<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Ichthyosis prematurity syndrome and explain in detail? [/INST] Ichthyosis prematurity syndrome (IPS) is a dermatological disease with known genetic causes. This syndrome is a rare subcategory of autosomal recessive  congenital ichthyosis (ARCI). It is associated with complications in the mid-trimester of a pregnancy leading to premature births. Although most prevalent in individuals of Scandinavian origin, there have also been scattered cases in people of Japanese, Italian and Indian ethnicity. This disorder is also referred to as ichthyosis congenital type IV.

Signs and symptoms
The symptoms associated with the disorder are often confused for other dermatological disorders. The symptoms below are ones specifically associated with IPS.

Premature birth
Pregnancies that have a foetus affected with this syndrome are complicated because of polyhydramnion. Complications arise because of opaque amnionic fluid resulting from the shedding of skin. As a result, ultrasounds are difficult to conduct. Triggered by the harsh environment in the uterus, delivery results around 30– 34 weeks of gestation (pregnancy) and the baby is born in prematurely.

Thick caseous layer of skin
A white layer of thick scaly substance covers the surface of the skin of the infant. This is characterized by aggregating membranes in the upper layer of skin on epidermal cells.

Desquamating skin
Red endemic skin as well as spongy and desquamating (peeling) skin are consistent with this syndrome.

Respiratory problems
After premature delivery, the baby often has neonatal asphyxia from breathing amnionic debris mainly composed of shedding skin cells. Neonatal refers to the very young infant and amniotic fluid refers to the liquid environment the baby is bathed in inside the uterus.

Eosinophilia
Eosinophils are a kind of a white blood cell which help protect the body from certain infections and involved in allergic responses. Eosionphelia is an abnormal increase of  eosinophils in tissue, blood or both and is present in individuals born with this syndrome.

Genetics
Mode of inheritance
This rare syndrome is associated with an autosomal recessive mode of inheritance. The parents are classified as heterozygote carriers of the disease and the chance that the offspring will be affected is 25%. Both parents need to have the mutant allele in order to pass on the disease to their offspring and the offspring need to inherit both mutant alleles in order to express the disorder.

Genetic cause
IPS is caused by a number of mutations at different loci of the FATP4 gene. One nonsense mutation and a number of missense mutation in the FATP4 (SLC27A4) gene which codes for the fatty acid transport protein 4 are associated with IPS. Splice site mutations have also been linked to IPS. When the splice site between exons and introns is mutated, it leads to a deletion or duplication event which would change the stability or soundness of the protein the RNA is coding for.
When a mutation is present in the gene coding for this protein, the protein product is not stable or able to perform its role. As a result, the pathway it is involved in is compromised and a diseased phenotype is often noted. In this particular case the fatty acid transport protein 4 is deformed due to the presence of mutations in the FATP4 gene and an interference occurs in the lipid metabolic pathway in the skin that this protein is involved with.This results in the abnormal formation of epidermal skin cells and a compromised formation and maintenance of an epidermal barrier. These underlying genetic causes explain the symptoms of the flaky, dry, cutaneous skin phenotype expressed.IPS genes segregate independently of the already known general ARCI locus. As a result, IPS has been identified to have its own gene locus making it easier to diagnose.

Diagnosis
Diagnosis can be made at birth by identifying the symptoms of the child. Ultrastructural diagnosis where tissues are analyzed is using electron microscopy is also conducted. A specimen of skin is obtained via a skin biopsy and analyzed to see any tell tale characteristics. Genetic testing can also be done to identify the mutation on the FATP4 gene associated with fatty acid synthesis </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Nevus of Ito and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Far East scarlet-like fever and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Adenomyomatosis and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Orthokeratosis and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Borderline tuberculoid leprosy and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Pityriasis rotunda and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Congenital bilateral perisylvian syndrome and explain in detail? [/INST] Congenital bilateral perisylvian syndrome (CBPS) is a rare neurological disease characterized by paralysis of certain facial muscles and epileptic seizures.

Signs and symptoms
Signs and symptoms of CBPS typically appear in infancy or at birth, but can appear later in childhood </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Solar erythema and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Acute posterior multifocal placoid pigment epitheliopathy and explain in detail? [/INST] Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is an acquired inflammatory uveitis that belongs to the heterogenous group of white dot syndromes in which light-coloured (yellowish-white) lesions begin to form in the macular area of the retina. Early in the course of the disease, the lesions cause acute and marked vision loss (if it interferes with the optic nerve) that ranges from mild to severe but is usually transient in nature. APMPPE is classified as an inflammatory disorder that is usually bilateral and acute in onset but self-limiting. The lesions leave behind some pigmentation, but visual acuity eventually improves even without any treatment (providing scarring doesnt interfere with the optic nerve).
It occurs more commonly in females and is more likely to affect persons between 20 and 30 years of age, but has been seen in people aged 16 to 40. It is known to occur after or concurrently with a systemic infection (but not always), showing that it is related generally to an altered immune system. Recurrent episodes can happen, but are extremely rare.

Signs and symptoms
The onset of ocular symptoms are usually preceded by episode of viral or flu-like symptoms such as fever, cough or sore throat (however this is not always the case). Patients can typically present erythema nodosum, livido reticularus, bilateral uveitis, and sudden onset of marked visual loss associated with the appearance of multiple lesions in the retina. These lesions may be colored from grey-white to cream-shaded yellow.
Other symptoms include scotomata and photopsia. In weeks to a month times the lesions begin to clear and disappear (with prednisone) leaving behind areas of retinal pigment epithelial atrophy and diffuse fine pigmentation (scarring). Rarely choroidal neovascularization occur as a late onset complication.

Cause
Since The cause of the inflammation remains unknown, with various theories of it occurring as an autoimmune response to a mild infection, or the possibility of it being viral because of the preceding flu-like illness that generally accompanies it </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Cryptophthalmos and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Septicemic plague and explain in detail? [/INST] Septicemic plague is one of the three forms of plague, and is caused by Yersinia pestis, a gram-negative species of bacterium. Septicemic plague is a systemic disease involving infection of the blood, and is most commonly spread by bites from infected fleas. Septicemic plague can cause disseminated intravascular coagulation, and is almost always fatal when untreated. The other varieties of the plague are bubonic plague and pneumonic plague.

Signs and symptoms
The usual symptoms are:
Abdominal pain
Bleeding under skin due to blood clotting problems
Bleeding from mouth, nose or rectum
Gastrointestinal symptoms, including nausea, vomiting, which can be with blood, and diarrhea
Fever
Chills
Low blood pressure
Organ failure
Shock
Death of tissue (gangrene) in extremities, mostly fingers, nose, and toes
Difficulty breathingThese symptoms are common to many human illnesses, and are not considered, in and of themselves, to signify infection with any form of plague.It is important to note that septicemic plague may be asymptomatic, and may cause death absent of any symptoms.

