<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 Neonatal hypoglycemia and can you explain it in depth? [/INST] Neonatal hypoglycemia occurs when the neonates blood glucose level is less than the newborns body requirements for factors such as cellular energy and metabolism. There is inconsistency internationally for diagnostic thresholds. In the US, hypoglycemia is when the blood glucose level is below 30 mg/dL within the first 24 hours of life and below 45 mg/dL thereafter. In the UK, however, lower and more variable thresholds are used (<18 mg/dL at any time OR baby with abnormal clinical signs and a single value <45 mg/dL OR baby at risk of impaired metabolic adaptation but without abnormal clinical signs and a measurement <36 mg/dL and remaining <36 mg/dL at next measurement). The neonates gestational age, birth weight, metabolic needs, and wellness state of the newborn has a substantial impact on the neonates blood glucose level. There are known risk factors that can be both maternal and neonatal. This is a treatable condition. Its treatment depends on the cause of the hypoglycemia. Though it is treatable, it can be fatal if gone undetected.  Hypoglycemia is the most common metabolic problem in newborns.Neonatal hypoglycemia occurs in between 1 in 3 births out of every 1,000 births but is hard to quantify internationally due to lack of consensus about diagnostic thresholds. It often occurs in premature babies, small full-term babies, babies of diabetic mothers, and is more common in neonatal hypoxic asphyxia, sclerosis, and infected sepsis. Severe hypoglycaemia with persistent or repeated episodes can cause damage to the central nervous system. Neonatal hypoglycaemia can be a stand-alone condition or a clinical manifestation of other conditions.

Signs and symptoms
The way in which neonatal hypoglycemia symptoms may be presented is vague or hard to tell apart from other conditions. The symptoms can be confused with:

hypocalcemia
Sepsis
CNS disorders
Cardiorespiratory problemsNeonatal hypoglycemia can also show no symptoms in some newborns or may be life-threatening.Some observed symptoms are (these symptoms may be transient but reoccurring):

Jitteriness
hypothermia
irritability
pallor
tremors
twitching
weak or high pitched cry
lethargy
hypotonia
generalized seizures
coma
cyanosis
apnea
rapid and irregular respirations
diaphoresis
eye rolling
refusal to feed
hunger

Causes
Risk Factors
Mother
Risk factors in the mother that increased the risk of developing hypoglycemia shortly after birth include:

Type 1 diabetes
Gestational diabetes mellitus (Transient)
Intrapartum glucose administration (Transient)
Gestational hypertension
Preeclampsia
Terbutaline administration (Transient)
Intrauterine growth restriction (Transient)
Perinatal stress or asphyxia (Transient)

Baby
Babies which have an increased risk of developing hypoglycemia shortly after birth are:

hypothermia (Transient)
polycythemia (Transient)
hyperinsulinism (Recurrent)
IEMs (Recurrent)
Beckwith-Wiedmann syndrome (Recurrent)
nesidioblastosis (Recurrent)
Rh isoimmunization (Recurrent)
Certain endocrine disorders (Recurrent)
fetal hydrops
Prematurity (Transient)
congenital malformations
small for gestational age (Transient)
Large for gestational age (Transient)

Hyperinsulinism
The most common cause on neonatal hypoglycemia is hyperinsulinism. Hyperinsulinism is also called persistent hyperinsulemic hypoglycemia of infancy (PHHI). This is seen very frequently to the neonates born from mothers with diabetes. Congenital hyperinsulinism is correlated with the abnormality of beta-cell regulation within the pancreas. Isolated islet adenoma, which is a focal disease, is often the cause of congenital hyperinsulism. Drug-induced hyperinsulisim is correlated with the administration insulin or use of hypoglycemic medication. In critical cases, a drug called Diazoxide is availed to stop any secretion of insulin.

Limited glycogen stores
Limited glycogen storage occurs in premature newborns or newborns that had intrauterine growth retardation.

Increased glucose use
Major causes of increased glucose use in a newborn include hyperthermia, polycythemia, sepsis, and growth hormone deficiency.

Decreased gluconeogenesis
Two major issues that cause decreased gluconogeneis are inborn errors of metabolism and adrenal insufficiency.

Depeleted glycogen stores
Most common causes of depleted glycogen stores are starvation and asphyxia-perinatal stress.

Mechanism
There are many types of hypoglycemia, including transient and reoccurring. Each is associated with different risk factors and may have many underlying causes. Neonatal hypoglycemia occurs because an infants brain is dependent on a healthy supply of glucose. During the last trimester of pregnancy, glucose is stored in the liver, heart, and skeletal muscles. All newborns experience a physiological and transient fall in blood glucose, reaching a nadir at 2–3 hours of age before slowly rising over the next 24 hours. Newborns do have the ability to use an alternative form of energy, especially if breastfed. However, some newborns are only able to compensate this glucose deficiency up to a certain limit. Infants who have hyperinsulinism may increase the risk to develop hypoglycemia. There are other conditions that can increase the risk of an infant becoming hypoglycemic (See Risks).

Diagnosis
Screening for hypoglycemia is done on every neonate on admission in the USA  but this is not recommended practice in all developed countries. One way of screening includes a heel stick to test the blood glucose level at the bedside. Diagnosing hypoglycemia in neonates requires two consecutive blood glucose readings of less than 40 mg/dL to properly diagnose hypoglycemia. Bedside glucose monitoring is only effective if the equipment is accurate, rapid, and reliable.  This form of testing is often faster and more cost effective.  Laboratory serum glucose testing is the most accurate way of testing blood glucose levels.  These specimens are either taken from the heel, arterial, or venous punctures and must be store immediately on ice in order to prevent glycolysis, further altering the results.  USA guidelines recommended that the hypoglycemic neonate should have a glucose test every 2–4 hours for the first 24 hours of life. Guidelines in the UK, however, recommend pre-feed screening of at-risk infants at 2–4 hours of age (to avoid false positives when blood glucose is, ordinarily, at its lowest at 2–3 hours of age) and at the subsequent feed until a blood glucose level of  >2.0 mmol/L (36 mg/dL) on at least two consecutive occasions and is feeding well.
1. Medical history
Maternal diabetes mellitus, gestational hypertension, neonatal erythrocytosis, neonatal haemolysis of incompatible blood groups, perinatal asphyxia, severe infection, sclerosis, neonatal respiratory distress syndrome, etc., especially in premature babies, babies younger than gestational age and those who are underfed in the early stages of life are at risk of neonatal hypoglycaemia.
2. Clinical manifestations
Neonatal hypoglycemia should be considered if there are atypical clinical manifestations, if the symptoms improve after glucose infusion, or if there are neurological symptoms and signs that cannot be easily explained.
3. Blood glucose measurement
Postnatal glucose monitoring is the main method of early detection of neonatal hypoglycaemia. In particular, children at risk of neonatal hypoglycaemia should have their blood glucose monitored within one hour of birth.

Management
Some infants are treated with 40% dextrose (a form of sugar) gel applied directly to the infants mouth. There are two main ways that neonatal hypoglycemia is treated.  The first way includes intravenous infusion of glucose.  For less severe, borderline, asymptomatic hypoglycemic neonates early introduction of breast milk can be effective for raising glucose levels to a healthy level.  Any infant at risk of hypoglycemia should have their blood sugar taken again one hour after birth.  Oral glucose is another option to restore normal glucose levels if the newborn is having difficulty latching to the breast or breastfeeding is not an option, however, breast milk is proven to be a better source as it includes glucose and carbohydrates.  It is recommended by The American Academy of Pediatrics that infants feed within the first hour of life with the glucose reading being 30 minutes after this feeding for an accurate result.  If the initial feeding does not raise the newborns blood glucose above 40 mg/dL then the newborn must receive an IV infusion of 10% dextrose in water as a mini bolus as 2 mL/kg over 1 minute. Following the mini bolus a continuous infusion of 10% dextrose in water at 80-100 mL/kg/day in order to maintain a healthy serum glucose level between 40 and 50 mg/dL.  Maintaining newborn thermoregulation is a large part in preventing further hypoglycemia as well.

