<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 Pericoronitis and can you explain it in depth? [/INST] Pericoronitis is inflammation of the soft tissues surrounding the crown of a partially erupted tooth, including the gingiva (gums) and the dental follicle. The soft tissue covering a partially erupted tooth is known as an operculum, an area which can be difficult to access with normal oral hygiene methods. The hyponym operculitis technically refers to inflammation of the operculum alone.
Pericoronitis is caused by an accumulation of bacteria and debris beneath the operculum, or by mechanical trauma (e.g. biting the operculum with the opposing tooth). Pericoronitis is often associated with partially erupted and impacted mandibular third molars (lower wisdom teeth), often occurring at the age of wisdom tooth eruption (15-26). Other common causes of similar pain from the third molar region are food impaction causing periodontal pain, pulpitis from dental caries (tooth decay), and acute myofascial pain in temporomandibular joint disorder.
Pericoronitis is classified into chronic and acute. Chronic pericoronitis can present with no or only mild symptoms and long remissions between any escalations to acute pericoronitis. Acute pericoronitis is associated with a wide range of symptoms including severe pain, swelling and fever.  Sometimes there is an associated pericoronal abscess (an accumulation of pus). This infection can spread to the cheeks, orbits/periorbits, and other parts of the face or neck, and occasionally can lead to airway compromise (e.g. Ludwigs angina) requiring emergency hospital treatment. The treatment of pericoronitis is through pain management and by resolving the inflammation. The inflammation can be resolved by flushing the debris or infection from the pericoronal tissues or by removing the associated tooth or operculum. Retaining the tooth requires improved oral hygiene in the area to prevent further acute pericoronitis episodes. Tooth removal is often indicated in cases of recurrent pericoronitis. The term is from the Greek peri, "around", Latin corona "crown" and -itis, "inflammation".

Classification
The definition of pericoronitis is inflammation in the soft tissues surrounding the crown of a tooth. This encompasses a wide spectrum of severity, making no distinction to the extent of the inflammation into adjacent tissues or whether there is associated active infection (pericoronal infection caused by micro-organisms sometimes leading to a pus filled pericoronal abscess or cellulitis).
Typically cases involve acute pericoronitis of lower third molar teeth. During "teething" in young children, pericoronitis can occur immediately preceding eruption of the deciduous teeth (baby or milk teeth).
The International Classification of Diseases entry for pericoronitis lists acute and chronic forms.

Acute
Acute pericoronitis (i.e. sudden onset and short lived, but significant, symptoms) is defined as "varying degrees of inflammatory involvement of the pericoronal flap and adjacent structures, as well as by systemic complications." Systemic complications refers to signs and symptoms occurring outside of the mouth, such as fever, malaise or swollen lymph nodes in the neck.

Chronic
Pericoronitis may also be chronic or recurrent, with repeated episodes of acute pericoronitis occurring periodically. Chronic pericoronitis may cause few if any symptoms, but some signs are usually visible when the mouth is examined.

Signs and symptoms
The signs and symptoms of pericoronitis depend upon the severity, and are variable:

Pain, which gets worse as the condition develops and becomes severe. The pain may be throbbing and radiate to the ear, throat, temporomandibular joint, posterior submandibular region and floor of the mouth. There may also be pain when biting. Sometimes the pain disturbs sleep.
Tenderness, erythema (redness) and edema (swelling) of the tissues around the involved tooth, which is usually partially erupted into the mouth. The operculum is characteristically very painful when pressure is applied.
Halitosis resulting from the bacteria putrefaction of proteins in this environment releasing malodorous volatile sulfur compounds.
Bad taste or sour taste in the mouth from exudation of pus.
Intra-oral halitosis.
Formation of pus, which can be seen exuding from beneath the operculum (i.e. a pericoronal abscess), especially when pressure is applied to the operculum.
Signs of trauma on the operculum, such as indentations of the cusps of the upper teeth, or ulceration. Rarely, the soft tissue around the crown of the involved tooth may show a similar appearance to necrotizing ulcerative gingivitis.
Trismus (difficulty opening the mouth).  resulting from inflammation/infection of the muscles of mastication.
Dysphagia (difficulty swallowing).
Cervical lymphadenitis (inflammation and swelling of the lymph nodes in the neck), especially of the submandibular nodes.
Facial swelling, and rubor, often of the cheek that overlies the angle of the jaw.
Pyrexia (fever).
Leukocytosis (increased white blood cell count).
Malaise (general feeling of being unwell).
Loss of appetite.
The radiographic appearance of the local bone can become more radiopaque in chronic pericoronitis.

Causes
Pericoronitis occurs because the operculum (the soft tissue directly overlying the partially erupted tooth) creates a "plaque stagnation area", which can accumulate food debris and micro-organisms (particularly plaque). This leads to an inflammatory response in the adjacent soft tissues.Sometimes pericoronal infection can spread into adjacent potential spaces (including the sublingual space, submandibular space, parapharyngeal space, pterygomandibular space, infratemporal space, submasseteric space and buccal space) to areas of the neck or face resulting in facial swelling, or even airway compromise (called Ludwigs angina).

Bacteria
Inadequate cleaning of the operculum space allows stagnation of bacteria and any accumulated debris. This can be a result of poor access due to limited room in the case of the 3rd molars.
Pericoronal infection is normally caused by a mixture of bacterial species present in the mouth, such as Streptococci and particularly various anaerobic species.
This can result in abscess formation. Left untreated, the abscess can spontaneously drain into the mouth from beneath the operculum. In chronic pericoronitis, drainage may happen through an approximal sinus tract.
The chronically inflamed soft tissues around the tooth may give few if any symptoms. This can suddenly become symptomatic if new debris becomes trapped or if the host immune system becomes compromised and fails to keep the chronic infection in check (e.g. during influenza or upper respiratory tract infections, or a period of stress).

Tooth position
When an opposing tooth bites into the operculum, it can initiate or exacerbate pericoronitis resulting in a spiraling cycle  of inflammation and trauma.
Over-eruption of the opposing tooth into the unoccupied space left by the stalled eruption of a tooth is a risk factor to operculum trauma from biting.
Teeth that fail to erupt completely (commonly the lower mandibular third molars) are often the result of limited space for eruption, or a non-ideal angle of tooth eruption causing tooth impaction.
The presence of supernumerary teeth (extra teeth) makes pericoronitis more likely.

Diagnosis
The presence of dental plaque or infection beneath an inflamed operculum without other obvious causes of pain will often lead to a pericoronitis diagnosis; therefore, elimination of other pain and inflammation causes is essential. For pericoronal infection to occur, the affected tooth must be exposed to the oral cavity, which can be difficult to detect if the exposure is hidden beneath thick tissue or behind an adjacent tooth.  Severe swelling and restricted mouth opening may limit examination of the area. Radiographs can be used to rule out other causes of pain and to properly assess the prognosis for further eruption of the affected tooth.Sometimes a "migratory abscess" of the buccal sulcus occurs with pericoronal infection, where pus from the lower third molar region tracks forwards in the submucosal plane, between the body of the mandible and the attachment of the buccinator muscle to the mandible. In this scenario, pus may spontaneously discharge via an intra-oral sinus located over the mandibular second or first molar, or even the second premolar.
Similar causes of pain, some which can occur in conjunction with pericoronitis may include:

Dental caries (tooth decay) of the wisdom tooth and of the distal surface of the second molar is common. Tooth decay may cause pulpitis (toothache) to occur in the same region, and this may cause pulp necrosis and the formation of a periapical abscess associated with either tooth.
Food can also become stuck between the wisdom tooth and the tooth in front, termed food packing, and cause acute inflammation in a periodontal pocket when the bacteria become trapped. A periodontal abscess may even form by this mechanism.
Pain associated with temporomandibular joint disorder and myofascial pain also often occurs in the same region as pericoronitis. J are easily missed diagnoses in the presence of mild and chronic pericoronitis, and the latter may not be contributing greatly to the individuals pain (see table).It is rare for pericoronitis to occur in association with both lower third molars at the same time, despite the fact that many young people will have both lower wisdom teeth partially erupted. Therefore, bilateral pain from the lower third molar region is unlikely to be caused by pericoronitis and more likely to be muscular in origin.

