<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 Hemoglobin C and can you explain it in depth? [/INST] Hemoglobin C (abbreviated as HbC) is an abnormal hemoglobin in which glutamic acid residue at the 6th position of the β-globin chain is replaced with a lysine residue due to a point mutation in the HBB gene. People with one copy of the gene for hemoglobin C do not experience symptoms, but can pass the abnormal gene on to their children. Those with two copies of the gene are said to have hemoglobin C disease and can experience mild anemia. It is possible for a person to have both the gene for hemoglobin S (the form associated with sickle cell anemia) and the gene for hemoglobin C; this state is called hemoglobin SC disease, and is generally more severe than hemoglobin C disease, but milder than sickle cell anemia.HbC was discovered by Harvey Itano and James V. Neel in 1950 in two African-American families. It has since been established that it is most common among people in West Africa. It confers survival benefits as individuals with HbC are naturally resistant to malaria caused by Plasmodium falciparum,  albeit incompletely.

Symptoms and signs
People with one copy of the gene for hemoglobin C (termed heterozygous) do not experience significant symptoms, but can pass the abnormal gene onto their children; this condition is called hemoglobin C trait. When two hemoglobin C genes are present (termed homozygous), the individual is said to have hemoglobin C disease, and may develop mild anemia, as red blood cells containing hemoglobin C have a decreased lifespan. The anemia in hemoglobin C disease is classified as hemolytic, because it is caused by the destruction of red blood cells. An enlarged spleen, and sometimes jaundice, may also occur. Some persons with this disease may develop gallstones that require treatment. Continued hemolysis may produce pigmented gallstones, an unusual type of gallstone composed of the dark-colored contents of red blood cells.

Red blood cell abnormalities
The red blood cells of people with hemoglobin C disease are usually abnormally small (microcytic) with a high mean corpuscular hemoglobin concentration (MCHC). The high MCHC is caused by a decreased concentration of water inside the cells. Target cells, microspherocytes, and HbC crystals can be seen on microscopic examination of blood smears from homozygous patients.

Combinations with other conditions
HbC can combine with other abnormal hemoglobins and cause serious hemoglobinopathies. Individuals with sickle cell–hemoglobin C (HbSC), have inherited the gene for sickle cell disease (HbS) from one parent and the gene for hemoglobin C disease (HbC) from the other parent.  Since HbC does not polymerize as readily as HbS, there is less sickling in most cases. There are fewer acute vaso-occlusive events and therefore in some cases fewer sickle cell crises. The peripheral smear demonstrates mostly target cells, occasional hemoglobin C crystals, and only a few sickle cells.  However, persons with hemoglobin SC disease (HbSC) have more significant retinopathy, ischemic necrosis of bone, and priapism than those with pure SS disease.There are also a few cases of HbC in combination with HbO, HbD and beta thalassemia.

Genetics
Hemoglobin C is produced when a point mutation in the HBB gene causes amino acid substitution of glutamic acid to lysine at the 6th position of the β-globin chain of the hemoglobin. The mutation can be homozygous, occurring on both the chromosomes (alleles), or heterozygous, affecting only one allele. Under heterozygous condition, people are said to have hemoglobin C trait, or as hemoglobin C carriers, and they have one gene for HbC with either one HbA gene or HbS gene. Their red blood cells contain both hemoglobin C and either normal hemoglobin A or hemoglobin S. Hemoglobin C mutation is an autosomal recessive disorder that results from the biparental inheritance of the allele that encodes for hemoglobin C. If both parents are carriers of hemoglobin C, there is a chance of having a child with hemoglobin C disease. Assuming both parents are carriers, there is a 25% chance of having a child with hemoglobin C disease, a 50% chance of having a child who is a carrier of hemoglobin C, and a 25% chance of having a child who is neither a carrier nor affected by hemoglobin C disease.This mutated form reduces the normal plasticity of host erythrocytes causing a hemoglobinopathy. In those who are heterozygous for the mutation, about 28–44% of total hemoglobin (Hb) is HbC, and no anemia develops. In homozygotes, nearly all Hb is in the HbC form, resulting in mild hemolytic anemia, jaundice and enlargement of spleen.

