronutrient deficiencies, including iodine deficiency, impair the development of intelligence. Lacking iodine during human development causes a fall, in average, of 12 intelligence quotient (IQ) points in China. A study of U.S. military data collected during the First and Second World Wars found that the introduction of salt iodization in the U.S. in the 1920s resulted in an increase in IQ, by approximately one standard deviation, for the quarter of the U.S. population most deficient in iodine, explaining about "one decades worth of the upward trend in IQ" in the U.S. (i.e., the Flynn effect). The same study documented "a large increase in thyroid-related deaths following the countrywide adoption of iodized salt, which affected mostly older individuals in localities with high prevalence of iodine deficiency".In iodine-deficient or mildly iodine-deficient areas of Europe, iodine deficiency is frequent during pregnancy despite the widespread use of iodised salt, posing risks to the neurodevelopment of foetuses. In one study performed in a mildly iodine-deficient area, iodine deficiency was found to be present in more than half of breastfeeding women; in contrast, the majority of their newborns had iodine excess, mostly due to neonatal exposure to iodine-containing disinfectants. A 2014 meta-analysis found that iodine supplementation "improves some maternal thyroid indices and may benefit aspects of cognitive function in school-age children, even in marginally iodine-deficient areas".

Deficient populations
In areas where there is little iodine in the diet, typically remote inland areas and semi-arid equatorial climates where no marine foods are eaten, iodine deficiency gives rise to hypothyroidism, symptoms of which are extreme fatigue, goiter, mental slowing, depression, weight gain, and low basal body temperatures.Iodine deficiency is the leading cause of preventable mental retardation, a result which occurs primarily when babies or small children are rendered hypothyroidic by a lack of the element. The addition of iodine to table salt has largely eliminated this problem in the wealthier nations, but as of March 2006, iodine deficiency remained a serious public health problem in the developing world.Iodine deficiency is also a problem in certain areas of Europe. In Germany it has been estimated to cause a billion dollars in health care costs per year. A modelling analysis suggests universal iodine supplementation for pregnant women in England may save £199 (2013 UK pounds) to the health service per pregnant woman and save £4476 per pregnant woman in societal costs.Iodine deficiency was previously a common disease in Norway, because the content of iodine in the drinking water was low.  Before 1950 goiter was a widespread disease caused by iodine deficiency. Up to 80 per cent of the population were affected in inland areas </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 Asplenia and explain in detail? [/INST] Asplenia refers to the absence of normal spleen function and is associated with some serious infection risks. Hyposplenism is used to describe reduced (hypo-) splenic functioning, but not as severely affected as with asplenism.
Functional asplenia occurs when splenic tissue is present but does not work well (e.g. sickle-cell disease, polysplenia) -such patients are managed as if asplenic-, while in anatomic asplenia, the spleen itself is absent.

Causes
Congenital
Congenital asplenia is rare. There are two distinct types of genetic disorders: heterotaxy syndrome and isolated congenital asplenia.
polysplenia

Acquired
Acquired asplenia occurs for several reasons:

Following splenectomy due to splenic rupture from trauma or because of tumor
After splenectomy with the goal of interfering with splenic function, as a treatment for diseases (e.g. idiopathic thrombocytopenic purpura, thalassemia, spherocytosis), in which the spleens usual activity exacerbates the disease
After splenectomy with the goal of arresting the progression of cancers (Chronic lymphocytic leukemia, Hodgkins disease (starting in the 1970s), non-Hodgkin lymphoma)
Due to underlying diseases that destroy the spleen (autosplenectomy), e.g. sickle-cell disease.
Celiac disease: unknown physiopathology. In a 1970 study, it was the second most common cause of abnormalities of red blood cells linked to hyposplenism, after surgical splenectomy.

Functional asplenia
Functional asplenia can occur when patients with metabolic or haematological disorders have their splenic tissue organisation altered. This can lead to results similar to those seen in patients who have undergone a splenectomy e.g. becoming infected with encapsulated bacteria such as Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis. Patients who have some form of asplenia have an increased susceptibility to these encapsulated bacterial infections mainly because they lack IgM memory B cells and their non-adherence to polysaccharide vaccines. Furthermore, there is a deficiency of other splenic cells e.g. splenic macrophages. This combined with the lack of B cells can provide an environment favourable for the development of bacterial infections.

Partial splenectomy and preservation of splenic function
In an effort to preserve some of the spleens protective roles, attempts are now often made to preserve a small part of the spleen when performing either surgical subtotal (partial) splenectomy, or partial splenic embolization.
This may be particularly important in poorer countries where protective measures for patients with asplenia are not available.
However, it has been advised that preoperative vaccination is advisable until the remnant splenic tissue can reestablish its function.

Risks
Asplenia is a form of immunodeficiency, increasing the risk of sepsis from polysaccharide encapsulated bacteria, and can result in overwhelming post splenectomy infection (OPSI), often fatal within a few hours. In particular, patients are at risk from Streptococcus pneumoniae, Haemophilus influenzae, and meningococcus. The risk is elevated as much as 350–fold.The increased risk of infection is due to inability to clear opsonised bacteria from circulating blood.  There is also a deficiency of T-cell independent antibodies, such as those reactive to the polysaccharide capsule of Streptococcus pneumoniae.The risk to asplenic patients has been expressed as equivalent to an adult dying in a road traffic accident (in every 100 people without spleens, 1 to 5 would develop a severe infection per decade) (reference UK Splenectomy Trust Advice)—hence sensible precautions are advisable. Increased platelet counts can be seen in individuals without a functioning spleen.