Prevention
Prevention of pericoronitis can be achieved by removing impacted third molars before they erupt into the mouth, or through preemptive operculectomy.  A treatment controversy exists about the necessity and timing of the removal of asymptomatic, disease-free impacted wisdom teeth which prevents pericoronitis. Proponents of early extraction cite the cumulative risk for extraction over time, the high probability that wisdom teeth will eventually decay or develop gum disease and costs of monitoring to retained wisdom teeth. Advocates for retaining wisdom teeth cite the risk and costs of unnecessary operations and the ability to monitor the disease through clinical exam and radiographs.

Management
Since pericoronitis is a result of inflammation of the pericoronal tissues of a partially erupted tooth, management can include applying pain management gels for the mouth consisting of Lignocaine, a numbing agent. Definitive treatment can only be through preventing the source of inflammation. This is either through improved oral hygiene or by removal of the plaque stagnation areas through tooth extraction or gingival resection, which can be done with diode lasers atraumatically.  Often acute symptoms of pericoronitis are treated before the underlying cause is addressed.

Acute pericoronitis
When possible, immediate definitive treatment of acute pericoronitis is recommended because surgical treatment has been shown to resolve the spread of the infection and pain, with a quicker return of function. Also immediate treatment avoids overuse of antibiotics (preventing antibiotic resistance).
However, surgery is sometimes delayed in an area of acute infection, with the help of pain relief and antibiotics, for the following reasons:

Reduces the risk of causing an infected surgical site with delayed healing (e.g. osteomyelitis or cellulitis).
Avoids reduced efficiency of local anesthetics caused by the acidic environment of infected tissues.
Resolves the limited mouth opening, making oral surgery easier.
Patients may better cope with the dental treatment when free from pain.
Allows for adequate planning with correctly allocated procedure time.Firstly, the area underneath the operculum is gently irrigated to remove debris and inflammatory exudate. Often warm saline is used but other solutions may contain hydrogen peroxide, chlorhexidine or other antiseptics. Irrigation may be assisted in conjunction with Debridement (removal of plaque, calculus and food debris) with periodontal instruments. Irrigation may be enough to relieve any associated pericoronal abscess; otherwise a small incision can be made to allow drainage.
Smoothing an opposing tooth which bites into the affected operculum can eliminate this source of trauma.Home care may involve regular use of warm salt water mouthwashes/mouth baths. A randomized clinical trial found green tea mouth rinse effective in controlling pain and trismus in acute cases of pericoronitis.Following treatment, if there are systemic signs and symptoms, such as facial or neck swelling, cervical lymphadenitis, fever or malaise, a course of oral antibiotics is often prescribed,. Common antibiotics used are from the β-lactam antibiotic group, clindamycin and metronidazole.If there is dysphagia or dyspnoea (difficulty swallowing or breathing), then this usually means there is a severe infection and an emergency admission to hospital is appropriate so that intravenous medications and fluids can be administered and the threat to the airway monitored. Sometimes semi-emergency surgery may be arranged to drain a swelling that is threatening the airway.

Definitive treatment
If the tooth will not continue to erupt completely, definitive treatment involves either sustained oral hygiene improvements or removal of the offending tooth or operculum. The latter surgical treatment options are usually chosen in the case of impacted teeth with no further eruption potential, or in the case of recurrent episodes of acute pericoronitis despite oral hygiene instruction.

Oral hygiene
In some cases, removal of the tooth may not be necessary with meticulous oral hygiene to prevent buildup of plaque in the area. Long term maintenance is needed to keep the operculum clean in order to prevent further acute episodes of inflammation. A variety of specialized oral hygiene methods are  available to deal with hard to reach areas of the mouth, including small headed tooth brushes, interdental brushes, electronic irrigators and dental floss.

Operculectomy
This is a minor surgical procedure where the affected soft tissue covering and surrounding the tooth is removed. This leaves an area that is easy to keep clean, preventing plaque buildup and subsequent inflammation. Sometimes operculectomy is not an effective treatment.  Typically operculectomy is done with a surgical scalpel, electrocautery, with lasers or, historically, with caustic agents (trichloracetic acid)

Tooth extraction
Removal of the associated tooth will eliminate the plaque stagnation area, and thus eliminate any further episodes of pericoronitis. Removal is indicated when the involved tooth will not erupt any further due to impaction or ankylosis; if extensive work would be required to restore structural damage; or to allow improved oral hygiene. Sometimes the opposing tooth is also extracted if no longer required.Extraction of teeth which are involved in pericoronitis carries a higher risk of dry socket, a painful complication which results in delayed healing.

Prognosis
Once the plaque stagnation area is removed either through further complete tooth eruption or tooth removal then pericoronitis will likely never return. A non-impacted tooth may continue to erupt, reaching a position which eliminates the operculum. A transient and mild pericoronal inflammation often continues while this tooth eruption completes. With adequate space for sustained improved oral hygiene methods, pericoronitis may never return </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 Oculocutaneous albinism 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 Hyperlipidemia and can you explain it in depth? [/INST] Hyperlipidemia is abnormally elevated levels of any or all lipids (fats, cholesterol, or triglycerides) or lipoproteins in the blood. The term hyperlipidemia refers to the laboratory finding itself and is also used as an umbrella term covering any of various acquired or genetic disorders that result in that finding. Hyperlipidemia represents a subset of dyslipidemia and a superset of hypercholesterolemia. Hyperlipidemia is usually chronic and requires ongoing  medication to control blood lipid levels.Lipids (water-insoluble molecules) are transported in a protein capsule. The size of that capsule, or lipoprotein, determines its density. The lipoprotein density and type of apolipoproteins it contains determines the fate of the particle and its influence on metabolism.
Hyperlipidemias are divided into primary and secondary subtypes. Primary hyperlipidemia is usually due to genetic causes (such as a mutation in a receptor protein), while secondary hyperlipidemia arises due to other underlying causes such as diabetes. Lipid and lipoprotein abnormalities are common in the general population and are regarded as modifiable risk factors for cardiovascular disease due to their influence on atherosclerosis. In addition, some forms may predispose to acute pancreatitis.

Classification
Hyperlipidemias may basically be classified as either familial (also called primary) when caused by specific genetic abnormalities or acquired (also called secondary) when resulting from another underlying disorder that leads to alterations in plasma lipid and lipoprotein metabolism. Also, hyperlipidemia may be idiopathic, that is, without a known cause.Hyperlipidemias are also classified according to which types of lipids are elevated, that is hypercholesterolemia, hypertriglyceridemia or both in combined hyperlipidemia. Elevated levels of Lipoprotein(a) may also be classified as a form of hyperlipidemia.

Familial (primary)
Familial hyperlipidemias are classified according to the Fredrickson classification, which is based on the pattern of lipoproteins on electrophoresis or ultracentrifugation. It was later adopted by the World Health Organization (WHO). It does not directly account for HDL, and it does not distinguish among the different genes that may be partially responsible for some of these conditions.

Type I
Type I hyperlipoproteinemia exists in several forms:

Lipoprotein lipase deficiency (type Ia), due to a deficiency of lipoprotein lipase (LPL) or altered apolipoprotein C2, resulting in elevated chylomicrons, the particles that transfer fatty acids from the digestive tract to the liver
Familial apoprotein CII deficiency (type Ib), a condition caused by a lack of lipoprotein lipase activator.: 533
Chylomicronemia due to circulating inhibitor of lipoprotein lipase (type Ic)Type I hyperlipoproteinemia usually presents in childhood with eruptive xanthomata and abdominal colic. Complications include retinal vein occlusion, acute pancreatitis, steatosis, and organomegaly, and lipemia retinalis.