Resistance to malaria
Individuals with HbC have reduced risk of P. falciparum malaria infection. HbC has been described as being more advantageous than HbS because, even in homozygous individuals, it is usually non-fatal. However, in contrast to HbS, it does not prevent malaria due to P. vivax, and is less effective in resistance to falciparum malaria in heterozygous conditions. Homozygous HbC is more resistant to heterozygous condition, or to thalassemias. But HbC mutation  does not prevent the infection. P. falciparum do not survive in red blood cells with homozygous hemoglobins, but can survive in the presence of heterozygous hemoglobins. HbC reduced the binding force (cytoadherence) of P. falciparum by reducing the activity of PfEMP1. Evidences indicate that HbC reduced the level of  PfEMP1, which is required for effective binding and invasion of RBC by the malarial parasite. It has been predicted that with the trend of HbC mutation and falciparum prevalence, HbC would replace HbS in central West Africa in the future.

Diagnosis
Physical examination may show an enlarged spleen. Tests that may be done include: complete blood count (CBC), hemoglobin electrophoresis, and peripheral blood smear.

Prevention
Genetic counseling may be appropriate for high-risk couples who wish to have a baby.

Treatment
Usually no treatment is needed. Folic acid supplementation may help produce normal red blood cells and improve the symptoms of anemia

Prognosis
Overall, hemoglobin C disease is one of the more benign hemoglobinopathies. Mild-to-moderate reduction in RBC lifespan may accompany from mild hemolytic anemia.  Individuals with hemoglobin C disease have sporadic episodes of musculoskeletal (joint) pain. People with hemoglobin C disease can expect to lead a normal life.

Epidemiology
Hemoglobin C is found most abundantly in areas of West Africa, such as Nigeria, where Yorubas live. Hemoglobin C gene is found in 2-3% of African-Americans while 8% of African-Americans have hemoglobin S (Sickle) gene. Thus Hemoglobin SC disease is significantly more common than Hemoglobin CC disease. The trait also affects people whose ancestors came from Italy, Greece, Latin America, and the Caribbean region. However, it is possible for a person of any race or nationality to have hemoglobin C trait. In terms of geographic distribution, the hemoglobin C allele is found at the highest frequencies in West Africa, where it has been associated with protection against malaria. Hemoglobin C disease is present at birth, though some cases may not be diagnosed until adulthood. Both males and females are affected equally.

History
Studying the molecular basis of sickle cell disease, Linus Pauling and Harvey Itano at the California Institute of Technology discovered in 1949 that the disease was due to abnormal hemoglobin called HBS. In 1950, Itano and James V </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 Axis (anatomy) and can you explain it in depth? [/INST] In anatomy,  the axis (from Latin axis, "axle") or epistropheus is the second cervical vertebra (C2) of the spine, immediately inferior to the atlas, upon which the head rests.
The axis defining feature is its strong odontoid process (bony protrusion) known as the dens, which rises dorsally from the rest of the bone.

Structure
The body is deeper in front or in the back and is prolonged downward anteriorly to overlap the upper and front part of the third vertebra.
It presents a median longitudinal ridge in front, separating two lateral depressions for the attachment of the longus colli muscles.

Dens
The dens, also called the odontoid process or the peg, is the most pronounced projecting feature of the axis.  The dens exhibits a slight constriction where it joins the main body of the vertebra. The condition where the dens is separated from the body of the axis is called os odontoideum and may cause nerve and circulation compression syndrome. On its anterior surface is an oval or nearly circular facet for articulation with that on the anterior arch of the atlas. On the back of the neck, and frequently extending on to its lateral surfaces, is a shallow groove for the transverse atlantal ligament which retains the process in position. The apex is pointed and gives attachment to the apical odontoid ligament. Below the apex, the process is somewhat enlarged and presents on either side a rough impression for the attachment of the alar ligament; these ligaments connect the process to the occipital bone.
The internal structure of the odontoid process is more compact than that of the body. The odontoid peg is the ascension of the atlas fused to the ascension of the axis. The peg has an articular facet at its front and forms part of a joint with the anterior arch of the atlas. It is a non-weight bearing joint. The alar ligaments, together with the apical ligaments, are attached from the sloping upper edge of the odontoid peg to the margins of the foramen magnum. The inner ligaments limit rotation of the head and are very strong. The weak apical ligament lies in front of the upper longitudinal bone of the cruciform ligament and joins the apex of the deltoid peg to the anterior margin of the foramen magnum. It is the fibrous remnant of the notochord.