Diagnosis
Diagnosis is confirmed by abdominal ultrasonography and detection of Howell-Jolly bodies in red blood cells.

Management
To minimise the risks associated with splenectomy, antibiotic and vaccination protocols have been established, but are often poorly adhered to by physicians and patients due to the complications resulting from antibiotic prophylaxis such as development of an overpopulation of Clostridium difficile in the intestinal tract.

Antibiotic prophylaxis
Because of the increased risk of infection, physicians administer oral antibiotics as prophylaxis after a surgical splenectomy, or starting at birth for congenital or functional asplenia.
Those with asplenia are also cautioned to start a full-dose course of antibiotics at the first onset of an upper or lower respiratory tract infection (for example, sore throat or cough), or at the onset of any fever. Even with a course of antibiotics and even with a history of relevant vaccination, persons without a functional spleen are at risk for Overwhelming post-splenectomy infection.In an emergency room or hospital setting, appropriate evaluation and treatment for an asplenic febrile patient should include a complete blood count with differential, blood culture with Gram stain, arterial blood gas analysis, chest x-ray, and consideration for lumbar puncture with CSF studies. None of these evaluations should delay the initiation of appropriate broad-spectrum intravenous antibiotics. The Surviving Sepsis Campaign guidelines state that antibiotics should be administered to a patient suspected of sepsis within 1 hour of presentation. Delay in starting antibiotics for any reason is associated with a poor outcome.

Vaccinations
It is suggested that splenectomized persons receive the following vaccinations, and ideally prior to planned splenectomy surgery:

Pneumococcal polysaccharide vaccine (not before 2 years of age).  Children may first need one or more boosters of  pneumococcal conjugate vaccine if they did not complete the full childhood series.
Haemophilus influenzae type b vaccine, especially if not received in childhood.  For adults who have not been previously vaccinated,  two doses given two months apart was advised in the new 2006 UK vaccination guidelines (in the UK may be given as a combined Hib/MenC vaccine).
Meningococcal conjugate vaccine, especially if not received in adolescence.  Previously vaccinated adults require a single booster and non-immunised adults advised, in UK since 2006, to have two doses given two months apart.  Children too young for the conjugate vaccine should receive meningococcal polysaccharide vaccine in the interim.
Influenza vaccine, every winter, to help prevent getting secondary bacterial infection.

Travel measures
In addition to the normal immunizations advised for the countries to be visited, Group A meningococcus should be included if visiting countries of particular risk (e.g </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 Acid–base homeostasis and explain in detail? [/INST] Acid–base homeostasis is the homeostatic regulation of the pH of the bodys extracellular fluid (ECF). The proper balance between the acids and bases (i.e. the pH) in the ECF is crucial for the normal physiology of the body—and for cellular metabolism. The pH of the intracellular fluid and the extracellular fluid need to be maintained at a constant level.The three dimensional structures of many extracellular proteins, such as the plasma proteins and membrane proteins of the bodys cells, are very sensitive to the extracellular pH. Stringent mechanisms therefore exist to maintain the pH within very narrow limits. Outside the acceptable range of pH, proteins are denatured (i.e. their 3D structure is disrupted), causing enzymes and ion channels (among others) to malfunction.
An acid–base imbalance is known as acidemia when the pH is acidic, or alkalemia when the pH is alkaline.

Lines of defense
In humans and many other animals, acid–base homeostasis is maintained by multiple mechanisms involved in three lines of defense:
Chemical: The first lines of defense are immediate, consisting of the various chemical buffers which minimize pH changes that would otherwise occur in their absence. These buffers include the bicarbonate buffer system, the phosphate buffer system, and the protein buffer system.
Respiratory component: The second line of defense is rapid consisting of the control the carbonic acid (H2CO3) concentration in the ECF by changing the rate and depth of breathing by hyperventilation or hypoventilation. This blows off or retains carbon dioxide (and thus carbonic acid) in the blood plasma as required.
Metabolic component: The third line of defense is slow, best measured by the base excess, and mostly depends on the renal system which can add or remove bicarbonate ions (HCO−3) to or from the ECF. Bicarbonate ions are derived from metabolic carbon dioxide which is enzymatically converted to carbonic acid in the renal tubular cells. There, carbonic acid spontaneously dissociates into hydrogen ions and bicarbonate ions. When the pH in the ECF falls, hydrogen ions are excreted into urine, while bicarbonate ions are secreted into blood plasma, causing the plasma pH to rise. The converse happens if the pH in the ECF tends to rise: bicarbonate ions are then excreted into the urine and hydrogen ions into the blood plasma.The second and third lines of defense operate by making changes to the buffers, each of which consists of two components: a weak acid and its conjugate base. It is the ratio concentration of the weak acid to its conjugate base that determines the pH of the solution. Thus, by manipulating firstly the concentration of the weak acid, and secondly that of its conjugate base, the pH of the extracellular fluid (ECF) can be adjusted very accurately to the correct value. The bicarbonate buffer, consisting of a mixture of carbonic acid (H2CO3) and a bicarbonate (HCO−3) salt in solution, is the most abundant buffer in the extracellular fluid, and it is also the buffer whose acid-to-base ratio can be changed very easily and rapidly.

