<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 Guillain–Barré syndrome and can you explain it in depth? [/INST] Guillain–Barré syndrome (GBS) is a rapid-onset muscle weakness caused by the immune system damaging the peripheral nervous system. Typically, both sides of the body are involved, and the initial symptoms are changes in sensation or pain often in the back along with muscle weakness, beginning in the feet and hands, often spreading to the arms and upper body. The symptoms may develop over hours to a few weeks. During the acute phase, the disorder can be life-threatening, with about 15% of people developing weakness of the breathing muscles and, therefore, requiring mechanical ventilation. Some are affected by changes in the function of the autonomic nervous system, which can lead to dangerous abnormalities in heart rate and blood pressure.Although the cause is unknown, the underlying mechanism involves an autoimmune disorder in which the bodys immune system mistakenly attacks the peripheral nerves and damages their myelin insulation. Sometimes this immune dysfunction is triggered by an infection or, less commonly, by surgery, and rarely, by vaccination. The diagnosis is usually based on the signs and symptoms through the exclusion of alternative causes and supported by tests such as nerve conduction studies and examination of the cerebrospinal fluid. There are a number of subtypes based on the areas of weakness, results of nerve conduction studies, and the presence of certain antibodies. It is classified as an acute polyneuropathy.In those with severe weakness, prompt treatment with intravenous immunoglobulins or plasmapheresis, together with supportive care, will lead to good recovery in the majority of cases. Recovery may take weeks to years, with about a third having some permanent weakness. Globally, death occurs in approximately 7.5% of those affected. Guillain–Barré syndrome is rare, at 1 or 2 cases per 100,000 people every year. Both sexes and all parts of the world have similar rates of disease.The syndrome is named after the French neurologists Georges Guillain and Jean Alexandre Barré, who, together with French physician André Strohl, described the condition in 1916.

Signs and symptoms
The first symptoms of Guillain–Barré syndrome are numbness, tingling, and pain, alone or in combination. This is followed by weakness of the legs and arms that affects both sides equally and worsens over time. The weakness can take half a day to over two weeks to reach maximum severity, and then becomes steady. In one in five people, the weakness continues to progress for as long as four weeks. The muscles of the neck may also be affected, and about half experience involvement of the cranial nerves that supply the head and face; this may lead to weakness of the muscles of the face, swallowing difficulties and sometimes weakness of the eye muscles. In 8%, the weakness affects only the legs (paraplegia or paraparesis). Involvement of the muscles that control the bladder and anus is unusual. In total, about a third of people with Guillain–Barré syndrome continue to be able to walk. Once the weakness has stopped progressing, it persists at a stable level ("plateau phase") before improvement occurs. The plateau phase can take between two days and six months, but the most common duration is a week. Pain-related symptoms affect more than half, and include back pain, painful tingling, muscle pain, and pain in the head and neck relating to irritation of the lining of the brain.Many people with Guillain–Barré syndrome have experienced the signs and symptoms of an infection in the 3–6 weeks before the onset of the neurological symptoms. This may consist of upper respiratory tract infection (rhinitis, sore throat), or diarrhea.

In children, particularly those younger than six years old, the diagnosis can be difficult and the condition is often initially mistaken (sometimes for up to two weeks) for other causes of pains and difficulty walking, such as viral infections, or bone and joint problems.On neurological examination, characteristic features are the reduced strength of muscles and reduced or absent tendon reflexes (hypo- or areflexia, respectively). However, a small proportion have normal reflexes in affected limbs before developing areflexia, and some may have exaggerated reflexes. In the Miller Fisher variant of Guillain–Barré syndrome (see below), a triad of weakness of the eye muscles, abnormalities in coordination, as well as absent reflexes can be found. The level of consciousness is normally unaffected in Guillain–Barré syndrome, but the Bickerstaff brainstem encephalitis subtype may feature drowsiness, sleepiness, or coma.

Respiratory failure
A quarter of all people with Guillain–Barré syndrome develop weakness of the breathing muscles leading to respiratory failure, the inability to breathe adequately to maintain healthy levels of oxygen, and/or carbon dioxide in the blood. This life-threatening scenario is complicated by other medical problems such as pneumonia, severe infections, blood clots in the lungs, and bleeding in the digestive tract in 60% of those who require artificial ventilation.

Autonomic dysfunction
The autonomic or involuntary nervous system, which is involved in the control of body functions such as heart rate and blood pressure, is affected in two-thirds of people with Guillain–Barré syndrome, but the impact is variable. Twenty percent may experience severe blood-pressure fluctuations and irregularities in the heart beat, sometimes to the point that the heart beat stops and requires pacemaker-based treatment. Other associated problems are abnormalities in perspiration and changes in the reactivity of the pupils. Autonomic nervous system involvement can affect even those who do not have severe muscle weakness.

Causes
Infection onset
Two-thirds of people with Guillain–Barré syndrome have experienced an infection before the onset of the condition. Most commonly, these are episodes of gastroenteritis or a respiratory tract infection. In many cases, the exact nature of the infection can be confirmed. Approximately 30% of cases are provoked by Campylobacter jejuni bacteria, which cause diarrhea. A further 10% are attributable to cytomegalovirus (CMV, HHV-5). Despite this, only very few people with Campylobacter or CMV infections develop Guillain–Barré syndrome (0.25–0.65 per 1000 and 0.6–2.2 per 1000 episodes, respectively). The strain of Campylobacter involved may determine the risk of GBS; different forms of the bacteria have different lipopolysaccharides on their surface, and some may induce illness (see below) while others will not.Links between other infections and GBS are less certain. Two other herpes viruses (Epstein–Barr virus/HHV-4 and varicella zoster virus/HHV-3) and the bacterium Mycoplasma pneumoniae have been associated with GBS. GBS is known to occur after influenza, and influenza vaccination has been demonstrated to be associated with a reduced risk. The tropical flaviviral infections dengue fever and Zika virus have also been associated with episodes of GBS. Previous hepatitis E virus infection has been found to be more common in people with GBS.

Vaccine onset
An increased incidence of Guillain–Barré syndrome followed influenza immunization that followed the 1976 swine flu outbreak (H1N1 A/NJ/76); 8.8 cases per million (0.0088 per 1000) recipients developed it as a complication. GBS cases occurred in 362 patients during the 6 weeks after influenza vaccination of 45 million persons, an 8.8-fold increase over normal rates. The 1976 swine flu vaccination-induced GBS was an outlier; small increases in incidence have been observed in subsequent vaccination campaigns, but not to the same extent. The 2009 flu pandemic vaccine against pandemic swine flu virus H1N1/PDM09 did not cause a significant increase in cases. In fact, "studies found a small increase of approximately 1 case per million vaccines above the baseline rate, which is similar to that observed after administration of seasonal influenza vaccines over the past several years." The benefits to the population as a whole of vaccination in preventing influenza outweigh the small risks to individuals of that group of GBS after vaccination. Natural influenza infection is a stronger risk factor for the development of GBS than is influenza vaccination and the vaccination reduced the risk of GBS overall by lowering the risk of catching influenza.In the United States, GBS after seasonal influenza vaccination is listed on the federal governments vaccine injury table. On March 24, 2021, after reviewing several post-marketing observational studies, where an increased risk of Guillain–Barré syndrome was observed after 42 days following vaccination with the Zoster vaccine Shingrix, the FDA required safety label changes from the manufacturer GlaxoSmithKline to include warnings for risk of Guillain–Barré syndrome.

COVID-19 infection or vaccine related
GBS has been reported in association with COVID-19, and may be a potential neurological complication of the disease.
GBS has been reported as a very rare side effect of the Janssen and the Oxford–AstraZeneca COVID-19 vaccine for COVID-19 and European Medicines Agency (EMA) had issued warning to the patients and healthcare providers. The incidence of GBS following the vaccination with the Oxford-AstraZeneca vaccine was originally reported as being lower than the incidence of GBS following a COVID-19 infection. More recent studies, however, found no measurable link between COVID-19 infection and GBS, while correlations with a first dose of AstraZeneca or Janssen vaccines were still positive.COVID-19 has been reported as causing peripheral neuropathy and more recently some evidence of aggravation of autoimmune disorders including GBS. Some studies are now finding Parkinsons Disease is more common in infection survivors.