Nursing care management
The biggest nursing concern for a neonate experiencing hypoglycemia is the physical assessment to potentially find the cause </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 Spindle cell lipoma 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 Congenital hyperinsulinism and can you explain it in depth? [/INST] Congenital hyperinsulinism  is a medical term referring to a variety of congenital disorders in which hypoglycemia is caused by excessive insulin secretion. Congenital forms of hyperinsulinemic hypoglycemia can be transient or persistent, mild or severe. These conditions are present at birth and most become apparent in early infancy. Mild cases can be treated by frequent feedings, more severe cases can be controlled by medications that reduce insulin secretion or effects.

Signs and symptoms
Hypoglycemia in early infancy can cause jitteriness, lethargy, unresponsiveness, or seizures. The most severe forms may cause macrosomia in utero, producing a large birth weight, often accompanied by abnormality of the pancreas. Milder hypoglycemia in infancy causes hunger every few hours, with increasing jitteriness or lethargy. Milder forms have occasionally been detected by investigation of family members of infants with severe forms, adults with the mildest degrees of congenital hyperinsulinism have a decreased tolerance for prolonged fasting.Other presentations are:
Dizziness
Intellectual disability
Hypoglycemic coma
CardiomegalyThe variable ages of presentations and courses suggest that some forms of congenital hyperinsulinism, especially those involving abnormalities of KATP channel function, can worsen or improve with time. The potential harm from hyperinsulinemic hypoglycemia depends on the severity, and duration. Children who have recurrent hyperinsulinemic hypoglycemia in infancy can suffer harm to the brain.

Cause
The cause of congenital hyperinsulinism has been linked to anomalies in nine genes. The diffuse form of this condition is inherited via the autosomal recessive manner (though sometimes in autosomal dominant).

Pathophysiology
In terms of the mechanism of congenital hyperinsulinism one sees that channel trafficking requires KATP channels need the shielding of ER retention signal.E282K prevents the KATP channel surface expression, the C-terminus (SUR1 subunit) is needed in KATP channel mechanism.R1215Q mutations (ABCC8 gene) affect ADP gating which in turn inhibits KATP channel.

Diagnostic
In terms of the investigation of congenital hyperinsulinism, valuable diagnostic information is obtained from a blood sample drawn during hypoglycemia,  detectable amounts of insulin during hypoglycemia are abnormal and indicate that hyperinsulinism is likely to be the cause. Inappropriately low levels of free fatty acids and ketones provide additional evidence of insulin excess. An additional piece of evidence indicating hyperinsulinism is a usually high requirement for intravenous glucose to maintain adequate glucose levels, the minimum glucose required to maintain a plasma glucose above 70 mg/dl. A GIR above 8 mg/kg/minute in infancy suggests hyperinsulinism. A third form of evidence suggesting hyperinsulinism is a rise of the glucose level after injection of glucagon at the time of the low glucose.Diagnostic efforts then shift to determining the type- elevated ammonia levels or abnormal organic acids can indicate specific, rare types. Intrauterine growth retardation and other perinatal problems raise the possibility of transience, while large birthweight suggests one of the more persistent conditions. Genetic screening is now available within a useful time frame for some of the specific conditions. It is worthwhile to identify the minority of severe cases with focal forms of hyperinsulinism because these can be completely cured by partial pancreatectomy. A variety of pre-operative diagnostic procedures have been investigated but none has been established as infallibly reliable. Positron emission tomography is becoming the most useful imaging technique.

Differential diagnosis
The differential diagnosis of congenital hyperinsulinism is consistent with PMM2-CDG, as well as several syndromes. Among other diagnoses, the following are listed:
MPI-CDG
Beckwith-Wiedemann syndrome
Sotos syndrome
Usher 1 syndromes

Types
Congenital hyperinsulinism has two types, diffuse and focal, as indicated below:

Treatment
In terms of treatment, acute hypoglycemia is reversed by raising the blood glucose, but in most forms of congenital hyperinsulinism hypoglycemia recurs and the therapeutic effort is directed toward preventing falls and maintaining a certain glucose level. Some of the following measures are often tried:

Corn starch can be used in feeding; unexpected interruptions of continuous feeding regimens can result in sudden hypoglycemia, gastrostomy tube insertion (requires a minor surgical procedure) is used for such feeding. Prolonged glucocorticoid use incurs the many unpleasant side effects of Cushings syndrome, while diazoxide can cause fluid retention requiring concomitant use of a diuretic, and prolonged use causes hypertrichosis. Diazoxide works by opening the KATP channels of the beta cells. Octreotide must be given by injection several times a day or a subcutaneous pump must be inserted every few days, octreotide can cause abdominal discomfort and responsiveness to octreotide often wanes over time. Glucagon requires continuous intravenous infusion, and has a very short half-life.Nifedipine is effective only in a minority, and dose is often limited by hypotension.
Pancreatectomy (removal of a portion or nearly all of the pancreas) is usually a treatment of last resort when the less-drastic medical measures fail to provide prolonged normal blood sugar levels. For some time, the most common surgical procedure was removal of almost all of the pancreas; this cured some infants but not all. Insulin-dependent diabetes mellitus commonly develops, though in many cases it occurs many years after the pancreatectomy </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 Hypocalciuria 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 Acute fatty liver of pregnancy and can you explain it in depth? [/INST] Acute fatty liver of pregnancy is a rare life-threatening complication of pregnancy that occurs in the third trimester or the immediate period after delivery.  It is thought to be caused by a disordered metabolism of fatty acids by mitochondria in the fetus, caused by long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency. This leads to decreased metabolism of long chain fatty acids by the feto-placental unit, causing subsequent rise in hepatotoxic fatty acids in maternal plasma. The condition was previously thought to be universally fatal, but aggressive treatment by stabilizing the mother with intravenous fluids and blood products in anticipation of early delivery has improved prognosis.

Signs and symptoms
Acute fatty liver of pregnancy (or hepatic lipidosis of pregnancy) usually manifests in the third trimester of pregnancy, but may occur any time in the second half of pregnancy, or in the puerperium, the period immediately after delivery.  On average, the disease presents during the 35th or 36th week of pregnancy.  The usual symptoms in the mother are non-specific including nausea, vomiting, anorexia (or lack of desire to eat) and abdominal pain; excessive thirst may be the earliest symptom without overlap with otherwise considered normal pregnancy symptoms; however, jaundice and fever may occur in as many as 70% of patients.In patients with more severe disease, pre-eclampsia may occur, which involves elevation of blood pressure and accumulation of fluid (termed oedema).  This may progress to involvement of additional systems, including acute kidney failure, hepatic encephalopathy, and pancreatitis.  There have also been reports of diabetes insipidus complicating this condition.Many laboratory abnormalities are seen in acute fatty liver of pregnancy.  Liver enzymes are elevated, with the AST and ALT enzymes ranging from minimal elevation to 1000 IU/L, but usually staying in the 300-500 range.  Bilirubin is almost universally elevated.  Alkaline phosphatase is often elevated in pregnancy due to production from the placenta, but may be additionally elevated.  Other abnormalities may include an elevated white blood cell count, hypoglycemia, elevated coagulation parameters, including the international normalized ratio, and decreased fibrinogen.  Frank disseminated intravascular coagulation, or DIC, may occur in as many as 70% of people.Abdominal ultrasound may show fat deposition in the liver, but, as the hallmark of this condition is microvesicular steatosis (see pathology below), this is not seen on ultrasound.  Rarely, the condition can be complicated by rupture or necrosis of the liver, which may be identified by ultrasound.

Pathophysiology
The understanding of the causes of acute fatty liver of pregnancy
has been improved by advances in mitochondrial biochemistry.  Deficiency of LCHAD (3-hydroxyacyl-CoA dehydrogenase) leads to an accumulation of medium and long chain fatty acids.  When this occurs in the foetus, the unmetabolized fatty acids will re-enter the maternal circulation through the placenta, and overwhelm the beta-oxidation enzymes of the mother.  The gene responsible for LCHAD has been isolated, and the most common mutation found in acute fatty liver of pregnancy is the E474Q missense mutation.  LCHAD deficiency is autosomal recessive in inheritance and mothers are often found to be heterozygous for the affected mutation.