Other features
The pedicles are broad and strong, especially in the front, where they coalesce with the sides of the body and the root of the odontoid process </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 Black heel and palm 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 Transplant glomerulopathy 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 Pseudobulbar palsy 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 Periorbital dermatitis 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 Langer–Giedion syndrome and can you explain it in depth? [/INST] Langer–Giedion syndrome (LGS) is a very uncommon autosomal dominant genetic disorder caused by a deletion of a small section of material on chromosome 8. It is named after the two doctors who undertook the main research into the condition in the 1960s. Diagnosis is usually made at birth or in early childhood.

Signs and symptoms
The features associated with this condition include: mild to moderate learning difficulties, short stature, unique facial features, small head and skeletal abnormalities including bony growths projecting from the surfaces of bones.

Craniofacial
Individuals with Langer–Giedion syndrome may display characteristic craniofacial abnormalities. These include a long prominent philtrum, a thin upper lip,  wide spaced eyes, a bulbous nasal tip, a broad nasal bridge, wide nostrils, micrognathia, retrognathia, deep set eyes and large ears. The head itself is often  unusually small in comparison to that of unaffected individuals of the same age and sex. Dental abnormalities, such as supernumerary central incisors and the absence of some teeth, may occur

Muscoskeletal
Langer–Giedion syndrome causes cone shaped epiphyses of the phalanges of the hands and short fingers and toes. The fifth fingers are sometimes  bent.  Skeletal abnormalities not affecting the hands and feet may also occur </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 Eruptive vellus hair cyst and can you explain it in depth? [/INST] Eruptive vellus hair cysts (or EVHC) are small lesions that occur most often in the chest wall, abdomen and extremities, often with a crusted surface.: 680  EVHC may occur randomly, or it can be inherited as an autosomal dominant trait. The condition affects males and females equally, and sporadic cases usually appear at 4–18 years of age. The cysts appear similar clinically to steatocystoma multiplex, as well as acneiform eruptions and milia. Therapeutic techniques that are safe and effective are rare, with incision and drainage being the primary form of treatment when sporadic regression does not occur </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 Obstructive shock and can you explain it in depth? [/INST] Obstructive shock is one of the four types of shock, caused by a physical obstruction in the flow of blood. Obstruction can occur at the level of the great vessels or the heart itself. Causes include pulmonary embolism, cardiac tamponade, and tension pneumothorax. These are all life-threatening. Symptoms may include shortness of breath, weakness, or altered mental status. Low blood pressure and tachycardia are often seen in shock. Other symptoms depend on the underlying cause.The physiology of obstructive shock is similar to cardiogenic shock. In both types, the hearts output of blood (cardiac output) is decreased. This causes a back-up of blood into the veins entering the right atrium. Jugular venous distension can be observed in the neck. This finding can be seen in obstructive and cardiogenic shock. With the decrease cardiac output, blood flow to vital tissues is decreased. Poor perfusion to organs leads to shock. Due to these similarities, some sources place obstructive shock under the category of cardiogenic shock.However, it is important to distinguish between the two types, because treatment is different. In cardiogenic shock, the problem is in the function of the heart itself. In obstructive shock, the underlying problem is not the pump. Rather, the input into the heart (venous return) is decreased or the pressure against which the heart is pumping (afterload) is higher than normal. Treating the underlying cause can reverse the shock. For example, tension pneumothorax needs rapid needle decompression. This decreases the pressure in the chest. Blood flow to and from the heart is restored, and shock resolves.

Signs and Symptoms
As in all types of shock, low blood pressure is a key finding in patients with obstructive shock. In response to low blood pressure, heart rate increases. Shortness of breath, tachypnea, and hypoxia may be present. Because of poor blood flow to the tissues, patients may have cold extremities. Less blood to the kidneys and brain can cause decreased urine output and altered mental status, respectively.Other signs may be seen depending on the underlying cause. For example, jugular venous distension is a significant finding in evaluating shock. This occurs in cardiogenic and obstructive shock. This is not observed in the other two types of shock, hypovolemic and distributive. Some particular clinical findings are described below.
A classic finding of cardiac tamponade is Becks triad. The triad includes hypotension, jugular vein distension, and muffled heart sounds. Kussmauls sign and pulsus paradoxus may also be seen. Low-voltage QRS complexes and electrical alternans are signs on EKG. However, EKG may not show these findings and most often shows tachycardia.Tension pneumothorax would have decreased breath sounds on the affected side. Tracheal deviation may also be present, shifted away from the affected side. Thus, a lung exam is important. Other findings may include decreased chest mobility and air underneath the skin (subcutaneous emphysema).Pulmonary embolism similarly presents with shortness of breath and hypoxia. Chest pain worse with inspiration is frequently seen. Chest pain can also be similar to a heart attack. This is due to the right ventricular stress and ischemia that can occur in PE. Other symptoms are syncope and hemoptysis. DVT is a common cause. Thus, symptoms including leg pain, redness, and swelling can be present. The likelihood of pulmonary embolism can be evaluated through various criteria. The Wells score is often calculated. It gives points based on these symptoms and patient risk factors.