Cause
Transmission
Human Yersinia infections most commonly result from the bite of an infected flea or occasionally an infected mammal, but like most bacterial systemic diseases, the disease may be transmitted through an opening in the skin or by inhaling infectious droplets of moisture from sneezes or coughs. In both cases septicemic plague need not be the result, and in particular, not the initial result, but it occasionally happens that bubonic plague for example leads to infection of the blood, and septicemic plague results. If the bacteria happen to enter the bloodstream rather than the lymph or lungs, they multiply in the blood, causing bacteremia and severe sepsis. In septicemic plague, bacterial endotoxins cause disseminated intravascular coagulation (DIC), where tiny blood clots form throughout the body, commonly resulting in localised ischemic necrosis, tissue death from lack of circulation and perfusion.DIC results in depletion of the bodys clotting resources, so that it can no longer control bleeding. Consequently, the unclotted blood bleeds into the skin and other organs, leading to red or black patchy rash and to hematemesis (vomiting blood) or hemoptysis (coughing up blood). The rash may cause bumps on the skin that look somewhat like insect bites, usually red, sometimes white in the center.Septicemic plague is caused by horizontal and direct transmission. Horizontal transmission is the transmitting of a disease from one individual to another regardless of blood relation. Direct transmission occurs from close physical contact with individuals, through common air usage, from direct bite from a flea or an infected rodent. Most common rodents may carry the bacteria and so may Leporidae such as rabbits:

Significant carriers of the bacteria in the United States include:
- Rats
- Prairie dogs
- Squirrels
- Chipmunks
- Rabbits
- Fleas
The bacteria are cosmopolitan, mainly in rodents in all continents except Australia and Antarctica. The greatest frequency of human plague infections occurs in Africa. The bacteria most commonly appear in rural areas and wherever there is poor sanitation, overcrowding, and high rodent populations in urban areas. Outdoor activities such as hiking, camping, or hunting where plague-infected animals may be found, increase the risk of contracting septicemic plague, and so do certain occupations such as veterinary or other animal-related work.

Diagnosis
A doctor or veterinarian will perform a physical exam which includes asking about the medical history and possible sources of exposure. The following possible test could include:

Blood samples (detecting antibodies)
Culture samples of body fluids (check for the bacteria Yersinia pestis)
Kidney and liver testing
Checking lymphatic system for signs of infection
Examining body fluids for abnormal signs
Checking for swelling
Checking for signs of dehydration
Checking for fever
Checking for lung infection

Prevention
The following steps and precautions should be used to avoid infection of the septicemic plague:
Caregivers of infected patients should wear masks, gloves, goggles and gowns
Take antibiotics if close contact with infected patient has occurred
Use insecticides throughout house
Avoid contact with dead rodents or sick cats
Set traps if mice or rats are present around the house
Do not allow family pets to roam in areas where plague is common
Flea control and treatment for animals (especially rodents)

Treatment
Starting antibiotics early is a first step in treating septicemic plague in humans. One of the following antibiotics may be used:
Streptomycin
Gentamicin
Tetracycline or Doxycycline
Chloramphenicol
CiprofloxacinLymph nodes may require draining and the patient will need close monitoring.In animals, antibiotics such as tetracycline or doxycycline can be used. Intravenous drip may be used to assist in dehydration scenarios. Flea treatment can also be used. In some cases euthanasia may be the best option for treatment and to prevent further spreading.

Prognosis
Untreated septicemic plague is almost always fatal. Early treatment with antibiotics reduces the mortality rate to between 4 and 15 percent. Death is almost inevitable if treatment is delayed more than about 24 hours, and some people may even die on the same day they present with the disease.

Epidemiology
In 2015, Taylor Gaes, a 16-year-old in Larimer County in northern Colorado, contracted septicemic plague and subsequently died after being bitten by a flea that had bitten a rodent on his familys rural property. Only three people in Colorado had contracted the bacteria in the previous thirty years.

History
Septicemic plague was the least common of the three plague varieties that occurred during the Black Death from 1348 to 1350 (the other two being bubonic plague and pneumonic plague). Like the others, septicemic plague spread from the East through trade routes on the Black Sea and down to the Mediterranean Sea.Major port cities and trade centers such as Venice and Florence were hit the hardest </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Heat syncope and explain in detail? [/INST] Heat syncope is fainting or dizziness as a result of overheating (syncope is the medical term for fainting).  It is a type of heat illness. The basic symptom of heat syncope is fainting, with or without mental confusion. Heat syncope is caused by peripheral vessel dilation, resulting in diminished blood flow to the brain and dehydration.

Signs and symptoms
Faintness, dizziness, headache, increased pulse, restlessness, nausea, vomiting, pale/clammy skin, and brief loss of consciousness.

Causes
Heat syncope occurs in a warm environment when blood pressure is lowered as the body dilates (widens) arterioles (small blood vessels) in the skin to radiate heat. This condition occurs within five days of heat acclimatization, before the blood volume expands.  The result is less blood to the brain, causing light-headedness and fainting when a person stands up quickly or stands for a long period of time </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is IgA pemphigus and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Angiolymphoid hyperplasia with eosinophilia and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Cerebro-costo-mandibular syndrome and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Paralytic shellfish poisoning and explain in detail? [/INST] Paralytic shellfish poisoning (PSP) is one of the four recognized syndromes of shellfish poisoning, which share some common features and are primarily associated with bivalve mollusks (such as mussels, clams, oysters and scallops). These shellfish are filter feeders and accumulate neurotoxins, chiefly saxitoxin, produced by microscopic algae, such as dinoflagellates, diatoms, and cyanobacteria. Dinoflagellates of the genus Alexandrium are the most numerous and widespread saxitoxin producers and are responsible for PSP blooms in subarctic, temperate, and tropical locations. The majority of toxic blooms have been caused by the morphospecies Alexandrium catenella, Alexandrium tamarense, Gonyaulax catenella and Alexandrium fundyense, which together comprise the A. tamarense species complex. In Asia, PSP is mostly associated with the occurrence of the species Pyrodinium bahamense.Some pufferfish, including the chamaeleon puffer, also contain saxitoxin, making their consumption hazardous.

PSP and cyanobacteria
Saxitoxin can be produced in both eukaryotic dinoflagellates as well as prokaryotic cyanobacteria (usually referred to as blue-green algae). The biosynthesis pathway of this toxin within cyanobacteria is well defined, while the pathway within dinoflagellates is mostly unknown.
Within cyanobacteria the saxitoxin pathway is complex with many steps, enzymes and chemical reactions. Using radioisotope tracing experiments scientists have determined how the initial reagent of the pathway, L-arginine (via acetyl-CoA), turns into this toxin. L-arginine goes through a rare reaction known as Claisen condensation forming four intermediates before turning into the final product of saxitoxin.Cyanobacteria is general responsible for the accumulation of PSP toxins, mainly being saxitoxin, within freshwater marine life. Studies have been completed showing that the Australian freshwater mussel Alathyria condola are highly susceptible to neurotoxin accumulation. This specific shellfish has shown upwards of 80 ug of neurotoxin accumulation for every 100g of the mussel after a 2-3 day of exposure to the cyanobacteria A. circinalis , which is significant enough to cause health risks for humans.