Diagnosis
The diagnosis of acute fatty liver of pregnancy is usually made on clinical grounds by the treating physician, but differentiation from other conditions affecting the liver may be difficult.  The diagnosis of acute fatty liver of pregnancy is suggested by jaundice with a lesser elevation of liver enzymes, elevated white blood cell count, disseminated intravascular coagulation, and a clinically unwell patient.A liver biopsy can provide a definitive diagnosis, but is not always done, due to the increased chance of bleeding in acute fatty liver of pregnancy.  Often testing will be done to exclude more common conditions that present in a similar fashion, including viral hepatitis, pre-eclampsia, HELLP syndrome, intrahepatic cholestasis of pregnancy, and autoimmune hepatitis.

Pathology
If a liver biopsy is needed for diagnosis of the condition, the mother should be appropriately stabilized and treated to reduce bleeding related complications.  The diagnosis can be made by a frozen-section (as opposed to a specimen in formalin) that is stained with the Oil red O stain, that shows microvesicular steatosis (or small collections of fat within the liver cells).  The microvesicular steatosis usually spares zone one of the liver, which is the area closest to the hepatic artery.  On the regular trichrome stain, the liver cell cytoplasm shows a foamy appearance due to the prominence of fat.  Necrosis is rarely seen.  The diagnosis can be enhanced by electron microscopy which can be used to confirm the presence of microvesicular steatosis, and specifically the presence of megamitochondria and paracrystalline inclusions.  Liver diseases with similar appearances include Reyes syndrome, drug-induced hepatitis from agents with mitochondrial toxicity, including nucleoside reverse transcriptase inhibitors used to treat HIV, and a rare condition known as Jamaican vomiting sickness which is caused by the eating of the unripened Ackee fruit.

Treatment
Acute fatty liver of pregnancy is best treated in a centre with expertise in hepatology, high-risk obstetrics, maternal-fetal medicine and neonatology.  The physicians who treat this condition will often consult with experts in liver transplantation in severe cases.  Admission to the intensive care unit is recommended.Initial treatment involves supportive management with intravenous fluids, intravenous glucose and blood products, including fresh frozen plasma and cryoprecipitate to correct DIC.  The foetus should be monitored with cardiotocography </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 Angiolipoma 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 Supraspinatus muscle and can you explain it in depth? [/INST] The supraspinatus (plural supraspinati) is a relatively small muscle of the upper back that runs from the supraspinous fossa superior portion of the scapula (shoulder blade) to the greater tubercle of the humerus. It is one of the four rotator cuff muscles and also abducts the arm at the shoulder. The spine of the scapula separates the supraspinatus muscle from the infraspinatus muscle, which originates below the spine.

Structure
The supraspinatus muscle arises from the supraspinous fossa, a shallow depression in the body of the scapula above its spine. The supraspinatus muscle tendon passes laterally beneath the cover of the acromion. Research in 1996 showed that the postero-lateral origin was more lateral than classically described.The supraspinatus tendon is inserted into the superior facet of the greater tubercle of the humerus. The distal attachments of the three rotator cuff muscles that insert into the greater tubercle of the humerus can be abbreviated as SIT when viewed from superior to inferior (for supraspinatus, infraspinatus, and teres minor), or SITS when the subscapularis muscle, which attaches to the lesser tubercle of the humerus, is included.

Nerve supply
The suprascapular nerve (C5) innervates the supraspinatus muscle as well as the infraspinatus muscle. It comes from the upper trunk of the brachial plexus.
This nerve can be damaged along its course in fractures of the overlying clavicle, which can reduce the persons ability to initiate the abduction.

Function
The supraspinatus muscle performs abduction of the arm, and pulls the head of the humerus medially towards the glenoid cavity. It independently prevents the head of the humerus from slipping inferiorly. The supraspinatus works in cooperation with the deltoid muscle to perform abduction, including when the arm is in an adducted position. Beyond 15 degrees the deltoid muscle becomes increasingly more effective at abducting the arm and becomes the main propagator of this action.

Clinical significance
The supraspinatus forms part of the rotator cuff and is one of its most frequently damaged components, whether from acute injury or gradual degeneration. Bad posture and age are leading risk factors, with a high prevalence of unsymptomatic partial and full tears, as well as symptomatic syndromes with chronic pain. Connected pathologies include acromial impingement, frozen shoulder, and poor sleep, especially on the side. Both ultrasound and MRI are now effective methods of diagnosis.

Tear
DiagnosisAntero-posterior projectional radiography of the shoulder may demonstrate a high-riding humeral head, with an acromiohumeral distance of less than 7 mm.
RepairOne study has indicated that arthroscopic surgery for full-thickness supraspinatus tears is effective for improving shoulder functionality.A comparative effectiveness review  of nonoperative and operative treatments for rotator cuff tears was performed at the University of Alberta Evidence-based Practice Center in 2010. The review identified one study which reported that, "Patients receiving early surgery had superior function compared with the delayed surgical group". The review noted that the level of significance of the study was not reported, and the review chose not to include it as one of their conclusions </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 Short anagen syndrome and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Accommodative excess 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 Hypersensitivity pneumonitis and can you explain it in depth? [/INST] Hypersensitivity pneumonitis (HP) or extrinsic allergic alveolitis (EAA) is a syndrome caused by the repetitive inhalation of antigens from the environment in susceptible or sensitized people. Common antigens include molds, bacteria, bird droppings, bird feathers, agricultural dusts, bioaerosols and chemicals from paints or plastics. People affected by this type of lung inflammation (pneumonitis) are commonly exposed to the antigens by their occupations, hobbies, the environment and animals. The inhaled antigens produce a hypersensitivity immune reaction causing inflammation of the airspaces (alveoli) and small airways (bronchioles) within the lung. Hypersensitivity pneumonitis may eventually lead to interstitial lung disease.

Signs and symptoms
Hypersensitivity pneumonitis (HP) can be categorized as acute, subacute, and chronic based on the duration of the illness.

Acute
In the acute form of HP dose of antigen exposure tends to be very high but only for a short duration. Symptoms may develop 4–6 hours following heavy exposure to the provoking antigen. Symptoms include fever, chills, malaise, cough, chest tightness, dyspnea, rash, swelling and headache. Symptoms resolve within 12 hours to several days upon cessation of exposure.

Subacute
Patients with subacute HP gradually develop a productive cough, dyspnea, fatigue, anorexia, weight loss, and pleurisy. Symptoms are similar to the acute form of the disease, but are less severe and last longer. Findings may be present in patients who have experienced repeated acute attacks.

Chronic
In chronic HP, dose of the antigen tends to be low volume but for a longer duration. Patients often lack a history of acute episodes. They have an insidious onset of cough, progressive dyspnea, fatigue, and weight loss. This is associated with partial to complete but gradual reversibility. Avoiding any further exposure is recommended. Clubbing is observed in 50% of patients. Tachypnea, respiratory distress, and inspiratory crackles over lower lung fields often are present. In fact, hypersensitivity pneumonitis can often resemble (IPF) in terms of pulmonary fibrosis and that many patients experience hypoxemia.

Epidemiology
Although the prevalence of hypersensitivity pneumonitis is not established it is thought to be low.  Data collection limitations are a result of difficulty in diagnosis, sub-clinical presentations that go undetected and variability in climate, region and proximity to local industries. The most common types are bird fanciers and farmers lung. Interestingly, cigarette smoking appears to be protective against the disease.

Pathophysiology
Hypersensitivity pneumonitis is caused by an exaggerated immune response (hypersensitivity). Type III hypersensitivity and type IV hypersensitivity can both occur depending on the cause. In general, acute HP is suspected to be attributed to a type III hypersensitivity while the subacute and chronic types are suspected to be caused by T cell infiltration and granuloma formation. Because different people react variably to antigen exposure, the exact mechanism is unclear but genetic and host factors are likely at play. The two hit hypothesis is often toted in the literature to explain why some people have a normal reaction to an antigenic exposure without clinical findings while others experience an exaggerated immune response. The "first hit" in the hypothesis is proposed to be genetic susceptibility and surrounding environmental factors and the "second hit" would be the introduction of the antigen into the respiratory system which causes the exaggerated immune response.

Diagnosis
The diagnosis is made through clinical judgement using a combination of findings because there does not exist a single, universal diagnostic criteria for the disease. The diagnosis is most commonly ascertained first with a detailed exposure history followed by a battery of clinical tests including: imaging, histopathology, pulmonary function testing, serology, bronchoscopy, and more. In 2020, official guidelines were published by American Thoracic Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax which provides a systematic approach to the diagnosis of HP that relies on high-resolution computed tomography.