Drug induced
Zimelidine, an antidepressant, had a very favorable safety profile but as a result of rare case reports of Guillain–Barré syndrome was withdrawn from the market.

Mechanism
The nerve dysfunction in Guillain–Barré syndrome is caused by an immune attack on the nerve cells of the peripheral nervous system and their support structures. The nerve cells have their body (the soma) in the spinal cord and a long projection (the axon) that carries electrical nerve impulses to the neuromuscular junction, where the impulse is transferred to the muscle. Axons are wrapped in a sheath of Schwann cells that contain myelin. Between Schwann cells are gaps (nodes of Ranvier) where the axon is exposed. Different types of Guillain–Barré syndrome feature different types of immune attack. The demyelinating variant (AIDP, see below) features damage to the myelin sheath by white blood cells (T lymphocytes and macrophages); this process is preceded by activation of a group of blood proteins known as complement. In contrast, the axonal variant is mediated by IgG antibodies and complement against the cell membrane covering the axon without direct lymphocyte involvement.Various antibodies directed at nerve cells have been reported in Guillain–Barré syndrome. In the axonal subtype, these antibodies have been shown to bind to gangliosides, a group of substances found in peripheral nerves. A ganglioside is a molecule consisting of ceramide bound to a small group of hexose-type sugars and containing various numbers of N-acetylneuraminic acid groups. The key four gangliosides against which antibodies have been described are GM1, GD1a, GT1a, and GQ1b, with different antiganglioside antibodies being associated with particular features; for instance, GQ1b antibodies have been linked with Miller Fisher variant GBS and related forms including Bickerstaff encephalitis. The production of these antibodies after an infection probably is the result of molecular mimicry, where the immune system is reacting to microbial substances, but the resultant antibodies also react with substances occurring naturally in the body. After a Campylobacter infection, the body produces antibodies of the IgA class; only a small proportion of people also produce IgG antibodies against bacterial substance cell wall substances (e.g. lipooligosaccharides) that cross react with human nerve cell gangliosides. It is not currently known how this process escapes central tolerance to gangliosides, which is meant to suppress the production of antibodies against the bodys own substances. Not all antiganglioside antibodies cause disease, and it has recently been suggested that some antibodies bind to more than one type of epitope simultaneously (heterodimeric binding) and that this determines the response. Furthermore, the development of pathogenic antibodies may depend on the presence of other strains of bacteria in the bowel.It has been suggested that a poor injection technique may also cause a direct injury to the axillary nerves adjacent to the injection site in deltoid muscle that may lead to peripheral neuropathy. The consequent vaccine transfection and translation in the nerves may spur an immune response against nerve cells potentially causing an autoimmune nerve damage, leading to conditions like Guillain–Barré syndrome.

Diagnosis
The diagnosis of Guillain–Barré syndrome depends on findings such as rapid development of muscle paralysis, absent reflexes, absence of fever, and absence of a likely cause. Cerebrospinal fluid analysis (through a lumbar spinal puncture) and nerve conduction studies are supportive investigations commonly performed in the diagnosis of GBS. Testing for antiganglioside antibodies is often performed, but their contribution to diagnosis is usually limited. Blood tests are generally performed to exclude the possibility of another cause for weakness, such as a low level of potassium in the blood. An abnormally low level of sodium in the blood is often encountered in Guillain–Barré syndrome. This has been attributed to the inappropriate secretion of antidiuretic hormone, leading to relative retention of water.In many cases, magnetic resonance imaging of the spinal cord is performed to distinguish between Guillain–Barré syndrome and other conditions causing limb weakness, such as spinal cord compression. If an MRI scan shows enhancement of the nerve roots, this may be indicative of GBS. In children, this feature is present in 95% of scans, but it is not specific to Guillain–Barré syndrome, so other confirmation is also needed.

Spinal fluid
Cerebrospinal fluid envelops the brain and the spine, and lumbar puncture or spinal tap is the removal of a small amount of fluid using a needle inserted between the lumbar vertebrae. Characteristic findings in Guillain–Barré syndrome are an elevated protein level, usually greater than 0.55 g/L, and fewer than 10 white blood cells per cubic millimeter of fluid ("albuminocytological dissociation"). This pattern distinguishes Guillain–Barré syndrome from other conditions (such as lymphoma and poliomyelitis) in which both the protein and the cell count are elevated. Elevated CSF protein levels are found in approximately 50% of patients in the first 3 days after onset of weakness, which increases to 80% after the first week.Repeating the lumbar puncture during the disease course is not recommended. The protein levels may rise after treatment has been administered.

Neurophysiology
Directly assessing nerve conduction of electrical impulses can exclude other causes of acute muscle weakness, as well as distinguish the different types of Guillain–Barré syndrome. Needle electromyography (EMG) and nerve conduction studies may be performed. In the first two weeks, these investigations may not show any abnormality. Neurophysiology studies are not required for the diagnosis.Formal criteria exist for each of the main subtypes of Guillain–Barré syndrome (AIDP and AMAN/AMSAN, see below), but these may misclassify some cases (particularly where there is reversible conduction failure) and therefore changes to these criteria have been proposed. Sometimes, repeated testing may be helpful.

Clinical subtypes
A number of subtypes of Guillain–Barré syndrome are recognized. Despite this, many people have overlapping symptoms that can make the classification difficult in individual cases. All types have partial forms. For instance, some people experience only isolated eye-movement or coordination problems; these are thought to be a subtype of Miller Fisher syndrome and have similar antiganglioside antibody patterns.
Other diagnostic entities are often included in the spectrum of Guillain–Barré syndrome. Bickerstaffs brainstem encephalitis (BBE), for instance, is part of the group of conditions now regarded as forms of Miller Fisher syndrome (anti-GQ1b antibody syndrome), as well as a related condition labelled "acute ataxic hypersomnolence" where coordination problems and drowsiness are present but no muscle weakness can be detected. BBE is characterized by the rapid onset of ophthalmoplegia, ataxia, and disturbance of consciousness, and may be associated with absent or decreased tendon reflexes and as well as Babinskis sign. The course of the disease is usually monophasic, but recurrent episodes have been reported. MRI abnormalities in the brainstem have been reported in 11%.Whether isolated acute sensory loss can be regarded as a form of Guillain–Barré syndrome is a matter of dispute; this is a rare occurrence compared to GBS with muscle weakness but no sensory symptoms.

Treatment
Immunotherapy
Plasmapheresis and intravenous immunoglobulins (IVIG) are the two main immunotherapy treatments for GBS. Plasmapheresis attempts to reduce the bodys attack on the nervous system by filtering antibodies out of the bloodstream. Similarly, administration of IVIG neutralizes harmful antibodies and inflammation. These two treatments are equally effective, but a combination of the two is not significantly better than either alone. Plasmapheresis speeds recovery when used within four weeks of the onset of symptoms. IVIG works as well as plasmapheresis when started within two weeks of the onset of symptoms, and has fewer complications. IVIG is usually used first because of its ease of administration and safety; the risks include occasionally causing liver inflammation, or in rare cases, kidney failure. Glucocorticoids alone have not been found to be effective in speeding recovery and could potentially delay recovery.

Respiratory failure
Respiratory failure may require intubation of the trachea and breathing support through mechanical ventilation, generally on an intensive care unit. The need for ventilatory support can be anticipated by measurement of two spirometry-based breathing tests: the forced vital capacity (FVC) and the negative inspiratory force (NIF). An FVC of less than 15 mL per kilogram body weight or an NIF of less than 60 cmH2O are considered markers of severe respiratory failure.

Pain
While pain is common in people with Guillain–Barré syndrome, studies comparing different types of pain medication are insufficient to make a recommendation as to which should be used.