Pathophysiology
The toxins responsible for most shellfish poisonings are water insoluble,  heat and acid-stable, and ordinary cooking methods do not eliminate the toxins. The principal toxin responsible for PSP is saxitoxin. Some shellfish can store this toxin for several weeks after a harmful algal bloom passes, but others, such as butter clams, are known to store the toxin for up to two years. Additional toxins are found, such as neosaxitoxin and gonyautoxins I to IV. All of them act primarily on the nervous system.
PSP and its associated toxin can cause paralysis in extreme cases by targeting the sodium ion channels. Saxitoxin is able to bind to the receptor site of a cellular membrane near the sodium ion channel, blocking the entrance and not allowing potassium or sodium to pass into the cell. This blockage restricts the transmission of signals between neurons potentially resulting in paralysis.PSP can be fatal in extreme cases, particularly in immunocompromised individuals </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Barrel chest and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy and explain in detail? [/INST] Nasu–Hakola disease also known as polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy is a rare disease characterised by early-onset dementia and multifocal bone cysts. It is caused by autosomal recessive loss of function mutations in either the TREM2 or TYROBP gene that are found most frequently in the Finnish and Japanese populations.

Signs and symptoms
Four stages are recognised in this condition. The first (latent stage) show no symptoms or signs. This stage typically lasts up to the early 20s. This is followed by the osseous stage. This is characterised by recurrent bone pain usually affecting the long bones of the limbs. This is usually followed by pathological fractures of these bones. The third stage (early neurological) is marked by the onset of symptoms typical of a frontal lobe syndrome (euphoria, lack of concentration, loss of judgment and social inhibitions) with memory loss. Epilepsy may occur </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Absent pulmonary valve syndrome and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Anomalous pulmonary venous connection and explain in detail? [/INST] Anomalous pulmonary venous connection (or anomalous pulmonary venous drainage or anomalous pulmonary venous return) is a congenital defect of the pulmonary veins.

Total anomalous pulmonary venous connection
Total anomalous pulmonary venous connection, also known as total anomalous pulmonary venous return, is a rare cyanotic congenital heart defect in which all four pulmonary veins are malpositioned and make anomalous connections to the systemic venous circulation. (Normally, pulmonary veins return oxygenated blood from the lungs to the left atrium where it can then be pumped to the rest of the body). A patent foramen ovale, patent ductus arteriosus or an atrial septal defect must be present, or else the condition is fatal due to a lack of systemic blood flow.In some cases, it can be detected prenatally.There are four variants: Supracardiac (50%): blood drains to one of the innominate veins (brachiocephalic veins) or the superior vena cava; Cardiac (20%), where blood drains into coronary sinus or directly into right atrium; Infradiaphragmatic (20%), where blood drains into portal or hepatic veins; and a mixed (10%) variant.TAPVC can occur with obstruction, which occurs when the anomalous vein enters a vessel at an acute angle and can cause pulmonary venous hypertension and cyanosis because blood cannot enter the new vein as easily.

Signs and symptoms
right ventricular heave
Loud S1
fixed split S2
S3 gallop
systolic ejection murmur at left upper sternal border
cardiomegaly
right axis deviation on ECG
Snowman sign or figure of 8 configuration on chest radiograph
right ventricular hypertrophy
cyanosis, tachypnea, dyspnea since the overloaded pulmonary circuit can cause pulmonary edema
Cottage-loaf sign, that is, chest X-ray appearance similar to a cottage loaf, also known as the snow man sign or figure of 8 sign.

Treatment
In TAPVC without obstruction, surgical redirection can be performed within the first month of life. The operation is performed under general anesthesia </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Hoarse voice and explain in detail? [/INST] A hoarse voice, also known as dysphonia or hoarseness, is when the voice involuntarily sounds breathy, raspy, or strained, or is softer in volume or lower in pitch. A hoarse voice, can be associated with a feeling of unease or scratchiness in the throat. Hoarseness is often a symptom of problems in the vocal folds of the larynx. It may be caused by laryngitis, which in turn may be caused by an upper respiratory infection, a cold, or allergies. Cheering at sporting events, speaking loudly in noisy situations, talking for too long without resting ones voice, singing loudly, or speaking with a voice thats too high or too low can also cause temporary hoarseness. A number of other causes for losing ones voice exist, and treatment is generally by resting the voice and treating the underlying cause. If the cause is misuse or overuse of the voice, drinking plenty of water may alleviate the problems.It appears to occur more commonly in females and the elderly. Furthermore, certain occupational groups, such as teachers and singers, are at an increased risk.Long-term hoarseness, or hoarseness that persists over three weeks, especially when not associated with a cold or flu should be assessed by a medical doctor. It is also recommended to see a doctor if hoarseness is associated with coughing up blood, difficulties swallowing, a lump in the neck, pain when speaking or swallowing, difficulty breathing, or complete loss of voice for more than a few days. For voice to be classified as "dysphonic", abnormalities must be present in one or more vocal parameters: pitch, loudness, quality, or variability. Perceptually, dysphonia can be characterised by hoarse, breathy, harsh, or rough vocal qualities, but some kind of phonation remains.Dysphonia can be categorized into two broad main types: organic and functional, and classification is based on the underlying pathology. While the causes of dysphonia can be divided into five basic categories, all of them result in an interruption of the ability of the vocal folds to vibrate normally during exhalation, which affects the voice. The assessment and diagnosis of dysphonia is done by a multidisciplinary team, and involves the use of a variety of subjective and objective measures, which look at both the quality of the voice as well as the physical state of the larynx. Multiple treatments have been developed to address organic and functional causes of dysphonia. Dysphonia can be targeted through direct therapy, indirect therapy, medical treatments, and surgery. Functional dysphonias may be treated through direct and indirect voice therapies, whereas surgeries are recommended for chronic, organic dysphonias.

Types
Voice disorders can be divided into 2 broad categories: organic and functional. The distinction between these broad classes stems from their cause, whereby organic dysphonia results from some sort of physiological change in one of the subsystems of speech (for voice, usually respiration, laryngeal anatomy, and/or other parts of the vocal tract are affected). Conversely, functional dysphonia refers to hoarseness resulting from vocal use (i.e. overuse/abuse). Furthermore, according to ASHA, organic dysphonia can be subdivided into structural and neurogenic; neurogenic dysphonia is defined as impaired functioning of the vocal structure due to a neurological problem (in the central nervous system or peripheral nervous system); in contrast, structural dysphonia is defined as impaired functioning of the vocal mechanism that is caused by some sort of physical change (e.g. a lesion on the vocal folds). Notably, an additional subcategory of functional dysphonia recognized by professionals is psychogenic dysphonia, which can be defined as a type of voice disorder that has no known cause and can be presumed to be a product of some sort of psychological stressors in ones environment. It is important to note that these types are not mutually exclusive and much overlap occurs. For example, Muscle Tension Dysphonia (MTD) has been found to be a result of many different causes including the following: MTD in the presence of an organic pathology (i.e. organic type), MTD stemming from vocal use (i.e. functional type), and MTD as a result of personality and/or psychological factors (i.e. psychogenic type).