Exposure History
A detailed occupational, home and environmental exposure history is the first step in diagnosis. Unfortunately, only 60% of inciting antigens are identified in exposure assessment. Re-exposure to the antigen can help aid in diagnosis. Standardized questionnaires have been created to help in obtaining an exposure history although no official questionnaire has been purported. It has been recommended that the questionnaire administered should be relevant to the region in which the exposure has potentially occurred.Detailed exposure assessments are warranted in the cause of damp indoor environments which have the potential to propagate mold throughout the dwelling. The decision to enlist an industrial hygienist should be made based on the answers to evidence based questions during the environmental assessment. The industrial hygeinst or environmental scientist will make the decision to conduct additional sampling.

Types
Hypersensitivity pneumonitis may also be called many different names, based on the provoking antigen. These include:

Of these types, Farmers Lung and Bird-Breeders Lung are the most common. "Studies document 8-540 cases per 100,000 persons per year for farmers and 6000-21,000 cases per 100,000 persons per year for pigeon breeders. High attack rates are documented in sporadic outbreaks. Prevalence varies by region, climate, and farming practices. HP affects 0.4–7% of the farming population. Reported prevalence among bird fanciers is estimated to be 20-20,000 cases per 100,000 persons at risk."

Imaging
No single imaging finding is singularly definitive of a diagnosis rather clinicians rely on a constellation of findings. Both chest radiographs and high resolution CT scans can be normal.

Chest Radiographs
Acute presentation may reveal poorly defined a micro-nodular interstitial pattern and ground-glass opacities in the lower and mid lung zones. In addition to this, subacute presentations may show reticular nodular opacities in mid-to-lower lung zones. Chronic forms may show fibrotic changes and appear like Idiopathic pulmonary fibrosis.

High-Resolution Computed Tomography
This has become a common diagnostic imaging for the diagnosis and is the modality used in the Official ATS/JRS/ALAT Clinical Practice Guideline. Two forms of hypersensitivity pneumonitis are fibrotic and non-fibrotic findings on chest CT. The two differ in terms of their diagnostic work up and management although there is overall between them. The non-fibrotic form is typically characterized by ground glass opacities, mosaic attenuation, ill-defined centrilobular nodules (<5 mm), and air trapping. The fibrotic form is typically characterized by irregular linear opacities/coarse reticulations, traction bronchiectasis, and honeycombing, patchy ground-glass attenuation, centrilobular nodules, and mosaic attenuation. Three-density pattern (head cheese sign) is radiological sign which shows a region of the lung with three or more different types of attenuation which can be typical for the fibrotic type.

Histopathology
The acute form can be characterized by poorly formed noncaseating interstitial granulomas and mononuclear cell infiltration in a peribronchial distribution with prominent giant cells. The subacute, or intermittent, form produces more well-formed noncaseating granulomas, bronchiolitis with or without organizing pneumonia, and interstitial fibrosis. Much like the pathogenesis of idiopathic pulmonary fibrosis (IPF), chronic HP is related to increased expression of Fas antigen and Fas ligand, leading to increased epithelial apoptosis activation in the alveoli. Cholesterol clefts or asteroid bodies are present within or outside granulomas.

Pulmonary Function Testing
Pulmonary function tests (PFTs) can generally reveal a restrictive pattern  however, either a restrictive or obstructive pattern (or both) may emerge on PFTs. PFTs, therefore, are less useful in making a diagnosis but rather tracking improvement or deterioration in lung function following removal or addition of suspected antigens. They may also demonstrate reduced diffusion capacity of lungs for carbon monoxide (DLCO).

Bronchoscopy
Bronchoalveolar lavage (BAL) is a reliable way to detect inflammation in the lung airways. Fluid analysis from the lavage extracted from the airways on bronchoscopy often reveals a total elevation in cell count in addition to an elevation in the percentage of T lymphocytes. This is a good way to help exclude other similar lung diseases like sarcoidosis, infection and Idiopathic pulmonary fibrosis.

Lung biopsy
Lung biopsies can be diagnostic in cases of chronic hypersensitivity pneumonitis, or may help to suggest the diagnosis and trigger or intensify the search for an allergen. The main feature of chronic hypersensitivity pneumonitis on lung biopsies is expansion of the interstitium by lymphocytes accompanied by an occasional multinucleated giant cell or loose granuloma.When fibrosis develops in chronic hypersensitivity pneumonitis, the differential diagnosis in lung biopsies includes the idiopathic interstitial pneumonias. This group of diseases includes usual interstitial pneumonia, non-specific interstitial pneumonia and cryptogenic organizing pneumonia, among others.The prognosis of some idiopathic interstitial pneumonias, e.g. idiopathic usual interstitial pneumonia (i.e. idiopathic pulmonary fibrosis), are very poor and the treatments of little help.  This contrasts the prognosis (and treatment) for hypersensitivity pneumonitis, which is generally fairly good if the allergen is identified and exposures to it significantly reduced or eliminated.  Thus, a lung biopsy, in some cases, may make a decisive difference.

Serum Precipitins
Assays for serum IgGs can aid in identifying possible antigenic exposures and are used as markers of exposure  However, there use is limited in making a definitive diagnosis because serum antibody levels are often elevated in those people who are exposed to an antigen but do not have the disease. Up to 90% of people exposed to the antigen have precipitins but only 50% of similarly exposed people who are asymptomatic have the same precipitins. False negatives are often common with serum precipitins because of lack of testing reagents for many antigens.Precipitating IgG antibodies against fungal or avian antigens can be detected in the laboratory using the traditional Ouchterlony immunodiffusion method wherein precipitin lines form on agar plate. The ImmunoCAP technology has replaced this time-consuming, labor-intensive method with their automated CAP assays and FEIA (Fluorescence enzyme immunoassay) that can detect IgG antibodies against Aspergillus fumigatus (Farmers lung or for ABPA) or avian antigens (Bird Fanciers Lung).

Differential Diagnosis
Organic dust toxic syndrome presents similarly with fevers, chills a few hours after exposure to bioaerosols with toxins from fungi, however this is not a true hypersensitivity reaction because it occurs on initial exposure without a preceding sensitization In chronic disease, HP must be differentiated from very similarly presenting idiopathic pulmonary fibrosis.Although overlapping in many cases, hypersensitivity pneumonitis may be distinguished from occupational asthma in that it is not restricted to only occupational exposure, and that asthma generally is classified as a type I hypersensitivity. Unlike asthma, hypersensitivity pneumonitis targets lung alveoli rather than bronchi.Similarly, sarcoidosis has noncaseating granuloma formation, however hilar adenopathy is often seen on chest radiographs.

Treatment
The best treatment is to avoid the provoking allergen, as chronic exposure can cause permanent damage and acute disease is often self-limiting </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 Bruise and can you explain it in depth? [/INST] A bruise, also known as a contusion, is a type of hematoma of tissue, the most common cause being capillaries damaged by trauma, causing localized bleeding that extravasates into the surrounding interstitial tissues. Most bruises are not very deep under the skin so that the bleeding causes a visible discoloration. The bruise then remains visible until the blood is either absorbed by tissues or cleared by immune system action. Bruises which do not blanch under pressure can involve capillaries at the level of skin, subcutaneous tissue, muscle, or bone. Bruises are not to be confused with other similar-looking lesions. (Such lesions include petechia (less than 3 mm (0.12 in), resulting from numerous and diverse etiologies such as adverse reactions from medications such as warfarin, straining, asphyxiation, platelet disorders and diseases such as cytomegalovirus), purpura (3–10 mm (0.12–0.39 in), classified as palpable purpura or non-palpable purpura and indicates various pathologic conditions such as thrombocytopenia),  and ecchymosis (more than 1 cm (0.39 in), caused by blood dissecting through tissue planes and settled in an area remote from the site of trauma or pathology such as periorbital ecchymosis, e.g. "raccoon eyes", arising from a basilar skull fracture or from a neuroblastoma).As a type of hematoma, a bruise is always caused by internal bleeding into the interstitial tissues which does not break through the skin, usually initiated by blunt trauma, which causes damage through physical compression and deceleration forces. Trauma sufficient to cause bruising can occur from a wide variety of situations including accidents, falls, and surgeries. Disease states such as insufficient or malfunctioning platelets, other coagulation deficiencies, or vascular disorders, such as venous blockage associated with severe allergies can lead to the formation of purpura which is not to be confused with trauma-related bruising/contusion. If the trauma is sufficient to break the skin and allow blood to escape the interstitial tissues, the injury is not a bruise but bleeding, a different variety of hemorrhage. Such injuries may be accompanied by bruising elsewhere.