Causes
Causes include any obstruction of blood flow to and from the heart. There are multiple, including pulmonary embolism, cardiac tamponade, and tension pneumothorax. Other causes include abdominal compartment syndrome, severe aortic valve stenosis, and disorders of the aorta. Constrictive pericarditis is a rare cause. Masses can grow to press on major blood vessels causing shock.

Tension pneumothorax
A pneumothorax occurs when air collects in the pleural space around the lungs. Normally, this space has negative pressure to allow the lung to fill. Pressure increases as more air enters this space. The lung collapses, impairing normal breathing. Surrounding structures may also shift. When severe enough to cause these shifts and hypotension, it is called a tension pneumothorax. This is life-threatening. The veins supplying the heart are compressed. Thus, venous return is decreased. With the heart unable to fill, cardiac output drops. Hypotension and shock ensue. If not rapidly treated, it can lead to cardiac arrest and death.

Pulmonary embolism
A pulmonary embolism (PE) is an obstruction of the pulmonary arteries. Deaths from PE have been estimated at ~100,000 per year in the United States. However, this may be higher in recent years. Most often, the obstruction is a blood clot that traveled from elsewhere in the body. Most commonly, this is from a deep vein thrombosis (DVT) in the legs or pelvis. Risk factors are conditions that increase the risk of clotting. This includes genetic (factor V Leiden) and acquired conditions (cancer). Trauma, surgery, and prolonged bed-rest are common risks. Covid-19 is a recent risk factor.This obstruction increases the pulmonary vascular resistance. If large enough, the clot increases the load on the right side of the heart. The right ventricle must work harder to pump blood to the lungs. With back-up of blood, the right ventricle can begin to dilate. Right heart failure can ensue, leading to shock and death.A PE is considered "massive" when it causes hypotension or shock. A submassive PE causes right heart dysfunction without hypotension.

Cardiac tamponade
A pericardial effusion is fluid in the pericardial sac. When large enough, the pressure compresses the heart. This causes shock by preventing the heart from filling with blood. This is called cardiac tamponade. The chambers of the heart can collapse from this pressure. The right heart has thinner walls and collapses more easily. With less venous return, cardiac output decreases. The lack of blood flow to vital organs can cause death.Various conditions can cause a pericardial effusion. Inflammation of the pericardium is called pericarditis. This is caused by infection, renal failure or autoimmune disease. Trauma can cause blood to fill the pericardium. Cancer can also cause effusions.
Whether an effusion causes tamponade depends on the amount of fluid and how long it took to accumulate. When fluid collects slowly, the pericardium can stretch. Thus, a chronic effusion can be as large as 1 liter. Acute effusions can cause tamponade when small because the tissue does not have time to stretch.

Diagnosis
Rapid evaluation of shock is essential given its life-threatening nature. Diagnosis requires a thorough history, physical exam, and additional tests. One must also consider the possibility of multiple types of shock being present. For example, a trauma patient may be hypovolemic from blood loss. This patient could also have tension pneumothorax due to trauma to the chest.Vital signs in obstructive shock may show hypotension, tachycardia, and/or hypoxia. A physical exam include be thorough, including jugular vein exam, cardiac and lung exams, and assessing skin tone and temperature. Response to fluids may aid in diagnosis. Labs including a metabolic panel can assess electrolytes and kidney and liver function. Lactic acid rises due to poor tissue perfusion. This may even be an initial sign of shock and rise before blood pressure decreases. Lactic acid should lower with appropriate treatment of shock. EKG should also be performed. Tachycardia is often present, but other specific findings may be present based on the underlying cause.At the bedside, point-of-care echocardiography should be used. This is non-invasive and can help diagnose the four types of shock. Echocardiography can look for ventricular dysfunction, effusions, or valve dysfunction. Measurement of the vena cava during the breathing cycle can help assess volume status. A point-of-care echocardiogram can also assess for causes of obstructive shock. The vena cava would be dilated due to the obstruction. In pulmonary embolism, the right ventricle will be dilated. Other findings include paradoxical septal motion or clots in the right heart or pulmonary artery. Echocardiography can assess for pericardial effusion. In tamponade, collapse of the right atrium and ventricle would be seen due to pressure in the pericardial sac.A chest X-ray can rapidly identify a pneumothorax, seen as absence of lung markings. Ultrasound can show the lack of lung sliding. However, imaging should not delay treatment. CT angiography is the standard of diagnosis of pulmonary embolism. Clots appear in the vasculature as filling defects.

