<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Barraquer–Simons syndrome and can you explain it in depth? [/INST] Barraquer–Simons syndrome is a rare form of lipodystrophy,
which usually first affects the head, and then spreads to the thorax. It is named for Luis Barraquer Roviralta (1855–1928), a Spanish physician, and Arthur Simons (1879–1942), a German physician. Some evidence links it to LMNB2.

Causes
The etiology of this condition has not been fully elucidated.  Lipodystrophy is often associated with glomerulonephritis, low C3 serum complement levels, and the presence of a C3 nephritic factor. C3 nephritic factor is a serum immunoglobulin G that interacts with the C3bBb alternative pathway convertase to activate C3. C3 nephritic factor induces the lysis of adipocytes that secrete adipsin, a product identical to complement factor D. The distribution of the lipoatrophy is postulated to be dictated by the variable amounts of adipsin secreted by the adipocytes at different locations.Human PTRF mutations may cause secondary deficiency of caveolins, resulting in generalized lipodystrophy in association with in muscular dystrophy. Complement dysfunction may predispose some patients to bacterial infections.

Diagnosis
The diagnosis of the disease is mainly clinical (see diagnostic criteria). A laboratory workup is needed primarily to investigate for the presence of associated disorders (metabolic, autoimmune, and renal diseases).
Every patient should have a fasting blood glucose and lipid profile, creatinine evaluation, and urinalysis for protein content at the first visit, after which he/she should have these tests on a regular basis.
Although uncommon, lipid abnormalities can occur in the form of raised triglyceride levels and low high-density lipoprotein cholesterol levels.
Patients usually have decreased serum C3 levels, normal levels of C1 and C4, and high levels of C3NeF (autoantibody), which may indicate the presence of renal involvement.
Antinuclear antibodies (ANA) and antidouble-stranded deoxyribonucleic acid (DNA) antibodies have reportedly been observed in some patients with acquired partial lipodystrophy.
A genetic workup should be performed if the familial form of lipodystrophy is suggested.Laboratory work for associated diseases includes:
Metabolic disease - fasting glucose, glucose tolerance test, lipid profile, and fasting insulin to characterize the insulin resistance state; free testosterone (in women) to look for polycystic ovary syndrome.
Autoimmune disease - ANA, antidouble-stranded DNA, rheumatoid factor, thyroid antibodies, C3, and C3NeF.As a confirmatory test, whole-body MRI usually clearly demonstrates the extent of lipodystrophy. MRI is not recommended on a routine basis.

Diagnostic criteria
A review published in 2004, which was based on 35 patients seen by the respective authors over 8 years and also a literature review of 220 cases of acquired partial lipodystrophy (APL), proposed an essential diagnostic criterion. Based on the review and the authors experience, they proposed that APL presents as a gradual onset of bilaterally symmetrical loss of subcutaneous fat from the face, neck, upper extremities, thorax, and abdomen, in the "cephalocaudal" sequence, sparing the lower extremities. The median age of the onset of lipodystrophy was seven years. Several autoimmune diseases, in particular systemic lupus erythematosus and dermatomyositis, were associated with APL. The prevalence rates of diabetes mellitus and impaired glucose tolerance were 6.7% and 8.9%, respectively. Around 83% of APL patients had low complement 3 (C3) levels and the presence of polyclonal immunoglobulin C3 nephritic factor. About 22% of patients developed membranoproliferative glomerulonephritis (MPGN) after a median of about 8 years following the onset of lipodystrophy. Compared with patients without renal disease, those with MPGN had earlier age of onset of lipodystrophy (12.6 ± 10.3 yr vs 7.7 ± 4.4 yr, respectively; p < 0.001) and a higher prevalence of C3 hypocomplementemia (78% vs 95%, respectively; p = 0.02).The adipose stores of the gluteal regions and lower extremities (including soles) tend to be either preserved or increased, particularly among women.  Variable fat loss of the palms, but no loss of intramarrow or retro-orbital fat, has been demonstrated.

Treatment
In general, treatment for acquired partial lipodystrophy is limited to cosmetic, dietary, or medical options. Currently, no effective treatment exists to halt its progression.
Diet therapy has been shown to be of some value in the control of metabolic problems.  The use of small, frequent feedings and partial substitution of medium-chain triglycerides for polyunsaturated fats appears to be beneficial.Plastic surgery with implants of monolithic silicon rubber for correction of the deficient soft tissue of the face has been shown to be effective.  False teeth may be useful in some cases for cosmetic reasons.  Long-term treatment usually involves therapy for kidney and endocrine dysfunction.Data on medications for APL are very limited.  Thiazolidinediones have been used in the management of various types of lipodystrophies. They bind to peroxisome proliferator-activator receptor gamma (PPAR-gamma), which stimulates the transcription of genes responsible for growth and differentiation of adipocytes. A single report has suggested a beneficial effect from treatment with rosiglitazone on fat distribution in acquired partial lipodystrophy; however, preferential fat gain was in the lower body.Direct drug therapy is administered according to the associated condition. Membranoproliferative glomerulonephritis and the presence of renal dysfunction largely determine the prognosis of acquired partial lipodystrophy. Standard guidelines for the management of renal disease should be followed. The course of membranoproliferative glomerulonephritis in acquired partial lipodystrophy has not been significantly altered by treatment with corticosteroids or cytotoxic medications.  Recurrent bacterial infections, if severe, might be managed with prophylactic antibiotics.

Prognosis
Estimating the mortality rate based on the available literature is difficult.  Several case reports have revealed an association between acquired partial lipodystrophy and other diseases.Nephropathy, in the form of membranoproliferative glomerulonephritis, occurs in about 20% of patients. Usually, patients do not have clinically evident renal disease or abnormalities in renal function until they have had the disease for 8 or more years </s>


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


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Nontuberculous mycobacteria and can you explain it in depth? [/INST] Nontuberculous mycobacteria (NTM), also known as environmental mycobacteria, atypical mycobacteria and mycobacteria other than tuberculosis (MOTT), are mycobacteria which do not cause tuberculosis or leprosy (also known as Hansens disease). NTM do cause pulmonary diseases that resemble tuberculosis. Mycobacteriosis is any of these illnesses, usually meant to exclude tuberculosis. They occur in many animals, including humans and are commonly found in soil and water.

Introduction
Mycobacteria are a family of small, rod-shaped bacilli that can be classified into three main groups for the purpose of diagnosis and treatment:

Mycobacterium tuberculosis complex, which can cause tuberculosis: M. tuberculosis, M. bovis, M. africanum, M. microti and M. canetti
M. leprae and M. lepromatosis,  which cause Hansens disease, also called leprosy
Nontuberculous mycobacteria (NTM) are all the other mycobacteria that can cause pulmonary disease resembling tuberculosis, lymphadenitis, skin disease, or disseminated disease. Although over 150 different species of NTM have been described, pulmonary infections are most commonly due to Mycobacterium avium complex (MAC), Mycobacterium kansasii, and Mycobacterium abscessus (see image).

Taxonomy
In 1959, botanist Ernest Runyon put these human disease-associated bacteria into four groups (Runyon classification):
Photochromogens develop pigments in or after being exposed to light. Examples include M. kansasii, M. simiae, and M. marinum.
Scotochromogens become pigmented in darkness. Examples include M. scrofulaceum and M. szulgai.
Nonchromogens include a group of prevalent opportunistic pathogens called M. avium complex (MAC). Other examples are M. ulcerans, M. xenopi, M. malmoense, M. terrae, M. haemophilum, and M. genavense.
Rapid growers include four well-recognized, pathogenic, rapidly growing, nonchromogenic species: M. chelonae, M. abscessus, M. fortuitum, and M. peregrinum. Other examples cause disease rarely, such as M. smegmatis and M. flavescens.The number of identified and cataloged NTM species has been increasing rapidly, from about 50 in 1997 to over 125 by January 2007. The surge is mainly due to improved isolation and identification techniques.Even with these new techniques, though, the Runyon classification is still sometimes used to organize the mycobacteria into categories.

Epidemiology
NTM are widely distributed in the environment, particularly in wet soil, marshland, streams, rivers and estuaries. Different species of NTM prefer different types of environment. Human disease is believed to be acquired from environmental exposures. Unlike tuberculosis and leprosy, animal-to-human or human-to-human transmission of NTM rarely occurs.NTM diseases have been seen in most industrialized countries, where incidence rates vary from 1.0 to 1.8 cases per 100,000 persons. Recent studies, including one done in Ontario, Canada, suggest that incidence is much higher.  Pulmonary NTM is estimated by some experts in the field to be at least ten times more common than TB in the U.S., with at least 150,000 cases per year.
Most NTM disease cases involve the species known as Mycobacterium avium complex or MAC for short, M. abscessus, M. fortuitum and M. kansasii. M. abscessus is being seen with increasing frequency and is particularly difficult to treat.Mayo Clinic researchers found a three-fold increased incidence of cutaneous NTM infection between 1980 and 2009 in a population-based study of residents of Olmsted County, Minnesota. The most common species were M. marinum, accounting for 45% of cases and M. chelonae and M. abscessus, together accounting for 32% of patients. M. chelonae infection outbreaks, as a consequence of tattooing with infected ink, have been reported in the United Kingdom and the United States.Rapidly growing NTMs are implicated in catheter infections, post-LASIK, skin and soft tissue (especially post-cosmetic surgery) and pulmonary infections.