Signs and symptoms
Bruises often induce pain immediately after the trauma that results in their formation, but small bruises are not normally dangerous alone. Sometimes bruises can be serious, leading to other more life-threatening forms of hematoma, such as when associated with serious injuries, including fractures and more severe internal bleeding.  The likelihood and severity of bruising depends on many factors, including type and healthiness of affected tissues. Minor bruises may be easily recognized in people with light skin color by characteristic blue or purple appearance (idiomatically described as "black and blue") in the days following the injury.
Hematomas can be subdivided by size. By definition, ecchymoses are 1 centimetres in size or larger, and are therefore larger than petechiae (less than 3 millimetres in diameter) or purpura (3 to 10 millimetres in diameter). Ecchymoses also have a more diffuse border than other purpura. A broader definition of ecchymosis is the escape of blood into the tissues from ruptured blood vessels. The term also applies to the subcutaneous discoloration resulting from seepage of blood within the injured tissue.
Bruise colors vary from red, blue, or almost black, depending on the severity of broken capillaries or blood vessels within the bruise site. Broken venules or arterioles often result in a deep blue or dark red bruise, respectively. Darker colored bruises may result from a more severe bleeding from both blood vessels. Older bruises may appear yellow, green or brown.

Cause
There are many causes of subcutaneous hematomas including ecchymoses. Coagulopathies such as Hemophilia A may cause ecchymosis formation in children. The medication betamethasone can have the adverse effect of causing ecchymosis.The presence of bruises may be seen in patients with platelet or coagulation disorders, or those who are being treated with an anticoagulant. Unexplained bruising may be a warning sign of child abuse, domestic abuse, or serious medical problems such as leukemia or meningoccocal infection. Unexplained bruising can also indicate internal bleeding or certain types of cancer. Long-term glucocorticoid therapy can cause easy bruising. Bruising present around the navel (belly button) with severe abdominal pain suggests acute pancreatitis. Connective tissue disorders such as Ehlers-Danlos syndrome may cause relatively easy or spontaneous bruising depending on the severity. Spontaneous bruising or bruising with minimal trauma in the absence of other explanations and together with other minor or major criteria suggestive of Vascular Ehlers-Danlos Syndrome (vEDS) suggests genetic testing for the condition.During an autopsy, bruises accompanying abrasions indicate the abrasions occurred while the individual was alive, as opposed to damage incurred post mortem.

Size and shape
Bruise shapes may correspond directly to the instrument of injury or be modified by additional factors. Bruises often become more prominent as time lapses, resulting in additional size and swelling, and may grow to a large size over the course of the hours after the injury that caused the bruise was inflicted.

Condition and type of tissue: In soft tissues, a larger area is bruised than would be in firmer tissue due to ease of blood to invade tissue.
Age: elderly skin and other tissues are often thinner and less elastic and thus more prone to bruising.
Gender: More bruising occurs in females due to increased subcutaneous fat.
Skin tone: Discoloration caused by bruises is more prominent in lighter complexions.
Diseases: Coagulation, platelet and blood vessel diseases or deficiencies can increase bruising due to more bleeding.
Location: More extensive vascularity causes more bleeding. Areas such as the arms, knees, shins and the facial area are especially common bruise sites.
Forces: Greater striking forces cause greater bruising.
Genes: Despite having completely normal coagulation factors, natural redheads have been shown to bruise more, although this may just be due to greater visibility on commonly associated lighter complexion.

Severity
Bruises can be scored on a scale from 0–5 to categorize the severity and danger of the injury.

The harm score is determined by the extent and severity of the injuries to the organs and tissues causing the bruising, in turn depending on multiple factors.  For example, a contracted muscle will bruise more severely, as will tissues crushed against underlying bone.  Capillaries vary in strength, stiffness and toughness, which can also vary by age and medical conditions.
Low levels of damaging forces produce small bruises and generally cause the individual to feel minor pain straight away. Repeated impacts worsen bruises, increasing the harm level. Normally, light bruises heal nearly completely within two weeks, although duration is affected by variation in severity and individual healing processes; generally, more severe or deeper bruises take somewhat longer.
Severe bruising (harm score 2–3) may be dangerous or cause serious complications.  Further bleeding and excess fluid may accumulate causing a hard, fluctuating lump or swelling hematoma.  This has the potential to cause compartment syndrome in which the swelling cuts off blood flow to the tissues.  The trauma that induced the bruise may also have caused other severe and potentially fatal harm to internal organs.  For example, impacts to the head can cause traumatic brain injury: bleeding, bruising and massive swelling of the brain with the potential to cause concussion, coma and death.  Treatment for brain bruising may involve emergency surgery to relieve the pressure on the brain.
Damage that causes bruising can also cause bones to be broken, tendons or muscles to be strained, ligaments to be sprained, or other tissue to be damaged.  The symptoms and signs of these injuries may initially appear to be those of simple bruising. Abdominal bruising or severe injuries that cause difficulty in moving a limb or the feeling of liquid under the skin may indicate life-threatening injury and require the attention of a physician.

Mechanism
Increased distress to tissue causes capillaries to break under the skin, allowing blood to escape and build up. As time progresses, blood seeps into the surrounding tissues, causing the bruise to darken and spread. Nerve endings within the affected tissue detect the increased pressure, which, depending on severity and location, may be perceived as pain or pressure or be asymptomatic. The damaged capillary endothelium releases endothelin, a hormone that causes narrowing of the blood vessel to minimize bleeding. As the endothelium is destroyed, the underlying von Willebrand factor is exposed and initiates coagulation, which creates a temporary clot to plug the wound and eventually leads to restoration of normal tissue.
During this time, larger bruises may change color due to the breakdown of hemoglobin from within escaped red blood cells in the extracellular space. The striking colors of a bruise are caused by the phagocytosis and sequential degradation of hemoglobin to biliverdin to bilirubin to hemosiderin, with hemoglobin itself producing a red-blue color, biliverdin producing a green color, bilirubin producing a yellow color, and hemosiderin producing a golden-brown color. As these products are cleared from the area, the bruise disappears </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 Omental infarction and can you explain it in depth? [/INST] Omental infarction, or omental torsion, is an acute vascular disorder which compromises tissue of the greater omentum—the largest peritoneal fold in the abdomen.

Signs and symptoms
Patients will present with a sudden onset of cramps/abdominal pain or a stitch </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 Exophthalmos and can you explain it in depth? [/INST] Exophthalmos (also called exophthalmus, exophthalmia, proptosis, or exorbitism) is a bulging of the eye anteriorly out of the orbit.  Exophthalmos can be either bilateral (as is often seen in Graves disease) or unilateral (as is often seen in an orbital tumor). Complete or partial dislocation from the orbit is also possible from trauma or swelling of surrounding tissue resulting from trauma.
In the case of Graves disease, the displacement of the eye results from abnormal connective tissue deposition in the orbit and extraocular muscles, which can be visualized by CT or MRI.If left untreated, exophthalmos can cause the eyelids to fail to close during sleep, leading to corneal dryness and damage. Another possible complication is a form of redness or irritation called superior limbic keratoconjunctivitis, in which the area above the cornea becomes inflamed as a result of increased friction when blinking. The process that is causing the displacement of the eye may also compress the optic nerve or ophthalmic artery, and lead to blindness.