Treatment
In any type of shock, rapid treatment is essential. Delays in therapy increase the risk of mortality. This is often done as diagnostic assessment is still occurring. Resuscitation addresses the ABCs - airway, breathing, and circulation. Supplemental oxygen is given, and intubation is performed if indicated. Intravenous fluids can increase blood pressure and maintain blood flow to organs.However, fluids should be given with caution. Too much fluid can cause overload and pulmonary edema. In some cases, fluids may be beneficial. Fluids can improve venous return. For example, tamponade prevents normal cardiac filling due to pressure compressing the heart. In this case, giving fluids can improve right heart filling. However, in other causes of obstructive shock, too much fluid can worsen cardiac output. Thus, fluid therapy should be monitored closely.After these stabilizing measures, further treatment depends on the cause. Treatment of the underlying condition can quickly resolve the shock. For tension pneumothorax, needle decompression should be done immediately. A chest tube is also inserted. Cardiac tamponade is treated through needle or surgical decompression. Needle pericardiocentesis can be done at the bedside. This is often the preferred therapy. A catheter may be placed for continued drainage </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 Cleidocranial dysostosis and can you explain it in depth? [/INST] Cleidocranial dysostosis (CCD), also called cleidocranial dysplasia, is a birth defect that mostly affects the bones and teeth. The collarbones are typically either poorly developed or absent, which allows the shoulders to be brought close together. The front of the skull often does not close until later, and those affected are often shorter than average. Other symptoms may include a prominent forehead, wide set eyes, abnormal teeth, and a flat nose. Symptoms vary among people; however, intelligence is typically unaffected.The condition is either inherited from a persons parents or occurs as a new mutation. It is inherited in an autosomal dominant manner. It is due to a defect in the RUNX2 gene which is involved in bone formation. Diagnosis is suspected based on symptoms and X-rays with confirmation by genetic testing. Other conditions that can produce similar symptoms include mandibuloacral dysplasia, pyknodysostosis, osteogenesis imperfecta, and Hajdu-Cheney syndrome.Treatment includes supportive measures such as a device to protect the skull and dental care. Surgery may be performed to fix certain bone abnormalities. Life expectancy is generally normal.It affects about one per million people. Males and females are equally commonly affected. Modern descriptions of the condition date to at least 1896. The term is from cleido meaning collarbone, cranial from the Greek κρανιὀς meaning skull, and dysostosis meaning formation of abnormal bone.

Signs and symptoms
Cleidocranial dysostosis is a general skeletal condition so named from the collarbone (cleido-) and cranium deformities which people with it often have.
People with the condition usually present with a painless swelling in the area of the clavicles at 2–3 years of age. Common features are:

Clavicles (collarbones) can be partly missing leaving only the medial part of the bone. In 10% of cases, they are completely missing. If the collarbones are completely missing or reduced to small vestiges, this allows hypermobility of the shoulders including ability to touch the shoulders together in front of the chest. The defect is bilateral 80% of the time. Partial collarbones may cause nerve damage symptoms and therefore have to be removed by surgery.
The mandible is prognathic due to hypoplasia of maxilla (micrognathism) and other facial bones.
A soft spot or larger soft area in the top of the head where the fontanelle failed to close, or the fontanelle closes late.
Bones and joints are underdeveloped. People are shorter and their frames are smaller than their siblings who do not have the condition.
The permanent teeth include supernumerary teeth. Unless these supernumeraries are removed they will crowd the adult teeth in what already may be an underdeveloped jaw. If so, the supernumeraries will probably need to be removed to make space for the adult teeth. Up to 13 supernumerary teeth have been observed. Teeth may also be displaced. Cementum formation may be deficient.
Failure of eruption of permanent teeth.
Bossing (bulging) of the forehead.
Open skull sutures, large fontanelles.
Hypertelorism.
Delayed ossification of bones forming symphysis pubis, producing a widened symphysis.
Coxa vara can occur, limiting abduction and causing Trendelenburg gait.
Short middle fifth phalanges, sometimes causing short and wide fingers.
Vertebral abnormalities.
On rare occasions, brachial plexus irritation can occur.
Scoliosis, spina bifida and syringomyelia have also been described.Other features are: parietal  bossing, basilar invagination (atlantoaxial impaction), persistent metopic suture, abnormal  ear structures with hearing loss, supernumerary ribs, hemivertebrae with spondylosis,  small and high scapulae, hypoplasia of illiac bones, absence of the pubic bone, short / absent fibular bones, short / absent  radial bones, hypoplastic terminal phalanges.