Pathogenesis
The most common clinical manifestation of NTM disease is lung disease, but lymphatic, skin/soft tissue, and disseminated diseases are also important.Pulmonary disease caused by NTM is most often seen in postmenopausal women and patients with underlying lung disease such as cystic fibrosis, bronchiectasis, and prior tuberculosis. It is not uncommon for alpha 1-antitrypsin deficiency, Marfan syndrome, and primary ciliary dyskinesia patients to have pulmonary NTM colonization and/or infection.  Pulmonary NTM can also be found in individuals with AIDS and malignant disease. It can be caused by many NTM species, which depends on region, but most frequently MAC and M. kansasii.Clinical symptoms vary in scope and intensity, but commonly include chronic cough, often with purulent sputum. Hemoptysis may also be present. Systemic symptoms include malaise, fatigue, and weight loss in advanced disease. The diagnosis of M. abscessus pulmonary infection requires the presence of symptoms, radiologic abnormalities, and microbiologic cultures.
Lymphadenitis can be caused by various species that differ from one place to another, but again, MAC is the main cause worldwide. Most patients are aged less than 5 years, but the incidence is rare for children having BCG vaccine. The disease has a high curability.Soft-tissue disease due to NTM infection include post-traumatic abscesses (caused by rapid growers), swimming pool granuloma (caused by M. marinum) and Buruli ulcer (caused by M. ulcerans or M. shinshuense). Post-traumatic abscesses most commonly occur after injection.Disseminated mycobacterial disease was common in US and European AIDS patients in the 1980s and early 1990s, though the incidence has declined in developed nations since the introduction of highly active antiretroviral therapy. It can also occur in individuals after having renal transplantation.

Diagnosis
Diagnosis of opportunistic mycobacteria is made by repeated isolation and identification of the pathogen with compatible clinical and radiological features. Similar to M. tuberculosis, most nontuberculous mycobacteria can be detected microscopically and grow on Löwenstein-Jensen medium. Many reference centres now use a nucleic acid-based method such as sequence differences detection in the gene coding for 16S ribosomal RNA to identify the species.Pulmonary NTM disease diagnosis requires both identification of the mycobacterium in the patients lung(s), as well as a high-resolution CT scan of the lungs.

Research
French researchers finalized the genome sequence of M. abscessus in March 2008.  The genome is available at https://www.ncbi.nlm.nih.gov/sites/entrez?db=genome&cmd=search&term=abscessus.

References
Further reading
Griffith David E.; Aksamit Timothy; Brown-Elliott Barbara;  et al. (2007). "American Thoracic Society Guidelines: Diagnosis, Treatment and Prevention of Nontuberculous Mycobacterial Diseases". American Journal of Respiratory and Critical Care Medicine. 175 (4): 367–417. doi:10.1164/rccm.200604-571st. PMID 17277290.
New BTS Guideline has been published in 2017, https://www.brit-thoracic.org.uk/standards-of-care/guidelines/bts-guidelines-for-non-tuberculous-mycobacteria/
Grange, J. M. (2007). "Environmental mycobacteria". In Greenwood, David; Slack, Richard; Peitherer, John; & Barer, Mike (Eds.), Medical Microbiology (17th ed.), pp. 221–227 </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Fetal hydantoin syndrome and can you explain it in depth? [/INST] Fetal hydantoin syndrome, also called fetal dilantin syndrome, is a group of defects caused to the developing fetus by exposure to  teratogenic effects of phenytoin. Dilantin is the brand name of the drug phenytoin sodium in the United States, commonly used in the treatment of epilepsy.
It may also be called congenital hydantoin syndrome, fetal hydantoin syndrome, dilantin embryopathy, or phenytoin embryopathy.
Association with EPHX1 has been suggested.

Signs and symptoms
About one third of children whose mothers are taking this drug during pregnancy typically have intrauterine growth restriction with a small head and develop minor dysmorphic craniofacial features (microcephaly and intellectual disability) and limb defects including hypoplastic nails and distal phalanges (birth defects). Heart defects including ventricular septal defect, atrial septal defect, patent ductus arteriosus and coarctation of the aorta may occur in these children. A smaller population will have growth problems and developmental delay, or intellectual disability.
Heart defects and cleft lip may also be featured.

Diagnosis
There is no diagnostic testing that can identify fetal hydantoin syndrome. A diagnosis is made clinically based upon identification of characteristic symptoms in an affected infant in conjunction with a history of phenytoin exposure during gestation. It is important to note that the majority of infants born to women who take phenytoin during pregnancy will not develop fetal hydantoin syndrome.

Treatment
The treatment of fetal hydantoin syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, oral surgeons, plastic surgeons, neurologists, psychologists, and other healthcare professionals may need to systematically and comprehensively plan an affected childs treatment. Infants with fetal hydantoin syndrome can benefit from early developmental intervention to ensure that affected children reach their potential </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Thyroid storm and can you explain it in depth? [/INST] Thyroid storm  is a rare but severe and potentially life-threatening complication of hyperthyroidism (overactivity of the thyroid gland). It is characterized by a high fever (temperatures often above 40 °C/104 °F), fast and often irregular heart beat, elevated blood pressure, vomiting, diarrhea, and agitation. Hypertension with a wide pulse pressure occurs in early to mid crisis, with hypotension accompanying shock occurring in the late stage. Heart failure and heart attack may occur. Death may occur despite treatment. Most episodes occur either in those with known hyperthyroidism whose treatment has been stopped or become ineffective, or in those with untreated mild hyperthyroidism who have developed an intercurrent illness (such as an infection).The primary treatment of thyroid storm is with inorganic iodine and antithyroid drugs (propylthiouracil or methimazole) to reduce synthesis and release of thyroid hormone. Temperature control and intravenous fluids are also mainstays of management. Beta blockers are often used to reduce the effects of thyroid hormone. Patients often require admission to the intensive care unit.

Signs and symptoms
Thyroid storm is characterized by an acute onset of symptoms of hyperthyroidism (fast heart rate, restlessness, agitation) accompanied by other features such as fever (temperatures often above 40 °C/104 °F), hypertension, mental status changes, diarrhea, and vomiting.Individuals can exhibit varying signs of organ dysfunction. Patients may experience liver dysfunction, and jaundice (yellowing of the skin), which is considered a poor prognostic sign. Cardiac (heart) symptoms include abnormal heart rhythms, myocardial infarction (heart attack), and congestive heart failure, which may lead to cardiovascular collapse. Mortality can be as high as 20-30%.In some situations, individuals may not experience the classic signs of restlessness and agitation, but instead present with apathetic signs of weakness and confusion.

Causes
The transition from hyperthyroidism to thyroid storm is typically triggered by a non-thyroidal insult including, but not limited to fever, sepsis, dehydration, myocardial infarction, and psychiatric diseases. Individuals are at higher risk of thyroid storm if their hyperthyroidism is incompletely treated or if their anti-thyroid drugs are discontinued. Many of these individuals have underlying primary causes of hyperthyroidism (Graves disease, toxic multi-nodular goiter, solitary toxic adenoma, amiodarone). However, thyroid storm can occur in individuals with unrecognized thyrotoxicosis experiencing non-thyroid surgery, labor, infection, or exposure to certain medications and radiocontrast dyes.

Pathophysiology
The precise mechanism for the development of thyroid storm is poorly understood. In the human body, thyroid hormone may be free (biologically active T3/T4) or bound to thyroid binding hormone (biologically inactive) to be transported. The release of thyroid hormone is tightly regulated by a feedback system involving the hypothalamus, pituitary gland, and thyroid gland. Hyperthyroidism results from a dysregulation of this system that eventually leads to increases in levels of free T3/T4. The transition from simple hyperthyroidism to the medical emergency of thyroid storm may be triggered by conditions (see Causes) that lead to the following:

Increases in free thyroid hormone
Individuals with thyroid storm tend to have increased levels of free thyroid hormone, although total thyroid hormone levels may not be much higher than in uncomplicated hyperthyroidism. The rise in the availability of free thyroid hormone may be the result of manipulating the thyroid gland. In the setting of an individual receiving radioactive iodine therapy, free thyroid hormone levels may acutely increase due to the release of hormone from ablated thyroid tissue.

Decrease in thyroid hormone binding protein
A decrease in thyroid hormone binding protein in the setting of various stressors or medications may also cause a rise in free thyroid hormone.

Increased sensitivity to thyroid hormone
Along with increases in thyroid hormone availability, it is also suggested that thyroid storm is characterized by the bodys heightened sensitivity to thyroid hormone, which may be related to sympathetic activation (see below).

Sympathetic activation
Sympathetic nervous system activation during times of stress may also play a significant role in thyroid storm. Sympathetic activation increases production of thyroid hormone by the thyroid gland. In the setting of elevated thyroid hormone, the density of thyroid hormone receptors (esp. beta-receptors) also increases, which enhances the response to catecholamines. This is likely responsible for several of the cardiovascular symptoms (increased cardiac output, heart rate, stroke volume) seen in thyroid storm.

Thyroid storm as allostatic failure
According to newer theories, thyroid storm results from allostatic failure in a situation where thyrotoxicosis hampers the development of non-thyroidal illness syndrome, which would help to save energy in critical illness and other situations of high metabolic demand.Usually, in critical illness (e.g. sepsis, myocardial infarction and other causes of shock) thyroid function is tuned down to result in low-T3 syndrome and, occasionally, also low TSH concentrations, low-T4 syndrome and impaired plasma protein binding of thyroid hormones. This endocrine pattern is referred to as euthyroid sick syndrome (ESS), non-thyroidal illness syndrome (NTIS) or thyroid allostasis in critical illness, tumours, uraemia and starvation (TACITUS). Although NTIS is associated with significantly worse prognosis, it is also assumed to represent a beneficial adaptation (type 1 allostasis). In cases, where critical illness is accompanied by thyrotoxicosis, this comorbidity prevents the down-regulation of thyroid function. Therefore, the consumption of energy, oxygen and glutathione remains high, which leads to further increased mortality.These new theories imply that thyroid storm results from an interaction of thyrotoxicosis with the specific response of the organism to an oversupply of thyroid hormones.