Causes
Inflammatory/Infection:

Graves ophthalmopathy due to Graves disease, usually causes bilateral proptosis.
Orbital cellulitis – often with unilateral proptosis, severe redness, and moderate to severe pain, sinusitis and an elevated white blood cell count.
Dacryoadenitis
Erdheim–Chester disease
Mucormycosis
Orbital pseudotumor – presents with acute, usually unilateral proptosis with severe pain.
High-altitude cerebral edema
Granulomatosis with polyangiitisNeoplastic:

Leukemias
Meningioma, (of sphenoid wing)
Nasopharyngeal angiofibroma
Hand–Schüller–Christian disease
Hemangioma, cavernousCystic:

Dermoid cystVascular:

Carotid-cavernous fistula
Aortic insufficiency: manifests as a pulsatile pseudoproptosis, described by British cardiothoracic surgeon Hutan Ashrafian in 2006Others:

Orbital fracture: apex, floor, medial wall, zygomatic
Retrobulbar hemorrhage: trauma to the orbit can lead to bleeding behind the eye. The hemorrhage has nowhere to escape and the increased pressure pushes the eye out of the socket, leading to proptosis and can also cause blindness if not treated promptly.
Cushings syndrome (due to fat in the orbital cave)
Some forms of craniosynostosis:
Crouzon syndrome
Pfeiffer syndrome
Pansynostosis

Anatomy
Proptosis is the anterior displacement of the eye from the orbit.  Since the orbit is closed off posteriorly, medially and laterally, any enlargement of structures located within will cause the anterior displacement of the eye.  Swelling or enlargement of the lacrimal gland causes inferior medial and anterior dislocation of the eye.  This is because the lacrimal glands are located superiorly and laterally in the orbit.

Diagnosis
Measurement
Measurement of the degree of exophthalmos is performed using an exophthalmometer.
Most sources define exophthalmos/proptosis as a protrusion of the globe greater than 18 mm.The term exophthalmos is often used when describing proptosis associated with Graves disease.

Animals
Exophthalmos is commonly found in dogs.  It is seen in brachycephalic (short-nosed) dog breeds because of the shallow orbit.  It can lead to keratitis secondary to exposure of the cornea.  Exophthalmos is commonly seen in the pug, Boston terrier, Pekingese, and shih tzu </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 Char syndrome and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Endometrioma and can you explain it in depth? [/INST] Endometrioma is the presence of tissue similar but distinct to the endometrium in and sometimes on the ovary. It is the most common form of endometriosis.  Endometrioma is found in 17–44% patients with endometriosis. More broadly, endometriosis is the presence of tissue similar but distinct to endometrial tissue located outside the uterus. The presence of endometriosis can result in the formation of scar tissue, adhesions and an inflammatory reaction. It usually is a benign growth. An endometrioma is most often found in the ovary. This ovarian endometriosis forms dark, fluid-filled cysts. These fluid-filled sacs can vary greatly in size and are known as endometriomas, also called "chocolate cysts". The fluid inside the cysts is thick, dark, old blood, giving it a chocolate-like appearance. It can also develop in the cul-de-sac (the space behind the uterus), the surface of the uterus, and between the vagina and rectum.

Pathophysiology
Endometrial tissue is the mucous membrane that normally lines the uterus. The endometrium is richly supplied with blood and its growth is regulated by estrogen and progesterone. It consists of glandular and stroma tissue from the lining of the uterus. When the endometrial mucous membrane is found outside of the uterus in places such as the ovaries, it causes chronic pelvic pain with intercourse and menstrual cycles.
Endometriomas can produce a toxic environment by producing estrogen, cytokines, interleukins, and other inflammatory substances, that could damage healthy endometriomal tissue. This toxic fluid content can cause dire alterations to the normal surrounding endometriotic cells, potentially impacting the embryo, the ability of an embryo to implant successfully, and the responsiveness of the endometrium. Endometrioma can potentially lead to premature ovarian failure, decreased ovarian function, or problems with ovulation. Studies have also found that endometriomas occur two times more frequently in the left ovary (67%) than in the right one (33%), possibly due to the presence of the sigmoid colon on the left side.

Risks
Endometriomas can increase the risk of ovarian cancer in reproductive women, decrease normal ovarian function, and cause pain in the pelvis during or after periods or during sexual intercourse. Although most endometriomas are found to be benign, the possibility of malignant tumors still exists, and surgery is needed to confirm malignancy and determine what future treatment must be administered.
Another factor that endometrioma can impact is the ovarian reserve, or the number of quality follicles left in the ovary to produce viable eggs. Ovaries with endometriomas showed significantly less follicular density as compared to healthy ovaries, leading to a decrease in fertility.

Treatment
Medication
Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used first in patients with pelvic pain, particularly if the diagnosis of endometriosis has not been definitively (excision and biopsy) established.  The goal of directed medical treatment is to achieve an anovulatory state. Typically, this is achieved initially using hormonal contraception.  This can also be accomplished with progestational agents (i.e., medroxyprogesterone acetate), danazol, gestrinone, or gonadotropin-releasing hormone agonists (GnRH), as well as other less well-known agents.  These agents are generally used if oral contraceptives and NSAIDs are ineffective. GnRH can be combined with estrogen and progestogen (add-back therapy) without loss of efficacy but with fewer hypoestrogenic symptoms. These medications are often ineffective in treating endometriomas and any relief is short lived while taking the medications. Therapy with these agents has a large number of sometimes permanent side effects, such as hot flushes, loss of bone mass, deepening of voice, weight gain, and facial hair growth.

Surgery
Laparoscopic surgical approaches include excision of ovarian adhesions and of endometriomas. Endometriomas require surgical removal and excision is considered to be superior to cyst vaporization or coagulation in terms of permanent removal of the disease and pain relief. Surgery can sometimes have the effect of improving fertility but can have the adverse effect of leading to increases in cycle day 2 or 3 FSH for many patients. It can also pose the risk of diminishing the ovarian reserve, which could lead to post-surgery infertility </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 Autoimmune optic neuropathy and can you explain it in depth? [/INST] Autoimmune optic neuropathy (AON), sometimes called autoimmune optic neuritis, may be a forme fruste of systemic lupus erythematosus (SLE) associated optic neuropathy. AON is more than the presence of any optic neuritis in a patient with an autoimmune process, as it describes a relatively specific clinical syndrome. AON is characterized by chronically progressive or recurrent vision loss associated with serological evidence of autoimmunity. Specifically, this term has been suggested for cases of optic neuritis with serological evidence of vasculitis by positive ANA, despite the lack of meeting criteria for SLE. The clinical manifestations include progressive vision loss that tends to be steroid-responsive and steroid dependent.
Patients with defined SLE that go on to develop optic neuritis should be better identified as lupus optic neuritis.

Signs and symptoms
AON was first described in 1982. It presents with visual loss and signs of optic nerve dysfunction, such as loss of color vision, afferent pupil defect, and sometimes abnormalities of the optic disc. The clinical features of AON can be variable and present in several unilateral or bilateral forms:

Acute anterior or retrobulbar optic neuritis sometimes associated with pain.
Anterior or retrobulbar ischemic optic neuropathy not associated with pain.
Chronic progressive vision loss that mimics a compressive lesion.The main features that differentiate AON from the more common typical demyelinating optic neuritis is the poor recovery of vision and the chronic or recurrent or bilateral course of AON. Furthermore, the workup for multiple sclerosis including MRI, will be negative. Thus, it may be necessary to diagnose AON after a period of observation, noting the problem is not behaving as expected for demyelinative disease.

Pathogenesis
Approximately 1-2% of patients with defined SLE develop an optic neuropathy during the course of their disease. SLE-associated optic neuritis is rarely the presenting sign of the disease. The molecular pathogenesis is hypothesized, based on clinical features and the emerging understanding of mechanisms in SLE </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 Iminoglycinuria and can you explain it in depth? [/INST] Iminoglycinuria is an autosomal recessive disorder of renal tubular transport affecting reabsorption of the amino acid glycine, and the imino acids proline and hydroxyproline. This results in excess urinary excretion of all three acids (-uria denotes "in the urine").Iminoglycinuria is a rare and complex disorder, associated with a number of genetic mutations that cause defects in both renal and intestinal transport systems of glycine and imino acids.Imino acids typically contain an imine functional group, instead of the amino group found in amino acids. Proline is considered and usually referred to as an amino acid, but unlike others, it has a secondary amine. This feature, unique to proline, identifies proline also as an imino acid. Hydroxyproline is another imino acid, made from the naturally occurring hydroxylation of proline.