Type II
Hyperlipoproteinemia type II is further classified into types IIa and IIb, depending mainly on whether elevation in the triglyceride level occurs in addition to LDL cholesterol.

Type IIa
This may be sporadic (due to dietary factors), polygenic, or truly familial as a result of a mutation either in the LDL receptor gene on chromosome 19 (0.2% of the population) or the ApoB gene (0.2%). The familial form is characterized by tendon xanthoma, xanthelasma, and premature cardiovascular disease.  The incidence of this disease is about one in 500 for heterozygotes, and one in 1,000,000 for homozygotes.HLPIIa is a rare genetic disorder characterized by increased levels of LDL cholesterol in the blood due to the lack of uptake (no Apo B receptors) of LDL particles. This pathology, however, is the second-most common disorder of the various hyperlipoproteinemias, with individuals with a heterozygotic predisposition of one in every 500 and individuals with homozygotic predisposition of one in every million. These individuals may present with a unique set of physical characteristics such as xanthelasmas (yellow deposits of fat underneath the skin often presenting in the nasal portion of the eye), tendon and tuberous xanthomas, arcus juvenilis (the graying of the eye often characterized in older individuals), arterial bruits, claudication, and of course atherosclerosis. Laboratory findings for these individuals are significant for total serum cholesterol levels two to three times greater than normal, as well as increased LDL cholesterol, but their triglycerides and VLDL values fall in the normal ranges.To manage persons with HLPIIa, drastic measures may need to be taken, especially if their HDL cholesterol levels are less than 30 mg/dL and their LDL levels are greater than 160 mg/dL. A proper diet for these individuals requires a decrease in total fat to less than 30% of total calories with a ratio of monounsaturated:polyunsaturated:saturated fat of 1:1:1. Cholesterol should be reduced to less than 300 mg/day, thus the avoidance of animal products and to increase fiber intake to more than 20 g/day with 6g of soluble fiber/day. Exercise should be promoted, as it can increase HDL. The overall prognosis for these individuals is in the worst-case scenario if uncontrolled and untreated individuals may die before the age of 20, but if one seeks a prudent diet with correct medical intervention, the individual may see an increased incidence of xanthomas with each decade, and Achilles tendinitis and accelerated atherosclerosis will occur.

Type IIb
The high VLDL levels are due to overproduction of substrates, including triglycerides, acetyl-CoA, and an increase in B-100 synthesis. They may also be caused by the decreased clearance of LDL. Prevalence in the population is 10%.
Familial combined hyperlipoproteinemia (FCH)
Lysosomal acid lipase deficiency (often called Cholesteryl ester storage disease)
Secondary combined hyperlipoproteinemia (usually in the context of metabolic syndrome, for which it is a diagnostic criterion)

Type III
This form is due to high chylomicrons and IDL (intermediate density lipoprotein). Also known as broad beta disease or dysbetalipoproteinemia, the most common cause for this form is the presence of ApoE E2/E2 genotype. It is due to cholesterol-rich VLDL (β-VLDL). Its prevalence has been estimated to be approximately 1 in 10,000.It is associated with hypercholesterolemia (typically 8–12 mmol/L), hypertriglyceridemia (typically 5–20 mmol/L), a normal ApoB concentration, and two types of skin signs (palmar xanthomata or orange discoloration of skin creases, and tuberoeruptive xanthomata on the elbows and knees). It is characterized by the early onset of cardiovascular disease and peripheral vascular disease. Remnant hyperlipidemia occurs as a result of abnormal function of the ApoE receptor, which is normally required for clearance of chylomicron remnants and IDL from the circulation. The receptor defect causes levels of chylomicron remnants and IDL to be higher than normal in the blood stream. The receptor defect is an autosomal recessive mutation or polymorphism.

Type IV
Familial hypertriglyceridemia is an autosomal dominant condition occurring in approximately 1% of the population.This form is due to high triglyceride level. Other lipoprotein levels are normal or increased a little.Treatment include diet control, fibrates and niacins. Statins are not better than fibrates when lowering triglyceride levels.

Type V
Hyperlipoproteinemia type V, also known as mixed hyperlipoproteinemia familial or mixed hyperlipidemia, is very similar to type I, but with high VLDL in addition to chylomicrons.
It is also associated with glucose intolerance and hyperuricemia.In medicine, combined hyperlipidemia (or -aemia) (also known as "multiple-type hyperlipoproteinemia") is a commonly occurring form of hypercholesterolemia (elevated cholesterol levels) characterized by increased LDL and triglyceride concentrations, often accompanied by decreased HDL. On lipoprotein electrophoresis (a test now rarely performed) it shows as a hyperlipoproteinemia type IIB. It is the most common inherited lipid disorder, occurring in about one in 200 persons. In fact, almost one in five individuals who develop coronary heart disease before the age of 60 has this disorder.
The elevated triglyceride levels (>5 mmol/L) are generally due to an increase in very low density lipoprotein (VLDL), a class of lipoprotein prone to cause atherosclerosis.
Both conditions are treated with fibrate drugs, which act on the peroxisome proliferator-activated receptors (PPARs), specifically PPARα, to decrease free fatty acid production.
Statin drugs, especially the synthetic statins (atorvastatin and rosuvastatin) can decrease LDL levels by increasing hepatic reuptake of LDL due to increased LDL-receptor expression.

Unclassified familial forms
These unclassified forms are extremely rare:

Hyperalphalipoproteinemia
Polygenic hypercholesterolemia

Acquired (secondary)
Acquired hyperlipidemias (also called secondary dyslipoproteinemias) often mimic primary forms of hyperlipidemia and can have similar consequences. They may result in increased risk of premature atherosclerosis or, when associated with marked hypertriglyceridemia, may lead to pancreatitis and other complications of the chylomicronemia syndrome. The most common causes of acquired hyperlipidemia are:

Diabetes mellitus
Use of drugs such as thiazide diuretics, beta blockers, and estrogensOther conditions leading to acquired hyperlipidemia include:

Hypothyroidism
Kidney failure
Nephrotic syndrome
Alcohol consumption
Some rare endocrine disorders and metabolic disordersTreatment of the underlying condition, when possible, or discontinuation of the offending drugs usually leads to an improvement in the hyperlipidemia.
Another acquired cause of hyperlipidemia, although not always included in this category, is postprandial hyperlipidemia, a normal increase following ingestion of food.

Presentation
Relation to cardiovascular disease
Hyperlipidemia predisposes a person to atherosclerosis. Atherosclerosis is the accumulation of lipids, cholesterol, calcium, fibrous plaques within the walls of arteries. This accumulation narrows the blood vessel and reduces blood flow and oxygen to muscles of the heart. Over time fatty deposits can build up, hardening and narrowing the arteries until organs and tissues dont receive enough blood to properly function.  If arteries that supply the heart with blood are affected, a person might have angina (chest pain). Complete blockage of the artery causes infarction of the myocardial cells, also known as heart attack. Fatty buildup in the arteries can also lead to stroke, if a blood clot blocks blood flow to the brain.

Screening
Adults 20 years and older should have the cholesterol checked every four to six years. Serum level of  Low Density Lipoproteins (LDL) cholesterol, High Density Lipoproteins (HDL) Cholesterol, and triglycerides are commonly tested in primary care setting using a lipid panel. Quantitative levels of lipoproteins and triglycerides contribute toward cardiovascular disease risk stratification via models/calculators such as Framingham Risk Score, ACC/AHA Atherosclerotic Cardiovascular Disease Risk Estimator, and/or Reynolds Risk Scores. These models/calculators may also take into account of family history (heart disease and/or high blood cholesterol), age, gender, Body-Mass-Index, medical history (diabetes, high cholesterol, heart disease), high sensitivity CRP levels, coronary artery calcium score, and ankle-brachial index. The cardiovascular stratification further determines what medical intervention may be necessary to decrease the risk of future cardiovascular disease.