Rehabilitation
Following the acute phase, around 40% of people require intensive rehabilitation with the help of a multidisciplinary team to focus on improving activities of daily living (ADLs). Studies into the subject have been limited, but it is likely that intensive rehabilitation improves long-term symptoms. Teams may include physical therapists, occupational therapists, speech language pathologists, social workers, psychologists, other allied health professionals and nurses. The team usually works under the supervision of a neurologist or rehabilitation physician directing treatment goals.Physiotherapy interventions include strength, endurance, and gait training with graduated increases in mobility, maintenance of posture and alignment as well as joint function. Occupational therapy aims to improve everyday function with domestic and community tasks as well as driving and work. Home modifications, gait aids, orthotics, and splints may be provided. Speech-language pathology input may be required in those with speech and swallowing problems, as well as to support communication in those who require ongoing breathing support (often through a tracheostomy). Nutritional support may be provided by the team and by dietitians. Psychologists may provide counseling and support. Psychological interventions may also be required for anxiety, fear, and depression.

Prognosis
Guillain–Barré syndrome can lead to death as a result of many complications: severe infections, blood clots, and cardiac arrest likely due to autonomic neuropathy. Despite optimum care, this occurs in about 5% of cases.There is a variation in the rate and extent of recovery. The prognosis of Guillain–Barré syndrome is determined mainly by age (those over 40 may have a poorer outcome), and by the severity of symptoms after two weeks. Furthermore, those who experienced diarrhea before the onset of the disease have a worse prognosis. On the nerve conduction study, the presence of conduction block predicts poorer outcome at 6 months. In those who have received intravenous immunoglobulins, a smaller increase in IgG in the blood two weeks after administration is associated with poorer mobility outcomes at six months than those whose IgG level increased substantially. If the disease continues to progress beyond four weeks, or there are multiple fluctuations in the severity (more than two in eight weeks), the diagnosis may be chronic inflammatory demyelinating polyneuropathy, which is treated differently.In research studies, the outcome from an episode of Guillain–Barré syndrome is recorded on a scale from 0 to 6, where 0 denotes completely healthy; 1 very minor symptoms but able to run; 2 able to walk but not to run; 3 requiring a stick or other support; 4 confined to bed or chair; 5 requiring long-term respiratory support; 6 death.The health-related quality of life (HRQL) after an attack of Guillain–Barré syndrome can be significantly impaired. About a fifth are unable to walk unaided after six months, and many experience chronic pain, fatigue and difficulty with work, education, hobbies and social activities. HRQL improves significantly in the first year.

Epidemiology
In Western countries, the number of new episodes per year has been estimated to be between 0.89 and 1.89 cases per 100,000 people. Children and young adults are less likely to be affected than the elderly: the relative risk increases by 20% for every decade of life. Men are more likely to develop Guillain–Barré syndrome than women; the relative risk for men is 1.78 compared to women.The distribution of subtypes varies between countries. In Europe and the United States, 60–80% of people with Guillain–Barré syndrome have the demyelinating subtype (AIDP), and AMAN affects only a small number (6–7%). In Asia and Central and South America, that proportion is significantly higher (30–65%). This may be related to the exposure to different kinds of infection, but also the genetic characteristics of that population. Miller Fisher variant is thought to be more common in Southeast Asia.

History
Jean-Baptiste Octave Landry first described the disorder in 1859. In 1916, Georges Guillain, Jean Alexandre Barré, and André Strohl diagnosed two soldiers with the illness and described the key diagnostic abnormality—albuminocytological dissociation—of increased spinal fluid protein concentration but a normal cell count.C. Miller Fisher described the variant that bears his name in 1956. British neurologist Edwin Bickerstaff described the encephalitis type in 1951 and made further contributions with another paper in 1957. Guillain had reported on some of these features before their full description in 1938. Further subtypes have been described since then, such as the form featuring pure ataxia and the type causing pharyngeal-cervical-brachial weakness. The axonal subtype was first described in 1986.Diagnostic criteria were developed in the late 1970s after the series of cases associated with swine flu vaccination. These were refined in 1990. The case definition was revised by the Brighton Collaboration for vaccine safety in 2009, but is mainly intended for research. Plasma exchange was first used in 1978, and its benefit was confirmed in larger studies in 1985 </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 Phacodonesis 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 Trisomy 22 and can you explain it in depth? [/INST] Trisomy 22 is a chromosomal disorder in which  three copies of chromosome 22 are present rather than two. It is a frequent cause of spontaneous abortion during the first trimester of pregnancy. Progression to the second trimester and live birth are rare. This disorder is found in individuals with an extra copy or a variation of chromosome 22 in some or all cells of their bodies.

Associated disorders
Many kinds of disorders are associated with trisomy 22:

Emanuel syndrome is named after the genetic contributions made by researcher Dr. Beverly Emanuel. This condition is assigned to individuals born with an unbalanced 11/22 translocation. That is, a fragment of chromosome 11 is moved, or translocated, to chromosome 22.
22q11 deletion syndrome is a rare condition which occurs in about one in 4000 births. This condition is identified when a band in the q11.2 section of the arm of chromosome 22 is missing or deleted. This condition has several different names: 22q11.2 deletion syndrome, velocardiofacial syndrome, DiGeorge syndrome, conotruncal anomaly face syndrome, Opitz G/BBB syndrome, and Cayler cardiofacial syndrome. The effects of this disorder are different in each individual, but similarities exist, such as heart defects, immune system problems, a distinctive facial appearance, learning challenges, cleft palate, hearing loss, kidney problems, hypocalcemia, and sometimes psychiatric issues.
22q11 microduplication syndrome is the opposite of the 22q11 deletion syndrome; in this condition, a band of q.11.2 section of chromosome 22 is duplicated. Individuals carrying this deficiency are relatively "normal", as in they do not possess any major birth defects or major medical illnesses. This microduplication is more common than the deletion; this might relate to the milder phenotype of the individuals.
22q13 deletion syndrome (Phelan–McDermid syndrome) is a condition caused by the deletion of the tip of the q arm on chromosome 22. Most individuals with this disorder experience cognitive delays, low muscle tone, and sleeping, eating, and behavioural issues.
Chromosome ring 22 is a rare disorder caused by the break and rejoining of both ends of chromosome 22, forming a ring. The effects on the individual with this disorder are dependent on the amount of genetic information lost during the process. Major characteristics for this disorder are intellectual disability, muscle weakness, and lack of coordination.
Cat eye syndrome (Schmid Fraccaro syndrome) is a condition caused by a partial trisomy or tetrasomy in chromosome 22. A small extra chromosome is found, made up of the top half of chromosome 22 and a portion of the q arm at the q11.2 break. This chromosome can be found three or four times. This syndrome is referred as "cat eye" due to the eye appearance of reported affected individuals who have coloboma of the iris, but this feature is only seen in about half of the cases.
Mosaic trisomy 22 is a disorder in which an extra chromosome 22 is found only in some cells of the body. The severity of each case is determined by the number of cells with this extra copy </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 Aortopulmonary window 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 Carnosinemia and can you explain it in depth? [/INST] Carnosinemia is a rare autosomal recessive metabolic disorder caused by a deficiency of carnosinase, a dipeptidase (a type of enzyme that splits dipeptides into their two amino acid constituents).Carnosine is a dipeptide composed of beta-alanine and histidine, and is found in skeletal muscle and cells of the nervous system. This disorder results in an excess of carnosine in the urine, cerebrospinal fluid, blood, and nervous tissue. Neurological disorders associated with a deficiency of carnosinase, and the resulting carnosinemia ("carnosine in the blood") are common.

Symptoms and signs
A variety of neurological symptoms have been associated with carnosinemia. They include: hypotonia, developmental delay, intellectual disability, degeneration of axons, sensory neuropathy, tremors, demyelinization, gray matter anomalies, myoclonic seizures, and loss of purkinje fibers.

