<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 Unverricht–Lundborg disease and can you explain it in depth? [/INST] Unverricht–Lundborg disease (abbreviated ULD or EPM1) is the most common form of an uncommon group of genetic epilepsy disorders called the progressive myoclonus epilepsies. It is caused due to a mutation in the cystatin B gene (CSTB). The disease is named after Heinrich Unverricht, who first described it in 1891, and Herman Bernhard Lundborg, who researched it in greater detail in 1901 and 1903. ULD onsets in children between the ages of 6 and 16; there are no known cases in which the person was older than 18. Most cases originate from the Baltic region of Europe, though many have been reported from countries in the Mediterranean.Onset of the disease is characterized by myoclonic jerks and tonic-clonic seizures. Early cases often resulted in the need of a wheelchair and death before the age of 24, but new treatments and medications have increased the life expectancy of individuals with ULD, in some cases even to near that of an unaffected individual.

Signs and symptoms
Patients with Unverricht–Lundborg disease exhibit myoclonic jerks and tonic-clonic seizures at a young age, between ages 6–16. The myoclonic jerks occur in the muscles of the arms and legs closest to the torso, and are triggered due to a variety of common external stimuli. Seizures begin at an average age of 10.8 years, with myoclonus beginning around 12.1 years. It is not currently possible to diagnose without a genetic test, and since early symptoms are general, it is often mistaken for another more common epilepsy, in many cases juvenile myoclonic epilepsy (JME).

Causes
The genetic cause of ULD is known, but research has led to new areas of study that may lead to an increase in knowledge of what causes ULD.

Genetic factors
The cause of ULD is known to be a mutation of the gene that produces cystatin B. The disease is autosomal recessive, so both parents of an individual must be carriers of the recessive CSTB gene for the individual to inherit it, and for an individual to show symptoms of ULD, they must have both recessive CSTB genes. Siblings of affected individuals who only have one recessive gene have been monitored and generally do not show the signs of ULD, though in some cases mild symptoms may be present.

New developments
New research shows that cystatin B may not be the only factor involved in Unverricht–Lundborg disease. In a study, it was determined that patients with ULD had more dopamine receptors in certain areas of their brain than unaffected individuals. The researchers chose to investigate dopamine receptors because they are known to be a factor in myoclonus, which are a significant part of the symptoms of ULD. The results of this study indicate that the cause of ULD may be more complex than currently thought.

Mechanism
While the genetic cause of Unverricht–Lundborg disease is known, the mechanism by which it works is not fully known. Current research has provided promising results that may lead to a confirmation of the mechanism. This research has been performed on mice with the gene for producing cystatin B removed, to provide a similar set of symptoms to individuals with ULD. The mechanism currently supported by research is very similar to another theory of epilepsy progression known as kindling.

Onset
Current research links cystatin B to production of inhibitory neurons known as GABAergic neurons. It has shown that a lack of cystatin B due to a mutation of the CSTB gene leads to a decrease in the number of inhibitory neurons, and this lack of inhibition makes the cells in the brain, particularly the hippocampus, more excitable. It is hypothesized that this increase in excitability is what causes the myoclonic jerks and tonic-clonic seizures in patients with ULD.

Progression
Research also gives evidence to support the idea that cystatin B may be a type of "protecting" molecule in the brain. Normally, after a seizure, the presence of cystatin B prevents the neurons from dying due to toxic levels of neurotransmitters. Studies suggest that the absence of cystatin B leads to the death of affected neurons, leading to a damaged portion of the brain. This damage coupled with the increased excitability of the cells then leads to more damage, which is what makes Unverricht–Lundborg disease progressive.

Diagnosis
The only currently available method to diagnose Unverricht–Lundborg disease is a genetic test to check for the presence of the mutated cystatin B gene. If this gene is present in an individual suspected of having the disease, it can be confirmed. However, genetic tests of this type are prohibitively expensive to perform, especially due to the rarity of ULD. The early symptoms of ULD are general and in many cases similar to other more common epilepsies, such as juvenile myoclonic epilepsy. For these reasons, ULD is generally one of the last options doctors explore when looking to diagnose patients exhibiting its symptoms. In most cases, a misdiagnosis is not detrimental to the patient, because many of the same medications are used to treat both ULD and whatever type of epilepsy the patient has been misdiagnosed with. However, there are a few epilepsy medications that increase the incidence of seizures and myoclonic jerks in patients with ULD, which can lead to an increase in the speed of progression, including phenytoin, fosphenytoin, sodium channel blockers, GABAergic drugs, gabapentin and pregabalin.Other methods to diagnose Unverricht–Lundborg disease are currently being explored. While electroencephalogram (EEG) is useful in identifying or diagnosing other forms of epilepsy, the location of seizures in ULD is currently known to be generalized across the entire brain. Without a specific region to pinpoint, it is difficult to accurately distinguish an EEG reading from an individual with ULD from an individual with another type of epilepsy characterized by generalized brain seizures. However, with recent research linking ULD brain damage to the hippocampus, the usefulness of EEG as a diagnostic tool may increase.
Magnetic Resonance Imaging (MRI) is also often used during diagnosis of patients with epilepsy. While MRIs taken during the onset of the disease are generally similar to those of individuals without ULD, MRIs taken once the disease has progressed show characteristic damageWhile ULD is a rare disease, the lack of well defined cases to study and the difficulty in confirming diagnosis provide strong evidence that this disease is likely under diagnosed.

Classification
Unverricht–Lundborg disease is also known as EPM1, as it is a form of progressive myoclonic epilepsy (PME). Other progressive myoclonic epilepsies include myoclonus epilepsy and ragged red fibers (MERRF syndrome),  Lafora disease (EPM2a or EMP2b), Neuronal ceroid lipofuscinosis (NCL) and sialidosis. Progressive myoclonic epilepsies generally constitute only a small percentage of epilepsy cases seen, and ULD is the most common form. While ULD can lead to an early death, it is considered to be the least severe form of progressive myoclonic epilepsy.

Treatment
While there is no current cure to repair the mutated CSTB gene, several antiepileptic drugs are effective in reducing seizures and helping patients with ULD to manage the symptoms. In addition, new research is being performed to examine the effectiveness of other types of treatments.

Current methods
Valproic acid is the first line drug choice for reducing generalised seizures and myoclonus. Levetiracetam is also effective for both generalised seizures and myoclonus. Clonazepam and high-dose piracetam can alleviate myoclonus. Phenytoin can worsen seizures and may speed up neurodegeneration; carbamazepine, oxcarbazepine, tiagabine, vigabatrin, gabapentin and pregabalin may worsen myoclonus and myoclonic seizures. Other common medications to treat ULD include topiramate and zonisamide. If an individual with Unverricht–Lundborg disease is particularly sensitive to a certain type of stimulus, it is also beneficial to reduce the patients exposure to that stimulus in order to reduce the likelihood of seizures. Since ULD is progressive and may not get better over time, depression has been documented in many cases, so providing a strong support group of friends, family, and even other individuals with ULD is very beneficial.

Prognosis
For early Unverricht–Lundborg disease patients, the disease would begin to progress early and lack of effective treatment meant a quick progression. In many cases the patient would require a wheelchair for mobility, and would die at a young age.However, increased knowledge about the disease and improved treatment and medication has led to a dramatic improvement in prognosis for individuals with ULD. Antiepileptic drugs reduce the occurrence of seizures and myoclonus, which leads to a decrease in the damage caused in the brain due to seizures and the body due to falls resulting from the seizures. As a result, individuals with Unverricht–Lundborg disease are now much less likely to end up in a wheelchair, which eliminates the chance of complications involved with being a wheelchair user. All these factors have increased the outlook for patients. Due to the progressive nature of the disease, depression is prevalent, but support of family and friends as well as proper treatment can help. While early patients with ULD had a life expectancy of around 24 years, there have recently been reported cases of individuals living to near-normal ages.

Epidemiology
The only country that Unverricht–Lundborg disease has a reported incidence is in Finland, where it is reported to occur in 4 in 100,000 individuals. However, ULD has only become well defined recently, and it is likely still under diagnosed, so the actual incidence may be different that what is currently known. Other countries with known cases include countries in the Mediterranean region including Italy, France, Tunisia, Algeria, and Morocco, next is Czech Republic  as well as the United States.

History
Unverricht–Lundborg disease was first known as one of two different diseases, depending on the location of the individual who had it: Baltic myoclonus or Mediterranean myoclonus. The reason for the different names was partly regional but also because the prognosis of the disease was different for individuals with each due to the way that it was treated in that region </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 Glucocorticoid deficiency 1 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 High-functioning autism and can you explain it in depth? [/INST] High-functioning autism (HFA) is an autism classification where a person exhibits no intellectual disability, but may exhibit deficits in communication, emotion recognition and expression, and social interaction. HFA is not included in either the American Psychological Associations DSM-5 or the World Health Organizations ICD-10, neither of which subdivides autism based on intellectual capabilities.

Characterization
High-functioning autism is characterized by features similar to those of Asperger syndrome. The defining characteristic recognized by psychologists is a significant delay in the development of early speech and language skills, before the age of three years. The diagnostic criteria of Asperger syndrome exclude a general language delay.Further differences in features of people with high-functioning autism from those with Asperger syndrome include the following:
Lower verbal reasoning ability
Better visual/spatial skills (higher performance IQ)
Less deviating locomotion (e.g. clumsiness)
Problems functioning independently
Curiosity and interest for many different things
Not as good at empathizing with other people
Male to female ratio (4:1) much smallerAs of 2013, Asperger Syndrome and High-functioning autism are no longer terms used by the American Psychological Association, and have instead both been merged into autism spectrum disorder (ASD). As of 2021, the World Health Organization also retired the terms and merged them into autism spectrum disorder.