Acid–base balance
The pH of the extracellular fluid, including the blood plasma, is normally tightly regulated between 7.32 and 7.42 by the chemical buffers, the respiratory system, and the renal system. The normal pH in the fetus differs from that in the adult. In the fetus, the pH in the umbilical vein pH is normally 7.25 to 7.45 and that in the umbilical artery is normally 7.18 to 7.38.Aqueous buffer solutions will react with strong acids or strong bases by absorbing excess H+ ions, or OH− ions, replacing the strong acids and bases with weak acids and weak bases. This has the effect of damping the effect of pH changes, or reducing the pH change that would otherwise have occurred. But buffers cannot correct abnormal pH levels in a solution, be that solution in a test tube or in the extracellular fluid. Buffers typically consist of a pair of compounds in solution, one of which is a weak acid and the other a weak base. The most abundant buffer in the ECF consists of a solution of carbonic acid (H2CO3), and the bicarbonate (HCO−3) salt of, usually, sodium (Na+). Thus, when there is an excess of OH− ions in the solution carbonic acid partially neutralizes them by forming H2O and bicarbonate (HCO−3) ions. Similarly an excess of H+ ions is partially neutralized by the bicarbonate component of the buffer solution to form carbonic acid (H2CO3), which, because it is a weak acid, remains largely in the undissociated form, releasing far fewer H+ ions into the solution than the original strong acid would have done.The pH of a buffer solution depends solely on the ratio of the molar concentrations of the weak acid to the weak base. The higher the concentration of the weak acid in the solution (compared to the weak base) the lower the resulting pH of the solution. Similarly, if the weak base predominates the higher the resulting pH.
This principle is exploited to regulate the pH of the extracellular fluids (rather than just buffering the pH). For the carbonic acid-bicarbonate buffer, a molar ratio of weak acid to weak base of 1:20 produces a pH of 7.4; and vice versa—when the pH of the extracellular fluids is 7.4 then the ratio of carbonic acid to bicarbonate ions in that fluid is 1:20.

Henderson–Hasselbalch equation
The Henderson–Hasselbalch equation, when applied to the carbonic acid-bicarbonate buffer system in the extracellular fluids, states that:

          p
          H

        =

          p

          K

              a

                H

                2

                C
                O

                3

        +

          log

            10

          (

                [

                    H
                    C
                    O

                    3

                    −

                ]

                [

                    H

                    2

                    C
                    O

                    3

                ]

          )

        ,

    {\displaystyle \mathrm {pH} =\mathrm {p} K_{\mathrm {a} ~\mathrm {H} _{2}\mathrm {CO} _{3}}+\log _{10}\left({\frac {[\mathrm {HCO} _{3}^{-}]}{[\mathrm {H} _{2}\mathrm {CO} _{3}]}}\right),}

where:

pH is the negative logarithm (or cologarithm) of molar concentration of hydrogen ions in the extracellular fluid.
pKa H2CO3 is the cologarithm of the acid dissociation constant of carbonic acid. It is equal to 6.1.
[HCO−3] is the molar concentration of bicarbonate in the blood plasma.
[H2CO3] is the molar concentration of carbonic acid in the extracellular fluid.However, since the carbonic acid concentration is directly proportional to the partial pressure of carbon dioxide (

          P

                  C
                  O

                2

    {\displaystyle P_{{\mathrm {CO} }_{2}}}
  ) in the extracellular fluid, the equation can be rewritten as follows:

          p
          H

        =
        6.1
        +

          log

            10

          (

                [

                    H
                    C
                    O

                    3

                    −

                ]

                0.0307
                ×

                  P

                        C
                        O

                        2

          )

        ,

    {\displaystyle \mathrm {pH} =6.1+\log _{10}\left({\frac {[\mathrm {HCO} _{3}^{-}]}{0.0307\times P_{\mathrm {CO} _{2}}}}\right),}

where:

pH is the negative logarithm of molar concentration of hydrogen ions in the extracellular fluid.
[HCO−3] is the molar concentration of bicarbonate in the plasma.
PCO2 is the partial pressure of carbon dioxide in the blood plasma.The pH of the extracellular fluids can thus be controlled by the regulation of

          P

                  C
                  O

                2

    {\displaystyle P_{{\mathrm {CO} }_{2}}}
   and the other metabolic acids.

Homeostatic mechanisms
Homeostatic control can change the PCO2 and hence the pH of the arterial plasma within a few seconds. The partial pressure of carbon dioxide in the arterial blood is monitored by the central chemoreceptors of the medulla oblongata. These chemoreceptors are sensitive to the levels of carbon dioxide and pH in the cerebrospinal fluid.The central chemoreceptors send their information to the respiratory centers in the medulla oblongata and pons of the brainstem. The respiratory centres then determine the average rate of ventilation of the alveoli of the lungs, to keep the PCO2 in the arterial blood constant. The respiratory center does so via motor neurons which activate the muscles of respiration (in particular, the diaphragm). A rise in the PCO2 in the arterial blood plasma above 5.3 kPa (40 mmHg) reflexly causes an increase in the rate and depth of breathing. Normal breathing is resumed when the partial pressure of carbon dioxide has returned to 5.3 kPa. The converse happens if the partial pressure of carbon dioxide falls below the normal range. Breathing may be temporally halted, or slowed down to allow carbon dioxide to accumulate once more in the lungs and arterial blood.
The sensor for the plasma HCO−3 concentration is not known for certain. It is very probable that the renal tubular cells of the distal convoluted tubules are themselves sensitive to the pH of the plasma. The metabolism of these cells produces CO2, which is rapidly converted to H+ and HCO−3 through the action of carbonic anhydrase. When the extracellular fluids tend towards acidity, the renal tubular cells secrete the H+ ions into the tubular fluid from where they exit the body via the urine. The HCO−3 ions are simultaneously secreted into the blood plasma, thus raising the bicarbonate ion concentration in the plasma, lowering the carbonic acid/bicarbonate ion ratio, and consequently raising the pH of the plasma. The converse happens when the plasma pH rises above normal: bicarbonate ions are excreted into the urine, and hydrogen ions into the plasma. These combine with the bicarbonate ions in the plasma to form carbonic acid (H+ + HCO−3

        ⇌

    {\displaystyle \rightleftharpoons }
   H2CO3), thus raising the carbonic acid:bicarbonate ratio in the extracellular fluids, and returning its pH to normal.In general, metabolism produces more waste acids than bases. Urine produced is generally acidic and is partially neutralized by the ammonia (NH3) that is excreted into the urine when glutamate and glutamine (carriers of excess, no longer needed, amino groups) are deaminated by the distal renal tubular epithelial cells. Thus some of the "acid content" of the urine resides in the resulting ammonium ion (NH4+) content of the urine, though this has no effect on pH homeostasis of the extracellular fluids.