Genetics
CCD is usually autosomal dominant, but in some cases its cause is not known.  The main mechanism is thought to involve haploinsufficiency caused by mutations in CBFA1 (also known as Runx2), a gene located on the short arm of chromosome 6 (6p21), which encodes a transcription factor required for the differentiation of stem cells into osteoblasts. This results in delayed ossification of midline structures of the body and ensuing defects in membranous and endochondral bone formation.

Diagnosis
Different features of the dysostosis are significant </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 Delayed pressure urticaria 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 Bruck syndrome and can you explain it in depth? [/INST] Bruck syndrome is characterized as the combination of arthrogryposis multiplex congenita and osteogenesis imperfecta. Both diseases are uncommon, but concurrence is extremely rare which makes Bruck syndrome very difficult to research. Bruck syndrome is thought to be an atypical variant of osteogenesis imperfecta most resembling type III, if not its own disease. Multiple gene mutations associated with osteogenesis imperfecta are not seen in Bruck syndrome. Many affected individuals are within the same family, and pedigree data supports that the disease is acquired through autosomal recessive inheritance. Bruck syndrome has features of congenital contractures, bone fragility, recurring bone fractures, flexion joint and limb deformities, pterygia, short body height, and progressive kyphoscoliosis. Individuals encounter restricted mobility and pulmonary function. A reduction in bone mineral content and larger hydroxyapatite crystals are also detectable Joint contractures are primarily bilateral and symmetrical, and most prone to ankles. Bruck syndrome has no effect on intelligence, vision, or hearing.

Genetics
The genetics of Bruck syndrome differs from osteogenesis imperfecta. Osteogenesis imperfecta involves autosomal dominant mutations to Col 1A2 or Col 1A2 which encode type 1 procollagen. Bruck syndrome is linked to mutations in two genes, and therefore is divided in two types. Bruck syndrome type 1 is caused by a homozygous mutation in the FKBP10 gene.  Type 2 is caused by a homozygous mutation in the PLOD2 gene.

Mechanism
Type 1  encodes FKBP65, an endoplasmic reticulum associated peptidyl-prolyl cis/trans isomerase (PPIase) that functions as a chaperone in collagen biosynthesis. Osteoblasts deficient in FKBP65 have a buildup of procollagen aggregates in the endoplasmic reticulum which reduces their ability to form bone. Furthermore, Bruck syndrome type 1 patients have under-hydroxylated  lysine residues in the collagen telopeptide and as a result show diminished hydroxylysylpyridinoline cross-links.Type 2  encodes the enzyme, lysyl hydroxylase 2, which catalyzes hydroxylation of lysine residues in collagen cross-links. PLOD2 is most expressed in active osteoblasts since collagen cross-linking is tissue-specific. Mutation in PLOD2 alters the structure of telopeptide lysyl hydroxylase and prevents fibril formation of collagen type 1. Bone analysis shows the lysine residues of telopeptides in collagen type 1 are under-hydroxylated.

Diagnosis
Diagnosis of Bruck syndrome must distinguish the association of contractures and skeletal fragility. Ultrasound is used for prenatal diagnosis. The diagnosis of a neonate bears resemblance to arthrogryposis multiplex congenital, and later in childhood to osteogenesis imperfecta.