Causes
The most common causes of hoarseness is laryngitis (acute 42.1%; chronic 9.7%) and functional dysphonia (30%). Hoarseness can also be caused by laryngeal tumours (benign 10.7 - 31%; malignant 2.2 - 3.0%). Causes that are overall less common include neurogenic conditions (2.8 - 8.0%), psychogenic conditions (2.0 - 2.2%), and aging (2%).A variety of different causes, which result in abnormal vibrations of the vocal folds, can cause dysphonia. These causes can range from vocal abuse and misuse to systemic diseases. Causes of dysphonia can be divided into five basic categories, although overlap may occur between categories. (Note that this list is not exhaustive):

Employment
It has been suggested that certain occupational groups may be at increased risk of developing dysphonia due to the excessive or intense vocal demands of their work. Research on this topic has primarily focused on teachers and singers, although some studies have examined other groups of heavy voice users (e.g. actors, cheerleaders, aerobic instructors, etc.). At present, it is known that teachers and singers are likely to report dysphonia. Moreover, physical education teachers, teachers in noisy environments, and those who habitually use a loud speaking voice are at increased risk. The term clergymans throat or dysphonia clericorum was previously used for painful dysphonia associated with public speaking, particularly among preachers. However, the exact prevalence rates for occupational voice users are unclear, as individual studies have varied widely in the methodologies used to obtain data (e.g. employing different operational definitions for "singer").

Mechanism
Located in the anterior portion of the neck is the larynx (also known as the voice box), a structure made up of several supporting cartilages and ligaments, which houses the vocal folds. In normal voice production, exhaled air moves out of the lungs and passes upward through the vocal tract. At the level of the larynx, the exhaled air causes the vocal folds to move toward the midline of the tract (a process called adduction). The adducted vocal folds do not close completely but instead remain partially open. The narrow opening between the folds is referred to as the glottis. As air moves through the glottis, it causes a distortion of the air particles which sets the vocal folds into vibratory motion. It is this vibratory motion that produces phonation or voice. In dysphonia, there is an impairment in the ability to produce an appropriate level of phonation. More specifically, it results from an impairment in vocal fold vibration or the nerve supply of the larynx.

Diagnosis
The assessment and diagnosis of a dysphonic voice is completed by a multidisciplinary team, such as an otolaryngologist (ear, nose and throat doctor) and Speech-Language Pathologist, involving the use of both objective and subjective measures to evaluate the quality of the voice as well as the condition of the vocal fold tissue and vibration patterns.

Definition
Dysphonia is a broad clinical term which refers to abnormal functioning of the voice. More specifically, a voice can be classified as "dysphonic" when there are abnormalities or impairments in one or more of the following parameters of voice: pitch, loudness, quality, and variability. For example, abnormal pitch can be characterized by a voice that is too high or low whereas abnormal loudness can be characterized by a voice that is too quiet or loud. Similarly, a voice that has frequent, inappropriate breaks characterizes abnormal quality while a voice that is monotone (i.e., very flat) or inappropriately fluctuates characterizes abnormal variability. While hoarseness is used interchangeably with the term dysphonia, it is important to note that the two are not synonymous. Hoarseness is merely a subjective term to explain the perceptual quality (or sound) of a dysphonic voice. While hoarseness is a common symptom (or complaint) of dysphonia, there are several other signs and symptoms that can be present such as: breathiness, roughness, and dryness. Furthermore, a voice can be classified as dysphonic when it poses problems in the functional or occupational needs of the individual or is inappropriate for their age or sex.

Auditory-perceptual measures
Auditory-perceptual measures are the most commonly used tool by clinicians to evaluate the voice quality due to its quick and non-invasive nature. Additionally, these measures have been proven to be reliable in a clinical setting. Ratings are used to evaluate the quality of a patients voice for a variety of voice features, including overall severity, roughness, breathiness, strain, loudness and pitch. These evaluations are done during spontaneous speech, sentence or passage reading or sustained vowel productions. The GRBAS (Grade, Roughness, Breathiness, Asthenia, Strain) and the CAPE-V (Consensus Auditory Perceptual Evaluation—Voice) are two formal voice rating scales commonly used for this purpose.

Vocal fold imaging
Vocal fold imaging techniques are used by clinicians to examine the vocal folds and allows them to detect vocal pathology and assess the quality of the vocal fold vibrations. Laryngeal stroboscopy is the primary clinical tool used for this purpose. Laryngeal stroboscopy uses a synchronized flashing light passed through either a rigid or flexible laryngoscope to provide an image of the vocal fold motion; the image is created by averaging over several vibratory cycles and is thus not provided in real-time. As this technique relies on periodic vocal fold vibration, it cannot be used in patients with moderate to severe dysphonia. High speed digital imaging of the vocal folds (videokymography), another imaging technique, is not subject to the same limitations as laryngeal stroboscopy. A rigid endoscope is used to take images at a rate of 8000 frames per second, and the image is displayed in real time. As well, this technique allows imaging of aperiodic vibrations and can thus be used with patients presenting with all severities of dysphonia.

Acoustic measures
Acoustic measures can be used to provide objective measures of vocal function. Signal processing algorithms are applied to voice recordings made during sustained phonation or during spontaneous speech. The acoustic parameters which can then be examined include fundamental frequency, signal amplitude, jitter, shimmer, and noise-to-harmonic ratios. However, due to limitations imposed by the algorithms employed, these measures cannot be used with patients who exhibit severe dysphonia.

Aerodynamic measures
Aerodynamic measures of voice include measures of air volume, air flow and sub glottal air pressure. The normal aerodynamic parameters of voice vary considerably among individuals, which leads to a large overlapping range of values between dysphonic and non-dysphonic patients. This limits the use of these measures as a diagnostic tool. Nonetheless, they are useful when used in adjunct with other voice assessment measures, or as a tool for monitoring therapeutic effects over time.

Prevention
Given that certain occupations are more at risk for developing dysphonia (e.g. teachers) research into prevention studies have been conducted. Research into the effectiveness of prevention strategies for dysphonia have yet to produce definitive results, however, research is still ongoing. Primarily, there are two types of vocal training recognized by professionals to help with prevention: direct and indirect. Direct prevention describes efforts to reduce conditions that may serve to increase vocal strain (such as patient education, relaxation strategies, etc.), while indirect prevention strategies refer to changes in the underlying physiological mechanism for voice production (e.g., adjustments to the manner in which vocal fold adduction occurs, respiratory training, shifting postural habits, etc.).

Treatment
Although there is no universal classification of voice problems, voice disorders can be separated into certain categories: organic (structural or neurogenic), functional, neurological (psychogenic) or iatrogenic, for example. Depending on the diagnosis and severity of the voice problem, and depending on the category that the voice disorder falls into, there are various treatment methods that can be suggested to the patient. The professional has to keep in mind there is not one universal treatment, but rather the clinical approach must find what  the optimal effective course of action for that particular patient is.There are three main type of treatments: medical treatments, voice therapy and surgical treatments. When necessary, certain voice disorders use a combination of treatment approaches. A medical treatment involves the use of botulinum toxin (botox) or anti-reflux medicines, for example. Botox is a key treatment for voice disorders such as Spasmodic Dysphonia. Voice therapy is mainly used with patients who have an underlying cause of voice misuse or abuse. Laryngologists also recommend this type of treatment to patients who have an organic voice disorder - such as vocal fold nodules, cysts or polyps as well as to treat functional dysphonia. Certain surgical treatments can be implemented as well - phono microsurgery (removal of vocal fold lesions performed with a microscope), laryngeal framework surgery (the manipulation of the voice box), as well as injection augmentation (injection of substance to vocal folds to improve closure). Surgical treatments may be recommended for patients having an organic dysphonia.A combination of both an indirect treatment method (an approach used to change external factors affecting the vocal folds) and a direct treatment method (an approach used where the mechanisms functioning during the use of the vocal folds, such as phonation or respiration, are the main focus) may be used to treat dysphonia.