Genetics
The gene for carnosinase is located on chromosome 18, an autosome. The carnosine dipeptidase-1 gene (CNDP1) controls tissue and serum carnosinase. Mutations in CNDP1 are  responsible for carnosinase deficiency, resulting in carnosinemia.Carnosinemia is an autosomal recessive disorder, which means the defective gene is located on an autosome, and two copies of the defective gene - one from each parent - are required to inherit the disorder </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 Tenosynovitis and can you explain it in depth? [/INST] Tenosynovitis is the inflammation of the fluid-filled sheath (called the synovium) that surrounds a tendon, typically leading to joint pain, swelling, and stiffness. Tenosynovitis can be either infectious or noninfectious. Common clinical manifestations of noninfectious tenosynovitis include de Quervain tendinopathy and stenosing tenosynovitis (more commonly known as trigger finger)

Signs and symptoms
Infectious tenosynovitis occurs between 2.5% and 9.4% of all hand infections. Kanavels cardinal signs is used to diagnose infectious tenosynovitis. They are: tenderness to touch along the flexor aspect of the finger, fusiform enlargement of the affected finger, the finger being held in slight flexion at rest, and severe pain with passive extension. Fever may also be present but is uncommon.

Pathogenesis
Infectious tenosynovitis is the infection of closed synovial sheaths in the flexor tendons of the fingers. It is usually caused by trauma, but bacteria can spread from other sites of the body. Although tenosynovitis usually affects the flexor tendon of the fingers, the disease can also affect the extensor tendons occasionally. The clinical presentation is therefore as acute infection following trauma. The infection can be mono- or polymicrobial and can vary depending on the nature of the trauma. The most common pathogenic agent is Staphylococcus aureus introduced from the skin. Other bacteria linked to infectious tenosynovitis include Pasteurella multocida (associated with animal bites), Eikenella spp. (associated with IV drug use), and Mycobacterium marinum (associated with wounds exposed to fresh or salt water). Additionally, sexually active patients are at risk for hematogenous spread due to Neisseria gonorrhoeae (see infectious arthritis).
Common noninfectious tenosynovitis are: stenosing tenosynovitis, intersection syndrome, extensor pollicis longus (EPL) tenosynovitis, de Quervains and fourth compartment tenosynovitis.

Diagnosis
Diagnosis of tenosynovitis is typically made clinically after a thorough patient history and physical exam </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 Chromosome abnormality and can you explain it in depth? [/INST] A chromosomal abnormality, chromosomal anomaly, chromosomal aberration, chromosomal mutation, or chromosomal disorder, is a missing, extra, or irregular portion of chromosomal DNA. These can occur in the form of numerical abnormalities, where there is an atypical number of chromosomes, or as structural abnormalities, where one or more individual chromosomes are altered. Chromosome mutation was formerly used in a strict sense to mean a change in a chromosomal segment, involving more than one gene. Chromosome anomalies usually occur when there is an error in cell division following meiosis or mitosis. Chromosome abnormalities may be detected or confirmed by comparing an individuals karyotype, or full set of chromosomes, to a typical karyotype for the species via genetic testing.

Numerical abnormality
An abnormal number of chromosomes is called aneuploidy, and occurs when an individual is either missing a chromosome from a pair (resulting in monosomy) or has more than two chromosomes of a pair (trisomy, tetrasomy, etc.). Aneuploidy can be full, involving a whole chromosome missing or added, or partial, where only part of a chromosome is missing or added. Aneuploidy can occur with sex chromosomes or autosomes.An example of trisomy in humans is Down syndrome, which is a developmental disorder caused by an extra copy of chromosome 21; the disorder is therefore also called trisomy 21.An example of monosomy in humans is Turner syndrome, where the individual is born with only one sex chromosome, an X.

Sperm aneuploidy
Exposure of males to certain lifestyle, environmental and/or occupational hazards may increase the risk of aneuploid spermatozoa. In particular, risk of aneuploidy is increased by tobacco smoking, and occupational exposure to benzene, insecticides, and perfluorinated compounds. Increased aneuploidy is often associated with increased DNA damage in spermatozoa.

Structural abnormalities
When the chromosomes structure is altered, this can take several forms:
Deletions: A portion of the chromosome is missing or has been deleted. Known disorders in humans include Wolf–Hirschhorn syndrome, which is caused by partial deletion of the short arm of chromosome 4; and Jacobsen syndrome, also called the terminal 11q deletion disorder.
Duplications: A portion of the chromosome has been duplicated, resulting in extra genetic material. Known human disorders include Charcot–Marie–Tooth disease type 1A, which may be caused by duplication of the gene encoding peripheral myelin protein 22 (PMP22) on chromosome 17.
Inversions: A portion of the chromosome has broken off, turned upside down, and reattached, therefore the genetic material is inverted.
Insertions: A portion of one chromosome has been deleted from its normal place and inserted into another chromosome.
Translocations: A portion of one chromosome has been transferred to another chromosome. There are two main types of translocations:
Reciprocal translocation: Segments from two different chromosomes have been exchanged.
Robertsonian translocation: An entire chromosome has attached to another at the centromere - in humans, these only occur with chromosomes 13, 14, 15, 21, and 22.
Rings: A portion of a chromosome has broken off and formed a circle or ring. This can happen with or without the loss of genetic material.
Isochromosome: Formed by the mirror image copy of a chromosome segment including the centromere.Chromosome instability syndromes are a group of disorders characterized by chromosomal instability and breakage. They often lead to an increased tendency to develop certain types of malignancies.

Inheritance
Most chromosome abnormalities occur as an accident in the egg cell or sperm, and therefore the anomaly is present in every cell of the body. Some anomalies, however, can happen after conception, resulting in Mosaicism (where some cells have the anomaly and some do not) </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 Trematoda and can you explain it in depth? [/INST] Trematoda is a class within the phylum Platyhelminthes. It includes two groups of parasitic flatworms, known as flukes.
They are internal parasites of molluscs and vertebrates. Most trematodes have a complex life cycle with at least two hosts. The primary host, where the flukes sexually reproduce, is a vertebrate. The intermediate host, in which asexual reproduction occurs, is usually a snail.

Taxonomy and biodiversity
The trematodes or flukes include 18,000 to 24,000 species, divided into two subclasses. Nearly all trematodes are parasites of mollusks and vertebrates. The smaller Aspidogastrea, comprising about 100 species, are obligate parasites of mollusks and may also infect turtles and fish, including cartilaginous fish. The Digenea, the majority of trematodes, are obligate parasites of both mollusks and vertebrates, but rarely occur in cartilaginous fish.
Two other parasitic classes, the Monogenea and Cestoda, are sister classes in the Neodermata, a group of Rhabditophoran Platyhelminthes.Flukes can be classified into two groups based on, the system in which they infect their vertebrate host.
They may also be classified according to the environment in which they are found. For instance, pond flukes infect fish in ponds.

Tissue flukes infect the bile ducts, lungs, or other biological tissues. This group includes the lung fluke, Paragonimus westermani, and the liver flukes, Clonorchis sinensis and Fasciola hepatica.
Blood flukes inhabit the blood in some stages of their life cycle. Blood flukes include species of the genus Schistosoma.Lung flukes: there are eight species of lung flukes that infect humans: Paragonimus westermani, P. heterotremus, P. skryabini, P. miyazakii, P. africanus, P. uterobilateralis, P. kellicotti, and P. mexicanus. Paragonimus westermani needs three different hosts in order to survive, reproduce, and complete its life cycle. The completion of a lung flukes life cycle follows the cycle of first, second, and final hosts. The first intermediate host of the lung fluke is a snail, the second intermediate host is a crab or crayfish, and the final host for lung flukes is an animal or human host.Liver flukes: include Clonorchis, Opisthorchis, and Fasciola. Clonorchis and Opisthorchis are considered the most important human pathogens because they are classified as class 1 carcinogens. Liver flukes are commonly found within bile ducts, liver, and gallbladder in mammalian and avian species. There are high numbers of human infection with all three of these liver flukes.Blood flukes: include five species of Schistosoma: Schistosoma japonicum, S. mekongi, S. mansoni, S. haematobium, and S. intercalatum. Humans get infected by the cercariae, which are the larval forms of trematodes. Any contact with water can cause potential human infection. Adult blood flukes can live indefinitely in human or animal reservoir hosts.