Comorbidities
Individuals with autism spectrum disorders, including high-functioning autism, risk developing symptoms of anxiety. While anxiety is one of the most commonly occurring mental health symptoms, children and adolescents with high functioning autism are at an even greater risk of developing symptoms.There are other comorbidities, the presence of one or more disorders in addition to the primary disorder, associated with high-functioning autism. Some of these include bipolar disorder and obsessive–compulsive disorder (OCD). In particular the link between HFA and OCD, has been studied; both have abnormalities associated with serotonin.Observable comorbidities associated with HFA include ADHD and Tourette syndrome. HFA does not cause, nor include, intellectual disabilities. This characteristic distinguishes HFA from low-functioning autism; between 40 and 55% of individuals with autism also have an intellectual disability.

Behavior
An association between HFA and criminal behavior is not completely characterized. Several studies have shown that the features associated with HFA may increase the probability of engaging in criminal behavior. While there is still a great deal of research that needs to be done in this area, recent studies on the correlation between HFA and criminal actions suggest that there is a need to understand the attributes of HFA that may lead to violent behavior. There have been several case studies that link the lack of empathy and social naïveté associated with HFA to criminal actions.There is still a need for more research on the link between HFA and crimes, because many other studies point out that most people with ASD are more likely to be victims and less likely to commit crimes than the general population. But there are also small-subgroups of people with autism that commit crimes because they lack understanding of the laws they have broken. Misunderstandings are especially common regarding autism and sex offenses, since many people with autism do not receive sex education.

Cause
Although little is known about the biological basis of autism, studies have revealed structural abnormalities in specific brain regions. Regions identified in the "social" brain include the amygdala, superior temporal sulcus, fusiform gyrus area and orbitofrontal cortex. Further abnormalities have been observed in the caudate nucleus, believed to be involved in restrictive behaviors, as well as in a significant increase in the amount of cortical grey matter and atypical connectivity between brain regions.

Diagnosis and IQ
HFA is not a recognised diagnosis by the American Psychological Association (DSM-5) or the World Health Organization (ICD-10). HFA is often, however, used in clinical settings to describe a set of symptoms related to an autism spectrum disorder whereby they exhibit standard autism indicators although have an intelligence quotient (IQ) of 70 or greater.For modern IQ tests, the raw score is transformed to a normal distribution with mean 100 and standard deviation 15. This results in approximately two-thirds of the population scoring between IQ 85 and IQ 115 and about 2.5 percent each above 130 and below 70.IQ scales are ordinally scaled. The raw score of the norming sample is usually (rank order) transformed to a normal distribution with mean 100 and standard deviation 15. While one standard deviation is 15 points, and two SDs are 30 points, and so on, this does not imply that mental ability is linearly related to IQ, such that IQ 50 would mean half the cognitive ability of IQ 100. In particular, IQ points are not percentage points.
A diagnosis of intellectual disability is in part based on the results of IQ testing. Borderline intellectual functioning is the categorization of individuals of below-average cognitive ability (an IQ of 71–85), although not as low as those with an intellectual disability (70 or below).
People with high IQs are found at all levels of education and occupational categories. The biggest difference occurs for low IQs with only an occasional college graduate or professional scoring below 90.

Treatment
While there exists no single treatment or medicine for people with autism, there exists several strategies to help lessen the symptoms and effects of the condition.

Augmentative and alternative communication
Augmentative and alternative communication (AAC) is used for autistic people who cannot communicate orally. People who have problems speaking may be taught to use other forms of communication, such as body language, computers, interactive devices, and pictures. The Picture Exchange Communication System (PECS) is a commonly used form of augmentative and alternative communication with children and adults who cannot communicate well orally. People are taught how to link pictures and symbols to their feelings, desires and observation, and may be able to link sentences together with the vocabulary that they form.

Speech-language therapy
Speech–language therapy can help those with autism who need to develop or improve communication skills. According to the organization Autism Speaks, "speech-language therapy is designed to coordinate the mechanics of speech with the meaning and social use of speech". People with autism may have issues with communication, or speaking spoken words. Speech-language pathologists (SLP) may teach someone how to communicate more effectively with others or work on starting to develop speech patterns. The SLP will create a plan that focuses on what the child needs.

Occupational therapy
Occupational therapy helps autistic children and adults learn everyday skills that help them with daily tasks, such as personal hygiene and movement. These skills are then integrated into their home, school, and work environments. Therapists will oftentimes help people learn to adapt their environment to their skill level. This type of therapy could help autistic people become more engaged in their environment. An occupational therapist will create a plan based on a persons needs and desires and work with them to achieve their set goals.

Applied behavioral analysis (ABA)
Applied behavior analysis (ABA) is considered the most effective therapy for autism spectrum disorders by the American Academy of Pediatrics. ABA focuses on teaching adaptive behaviors like social skills, play skills, or communication skills and diminishing problematic behaviors such as self-injury by creating a specialized plan that uses behavioral therapy techniques, such as positive or negative reinforcement, to encourage or discourage certain behaviors over-time. However, ABA has been strongly criticised by the autistic community, who view it as abusive and detrimental to autistic childrens growth.

Sensory integration therapy
Sensory integration therapy helps people with autism adapt to different kinds of sensory stimuli. Many with autism can be oversensitive to certain stimuli, such as lights or sounds, causing them to overreact. Others may not react to certain stimuli, such as someone speaking to them </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 Pervasive developmental disorder not otherwise specified and can you explain it in depth? [/INST] A pervasive developmental disorder not otherwise specified (Including atypical autism) (PDD-NOS) is one of the four autistic spectrum disorders in the DSM-5 and also was one of the five disorders classified as a pervasive developmental disorder (PDD) in the DSM-IV. According to the DSM-4, PDD-NOS is a diagnosis that is used for "severe or pervasive impairment in the development of reciprocal social interaction and/or verbal and nonverbal communication skills, or when stereotyped behavior, interests, and/or activities are present, but the criteria are not met for a specific PDD" or for several other disorders.  PDD-NOS includes atypical autism, because the criteria for autistic disorder are not met, for instance because of late age of onset, atypical symptomatology, or subthreshold symptomatology, or all of these. Even though PDD-NOS is considered milder than typical autism, this is not always true. While some characteristics may be milder, others may be more severe.

Signs and symptoms
It is common for individuals with PDD-NOS to have more intact social skills and a lower level of intellectual deficit than individuals with other PDDs </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 Pathergy and can you explain it in depth? [/INST] Pathergy is a skin condition in which a minor trauma such as a bump or bruise leads to the development of skin lesions or ulcers that may be resistant to healing.  Pathergy can also lead to ulcerations at the site of surgical incisions </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 Foix–Alajouanine syndrome 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 Adrenoleukodystrophy and can you explain it in depth? [/INST] Adrenoleukodystrophy (ALD) is a disease linked to the X chromosome. It is a result of fatty acid buildup caused by peroxisomal fatty acid beta oxidation which results in the accumulation of very long chain fatty acids in tissues throughout the body.  The most severely affected tissues are the myelin in the central nervous system, the adrenal cortex, and the Leydig cells in the testes. The long chain fatty acid buildup causes damage to the myelin sheath of the nerves of the brain, resulting in seizures and hyperactivity. Other symptoms include problems in speaking, listening, and understanding verbal instructions.
Clinically, ALD presents as a heterogeneous disorder, showing several distinct phenotypes, and no clear pattern of genotype–phenotype correlation. As an X-linked disorder, ALD presents most commonly in males; however, approximately 50% of heterozygote females show some symptoms later in life.  Approximately two-thirds of ALD patients will present with the childhood cerebral form of the disease, which is the most severe form.  It is characterized by normal development in early childhood, followed by rapid degeneration to a vegetative state. The other forms of ALD vary in timing of onset and in clinical severity, ranging from adrenal insufficiency alone to progressive paraparesis in early adulthood.
ALD is caused by mutations in  ABCD1, a gene located on the X chromosome that codes for ALD, a peroxisomal membrane transporter protein. The exact mechanism of the pathogenesis of the various forms of ALD is not known. Biochemically, individuals with ALD show very high levels of unbranched, saturated, very long chain fatty acids, particularly cerotic acid (26:0).  The level of cerotic acid in plasma does not correlate with clinical presentation. Treatment options for ALD are limited. For the childhood cerebral form, stem cell transplant and gene therapy are options if the disease is detected early in the clinical course.  Adrenal insufficiency in ALD patients can be successfully treated.  ALD is the most common peroxisomal inborn error of metabolism, with an incidence estimated between 1:18,000 and 1:50,000. It does not have a significantly higher incidence in any specific ethnic group.

Signs and symptoms
ALD can present in different ways. The different presentations are complicated by the pattern of X-linked recessive inheritance. There have been seven phenotypes described in males with ABCD1 mutations and five in females.  Initial symptoms in boys affected with the childhood cerebral form of ALD include emotional instability, hyperactivity and disruptive behavior at school. Older patients affected with the cerebral form will present with similar symptoms.  Untreated, cerebral ALD is characterized by progressive demyelination leading to a vegetative state and death.  Adult males with an adrenomyeloneuropathy presentation typically present initially with muscle stiffness, paraparesis and sexual dysfunction.  All patients with clinically recognized ALD phenotypes are at risk for adrenal insufficiency.  There is no reliable way to predict which form of the disease an affected individual will develop, with multiple phenotypes being demonstrated within families.  Onset of adrenal insufficiency is often the first symptom, appearing as early as two years of age.