Imbalance
Acid–base imbalance occurs when a significant insult causes the blood pH to shift out of the normal range (7.32 to 7.42). An abnormally low pH in the extracellular fluid is called an acidemia and an abnormally high pH is called an alkalemia.
Acidemia and alkalemia unambiguously refer to the actual change in the pH of the extracellular fluid (ECF) </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 Treacher Collins syndrome and explain in detail? [/INST] Treacher Collins syndrome (TCS) is a genetic disorder characterized by deformities of the ears, eyes, cheekbones, and chin. The degree to which a person is affected, however, may vary from mild to severe. Complications may include breathing problems, problems seeing, cleft palate, and hearing loss. Those affected generally have normal intelligence.TCS is usually autosomal dominant. More than half the time it occurs as a result of a new mutation rather than being inherited from a persons parents. The involved genes may include TCOF1, POLR1C, or POLR1D. Diagnosis is generally suspected based on symptoms and X-rays, and potentially confirmation by genetic testing.Treacher Collins syndrome is not curable. Symptoms may be managed with reconstructive surgery, hearing aids, speech therapy, and other assistive devices. Life expectancy is generally normal. TCS occurs in about one in 50,000 people. The syndrome is named after Edward Treacher Collins, an English surgeon and ophthalmologist, who described its essential traits in 1900.

Signs and symptoms
Symptoms in people with Treacher Collins syndrome vary. Some individuals are so mildly affected that they remain undiagnosed, while others have moderate to severe facial involvement and life-threatening airway compromise. Most of the features of TCS are symmetrical and are already recognizable at birth.The most common symptom of Treacher Collins syndrome is underdevelopment of the lower jaw and underdevelopment of the zygomatic bone. This can be accompanied by the tongue being retracted. The small mandible can result in a poor occlusion of the teeth or in more severe cases, trouble breathing or swallowing. The respiratory system of a child with Treacher Collins syndrome is the primary concern at birth, with other issues only addressed once respiratory function has been stabilized. Underdevelopment of the zygomatic bone gives the cheeks a sunken appearance.The external ear is sometimes small, rotated, malformed, or absent entirely in people with TCS. Symmetric, bilateral narrowing or absence of the external ear canal, is also described. In most cases, the bones of the middle ear and the middle ear cavity are misshapen. Inner ear malformations are rarely described. As a result of these abnormalities, a majority of the individuals with TCS have conductive hearing loss.Most affected people also experience eye problems, including coloboma (notches) in the lower eyelids, partial or complete absence of eyelashes on the lower lid, downward angled eyelids, drooping of upper and lower eyelids, and narrowing of the tear ducts. Vision loss can occur and is associated with strabismus, refractive errors, and anisometropia. It can also be caused by severely dry eyes, a consequence of lower eyelid abnormalities and frequent eye infections.Although an abnormally shaped skull is not distinctive for Treacher Collins syndrome, brachycephaly with bitemporal narrowing is sometimes observed. Cleft palate is also common.Dental anomalies are seen in 60% of affected people, including tooth agenesis (33%), discoloration (enamel opacities) (20%), malplacement of the maxillary first molars (13%), and wide spacing of the teeth. In some cases, dental anomalies in combination with mandible hypoplasia result in a malocclusion. This can lead to problems with food intake and the ability to close the mouth.Less common features of TCS may add to an affected persons breathing problems, including sleep apnea. Choanal atresia or stenosis is a narrowing or absence of the choanae, the internal opening of the nasal passages, which may also be observed. Underdevelopment of the pharynx can also narrow the airway.Features related to TCS that are seen less frequently include nasal deformities, high-arched palate, macrostomia, preauricular hair displacement, cleft palate, hypertelorism, notched upper eyelid, and congenital heart defects.Although facial deformity is often associated with developmental delay and intellectual disability, more than 95% of people affected with TCS have normal intelligence. The psychological and social problems associated with facial deformity can affect quality of life in individuals with TCS.

Genetics
Mutations in TCOF1, POLR1C, or POLR1D genes can cause Treacher Collins syndrome. TCOF1 gene mutations are the most common cause of the disorder, with POLR1C and POLR1D gene mutations causing an additional 2% of cases. In individuals without an identified mutation in one of these genes, the genetic cause of the condition is unknown. The TCOF1, POLR1C, and POLR1D genes code for proteins which play important roles in the early development of bones and other tissues of the face. Mutations in these genes  reduce the production of rRNA, which may trigger the self-destruction (apoptosis) of certain cells involved in the development of facial bones and tissues. It is unclear why the effects of a reduction in rRNA are limited to facial development. Mutations in TCOF1 and POLR1D cause the autosomal dominant form of Treacher Collins, and mutations in POLR1C cause the autosomal recessive form.