Presentation
The primary characteristic of iminoglycinuria is the presence of glycine and imino acids in the urine. Otherwise, it is thought to be a relatively benign disorder, although symptoms associated with disruptions of proline and glycine metabolism caused by malabsorption may be present with iminoglycinuria. These include encephalopathy, mental retardation, deafness, blindness, kidney stones, hypertension and gyrate atrophy.Gyrate atrophy is an inherited degenerative disorder of the retina and choroid, sometimes accompanying the metabolic condition hyperornithinemia. The presence of gyrate atrophy with iminoglycinuria stems from a deficiency of proline in chorioretinal tissues, while processes behind hyperornithinemia disrupt the metabolic pathway from ornithine to proline, which alters the catabolism of ornithine, and also results in reduced levels of proline. Thus, gyrate atrophy can be found with either disorder, with proline deficiency as an underlying feature.Hyperglycinuria is another disorder affecting reabsorption of glycine and imino acids, similar to iminoglycinuria and considered to be a heterozygous form. When accompanied by a specific type of kidney stone (nephrolithiasis), it is sometimes referred to as "iminoglycinuria, type II".

Genetics
Iminoglycinuria is believed to be inherited in an autosomal recessive manner. This means a defective gene responsible for the disorder is located on an autosome, and inheritance requires two copies of the defective gene—one from each parent. Parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.A non-inherited cause of excess urinary excretion of proline and glycine, similar to that found in iminoglycinuria, is quite common to newborn infants younger than six months. Sometimes referred to as neonatal iminoglycinuria, it is due to underdevelopment of high-affinity transport mechanisms within the renal circuit, specifically PAT2, SIT1 and SLC6A18. The condition corrects itself with age. In cases where this persists beyond childhood, however, inherited hyperglycinuria or iminoglycinuria may be suspected.

Pathophysiology
Glycine, proline and hydroxyproline share common renal tubular mechanisms of reabsorption, a function specific to the proximal tubule. Both reabsorption or absorption of glycine and imino acids takes place respectively at the proximal tubule or intestinal brush border epithelium. The more selective transport of proline and other imino acids is driven at the molecular level by a mammalian cellular transport mechanism aptly known as system IMINO.

While no single genetic mutation has been established as the cause of iminoglycinuria; several mutations, affecting transport mechanisms shared by glycine, proline and hydroxyproline, as well as those that selectively transport either glycine or imino acids, including the IMINO system, are known to be associated with the disorder. When combined, these factors will result in a variable phenotype for iminoglycinuria depending on which mutations are present. However, despite the role that intestinal malabsorption of glycine and imino acids can play in iminoglycinuria, the primary defect disrupts their renal transport and reabsorption. This is evident, as inherited iminoglycinuria can be clinically present with no intestinal involvement.In mammals, including humans, the transport of amino and imino acids from the lumen (interior) of the intestine or the renal proximal tubule into the cells occurs at the brush border membrane of the epithelium (moist, tightly packed cellular lining of many tissues and organs of the body). Here, cotransporters such as sodium or chloride (part of the system of Na-K-Cl cotransporters) couple with the amino or imino acids on the molecular level and transport them through specific integral membrane proteins that form ion channels, which are located within the cell membrane. From the cells, the absorbed or reabsorbed amino and imino acids eventually reach the blood. Absorption refers to the overall process happening in the intestine in lieu of normal digestive breakdown of proteins, while reabsorption refers to the process occurring in the renal proximal tubule to reclaim amino and imino acids that have been filtered out of the blood via the glomerulus.These forms of transport require energy, as the products being transported are usually moving against a higher concentration gradient. This process, called active transport, get its energy from ATP and other ATP-related cotransport systems that produce energy, like the sodium-potassium pump.

Mechanism
The primary defect associated with iminoglycinuria is a homozygous (recessive) mutation of the SLC36A2 (PAT2) gene. One of several membrane transport proteins in the solute carrier family of amino acid transporters, PAT2 is the high-affinity renal transporter of glycine, proline and hydroxyproline found to be defective in both alleles when iminoglycinuria is present in an individual. This is in contrast to the fact that when only one PAT2 allele is defective, hyperglycinuria will be present instead of iminoglycinuria. These findings delineate iminoglycinuria as the homozygous form of hyperglycinuria, with the former having a higher degree of urinary excretion of glycine and imino acids correlating to mutations in both alleles.Another mutation suspected to convey the iminoglycinuria phenotype may be found in the SLC36A1 (PAT1) gene. Identified as the low-affinity intestinal transporter of glycine and imino acids, PAT1 works in cooperation with the renal sodium-hydrogen exchanger NHE3 (SLC9A3) </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 Immersion 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 Malonyl-CoA decarboxylase deficiency and can you explain it in depth? [/INST] Malonyl-CoA decarboxylase deficiency (MCD) is an autosomal-recessive metabolic disorder caused by a genetic mutation that disrupts the activity of Malonyl-CoA decarboxylase. This enzyme breaks down Malonyl-CoA (a fatty acid precursor and a fatty acid oxidation blocker) into acetyl-CoA and carbon dioxide.

Signs and symptoms
The signs and symptoms of this disorder typically appear in early childhood. Almost all affected children have delayed development. Additional signs and symptoms can include weak muscle tone (hypotonia), seizures, diarrhea, vomiting, and low blood sugar (hypoglycemia). A heart condition called cardiomyopathy, which weakens and enlarges the heart muscle, is another common feature of malonyl-CoA decarboxylase deficiency.
Some common symptoms in Malonyl-CoA decarboxylase deficiency, such as cardiomyopathy and metabolic acidosis, are triggered by the high concentrations of Malonyl-CoA in the cytoplasm. High levels of Malonyl-CoA will inhibit β-oxidation of fatty acids through deactivating the carrier of fatty acyl group, CPT1, and thus, blocking fatty acids from going into the mitochondrial matrix for oxidation.A research conducted in Netherlands has suggested that carnitine supplements and a low fat diet may help to reduce the level of malonic acid in our body.

Genetics
Malonyl-CoA decarboxylase deficiency is caused by mutations in the MLYCD gene, located on chromosome 16q24. The gene encodes the enzyme malonyl-CoA decarboxylase. Within cells, this enzyme helps regulate the formation and breakdown of a certain group of fats called fatty acids.
Many tissues, including heart muscle, use fatty acids as a major source of energy. Mutations in the MLYCD gene reduce or eliminate the function of malonyl-CoA decarboxylase. A lack of this enzyme disrupts the normal balance of fatty acid formation and breakdown. As a result, fatty acids cannot be converted to energy, which can lead to characteristic features of this disorder, such as low blood sugar and cardiomyopathy. By-products of fatty acid processing build up in tissues, which also contributes to the signs and symptoms of malonyl-CoA decarboxylase deficiency.
Malonyl-CoA decarboxylase deficiency is inherited in an autosomal recessive pattern. This means that the defective gene is located on an autosome (chromosome 16 is an autosome), and two copies of the defective gene - one inherited from each parent - are required to be born with the disorder. The parents of a child with an autosomal recessive disorder both carry one copy of the defective gene, but are usually not affected by the disorder.
Malonyl-CoA decarboxylase deficiency is extremely rare, evidence suggests that it is caused by the abnormality in the protein transcription regulation. Looking at the molecular basis, two distinct homozygous mutations are found to cause Malonyl-CoA  Decarboxylase deficiency in human. The first mutation is the transversion of gene from C to G causing a premature stop signal in the protein </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 Ross syndrome and can you explain it in depth? [/INST]  </s>


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


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Blepharochalasis 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 Nephronophthisis and can you explain it in depth? [/INST] Nephronophthisis is a genetic disorder of the kidneys which affects children. It is classified as a medullary cystic kidney disease. The disorder is inherited in an autosomal recessive fashion and, although rare, is the most common genetic cause of childhood kidney failure. It is a form of ciliopathy. Its incidence has been estimated to be 0.9 cases per million people in the United States, and 1 in 50,000 births in Canada.

Signs and symptoms
Infantile, juvenile, and adolescent forms of nephronophthisis have been identified. Although the range of characterizations is broad, people affected by nephronophthisis typically present with polyuria (production of a large volume of urine), polydipsia (excessive liquid intake), and after several months to years, end-stage kidney disease, a condition necessitating either dialysis or a kidney transplant in order to survive. Some individuals with nephronophthisis also have so-called "extra-renal symptoms" which can include tapetoretinal degeneration, liver problems, oculomotor apraxia, and cone-shaped epiphysis (Saldino-Mainzer syndrome).