Anatomy
Trematodes are flattened oval or worm-like animals, usually no more than a few centimeters in length, although species as small as 1 millimetre (0.039 in) are known. Their most distinctive external feature is the presence of two suckers, one close to the mouth, and the other on the underside of the animal.The body surface of trematodes comprises a tough syncytial tegument, which helps protect against digestive enzymes in those species that inhabit the gut of larger animals. It is also the surface of gas exchange; there are no respiratory organs.The mouth is located at the forward end of the animal, and opens into a muscular, pumping pharynx. The pharynx connects, via a short oesophagus, to one or two blind-ending caeca, which occupy most of the length of the body. In some species, the caeca are themselves branched. As in other flatworms, there is no anus, and waste material must be egested through the mouth.Although the excretion of nitrogenous waste occurs mostly through the tegument, trematodes do possess an excretory system, which is instead mainly concerned with osmoregulation. This consists of two or more protonephridia, with those on each side of the body opening into a collecting duct. The two collecting ducts typically meet up at a single bladder, opening to the exterior through one or two pores near the posterior end of the animal.The brain consists of a pair of ganglia in the head region, from which two or three pairs of nerve cords run down the length of the body. The nerve cords running along the ventral surface are always the largest, while the dorsal cords are present only in the Aspidogastrea. Trematodes generally lack any specialized sense organs, although some ectoparasitic species do possess one or two pairs of simple ocelli.

Reproductive system
Most trematodes are simultaneous hermaphrodites, having both male and female organs. Blood flukes are the only form of trematodes that are not hermaphrodites, meaning they have both a male and female sex.  Blood flukes are unique in the way that they can reproduce sexually and asexually. In order for the reproduction of blood flukes to occur asexually, infecting a freshwater snail must happen to act as an intermediate host. Acting as an intermediate host, an organism that supports non-reproductive parasites, allows for the blood flukes to gather nourishment to reproduce. The asexual reproduction takes place in the hepatopancreas of the snail. Reproduction of blood flukes sexually involves finding a mammal host to act as an intermediate host to support their nutritional needs.The reproductive system of trematodes usually consist of having two testes, which are found posterior and dorsal to the ventral sucker.  Having sperm ducts that join together on the underside of the front half of the animal. This final part of the male system varies considerably in structure between species, but may include sperm storage sacs and accessory glands, in addition to the copulatory organ, which is either eversible, and termed a cirrus, or non-eversible, and termed a penis.There is usually only a single ovary. Eggs pass from it into an oviduct. The distal part of the oviduct, called ootype, is dilated. It is connected via a pair of ducts to a number of vitelline glands on either side of the body, that produce yolk cells. After the egg is surrounded by yolk cells, its shell is formed from the secretion of another gland called Mehlis gland or shell gland, the duct of which also opens in the ootype.
The ootype is connected to an elongated uterus that opens to the exterior in the genital pore, close to the male opening. Most commonly found in trematodes, the sperm cells travel through the uterus to reach the ootype, where fertilization occurs. The ovary is sometimes also associated with a storage sac for sperm, and a copulatory duct termed  Laurers canal. Laurer’s canal is described to be the primitive vagina but it is a vestigial organ in some species. In some instances it can serve as a tube outside the worm for potential waste products from the egg-formation system.

Organ morphology
Body wall musculature: Formed of three different muscle layers: circular, longitudinal, and diagonal. The outermost layer is formed by the circular muscle fibers, directly behind that are the longitudinal muscle fibers. The inner layer is formed by the diagonal muscle fibers. Together these muscle fibers form the segmented body wall of trematodes.Oral sucker and acetabulum: In some species of Trematoda, such as T. bragai, there is an acetabulum. This saucer-shaped organ is attached to the oral sucker in some Trematodes and other parasitic worms. This allows for parasitic worms to attach to their host by penetrating the host’s tissue with spines lining the acetabulum organ. In trematodes, the oral sucker is linked to the pharynx via a canal composed of meridional, equatorial, and radial muscle fibers. Together, the mouth, pharynx, and esophagus form the foregut in Trematodes.Male reproductive system: The male reproductive system generally includes two testes, while some species may have more. Along with this, the size and position of the testes in the body may vary depending on the species. Due to this species-level variation, the male reproductive system can be very useful in species identification. Sperm production, or spermatogenesis, occurs in the testes. Spermatogenesis in Trematodes produces biflagellate sperm or sperm with two tails. This phenomenon occurs across very few invertebrate and vertebrate species. Sperm is stored in the seminal vesicle, this organ is connected to the testes by the vas deferens.Female reproductive system: The female reproductive system consists of one ovary in Trematodes. The location of the ovary varies between species, making the female reproductive system useful in species identification. The oocytes are released from the ovary via the oocapt, from here, the stored sperm in the seminal vesicles will meet with the oocyte. In the Mehlis’ gland, the oocyte and sperm will be joined and start developing. As the embryo is forming, the vitelline ducts will begin to release materials that will be used to create the eggshell around the embryo. Finally, the Laurers’ canal will lead outside of the body. The egg can be released from the body, this canal can also serve as a way to expel excess stored sperm.

Life cycles
Trematodes have a very complex life cycle and depending on what taxa they belong to, their life cycles can be completed with as little as one host compared to the typical three hosts.  When there is one host, this is normally a specific species of snail of the family Lymnaeidae. Almost all trematodes infect molluscs as the first host in the life cycle, and most have a complex life cycle involving other hosts. Most trematodes are monoecious and alternately reproduce sexually and asexually. The two main exceptions to this are the Aspidogastrea, which have no asexual reproduction, and the schistosomes, which are dioecious.
In the definitive host, in which sexual reproduction occurs, eggs are commonly shed along with host feces. Eggs shed in water release free-swimming larval forms (Miracidia) that are infective to the intermediate host, in which asexual reproduction occurs.
A species that exemplifies the remarkable life history of the trematodes is the bird fluke, Leucochloridium paradoxum. The definitive hosts, in which the parasite reproduces, are various woodland birds, while the hosts in which the parasite multiplies (intermediate host) are various species of snail. The adult parasite in the birds gut produces eggs and these eventually end up on the ground in the birds feces. Some eggs may be swallowed by a snail and hatch into larvae (miracidia). These larvae grow and take on a sac-like appearance. This stage is known as the sporocyst and it forms a central body in the snails digestive gland that extends into a brood sac in the snails head, muscular foot and eye-stalks. It is in the central body of the sporocyst where the parasite replicates itself, producing many tiny embryos (redia). These embryos move to the brood sac and mature into cercaria.

Life cycle adaptations
Trematodes have a large variation of forms throughout their life cycles. Individual trematode parasites life cycles may vary from this list. They have five larval stages along with the cystic and fully matured adult phases.

Trematodes are released from the definitive host as eggs, which have evolved to withstand the harsh environment
Released from the egg which hatches into the miracidium. This infects the first intermediate host in one of two ways, either active or passive transmission. The first host is normally a mollusk.  a) Active transmission has adapted for dispersal in space as a free swimming ciliated miracidium with adaptations for recognizing and penetrating the first intermediate host. b) Passive transmission has adapted for dispersal in time and infects the first intermediate host contained within the egg.
The sporocyst forms inside the snail first intermediate host and feeds through diffusion across the tegument.
The rediae also forms inside the snail first intermediate host and feeds through a developed pharynx. Either the rediae or the sporocyst develops into the cercariae through polyembryony in the snail.
The cercariae are adapted for dispersal in space and exhibit a large variety in morphology. They are adapted to recognize and penetrate the second intermediate host, and contain behavioral and physiological adaptations not present in earlier life stages.
The metacercariae are an adapted cystic form dormant in the secondary intermediate host.
The adult is the fully developed form which infects the definitive host.The first stage is the miracidium that is triangular in shape and covered by a ciliated ectoderm which is the outermost layer of the three germ layers. The epidermis and epidemic tissues of the parasite are going to evolve from the miracidium. They also have an anterior spin which helps them drill into the snail. The miracidium develops into the sporocyst, which is a sac-like structure, and in this sac the larvae begin to develop. The cells multiply. The rediae and cercariae develop from the larvae which are then released and encyst as metacercariae on aquatic plants. Humans as well as larger sea creatures then get infected when they eat these plants.
When they infect humans, it takes 3–4 months for the metacercariae to mature into adult flukes and lay eggs.