Male adrenoleukodystrophy phenotypes
Female adrenoleukodystrophy phenotypes
Genetics
ALD is caused by mutations in ABCD1, located at Xq28 and demonstrates X-linked recessive inheritance. The gene ABCD1 encodes a peroxisomal membrane transporter which is responsible for transporting very long chain fatty acid substrate into the peroxisomes for degradation. Mutations in this gene that interfere with this process cause this syndrome.Males with an ABCD1 mutation are hemizygous, as they only have a single X chromosome. Female carriers will typically avoid the most severe manifestations of the disease, but often become symptomatic later in life. Although the detection of an ABCD1 mutation identifies an individual who is affected with a form of ALD, there is no genotype–phenotype correlation. Within a family, there will often be several different phenotypes, despite the presence of the same causative mutation. In one case, a family with six affected members displayed five different phenotypes. There are no common mutations that cause ALD, most are private or familial.  Almost 600 different mutations have been identified, approximately half are missense mutations, one quarter are frameshifts, with in-frame deletions and splicing defects making up the remainder. The incidence of new mutations in ALD (those occurring spontaneously, rather than being inherited from a carrier parent) is estimated at 4.1%, with the possibility that these are due to germline mosaicism.

Pathogenesis
The exact cause for the varied collection of symptoms found in the different ALD phenotypes is not clear.  The white matter of the brain, the Leydig cells of the testes and the adrenal cortex are the most severely affected systems. The excess VLCFA can be detected in almost all tissues of the body, despite the localization of symptoms. The lack of Coenzyme A does not permit the disintegration of the VLCFA, accumulating the same in the white matter, adrenal glands, and the testes more specifically in the Leydig cells not allowing the proper function of these organs. Successful treatment of the demyelination process that affects the brain with either stem cell transplant or gene therapy does not immediately normalize the VLCFA levels in body tissues.  The levels of VLCFA can be normalized by treatment with Lorenzos oil, but this does not alter the progression of the disease.  It is unclear whether the accumulation of VLCFA is associated with the pathogenesis of the disease in a specific way, or if it is a biochemical phenotype, useful for identification.

Diagnosis
The clinical presentation of ALD can vary greatly, making diagnosis difficult.  With the variety of phenotypes, clinical suspicion of ALD can result from a variety of different presentations.  Symptoms vary based on the disease phenotype, and even within families or between twins.  When ALD is suspected based on clinical symptoms, the initial testing usually includes plasma very long chain fatty acid (VLCFA) determination using gas chromatography-mass spectrometry.  The concentration of unsaturated VLCFA, particularly 26 carbon chains is significantly elevated in males with ALD, even prior to the development of other symptoms. Confirmation of ALD after positive plasma VLCFA determination usually involves molecular genetic analysis of ABCD1.  In females, where plasma VLCFA measurement is not always conclusive (some female carriers will have normal VLCFA in plasma), molecular analysis is preferred, particularly in cases where the mutation in the family is known.  Although the clinical phenotype is highly variable among affected males, the elevations of VLCFA are present in all males with an ABCD1 mutation.Because the characteristic elevations associated with ALD are present at birth, well before any symptoms are apparent, there have been methods developed in the interests of including it in newborn screening programs.  One of the difficulties with ALD as a disease included in universal newborn screening is the difficulty in predicting the eventual phenotype that an individual will express.  The accepted treatment for affected boys presenting with the cerebral childhood form of the disease is a bone marrow transplant, a procedure which carries significant risks.  However, because most affected males will demonstrate adrenal insufficiency, early discovery and treatment of this symptom could potentially prevent complications and allow these patients to be monitored for other treatment in the future, depending on the progression of their disease.The Loes score is a rating of the severity of abnormalities in the brain found on MRI. It ranges from 0 to 34, based on a point system derived from the location and extent of disease and the presence of atrophy in the brain, either localized to specific points or generally throughout the brain. A Loes score of 0.5 or less is classified as normal, while a Loes score of 14 or greater is considered severe. It was developed by neuroradiologist Daniel J. Loes MD and is an important tool in assessing disease progression and the effectiveness of therapy.

Treatments
Dietary therapy
Initial attempts at dietary therapy in ALD involved restricting the intake of very-long chain fatty acids (VLCFA).  Dietary intake is not the only source for VLCFA in the body, as they are also synthesized endogenously.  This dietary restriction did not impact the levels of VLCFA in plasma and other body tissues.  After the realization that endogenous synthesis was an important contribution to VLCFA in the body, efforts at dietary therapy shifted to inhibiting these synthetic pathways in the body.  The parents of Lorenzo Odone, a boy with ALD, spearheaded efforts to develop a dietary treatment to slow the progression of the disease.  They developed a mixture of unsaturated fatty acids (glycerol trioleate and glyceryl trierucate in a 4:1 ratio), known as Lorenzos oil that inhibits elongation of saturated fatty acids in the body. Supplementation with Lorenzos oil has been found to normalize the VLCFA concentrations in the body, although its effectiveness at treating the cerebral manifestations of the disease is still controversial and unproven.  Trials with Lorenzos oil have shown that it does not stop the neurological degradation in symptomatic patients, nor does it improve adrenal function, but asymptomatic patients, and speculatively AMN variants without cerebral involvement, as well as female carriers may benefit from early intake of oleic and erucic acids in addition to VLCFA restriction.

Lorenzos oil
A solution of 4 parts glycerol trioleate and 1 part glycerol trierucate, which are the triacylglycerol forms of oleic acid and erucic acid, has been tested for ALD. Results are mixed, showing possible benefit for asymptomatic patients in conjunction with dietary therapy, but little or no benefit for those with symptomatic ALD.

Transplant
While dietary therapy has been shown to be effective to normalize the very-long chain fatty acid concentrations in the plasma of individuals with ALD, allogeneic hematopoietic stem cell transplants is the only treatment that can stop demyelination that is the hallmark of the cerebral forms of the disease.  In order to be effective, the transplant must be done at an early stage of the disease; if the demyelination has progressed, transplant can worsen the outcome, and increase the rate of decline.  While transplants have been shown to be effective at halting the demyelination process in those presenting with the childhood cerebral form of ALD, follow-up of these patients has shown that it does not improve adrenal function.

Gene therapy
For patients where an appropriate match for a transplant cannot be found, there have been investigations into the use of gene therapy.  Appropriate vectors are selected and modified to express wild type ABCD1, which is then transplanted into the patients using a similar procedure as for a bone marrow or stem cell transplant.  Gene therapy has only been tried on a small number of patients, mainly in France.  These patients were only considered for gene therapy after there was no HLA match for a traditional transplant </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 Juvenile primary lateral sclerosis 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 Hangnail 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 Langerhans cell histiocytosis and can you explain it in depth? [/INST] Langerhans cell histiocytosis (LCH) is an abnormal clonal proliferation of Langerhans cells, abnormal cells deriving from bone marrow and capable of migrating from skin to lymph nodes.
Symptoms range from isolated bone lesions to multisystem disease. LCH is part of a group of syndromes called histiocytoses, which are characterized by an abnormal proliferation of histiocytes (an archaic term for activated dendritic cells and macrophages). These diseases are related to other forms of abnormal proliferation of white blood cells, such as leukemias and lymphomas.The disease has gone by several names, including Hand–Schüller–Christian disease, Abt-Letterer-Siwe disease, Hashimoto-Pritzker disease (a very rare self-limiting variant seen at birth) and histiocytosis X, until it was renamed in 1985 by the Histiocyte Society.

Classification
The disease spectrum results from clonal accumulation and proliferation of cells resembling the epidermal dendritic cells called Langerhans cells, sometimes called dendritic cell histiocytosis. These cells in combination with lymphocytes, eosinophils, and normal histiocytes form typical LCH lesions that can be found in almost any organ. A similar set of diseases has been described in canine histiocytic diseases.LCH is clinically divided into three groups: unifocal, multifocal unisystem, and multifocal multisystem.

Unifocal
Unifocal LCH, also called eosinophilic granuloma (an older term which is now known to be a misnomer), is a disease characterized by an expanding proliferation of Langerhans cells in one organ, where they cause damage called lesions. It typically has no extraskeletal involvement, but rarely a lesion can be found in the skin, lungs, or stomach. It can appear as a single lesion in an organ, up to a large quantity of lesions in one organ. When multiple lesions are scattered throughout an organ, it can be called a multifocal unisystem variety. When found in the lungs, it should be distinguished from Pulmonary Langerhans cell hystiocytosis—a special category of disease most commonly seen in adult smokers. When found in the skin it is called cutaneous single system Langerhans cell LCH. This version can heal without therapy in some rare cases. This primary bone involvement helps to differentiate eosinophilic granuloma from other forms of Langerhans Cell Histiocytosis (Letterer-Siwe or Hand-Schüller-Christian variant).

Multifocal unisystem
Seen mostly in children, multifocal unisystem LCH is characterized by fever, bone lesions and diffuse eruptions, usually on the scalp and in the ear canals. 50% of cases involve the pituitary stalk, often leading to diabetes insipidus. The triad of diabetes insipidus, exophthalmos, and lytic bone lesions is known as the Hand-Schüller-Christian triad. Peak onset is 2–10 years of age.

Multifocal multisystem
Multifocal multisystem LCH, also called Letterer-Siwe disease, is an often rapidly progressing disease in which Langerhans Cell cells proliferate in many tissues. It is mostly seen in children under age 2, and the prognosis is poor: even with aggressive chemotherapy, the five-year survival is only 50%.

Pulmonary Langerhans cell histiocytosis (PLCH)
Pulmonary Langerhans cell histiocytosis (PLCH) is a unique form of LCH in that it occurs almost exclusively in cigarette smokers. It is now considered a form of smoking-related interstitial lung disease. PLCH develops when an abundance of monoclonal CD1a-positive Langerhans (immature histiocytes) proliferate the bronchioles and alveolar interstitium, and this flood of histiocytes recruits granulocytes like eosinophils and neutrophils and agranulocytes like lymphocytes further destroying bronchioles and the interstitial alveolar space that can cause damage to the lungs. It is hypothesized that bronchiolar destruction in PLCH is first attributed to the special state of Langerhans cells that induce cytotoxic T-cell responses, and this is further supported by research that has shown an abundance of T-cells in early PLCH lesions that are CD4+ and present early activation markers. Some affected people recover completely after they stop smoking, but others develop long-term complications such as pulmonary fibrosis and pulmonary hypertension.