Direct therapies
Direct therapies address the physical aspects of vocal production. Techniques work to either modify vocal fold contact, manage breathing patterns, and/or change the tension at level of the larynx. Notable techniques include, but are not limited to, the yawn-sigh method, optimal pitch, laryngeal manipulation, humming, the accent method, and the Lee Silverman Voice Treatment. An example of a direct therapy is circumlaryngeal manual therapy, which has been used to reduce tension and massage hyoid-laryngeal muscles. This area is often tense from chronic elevation of the larynx. Pressure is applied to these areas as the patient hums or sustains a vowel. Traditional voice therapy is often used to treat muscular tension dysphonia.

Indirect therapies
Indirect therapies take into account external factors that may influence vocal production. This incorporates maintenance of vocal hygiene practices, as well as the prevention of harmful vocal behaviours. Vocal hygiene includes adequate hydration of the vocal folds, monitoring the amount of voice use and rest, avoidance of vocal abuse (e.g., shouting, clearing of the throat), and taking into consideration lifestyle choices that may affect vocal health (e.g., smoking, sleeping habits). Vocal warm-ups and cool-downs may be employed to improve muscle tension and decrease risk of injury before strenuous vocal activities. It should be taken into account that vocal hygiene practices alone are minimally effective in treating dysphonia, and thus should be paired with other therapies.

Medication and surgery
Medical and surgical treatments have been recommended to treat organic dysphonias. An effective treatment for spasmodic dysphonia (hoarseness resulting from periodic breaks in phonation due to hyperadduction of the vocal folds) is botulinum toxin injection. The toxin acts by blocking acetylcholine release at the thyro-arytenoid muscle. Although the use of botulinum toxin injections is considered relatively safe, patients responses to treatment differ in the initial stages; some have reported experiencing swallowing problems and breathy voice quality as a side-effect to the injections. Breathiness may last for a longer period of time for males than females.Surgeries involve myoectomies of the laryngeal muscles to reduce voice breaks, and laryngoplasties, in which laryngeal cartilage is altered to reduce tension.

Epidemiology
Dysphonia is a general term for voice impairment that is sometimes used synonymously with the perceptual voice quality of hoarseness. It is the reason for 1% of all visits to primary care providers. The lifetime risk of hoarse voice complaints among primary care patients is 30%. Since hoarseness is a general symptom, it is associated with a number of laryngeal diagnoses.There is an interplay of sex and age differences associated with dysphonia. The point prevalence of dysphonia in adults under the age of 65 is 6.6%. Dysphonia is more common in adult females than males, possibly due to sex-related anatomical differences of the vocal mechanism </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Walker–Warburg syndrome and explain in detail? [/INST] Walker–Warburg syndrome (WWS), also called Warburg syndrome, Chemke syndrome, HARD syndrome (Hydrocephalus, Agyria and Retinal Dysplasia), Pagon syndrome, cerebroocular dysgenesis (COD) or cerebroocular dysplasia-muscular dystrophy syndrome (COD-MD), is a rare form of autosomal recessive congenital muscular dystrophy. It is associated with brain (lissencephaly, hydrocephalus, cerebellar malformations) and eye abnormalities. This condition has a worldwide distribution. The overall incidence is unknown but a survey in North-eastern Italy has reported an incidence rate of 1.2 per 100,000 live births. It is the most severe form of congenital muscular dystrophy with most children dying before the age of three years.

Presentation
The clinical manifestations present at birth are generalized hypotonia, muscle weakness, developmental delay with mental retardation and occasional seizures. The congenital muscular dystrophy is characterized by hypoglycosylation of α-dystroglycan.
Those born with the disease also experience severe ocular and brain defects. Half of all children with WWS are born with encephalocele, which is a gap in the skull that will not seal. The meninges of the brain protrude through this gap due to the neural tube failing to close during development. A malformation of the a babys cerebellum is often a sign of this disease </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Autoimmune enteropathy and explain in detail? [/INST] Autoimmune enteropathy (AIE) is a rare disorder of the immune system that affects infants, young children and (rarely) adults causing severe diarrhea, vomiting, and other morbidities of the digestive tract.  AIE causes malabsorption of food, vitamins, and minerals often necessitating replacement fluids and total parenteral nutrition. Some disorders, such as IPEX syndrome, include autoimmune enteropathy as well as autoimmune "pathies" of the skin,  thyroid,  other glands, or kidneys.

Symptoms
The main symptoms of AIE include:

Diarrhea (frequent loss of fluids)
Intestinal inflammation
Vomiting
Intestinal bleeding
Difficulty or inability to gain weight
Rapid weight loss
Decreased urine output from dehydration

Diagnosis
There is a diagnostic test for AIE that looks for an antibody against the enterocyte. The diagnostic test contains the Western Blot which can identify the antibody IgG or IgA and with the immunohistochemistry can localize these antibodies. Endoscopy with biopsies of the colon, small colon, stomach, and other locations may be helpful in diagnosing. This test is done to look at the stomach and small intestines and to see what cells are infiltrating the digestive tract.  There are also documented cases of autoimmune enteropathy where the auto-antibodies were undetectable and the diagnosis was made on the basis of clinical presentation and response to treatment.

Types
There are 3 types of autoimmune enteropathy:Type 1: IPEX syndrome: Immune dysregulation, Polyendocrinopathy, Enteropathy, X – linked
	syndrome, which is caused by a mutation in the FOXP3 gene. This can only affect boys.
Type 2: IPEX-like, which manifests similarly to IPEX syndrome but without recognizable mutations in the FOXP3 gene. This can affect both genders and includes a variety of manifestations of varying severity.
Type 3: Autoimmune manifestations primarily limited to the GI tract. This can affect both genders and may also be considered IPEX-like.
There is considerable overlap in these disorders, and it is often unclear how to properly distinguish between them as the responsible genes are generally poorly understood at this time.

Treatment
Medical therapy is commonly used, most typically with corticosteroids (budesonide and prednisone) </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Anisometropia and explain in detail? [/INST] Anisometropia refers to a condition when two eyes have unequal refractive power. Generally, a difference in power of one diopter (1D) or more is the accepted threshold to label the condition anisometropia. Patients can tolerate 3 D of anisometropia before it becomes clinically symptomatic with headaches, asthenopia, double vision and photophobia.In certain types of anisometropia, the visual cortex of the brain will not process images from both eyes together (binocular summation), and will instead suppress the central vision of one of the eyes. If this occurs often enough during the first 10 years of life while the visual cortex is developing, it can result in amblyopia, a condition where even when correcting the refractive error properly, the persons vision in the affected eye is still not correctable to 20/20.
The name is from four Greek components: an- "not," iso- "same," metr- "measure," ops "eye."
Antimetropia is a rare sub-type of anisometropia, in which one eye is myopic (nearsighted) and the other eye is hyperopic (farsighted). Around 0.1% of the population may be antimetropic.