Management
Until more molecular and clinical studies are performed there will be no way to prevent the disease. Treatments are directed towards alleviating the symptoms </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 rhabdomyosarcoma 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 Hereditary mucoepithelial dysplasia 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 Pancreas divisum and can you explain it in depth? [/INST] Pancreatic divisum is a congenital anomaly in the anatomy of the ducts of the pancreas in which a single pancreatic duct is not formed, but rather remains as two distinct dorsal and ventral ducts. Most individuals with pancreas divisum remain without symptoms or complications. A minority of people with pancreatic divisum may develop episodes of abdominal pain, nausea or vomiting due to acute or chronic pancreatitis. The presence of pancreas divisum is usually identified with cross sectional diagnostic imaging, such as MRI or computed tomography (CT) imaging. In some cases, endoscopic retrograde cholangiopancreatography (ERCP) is performed, revealing the diagnosis of pancreas divisum. If no symptoms or complications are present, then treatment is not necessary. However, if there is recurrent pancreatitis, then a sphincterotomy of the minor papilla may be indicated.

Causes
The human embryo begins life with two ducts in the pancreas, the ventral duct and the dorsal duct. Normally, the two ducts will fuse together to form one main pancreatic duct; this occurs in more than 90% of embryos. In approximately 10% of embryos the ventral and dorsal ducts fail to fuse together, resulting in pancreas divisum. In utero, the majority of the pancreas is drained by the dorsal duct which opens up into the minor duodenal papilla. The ventral duct drains the minority of the pancreas and opens into the major duodenal papilla. In adults however, this situation is reversed whereby 70% of the pancreas is drained by the ventral duct. Therefore in pancreas divisum, where fusion of the ducts does not occur, the major drainage of the pancreas is done by the dorsal duct which opens up into the minor papilla.

Diagnosis
The most common and accurate way of diagnosing an individual with this anomaly is by MRCP (Magnetic Resonance Cholangiopancreatography) or ERCP (Endoscopic Retrograde Cholangiopancreatography) </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 Breastfeeding difficulties and can you explain it in depth? [/INST] Breastfeeding difficulties refers to problems that arise from breastfeeding, the feeding of an infant or young child with milk from a womans breasts.  Although babies have a sucking reflex that enables them to suck and swallow milk, and human breast milk is usually the best source of nourishment for human infants, there are circumstances under which breastfeeding can be problematic, or even in rare instances, contraindicated.
Difficulties can arise both in connection with the act of breastfeeding and with the health of the nursing infant.

Breastfeeding problems
While breastfeeding difficulties are not uncommon, putting the baby to the breast as soon as possible after birth helps to avoid many problems. The policy of the American Academy of Pediatrics on breastfeeding instructs to, "delay weighing, measuring, bathing, needle-sticks, and eye prophylaxis until after the first feeding is completed."  Many breastfeeding difficulties can be resolved with research based hospital procedures, properly trained nurses and hospital staff, speech pathologists and lactation consultants. Another source of information is the volunteer-based breastfeeding promotion organization, La Leche League.
A variety of factors and conditions can interfere with successful breastfeeding:

Ankyloglossia (tongue tie)
Formula feeding
Distractions or interruptions during feeds
Long separations from the mother
Tachypnea (rapid breathing) such as in transient tachypnea of the newborn, surfactant deficiency, respiratory distress syndrome or other infant medical conditions
Presence of an actual physical barrier between mother and infant
Swallowing difficulties such as with prematurity and coordination of sucking, swallowing and breathing, or gastro-intestinal tract abnormalities like tracheo-oesophageal fistula.
Pain resulting from surgical procedures like circumcision, blood tests, or vaccinations.
Latching onto the breast
Hypoplastic breasts/insufficient glandular tissue
Galactorrhea
Lactation failure
Polycystic ovarian syndrome
Diabetes
Maternal stress
Insufficient rest/support of the mother during the first 6 weeks post-partum
Early return to work due to lack of financial support/maternity leave of mother
Cleft palate
Thrush
Hypoglycemia or hyperglycemia
Hypotonia, or "low-tone" infant disorder
Hyperlactation syndrome
Overactive let-down
Premature babies can have difficulties coordinating their sucking reflex with breathing. They may need to be fed more frequently because their stomachs tend to be smaller, and they may get sleepier during feedings. Premature infants unable to take enough calories by mouth may need enteral or gavage feeding - inserting a feeding tube into the stomach to provide enough breast milk or a substitute. This is often done together with Kangaroo care (prolonged skin-to-skin contact with the mother) which makes later breastfeeding easier. For some suckling difficulties, such as may happen with cleft lip/palate, the baby can be fed with a Haberman Feeder.
Dysphoric milk ejection reflex (D-MER) is a newly recognized condition affecting lactating women that is characterized by an abrupt dysphoria, or negative emotions that occur just before milk release and continuing not more than a few minutes. Preliminary testing tells us that D-MER is treatable and preliminary research tells us that inappropriate dopamine activity at the time of the milk ejection reflex is the cause of D-MER.