Total cholesterol
The combined quantity of LDL and HDL. A total cholesterol of higher than 240 mg/dL is abnormal, but medical intervention is determined by the breakdown of LDL and HDL levels.

LDL cholesterol
LDL, commonly known as "bad cholesterol", is associated with increased risk of cardiovascular disease.  LDL cholesterol transports cholesterol particles throughout the body, and can build up in the walls of the arteries, making them hard and narrow. LDL cholesterol is produced naturally by the body, but eating a diet high in saturated fat, trans fats, and cholesterol can increase LDL levels. Elevated LDL levels are associated with diabetes, hypertension, hypertriglyceridemia, and atherosclerosis. In a fasting lipid panel, a LDL greater than 160 mg/dL is abnormal.

HDL cholesterol
HDL, also known as "good cholesterol", is associated with decreased risk of cardiovascular disease. HDL cholesterol carries cholesterol from other parts of the body back to the liver and then removes the cholesterol from the body. It can be affected by acquired or genetic factors, including tobacco use, obesity, inactivity, hypertriglyceridemia, diabetes, high carbohydrate diet, medication side effects (beta-blockers, androgenic steroids, corticosteroids, progestogens, thiazide diuretics, retinoic acid derivatives, oral estrogens, etc.) and genetic abnormalities (mutations ApoA-I, LCAT, ABC1). Low level is defined as less than 40 mg/dL.

Triglycerides
Triglyceride level is an independent risk factor for cardiovascular disease and/or metabolic syndrome. Food intake prior to testing may cause elevated levels, up to 20%. Normal level is defined as less than 150 mg/dL. Borderline high is defined as 150 to 199 mg/dL. High level is between 200 and 499 mg/dL. Greater than 500 mg/dL is defined as very high, and is associated with pancreatitis and requires medical treatment.

Screening age
Health organizations does not have a consensus on the age to begin screening for hyperlipidemia. The CDC recommends cholesterol screenings once between ages 9 and 11, once again between 17 and 21, and every 4 to 6 years in adulthood. Doctors may recommend more frequent screenings for people with a family history of early heart attacks, heart disease, or if a child has obesity or diabetes. USPSTF recommends men older than 35 and women older than 45 to be screened. NCE-ATP III recommends all adults older than 20 to be screened as it may lead potential lifestyle modification that can reduce risks of other diseases.  However, screening should be done for those with known CHD or risk-equivalent conditions (e.g. Acute Coronary Syndrome, history of heart attacks, Stable or Unstable angina, Transient ischemic attacks, Peripheral arterial disease of atherosclerotic origins, coronary or other arterial revascularization).

Screening frequency
Adults 20 years and older should have the cholesterol checked every four to six years, and most screening guidelines recommends testing every 5 years. USPSTF recommends increased frequency for people with elevated risk of CHD, which may be determined using cardiovascular disease risk scores.

Management
Management of hyperlipidemia includes maintenance of a normal body weight, increased physical activity, and decreased consumption of refined carbohydrates and simple sugars. Prescription drugs may be used to treat some people having significant risk factors, such as cardiovascular disease, LDL cholesterol greater than 190 mg/dL or diabetes </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 Lipedematous alopecia 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 Corneal dystrophy and can you explain it in depth? [/INST] Corneal dystrophy is a group of rare hereditary disorders characterised by bilateral abnormal deposition of substances in the transparent front part of the eye called the cornea.

Signs and symptoms
Corneal dystrophy may not significantly affect vision in the early stages. However, it does require proper evaluation and treatment for restoration of optimal vision. Corneal dystrophies usually manifest themselves during the first or second decade but sometimes later. It appears as grayish white lines, circles, or clouding of the cornea.  Corneal dystrophy can also have a crystalline appearance.There are over 20 corneal dystrophies that affect all parts of the cornea. These diseases share many traits:
They are usually inherited.
They affect the right and left eyes equally.
They are not caused by outside factors, such as injury or diet.
Most progress gradually.
Most usually begin in one of the five corneal layers and may later spread to nearby layers.
Most do not affect other parts of the body, nor are they related to diseases affecting other parts of the eye or body.
Most can occur in otherwise totally healthy people, male or female.Corneal dystrophies affect vision in widely differing ways. Some cause severe visual impairment, while a few cause no vision problems and are diagnosed during a specialized eye examination by an ophthalmologist. Other dystrophies may cause repeated episodes of pain without leading to permanent loss of vision.

Genetics
Different corneal dystrophies are caused by mutations in the CHST6, KRT3, KRT12, PIP5K3, SLC4A11, TACSTD2, TGFBI, and UBIAD1 genes. Mutations in TGFBI which encodes transforming growth factor beta induced cause several forms of corneal dystrophies including granular corneal dystrophy, lattice corneal dystrophy, epithelial basement membrane dystrophy, Reis-Bucklers corneal dystrophy, and Thiel–Behnke dystrophy.Corneal dystrophies may have a simple autosomal dominant, autosomal recessive or rarely X-linked recessive Mendelian mode of inheritance:

Pathophysiology
A corneal dystrophy can be caused by an accumulation of extraneous material in the cornea, including lipids and cholesterol crystals.

Diagnosis
Diagnosis can be established on clinical grounds and this may be enhanced with studies on surgically excised corneal tissue and in some cases with molecular genetic analyses. As clinical manifestations widely vary with the different entities, corneal dystrophies should be suspected when corneal transparency is lost or corneal opacities occur spontaneously, particularly in both corneas, and especially in the presence of a positive family history or in the offspring of consanguineous parents.Superficial corneal dystrophies – Meesmann dystrophy is characterized by distinct tiny bubble-like, punctate opacities that form in the central corneal epithelium and to a lesser extent in the peripheral cornea of both eyes during infancy that persists throughout life. Symmetrical reticular opacities form in the superficial central cornea of both eyes at about 4–5 years of age in Reis-Bücklers corneal dystrophy. Patient remains asymptomatic until epithelial erosions precipitate acute episodes of ocular hyperemia, pain, and photophobia. Visual acuity eventually becomes reduced during the second and third decades of life following a progressive superficial haze and an irregular corneal surface. In Thiel–Behnke dystrophy, sub-epithelial corneal opacities form a honeycomb-shaped pattern in the superficial cornea. Multiple prominent gelatinous mulberry-shaped nodules form beneath the corneal epithelium during the first decade of life in gelatinous drop-like corneal dystrophy which cause photophobia, tearing, corneal foreign body sensation and severe progressive loss of vision. Lisch epithelial corneal dystrophy is characterized by feather shaped opacities and microcysts in the corneal epithelium that are arranged in a band-shaped and sometimes whorled pattern. Painless blurred vision sometimes begins after sixty years of life.Corneal stromal dystrophies – Macular corneal dystrophy is manifested by a progressive dense cloudiness of the entire corneal stroma that usually first appears during adolescence and eventually causing severe visual impairment. In granular corneal dystrophy multiple small white discrete irregular spots that resemble bread crumbs or snowflakes become apparent beneath Bowman zone in the superficial central corneal stroma. They initially appear within the first decade of life. Visual acuity is more or less normal. Lattice dystrophy starts as fine branching linear opacities in Bowmans layer in the central area and spreads to the periphery. Recurrent corneal erosions may occur. The hallmark of Schnyder corneal dystrophy is the accumulation of crystals within the corneal stroma which cause corneal clouding typically in a ring-shaped fashion.Posterior corneal dystrophies – Fuchs corneal dystrophy presents during the fifth or sixth decade of life. The characteristic clinical findings are excrescences on a thickened Descemet membrane (cornea guttae), generalized corneal edema and decreased visual acuity. In advanced cases, abnormalities are found in all the layers of the cornea. In posterior polymorphous corneal dystrophy small vesicles appear at the level of Descemet membrane. Most patients remain asymptomatic and corneal edema is usually absent </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 Chronic diarrhea of infancy and can you explain it in depth? [/INST] Chronic diarrhea (alternate spelling: diarrhoea) of infancy, also called toddlers diarrhea, is a common condition typically affecting up to 1.7 billion children between ages 6–30 months worldwide every year, usually resolving by age 4. According to the World Health Organization (WHO), diarrheal disease is the second greatest cause of death in children 5 years and younger. Diarrheal disease takes the lives of 525,000 or more children per year. Diarrhea is characterized as the condition of passing of three or more loose or watery bowel movements within a day sometimes with undigested food visible. Diarrhea is separated into three clinical categories; acute diarrhea may last multiple hours or days, acute bloody diarrhea, also known as dysentery, and finally, chronic or persistent diarrhea which lasts 2–4 weeks or more. There is normal growth with no evidence of malnutrition in the child experiencing persistent diarrhea. In chronic diarrhea there is no evidence of blood in the stool and there is no sign of infection. The condition may be related to irritable bowel syndrome. There are various tests that can be performed to rule out other causes of diarrhea that dont fall under the chronic criteria, including blood test, colonoscopy, and even genetic testing. Most acute or severe cases of diarrhea have treatment guidelines revolving around prescription or non prescription (also known as over the counter or OTC) medications based on the cause, but the treatment protocols for chronic diarrhea focus on replenishing the body with lost fluids and electrolytes, because there typically isnt a treatable cause.