TCOF1
TCOF1 is the primary gene associated with TCS, a mutation in this gene being found in 90–95% of the individuals with TCS. However, in some individuals with typical symptoms of TCS, mutations in TCOF1 have not been found. Investigation of the DNA has resulted in the identification of the kind of mutations found in TCOF1. The majority of mutations are small deletions or insertions, though splice site and missense mutations also have been identified.Mutation analysis has unveiled more than 100 disease-causing mutations in TCOF1, which are mostly family-specific mutations. The only recurrent mutation accounts for about 17% of the cases.TCOF1 is found on the 5th chromosome in the 5q32 region. It codes for a relatively simple nucleolar protein called treacle, that is thought to be involved in ribosome assembly. Mutations in TCOF1 lead to haploinsufficiency of the treacle protein. Haploinsufficiency occurs when a diploid organism has only one functional copy of a gene, because the other copy is inactivated by a mutation. The one normal copy of the gene does not produce enough protein, causing disease. Haploinsufficiency of the treacle protein leads to a depletion of the neural crest cell precursor, which leads to a reduced number of crest cells migrating to the first and second pharyngeal arches. These cells play an important role in the development of the craniofacial appearance, and loss of one copy of treacle affects the cells ability to form the bones and tissues of the face.

Other mutations
POLR1C and POLR1D mutations are responsible for a minority of cases of Treacher Collins. POLR1C is found on chromosome 6 at position 6q21.2 and POLR1D is found on chromosome 13 at position 13q12.2. Those genes code for a protein subunits shared between RNA polymerase I and III. Both of these polymerases are important for ribosome biogenesis.

Diagnosis
Genetic counseling
TCS is inherited in an autosomal dominant manner and the penetrance of the affected gene is almost complete. Some recent investigations, though, described some rare cases in which the penetrance in TCS was not complete. Causes may be a variable expressivity, an incomplete penetrance or germline mosaicism. Only 40% of the mutations are inherited. The remaining 60% are a result of a de novo mutation, where a child has a new mutation in the responsible gene and did not inherit it from either parent. In the outcome of the disease, inter- and intrafamilial variability occurs. This suggests that when an affected child is born, it is important to investigate the parents to determine whether the affected gene is present, because the parent could have a mild form of the disease that has not been diagnosed. In this case, the risk of having another affected child is 50%. If the parents do not have the affected gene, the recurrence risk appears to be low. In following generations, the severity of the clinical symptoms increases.

Prenatal diagnosis
Mutations in the main genes responsible for TCS can be detected with chorionic villus sampling or amniocentesis. Rare mutations may not be detected by these methods. Ultrasonography can be used to detect craniofacial abnormalities later in pregnancy, but may not detect milder cases.

Clinical findings
TCS is often first suspected with characteristic symptoms observed during a physical exam. However, the clinical presentation of TCS can resemble other diseases, making diagnosis difficult. The OMENS classification was developed as a comprehensive and stage-based approach to differentiate the diseases. This acronym describes five distinct dysmorphic manifestations, namely orbital asymmetry, mandibular hypoplasia, auricular deformity, nerve development, and soft-tissue disease.Orbital symmetry

O0: normal orbital size, position
O1: abnormal orbital size
O2: abnormal orbital position
O3: abnormal orbital size and positionMandible

M0: normal mandible
M1: small mandible and glenoid fossa with short ramus
M2: ramus short and abnormally shaped2A: glenoid fossa in anatomical acceptable position
2B: Temperomandibular joint inferiorly (TMJ), medially, anteriorly displaced, with severely hypoplastic condyleM3: Complete absence of ramus, glenoid fossa, and TMJEar

E0: normal ear
E1: Minor hypoplasia and cupping with all structures present
E2: Absence of external auditory canal with variable hypoplasia of the auricle
E3: Malposition of the lobule with absent auricle, lobular remnant usually inferior anteriorly displacedFacial nerve

N0: No facial nerve involvement
N1: Upper facial nerve involvement (temporal or zygomatic branches)
N2: Lower facial nerve involvement (buccal, mandibular or cervical)
N3: All branches affectedSoft tissue

S0: No soft tissue or muscle deficiency
S1: Minimal tissue or muscle deficiency
S2: Moderate tissue or muscle deficiency
S3: Severe tissue or muscle deficiency

Radiographs
A few techniques are used to confirm the diagnosis in TCS.An orthopantomogram (OPG) is a panoramic dental X-ray of the upper and lower jaw. It shows a two-dimensional image from ear to ear. Particularly, OPG facilitates an accurate postoperative follow-up and monitoring of bone growth under a mono- or double-distractor treatment. Thereby, some TCS features could be seen on OPG, but better techniques are used to include the whole spectrum of TCS abnormalities instead of showing only the jaw abnormalities.Another method of radiographic evaluation is taking an X-ray image of the whole head. The lateral cephalometric radiograph in TCS shows hypoplasia of the facial bones, like the malar bone, mandible, and the mastoid.Finally, occipitomental radiographs are used to detect hypoplasia or discontinuity of the zygomatic arch.

CT scan
A temporal-bone CT using thin slices makes it possible to diagnose the degree of stenosis and atresia of the external auditory canal, the status of the middle ear cavity, the absent or dysplastic and rudimentary ossicles, or inner ear abnormalities such as a deficient cochlea. Two- and three-dimensional CT reconstructions with VRT and bone and skin-surfacing are helpful for more accurate staging and the three-dimensional  planning of mandibular and external ear reconstructive surgery.