Causes
Anisometropia is caused by common refractive errors, such as astigmatism, far-sightedness, and myopia, in one eye.Anisometropia is likely the result of both genetic and environmental influences.Some studies suggest, in older adults, developing asymmetric cataracts may cause worsen anisometropia. However, anisometropia is associated with age regardless of cataract development: a rapid decrease in anisometropia during the first years of life, an increase during the transition to adulthood, relatively unchanging levels during adulthood but significant increases in older age.

Diagnosis
Anisometropia causes some people to have mild vision problems, or occasionally more serious symptoms like alternating vision or frequent squinting. However, since most people do not show any clear symptoms, the condition usually is found during a routine eye exam.For early detection in preverbal children, photoscreening can be used. In this brief vision test specialized cameras detect each eyes light reflexes, which the equipments software or a test administrator then interprets. If photoscreening indicates the presence of risk factors, an ophthalmologist can then diagnose the condition after a complete eye exam, including dilating the pupils and measuring the focusing power of each eye.

Treatment
Spectacle correction
For those with large degrees of anisometropia, the wearing of standard spectacles may cause the person to experience a difference in image magnification between the two eyes (aniseikonia) which could also prevent the development of good binocular vision. This can make it very difficult to wear glasses without symptoms such as headaches and eyestrain. However, the earlier the condition is treated, the easier it is to adjust to glasses.
It is possible for spectacle lenses to be made which can adjust the image sizes presented to the eye to be approximately equal. These are called iseikonic lenses. In practice though, this is rarely ever done.
The formula for iseikonic lenses (without cylinder) is:

            Magnification

        =

            1

              (
              1
              −
              (

                  t
                  n

              )
              P
              )

        ⋅

            1

              (
              1
              −
              h
              F
              )

    {\displaystyle {\textrm {Magnification}}={\frac {1}{(1-({\frac {t}{n}})P)}}\cdot {\frac {1}{(1-hF)}}}
  where:  t = center thickness (in metres);n = refractive index;P = front base curve (in 1/metres);h = vertex distance (in metres);F = back vertex power (in 1/metres), (essentially, the prescription for the lens, quoted in diopters).
If the difference between the eyes is up to 3 diopters, iseikonic lenses can compensate. At a difference of 3 diopters the lenses would however be very visibly different — one lens would need to be at least 3 mm thicker and have a base curve increased by 7.5 spheres.

Example
Consider a pair of spectacles to correct for myopia with a prescription of −1.00 m−1 in one eye and −4.00 m−1 in the other.  Suppose that for both eyes the other parameters are identical, namely t = 1 mm = 0.001 m, n = 1.6, P = 5 m−1, and h = 15 mm = 0.015 m.
Then for the first eye

            Magnification

        =

            1

              (
              1
              −
              (
              0.001

                /

              1.6
              )
              ×
              5
              )

        ⋅

            1

              (
              1
              −
              0.015
              ×
              −
              1
              )

        =
        1.0031
        ×
        0.9852
        =
        0.9883
        =
        98.83

        %

    {\displaystyle {\textrm {Magnification}}={\frac {1}{(1-(0.001/1.6)\times 5)}}\cdot {\frac {1}{(1-0.015\times -1)}}=1.0031\times 0.9852=0.9883=98.83\,\%}
  ,
while for the second eye

            Magnification

        =

            1

              (
              1
              −
              (
              0.001

                /

              1.6
              )
              ×
              5
              )

        ⋅

            1

              (
              1
              −
              0.015
              ×
              −
              4
              )

        =
        1.0031
        ×
        0.9434
        =
        0.9464
        =
        94.64

        %

    {\displaystyle {\textrm {Magnification}}={\frac {1}{(1-(0.001/1.6)\times 5)}}\cdot {\frac {1}{(1-0.015\times -4)}}=1.0031\times 0.9434=0.9464=94.64\,\%}
  .
Thus, in the first eye the size of the image formed on the retina will be 1.17% smaller than without spectacles (although it will be sharp, rather than blurry), whilst in the second eye the image formed on the retina will be 5.36% smaller.
As alluded to above, one method of producing more iseikonic lenses would be to adjust the thickness and base curve of the second lens.  For instance, theoretically it could be set to t = 5 mm = 0.005 m and P = 14.5 m−1, with all other parameters unchanged.  Then for the second eye the magnification would become

            Magnification

        =

            1

              (
              1
              −
              (
              0.005

                /

              1.6
              )
              ×
              14.5
              )

        ⋅

            1

              (
              1
              −
              0.015
              ×
              −
              4
              )

        =
        1.0475
        ×
        0.9434
        =
        0.9882
        =
        98.82

        %

    {\displaystyle {\textrm {Magnification}}={\frac {1}{(1-(0.005/1.6)\times 14.5)}}\cdot {\frac {1}{(1-0.015\times -4)}}=1.0475\times 0.9434=0.9882=98.82\,\%}
  ,
which is much closer to that of the first eye.
In this example the first eye, with a −1.00 diopter prescription, is the stronger eye, needing only slight correction to sharpen the image formed, and hence a thin spectacle lens </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Nutcracker esophagus and explain in detail? [/INST] Nutcracker esophagus, Jackhammer esophagus, or hypercontractile peristalsis, is a disorder of the movement of the esophagus characterized by contractions in the smooth muscle of the esophagus in a normal sequence but at an excessive amplitude or duration. Nutcracker esophagus is one of several motility disorders of the esophagus, including achalasia and diffuse esophageal spasm.  It causes difficulty swallowing, or dysphagia, to both solid and liquid foods, and can cause significant chest pain; it may also be asymptomatic.  Nutcracker esophagus can affect people of any age but is more common in the sixth and seventh decades of life.
The diagnosis is made by an esophageal motility study (esophageal manometry), which evaluates the pressure of the esophagus at various points along its length.  The term "nutcracker esophagus" comes from the finding of increased pressures during peristalsis, with a diagnosis made when pressures exceed 180 mmHg; this has been likened to the pressure of a mechanical nutcracker. The disorder does not progress, and is not associated with any complications; as a result, treatment of nutcracker esophagus targets control of symptoms only.

Signs and symptoms
Nutcracker esophagus is characterized as a motility disorder of the esophagus, meaning that it is caused by abnormal movement, or peristalsis of the esophagus. People with motility disorders present with two main symptoms: chest pain or difficulty with swallowing. Chest pain is the more common. The chest pain is very severe and intense, and mimics cardiac chest pain. It may spread into the arm and back. The symptoms of nutcracker esophagus are intermittent, and may occur with or without food. Rarely, patients can present with a sudden obstruction of the esophagus after eating food (termed a food bolus obstruction, or the steakhouse syndrome) requiring urgent treatment. The disorder does not progress to produce worsening symptoms or complications, unlike other motility disorders (such as achalasia) or anatomical abnormalities of the esophagus (such as peptic strictures or esophageal cancer). Many patients with nutcracker esophagus do not have any symptoms at all, as esophageal manometry studies done on patients without symptoms may show the same motility findings as nutcracker esophagus. Nutcracker esophagus may also be associated with metabolic syndrome. The incidence of nutcracker esophagus in all patients is uncertain.