Cause
Nephronophthisis is characterized by fibrosis and the formation of cysts at the cortico-medullary junction, it is an autosomal recessive disorder which eventually leads to terminal kidney failure.

Pathophysiology
Mechanism of nephronophthisis indicates that all proteins mutated in cystic kidney diseases express themselves in primary cilia. NPHP gene mutations cause defects in signaling resulting in flaws of planar cell polarity. The ciliary theory indicates that  multiple organs are involved in NPHP (retinal degeneration, cerebellar hypoplasia, liver fibrosis, and intellectual disability).

Related rare genetic disorders
Nephronophthisis is a ciliopathy.  Other known ciliopathies include primary ciliary dyskinesia, Bardet–Biedl syndrome, polycystic kidney and liver disease, Alström syndrome, Meckel–Gruber syndrome and some forms of retinal degeneration.NPHP2 is infantile type of nephropthisis and sometimes associated with situs inversus this can be explained by its relation with inversin gene. NPHP1, NPHP3, NPHP4, NPHP5, and NPHP6 are sometimes seen with retinitis pigmentosa, this particular association has a name, Senior-Loken syndrome.

Diagnosis
The diagnosis of nephronophthisis can be obtained via a kidney ultrasound, family history and clinical history of the affected individual according to Stockman, et al.

Types
Infantile NPH
Juvenile NPH
Adult NPH

Management
The management of this condition can be done via-improvement of any electrolyte imbalance, as well as, high blood pressure and low red blood cell counts (anemia) treatment as the individuals condition warrants.

Epidemiology
Nephronophthisis occurs equally in both sexes and has an estimate 9 in about 8 million rate in individuals. Nephronophthisis is the leading monogenic cause of end-stage kidney disease.

References
Further reading
Simms, Roslyn J.; Hynes, Ann Marie; Eley, Lorraine; Sayer, John A. (2011). "Nephronophthisis: A Genetically Diverse Ciliopathy". International Journal of Nephrology. 2011: 1–10. doi:10.4061/2011/527137. PMC 3108105. PMID 21660307.
Hildebrandt, Friedhelm; Attanasio, Massimo; Otto, Edgar (2009-01-01). "Nephronophthisis: Disease Mechanisms of a Ciliopathy" </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 Familial multiple lipomatosis and can you explain it in depth? [/INST] Familial multiple lipomatosis is a hereditary adipose tissue disorder that is characterized by the formation of multiple lipomas that occur in a particular distribution. The lipomas are well-encapsulated, slow-growing, benign fatty tumors. The distribution is defined as being focused in the trunk of the body and extremities.  Familial Multiple Lipomatosis can be identified when multiple lipomas occur in multiple family members that span different generations. Some people may have hundreds of lipomas present.

Symptoms
The source of this disease is from family history, and symptoms most often arise in middle age. Newly formed lipomas frequently present themselves as a bead-like lump under the skin, and become rubbery and movable. They may be seen throughout the body and in some areas more than others, however, it does not make an appearance on the head or shoulders of the individual. The size of those bumps may vary and could possibly get in the way of an individual living their life peacefully. There are usually no feelings of discomfort or pain unless a lipoma has been aggravated or is directly on a nerve. Lipomas that sit over bony areas such as the ribs and lower back can cause discomfort when lying down or receiving any kind of pressure. The age at which familial multiple lipomatosis begins to make an appearance on the individual’s body varies; for some it may be as early as 5 years of age.

Diagnosis
Familial multiple lipomatosis is usually diagnosed through a physical exam via palpation, medical history and imaging studies such as ultrasound, CT scan, or magnetic resonance imaging (MRI). A CT scan is an imaging method that uses x-rays to create images of cross sections of the body, while an MRI uses powerful magnets and radio waves to create images of lipomas and surrounding tissues. Both tests are useful to establish the diagnosis of multiple symmetric lipomatosis, although magnetic resonance imaging provides more details and may be used when lipomas are large, deep, or have infiltrated muscle fibers or nerves. In some cases, a biopsy of the lipomas may be necessary to confirm the diagnosis.

Differential diagnoses
Liposarcoma
Dercum’s disease
Benign symmetric lipomatosis
Madelung’s disease
Cyst

Causes
The exact cause of FML is not yet known, but there are several theories of different causes:
Hormonal disorder due to the bodys inability to properly metabolize fat
Increase in fat cells (adipocytes)
Enzymatic defect or a change in the surface of the cells that could prevent the breakdown of fat
Poor lymphatic drainage
Defective regulation of mitochondria in brown fat. Brown fat is responsible for causing heat in times of stress or cold. For general callus tissue is stimulated by the sympathetic nervous system and this response is mediated by a substance called norepinephrine. This process occurs in the mitochondria
In most families, the mode of inheritance has not been determined </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 Hypochondrogenesis and can you explain it in depth? [/INST] Hypochondrogenesis is a severe genetic disorder causing malformations of bone growth. The condition is characterized by a short body and limbs and abnormal bone formation in the spine and pelvis.
Hypochondrogenesis is a subtype of collagenopathy, types II and XI, and is similar to another skeletal disorder, achondrogenesis type 2, although the spinal changes seen in hypochondrogenesis tend to be somewhat milder.

Signs and symptoms
Symptoms of hypochondrogenesis include: edema, limb undergrowth, spondyloepiphyseal dysplasia, short ribs, respiratory failure, short chin, upper limb undergrowth, thoracic hypoplasia, hypertelorism, hydrops fetalis, pulmonary hypoplasia, and a cleft palate.

Pathophysiology
Hypochondrogenesis is one of the most severe conditions in a spectrum of disorders caused by mutations in the COL2A1 gene. The protein made by this gene forms type II collagen, a molecule found mostly in cartilage and in the clear gel that fills the eyeball (the vitreous) </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 Ependymoma and can you explain it in depth? [/INST] An ependymoma is a tumor that arises from the ependyma, a tissue of the central nervous system. Usually, in pediatric cases the location is intracranial, while in adults it is spinal. The common location of intracranial ependymomas is the fourth ventricle. Rarely, ependymomas can occur in the pelvic cavity.
Syringomyelia can be caused by an ependymoma.
Ependymomas are also seen with neurofibromatosis type II.

Signs and symptoms
Source:
severe headache
visual loss (due to papilledema)
vomiting
bilateral Babinski sign
drowsiness (after several hours of the above symptoms)
gait change (rotation of feet when walking)
impaction/constipation
back flexibility

Morphology
Ependymomas are composed of cells with regular, round to oval nuclei.  There is a variably dense fibrillary background. Tumor cells may form gland-like round or elongated structures that resemble the embryologic ependymal canal, with long, delicate processes extending into the lumen; more frequently present are perivascular pseudorosettes in which tumor cells are arranged around vessels with an intervening zone consisting of thin ependymal processes directed toward the wall of the vessel.It has been suggested that ependymomas are derived from radial glia, despite their name suggesting an ependymal origin.

Ependymoma tumors
Ependymomas make up about 5% of adult intracranial gliomas and up to 10% of childhood tumors of the central nervous system (CNS). Their occurrence seems to peak at age 5 years and then again at age 35. They develop from cells that line both the hollow cavities of the brain and the canal containing the spinal cord, but they usually arise from the floor of the fourth ventricle, situated in the lower back portion of the brain, where they may produce headache, nausea and vomiting by obstructing the flow of cerebrospinal fluid. This obstruction may also cause hydrocephalus. They may also arise in the spinal cord, conus medullaris and supratentorial locations. Other symptoms can include (but are not limited to): loss of appetite, difficulty sleeping, temporary inability to distinguish colors, uncontrollable twitching, seeing vertical or horizontal lines when in bright light, and temporary memory loss.  It should be remembered that these symptoms also are prevalent in many other illnesses not associated with ependymoma.About 10% of ependymomas are benign myxopapillary ependymoma (MPE). MPE is a localized and slow-growing low-grade tumor, which originates almost exclusively from the lumbosacral nervous tissue of young patients. On the other hand, it is the most common tumor of the lumbosacral canal comprising about 90% of all tumoral lesions in this region.Although some ependymomas are of a more anaplastic and malignant type, most of them are not anaplastic </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 Primary pulmonary coccidioidomycosis and can you explain it in depth? [/INST]  </s>