Signs and symptoms
LCH provokes a non-specific inflammatory response, which includes fever, lethargy, and weight loss. Organ involvement can also cause more specific symptoms.

Bone: The most-frequently seen symptom in both unifocal and multifocal disease is painful bone swelling. The skull is most frequently affected, followed by the long bones of the upper extremities and flat bones. Infiltration in hands and feet is unusual. Osteolytic lesions can lead to pathological fractures.
Skin: Commonly seen are a rash which varies from scaly erythematous lesions to red papules pronounced in intertriginous areas. Up to 80% of LCH patients have extensive eruptions on the scalp.
Bone marrow: Pancytopenia with superadded infection usually implies a poor prognosis. Anemia can be due to a number of factors and does not necessarily imply bone marrow infiltration.
Lymph node: Enlargement of the liver in 20%, spleen in 30% and lymph nodes in 50% of Histiocytosis cases.
Endocrine glands: Hypothalamic pituitary axis  commonly involved. Diabetes insipidus is most common. Anterior pituitary hormone deficiency is usually permanent.
Lungs: some patients are asymptomatic, diagnosed incidentally because of lung nodules on radiographs; others experience chronic cough and shortness of breath.
Less frequently gastrointestinal tract, central nervous system, and oral cavity.

Pathophysiology
The pathogenesis of Langerhans cell histiocytosis (LCH) is a matter of debate. There are ongoing investigations to determine whether LCH is a reactive (non-cancerous) or neoplastic (cancerous) process. Arguments supporting the reactive nature of LCH include the occurrence of spontaneous remissions, the extensive secretion of multiple cytokines by dendritic cells and bystander-cells (a phenomenon known as cytokine storm) in the lesional tissue, favorable prognosis and relatively good survival rate in patients without organ dysfunction or risk organ involvement.On the other hand, the infiltration of organs by monoclonal population of pathologic cells, and the successful treatment of subset of disseminated disease using chemotherapeutic regimens are all consistent with a neoplastic process. In addition, a demonstration, using X chromosome–linked DNA probes, of LCH as a monoclonal proliferation provided additional support for the neoplastic origin of this disease. While clonality is an important attribute of cancer, its presence does not prove that a proliferative process is neoplastic.  Recurrent cytogenetic or genomic abnormalities would also be required to demonstrate convincingly that LCH is a malignancy.An activating somatic mutation of a proto-oncogene in the Raf family, the BRAF gene, was detected in 35 of 61 (57%) LCH biopsy samples with mutations being more common in patients younger than 10 years (76%) than in patients aged 10 years and older (44%). This study documented the first recurrent mutation in LCH samples. Two independent studies have confirmed this finding. Presence of this activating mutation could support the notion to characterize LCH as myeloproliferative disorder.

Diagnosis
Diagnosis is confirmed histologically by tissue biopsy. Hematoxylin-eosin stain of biopsy slide will show features of Langerhans Cell e.g. distinct cell margin, pink granular cytoplasm. Presence of Birbeck granules on electron microscopy and immuno-cytochemical features e. g. CD1 positivity are more specific. Initially routine blood tests e.g. full blood count, liver function test, U&Es, bone profile are done to determine disease extent and rule out other causes.Imaging may be evident in chest X-rays with micronodular and reticular changes of the lungs with cyst formation in advanced cases. MRI and High-resolution CT may show small, cavitated nodules with thin-walled cysts. MRI scan of the brain can show three groups of lesions such as tumourous/granulomatous lesions, nontumourous/granulomatous lesions, and atrophy. Tumourous lesions are usually found in the hypothalamic-pituitary axis with space-occupying lesions with or without calcifications. In non-tumourous lesions, there is a symmetrical hyperintense T2 signal with hypointense or hyperintense T1 signal extending from grey matter into the white matter. In the basal ganglia, MRI shows a hyperintense T1 signal in the globus pallidus.Assessment of endocrine function and bonemarrow biopsy are also performed when indicated.
S-100 protein is expressed in a cytoplasmic pattern
peanut agglutinin (PNA) is expressed on the cell surface and perinuclearly
major histocompatibility (MHC) class II is expressed (because histiocytes are macrophages)
CD1a
langerin (CD207), a Langerhans Cell–restricted protein that induces the formation of Birbeck granules and is constitutively associated with them, is a highly specific marker.

Treatment
Guidelines for management of patients up to 18 years with Langerhans cell histiocytosis have been suggested. Treatment is guided by extent of disease. Solitary bone lesion may be amenable through excision or limited radiation, dosage of 5-10 Gy for children, 24-30 Gy for adults. However systemic diseases often require chemotherapy. Use of systemic steroid is common, singly or adjunct to chemotherapy. Local steroid cream is applied to skin lesions. Endocrine deficiency often require lifelong supplement e.g. desmopressin for diabetes insipidus which can be applied as nasal drop </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 Snatiation 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 Albinism and can you explain it in depth? [/INST] Albinism is the congenital absence of melanin in an animal or plant resulting in white hair, feathers, scales and skin and pink or blue eyes. Individuals with the condition are referred to as albino.
Varied use and interpretation of the terms mean that written reports of albinistic animals can be difficult to verify. Albinism can reduce the survivability of an animal; for example, it has been suggested that albino alligators have an average survival span of only 24 hours due to the lack of protection from UV radiation and their lack of camouflage to avoid predators. It is a common misconception that all albino animals have characteristic pink or red eyes (resulting from the lack of pigment in the iris allowing the blood vessels of the retina to be visible), however this is not the case for some forms of albinism. Familiar albino animals include in-bred strains of laboratory animals (rats, mice and rabbits), but populations of naturally occurring albino animals exist in the wild, e.g. Mexican cave tetra. Albinism is a well-recognized phenomenon in molluscs, both in the shell and in the soft parts. It has been claimed by some, e.g. that albinism can occur for a number of reasons aside from inheritance, including genetic mutations, diet, living conditions, age, disease, or injury. However, this is contrary to definitions where the condition is inherited.
Oculocutaneous albinism (OCA) is a clearly defined set of seven types of genetic mutations which reduce or completely prevent the synthesis of eumelanin or pheomelanin, resulting in reduced pigmentation. Type I oculocutaneous albinism (OCA1a) is the form most commonly recognised as albino as this results in a complete absence of melanin in the skin, hair/fur/feathers, and pink pupils, however this has led many to assume that all albinos are pure white with pink pupils, which is not the case.In plants, albinism is characterised by partial or complete loss of chlorophyll pigments and incomplete differentiation of chloroplast membranes. Albinism in plants interferes with photosynthesis, which can reduce survivability. Some plant variations may have white flowers or other parts.  However, these plants are not totally devoid of chlorophyll. Terms associated with this phenomenon are "hypochromia" and "albiflora".

Biological colouration
Biological pigments are substances produced by living organisms that have a colour resulting from selective colour absorption. What is perceived as a plant or animals "colour" is the wavelengths of light that are not absorbed by the pigment, but instead are reflected. Biological pigments include plant pigments and flower pigments.

Animal colouration
Animals can appear coloured due to two mechanisms, pigments and structural colours. Animals may have both biological pigments and structural colours, for example, some butterflies with white wings.

Pigments
Many animal body-parts, such as skin, eyes, feathers, fur, hair, scales and cuticles, contain pigments in specialized cells called chromatophores. These cells are found in a wide range of animals including amphibians, fish, reptiles, crustaceans and cephalopods. Mammals and birds, in contrast, have a class of cells called melanocytes for colouration. The term chromatophore can also refer to coloured, membrane-associated vesicles found in some forms of photosynthetic bacteria. Chromatophores are largely responsible for generating skin and eye colour in poikilothermic animals and are generated in the neural crest during embryonic development. Mature chromatophores are grouped into subclasses based on their colour under white light:

xanthophores (yellow): contain yellow pigments in the forms of carotenoids
erythrophores (red): contain reddish pigments such as carotenoids and pteridine
melanophores (black/brown): contain black and brown pigments such as the melanins
cyanophores (blue): limited taxonomic range but found in some fish and amphibians

Structural colours
Animals can also appear coloured due to structural colour, the result of coherent scattering perceived as iridescence. The structures themselves are colourless. Light typically passes through multiple layers and is reflected more than once. The multiple reflections compound one another and intensify the colours. Structural colour differs according to the observers position whereas pigments appear the same regardless of the angle-of-view. Animals that show iridescence include mother of pearl seashells, fish, and peacocks. These are just a few examples of animals with this quality, but it is most pronounced in the butterfly family.

iridophores (reflective/iridescent): sometimes called "guanophores", reflect light using plates of crystalline chemochromes made from guanine
leucophores (reflective white): found in some fish, utilize crystalline purines (often guanine) to produce a reflective, shiny, white colour.

Plant colouration
The primary function of pigments in plants is photosynthesis, which uses the green pigment chlorophyll along with several red and yellow pigments including porphyrins, carotenoids, anthocyanins and betalains.