Pathophysiology
Pathology specimens of the esophagus in patients with nutcracker esophagus show no significant abnormality, unlike patients with achalasia, where destruction of the Auerbachs plexus is seen.  The pathophysiology of nutcracker esophagus may be related to abnormalities in neurotransmitters or other mediators in the distal esophagus.  Abnormalities in nitric oxide levels, which have been seen in achalasia, are postulated as the primary abnormality.  As GERD is associated with nutcracker esophagus, the alterations in nitric oxide and other released chemicals may be in response to reflux.

Diagnosis
In patients who have dysphagia, testing may first be done to exclude an anatomical cause of dysphagia, such as distortion of the anatomy of the esophagus.  This usually includes visualization of the esophagus with an endoscope, and can also include barium swallow X-rays of the esophagus. Endoscopy is typically normal in patients with nutcracker esophagus; however, abnormalities associated with gastroesophageal reflux disease, or GERD, which associates with nutcracker esophagus, may be seen. Barium swallow in nutcracker esophagus is also typically normal, but may provide a definitive diagnosis if contrast is given in tablet or granule form. Studies on endoscopic ultrasound show slight trends toward thickening of the muscularis propria of the esophagus in nutcracker esophagus, but this is not useful in making the diagnosis.

Esophageal motility studies
The diagnosis of nutcracker esophagus is typically made with an esophageal motility study, which shows characteristic features of the disorder.  Esophageal motility studies involve pressure measurements of the esophagus after a patient takes a wet (fluid-containing) or dry (solid-containing) swallow.  Measurements are usually taken at various points in the esophagus.Nutcracker esophagus is characterized by a number of criteria described in the literature.  The most commonly used criteria are the Castell criteria, named after American gastroenterologist D.O. Castell.  The Castell criteria include one major criterion: a mean peristaltic amplitude in the distal esophagus of more than 180 mm Hg.  The minor criterion is the presence of repetitive contractions (meaning two or more) that are greater than six seconds in duration.  Castell also noted that the lower esophageal sphincter relaxes normally in nutcracker esophagus, but has an elevated pressure of greater than 40 mm Hg at baseline.Three other criteria for the definition of the nutcracker esophagus have been defined.  The Gothenburg criterion consists of the presence of peristaltic contractions, with an amplitude of 180 mm Hg at any place in the esophagus.  The Richter criterion involves the presence of peristaltic contractions with an amplitude of greater than 180 mm Hg from an average of measurements taken 3 and 8 cm above the lower esophageal sphincter. It has been incorporated into a number of clinical guidelines for the evaluation of dysphagia.  The Achem criteria are more stringent, and are an extension of the study of 93 patients used by Richter and Castell in the development of their criteria, and require amplitudes of greater than 199 mm Hg at 3 cm above the lower esophageal sphincter (LES), greater than 172 mm Hg at 8 cm above the LES, or greater than 102 mm Hg at 13 cm above the LES.

Treatment
People are usually reassured that the disease is unlikely to worsen </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Noonan syndrome and explain in detail? [/INST] Noonan syndrome (NS) is a genetic disorder that may present with mildly unusual facial features, short height, congenital heart disease, bleeding problems, and skeletal malformations. Facial features include widely spaced eyes, light-colored eyes, low-set ears, a short neck, and a small lower jaw. Heart problems may include pulmonary valve stenosis. The breast bone may either protrude or be sunken, while the spine may be abnormally curved. Intelligence in the syndrome is often normal. Complications of NS can include leukemia.A number of genetic mutations can result in Noonan syndrome. The condition may be inherited from a persons parents as an autosomal dominant condition or occur as a new mutation. Noonan syndrome is a type of RASopathy, the underlying mechanism for which involves overactivation within the RAS/MAPK cell signaling pathway. The diagnosis may be suspected based on symptoms, medical imaging, and blood tests. Confirmation may be achieved with genetic testing.No cure for NS is known. Treatment is based on the symptoms and underlying problems, and extra support in school may be required. Growth hormone therapy during childhood can increase an affected persons final height. Long-term outcomes typically depend on the severity of heart problems.An estimated 1 in 1000 people are mildly affected by NS, while about 1 in 2,000 have a more severe form of the condition. Males appear to be affected more often than females. The condition was first described in 1883 and was named after American pediatric cardiologist Jacqueline Noonan, who described further cases in 1963.

Signs and symptoms
The most common signs leading to the diagnosis of Noonan syndrome are unique facial characteristics and musculoskeletal features. The facial characteristics are most prominent in infancy, becoming less apparent with age in many people with Noonan syndrome.

Head
Some of the characteristic features of Noonan syndrome include a large head with excess skin on the back of the neck, low hairline at the nape of the neck, high hairline at the front of the head, triangular face shape, broad forehead, and a short, webbed neck.
In the eyes, hypertelorism (widely set eyes) is a defining characteristic, present in 95% of people with Noonan syndrome. This may be accompanied by epicanthal folds (extra fold of skin at the inner corner of the eye), ptosis (drooping of the eyelids), proptosis (bulging eyes), strabismus (inward or outward turning of the eyes), nystagmus (jerking movement of the eyes) and refractive visual errors.
The nose may be small, wide, and upturned.
The development of the ears and auditory system may be affected in people with Noonans syndrome. This can result in low-set ears (in over 90%), backward-rotated ears (over 90%), thick helix (outer rim) of ear (over 90%), incomplete folding of ears, chronic otitis media (ear infections), and hearing loss.
Development of the mouth may also be affected in Noonan syndrome. This can result in deeply grooved philtrum (top lip line) (over 90%), micrognathia (undersized lower jaw), high arched palate, articulation difficulties (teeth dont line up) which can lead to dental problems. Similar to the muscular manifestations above, in the mouth, poor tongue control may be observed.

Skin
Skin signs and symptoms in Noonan syndrome include lymphedema (lymph swelling of the extremities), keloid formation, excessive scar formation, hyperkeratosis (overdevelopment of outer skin layer), pigmented nevi (darkly pigmented skin spots), and connective tissue disease.

Musculoskeletal
Abnormalities in the limbs and extremities may occur in Noonan syndrome. This may manifest as bluntly ended fingers, extra padding on fingers and toes, edema of the back of hands and tops of feet, and cubitus valgus (wide carrying angle of the elbows).
For short stature, growth hormone is sometimes combined with IGF-1 (or as an alternative, IGF-1 as a stand-alone) can be used to achieve an increased height/final height quicker. The final adult height of individuals with Noonan syndrome is about 161–167 cm in males and 150–155 cm in females, which approaches the lower limit of normal.Spinal abnormalities may be present up to 30% of the time and this may require surgery to correct in over 60% of these cases. Other musculoskeletal manifestations in Noonan syndrome are associated with undifferentiated connective-tissue disorders which can be associated with joint contractures (tightness) or joint hypermobility (looseness). Additional factors may present in the form of winging of the scapula, scoliosis, breast bone prominence (pectus carinatum), breast bone depression (pectus excavatum). Muscle abnormalities may present as hypotonia (low muscle tone), which may lead to lordosis (increased hollow in the back) due to poor abdominal muscle tone.