Differential diagnosis
Other diseases have similar characteristics to Treacher Collins syndrome. In the differential diagnosis, one should consider the acrofacial dysostoses. The facial appearance resembles that of Treacher Collins syndrome, but additional limb abnormalities occur in those persons. Examples of these diseases are Nager syndrome and  Miller syndrome.The oculoauriculovertebral spectrum should also be considered in the differential diagnosis. An example is hemifacial microsomia, which primarily affects development of the ear, mouth, and mandible. This anomaly may occur bilaterally. Another disease which belongs to this spectrum is Goldenhar syndrome, which includes vertebral abnormalities, epibulbar dermoids and facial deformities.

Treatment
The treatment of individuals with TCS may involve the intervention of professionals from multiple disciplines. The primary concerns are breathing and feeding, as a consequence of the hypoplasia of the mandibula and the obstruction of the hypopharynx by the tongue. Sometimes, they may require a tracheostomy to maintain an adequate airway, and a gastrostomy to assure an adequate caloric intake while protecting the airway. Corrective surgery of the face is performed at defined ages, depending on the developmental state.An overview of the present guidelines:

If a cleft palate is present, the repair normally takes place at 9–12 months old. Before surgery,  a polysomnography with a palatal plate in place is needed. This may predict the postoperative situation and gives insight on the chance of the presence of sleep apnea (OSAS) after the operation.
Hearing loss is treated by bone conduction amplification, speech therapy, and educational intervention to avoid language/speech problems. The bone-anchored hearing aid is an alternative for individuals with ear anomalies.
Zygomatic and orbital reconstruction is performed when the cranio-orbitozygomatic bone is completely developed, usually at the age of 5–7 years. In children, an autologous bone graft is mostly used. In combination with this transplantation, lipofilling can be used in the periorbital area to get an optimal result of the reconstruction. Reconstruction of the lower eyelid coloboma includes the use of a myocutaneous flap, which is elevated and in this manner closes the eyelid defect.
External ear reconstruction is usually done when the individual is at least eight years old. Sometimes, the external auditory canal or middle ear can also be treated.
The optimal age for the maxillomandibular reconstruction is controversial; as of 2004, this classification has been used:Type I (mild) and Type IIa (moderate)           13–16 years
Type IIb (moderate to severe malformation)     at skeletal maturity
Type III (severe)                              6–10 years
When the teeth are cutting, the teeth should be under supervision of an orthodontist to make sure no abnormalities occur. If abnormalities like dislocation or an overgrowth of teeth are seen, appropriate action can be undertaken as soon as possible.
Orthognatic treatments usually take place after the age of 16 years; at this point, all teeth are in place and the jaw and dentures are mature. Whenever OSAS is detected, the level of obstruction is determined through endoscopy of the upper airways. Mandibular advancement can be an effective way to improve both breathing and æsthetics, while a chinplasty only restores the profile.
If a nose reconstruction is necessary, it is usually performed after the orthognatic surgery and after the age of 18 years.
The contour of the facial soft tissues generally requires correction at a later age, because of the facial skeletal maturity. The use of microsurgical methods, like the free flap transfer, has improved the correction of facial soft tissue contours. Another technique to improve the facial soft tissue contours is lipofilling. For instance, lipofilling is used to reconstruct the eyelids.

Hearing loss
Hearing loss in Treacher Collins syndrome is caused by deformed structures in the outer and middle ear. The hearing loss is generally bilateral with a conductive loss of about 50–70 dB. Even in cases with normal auricles and open external auditory canals, the ossicular chain is often malformed.Attempts to surgically reconstruct the external auditory canal and improve hearing in children with TCS have not yielded positive results.Auditory rehabilitation with bone-anchored hearing aids (BAHAs) or a conventional bone conduction aid has proven preferable to surgical reconstruction.

Psychiatric
The disorder can be associated with a number of psychological symptoms, including anxiety, depression, social phobia, and distress about body image. People who have this disorder may also experience discrimination, bullying, and name calling, especially when young </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 Ototoxicity and explain in detail? [/INST] Ototoxicity is the property of being toxic to the ear (oto-), specifically the cochlea or auditory nerve and sometimes the vestibular system, for example, as a side effect of a drug. The effects of ototoxicity can be reversible and temporary, or irreversible and permanent.
It has been recognized since the 19th century.
There are many well-known ototoxic drugs used in clinical situations, and they are prescribed, despite the risk of hearing disorders, for very serious health conditions.
Ototoxic drugs include antibiotics (such as gentamicin, streptomycin, tobramycin), loop diuretics (such as furosemide), and platinum-based chemotherapy agents (such as cisplatin and carboplatin). A number of nonsteroidal anti-inflammatory drugs (NSAIDS) have also been shown to be ototoxic. This can result in sensorineural hearing loss, dysequilibrium, or both. Some environmental and occupational chemicals have also been shown to affect the auditory system and interact with noise.