Definition
Definitions of albinism vary and are inconsistent. While they are clear and precise for humans and other mammals, this is because the majority of mammals have only one pigment, melanin. Many animals have pigments other than melanin, and some also have structural colours. Some definitions of albinism, whilst taking most taxa into account, ignore others. So, "a person or animal with very pale skin, white hair or fur, and pink eyes caused by a medical condition that they were born with" and "a person or animal with white skin and hair and pink eyes" do not include feathers, scales or cuticles of birds, fish and invertebrates, nor do they include plants. Some definitions are too broad to be of much use, e.g. "an animal or plant with a marked deficiency in pigmentation".Other definitions of albinism encompass most of the major animal taxa, but ignore the several other pigments that non-mammalian animals have and also structural colouration. For example, "Absence of the pigment melanin in the eyes, skin, hair, scales, or feathers." refers only to the pigment melanin.
Because of the various uses of different terms applied to colouration, some authors have indicated that the colour of the eyes is the defining characteristic of albinism, e.g. "This leads to a good diagnostic feature with which to distinguish leucistic and albino individuals – the colour of the eye." However, there are multiple forms of albinism – currently seven types recognised for humans – most of which do not result in red or pink pupils.The term "partial albino" is sometimes used in the literature, however, it has been stated that "A common misnomer is partial albino – this is not possible since albinism affects the whole plumage of a bird, not just part" and the definition of albinism precludes the possibility of "partial albinism" in which a mostly white bird shows some form of melanin pigmentation. "It is simply impossible, just like being partially pregnant ". Conditions that are commonly termed "partial albino" include neural crest disorders such as piebaldism, Waardenburg syndrome, or other depigmentation conditions such as vitiligo. These conditions result from fundamentally different causes to the seven types of oculocutaneous albinism that have been identified in humans (and confirmed in some other animals) and the use of the term "partial albino" is therefore misleading.One definition states that "albinism, (from the Latin albus, meaning "white"), hereditary condition characterized by the absence of pigment in the eyes, skin, hair, scales, or feathers", however, this does not encompass invertebrates, nor does it include plants.  Furthermore, it could be interpreted that "...absence of pigment..." does not include an absence of structural colours.
The lack of clarity about the term is furthered when the name of an animal includes the term "albino" although the animals (clearly) do not have the condition. For example, the albino gaur has this name because it is ash-grey whereas other gaur are almost black.
A clear definition appears to be – "Congenital absence of any pigmentation or colouration in a person, animal, or plant, resulting in white hair and pink eyes in mammals." Whilst this does not state specifically that non-mammalian albino animals (or plants) are white, this can be inferred from "...absence of any pigmentation or colouration..." Due to the varied use and interpretation of the term "albino", written reports of albinistic organisms can often not be verified.

Mechanism and frequency
Melanin is an organic pigment that produces most of the colour seen in mammals. Depending on how it is created, melanin comes in two colour ranges, eumelanin (producing dark browns and blacks) and pheomelanin (producing light reddish tans and blondes). The dark and light melanins have their influence either alone or in conjunction, making either plain or multi-coloured coats. Sometimes, in a condition called agouti, they make multi-coloured individual hairs. The production of melanin occurs in melanocytes in a complex process involving the enzyme tyrosinase. Mammals have a gene that codes for the presence of tyrosinase in cells – called the TYR gene. If this gene is altered or damaged, melanin cannot be reliably produced and the mammal becomes an albino. Besides the TYR gene, several other genes can cause albinism. This is because other hormones and proteins are involved in melanin production, the presence of which is genetically determined. In mice, a total of 100 genes are known to affect albinism.All the genetic traits for albinism are recessive traits. This means that their influence is hidden when paired with stronger traits. For the recessive albino trait to be expressed in a mammal, the offspring must inherit a recessive gene from both parents.Albinism occurs throughout the animal kingdom. The condition is most commonly seen in birds, reptiles and amphibians, but more rarely seen in mammals and other taxa. It is often difficult to explain occasional occurrences, especially when only one documented incidence has occurred, such as only one albino gorilla and one albino koala. In mammals, albinism occurs once in every 10,000 births, but in birds, the rate is once in every 1,764 births.Some species, such as white peacocks, swans and geese, are not believed to be true albinos, as they do not have red eyes, rather, their colouration is suggested to be the expression of a white fur or feather gene, not a lack of melanin.

Consequences
Melanin has several functions in most mammals and other animals; these are disrupted by albinism.

Abnormal eye development and appearance
Melanin functions in the normal development of various parts of the eye, including the iris, retina, eye muscles, and optic nerve. The absence of melanin results in abnormal development of eyes and leads to problems with focusing, and depth perception. The eyes of albino animals appear red because the colour of the red blood cells in the retina can be seen through the iris, which has no pigment to obscure this. Some albino animals may have pale-blue eyes due to other colour generating processes. Albino vertebrates exposed to intense light typically lose photoreceptors due to apoptosis.

In all albino mammals studied, the centre of the retina is under-developed and there is a deficit of rod cells; the central ganglion cell density is approximately 25% below normal (except for the gray squirrel).  In nearly all mammals, the overwhelming majority of photoreceptors are rods rather than cones. Albinism specifically affects the rod cells, but the number and distribution of the cones is unaffected.  In contrast, the retinas of birds are cone rich meaning that the vision of albino birds is affected less than albino mammals.

Reduced protection from sunlight in albino creatures
Melanin protects the skin from ultra-violet radiation in sunlight. Melanosomes block harmful electromagnetic radiation from the sun while allowing beneficial frequencies to enter the body. This means some animals may die from UV radiation due to a lack of protection. Albino humans must use an excessive amount of sunscreen, even if the sun is hidden behind the clouds.

Survival disadvantages
Many animals with albinism lack their protective camouflage and are therefore less able to conceal themselves from their predators or prey: The survival rate of animals with albinism in the wild can be low, however, it has been stated that in studies where animals had many places to hide, predators captured albino and normally coloured animals at the same rate. Furthermore, albino animals may be excluded from families or other groups, or rejected as mates.The novelty of albino animals has occasionally led to their protection by groups such as the Albino Squirrel Preservation Society.  They have also been protected in studies on their ecology, sociology and behaviour.

Reduced viability
Studies on medaka fish in the laboratory, i.e. with no predators, sufficient food supply, controlled temperatures, etc., found that albinos had considerably reduced viability; from 800 albino embryos, only 29 survived to full adulthood. Early studies on fish led some researchers to describe albinism as a "semi-lethal mutation".

Hearing disorders
Pigmentation disorders such as albinism are occasionally associated with hearing impairments in mice, rats, guinea pigs and cats.

In mammals
Artificially selected
Intentionally bred albinistic strains of some animal species are commonly used as model organisms in biomedical research and also as pets. Examples include the BALB/c mouse and Wistar and Sprague Dawley rat strains, laboratory rabbits and ferrets. Albino axolotl (an amphibian) are also used widely in the laboratory as their transparent skin allows observation of the underlying tissues during limb regeneration. Some researchers have argued that albino animals are not always the best choice for scientific studies due to the consequences of albinism (e.g. hearing and visual impairments).Many individual albino mammals are in captivity and were caught while young. It is doubtful whether these individuals would have survived to become adults without the protection and care they receive in captivity.

Naturally occurring
It has been claimed that "Squirrels are the only known albino mammal to survive successfully in the wild". The retina of the squirrel (Sciurus carolinensis) is unusual for mammals as it is rich in cones.  Central cell densities are less than 5% lower in albino squirrels than in pigmented individuals.  This relatively minor disruption to vision is thought to assist in the survivability of albino squirrels in the wild.  This is supported by observations that the behaviour of albinos in the wild, e.g. leaping from branch to branch, is similar to pigmented squirrels.A 2012 survey of the literature reported that in India, there were several records of albino mammals including the tiger, lesser mouse-tailed bat, chital, common palm civet, northern palm squirrel, five-striped palm squirrel and wild boar.Albino macaques have been reported in several occasions including a toque macaque (M. sinica), rhesus macaque (M. mulatta), and bonnet macaque (M. radiata).Albinism was observed in jungle cats (Felis chaus) and jackals (Canis aureus) along the coastline of the southern Western Ghats (Kerala and Kanyakumari coast, India). Albinism was observed in jungle cats from the Amaravila area of Trivandrum district in the Kerala State. Albinism in jackals was observed from the Polooni area in Malappuram district and Chaliyam area of Calicut district (Kerala). As albinism is observed in those areas where the density of these mammals is comparatively low, it is concluded that continuous inbreeding could be the reason for expression of albinism.A study on albinistic prairie voles (Microtus ochrogaster) found that albinism in this species conferred an advantage for the males compared to the wild-type; albino males had higher mount frequencies than wild-type males. In addition, the albinos had greater differential fertilizing capacity.Albinism can also occur in marsupials and monotremes as well such as echidnas, kangaroos, koalas, possums, wallabies and wombats as well.

Marine mammals
The costs of albinism for marine mammals may include reduced heat absorption in colder waters, poor camouflage from predators, increased sensitivity to sunlight, and impaired visual communication. Despite the costs, some individuals do reach adult age and breeding status.Albino dolphins were first sighted in the Gulf of Mexico in 1962. Since 1994, three further individuals have been seen. These tend to be pink in colour due to blood vessels showing through the blubber and unpigmented skin.
A report published in 2008 stated that in marine mammals, "anomalously white" individuals have been reported for 21 cetacean species and 7 pinniped species but there were no known reports of anomalously white sea otters (Enhydra lutris) or sirenians.Whales and dolphins also may appear white if extensively scarred, or covered with a fungus, such as Lacazia loboi.

Famous albino mammals
Famous albino mammals include Migaloo, a humpback whale living off the coast of Australia; Pinky, a bottlenose dolphin living in and around in Calcasieu Lake, Louisiana; Carolina Snowball, a popular albino bottlenose dolphin displayed at the Miami Seaquarium in the early 1960s; Snowflake, a Barcelona Zoo gorilla, and Mahpiya Ska, (Sioux for White Cloud), a buffalo in Jamestown, North Dakota, and inspiration for Herman Melvilles novel Moby-Dick, a sperm whale known as Mocha Dick.