Diagnosis
The diagnosis of thyroid storm is based on the presence of signs and symptoms consistent with severe hyperthyroidism. Multiple approaches have been proposed to calculate the probability of thyroid storm based on clinical criteria, however, none have been universally adopted by clinicians. For instance, Burch and Wartofsky published the Burch-Wartofsky point scale (BWPS) in 1993, assigning a numerical value based on the presence of specific signs and symptoms organized within the following categories: temperature, cardiovascular dysfunction (including heart rate and presence of atrial fibrillation or congestive heart failure), central nervous system (CNS) dysfunction, gastrointestinal or liver dysfunction and presence of a precipitating event. A Burch-Wartofsky score below 25 is not suggestive of thyroid storm whereas 25 to 45 suggests impending thyroid storm and greater than 45 suggests current thyroid storm. Alternatively, the Japanese Thyroid Association (JTA) criteria, derived from a large cohort of patients with thyroid storm in Japan and published in 2012, provide a qualitative method to determine the probability of thyroid storm. The JTA criteria separate the diagnosis of thyroid storm into definite versus suspected based on the specific combination of signs and symptoms a patient exhibits and require elevated free triiodothyronine (T3) or free thyroxine (T4) for definite thyroid storm.

Laboratory findings
As with hyperthyroidism, TSH is suppressed. Both free and serum (or total) T3 and T4 are elevated. An elevation in thyroid hormone levels is suggestive of thyroid storm when accompanied by signs of severe hyperthyroidism but is not diagnostic as it may also correlate with uncomplicated hyperthyroidism. Moreover, serum T3 may be normal in critically ill patients due to decreased conversion of T4 to T3. Other potential abnormalities include the following:
Hyperglycemia likely due to catecholamine-mediated effects on insulin release and metabolism as well as increased glycogenolysis, evolving into hypoglycemia when glycogen stores are depleted
Elevated aspartate aminotransferase (AST), bilirubin and lactate dehydrogenase (LDH)
Hypercalcemia and elevated alkaline phosphatase due to increased bone resorption
Elevated white blood cell count

Management
The main strategies for the management of thyroid storm are reducing production and release of thyroid hormone, reducing the effects of thyroid hormone on tissues, replacing fluid losses, and controlling temperature. Thyroid storm requires prompt treatment and hospitalization. Often, admission to the intensive care unit is needed.In high fever, temperature control is achieved with fever reducers such as paracetamol/acetaminophen and external cooling measures (cool blankets, ice packs). Dehydration, which occurs due to fluid loss from sweating, diarrhea, and vomiting, is treated with frequent fluid replacement.  In severe cases, mechanical ventilation may be necessary. Any suspected underlying cause is also addressed.

Iodine
Guidelines recommend the administration of inorganic iodide (potassium iodide or Lugols iodine) to reduce the synthesis and release of thyroid hormone. In high dosage, iodine may reduce the synthesis of thyroid hormone via the Wolff-Chaikoff effect and its release via the Plummer effect </s>


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


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Sudden acquired retinal degeneration syndrome and can you explain it in depth? [/INST] Sudden acquired retinal degeneration syndrome (SARDS) is a disease in dogs causing sudden blindness.  It can occur in any breed, but female dogs may be predisposed.  Approximately 4000 cases are seen in the United States annually.

Characteristics
Symptoms include sudden permanent blindness, but may occur more slowly over several days, weeks or months, dilated pupils. Pupillary light reflexes  are usually reduced but present; the slow phase mediated by melanopsin in retinal ganglion cells is retained. Other symptoms commonly seen are similar to those seen with Cushings disease and include increased water consumption and urination, weight gain, confusion, restlessness, behavioral changes and lethargy. These symptoms may develop over a few months preceding the onset of SARDS. Clinical signs and disease progression vary markedly among individual animals, depending on the number and type of hormones that are increased, the degree of hormone elevation, and the age of the dog.Some owners notice a more obvious "eye shine" in photographs due to the dilated pupils and retinal atrophy creating what is described as a "hyper-reflective tapetum".

Causes
The cause of SARDS is considered to be idiopathic and the veterinary community is divided as to its cause, but the most common hypotheses on the causes of the disease possibly include autoimmune disease, or exposure to toxins </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Adenylosuccinate lyase deficiency and can you explain it in depth? [/INST] Adenylosuccinate lyase deficiency is a rare autosomal recessive metabolic disorder characterized by the appearance of succinylaminoimidazolecarboxamide riboside (SAICA riboside) and succinyladenosine (S-Ado) in cerebrospinal fluid, urine. These two succinylpurines are the dephosphorylated derivatives of SAICA ribotide (SAICAR) and adenylosuccinate (S-AMP), the two substrates of adenylosuccinate lyase (ADSL), which catalyzes an important reaction in the de novo pathway of purine biosynthesis. ADSL catalyzes two distinct reactions in the synthesis of purine nucleotides, both of which involve the β-elimination of fumarate to produce aminoimidazole carboxamide ribotide (AICAR) from SAICAR or adenosine monophosphate (AMP) from S-AMP.

Types
ASLD is divided into three categories based on the severity of symptoms: the fatal neonatal form, type I and type II. However, as symptoms occur along a spectrum there are no set criteria to determine which category a patient should be ascribed to.

Fatal neonatal form
Patients with this form of ASLD present with fatal neonatal encephalopathy,  respiratory failure, a lack of spontaneous movement and intractable seizures. Possible prenatal symptoms such as microcephaly, intrauterine growth restriction, loss of fetal heart rate variability and hypokinesia have been reported. Death occurs within the first few weeks of life.

Type I
This is the most common form of ASLD. Symptoms become apparent in the first months of life and include seizures, microcephaly and severe psychomotor retardation are purely neurological. Some patients display axial hypotonia, peripheral hypertonia and normal tendon reflexes. Autistic-like behaviour including poor eye contact, stereotypies, agitation, tantrums and self injurious behaviour may occur.

Type II
This is considered to be a mild to moderate form of ASLD. They may demonstrate a milder degree of psychomotor retardation and transient visual and auditory contact disturbances Seizures, if they occur, begin later than in Type I, typically between 2 and 4 years old but sometimes as late as 9 years old. Speech is impaired with receptive language skills and nonverbal communication skills being better than expressive language skills. Ataxia may occur and cause increasingly severe gait disturbances.

Signs and symptoms
Among the signs and symptoms of adenylosuccinate lyase deficiency are the following:
Aggressive behavior
Microcephaly
Autism
Brachycephaly
Mild Cerebellar hypoplasia
Seizures

Pathophysiology
Adenylosuccinate lyase deficiency is responsible for a range of symptoms that involve psychomotor retardation, often accompanied by epileptic seizures, and autistic features. Two common theories were proposed to account for these effects, the first is that they result from decreased concentrations of purine nucleotides needed for purine biosynthesis. Decreased concentrations, however, could not be found in various tissues taken from ADSL-deficient people, probably because purines are furnished via the purine salvage pathway. The second is the buildup of accumulating succinylpurines causes neurotoxic effects. In the severely affected individuals, the concentration levels of SAICA riboside and S-Ado are comparable, whereas in people with milder forms of the disease, the ratio of S-Ado is more than double that of those more severely affected, while SAICA riboside concentration levels remain comparable.

Biochemical studies of the enzyme have focused on proteins of ADSL from nonhuman species, the ADSL structure from the crystallized protein of Thermotoga maritime has been used, along with DNA sequencing data, to construct homology models for a variety of other organisms, including human ADSL. A variety of studies have been done using the equivalent enzyme from Bacillus subtilis, which shares a significant percentage of identity along with about some percentage of similarity in amino acid sequence with the human enzyme. Homology models overlaid on each other show a high degree of overlap between the enzymes.The family of enzymes to which ADSL belongs and that catalyze β-eliminations in which fumarate is one of the products are homotetramers with four active sites composed of amino acid residues from three distinct subunits. Much is known about the active site of human ADSL due to studies of the active site in the B. subtilis ADSL through affinity labeling and site-directed mutagenesis. While there is some variability among species in the sequencing of ADSL, the active site of the enzyme contains many residues that are conserved across species and have been shown to be critical to the enzymes function. His68 and His141 seem to serve as the general acid and base catalysts, and are critical to the catalyzing reaction of the substrate. His89 seems to enhance the binding of the substrates phosphoryl group and orient adenylosuccinate for catalysis. All three histidines are conserved throughout the 28 species for which the structure of ADSL is known. Glu275 and Lys268 have also been shown to contribute to the active site, indicating there are four active sites, each of which is formed from regions of three subunits. ADSL deficiency in different people is often caused by different mutations to the enzyme, more than 50 different mutations in the ADSL gene have been discovered

Diagnosis
In terms of the diagnosis of adenylosuccinate lyase deficiency one should look for (or exam/method):
MRI
Demonstration of succinylpurines in extracellular fluids like plasma, cerebrospinal fluid and/or urine using high-pressure liquid chromatography, with or without mass spectroscopy
Genetic testing - genomic cDNA sequencing of the ADSL gene and characterization of mutant proteins.

Treatment
Treatment of adenylosuccinate lyase deficiency can be done via epilepsy management with anticonvulsive drugs. Additionally the following options include:

D-ribose and uridine administration
Ketogenic diet
S-adenosyl-l-methionine

Prognosis
The prognosis of this condition in childhood usually has a stable outcome, whereas in neonatal is almost always fatal, according to Jurecka, et al.