Signs and symptoms
Symptoms of ototoxicity include partial or profound hearing loss, vertigo, and tinnitus.The cochlea is primarily a hearing structure situated in the inner ear. It is the snail-shaped shell containing several nerve endings that makes hearing possible.
Ototoxicity typically results when the inner ear is poisoned by medication that damages the cochlea, vestibule, semi-circular canals, or the auditory/ vestibulocochlear nerve. The damaged structure then produces the symptoms the patient presents with. Ototoxicity in the cochlea may cause hearing loss of the high-frequency pitch ranges or complete deafness, or losses at points between.  It may present with bilaterally symmetrical symptoms, or asymmetrically, with one ear developing the condition after the other or not at all. The time frames for progress of the disease vary greatly and symptoms of hearing loss may be temporary or permanent.The vestibule and semi-circular canal are inner-ear components that comprise the vestibular system. Together they detect all directions of head movement. Two types of otolith organs are housed in the vestibule: the saccule, which points vertically and detects vertical acceleration, and the utricle, which points horizontally and detects horizontal acceleration. The otolith organs together sense the heads position with respect to gravity when the body is static; then the heads movement when it tilts; and pitch changes during any linear motion of the head. The saccule and utricle detect different motions, which information the brain receives and integrates to determine where the head is and how and where it is moving.
The semi-circular canals are three bony structures filled with fluid. As with the vestibule, the primary purpose of the canals is to detect movement. Each canal is oriented at right angles to the others, enabling detection of movement in any plane. The posterior canal detects rolling motion, or motion about the X axis; the anterior canal detects pitch, or motion about the Y axis; the horizontal canal detects yaw motion, or motion about the Z axis.
When a medication is toxic in the vestibule or the semi-circular canals, the patient senses loss of balance or orientation rather than losses in hearing. Symptoms in these organs present as vertigo, difficulties walking in low light and darkness, disequilibrium, oscillopsia among others. Each of these problems is related to balance and the mind is confused with the direction of motion or lack of motion. Both the vestibule and semi-circular canals transmit information to the brain about movement; when these are poisoned, they are unable to function properly which results in miscommunication with the brain.
When the vestibule and/or semi-circular canals are affected by ototoxicity, the eye can also be affected. Nystagmus and oscillopsia are two conditions that overlap the vestibular and ocular systems. These symptoms cause the patient to have difficulties with seeing and processing images. The body subconsciously tries to compensate for the imbalance signals being sent to the brain by trying to obtain visual cues to support the information it is receiving. This results in that dizziness and "woozy" feeling patients use to describe conditions such as oscillopsia and vertigo.Cranial nerve VIII is the least affected component of the ear when ototoxicity arises, but if the nerve is affected, the damage is most often permanent. Symptoms present similar to those resulting from vestibular and cochlear damage, including tinnitus, ringing of the ears, difficulty walking, deafness, and balance and orientation issues.

Ototoxic agents
Antibiotics
Antibiotics in the aminoglycoside class, such as gentamicin and tobramycin, may produce cochleotoxicity through a poorly understood mechanism. It may result from antibiotic binding to NMDA receptors in the cochlea and damaging neurons through excitotoxicity. Aminoglycoside-induced production of reactive oxygen species may also injure cells of the cochlea. Once-daily dosing and co-administration of N-acetylcysteine may protect against aminoglycoside-induced ototoxicity. The anti-bacterial activity of aminoglycoside compounds is due to inhibition of ribosome function and these compounds similarly inhibit protein synthesis by mitochondrial ribosomes because mitochondria evolved from a bacterial ancestor. Consequently, aminoglycoside effects on production of reactive oxygen species as well as dysregulation of cellular calcium ion homeostasis may result from disruption of mitochondrial function. Ototoxicity of gentamicin can be exploited to treat some individuals with Ménières disease by destroying the inner ear,  which stops the vertigo attacks but causes permanent deafness.
Due to the effects on mitochondria, certain inherited mitochondrial disorders result in increased sensitivity to the toxic effects of aminoglycosides.
Macrolide antibiotics, including erythromycin, are associated with reversible ototoxic effects. The underlying mechanism of ototoxicity may be impairment of ion transport in the stria vascularis. Predisposing factors include renal impairment, hepatic impairment, and recent organ transplantation.

Loop diuretics
Certain types of diuretics are associated with varying levels of risk for ototoxicity. Loop and thiazide diuretics carry this side effect. The loop diuretic furosemide is associated with ototoxicity, particularly when doses exceed 240 mg per hour. The related compound ethacrynic acid has a higher association with ototoxicity, and is therefore used only in patients with sulfa allergies. Diuretics are thought to alter the ionic gradient within the stria vascularis. Bumetanide confers a decreased risk of ototoxicity compared to furosemide.

Chemotherapeutic agents
Platinum-containing chemotherapeutic agents, including cisplatin and carboplatin, are associated with cochleotoxicity characterized by progressive, high-frequency hearing loss with or without tinnitus (ringing in the ears). Ototoxicity is less frequently seen with the related compound oxaliplatin. The severity of cisplatin-induced ototoxicity is dependent upon the cumulative dose administered and the age of the patient, with young children being most susceptible. The exact mechanism of cisplatin ototoxicity is not known. The drug is understood to damage multiple regions of the cochlea, causing the death of outer hair cells, as well as damage to the spiral ganglion neurons and cells of the stria vascularis. Long-term retention of cisplatin in the cochlea may contribute to the drugs cochleotoxic potential. Once inside the cochlea, cisplatin has been proposed to cause cellular toxicity through a number of different mechanisms, including through the production of reactive oxygen species. The decreased incidence of oxaliplatin ototoxicity has been attributed to decreased uptake of the drug by cells of the cochlea. Administration of amifostine has been used in attempts to prevent cisplatin-induced ototoxicity, but the American Society of Clinical Oncology recommends against its routine use.The vinca alkaloids, including vincristine, are also associated with reversible ototoxicity.

Antiseptics and disinfectants
Topical skin preparations such as chlorhexidine and ethyl alcohol have the potential to be ototoxic should they enter the inner ear through the round window membrane. This potential was first noted after a small percentage of patients undergoing early myringoplasty operations experienced severe sensorineural hearing loss. It was found that in all operations involving this complication the preoperative sterilization was done with chlorhexidine. The ototoxicity of chlorhexidine was further confirmed by studies with animal models.Several other skin preparations have been shown to be potentially ototoxic in the animal model. These preparations include acetic acid, propylene glycol, quaternary ammonium compounds, and any alcohol-based preparations. However, it is difficult to extrapolate these results to human ototoxicity because the human round window membrane is much thicker than in any animal model.