In birds
The most important pigments that determine plumage colouration in birds are melanines and carotenoids.  The latter are ingested in food and transformed into colour pigments by enzymes.  Aberrations in this pigmentation are mostly caused by food deficiencies and usually do not have a genetic basis. Well-known examples are flamingos, which owe their distinct pink colour to the presence of red carotenoids in their natural food. When these carotenoids are in short supply, these birds appear white after the next moult.  Mutations causing changes in carotenoid-based colour pigments are rare; melanine mutations occur much more frequently.  Two types of melanin, eumelanin and phaeomelanin, are present in birds. In the skin and eyes, only eumelanin is present.  In some bird species, the colour is completely caused by eumelanin, however, both types of melanin are found in most species.  In birds, albinism has been defined as "a total lack of both melanins in feathers, eyes and skin as a result of an inherited absence of tyrosinase", however, this ignores the effects of other pigments and structural colours.
An albino bird has a white beak, white plumage, non-coloured skin, white talons and pink or red eyes.
Albinism is only seen in about 1 of every 1,800 birds.  The two most common species of albino birds are the common house martin and the American robin. Famous albino birds include "Snowdrop", a Bristol Zoo penguin.In one study, albinism in birds has been categorised according to the extent of pigment absence. –

Total albinism – a simultaneous complete absence of melanin from the eyes, skin, and feathers. This is the rarest form. Only 7% of 1,847 cases of avian albinism examined was this type.
Incomplete albinism – when melanin is not simultaneously absent from the eyes, skin and feathers.
Imperfect albinism – when melanin is reduced in the eyes, skin and feathers.
Partial albinism – when albinism is localized to certain areas of the body.However, it has been argued that the definition of albinism precludes the possibility of "partial albinism" in which a mostly white bird shows some form of melanin pigmentation. "It is simply impossible, just like being partially pregnant.

In fish
As with other animals, it has been stated that for fish to be properly described as "albino", they must have a white body and pink or red eyes.

Artificially selected
Zebrafish have three types of chromatophores—iridophores, melanophores, and xanthophores—which produce silver, black, and yellow pigmentation respectively.  Zebrafish that lack iridophores are known as roy mutants, those that lack melanophores as albino mutants, and those which lack both melanophores and iridophores are ruby mutants.  The gross eye morphology, feeding and swimming behaviours between wild-type and albino zebrafish were indistinguishable, except under dim or bright light or low contrast.
In mammals, albinism is occasionally associated with hearing impairments. However, when tested, there was no differences in responses between wild-type and albinistic European wels catfish (Silurus glanis) and South American bronze catfish (Corydoras aeneus).  Similarly, Mexican blind cave fish (Astyanax mexicanus) do not differ in hearing sensitivity from the normally pigmented and eyed surface-dwelling populations.  Fish lack melanin in the inner ear, meaning that hearing in fishes is less likely to be affected by albinism than in mammals.

Naturally occurring
There are several reports of total albinism in both freshwater and marine fish, however, frequently captured albino fish are only reported in aquarium magazines and local newspapers.The incidence of albinism can be artificially increased in fish by exposing the eggs to heavy metals (e.g. arsenic, cadmium, copper, mercury, selenium, zinc).In the wild, albinism is reasonably common in the teleosts, especially the Pleuronectiformes (flatfish), however, it is rarely reported in the elasmobranchs. Albinism has been reported in hagfish, lampreys, sharks, rays and numerous teleost fishes, e.g. catfishes, grunts or cyprinids.

In Actinopterygii
Albino and normally pigmented channel catfish (Ictalurus punctatus) differ in their characteristics. Normal individuals of this species are superior to albinos in body weight and total length. Albinos crossed with other albinos require 11 days longer to spawn and produce smaller egg masses. These masses contain eggs of lighter weight with poorer hatchability than crosses of normal fish. The albino fish have lower survival rates than normal fish but dress-out percentages are nearly equal.Some wild cave fish have populations that are albinistic.  The Mexican cave tetra is a species that has evolved specialized characteristics in a series of independent caves.  One of these is albinism linked to the Oca2 gene, a known pigmentation gene, This trait has evolved independently in at least two caves.

In Chondrichthyes
In the class Chondrichthyes, several species of naturally occurring albino rays and sharks have been recorded. Furthermore, an albino individual spotted ratfish (Hydrolagus colliei) from the order Chimaeriformes has been reported.Albinistic individuals of the following shark species have been reported:
Basking shark (Cetorhinus maximus) – 2 cases
Broadnose sevengill shark (Notorynchus cepedianus)
Great white shark (Carcharodon carcharias)
Grey smooth-hound (Mustelus californicus) – 2 cases
Japanese topeshark (Hemitriakis japanica)
Japanese wobbegong (Orectolobus japonicus)
Java shark (Carcharhinus amboinensis)
Leopard shark (Triakis semifasciata)
Narrownose smooth-hound (Mustelus schmitti)
Pigeye shark (Carcharhinus amboinensis)
Porbeagle (Lamna nasus)
Scalloped hammerhead shark (Sphyrna lewini)
Spiny dogfish (Squalus acanthias)
Tawny nurse shark (Nebrius ferigineus)
Tiger shark (Galeocerdo cuvier) – embryo
Whale shark (Rhincodon typus)
Whitespotted bamboo shark (Chiloscyllium plagiosum)
Zebra shark (Stegostoma fasciatum)A study published in 2006 reported albinistic individuals of the following ray species:
Bat ray (Myliobatis californica)
Common skate (Raja batis)
Common stingray (Dasyatis pastinaca)
Common torpedo (Torpedo torpedo)
Cownose ray (Rhinoptera bonasus)
Giant electric ray (Narcine entemedor)
Giant oceanic manta ray (Manta birostris)
Ocellate spot skate (Okamejei kenojei)
Southern stingray (Dasyatis americana)
Thornback ray (Raja clavata)
Cuckoo ray (Raja naevus)

In Hyperoartia
There are several reports of albino lampreys and it has been estimated that this occurs at a frequency of one in 100,000 normal individuals.

In Sarcopterygii
Albinism in the African lungfish has been reported on at least two occasions.

In reptiles
Many reptiles labeled as albino are, in fact, not completely lacking in all colour pigments.  They are actually amelanistic, not albino.  Reptiles often possess at least two pigments.  Among the most common are xanthin (yellow) and erythrin (red). An amelanistic reptile therefore, may still have pale yellow, orange, or red pigmentation.
The California Academy of Science, in the Steinhart Aquarium, as of 2015, has on display an albino American alligator named "Claude". The alligator is partially blind because of lack of pigment in its eyes. The albino alligator hatched from the egg in 1995 in Florida, and was brought to the academy in 2008. This alligator would not have survived in the wild because its whiteness would have made it too easy a prey object. The only known albino alligators are in captivity. While extremely rare, white-coloured crocodiles and alligators do exist in other places. However, most of these animals are leucistic given that they have a general loss of pigmentation with some colour tinges remaining on their bodies although looking at first like other albino creatures, thus creating the misconception that the reptiles are albino themselves when they are not. Four such alligators are kept at the Gatorland theme park in the U.S. state of Florida. In Australia, a crocodile believed to be "part-albino" and nicknamed by people in the area as "Michael Jackson", attacked and killed a man.In snakes, partial absence of pigment is more common than absolute albinism.  For snakes that are usually patterned in colours, they appear as a faint blue, peach or yellowish.  In these cases, there has been a genetic mutation in the melanin and pigment delivery.  The appearance comes from the inability for full colours to be present, such as black, red, brown and others. The eyes of an albino snake are typically red or pink. Albino snakes can remain in the sunlight for several hours with minimal harm.  Corn snakes and snakes of larger types, such as a boa or diamondback snakes, are the most commonly affected by albinism often appearing to be a pinkish or yellowish colour.Albino tortoises and turtles are uncommon; Sulcata tortoises are the most likely type of turtle to express albinism. The shells have an almost yellow colouration and they have pink eyes. For turtles, a pure white colour is nearly impossible, even with albinism. Albino turtles can have a longer lifespan than many other albino animals; their hard shells help to prevent predation and other environmental challenges. Vision and sensory organs are slightly affected.In 2012, an albino anole was reported and photographed. In 2007, it was reported that an albino stumpy-tail lizard (possibly a shingleback lizard), approximately 12 cm (4.7 in) long and roughly 1 year old, had been found in Victoria, Australia.There are three known "albino" strains of leopard gecko, however, breeders state that albinos are generally recognized by their lack of black pigment and having red eyes is not a requirement to be considered an albino.  These three strains are called "tremper albinos", "rainwater albinos" and "bell albinos".

In amphibians
As with reptiles, many amphibians labeled as albino are, in fact, not completely lacking in all colour pigments.  They are actually amelanistic, not albino.  Amphibians have six types of chromatophore in their skin, i.e. melanophores, xanthophores, erythrophores, leucophores, cyanophores and iridophores. An amelanistic amphibian therefore, may still have various pigmentation.

The incidence of albinism in frogs, salamanders, and newts is relatively higher than other taxa. It has been estimated that one in four hundred of these animals is albino. When albino tadpoles hatch, they are almost transparent. This may help camouflage them initially, however, after two weeks, when their hindlegs begin to emerge, they become milky white. A survey in 2001 found hundreds of tiny albino plains leopard frogs, but when the researcher returned a few months later, not a single albino adult could be found.In European Salamandridae, albinism has been recorded in the fire salamander (Salamandra salamandra), gold-striped salamander (Chioglossa lusitanica), Italian crested newt (Triturus carnifex), marbled newt (Triturus marmoratus), Iberian ribbed newt (Pleurodeles waltl), alpine newt (Ichthyosaura alpestris) and two sub-species of the smooth newt (Lissotriton vulgaris vulgaris and Lissotriton vulgaris meridionalis).