See also
Adenylosuccinate
Adenylosuccinate lyase
List of genetic disorders

References
Further reading
Saudubray, Jean-Marie; Berghe, Georges van den; Walter, John H </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Noise-induced hearing loss and can you explain it in depth? [/INST] Noise-induced hearing loss (NIHL) is a hearing impairment resulting from exposure to loud sound. People may have a loss of perception of a narrow range of frequencies or impaired perception of sound including sensitivity to sound or ringing in the ears. When exposure to hazards such as noise occur at work and is associated with hearing loss, it is referred to as occupational hearing loss.Hearing may deteriorate gradually from chronic and repeated noise exposure (such as to loud music or background noise) or suddenly from exposure to impulse noise, which is a short high intensity noise (such as a gunshot or airhorn). In both types, loud sound overstimulates delicate hearing cells, leading to the permanent injury or death of the cells. Once lost this way, hearing cannot be restored in humans.There are a variety of prevention strategies available to avoid or reduce hearing loss. Lowering the volume of sound at its source, limiting the time of exposure and physical protection can reduce the impact of excessive noise. If not prevented, hearing loss can be managed through assistive devices and communication strategies.
The largest burden of NIHL has been through occupational exposures; however, noise-induced hearing loss can also be due to unsafe recreational, residential, social and military service-related noise exposures. It is estimated that 15% of young people are exposed to sufficient leisure noises (i.e. concerts, sporting events, daily activities, personal listening devices, etc.) to cause NIHL. There is not a limited list of noise sources that can cause hearing loss; rather, exposure to excessively high levels from any sound source over time can cause hearing loss.

Signs and symptoms
The first symptom of NIHL may be difficulty hearing a conversation against a noisy background. The effect of hearing loss on speech perception has two components. The first component is the loss of audibility, which may be perceived as an overall decrease in volume. Modern hearing aids compensate this loss with amplification. The second component is known as "distortion" or "clarity loss" due to selective frequency loss. Consonants, due to their higher frequency, are typically affected first. For example, the sounds "s" and "t" are often difficult to hear for those with hearing loss, affecting clarity of speech. NIHL can affect either one or both ears. Unilateral hearing loss causes problems with directional hearing, affecting the ability to localize sound.

Temporary and permanent hearing changes
PTS (Permanent Threshold Shift) is a permanent change of the hearing threshold (the intensity necessary for one to detect a sound) following an event, which will never recover.  PTS is measured in decibels.
TTS (Temporary Threshold Shift) is a temporary change of the hearing threshold the hearing loss that will be recovered after a few hours to couple of days. Also called auditory fatigue. TTS is also measured in decibels.In addition to hearing loss, other external symptoms of an acoustic trauma can be:

Tinnitus
Otalgia
Hyperacusis
Dizziness or vertigo; in the case of vestibular damages, in the inner-ear

Tinnitus
Tinnitus is described as hearing a sound when an external sound is not present. Noise-induced hearing loss can cause high-pitched tinnitus. An estimated 50 million Americans have some degree of tinnitus in one or both ears; 16 million of them have symptoms serious enough for them to see a doctor or hearing specialist. As many as 2 million become so debilitated by the unrelenting ringing, hissing, chirping, clicking, whooshing or screeching, that they cannot carry out normal daily activities.Tinnitus is the largest single category for disability claims in the military, with hearing loss a close second. The third largest category is post-traumatic stress disorder, which itself may be accompanied by tinnitus and may exacerbate it.

Quality of life
NIHL has implications on quality of life that extend beyond related symptoms and the ability to hear. The annual disability-adjusted life years (DALYs) were estimated for noise-exposed U.S. workers.[20]  DALYs represent the number of healthy years lost due to a disease or other health condition. They were defined by the 2013 Global Burden of Disease (GBD) Study. The DALYs calculation accounts for life limitations experienced because of hearing loss as a lost portion of a healthy year of life. So the results indicate the number of healthy years lost by a group of people over a specific time period.
NIOSH used DALYs to estimate the impact of hearing loss on quality of life in the CDC Morbidity and Mortality Weekly Report article "Hearing Impairment Among Noise-Exposed Workers in the United States, 2003-2012."  It reported that 2.5 healthy years were lost each year for every 1,000 noise-exposed U.S. workers because of hearing impairment (hearing loss that impacts day-to-day activities). These lost years were shared among the 13% of workers with hearing impairment (about 130 workers out of each 1,000 workers). Mining, Construction and Manufacturing workers lost more healthy years than workers in other industry sectors; specifically and respectively in those sectors, 3.5, 3.1 and 2.7 healthy years were lost each year for every 1,000 workers.

Negative impacts
The negative impacts of NIHL on ones ability to reciprocate communication, socialize and interact with society are largely invisible. Hearing loss, in general, is not just an issue of volume; individuals may experience difficulty in understanding what is said over the phone, when several people are talking at once, in a large space, or when the speakers face cannot be seen.  Subsequently, challenging social interactions can negatively lead to decreased self-esteem, shame, and fear. This can be more acutely felt by those who experience hearing impairment or loss earlier in life, rather than later when it is more socially accepted. Such psychosocial states, regardless of age, can lead to social isolation, which is known to negatively impact ones overall health and well-being. The compounding impacts can also lead to depression, especially if hearing impairment leads to tinnitus. Research suggests that those with hearing impairment or loss may be at a greater risk for deterioration of quality of life, as captured by a quote from Helen Keller: "Blindness cuts us off from things, but deafness cuts us off from people." Hearing impairment and loss of hearing, regardless of source or age, also limits experiencing the many benefits of sound on quality of life. In addition to the interpersonal social benefits, new studies suggest the effects of nature sounds, such as birds chirping and water, can positively affect an individuals capacity to recover after being stressed or to increase cognitive focus.

Quality of life questionnaire
Hearing loss is typically quantified by results from an audiogram; however, the degree of loss of hearing does not predict the impact on ones quality of life. The impact that NIHL can have on daily life and psychosocial function can be assessed and quantified using a validated questionnaire tool, such as the Hearing Handicap Inventory for the Elderly (HHIE). The HHIE is considered a "useful tool for quantifying the perceived emotional and social/situational consequences of hearing loss." The original tool was designed to test adults 65 years of age and older; however, modified versions exist. For adults the Hearing Handicap Inventory for Adults (HHIA) can be used and for adolescents the modified 28-item Hearing Environments And Reflection on Quality of Life (HEAR-QL-28) can be used. The HHIA, for example, is a 25-item questionnaire that asks both social and emotional-specific questions such as: Does a hearing problem cause you to avoid groups of people?" (social) and "Does a hearing problem cause you to feel frustrated when talking to members of your family?" (emotional). Response options are yes, no and sometimes. A greater score indicates greater perceived handicap.

Cause
The ear can be exposed to short periods of sound in excess of 120 dB without permanent harm — albeit with discomfort and possibly pain; but long term exposure to sound levels over 85 dB(A) can cause permanent hearing loss.There are two basic types of NIHL:

NIHL caused by acoustic trauma and
gradually developing NIHL.

Acute acoustic trauma
NIHL caused by acute acoustic trauma refers to permanent cochlear damage from a one-time exposure to excessive sound pressure. This form of NIHL commonly results from exposure to high-intensity sounds such as explosions, gunfire, a large drum hit loudly, and firecrackers. According to one US study, excessive noise levels in cinemas are sufficiently brief that movie-goers do not experience hearing loss.

Perceived harmfulness vs. actual harmfulness
The discomfort threshold is the loudness level from which a sound starts to be felt as too loud and thus painful by an individual. Industry workers tend to have a higher discomfort threshold (i.e. the sounds must be louder to feel painful than for non-industry workers), but the sound is just as harmful to their ears. Industry workers often have NIHL because the discomfort threshold is not a relevant indicator of the harmfulness of a sound.

Gradually developing
Gradually developing NIHL refers to permanent cochlear damage from repeated exposure to loud sounds over a period of time. Unlike acoustic trauma, this form of NIHL does not occur from a single exposure to a high-intensity sound pressure level. Gradually developing NIHL can be caused by multiple exposures to excessive noise in the workplace or any source of repetitive, frequent exposures to sounds of excessive volume, such as home and vehicle stereos, concerts, nightclubs, and personal media players. Earplugs have been recommended for those people who regularly attend live music concerts. A range of earplugs are now available ranging from inexpensive disposable sets to custom fit, attenuated earplugs which provide true fidelity at reduced audio levels.

Personal listening devices
Although research is limited, it suggests that increased exposure to loud noise through personal listening devices is a risk factor for noise induced hearing loss. More than half of people are exposed to sound through music exposure on personal devices greater than recommended levels. Research suggests stronger correlations between extended duration or elevated usage of personal listening devices and hearing loss.