Signs and Symptoms
Toddlers diarrhea is characterized by three or more watery stools per day that persist for 2–4 weeks or more. Newborns and infants may normally have soft and frequent stools; however, any noticeable changes in stool frequency or form (i.e. watery) can indicate toddlers diarrhea. Other symptoms may include chills, fever, abdominal pain or cramping, nausea, and/or vomiting. Undigested food and/or mucus may also be observed in stools. More serious symptoms may include bloody stools, weight loss, greasy stools, and/or severe abdominal pain.Aside from these signs and symptoms, infants and children present as healthy individuals with appropriate weight gain (considering sufficient calorie intake), active lifestyles, and normal appetites.

Complications
Possible complications associated with toddlers diarrhea include malabsorption and dehydration.Malabsorption affects the small intestine and results in the impaired absorption of important nutrients from an infant or childs diet, leading to malnutrition. Malabsorption is indicated by symptoms of bloating, appetite changes, weight loss, and/or gas.Dehydration occurs when there is not enough fluid intake to compensate for increased loss of fluid and electrolytes that may result from chronic diarrhea. Dehydration is indicated by symptoms of thirst, absence of tears when crying, infrequent urination, dry mouth, and/or decreased energy.

Cause
Diarrhea happens when the amount of fluids absorbed in the intestine does not match the amount secreted. The imbalance can be achieved in two ways: an excess of secretion or a lack of absorption. Thus, diarrhea can be categorized into secretory diarrhea, an excess of secretion, or osmotic diarrhea which is a lack of absorption. Usually both categories are present in chronic diarrhea of infants.Secretory diarrhea can be caused by either infectious or non-infectious agents. Infectious agents include bacteria, viruses, and protozoans while non-infectious agents can be hormones, neurotransmitters, cytokines, and others. Osmotic diarrhea occurs when nutrients that are not absorbed exists in the intestines, typically due to damage to the intestines. The nutrients that are unable to be absorbed in the intestines draws water to itself.Some factors that lead to chronic diarrhea of infancy:
Underdeveloped digestive system, nutrients do not spend adequate time in the digestive tract for water to be absorbed which leads to diarrhea.
Imbalanced Diet - a diet that has excess fiber and/or a lack of fat, fat can slow down the digestion process and prolong the amount of time nutrients spend in the tract which increases absorption. Fiber can lead to diarrhea because it shortens the amount of time food spends in the intestines, decreasing absorption.
Inability to absorb carbohydratesThe specific source of chronic diarrhea typically depends on the age of the infant/child. Diarrhea is uncommon for newborns; consequently, its presence in newborns could indicate a congenital disorder which would need hospitalization. Rare causes of chronic diarrhea in young children include a group of genetic mutations known as "congenital diarrhea and enteropathies" (CODEs). This group of genetic disorders usually presents in the first weeks of birth as severe and debilitating diarrhea and can lead to malabsorption, growth failure, and difficulty feeding. CODEs are rare genetic changes to a single gene that affects the lining of the intestine or changes to the immune system that also affects the cell function of important nutrient and electrolyte transporters in the intestine such as Cl−/HCO3− mutation.Otherwise, socioeconomic factors and access to treatment/healthcare play a significant part in developing chronic diarrhea as an infant. For instance, leading causes of chronic diarrhea in developing countries are infections of the intestine. In developed countries, chronic diarrhea has a diverse range of causes such as chronic infection of the intestines, autoimmune enteropathy, and inability to absorb nutrients via celiac disease, food sensitivities, etc.From age 0–30 days, typical causes are:
Abetalipoproteinemia, a condition caused by a genetic mutation that creates abnormal absorption of fats and some vitamins.
Acrodermatitis enteropathica, a condition in which the intestine cannot absorb zinc.
Autoimmune enteropathy, a rare condition in which the intestines are perceived as a foreign threat by the immune system and are attacked leading to irritation and inflammation.
Microvillous inclusion disease, a condition caused by a genetic mutation leading to severe diarrhea because intestinal cells did not have normal development and thus the intestines are not able to absorb nutrients properly.
Congenital chloride diarrhea, a lifelong condition caused by a genetic mutation that leads to diarrhea with a high concentration of chloride.
Congenital sodium diarrhea, a genetic disorder caused by mutations in electrolyte transporters that disrupt the transport of Na+ across the intestine and results in high levels of Na+ greater than 145 mM in the stool.
Congenital short-bowel syndrome, a condition in which a portion of the small intestine is absent or not functioning properly leading to decreased absorption of both fluids and nutrients.
Congenital lactase deficiency, a condition caused by a genetic mutation in which the body cannot digest lactose properly.
Glucose-galactose malabsorption, a genetic disorder caused by changes in a protein critical for the transport of glucose and galactose across the intestine which leads to impaired glucose/galactose absorption, dehydration, and severe diarrhea in young children. Typically, the severe diarrhea improves with a diet low in glucose/galactose and the tolerability to glucose/galactose improves with age.
Hirschsprungs disease (HSCR), a gut motility disorder characterized by a lack of nerve cells in the large intestine which are needed to move the stool through the digestive tract. In infants, HSCR typically presents when a newborn is unable to pass the first feces, or meconium within 48 hours of birth. Other symptoms include blockage of the intestine, fever, rapid release of stool and flatulence upon rectal examination, and may present with diarrhea in infants.
Intestinal pseudo-obstruction (IPO), a gut motility disorder characterized by the inability to contract intestinal walls with symptoms similar to intestinal obstruction but lack a distinguishable cause of obstruction. Signs and symptoms include abdominal pain, dilated or enlarged bowel, constipation and may include diarrhea. Although rare in infants, IPO is a type of congenital disorder that may present with diarrhea in infants.
Primary bile acid malabsorption, a gut defect in the reabsorption of bile acids in the small intestine which results in increased levels of bile acids in the colon leading to watery diarrhea and bloating.
Chronic infection of C. difficile, G. lamblia
C. difficile - bacteria that can be the source of diarrhea.
G. lamblia - a parasite that can be the source diarrhea.From 1–12 months, typical causes of chronic diarrhea are the following:

Acrodermatitis enteropathica, a condition in which the intestine cannot absorb zinc.
Cystic fibrosis, a condition caused by a genetic mutation that can lead to injury to the bodys organs including the lungs and those in the digestive system.
Apple juice and pear nectar, the digestive tract of children have difficulty absorbing significant quantities of sugars and carbohydrates which certain fruit juices can have.
Celiac Disease, a disorder in which there is an immune response to eating gluten which can eventually cause damage to the small intestine over time and impedes absorption.
Food allergy.Most instances of chronic diarrhea in infancy are caused by infectious and post infectious disease of the intestine as well as food sensitivities or allergies.