Life cycle of liver flukes
Liver flukes, one of the different species, are responsible for causing liver fluke disease which is also known as fasciolosis. They are hermaphroditic internal parasites. They are caused by the migration of a large number of immature flukes through the liver passageway or by adult flukes that migrate to the bile ducts. Liver flukes infect all grazing animals and are passed from human to human when they eat raw or undercooked fish. Like other flukes, the liver flukes need intermediate hosts and as a result, the transmission from animals to humans happens in three phases. The first phase is the infection of the snail (the first intermediate host) via feces. They complete their gestation and hatch as cercariae. They leave their snail hosts and infect fish who are their second intermediate host. Lastly, humans ingest the metacercariae in raw and undercooked fish. In humans, the metacercariae complete their life cycle and become full grown liver flukes.

Infections
Human infections are most common in Asia, Africa and Latin America. However, trematodes can be found anywhere where untreated human waste is used as fertilizer. Humans can be infected by trematodes either by consuming undercooked contaminated fish or plants, or by ingesting contaminated water. The metacercariae of trematodes attach to fish and plants. In addition, humans can be infected by certain species through swimming in contaminated water. Humans cannot get infected by trematodes directly, trematodes require an intermediate host to do so.Schistosomiasis (also known as bilharzia, bilharziosis or snail fever) is an example of a parasitic disease caused by one of the species of trematodes (platyhelminth infection, or "flukes"), a parasitic worm of the genus Schistosoma.
Clonorchis, Opisthorchis, Fasciola and Paragonimus species, the foodborne trematodes, are another </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 Pneumonic plague and can you explain it in depth? [/INST] Pneumonic plague is a severe lung infection caused by the bacterium Yersinia pestis. Symptoms include fever, headache, shortness of breath, chest pain, and coughing. They typically start about three to seven days after exposure. It is one of three forms of plague, the other two being septicemic plague and bubonic plague.The pneumonic form may occur following an initial bubonic or septicemic plague infection. It may also result from breathing in airborne droplets from another person or animal infected with pneumonic plague. The difference between the forms of plague is the location of infection; in pneumonic plague the infection is in the lungs, in bubonic plague the lymph nodes, and in septicemic plague within the blood. Diagnosis is by testing the blood, sputum, or fluid from a lymph node.While vaccines are being developed, in most countries they are not yet commercially available. Prevention is by avoiding contact with infected rodents, people, or cats. It is recommended that those infected be isolated from others. Treatment of pneumonic plague is with antibiotics.Plague is present among rodents in Africa, the Americas, and Asia. Pneumonic plague is more serious and less common than bubonic plague. The total reported number of cases of all types of plague in 2013 was 783. Left untreated, pneumonic plague is nearly always fatal. Some hypothesize that the pneumonic version of the plague was mainly responsible for the Black Death that resulted in approximately 75 - 200 million deaths in the 1300s.

Signs and symptoms
The most apparent symptom of pneumonic plague is coughing, often with hemoptysis (coughing up blood). With pneumonic plague, the first signs of illness are fever, headache, weakness and rapidly developing pneumonia with shortness of breath, chest pain, cough and sometimes bloody or watery sputum.The pneumonia progresses for two to four days and may cause respiratory failure and shock. Patients will die without early treatment, some within 36 hours.
Initial pneumonic plague symptoms can often include the following:

Fever
Weakness
Headaches
NauseaRapidly developing pneumonia with:

Shortness of breath
Chest pain
Cough
Bloody or watery sputum (saliva and discharge from respiratory passages).

Causes
Pneumonic plague can be caused in two ways: primary, which results from the inhalation of aerosolized plague bacteria, or secondary, when septicemic plague spreads into lung tissue from the bloodstream. Pneumonic plague is not exclusively vector-borne like bubonic plague; instead, it can be spread from person to person. There have been cases of pneumonic plague resulting from the dissection or handling of contaminated animal tissue. This is one of the types of plague formerly known as the Black Death.

Treatment
Pneumonic plague is a very aggressive infection requiring early treatment, which must be given within 24 hours of first symptoms to reduce the risk of death. Streptomycin, gentamicin, tetracyclines and chloramphenicol are all able to kill the causative bacterium.
Antibiotic treatment for seven days will protect people who have had direct, close contact with infected patients. Wearing a close-fitting surgical mask also protects against infection.The mortality rate from untreated pneumonic plague approaches 100%.

Modern outbreaks
Since 2002, the World Health Organization (WHO) has reported seven plague outbreaks, though some may go unreported because they often happen in remote areas. Between 1998 and 2009, nearly 24,000 cases have been reported, including about 2,000 deaths, in Africa, Asia, the Americas, and Eastern Europe. Ninety-eight percent of the worlds cases occur in Africa.

Democratic Republic of the Congo
Two outbreaks occurred in the Democratic Republic of the Congo in 2005 and 2006. The outbreak in 2005 was only detected by looking back at blood samples.

India
In September 1994, India experienced an outbreak of plague that killed 50 and caused travel to New Delhi by air to be suspended until the outbreak was brought under control. The outbreak was feared to be much worse because the plague superficially resembles other common diseases such as influenza and bronchitis; over 200 people that had been quarantined were released when they did not test positive for the plague. All but two of the deaths occurred around the city of Surat.

China
A major outbreak of the pneumonic plague occurred in Manchuria from 1910 to 1911, in what became known as the Manchurian plague, killing around 60,000 people. The Qing court dispatched Wu Lien-teh, a doctor educated at Cambridge University, to oversee disease control and treatment efforts. He made the novel observation that the disease was transmitted by air, and developed prototypical respirators to help prevent its spread. A second, less deadly outbreak occurred in 1920–21, killing approximately 9,300 people.The Peoples Republic of China has eradicated pneumonic plague from most parts of the country, but still reports occasional cases in remote western areas, where the disease is carried by rats and the marmots that live across the Himalayan plateau. Outbreaks can be caused when a person eats an infected marmot or comes into contact with fleas carried by rats. A 2006 WHO report from an international meeting on plague cited a Chinese government disease expert as saying that most cases of the plague in Chinas northwest occur when hunters are contaminated while skinning infected animals.The expert said at the time that, due to the regions remoteness, the disease killed more than half the infected people. The report also said that since the 1990s, there was a rise in plague cases in humans—from fewer than 10 in the 1980s to nearly 100 cases in 1996 and 254 in 2000. In September 2008, two people in East Tibet died of pneumonic plague.An outbreak of the disease in China began in August 2009 in Ziketan Town located in Qinghai Province. The town was sealed off and several people died as a result of the disease. According to spokesperson Vivian Tan of the WHO office in Beijing, "In cases like this [in August 2009], we encourage the authorities to identify cases, to investigate any suspicious symptoms among close contacts, and to treat confirmed cases as soon as possible. So far, they have done exactly that. There have been sporadic cases reported around the country in the last few years so the authorities do have the experience to deal with this."In September 2010, five cases of pneumonic plague were reported in Tibet.In July 2014, Chinese media reported one case found in Gansu.On 12 November 2019, It was announced that two people from the Chinese province of Inner Mongolia were diagnosed with pneumonic plague. They received treatment in Chaoyang District, Beijing, and authorities implemented preventative control measures. Later in November, a third case of plague was confirmed. A 55-year-old man was diagnosed with bubonic plague after eating wild rabbit in Inner Mongolia. The regions health commission says it has no evidence to suggest that this case is linked to the previous two. By the end of November, a fourth case was confirmed. Chinese health authorities reported a fresh case of bubonic plague in the countrys northern Inner Mongolia region, bringing the total number of reported plague cases originating from Inner Mongolia to four.