Workplace
About 22 million workers are exposed to hazardous noise, with additional millions exposed to solvents and metals that could put them at increased risk for hearing loss. Occupational hearing loss is one of the most common occupational diseases. 49% of male miners have hearing loss by the age of 50. By the age of 60, this number goes up to 70%. Construction workers also have an elevated risk. A screening program focused on construction workers employed at US Department of Energy facilities found 58% with significant abnormal hearing loss due to noise exposures at work. Occupational hearing loss is present in up to 33% of workers overall. Occupational exposure to noise causes 16% of adult disabling hearing loss worldwide.The following is a list of occupations that are most susceptible to hearing loss:
Agriculture
Mining
Police
Construction
Manufacturing
Utilities
Transportation
Military
Musicians
Orchestra conductors

Among musicians
Musicians, from classical orchestras to rock groups, are exposed to high decibel ranges. Some rock musicians experience noise-induced hearing loss from their music, and some studies have found that "symphonic musicians suffer from hearing impairment and that the impairment might be ascribed to symphonic music."In terms of the population of musicians, usually the rates of hearing disorders is lower than other occupational groups. However, many exposure scenarios can be considered a risk of hearing disorders, and many individuals are negatively impacted by tinnitus and other hearing problems. While some population studies have shown that the risk for hearing loss increases as music exposure increases, other studies found little to no correlation between the two. Experts at the 2006 "Noise-Induced Hearing Loss in Children at Work and Play" Conference agreed that further research into this field was still required before making a broad generalization about music-induced hearing loss.Given the extensive research suggesting that industrial noise exposure can cause sensorineural hearing loss, a link between hearing loss and music exposures of similar level and duration (to industrial noise) seems highly plausible. Determining which individuals or groups are at risk for such exposures may be a difficult task. Despite concerns about the proliferation of personal music players, there is only scarce evidence supporting their impact on hearing loss, and some small-sample studies suggest that only a fraction of users are affected. People from ages to 6–19 have an approximately 15% rate of hearing loss. Recommendations for musicians to protect their hearing were released in 2015 by NIOSH. The recommendations emphasized education of musicians and those who work in or around the music industry. Annual hearing assessments were also recommended to monitor thresholds as were sound level assessments to help determine the amount of time musicians and related professionals should spend in that environment. Hearing protection was also recommended, and the authors of the NIOSH recommendations even suggested that musicians consider custom earplugs as a way to combat NIHL.In 2016, the National Association of Schools of Music (NASM), a music school accreditation body in the US, published a hearing health advisory to help with efforts directed at informing faculty and music students about potential risks associated with school activities, during rehearsal and performance.[1]  Specific resources are available for administrators, faculty and staff, and students.  The use of the documents is voluntary and are not to be used as standards or as part of accreditation procedures.
Despite these recommendations, musicians continue to face unique challenges in protecting their hearing when compared to individuals in industrial settings. Typically environmental controls are the first line of defense in a hearing conservation program, and depending on the type of musicians some recommendations have been proposed. These recommendations can include adjusting risers or level of the speakers and adjusting the layout of a band or orchestra. These changes in the environment can be beneficial to musicians, but the ability to accomplish them is not always possible. In the cases where these changes cannot be made, hearing protection is recommended. Hearing protection in musicians offers its own sets of benefits and complications. When used properly, hearing protection can limit the exposure of noise in individuals. Musicians have the ability to pick from several different types of hearing protection from conventional ear plugs to custom or high fidelity hearing protection. Despite this, use of hearing protection among musicians is low for several different reasons. Musicians often feel that hearing protective devices can distort how music sounds or makes it too quiet for them to hear important cues which makes them less likely to wear hearing protection even when aware of the risks. Research suggests that educations programs can be beneficial to musicians as well as working with hearing care professionals to help address the specific issues that musicians face.[2]
In 2018, a musician named Chris Goldscheider won a case against Royal Opera House for damaging his hearing in a rehearsal of Wagners thunderous opera Die Walkure.

Workplace standards
In the United States, the Occupational Safety and Health Administration (OSHA) describes standards for occupational noise exposure in articles 1910.95 and 1926.52. OSHA states that an employer must implement hearing conservation programs for employees if the noise level of the workplace is equal to or above 85 dB(A) for an averaged eight-hour time period. OSHA also states that "exposure to impulsive or impact noise should not exceed 140 dB peak sound pressure level".  The National Institute for Occupational Safety and Health (NIOSH) recommends that all worker exposures to noise should be controlled below a level equivalent to 85 dBA for eight hours to minimize occupational noise induced hearing loss. NIOSH also recommends a 3 dBA exchange rate so that every increase by 3 dBA doubles the amount of the noise and halves the recommended amount of exposure time.
The United States Department of Defense (DoD) instruction 605512 has some differences from OSHA 1910.95 standard, for example, OSHA 1910.95 uses a 5 dB exchange rate and DoD instruction 605512 uses a 3 dB exchange rate.
There are programs that seek to increase compliance and therefore effectiveness of hearing protection rules; the programs include the use of hearing tests and educating people that loud sound is dangerousEmployees are required to wear hearing protection when it is identified that their eight-hour time weighted average (TWA) is above the exposure action value of 90 dB. If subsequent monitoring shows that 85 dB is not surpassed for an eight-hour TWA, the employee is no longer required to wear hearing protection.In the European Union, directive 2003/10/EC mandates that employers shall provide hearing protection at noise levels exceeding 80 dB(A), and that hearing protection is mandatory for noise levels exceeding 85 dB(A).
Both values are based on 8 hours per day, with a 3 dB exchange rate.
A 2017 Cochrane review found low-quality evidence that legislation to reduce noise in the workplace was successful in reducing exposure both immediately and long-term.

Sporting events
Several sports stadiums pride themselves in having louder stadiums than their opponents because it may create a more difficult environment for opposing teams to play in. Currently, there are few studies on noise in sports stadiums, but some preliminary measurements show noise levels reaching 120 dB, and informal studies suggest that people may receive up to a 117% noise dose in one game. There are many challenges that face hearing conservationists such as sports culture. Sports fans will create noise in an attempt to distract other teams, and some sports teams have been known to create artificial noise in an attempt to make the stadium louder. In doing that, workers, teams, and fans may be at potential risk for damage to the auditory system.
NIOSH conducted a health hazard evaluation and studies at Monster Trucking and Stock Car racing events, spectators average noise levels ranged from 95 to 100 dBA at the Monster Truck event and over 100 dBA at the stock car racing event. NIOSH researchers also published noise exposure levels for drivers, crew members, and staff. Noise levels at the Bristol Motor Speedway ranged from 96 dBA in the stands to 114 dBA for a driver inside a car during practice. Peak noise levels in the Pit area reached or exceeded 130 dB SPL, a level often associated with human hearing threshold for pain. Several prominent NASCAR drivers have complete or partial hearing loss and other symptoms from their many years of exposure.During the FIFA World Cup in 2010, noise levels created by fans blowing Vuvuzela averaged 131 dBA at the horn opening and 113 dBA at 2 meter distance. Peak levels reached 144 dB SPL, louder than a jet engine at takeoff.A study of occupational and recreational noise exposure at indoor hockey arenas found noise levels from 81 dBA to 97 dBA, with peak sound pressure levels ranging from 105 dB SPLto 124 dB SPL. Another study examined the hearing threshold of hockey officials and found mean noise exposures of 93 dBA. Hearing threshold shifts were observed in 86% of the officials (25/29).In a study of noise levels at 10 intercollegiate basketball games showed noise levels in 6 of the 10 basketball games to exceed the national workplace noise exposure standards, with participants showing temporary threshold levels at one of the games.While there is no agency that currently monitors sports stadium noise exposure, organizations such as NIOSH or OSHA use occupational standards for industrial settings that some experts feel could be applied for those working at sporting events. Workers often will not exceed OSHA standards of 90 dBA, but NIOSH, whose focus is on best practice, has stricter standards which say that when exposed to noise at or exceeding 85 dBA workers need to be put on a hearing conservation program. Workers may also be at risk for overexposure because of impact noises that can cause instant damage. Experts are suggesting that sports complexes create hearing conservation programs for workers and warn fans of the potential damage that may occur with their hearing.Studies are still being done on fan exposure, but some preliminary findings show that there are often noises that can be at or exceed 120 dB which, unprotected, can cause damage to the ears in seconds.

Mechanisms
NIHL occurs when too much sound intensity is transmitted into and through the auditory system. An acoustic signal from a sound source, such as a radio, enters into the external auditory canal (ear canal), and is funneled through to the tympanic membrane (eardrum), causing it to vibrate. The vibration of the tympanic membrane drives the middle ear ossicles, the malleus, incus, and stapes to vibrate in sync with the eardrum. The middle ear ossicles transfer mechanical energy to the cochlea by way of the stapes footplate hammering against the oval window of the cochlea, effectively amplifying the sound signal. This hammering causes the fluid within the cochlea (perilymph and endolymph) to be displaced. Displacement of the fluid causes movement of the hair cells (sensory cells in the cochlea) and an electrochemical signal to be sent from the auditory nerve (CN VIII) to the central auditory system within the brain. This is where sound is perceived. Different groups of hair cells are responsive to different frequencies. Hair cells at or near the base of the cochlea are most sensitive to higher frequency sounds while those at the apex are most sensitive to lower frequency sounds. There are two known biological mechanisms of NIHL from excessive sound intensity: damage to the structures called stereocilia that sit atop hair cells and respond to sound, and damage to the synapses that the auditory nerve makes with hair cells, also termed "hidden hearing loss".

Physiological response
The symptoms mentioned above are the external signs of the physiological response to cochlear overstimulation. Here are some elements of this response:

Damaged sensory hairs (stereocilia) of the hair cells; damaged hair cells degenerate and die. In humans and other mammals, dead hair-cells are never replaced; the resulting hearing loss is permanent.
Inflammation of the exposed areas. This inflammation causes poor blood flow in the exposed blood vessels (vascular stasis), and poor oxygen supply for the liquid inside the cochlea (endolymphatic hypoxia) Those noxious conditions worsen the damaged hair cell degeneration.
Synaptic damages, by excitotoxicity. Noise overstimulation causes an excessive release of glutamate, causing the postsynaptic bouton to swell and burst. However the neuron connection can be repaired, and the hearing loss only caused by the "wiring" (i.e. excitotoxicity) can thus be recovered within 2–3 days.