Genetics
Genetic studies of albinism in amphibians have focused on mutations in the tyrosinase gene. The albino phenotype of the leopard frog (Rana pipiens) has been attributed to a failure in post-translational control in a single recessive tyrosinase gene which still has some tyrosinase and DOPA oxidase activity. This is in contrast with mammals, some of which have mutations that show no tyrosinase or DOPA oxidase activity in albinos. The albino phenotype of the pond frog (Pelophylax nigromaculatus) has been attributed to one of three mutations that created a dysfunctional tyrosinase. Two of those mutations involve an insertion of a thymine (T), a frameshift mutation, resulting in a truncated isoform of the TYR protein that is defective. The other mutation involves the deletion of a codon, three nucleotides that code for a lysine (Lys). In the wrinkled frog (Glandirana rugosa) and in the rice frog (Fejervarya kawamurai), a substitution from a guanine (G) to an adenine (A) creates a missense mutation, in which a glycine (Gly) changes to an aspartic acid (Asp) and an arginine (Arg), respectively. These changes in the polypeptide chain causes a dysfunctional tyrosinase.

In invertebrates
Albinism in molluscs has been recognized to be a hereditary phenomenon at least since 1900. Albinism in molluscs can exist to a variable degree. Sometimes an individual snail has a normally pigmented body, but the shell is completely without the normal pigmentation because of a defect in the cells of the mantle.  Shells of certain mollusc species can be translucent when they lack the normal pigmentation.

In insects
The neurohormone [His7]-corazonin induces darkening of the cuticle of Locusta migratoria.  The Okinawa strain of this species is deficient in [His7]-corazonin and is albino.  One of the typical features of Locusta migratoria is that they are gregarious locusts.  However, the albino strain shows more solitarious behaviour.The yellow mutation in fruit flies is a mutation causing a congenital lack of normal pigment; it is a similar phenomenon to albinism in other organisms.

In echinoderms
The Japanese sea cucumber (Apostichopus japonicus) is an echinoderm that is caught in the wild or cultivated for food.
Normal Japanese sea cucumbers start to develop pigmentation when they are about 1 cm long.  The upperside becomes a dull, yellowish -brown to maroon and the underside a light brown.  The body walls of adult, albino Japanese sea cucumbers contain only 0.24% melanin compared to 3.12% in normal adults.  The difference in melanin content becomes visually apparent at 60 days of age.  The epidermis is thinner in the albinos and contains fewer melanocytes.  Albino individuals are similar to normal individuals in growth rate, digestion rate and fertility.Astaxanthin is the main carotenoid in marine crustaceans (and fish).  It has been shown that adding astaxanthin to the feed can improve the skin and muscle colour of marine organisms and thereby increase their commercial and ornamental value.

In arachnids
"Depigmented" arthropods have been found, usually in cave populations.
"Albino" individuals of normally red citrus red mites (Panonychus citri) occasionally appear in laboratory colonies, however, these still contain green and yellow pigments. This albinism does not affect mortality.

Related pigment disorders
In some animals, albinism-like conditions may affect other pigments or pigment-production mechanisms:

"Whiteface," a condition that affects some parrot species, is caused by a lack of psittacins.
Axanthism is a condition common in reptiles and amphibians, in which xanthophore metabolism is affected rather than synthesis of melanin, resulting in reduction or absence of red and yellow pteridine pigments.
Leucism differs from albinism in that the melanin is, at least, partially absent but the eyes retain their usual colour. Some leucistic animals are white or pale because of chromatophore (pigment cell) defects, and do not lack melanin.
Melanism is the direct opposite of albinism </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 Menstrual migraine and can you explain it in depth? [/INST] Menstrual migraine (also called catamenial migraine) is term used to describe both true menstrual migraines and menstrually related migraines. About 7%–14% of women have migraines only at the time of menstruation, these are called true menstrual migraines. Most female migraneurs experience migraine attacks throughout the menstruation cycle with an increased number perimenstrually, these are referred to as menstrually related or menstrually triggered migraine.It used to believed that treatments for migraine would work in menstrual migraine but that has not proven to be the case because menstrual migraines are harder to treat. Because of this, menstrual migraines are now considered a separate medical disorder from migraine. In 2008, menstrual migraines were given ICD-9 codes (346.4-346.43) of their own which separate menstrual migraine from other types of migraine.
About 40% of women and 20% of men will get a migraine at sometime in their life; most of them will get their first migraine before they are 35-years-old. Menstrual-related migraines happen in more than 50 percent of women who have migraine headaches. Menstrual migraine attacks usually last longer than other migraine attacks, and short-term treatments do not work as well with menstrual migraine as they do in other kinds of migraine. They are usually migraines without aura, but in 2012 a case of menstrual migraine with aura was reported, so it is possible. Auras are a kind of condition which affect certain parts of the brain, usually the parts that control vision but they can also affect the parts of the brain which control the other senses like touch, motor control (moving parts of the body) and the parts of the brain that control speech.

Signs and symptoms
Warning symptoms
Warning symptoms also called prodrome symptoms often happen before a migraine attack.

Sleepiness
Fatigue
Depression (feeling sad), euphoria (feeling very happy) or irritability
Restlessness
Excessive (too much) yawning
Food cravings especially for sweet or salty foods or loss of appetite
Increased thirst
Diarrhea
Nausea
Bloating: the body retains (keeps) too much water
Neck stiffness
Talkativeness (talking too much)
Feeling light-headed
Uterine pain and cramping

Headache
A pounding throbbing headache with the pain being on one side of the head (unilateral). The side of the head that has the pain changes from one headache to the next.

Associated conditions
Often, having one medical condition makes it more likely a person will also have one or more other medical or psychiatric disorders. These other disorders are the "comorbid disorders" or "comorbidities". There are various comorbid medical and psychiatric conditions associated with migraines. The treatment and prognosis (if a disease gets better, worse or stays the same over time) of migraine is affected by the comorbid disorders which may be present and/or the chance of getting comorbid disorders.
Asthma – Premenstrual asthma (PMA): is when asthma symptoms get worse during the premenstrual period. This condition may affect up to 40% of females with asthma. For a diagnosis of PMA to be made it is necessary to have a detailed history of the timing of menstrual cycles along with asthma symptoms experienced, and the peak expiratory flow rate (PMA may cause the PEF to be lowered in the premenstrual period). It is helpful in making a diagnosis to keep a diary of symptoms and peak expiratory flow (PEF) rates.
Raynauds disease: is a circulatory disorder in which the smaller arteries that supply blood to the extremities – most often the hands, but it may also affect the, toes, the tip of the nose and the ears – become narrower reducing blood flow </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 Irritant contact dermatitis and can you explain it in depth? [/INST] Irritant contact dermatitis is a form of contact dermatitis that can be divided into forms caused by chemical irritants and those caused by physical irritants.

Chemical
Chemical irritant contact dermatitis is either acute or chronic, which is usually associated with strong and weak irritants respectively. The following definition is provided by Mathias and Maibach (1978): The mechanism of action varies. Detergents, surfactants, extremes of pH, and organic solvents all directly affecting the barrier properties of the epidermis. These effects include removing fat emulsion, defatting of dermal lipids, inflicting cellular damage on the epithelium, and increasing the transepidermal water loss by damaging the horny layer water-binding mechanisms and damaging the DNA, which causes the layer to thin </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 Scarring hair loss and can you explain it in depth? [/INST] Scarring hair loss, also known as cicatricial alopecia, is the loss of hair which is accompanied with scarring. This is in contrast to non scarring hair loss.
It can be caused by a diverse group of rare disorders that destroy the hair follicle, replace it with scar tissue, and cause permanent hair loss.  A variety of distributions are possible. In some cases, hair loss is gradual, without symptoms, and is unnoticed for long periods. In other cases, hair loss is associated with severe itching, burning and pain and is rapidly progressive. The inflammation that destroys the follicle is below the skin surface and there is usually no "scar" seen on the scalp. Affected areas of the scalp may show little signs of inflammation, or have redness, scaling, increased or decreased pigmentation, pustules, or draining sinuses. Scarring hair loss occurs in otherwise healthy men and women of all ages and is seen worldwide.

Signs and symptoms
It is important to continue to watch for symptoms and signs of active disease during and after treatment to ensure that the disease is responding adequately and has not re-activated after therapy has been discontinued. Response to therapy may be indicated by the resolution of scalp symptoms such as itching, pain, tenderness, or burning, by improvement in the signs of scalp inflammation such as decreased redness, scaling or pustules, and by halting or slowing the progression of hair loss. A dermatologist can document and monitor a patients cicatricial alopecia using these guidelines, and with the pull test. Photographs of the scalp may be useful in monitoring the course of the disease and response to treatment.

Causes
The cause of the various cicatricial alopecias is poorly understood. However, all cicatricial alopecias involve inflammation directed at the upper part of the hair follicle where the stem cells and sebaceous gland (oil gland) are located. If the stem cells and sebaceous gland are destroyed, there is then no possibility for regeneration of the hair follicle, and permanent hair loss results.
Cicatricial alopecias are not contagious.  In general, cicatricial alopecias are not associated with other illnesses, and usually occur in otherwise healthy men and women.
Cicatricial alopecias affect both men and women, most commonly adults, although all ages may be affected. Epidemiologic studies have not been performed to determine the incidence of cicatricial alopecias. In general, they are not common.
The majority of patients with cicatricial alopecia have no family history of a similar condition. The one exception is Central centrifugal cicatricial alopecia, which primarily affects women of African ancestry and may occur in several women in the same family.  While it is possible to have more than one type of hair loss condition, non-scarring forms of hair loss do not turn into scarring forms of hair loss.