Diagnosis
Diagnosis of toddlers diarrhea involves the evaluation of history of present illness, any relevant past medical history, and physical examination to determine any causative factors to inform treatment regimens and further recommendations.Evaluation of history of present illness includes:
Stool characterization (i.e. appearance, consistency, frequency, etc.)
Time frame and duration (important for differentiation between acute and chronic diarrhea)
Food/drink allergies or restrictions (e.g. lactose intolerance)
Medications, especially antibiotics
Infection exposure (e.g. travel)Evaluation of past medical history includes:
Family history
Conditions such as inflammatory bowel disease, cystic fibrosis, and celiac diseasePhysical examination involves:
Abdominal examination (tenderness, distention, and/or bowel sounds)
Genital examination (rashes, anal fissures, and/or ulcerative lesions)
General assessment and vital signs (any signs of dehydration such as tachycardia and low blood pressure)
Examination of extremities and head (any signs of dehydration such as dry mucous membranes and skin turgor)

Diagnostic Tests
The following tests can also be performed to assist in the diagnosis of toddlers diarrhea and evaluation of any associated complications/underlying conditions:
Stool tests provide further information about bleeding, infectious agents, and/or anatomical problems.
Blood tests allow assessment of inflammatory markers and/or other criterion for causative diseases.
X-rays provide evaluations of any problems that may originate in the gastrointestinal tract/liver/etc.
Upper endoscopy or colonoscopy allows visualization of the gastrointestinal tract to assess location of inflammation.
Breath hydrogen tests are utilized to determine lactose, fructose, and/or sucrose intolerance. Small intestinal bacterial overgrowth (SIBO) may also be indicated by this test.

Genetic Testing
Most commonly, chronic diarrhea in infants and children are classified as acquired diarrhea, identified with the general diagnostic tests mentioned above. The other classification of chronic diarrhea, congenital diarrheas and enteropathies (CODEs), are rare diagnoses of exclusion. With recent advances in genome sequencing, the addition of targeted genetic testing to diagnostic algorithms has been proposed to allow faster diagnoses and earlier treatment of CODEs. While certain genes and mutations have been associated with various CODEs, further research and studies are necessary to support the role of diagnostic genetic testing.

Treatment
According to doctors of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), treating the cause of chronic diarrhea in infants is primarily through diet (e.g. avoiding foods their bodies dont tolerate such as gluten, lactose, fructose, and sucrose). Dietary fiber and fat can be increased and fluid intake, especially fruit juice intake, decreased. With these considerations, NIDDK doctors recommend that children consume a normal balanced diet based on their age to avoid malnutrition or growth restriction.Non-prescription medications such as loperamide are not recommended by the Centers for Disease Control and Prevention for children below 6 years of age as they dont address the underlying cause of the condition. According to Benjamin Ortiz, M.D., a pediatrician in the Food and Drug Administrations Office of Pediatric Therapeutics, bismuth subsalicylate is not recommended in children below 12 years of age because its contents, including magnesium, aluminum, and bismuth, are not readily cleared from their bodies, making them more susceptible to harm.Studies have shown that certain probiotic preparations such as Lactobacillus rhamnosus (a bacterium) and Saccharomyces boulardii (a yeast) may be effective at reducing the duration and severity of diarrhea in acute settings as a result of gastroenteritis, while other studies have found that the use of probiotics doesnt have an effect on the length of diarrhea in toddlers.While treatments for chronic diarrhea of infancy arent clear cut, it is crucial to address the complications of dehydration that may arise from chronic diarrhea with the American Academy of Pediatrics (AAP) guidelines recommendation of oral rehydration therapy (ORT). Oral rehydration solution (ORS), recommended by both AAP and the World Health Organization (WHO), must be composed of 50-90mEq/L sodium and 2% glucose or other complex carbohydrates. ORS is easily found in the US because it is available without a prescription. The typical amount of ORS administered is 50mL/kg over a 4-hour time period for mild dehydration and 100mL/kg over a 4-hour time period for moderate dehydration with an extra 10mL/kg for every loose stool. Repeat this administration regimen for as long as the signs and symptoms of dehydration continue. It is important to take measures early on to maintain hydration. Along with ORT, WHO recommends a 10-14 day course of 20 mg zinc tablet supplementation, stating it will shorten the length of diarrhea and potentially improving harmful outcomes.The NIDDK recommends a visit to the doctor when a child experiences stools containing pus or blood (black, tarry, or coffee ground-like appearance), signs of dehydration, diarrhea longer than 24 hours, or a fever of 102 degrees or more.

Epidemiology
Diarrheal illness in children accounts for 1.5 to 2.5 million deaths per year worldwide. It is responsible for the secondary cause of mortality among children less than 5 years of age surpassing the combined childhood deaths from malaria, measles, and AIDS. In 2009, the World Health Organization (WHO)/United Nations International Childrens Emergency Fund (UNICEF) reported 2.5 billion cases of diarrhea in children less than 5 years old. More than half of the cases occurred in Africa and South Asia. It is estimated that Africa and South Asia comprise more than 80% of deaths from diarrhea in children </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 Orofaciodigital 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 Parathyroid carcinoma and can you explain it in depth? [/INST] Parathyroid carcinoma is a rare cancer resulting in parathyroid adenoma to carcinoma progression </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 Shoulder impingement syndrome and can you explain it in depth? [/INST] Shoulder impingement syndrome is a syndrome involving tendonitis (inflammation of tendons) of the rotator cuff muscles as they pass through the subacromial space, the passage beneath the acromion. It is particularly associated with tendonitis of the supraspinatus muscle. This can result in pain, weakness, and loss of movement at the shoulder.

Signs and symptoms
The most common symptoms in impingement syndrome are pain, weakness and a loss of movement at the affected shoulder. The pain is often worsened by shoulder overhead movement and may occur at night, especially when lying on the affected shoulder. The onset of the pain may be acute if due to an injury or insidious if due to a gradual process such as an osteoarthritic spur. The pain has been described as dull rather than sharp, and lingers for long periods of time, making it hard to fall asleep. Other symptoms can include a grinding or popping sensation during movement of the shoulder.The range of motion at the shoulder may be limited by pain. A painful arc of movement may be present during forward elevation of the arm from 60° to 120°.  Passive movement at the shoulder will appear painful when a downward force is applied at the acromion but the pain will ease once the force is removed.

Causes
When the arm is raised, the subacromial space (gap between the anterior edge of the acromion and the head of the humerus) narrows; the supraspinatus muscle tendon passes through this space. Anything that causes further narrowing has the tendency to impinge the tendon and cause an inflammatory response, resulting in impingement syndrome. Such causes can be  bony structures such as subacromial spurs (bony projections from the acromion), osteoarthritic spurs on the acromioclavicular joint, and variations in the shape of the acromion. Thickening or calcification of the coracoacromial ligament can also cause impingement. Loss of function of the rotator cuff muscles, due to injury or loss of strength, may cause the humerus to move superiorly, resulting in impingement. Inflammation and subsequent thickening of the subacromial bursa may also cause impingement.Weight training exercises where the arms are elevated above shoulder height but in an internally rotated position such as the upright row have been suggested as a cause of subacromial impingement. Another common cause of Impingement syndrome is restrictions in the range movement of the scapulo-thoracic surfaces. Commonly, one or more ribs between rib 2 and rib 7/8 on the side of the impingement may jut out slightly and/or feel hard when the person springs on it or them. When this occurs, the scapula is raised and anteverted (angled forwards). This in turn pushes the acromion and the humeral head out of its usual anatomical position placing pressure downwards at the head of the humerus at the position of the nerve thus causing the impingement syndrome. This is visibly demonstrated by a slightly raised and protracted shoulder girdle. Note: the humerus anteverts in this position causing a more protrusive section of the humerus to press upwards towards the acromion.