Hair cell damage or death
When the ear is exposed to excessive sound levels or loud sounds over time, the overstimulation of the hair cells leads to heavy production of reactive oxygen species, leading to oxidative cell death. In animal experiments, antioxidant vitamins have been found to reduce hearing loss even when administered the day after noise exposure. They were not able to fully prevent it. Antioxidants however do not seem to be effective in protecting the human ear. Damage ranges from exhaustion of the hair (hearing) cells in the ear to loss of those cells. NIHL is, therefore, the consequence of overstimulation of the hair cells and supporting structures. Structural damage to hair cells (primarily the outer hair cells) will result in hearing loss that can be characterized by an attenuation and distortion of incoming auditory stimuli.
During hair cell death scars develop, which prevent potassium rich fluid of the endolymph from mixing with the fluid on the basal domain. The potassium rich fluid is toxic to the neuronal endings and can damage hearing of the entire ear. If the endolymph fluid mixes with the fluid on the basal domain the neurons become depolarized, causing complete hearing loss. In addition to complete hearing loss, if the area is not sealed and leakage continues further tissue damage will occur. The scars that form to replace the damaged hair cell are caused by supporting hair cells undergoing apoptosis and sealing the reticular lamina, which prevents fluid leakage. The cell death of two supporting hair cells rapidly expands their apical domain, which compresses the hair cell beneath its apical domain.

Nerve damage
Recent studies have investigated additional mechanisms of NIHL involving delayed or disabled electrochemical transmission of nerve impulses from the hair cell to and along the auditory nerve. In cases of extreme acute acoustic trauma, a portion of the postsynaptic dendrite (where the hair cell transfers electrochemical signals to the auditory nerve) can rupture from overstimulation, temporarily stopping all transmission of auditory input to the auditory nerve. This is known as excitotoxicity. Usually, this sort of rupture heals within about five days, resulting in functional recovery of that synapse. While healing, an over-expression of glutamate receptors can result in temporary tinnitus, or ringing in the ears. Repeated ruptures at the same synapse may eventually fail to heal, leading to permanent hearing loss.Prolonged exposure to high intensity noise has also been linked to the disruption of ribbon synapses located in the synaptic cleft between inner hair cells and spiral ganglion nerve fibers, leading to a disorder referred to as cochlear synaptopathy or hidden hearing loss.  This disorder is cumulative and over time, leads to degeneration of the spiral ganglion cells of the inner ear and overall dysfunction in the neural transmission between auditory nerve fibers and the central auditory pathway. The most common symptom of cochlear synaptopathy is difficulty understanding speech, especially in the presence of competing noise. However, this type of hearing impairment is often undetectable by conventional pure tone audiometry, thus the name "hidden" hearing loss.
Acoustic over-exposure can also result in decreased myelination at specific points on the auditory nerve. Myelin, an insulating sheath surrounding nerve axons, expedites electrical impulses along nerves throughout the nervous system. Thinning of the myelin sheath on the auditory nerve significantly slows the transmission of electrical signals from hair cell to auditory cortex, reducing comprehension of auditory stimuli by delaying auditory perception, particularly in noisy environments.

Individual susceptibility towards noise
There appear to be large differences in individual susceptibility to NIHL. The following factors have been implicated:

missing acoustic reflex
previous sensorineural hearing loss
a bad general health state: bad cardiovascular function, insufficient intake of oxygen, a high platelet aggregation rate; and most importantly, a high viscosity of the blood
cigarette smoking
exposure to ototoxic chemicals (medication or environmental chemicals that can damage the ear), including certain solvents and heavy metals
type 2 diabetes

Diagnosis
Both NIHL caused by acoustic trauma and gradually-developed-NIHL can often be characterized by a specific pattern presented in audiological findings. NIHL is generally observed to decrease hearing sensitivity in the higher frequencies, also called an audiometric notch, especially at 4000 Hz, but sometimes at 3000 or 6000 Hz. The symptoms of NIHL are usually presented equally in both ears.This typical 4000 Hz notch is due to the transfer function of the ear. As does any object facing a sound, the ear acts as a passive filter, although the inner ear is not an absolute passive filter because the outer hair cells provide active mechanisms. A passive filter is a low pass: the high frequencies are more absorbed by the object because high frequencies impose a higher pace of compression-decompression to the object. The high frequency harmonics of a sound are more harmful to the inner-ear.However, not all audiological results from people with NIHL match this typical notch. Often a decline in hearing sensitivity will occur at frequencies other than at the typical 3000–6000 Hz range. Variations arise from differences in peoples ear canal resonance, the frequency of the harmful acoustic signal, and the length of exposure. As harmful noise exposure continues, the commonly affected frequencies will broaden to lower frequencies and worsen in severity.

Prevention
NIHL can be prevented through the use of simple, widely available, and economical tools. This includes but is not limited to personal noise reduction through the use of ear protection (i.e. earplugs and earmuffs), education, and hearing conservation programs. For the average person, there are three basic things that one can do to prevent NIHL: turn down the volume on devices, move away from the source of noise, and wear hearing protectors in loud environments.Non-occupational noise exposure is not regulated or governed in the same manner as occupational noise exposure; therefore prevention efforts rely heavily on education awareness campaigns and public policy. The WHO cites that nearly half of those affected by hearing loss could have been prevented through primary prevention efforts such as: "reducing exposure (both occupational and recreational) to loud sounds by raising awareness about the risks; developing and enforcing relevant legislation; and encouraging individuals to use personal protective devices such as earplugs and noise-cancelling earphones and headphones."

Personal noise reduction devices
Personal noise reduction devices can be passive, active or a combination. Passive ear protection includes earplugs or earmuffs which can block noise up to a specific frequency. Earplugs and earmuffs can provide the wearer with 10 dB to 40 dB of attenuation. However, use of earplugs is only effective if the users have been educated and use them properly; without proper use, protection falls far below manufacturer ratings. A Cochrane review found that training of earplug insertion can reduce noise exposure at short term follow-up compared to workers wearing earplugs without training. Higher consistency of performance has been found with custom-molded earplugs. Because of their ease of use without education, and ease of application or removal, earmuffs have more consistency with both compliance and noise attenuation. Active ear protection (electronic pass-through hearing protection devices or EPHPs) electronically filter out noises of specific frequencies or decibels while allowing the remaining noise to pass through.  A personal attenuation rating can be objectively and subjectively measured by using a hearing protection fit testing system.

Education
Education is key to prevention. Before hearing protective actions will take place, a person must understand they are at risk for NIHL and know their options for prevention. Hearing protection programs have been hindered by people not wearing the protection for various reasons, including the desire to converse, uncomfortable devices, lack of concern about the need for protection, and social pressure against wearing protection. Although youth are at risk for hearing loss, one study found that 96.3% of parents did not believe their adolescents were at risk, and only 69% had talked to their children about hearing protection; those aware of NIHL risks were more likely to talk to their teens.A systematic review of the effectiveness of interventions to promote the use of hearing protection devices such as earplugs and earmuffs among workers found that tailored interventions improve the average use of such devices when compared with no intervention. Tailored interventions involve the use of communication or other types of interventions that are specific to an individual or a group and aim to change behavior. Mixed interventions such as mailings, distribution of hearing protection devices, noise assessments, and hearing testing are also more effective in improving the use of hearing protection devices compared with hearing testing alone. Programs that increased the proportion of workers wearing hearing protection equipment did reduce overall hearing loss.

Hearing conservation programs
Workers in general industry who are exposed to noise levels above 85 dBA are required by the Occupational Safety and Health Administration (OSHA) to be in a hearing conservation program (HCP), which includes noise measurement, noise control, periodic audiometric testing, hearing protection, worker education, and record keeping. Twenty-four states, Puerto Rico, and the U.S. Virgin Islands have OSHA-approved state plans and have adopted their own standards and enforcement policies. Most of these state standards are identical to those of federal OSHA. However, some states have adopted different standards or may have different enforcement policies.  Most health and safety regulations are designed to keep damage risk within "acceptable limits" — that is, some people are likely to incur a hearing loss even when exposed to less than the maximum daily amount of noise specified in a regulation. Hearing conservation programs in other arenas (schools, military) have become more common, and it has been established that unsafe listening behaviors, such as listening to loud noise for extended periods of time without protection, persist despite knowledge of potential hearing loss effects.However, it is understood that HCPs are designed to change behavior, which is known to be a complex issue that requires a multi-faceted approach. According to Keppler et al. in their 2015 study of such programming, they cite the necessary attitude change towards the susceptibility of risk and degree of severity of hearing loss. Among young adults, the concept of severity is most crucial because it has been found that behavior change may not occur unless an individual experiences NIHL or similarly related NIHL tinnitus, furthering warranting a multi-pronged approach based on hearing conservation programming and education.
Interventions to prevent noise-induced hearing loss often have many components. A 2017 Cochrane review found that hearing loss prevention programs suggest that stricter legislation might reduce noise levels. Giving workers information on their noise exposure levels by itself was not shown to decrease exposure to noise. Ear protection, if used correctly, has the potential to reduce noise to safer levels, but does not necessarily prevent hearing loss. External solutions such as proper maintenance of equipment can lead to noise reduction, but further study of this issue under real-life conditions is needed. Other possible solutions include improved enforcement of existing legislation and better implementation of well-designed prevention programmes, which have not yet been proven conclusively to be effective. The implications is that further research could affect conclusions reached.
Several hearing conservation programs have been developed to educate a variety of audiences about the dangers of NIHL and how to prevent it. Dangerous Decibels aims to significantly reduce the prevalence of noise induced hearing loss and tinnitus through exhibits, education and research. Were hEAR for You is a small non-profit that distributes information and ear plugs at concert and music festival venues. The Buy Quiet program was created to combat occupational noise exposures by promoting the purchase of quieter tools and equipment and encourage manufacturers to design quieter equipment. The National Institute on Deafness and Other Communication Disorders developed the Its a Noisy Planet. Protect their Hearing educational campaign to inform preteens, parents, and educators about the causes and prevention of NIHL. The National Institute for Occupational Safety and Health partnered with the National Hearing Conservation Association in 2007 to establish the Safe-in-Sound Excellence and Innovation in Hearing Loss Prevention Awards to recognize organizations that are successfully implementing hearing loss prevention concepts into their daily routines.