Peru
In August 2010, Perus health minister Oscar Ugarte announced that an outbreak of plague had killed a 14-year-old boy and had infected at least 31 people in a northern coastal province. The boy died of bubonic plague on 26 July 2010. Ugarte stated that authorities were screening sugar and fish meal exports from Ascope Province, located about 325 miles (520 km) northwest of Lima, not far from the popular Chicama beach. Most of the infections in Peru were bubonic plague, with four cases of pneumonic plague.The first recorded plague outbreak in Peru was in 1903. Prior to the above case, the last known outbreak was in 1994, killing 35 people.

Madagascar
In November 2013, an outbreak of plague occurred in the African island nation of Madagascar. As of 16 December, at least 89 people were infected, with 39 deaths with at least two cases involving pneumonic plague </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 Congenital erosive and vesicular dermatosis 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 Hypertropia and can you explain it in depth? [/INST] Hypertropia is a condition of misalignment of the eyes (strabismus), whereby the visual axis of one eye is higher than the fellow fixating eye.
Hypotropia is the similar condition, focus being on the eye with the visual axis lower than the fellow fixating eye.
Dissociated vertical deviation is a special type of hypertropia leading to slow upward drift of one or rarely both eyes, usually when the patient is inattentive.

Presentation
Associated defects
Refractive errors such as hyperopia and anisometropia may be associated abnormalities found in patients with vertical strabismus.
The vertical miscoordination between the two eyes may lead to

Strabismic amblyopia, (due to deprivation / suppression of the deviating eye)
cosmetic defect (most noticed by parents of a young child and in photographs)
Face turn, depending on presence of binocular vision in a particular gaze
diplopia or double vision - more seen in adults (maturity / plasticity of neural pathways) and suppression mechanisms of the brain in sorting out the images from the two eyes.
cyclotropia, a cyclotorsional deviation of the eyes (rotation around the visual axis), particularly when the root cause is an oblique muscle paresis causing the hypertropia.

Causes
Hypertropia may be either congenital or acquired, and misalignment is due to imbalance in extraocular muscle function </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 Peripheral ulcerative keratitis and can you explain it in depth? [/INST] Peripheral Ulcerative Keratitis (PUK) is a group of destructive inflammatory diseases involving the peripheral cornea in human eyes. The symptoms of PUK include pain, redness of the eyeball, photophobia, and decreased vision accompanied by distinctive signs of crescent-shaped damage of the cornea. The causes of this disease are broad, ranging from injuries, contamination of contact lenses, to association with other systemic conditions. PUK is associated with different ocular and systemic diseases. Moorens ulcer is a common form of PUK. The majority of PUK is mediated by local or systemic immunological processes, which can lead to inflammation and eventually tissue damage. Standard PUK diagnostic test involves reviewing the medical history and a completing physical examinations. Two major treatments are the use of medications such as corticosteroids or other immunosuppressive agents and surgical resection of the conjunctiva. The prognosis of PUK is unclear with one study providing potential complications. PUK is a rare condition with an estimated incidence of 3 per million annually.

Signs and symptoms
The most easily identifiable sign is a visible lesion of the cornea presented usually in a crescent shape. Common reasons for destruction are stromal degradation and epithelial defects on the inflammatory cells. There would be a change in conformation of the peripheral cornea, depending on the severity of corneal thinning. This process is usually accompanied by the possibility of concealing perforation. The formation of an oval-shaped ulcer at the margin of the cornea is also a sign.Symptoms of PUK include pain, redness, tearing, increased sensitivity to bright light, impaired or blurred vision, and the feeling of foreign objects trapped in the eyes.

Association
There are several associations of PUK to ocular and systemic diseases. Rheumatoid arthritis (RA),  Wegners granulomatosis (WG), and Polyarteritis Nodosa (PAN) are the most common systemic conditions.
Rheumatoid arthritis: Approximately 50% of PUK are related to collagen vascular diseases, in which RA is the most common category. Around 34-42% of PUK patients have RA.
Wegners granulomatosis: WG is a rare autoimmune disease associated with PUK. It causes vasculitis of the lower and upper respiratory tracts, and it also affects multiple organs, including eyes. Without timely initiation of systemic therapy, WG patients will develop conjunctival and scleral inflammations. The inflammation will eventually cause corneal thinning and worsen PUK.
Polyarteritis Nodosa: PAN is another autoimmune disease in which the bodys immune system attacks small and medium-sized arteries of its own by mistake. PUK is one of the predominant ocular inflammatory manifestations of PAN.

Causes
There are three major causes for PUK. One possible cause is injury due to any kind of scratches by sharp or hard objects on the surface of the cornea. The scratched area forms an opening in the cornea, allowing microorganisms to access the cornea and lead to infection. Contamination of contact lenses is another cause as fungi, bacteria and parasites, microscopic parasite acanthamoeba, in particular, could inhabit the surface of the carrying case of the contact lens. When placing the contact lens to ones eyes, invisible microorganisms may contaminate the cornea resulting in PUK. An extended period of wearing contact lenses could also cause damage on the cornea surface, allowing the entry of microorganisms to the cornea. Other than contamination of contact lenses, contamination occurring in water could also cause PUK. Especially in places like the ocean, rivers, lakes and hot tubs, massive amounts of bacteria, fungi, and parasites exist. When there is an injury on the cornea surface, contact with contaminated water could transfer unwanted microorganisms into the cornea resulting in PUK. Virus and bacteria are sources of infection to the cornea. Herpes virus and bacteria that cause gonorrhea are some examples.

Anatomy and pathogenesis
The corneal epithelium consists of five to six layers of cells with a total thickness of around 0.52mm. The cornea thickens to 0.65mm towards the periphery of the cornea. Stroma, which accounts for 90% of the corneal thickness, refers to the middle layer between epithelium and endothelium. It is present in the peripheral cornea to act as a transitional zone between the sclera and cornea. Limbal vasculature, deriving from capillaries that surround the peripheral cornea, supplies the stroma. Various molecules normally diffuse from these capillaries at the periphery to the central cornea. With limited diffusion, there is a higher concentration of IgM, factor C1 of the complement cascade, and Langerhans cells.
Any kind of inflammatory stimulus present in the peripheral cornea results in recruitment of neutrophil and activation of both classical and alternative pathways of immune response, namely the humoral and cell-mediated autoimmune responses. These responses will lead to the formation of antigen-specific antibodies to combat foreign antigens. However, antigen-antibody complexes formed may deposit in the vascular endothelium and activate complements leading to severe local inflammation. Under this circumstance, inflammatory cells, such as macrophages and neutrophils, enter the peripheral cornea. These inflammatory cells release enzymes protease and collagenases, causing potential disruption of the corneal stroma. The additional release of cytokines, for example, interleukin-1, from these cells further accelerates the process of stromal destruction.

Moorens ulcer and relevant classification
Moorens ulcer is a common form of PUK. One classification of Moorens ulcer, based on the clinical presentation, includes bilateral indolent moorens ulcer, bilateral aggressive moorens ulcer and unilateral moorens ulcer. Unilateral moorens ulcer, meaning ulcer of one eye, mainly affects elderly above 60 years old. Rapid onset with redness and severe pain of the affected eye and either slow or extremely quick progression are some typical characteristics of unilateral moorens ulcer. Bilateral aggressive moorens ulcer is prevalent in Indian between age 14 to 40. The common presentation includes the appearance of lesions in one eye, followed by the development of lesions in another eye. Finally, bilateral indolent moorens ulcer is common in patients of at least 50-year-old. It usually progresses slowly and causes little or no pain.Other classification methods also exist. The first one is classifying Moorens ulcers based on clinical presentation and prognosis into two categories. The first type is usually presented unilaterally, accompanied by symptoms ranging from mild to moderate. Therefore, it has a more effective response to treatment. In contrast, type II appears in a bilateral manner, with severe symptoms and poor outcome of treatment. The second classification is based on severity. Grade I refers to corneal thinning, grade II describes impending corneal perforation, and grade III is corneal perforation with a diameter greater than 2mm.