Mechanism
The scapula plays an important role in shoulder impingement syndrome. It is a wide, flat bone lying on the posterior thoracic wall that provides an attachment for three different groups of muscles. The intrinsic muscles of the scapula include the muscles of the rotator cuff- the subscapularis, infraspinatus, teres minor and supraspinatus. These muscles attach to the surface of the scapula and are responsible for the internal and external rotation of the glenohumeral joint, along with humeral abduction. The extrinsic muscles include the biceps, triceps, and deltoid muscles and attach to the coracoid process and supraglenoid tubercle of the scapula, infraglenoid tubercle of the scapula, and spine of the scapula. These muscles are responsible for several actions of the glenohumeral joint. The third group, which is mainly responsible for stabilization and rotation of the scapula, consists of the trapezius, serratus anterior, levator scapulae, and rhomboid muscles and attach to the medial, superior, and inferior borders of the scapula. Each of these muscles has its own role in shoulder function and must be in balance with the others in order to avoid shoulder pathology.
Abnormal scapular function is called scapular dyskinesis. One action the scapula performs during a throwing or serving motion is elevation of the acromion process in order to avoid impingement of the rotator cuff tendons. If the scapula fails to properly elevate the acromion, impingement may occur during the cocking and acceleration phase of an overhead activity. The two muscles most commonly inhibited during this first part of an overhead motion are the serratus anterior and the lower trapezius. These two muscles act as a force couple within the glenohumeral joint to properly elevate the acromion process, and if a muscle imbalance exists, shoulder impingement may develop.
The scapula may also be misplaced if a rib deep to it is not moving correctly. Often in the case of Shoulder impingement syndrome, the scapula may be anteverted such that the shoulder on the affected side appears protracted. The ribs that may cause such an anteversion of the scapula include ribs 2–8.

Diagnosis
Impingement syndrome can be diagnosed by a targeted medical history and physical examination, but it has also been argued that at least medical imaging (generally X-ray initially) and/or response to local anesthetic injection is necessary for workup.
On physical exam, the physician may twist or elevate the patients arm to test for reproducible pain (the Neer sign and Hawkins-Kennedy test). These tests help localize the pathology to the rotator cuff; however, they are not specific for impingement. Neer sign may also be seen with subacromial bursitis.

Response to local anesthetic
The physician may inject lidocaine (usually combined with a steroid) into the bursa, and if there is an improved range of motion and decrease in pain, this is considered a positive "Impingement Test".  It not only supports the diagnosis for impingement syndrome, but it is also therapeutic.

Imaging
Plain x-rays of the shoulder can be used to detect some joint pathology and variations in the bones, including acromioclavicular arthritis, variations in the acromion, and calcification.  However, x-rays do not allow visualization of soft tissue and thus hold a low diagnostic value.  Ultrasonography, arthrography and MRI can be used to detect rotator cuff muscle pathology.  MRI is the best imaging test prior to arthroscopic surgery.  Due to lack of understanding of the pathoaetiology, and lack of diagnostic accuracy in the assessment process by many physicians, several opinions are recommended before intervention.

Treatment
Impingement syndrome is usually treated conservatively, but sometimes it is treated with arthroscopic surgery or open surgery. Conservative treatment includes rest, cessation of painful activity, and physical therapy. Physical therapy treatments would typically focus at maintaining range of movement, improving posture, strengthening shoulder muscles, and reduction of pain. NSAIDs and ice packs may be used for pain relief.Therapeutic exercises might be favorable intervention compared to passive treatment approaches, electrotherapy and placebo. A recent meta-analysis done on rotator cuff tendinopathy has shown that nearly all types of active resistance training programs were proven to be effective in improving pain and shoulder function with no significant differences among the different exercise types, further cementing the favorability of a more active intervention over passive modalities when it comes to rotator cuff issues. Exercises may help to regain the scapulo-humeral rhythm and scapular control which may reduce pain.

Steroids
Therapeutic injections of corticosteroid and local anaesthetic may be used for persistent impingement syndrome. The total number of injections is generally limited to three due to possible side effects from the corticosteroid. A 2017 review found corticosteroid injections only give small and transient pain relief.

Surgery
A number of surgical interventions are available, depending on the nature and location of the pathology. Surgery may be done arthroscopically or as open surgery. The impinging structures may be removed in surgery, and the subacromial space may be widened by resection of the distal clavicle and excision of osteophytes on the under-surface of the acromioclavicular joint. Damaged rotator cuff muscles can be surgically repaired.
A 2019 review found that the evidence does not support decompression surgery in those with more than 3 months of shoulder pain without a history of trauma </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 lip pit 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 Neonatal alloimmune thrombocytopenia and can you explain it in depth? [/INST] Neonatal alloimmune thrombocytopenia (NAITP, NAIT, NATP or NAT) is a disease that affects babies in which the platelet count is decreased because the mothers immune system attacks her fetus or newborns platelets. A low platelet count increases the risk of bleeding in the fetus and newborn.  If the bleeding occurs in the brain, there may be long-term effects.
Platelet antigens are inherited from both mother and father.  NAIT is caused by antibodies specific for platelet antigens inherited from the father but which are absent in the mother.  Fetomaternal transfusions (or fetomaternal hemorrhage) results in the recognition of these antigens by the mothers immune system as non-self, with the subsequent generation of allo-reactive antibodies which cross the placenta. NAIT, hence, is caused by transplacental passage of maternal platelet-specific alloantibody and rarely human leukocyte antigen (HLA) allo-antibodies (which are expressed by platelets) to fetuses whose platelets express the corresponding antigens.
NAIT occurs in somewhere between 1/800 and 1/5000 live births. More recent studies of NAIT seem to indicate that it occurs in around 1/600 live births in the Caucasian population.

Signs and symptoms
The diagnosis of NAIT is usually made after an incidental finding of a low platelet count on a blood test or because of bleeding complications ranging from bruising or petechiae to intracranial hemorrhage in the fetus or newborn.Frequently, the reduction in platelet count is mild and the affected neonates remain largely asymptomatic.  NAIT is the commonest cause of a very low platelet count, and the commonest cause of intracranial haemorrhage in the term neonate.In case of severe thrombocytopenia, the neonates may exhibit bleeding complications at or a few hours after delivery. The most serious complication is intracranial hemorrhage, leading to death in approximately 10% of symptomatic babies or neurologic sequelae in 20% of cases. 80% of intracranial hemorrhages occur before birth. After birth the greatest risk of bleeding is in the first four days of life.

Related conditions
Immune thrombocytopenic purpura (ITP), sometimes called idiopathic thrombocytopenic purpura is a condition in which autoantibodies are directed against a patients own platelets, causing platelet destruction and thrombocytopenia.  Anti-platelet autoantibodies in a pregnant woman with immune thrombocytopenic purpura will attack the patients own platelets and will also cross the placenta and react against fetal platelets.  Therefore, ITP is a significant cause of fetal and neonatal immune thrombocytopenia.  Approximately 10% of newborns affected by ITP will have platelet counts <50,000 μL−1 and 1% to 2% will have a risk of intracerebral hemorrhage comparable to infants with NAIT.Mothers with thrombocytopenia or a previous diagnosis of ITP should be tested for serum anti-platelet antibodies.  A woman with symptomatic thrombocytopenia and an identifiable anti-platelet antibody should be started on therapy for their ITP which may include steroids or IVIG.  Fetal blood analysis to determine the platelet count is not generally performed as ITP-induced thrombocytopenia in the fetus is generally less severe than NAIT. Platelet transfusions may be performed in newborns, depending on the degree of thrombocytopenia.

Other conditions causing a low platelet count
Other conditions that can cause a low platelet count in the neonate include bacterial and viral infection, disseminated intravascular coagulation and other rare congenital conditions associated with a low platelet count.