Heart
Noonan syndrome is the second most common syndromic cause of congenital heart disease. This includes pulmonary valvular stenosis (50–60%), atrial septal defects (10–25%), ventricular septal defects (5–20%) and hypertrophic cardiomyopathy (12–35%).

Lungs
Restrictive lung function has been reported in some people.

Gastrointestinal
A number of diverse gastrointestinal (GI) symptoms have been associated with Noonan syndrome. These include swallowing difficulties, low gut motility, gastroparesis (delayed gastric emptying), intestinal malrotation, and frequent or forceful vomiting. These digestive issues may lead to decreased appetite, failure to thrive from infancy to puberty (75%), and occasionally the need for a feeding tube.

Genitourinary system
In some males with Noonan syndrome, testicles do not descend (cryptorchidism).

Circulation
Lymphatic anomalies including Posterior cervical hygroma (webbed neck) and Lymphedema may present in people with Noonan syndrome.
A number of bleeding disorders have been associated with Noonan syndrome, these include platelet dysfunction, Blood clotting disorders, partial deficiency of factor VIII:C, partial deficiency of factor XI:C, partial deficiency of factor XII:C, and an imbalance of plasminogen activator inhibitor type-1 (PAI-1) and tissue plasminogen activator (t-PA) activity. It has been associated with Von Willebrand disease, Amegakaryocytic thrombocytopenia (low platelet count), prolonged activated partial thromboplastin time, combined coagulation defects. When present, these Noonan-syndrome accompanying disorders can be associated with a predisposition to bruise easily, or hemorrhage.

Neurological
Occasionally, Chiari malformation (type 1), may occur, which can lead to hydrocephalus. Seizures have also been reported.

Causes
Recurrence in siblings and apparent transmission from parent to child has long suggested a genetic defect with autosomal dominant inheritance and variable expression. Mutations in the Ras/mitogen activated protein kinase signaling pathways are known to be responsible for about 70% of NS cases.Persons with NS have up to a 50% chance of transmitting it to their offspring. The fact that an affected parent is not always identified for children with NS suggests several possibilities:

Manifestations could be so subtle as to go unrecognized (variable expressivity)
NS is heterogeneous, comprising more than one similar condition of differing causes, and some of these may not be inherited.
A high proportion of cases may represent new, sporadic mutations.Heterozygous mutations in NRAS, HRAS, BRAF, SHOC2, MAP2K1, MAP2K2, and CBL have also been associated with a smaller percentage of NS and related phenotypes.A condition known as "neurofibromatosis–Noonan syndrome" is associated with neurofibromin.

Diagnosis
NS can be confirmed genetically by the presence of any of the known mutations listed above. However, despite identification of 14 causative genes, the absence of a known mutation will not exclude the diagnosis, as  more, as-yet-undiscovered genes can cause NS. Thus, the diagnosis of NS is still based on clinical features. In other words, it is made when a physician feels that a person has enough of the features to warrant the label. The principal values of making a genetic diagnosis are that it guides additional medical and developmental evaluations, it excludes other possible explanations for the features, and it allows more accurate recurrence risk estimates. With more genotype-phenotype correlation studies being performed, a positive genetic diagnosis will help the clinician to be aware of possible anomalies specific to that certain gene mutation. For example, an increase in hypertrophic cardiomyopathy is seen in people with a mutation of KRAS and an increased risk of juvenile myelomonocytic leukemia exists for a mutation of PTPN11. In the future, studies may lead to a targeted management of NS symptoms that depends on what genetic mutation a person has.

Before birth
Prenatal features that might lead physicians to consider a diagnosis of Noonan syndrome include cystic hygroma, increased nuchal translucency, pleural effusion, and edema.

Differential diagnosis
While Turner syndrome has similarities with renal anomalies and developmental delay, Turner syndrome is only found in females and often expresses differently. In Turner syndrome, there is a lower incidence of developmental delays, left-sided heart defects are constant and the occurrence of renal abnormalities is much lower.Other RASopathies

Watson syndrome - Watson Syndrome has a number of similar characteristics with Noonans Syndrome such as short stature, pulmonary valve stenosis, variable intellectual development, and skin pigment changes.
Cardiofaciocutaneous (CFC) syndrome - CFC syndrome is very similar to Noonans Syndrome due to similar cardiac and lymphatic features. However, In CFC syndrome intellectual disability and gastrointestinal problems are often more severe and pronounced.
Costello syndrome - Like CFC syndrome, Costello syndrome has overlapping features with Noonans Syndrome. However, the conditions can be distinguished by their genetic cause.
Neurofibromatosis 1 (NF1)
Williams syndrome

Management
The treatment varies depending on complications but tend to be quite standard, reflecting the treatment of the general population. Management guidelines, divided by systems, including general, developmental, dental, growth and feeding, cardiovascular, audiological, haematological, renal and skeletal, that account for actions to be taken at diagnosis, after diagnosis and if symptomatic, have been published by an American consortium.Specifically, treatment of cardiovascular complications resemble that of the general population and treatment of bleeding diathesis is guided by the specific factor deficiency or platelet aggregation.
Neuropsychological testing is recommended to find strengths and challenges to tailor support needed for school and career.
Educational customization such as an individualized education program plan is sometimes needed for school-aged children.
Speech therapy if speech and articulation issues present
Physical therapy and occupational therapy for gross- and fine-motor delays
Hypotonia and motor difficulties often impact handwriting. Accommodations for lessening handwriting demands will improve performance and save long-term hand function.
Periodic follow up and lifelong monitoring of abnormalities found in any system, especially the cardiovascular system, is recommended.

Anesthesia risk
Although a few people with Noonan syndrome have been reported to develop malignant hyperthermia, the gene mutation of diseases known to be associated with malignant hyperthermia is different from that of Noonan syndrome.

Prognosis
The lifespan of people with Noonans syndrome can be similar to the general population, however, Noonan syndrome can be associated with several health conditions that can contribute to mortality. The greatest contributor to mortality in individuals with Noonan syndrome is complications of cardiovascular disease. Prognosis is therefore largely dependent on the presence or absence of cardiac disease, as well as the type and severity of the disease (if disease is present). Most notably, Noonan syndrome with hypertrophic cardiomyopathy is associated with increased mortality.

History
Jacqueline Noonan was practicing as a pediatric cardiologist at the University of Iowa when she noticed that children with a rare type of heart defect, valvular pulmonary stenosis, often had a characteristic physical appearance, with short stature, webbed neck, wide spaced eyes, and low-set ears </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Majeed syndrome and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Intraocular hemorrhage and explain in detail? [/INST]  </s>