Other medicinal ototoxic drugs
At high doses, quinine, aspirin and other salicylates may also cause high-pitch tinnitus and hearing loss in both ears, typically reversible upon discontinuation of the drug. Erectile dysfunction medications may have the potential to cause hearing loss. However the link between erectile dysfunction medications and hearing loss remains uncertain.Previous noise exposure has not been found to potentiate ototoxic hearing loss. The American Academy of Audiology includes in their position statement that exposure to noise at the same time as aminoglycosides may exacerbate ototoxicity. The American Academy of Audiology recommends people being treated with ototoxic chemotherapeutics avoid excessive noise levels during treatment and for several months following cessation of treatment. Opiates in combination with excessive noise levels may also have an additive effect on ototoxic hearing loss.

Ototoxicants in the environment and workplace
Ototoxic effects are also seen with quinine, pesticides, solvents, asphyxiants, and heavy metals such as mercury and lead. When combining multiple ototoxicants, the risk of hearing loss becomes greater. As these exposures are common, this hearing impairment can affect many occupations and industries.  Examples of activities that often have exposures to both noise and solvents include:
Printing
Painting
Construction
Fueling vehicles and aircraft
Firefighting
Weapons firing
Pesticide sprayingOtotoxic chemicals in the environment (from contaminated air or water) or in the workplace interact with mechanical stresses on the hair cells of the cochlea in different ways. For mixtures containing organic solvents such as toluene, styrene or xylene, the combined exposure with noise increases the risk of occupational hearing loss in a synergistic manner. The risk is greatest when the co-exposure is with impulse noise. Carbon monoxide has been shown to increase the severity of the hearing loss from noise. Given the potential for enhanced risk of hearing loss, exposures and contact with products such as fuels, paint thinners, degreasers, white spirits, exhaust, should be kept to a minimum. Noise exposures should be kept below 85 decibels, and the chemical exposures should be below the recommended exposure limits given by regulatory agencies.
Drug exposures mixed with noise potentially lead to increased risk of ototoxic hearing loss. Noise exposure combined with the chemotherapeutic cisplatin puts individuals at increased risk of ototoxic hearing loss. Noise at 85 dB SPL or above added to the amount of hair cell death in the high frequency region of the cochlea in chinchillas.The hearing loss caused by chemicals can be very similar to a hearing loss caused by excessive noise.  A 2018 informational bulletin by the US Occupational Safety and Health Administration (OSHA) and the National Institute for Occupational Safety and Health (NIOSH) introduces the issue, provides examples of ototoxic chemicals, lists the industries and occupations at risk and provides prevention information.

Treatment
No specific treatment may be available, but withdrawal of the ototoxic drug may be warranted when the consequences of doing so are less severe than those of the ototoxicity. Co-administration of anti-oxidants may limit the ototoxic effects.Ototoxic monitoring during exposure is recommended by the American Academy of Audiology to allow for proper detection and possible prevention or rehabilitation of the hearing loss through a cochlear implant or hearing aid. Monitoring can be completed through performing otoacoustic emissions testing or high frequency audiometry. Successful monitoring includes a baseline test before, or soon after, exposure to the ototoxicant. Follow-up testing is completed in increments after the first exposure, throughout the cessation of treatment. Shifts in hearing status are monitored and relayed to the prescribing physician to make treatment decisions.It is difficult to distinguish between nerve damage and structural damage due to similarity of the symptoms.  Diagnosis of ototoxicity typically results from ruling out all other possible sources of hearing loss and is often the catchall explanation for the symptoms. Treatment options vary depending on the patient and the diagnosis </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 Syphilitic aortitis and explain in detail? [/INST] Syphilitic aortitis  is inflammation of the aorta associated with the tertiary stage of syphilis infection. SA begins as inflammation of the outermost layer of the blood vessel, including the blood vessels that supply the aorta itself with blood, the vasa vasorum. As SA worsens, the vasa vasorum undergo hyperplastic thickening of their walls thereby restricting blood flow and causing ischemia of the outer two-thirds of the aortic wall </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 Tuberculosis verrucosa cutis and explain in detail? [/INST] Tuberculosis verrucosa cutis is a rash of small, red papular nodules in the skin that may appear 2–4 weeks after inoculation by Mycobacterium tuberculosis in a previously infected and immunocompetent individual.
It is also known as "prosectors wart" because it was a common occupational disease of prosectors, the preparers of dissections and autopsies </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 Dialysis disequilibrium syndrome and explain in detail? [/INST] Dialysis disequilibrium syndrome (DDS) is the collection of neurological signs and symptoms, attributed to cerebral edema, during or following shortly after intermittent hemodialysis or CRRT.Classically, DDS arises in individuals starting hemodialysis due to end-stage chronic kidney disease and is associated, in particular, with "aggressive" (high solute removal) dialysis.   However, it may also arise in fast onset, i.e. acute kidney failure in certain conditions.

Symptoms and signs
Diagnosis of mild DDS is often complicated by other dialysis complications such as malignant hypertension, uremia, encephalopathy, subdural hemorrhage, hyper- and hypoglycaemia, or electrolyte imbalances. Presentation of moderate and severe DDS requires immediate identification and treatment as the condition can result in severe neurological issues and death.1. Headache
2. Nausea
3. Dizziness
4. Confusion
5. Visual disturbance
6. Tremor
7 </s>