Diagnosis
There are many investigative modalities available for diagnosing PUK, including history review and physical examination. A thorough history of ocular infections, contact lens usage, other medication, or surgery is necessary to identify possible presence of associated diseases. An ophthalmic examination helps identify whether it is due to local pathogenesis. Physical examinations allow more understanding of the underlying systemic process.A standard testing procedure includes hematological investigations, immunological testing, followed by chest X-ray. Hematological investigations are blood tests estimating hemoglobin, platelet counts, total white blood cell counts, erythrocyte sedimentation rate and viscosity. Other common body checks include urinalysis and liver and renal function tests. The selection of immunological testing for various markers is based on numerous additional medical examinations and clinical history of the patient. Possible markers are antinuclear antibodies, anti-rheumatoid antibodies, and antibodies to cyclic citrullinated peptides. Finally, a chest X-ray helps distinguish whether there are complications, such as pulmonary diseases, due to systemic conditions associated with PUK.One of the common causes of PUK is ocular infections by microorganisms such as bacteria, viruses, and fungi. To detect the causative microorganism, doctors usually collect samples before the commencement of therapy and send them to laboratories. Laboratory personnel then perform smear examination, inoculate the samples on culture media, and perform serological testing. Serological testing is an antibody test providing information on PUK etiology. The diagnosis of PUK due to systemic conditions requires a combination of serological and hematological testing, together with imaging techniques such as radiography and CT scanning.

Treatments
Various PUK therapies are of different objectives, for example, inflammation control, halting of disease progression, stroma repairment, avoidance of secondary complications, and vision restoration. A thorough understanding of PUK and different therapies is important. Medical and surgical treatments are two major approaches to manage PUK.

Medical therapy
As for medical therapy, there are several types of drugs available for PUK. Topical corticosteroids usually serve as therapy for milder unilateral cases of RA-associated PUK. Systemic corticosteroids in the form of an oral dose are the acute management of more severe cases. However, there are side effects with prolonged usage of oral corticosteroids. Immunosuppressive agents, such as azathioprine, cyclophosphamide, and methotrexate, have demonstrated efficacy in treating inflammatory eye diseases, including PUK. The combined therapy of systemic corticosteroids up to 100 mg/day and immunosuppressive agents are used for severe cases of PUK. Biological agents, such as anti-tissue necrosis factors (anti-TNF), is a well-established treatment of systemic inflammatory diseases, Infliximab and Adalimumab are TNF blockers for treating RA-associated PUK. However, the high cost and uncertainty of long-term side effects are the possible drawbacks.

Surgical treatment
In terms of surgical treatment, conjunctival resection is a common procedure, which can temporarily remove local inflammatory mediators and collagenases and therefore slow down the disease progression. Other surgical management includes corneal gluing, or keratoplasty procedures. Corneal transplantation is a management option when there is severe corneal melting or perforation although one possible disadvantage is the risk of rejection.Surgical treatment helps maintain the integrity of the globe, but it is usually complementary because it alone cannot influence the underlying immunological process. Therefore, medical and surgical treatments are commonly used in conjunction.

Choice of treatment
The choice of treatment may be different depending on the nature of PUK, infectious or noninfectious. Selection of the right targeted antimicrobial therapy for infectious PUK is based on clinical judgement and culture results. For example, the appropriate treatment for bacterial infections is antibiotics, such as fluoroquinolones. As for Moorens ulcers, 56% of unilateral PUK and 50% of bilateral PUK in one eye showed recovery with intensive topical steroids. Only 18% of patients with bilateral ulcers occurring simultaneously in both eyes show improvements with topical steroids alone; therefore a combination of immunosuppressive agents and systemic steroids should be given in early courses of management </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 Aplasia cutis congenita 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 Transient hypogammaglobulinemia of infancy 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 Trichofolliculoma 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 Pseudoporphyria and can you explain it in depth? [/INST] Pseudoporphyria is a bullous photosensitivity that clinically and histologically mimics porphyria cutanea tarda.: 524   The difference is that no abnormalities in urine or serum porphyrin is noted on laboratories.  Pseudoporphyria has been reported in patients with chronic kidney failure treated with hemodialysis and in those with excessive exposure to ultraviolet A (UV-A) by tanning beds.

Presentation
Pseudoporphyria is clinically characterized by increased skin fragility; erythema; and the appearance of tense bullae and erosions on sun-exposed skin, which are identical to those seen in patients with PCT. However, a clinical pearl that may prove helpful in differentiating between pseudoporphyria and PCT is that the classic features of hypertrichosis, hyperpigmentation, and sclerodermoid changes found with PCT are unusual with pseudoporphyria.
A second clinical pattern of pseudoporphyria has a similar presentation to erythropoietic protoporphyria (EPP), an autosomal dominant porphyria resulting from a reduced activity of ferrochelatase.In contrast to PCT, EPP usually begins in childhood with a history of photosensitivity, often described as a burning sensation immediately after sunlight exposure.
Clinically, EPP is characterized by erythema, edema, shallow scars, and waxy induration of the skin, particularly on the face.
Pseudoporphyria that clinically mimics EPP has been described almost exclusively in children taking naproxen for juvenile rheumatoid arthritis. Naproxen-induced pseudoporphyria seems to have a dimorphic presentation with the PCT-like pattern more often seen in the adult population and the EPP-like pattern more commonly seen in children, although some overlap has been documented.

Race
Although pseudoporphyria has no predilection toward any one race, it has been shown that fair-skinned children who are highly prone to sunburn are more likely to develop naproxen-induced pseudoporphyria than those children with skin types III or higher. Wallace et al </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 Brody myopathy and can you explain it in depth? [/INST] Brody myopathy, also called Brody disease, is a rare disorder that affects skeletal muscle function. BD was first characterized in 1969 by Dr. Irwin A. Brody at Duke University Medical Center. Individuals with BD have difficulty relaxing their muscles after exercise. This difficulty in relaxation leads to symptoms including cramps, stiffness, and discomfort in the muscles of the limbs and face.  Symptoms are heightened by exercise and commonly progress in severity throughout adulthood.

Signs and symptoms
Symptoms include stiffness and sometimes muscle cramping after exercise and especially when exposed to cold. The most commonly affected muscles are in the arms, legs, and eyelids. Individuals with Brody myopathy also sometimes experience weakness, myalgia, and rhabdomyolysis.

Cause
Most cases of BD are inherited through autosomal recessive mutations in ATP2A1,  where each copy of the affected individuals gene contain a mutation. The gene involved in BD encodes the fast-twitch skeletal muscle ATPase, SERCA1. SERCA1 is a protein pump that uses ATP to pump Ca2+ ions from the cytosol to the sarcoplasmic reticulum in skeletal muscle. In those with BD, SERCA1 pumps are unable to effectively move Ca2+ across the membrane, leading to increased levels of cytoplasmic Ca2+. Increases in cytoplasmic Ca2+ levels interfere with muscle contraction, leading to the characteristic symptoms of BD.In some cases of BD, no mutations in ATP2A1 have been observed. Disease transmission in cases of non-ATP2A1 BD have been characterized as autosomal dominant pattern of inheritance. These cases have revealed that the cause of the disease likely exhibits genetic heterogeneity, meaning the disease involves mutations in other locations within the genome (although no other loci have been identified in the development of BD as of now).

Diagnosis
Diagnosis of BD begins with clinical evaluation of individuals for characteristic symptoms of cramping and stiffness of exercised muscles. A few techniques are involved in confirming a diagnosis of BD.Blood testing may be used to measure serum creatine kinase, which ranges from normal to slightly elevated in those with BD. Skeletal muscle biopsies are used to examine muscle fibers </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 Subungual exostosis and can you explain it in depth? [/INST] Subungual exostoses are a type of non-cancerous bone tumor of the chondrogenic type, and consists of bone and cartilage </s>