Medication
Medications are still being researched to determine if they can prevent NIHL. No medication has been proven to prevent or repair NIHL in humans.
There is evidence that hearing loss can be minimized by taking high doses of magnesium for a few days, starting as soon as possible after exposure to the loud noise. A magnesium-high diet also seems to be helpful as an NIHL-preventative if taken in advance of exposure to loud noises. Along the same line of research, higher dietary or supplemental intakes of magnesium combined with antioxidant vitamins, specifically β-carotene and vitamin C, appear to be associated with a lower risk of hearing loss. Consuming excessive amounts of magnesium can be potentially harmful, so any treatments should be followed with caution.Tentative research in a mouse model suggests that blocking the GluA2-lacking, calcium-permeable forms of the AMPA receptor protects against hearing damage.

Sound or stress training
Despite different people having different thresholds for what noises are painful, this pain threshold has no correlation with which noises cause hearing damage. The ear can not get more resistant to noise harmfulness by training it to noise. The cochlea is partially protected by the acoustic reflex, but being frequently exposed to noise does not lower the reflex threshold. It had been observed that noise conditioning (i.e. exposure to loud non-traumatizing noise) several hours prior to the exposure to traumatizing sound level, significantly reduced the damages inflicted to the hair-cells. The same "protective effect" was also observed with other stressors such as heat-shock conditioning and stress (by restraint) conditioning. This "protective effect" only happens if the traumatizing noise is presented within an optimum interval of time after the sound-conditioning session (-24 hours for a 15 min. sound-conditioning; no more protection after 48 hours).
This "protective effect" had long been thought to involve the active mechanisms of the outer hair cells and the efferent system commanding them. The contractile effect of the outer hair cells, activated by the efferent nervous system has been proven to provide a protective effect against acoustic trauma.

However, a 2006 study revealed a different protective mechanism for stress conditioning. The study revealed that the stressor (sound, heat, or stress) conditioning increases the receptibility to glucocorticoid, a kind of anti-inflammatory hormone. The effects of glucocorticoid thus mitigate the inflammation from an acoustic trauma that can lead to hearing loss. In fact, high doses of corticoids are often prescribed by physicians after an acoustic-trauma in order to mitigate the inflammatory response.
Summarized, sound (or other stressor) conditioning is a pre-emptive medication against cochlea inflammation. It does not make the ear more resistant to noise. It reduces the inflammation caused by the acoustic trauma, which would cause subsequent damages to hair cells. While an anti-inflammatory medication would increase the quantity of anti-inflammatory hormone in the whole body, noise conditioning increases the number of receptors for the anti-inflammatory hormone, and only in the areas where it is much needed (i.e. cochlea).
Physiological response

stressor (noise, heat shock or stress) conditioning activates hormonal glands: the HPA axis. Note that the HPA axis is associated to the immune system
this HPA axis activation results in the up regulation of glucocorticoid receptors (GR) in the cochlea and the paraventricular nucleus (PVN) of the hypothalamus. Note that the glucocorticoid hormone is a kind of immune-reaction-inhibitor, including the inflammation reaction.
This up regulation of GR thus prevents GR down regulation induced by acoustic trauma
The protective effect of noise-conditioning is blocked by adrenalectomy or pharmacological treatment with RU486 + metyrapone (a glucocorticoid receptor antagonist).

Treatment
Treatment options that offer "cures" for NIHL are under research and development. Currently there are no commonly used cures, but rather assistive devices and therapies to try and manage the symptoms of NIHL.

Acute acoustic trauma
Several clinical trials have been conducted to treat temporary NIHL occurring after a traumatic noise event, such as a gunshot or firework. In 2007, individuals with acute acoustic trauma after firecracker exposure were injected intratympanically with a cell permeable ligand, AM-111. The trial found AM-111 to have a therapeutic effect on at least two cases of those with acute trauma. Treatment with a combination of prednisolone and piracetam appeared to rescue patients with acute trauma after exposure to gunshots. However, those who received the treatment within an hour of exposure had higher rates of recovery and significantly lower threshold shifts compared to those who received treatment after one hour.Additionally, clinical trials using antioxidants after a traumatic noise event to reduce reactive oxygen species have displayed promising results. Injections with allopurinol, lazaroids, α-D-tocopherol, and mannitol were found to reduce the threshold shift after noise exposure. Another antioxidant, Ebselen, has been shown to have promising results for both TTS and PTS. Ebselen mimics gluthathione peroxide, an enzyme that has many functions, including scavenging hydrogen peroxide and reactive oxygen species. After noise exposure, gluthathione peroxide decreases in the ear. An oral administration of ebselen in both preclinical tests on guinea pigs and human trials indicate that noise induced TTS and PTS was reduced.Recently, combination therapy with hyperbaric oxygen therapy (HBO) and corticosteroids has been found to be effective for acute acoustic trauma. Acute noise exposure causes inflammation and lower oxygen supply in the inner ear. Corticosteroids hinder the inflammatory reaction and HBO provides an adequate oxygen supply. This therapy has been shown to be effective when initiated within three days after acoustic trauma. Therefore, this condition is considered an ENT emergency.

Gradually occurring NIHL
At the present time, no established clinical treatments exist to reverse the effects of permanent NIHL. However, current research for the possible use of drug and genetic therapies look hopeful. In addition, management options such as hearing aids and counseling exist.
Many studies have been conducted looking at regeneration of hair cells in the inner ear. While hair cells are generally not replaced through cell regeneration, mechanisms are being studied to induce replacement of these important cells. One study involves the replacement of damaged hair cells with regenerated cells, via the mechanism of gene transfer of atonal gene Math1 to pluripotent stem cells within the inner ear. Other atonal genes are being studied to induce regeneration of hair cells in the inner ear.

Management
For people living with NIHL, there are several management options that can improve the ability to communicate.  These options include counseling, amplification, and other assisted listening devices, such as frequency modulation (FM) systems. FM systems can enhance the use of hearing aids and overcome the effects of poor listening conditions because the signal is sent from the microphone worn by the speaker directly to the listener. The prognosis has improved with the recent advancements in digital hearing aid technology, such as directional microphones, open-fit hearing aids, and more advanced algorithms. Hearing aids can mask or cover up the tinnitus, and many with hearing loss and tinnitus find relief by using hearing aids. Though there is no cure or agreed-upon treatment for tinnitus, some drugs have been shown to provide temporary reduction of tinnitus. Other treatments for tinnitus include cognitive-behavioral therapy, biofeedback, and electrical stimulation. Annual audiological evaluations are recommended to monitor any changes in a patients hearing and to modify hearing-aid prescriptions.
A systematic-review conducted by the American Academy of Audiology Task Force On the Health-Related Quality of Life Benefits of Amplification in Adults found the use of hearing aids to increase quality of life. The review pertained to adults who experienced sensorineural hearing loss, which can be caused by excessive, loud noise.

Epidemiology
The World Health Organization estimates that nearly 360 million people have moderate to profound hearing loss from all causes. Rates of hearing loss has traditionally been attributed to occupational or firearm-related exposure, as well as recreational exposure. The World Health Organization estimated in 2015 that 1.1 billion young people are at risk for hearing loss caused by unsafe listening practices. The over-exposure to excessive loud noise is partially attributed to recreational exposure, such as the use of personal audio devices with music at high volumes for long durations, or social settings such as bars, entertainment and sporting events.The International Organization for Standardization (ISO) developed the ISO 1999 standards for the estimation of hearing thresholds and noise-induced hearing impairment. They used data from two noise and hearing study databases, one presented by Burns and Robinson (Hearing and Noise in Industry, Her Majestys Stationery Office, London, 1970) and by Passchier-Vermeer (1968). As race and ethnicity are some of the factors that can affect the expected distribution of pure-tone hearing thresholds several other national or regional datasets exist, from Sweden, Norway, South Korea, the United States and Spain.
In the United States hearing is one of the health outcomes measure by the National Health and Nutrition Examination Survey (NHANES), a survey research program conducted by the National Center for Health Statistics. It examines health and nutritional status of adults and children in the United States.  While there is no perfect way to pinpoint hearing loss from excessive noise, researchers look for audiometric notches in a hearing test—dips in the ability to hear certain frequencies—as signs of possible NIHL. As of 2011 data, approximately 24% adults age 20–69 in the United States has an audiometric notch. This data identified differences in NIHL based on age, gender, race/ethnicity, and whether or not a person is exposed to noise at work. Among people aged 20–29, 19.2% had an audiometric notch, compared to 27.3% of people aged 50–59.  Males in general had a notch more often than females, regardless of occupational noise exposure, for both unilateral and bilateral audiometric notches. An epidemiological study of 6557 automotive manufacturing workers in China (median age 28 years old) reported that in 62% of the settings where noise exposures were evaluated, levels exceeded the recommended level of 85 dBA. The prevalence of hearing loss was 41% among auto part manufacturing workers, followed by 31% of power train workers and 24% in automotive manufacturing. Across job categories, the highest prevalence rate was observed among welders, of 53%.  The prevalence rates were associated with noise levels and the workers cumulative noise exposure.
Occupational noise exposure is the main risk factor for work-related hearing loss.  One study examined hearing test results obtained between 2000 and 2008 for workers ages 18–65 who had a higher occupational noise exposure than the average worker. Of the sample taken, 18% of the workers had hearing loss.  Of the occupations considered, the Mining industry had the highest prevalence and risk of hearing loss, at approximately 27%. Other industries with a higher prevalence and risk included Construction (23.48%) and Manufacturing, especially Wood Product and Non-metallic Mineral Product (19.89%), Apparel (20.18%), and Machinery (21.51%).  Estimates of rates of hearing loss have been reported for workers in the Agriculture, Forestry, Fishing, and Hunting (AFFH)  sector </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Sleep inertia and can you explain it in depth? [/INST] Sleep inertia is a physiological state of impaired cognitive and sensory-motor performance that is present immediately after awakening. It persists during the transition of sleep to wakefulness, where an individual will experience feelings of drowsiness, disorientation and a decline in motor dexterity. Impairment from sleep inertia may take several hours to dissipate. In the majority of cases, morning sleep inertia is experienced for 15 to 30 minutes after waking.Sleep inertia is of concern with decision-making abilities, safety-critical tasks and the ability to operate efficiently soon after awakening. In these situations, it poses an occupational hazard due to the cognitive and motor deficits that may be present.