Pathophysiology
Platelets have many proteins on their surface. Each person has a different set of proteins, which are inherited from their parents. These different platelet proteins make different platelet groups, just like different proteins on red blood cells make different blood groups. These differences do not affect how the platelets work. However, if a baby inherits a protein that is found on the fathers platelets but is absent from the mothers platelets, the mother may respond to this foreign protein by developing an antibody that fights against it.This antibody may pass from the mothers blood into the babys blood and attach to the babys platelets. This antibody destroys the babys platelets and suppresses production of fetal platelets, they are also thought to weaken the blood vessel walls (vascular integrity) and affect production of new blood vessels (angiogenesis). This results in an increased risk of bleeding for the baby, and this can lead to the babys death. The mothers antibodies can remain in the babys bloodstream for weeks, and bleeding can occur in the baby before birth (fetal), during birth or after birth (neonatal).A number of different proteins can cause NAIT, about 80% of cases are caused by antibodies against platelet antigen HPA-1a, 15% by anti-HPA-5b, and 5% by other antibodies (e.g. HPA-1b, HPA-15, HPA-3 and HPA-9b). HPA-1a is present in 98% of the population of the United States, suggesting that approximately 2% of women who are HPA-1a negative may be at risk for NAIT during pregnancy. Of course, the antigen expression of the father must also be taken into account - in most cases the father is HPA-1a/1a or 1a/1b and the mother is HPA-1b/1b with anti-HPA-1a antibodies.  In women of Asian descent, HPA-4 antigens are the most frequently implicated.Studies have shown a relationship between maternal HLA type DRw52a (DRB3* 0101) and the development of anti-HPA-1a.The offending antibodies are IgG subtype and therefore capable of crossing the placenta and entering the fetal circulation.Unlike hemolytic disease of the fetus and newborn, NAIT occurs during the first pregnancy in up to 50% of cases, and the affected fetuses may develop severe thrombocytopenia (<50,000 μL−1) very early during pregnancy (as early as 20 weeks gestation, consistent with the development of platelet antigens, and the majority of the time in utero). Usually, the thrombocytopenia increases as gestation progresses. During the first pregnancy, NAIT is often not detected until birth when the newborn presents with classic symptoms of thrombocytopenia including petechiae, bruising or intracranial hemorrhage. In utero intracranial hemorrhage occurs in about 10% to 30% of affected cases (and NAIT is thought to be the underlying cause in the majority of cases of intracranial hemorrhage due to thrombocytopenia- greater than all other causes of thrombocytopenia combined). The risk of hemorrhage is inversely related to the platelet count with the greatest risk when the platelet count is below 100,000 μL−1.The recurrence of NAIT has been estimated to be more than 80% in subsequent pregnancies in which the fetus also carries the target platelet antigen.  Subsequent cases of NAIT may be equivalent or more severe.The fetal response to NAIT is variable and may include compensatory extramedullary hematopoiesis.  Rarely, fetal hydrops may develop.  Fetal anemia (in presence of red cell incompatibility) may also occur.

Diagnosis
Doctors may consider a diagnosis of NAIT if they notice bleeding or bruising in a baby, or low platelet counts on a blood test after birth, or neurologic symptoms. Some babies may have a specific pinpoint rash called “petechiae”. If a diagnosis of NAIT is suspected, then the baby should be treated as if it had NAIT until the diagnosis is confirmed.The diagnosis is confirmed by taking blood samples from the babys parents, and sometimes the baby. Maternal and paternal platelet antigen phenotyping and screening of the maternal serum for anti-platelet antibodies can be performed. Additionally, platelet antigen genotyping can be performed on the maternal and paternal blood to determine the exact nature of the incompatibility.Neonatal platelet counts on laboratory testing are typically under 20,000 μL−1.  Higher counts may suggest a different diagnosis, such as maternal immune thrombocytopenic purpura.Even in mildly affected babies, it is important to fully investigate and diagnose the baby because the results can be critical for the effective management of any future pregnancies.

Treatment
During pregnancy
Antenatal management only occurs if a mother has had a previously affected baby or a family member has had an affected baby.Interventions can be classified as invasive or non-invasive.A review of the evidence has shown that invasive management resulted in a relatively high complication rate (mainly preterm emergency cesarean section) of 11% per treated pregnancy. Noninvasive management was also shown to be effective, but without the relatively high rate of adverse outcomes seen with invasive management. They concluded that first-line antenatal management in NAIT should be non-invasive with weekly intravenous immunoglobulin administration, with or without the addition of corticosteroids.Recent international guidelines have now recommended non-invasive management of NAIT. Previously there had been no international consensus on the optimal antenatal management of NAIT, and numerous strategies had been used in different centers that specialized in antenatal treatment.

Invasive management
Fetal blood sampling from the umbilical cord and intrauterine platelet transfusion was the first antenatal treatment for NAIT to prevent intracerebral hemorrhage. However, this is no longer recommended routinely because of the serious risk of harms. Cordocentesis in the presence of a low platelet count may lead to serious complications, these included slowing of the babys heart (fetal bradycardia), tamponade of the cord, and bleeding complications in the baby, including exsanguination.  Fetal blood sampling is estimated to cause death of the baby in 1.3% of procedures, however the incidence varies significantly from center to center. With an overall risk of death of the fetus due to the repeated procedures of about 3% (17 deaths out of 485 pregnancies).In addition, given the short life span of transfused platelets, transfusions are needed regularly, increasing the overall risk of death of the baby. If intrauterine platelet transfusions are performed, they are generally repeated weekly (platelet lifespan after transfusion is approximately 8 to 10 days).   Platelets administered to the fetus must be negative for the culprit antigen (often HPA-1a, as stated above).  Many blood suppliers (such as American Red Cross; NHS Blood and Transplant; United Blood Services) have identified HPA-1a and 5b negative donors.  An alternative donor is a mother who is, of course, negative for the culprit antigen.  However, she must meet general criteria for donation and platelets received from the mother must be washed to remove the offending alloantibody and irradiated to reduce the risk of graft-versus-host disease.  If platelet transfusions are needed urgently, incompatible platelets may be used, with the understanding that they may be less effective and that the administration of any blood product carries risk.Any administered cellular blood products must be irradiated to reduce the risk of graft-versus-host disease in the fetus. Additionally, all administered blood products should be CMV reduced-risk (CMV seronegative and leukoreduced are considered essentially equivalent for the purposes of CMV risk reduction).

Non-invasive management
The use of Intravenous immunoglobulin (IVIG) during pregnancy and immediately after birth has been shown to help reduce or alleviate the effects of NAIT in infants and reduce the severity of thrombocytopenia.  The most common treatment is weekly IVIG infusions at a dosage of 1 g/kg beginning at 12 to 16 weeks of pregnancy in women who have had a previously affected child with an intracranial hemorrhage. For all other pregnancies, use of IVIG should be discussed, and, if indicated, should be started before 24 weeks of pregnancy and continued until the birth of the child. In some cases this dosage is increased to 2 g/kg and/or combined with a course of prednisolone  depending on the exact circumstances of the case.In a review they found that giving IVIG alone during pregnancy prevented intracranial hemorrhage in 98.7% of treated pregnancies (4 cases occurred in 315 pregnancies). This is a similar estimate to a previous review that only assessed the evidence within randomised controlled trials. They also found no consistent benefit of adding steroids to IVIG.The goal of both IVIG and platelet transfusion is to avoid hemorrhage.  Ultrasound monitoring to detect hemorrhage in the fetus is not recommended as detection of intracranial hemorrhage generally indicates permanent brain damage (there is no intervention that can be performed to reverse the damage once it has occurred).Before delivery, the fetal platelet count may not be known, due to the high risks associated with cordocentesis (see above).  If the platelet count is not known then assisted forms of delivery, for example forceps or ventouse, should be avoided to reduce the risk of harm </s>


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