Diagnosis
A scalp biopsy is essential for the diagnosis of cicatricial alopecia and is the necessary first step, as it can be hard to know the diagnosis for sure without a biopsy. Findings of the scalp biopsy, including the type of inflammation present, location and amount of inflammation, and other changes in the scalp, are necessary to diagnose the type of cicatricial alopecia, to determine the degree of activity, and to select appropriate therapy.
Clinical evaluation of the scalp is also important. Symptoms of itching, burning, pain, or tenderness usually signal ongoing activity. Signs of scalp inflammation include redness, scaling, and pustules. However, in some cases there are few symptoms or signs and only the scalp biopsy demonstrates the active inflammation. The overall extent and pattern of hair loss is noted and sometimes photographed for future comparison. A hair "pull test" is performed to see if growing, or anagen, where hairs are pulled out easily. The pulled hairs are mounted on a slide and the hair bulbs are viewed with a light microscope to determine how many are growing hairs and how many are resting hairs. In addition, if pustules are present, cultures are taken to identify which microbes, if any, may be contributing to the inflammation. A thorough evaluation that includes all of these parameters is important in diagnosing a cicatricial alopecia and in identifying features in individual patients that will help the selection of therapy.
New diagnostic techniques, such as trichoscopy may be used for non-invasive differential diagnosis of cicatricial alopecia.
Diagnosis and treatment of cicatricial alopecias is often challenging. For this reason, it is helpful to be evaluated by a dermatologist with a special interest or expertise in scalp and hair disorders, and who is familiar with current diagnostic methods and therapies.

Classification
Cicatricial alopecias are classified as primary or secondary. This discussion is confined to the primary cicatricial alopecias in which the hair follicle is the target of the destructive inflammatory process. In secondary cicatricial alopecias, destruction of the hair follicle is incidental to a non-follicle-directed process or external injury, such as severe infections, burns, radiation, tumors, or traction.
Primary cicatricial alopecias are further classified by the type of inflammatory cells that destroy the hair follicle during the active stage of the disease. The inflammation may predominantly involve lymphocytes or neutrophils. Cicatricial alopecias that predominantly involve lymphocytic inflammation include lichen planopilaris, frontal fibrosing alopecia, central centrifugal alopecia, and pseudopelade (Brocq). Cicatricial alopecias that are due to predominantly neutrophilic inflammation include folliculitis decalvans, tufted folliculitis, and dissecting cellulitis of the scalp. Sometimes the inflammation shifts from a predominantly neutrophilic process to a lymphocytic process. A cicatricial alopecia with a mixed inflammatory infiltrate is folliculitis keloidalis.

Treatment
As mentioned above, primary cicatricial alopecias are classified by the predominant type of inflammatory cells that attack the hair follicles, such as lymphocytes, neutrophils, or mixed inflammatory cells. Treatment strategies are different for each subtype and detailed treatment options are beyond the scope of this discussion. However, certain general principals are reviewed below.
Treatment of the lymphocytic group of cicatricial alopecias (including lichen planopilaris, frontal fibrosing alopecia, central centrifugal alopecia, and pseudopelade (Brocq) involves use of anti-inflammatory medications. The goal of treatment is to decrease or eliminate the lymphocytic inflammatory cells that are attacking and destroying the hair follicle. Oral medications may include hydroxychloroquine, doxycycline, mycophenolate mofetil, cyclosporine, or corticosteroids. Topical medications may include corticosteroids, tacrolimus,  pimecrolimus, or Derma-Smoothe/FS scalp oil. Triamcinolone acetonide, a corticosteroid, may be injected into inflamed, symptomatic areas of the scalp.
Treatment of the neutrophilic group of cicatricial alopecias (folliculitis decalvans, tufted folliculitis) is directed at eliminating the predominant pathogenic microbes that are invariably involved in the inflammatory process. Oral antibiotics are the mainstay of therapy, and topical antibiotics may be used to supplement the oral antibiotics. In dissecting cellulitis, pathogenic microbes are not usually present. Isotretinoin in small doses may be helpful in treating dissecting cellulitis.Treatment of the mixed group of cicatricial alopecias (folliculitis keloidalis) may include antimicrobials, isotretinoin, and anti-inflammatory medications.
Patients are recommended to discuss any treatment with a dermatologist, who also explains potential side effects, as well as laboratory tests that are needed before starting treatment and sometimes are monitored during treatment.
The course of cicatricial alopecia is usually prolonged </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 Conductive hearing loss and can you explain it in depth? [/INST] Conductive hearing loss (CHL) occurs when there is a problem transferring sound waves anywhere along the pathway through the outer ear, tympanic membrane (eardrum), or middle ear (ossicles). If a conductive hearing loss occurs in conjunction with a sensorineural hearing loss, it is referred to as a mixed hearing loss. Depending upon the severity and nature of the conductive loss, this type of hearing impairment can often be treated with surgical intervention or pharmaceuticals to partially or, in some cases, fully restore hearing acuity to within normal range. However, cases of permanent or chronic conductive hearing loss may require other treatment modalities such as hearing aid devices to improve detection of sound and speech perception.

Causes
Common causes of conductive hearing loss include:

External ear
Cerumen (earwax) or foreign body in the external auditory canal
Otitis externa, infection or irritation of the outer ear
Exostoses, abnormal growth of bone within the ear canal
Tumor of the ear canal
Congenital stenosis or atresia of the external auditory canal (narrow or blocked ear canal).
Ear canal stenosis & atresia can exist independently or may result from congenital malformations of the auricle such as microtia or anotia.
Acquired stenosis (narrowing) of the external auditory canal following surgery or radiotherapy

Middle ear
Fluid accumulation is the most common cause of conductive hearing loss in the middle ear, especially in children. Major causes are ear infections or conditions that block the eustachian tube, such as allergies or tumors. Blocking of the eustachian tube leads to decreased pressure in the middle ear relative to the external ear, and this causes decreased motion of both the ossicles and the tympanic membrane.
Acute or Serous otitis media
Chronic suppurative otitis media (CSOM)
Perforated eardrum
Tympanosclerosis or scarring of the eardrum
Cholesteatoma
Eustachian Tube Dysfunction, inflammation or mass within the nasal cavity, middle ear, or eustachian tube itself
Otosclerosis, abnormal growth of bone in or near the middle ear
Middle ear tumour
Ossicular discontinuity as a consequence of infection or temporal bone trauma
Congenital malformation of the ossicles. This can be an isolated phenomenon or can occur as part of a syndrome where development of the 1st and 2nd branchial arches is seen such as in Goldenhar syndrome, Treacher Collins syndrome, branchio-oto-renal syndrome etc.
Barotrauma unequal air pressures in the external and middle ear. This can temporarily occur, for example, by the environmental pressure changes as when shifting altitude, or inside a train going into a tunnel. It is managed by any of various methods of ear clearing manoeuvres to equalize the pressures, like swallowing, yawning, or the Valsalva manoeuvre. More severe barotrauma can lead to middle ear fluid or even permanent sensorineural hearing loss.

Inner ear
Third window effect caused by:

Superior canal dehiscence – which may require surgical correction.
Enlarged vestibular aqueduct
Labyrinthine fistula

Presentation
Conductive hearing loss makes all sounds seem faint or muffled. The hearing loss is usually worse in lower frequencies.
Congenital conductive hearing loss is identified through newborn hearing screening or may be identified because the baby has microtia or other facial abnormalities. Conductive hearing loss developing during childhood is usually due to otitis media with effusion and may present with speech and language delay or difficulty hearing. Later onset of conductive hearing loss may have an obvious cause such as an ear infection, trauma or upper respiratory tract infection or may have an insidious onset related to chronic middle ear disease, otosclerosis or a tumour of the naso-pharynx. Earwax is a very common cause of a conductive hearing loss which may present suddenly when the wax blocks sound from getting through the external ear canal to the middle and inner ear.

Diagnosis
Diagnosis requires a detailed history, local examination of the ear, nose, throat and neck, and detailed hearing tests. In children a more detailed examination may be required if the hearing loss is congenital.

Otoscopy
Examination of the external ear canal and ear drum is important and may help identify problems located in the outer ear up to the tympanic membrane.

Differential testing
For basic screening, a conductive hearing loss can be identified using the Rinne test with a 256 Hz tuning fork. The Rinne test, in which a patient is asked to say whether a vibrating tuning fork is heard more loudly adjacent to the ear canal (air conduction) or touching the bone behind the ear (bone conduction), is negative indicating that bone conduction is more effective that air conduction. A normal, or positive, result, is when air conduction is more effective than bone conduction.
With a one-sided conductive component the combined use of both the Weber and Rinne tests is useful. If the Weber test is used, in which a vibrating tuning fork is touched to the midline of the forehead, the person will hear the sound more loudly in the affected ear because background noise does not mask the hearing on this side.
The following table compares sensorineural hearing loss to conductive:

Tympanometry
Tympanometry, or acoustic immitance testing, is a simple objective test of the ability of the middle ear to transmit sound waves from the outer ear to the middle ear and to the inner ear. This test is usually abnormal with conductive hearing loss.  A type B tympanogram reveals a flat response, due to fluid in the middle ear (otitis media), or an eardrum perforation. A type C tympanogram indicates negative middle ear pressure, which is commonly seen in eustachian tube dysfunction. A type As tympanogram indicates a shallow compliance of the middle ear, which is commonly seen in otosclerosis.

Audiometry
Pure tone audiometry, a standardized hearing test over a set of frequencies from 250 Hz to 8000 Hz, may be conducted by a medical doctor, audiologist or audiometrist, with the result plotted separately for each ear on an audiogram. The shape of the plot reveals the degree and nature of hearing loss, distinguishing conductive hearing loss from other kinds of hearing loss </s>