Symptoms
"Grogginess", as defined by a drowsy or disoriented state in which there is a dampening of sensory acuity and mental processing.
Impaired motor dexterity and decrease in cognitive ability. These gross impairments may be responsible for the associated increase in reaction time and drop in attentiveness.
Deficits in spatial memory
Reports of heightened subjective fatigueThese symptoms are expressed with the greatest intensity immediately after waking, and dissipate following a period of extended wakefulness. The duration of symptoms varies on a conditional basis, with primary expression during the first 15–60 minutes after waking and potentially extending for several hours.  Tasks that require more complex cognitive operations will feature greater deficits as compared to a simple motor task; the accuracy of sensory and motor functioning is more impaired by sleep inertia as compared to sheer speed.  In order to measure the cognitive and motor deficiencies associated with sleep inertia, a battery of tests may be utilized including psychomotor vigilance task, descending subtraction task (DST), auditory reaction time task, and the finger tapping task.

Causes
Studies have shown that abrupt awakening during stage 3 sleep, slow-wave sleep (SWS), produces more sleep inertia than awakening during sleep stages 1, 2 or REM sleep.
Prior sleep deprivation increases the percentage of time spent in slow-wave sleep (SWS). Therefore, an individual who was previously sleep deprived will have a greater chance of experiencing sleep inertia.
Adenosine levels in the brain progressively increase with sleep deprivation, and return to normal during sleep.  Upon awakening with sleep deprivation, high amounts of adenosine will be bound to receptors in the brain, neural activity slows down, and a feeling of tiredness will result.
Studies show that individuals express a lack of blood flow to the brain upon awakening. Levels of cerebral blood flow (CBF) and cerebral blood flow velocities (CBFV) will take up to 30 minutes to increase and reach daytime levels.  Studies using advanced imaging have shown that cerebral blood flow will return to waking levels in the brainstem and thalamus first. Then, after 15 minutes, the brains anterior cortical regions receive normal daytime blood flow. This 15 minute time period corresponds to the sleep inertia period.
Studies show that drinking alcoholic beverages in the evening causes physiological distress upon wake up. This phenomenon is known colloquially as a hangover.

Treatments / countermeasures
There has been a great deal of research into potential methods to relieve the effects of sleep inertia.  The demand for remedies is driven by the occupational hazards of sleep inertia for employees who work extended shifts such as medical professionals, emergency responders, or military personnel.  The motor functioning and cognitive ability of these professionals who must immediately respond to a call can pose a safety hazard in the workplace.  Below are some of the various methods that have been suggested to combat sleep inertia.

Napping
When a person is sleep deprived, re-entering sleep may provide a viable route to reduce mental and physical fatigue but it can also induce sleep inertia. In order to limit sleep inertia, one should avoid waking from the deeper stages of slow-wave sleep. The onset of slow-wave sleep occurs approximately 30 minutes after falling asleep, therefore a nap should be limited to under 30 minutes to prevent waking during slow-wave sleep and enhancing sleep inertia </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Cradle cap and can you explain it in depth? [/INST] Cradle cap or cradle hat causes crusty or oily scaly patches on a babys scalp. The condition is not painful or itchy, but it can cause thick white or yellow scales that are not easy to remove.  Cradle cap most commonly begins sometime in the first three months but can occur in later years. Similar symptoms in older children are more likely to be dandruff than cradle cap. The rash is often prominent around the ear, the eyebrows or the eyelids.  It may appear in other locations as well, where it is called infantile seborrhoeic dermatitis. Cradle cap is just a special - and more benign - case of this condition. The exact cause of cradle cap is not known. Cradle cap is not spread from person to person (contagious). It is also not caused by poor hygiene. It is not an allergy, and it is not dangerous. Cradle cap often lasts a few months. In some children, the condition can last until age 2 or 3.

Signs and symptoms
Cradle cap is seborrheic dermatitis that affects infants.  It presents on the scalp as greasy patches of scaling, which appear thick, crusty, yellow, white or brown. The affected regions are not usually itchy and do not bother the child. Other affected areas can include the eyelids, ear, around the nose, and in the groin. Hair loss can also occur.

Causes
Cradle cap is not caused by bacterial infection, allergy or poor hygiene. Cradle cap is also not contagious. Doctors do not agree on what causes cradle cap, but the two most common hypotheses are fungal infection and overactive sebaceous glands. Cradle cap is an inflammatory condition.Possibly it has to do with overactive sebaceous glands in the skin of newborn babies, due to the mothers hormones still in the babys circulation. The glands release a greasy substance that makes old skin cells attach to the scalp instead of falling off as they dry. There is a relationship with skin yeasts (Pityrosporum ovale, newly renamed Malassezia furfur).

Warning signs
If the condition thickens, turns red and irritated, starts spreading, appears on other body parts, or if the baby develops thrush (fungal mouth infection), fungal ear infection (an ear infection that does not respond to antibiotics) or a persistent diaper rash, medical intervention is recommended.
Severe cases of cradle cap, especially with cracked or bleeding skin, can provide a place for bacteria to grow. If the cradle cap is caused by a fungal infection which has worsened significantly over days or weeks to allow bacterial growth (impetigo, most commonly), a combination treatment of antibiotics and antifungals may be necessary.  Since it is difficult for a layperson to distinguish the difference between sebaceous gland cradle cap, fungal cradle cap, or either of these combined with a bacterial infection, medical advice should be sought if the condition appears to worsen.
Cradle cap is occasionally linked to immune disorders. If the baby is not thriving and has other problems (e.g. diarrhea), a doctor should be consulted.

Treatment
To help with cradle cap, parents can gently massage their babys scalp with their fingers or a soft brush to loosen the scales. They may want to shampoo the babys hair more frequently (no more than once a day), and after shampooing gently brush the babys scalp with a soft brush or a terrycloth towel. Oil remedies can be used by rubbing a small amount of pure, plant-derived oil (coconut oil, pure olive oil, almond oil) on the babys scalp and leaving it on for 15 minutes. After 15 minutes, gently comb out the flakes with a fine tooth comb or brush. Be sure to wash out all of the oil to avoid making the cradle cap worse.In cases that are related to fungal infection, such as Tinea capitis, doctors may recommend a treatment application of clotrimazole (commonly prescribed for jock itch or athletes foot) or miconazole (commonly prescribed for vaginal candidiasis).
Doctors may recommend a treatment with a mild dandruff shampoo such as Selsun Blue even though the treatment may cause initial additional scalp irritation. A doctor may instead prescribe an antifungal soap such as ketoconazole (2%) shampoo, which can work in a single treatment and shows significantly less irritation than over-the-counter shampoos such as selenium disulfide shampoos.There are only a limited number of studies regarding the efficacy and safety of treatments for cradle cap and infantile seborrheic dermatitis. Several treatments including Promiseb, lactamide MEA gel, hydrocortisone 1% lotion, licochalcone 0.025%, flumethasone pivalate 0.02% ointment, and eosin 2% aqueous solution have been studied, however there is uncertainty regarding the efficacy and safety of these treatments.For adults: see the article on seborrheic dermatitis (the adult version of cradle cap).

Scalp, behind ears, eyebrows
If the cradle cap is not severe, it could simply be combed out gently after bathing. The softened scales can then be brushed away with a soft brush, comb or cloth, but if not done very gently, this could worsen the condition and bring about temporary hair loss.  Applying petroleum jelly (e.g., Vaseline) liberally overnight is another popular treatment. The softened scales either fall off during the night, or can be brushed off in the morning.There is broad disagreement regarding the role of shampoos. Some sources warn against frequent shampooing, others recommend it. Mild baby shampoo is often recommended, but the exact denotation of the label "mild" in this context is not quite clear. Baby shampoos often contain detergent surfactants, perfumes, quaternium-15 and other eczemagenic irritants. No studies have been performed on non-prescription shampoos.In stubborn cases some doctors may recommend keratolytic (dandruff) shampoos (e.g. with sulfur, selenium, zinc pyrithione, or salicylic acid) while others warn against the use of medicated shampoos in newborns due to systemic absorption. Dandruff shampoos often contain sodium dodecyl sulfate, a noted skin irritant.Steroid and tar preparations have also been used but may have drawbacks. The immunomodulators tacrolimus/Protopic and pimecrolimus/Elidel have not been approved for children under two years </s>


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