Low milk supply
Primary lactation failure: occurs when the mother has a condition incompatible with full milk production, for example breast hypoplasia, breast reduction surgery, or bilateral mastectomy.
Secondary lactation failure: milk production that is low due to preventable factors, such as formula supplementation, poor milk transfer by the baby, or unrelieved breast engorgement.
Chronic low milk supply is estimated to be experienced by 10-15% of women.

Breast pain
Pain often interferes with successful breastfeeding. It is cited as the second most common cause for the abandonment of exclusive breastfeeding after perceived low milk supply.

Inverted nipples
Inverted or retracted nipples sometimes make attachment to the breast difficult. These mothers need additional support to feed their babies. Treatment is started after the birth of the baby. The nipple is manually stretched out several times a day. A pump or a plastic syringe is used to draw out the nipple and the baby is then put to the breast.

Engorgement
Breast engorgement is the sense of breast fullness experienced by most women within 36 hours of delivery. Normally, this is a painless sensation of "heaviness". Breastfeeding on demand is the primary way of preventing painful engorgement.
When the breast overfills with milk it becomes painful. Engorgement comes from not getting enough milk from the breast. It happens about 3 to 7 days after delivery and occurs more often in first time mothers. The increased blood supply, the accumulated milk and the swelling all contribute to the painful engorgement. Engorgement may affect the areola, the periphery of the breast or the entire breast, and may interfere with breastfeeding both from the pain and also from the distortion of the normal shape of the areola/nipple. This makes it harder for the baby to latch on properly for feeding. Latching may occur over only part of the areola. This can irritate the nipple more, and may lead to ineffective drainage of breast milk and more pain. Reverse pressure softening (RPS) is a technique that can soften the areola enabling deeper latching and more milk transfer; RPS involves gentle positive pressure in the direction of the chest wall from the fingertips around the areola. Engorgement may begin as a result of several factors such as nipple pain, improper feeding technique, infrequent feeding or infant-mother separation.
To prevent or treat engorgement, remove the milk from the breast, by breastfeeding, expressing or pumping. Gentle massage can help start the milk flow and so reduce the pressure. The reduced pressure softens the areola, perhaps even allowing the infant to feed. Warm water or warm compresses and expressing some milk before feeding can also help make breastfeeding more effective. Some researchers have suggested that after breastfeeding, mothers should pump and/or apply cold compresses to reduce swelling pain and vascularity even more. One published study suggested the use of "chilled cabbage leaves" applied to the breasts. Attempts to reproduce this technique met with mixed results. Nonsteroidal anti-inflammatory drugs or paracetamol (acetaminophen) may relieve the pain. A warm shower and using cold compresses to help ease the discomfort.

Nipple pain
Sore nipples (nipple pain, or thelalgia) are probably the most common complaint after the birth. They are generally reported by the second day after delivery but improve within 5 days. Pain beyond the first week, severe pain, cracking, fissures or localized swelling is not normal. The mother should see a doctor for further evaluation. Sore nipples, a common cause of pain, often come from the baby not latching on properly. Factors include too much pressure on the nipple when not enough of the areola is latched onto and an improper release of suction at the end of the feeding. Improper use of breast pumps or topical remedies can also contribute. Nipple pain can also be a sign of infection.

Candidiasis
Symptoms of candidiasis of the breast include pain, itching, burning and redness, or a shiny or white patchy appearance. The baby could have a white tongue that does not wipe clean. Candidiasis is common and may be associated with infant thrush.
Both mother and baby must be treated to get rid of this infection. First-line therapies include nystatin, ketaconazole or miconazole applied to the nipple and given by mouth to the baby. Strict cleaning of clothing and breast pumps is also required to eradicate the infection.Another non-prescription treatment of candidia is gentian violet. It usually works, and relief is rapid. It is messy, and will stain clothing. The babys lips will turn purple, but the purple will disappear after a few days.

Milk stasis
Milk stasis is when the milk ducts are blocked and cannot drain properly, usually due to swelling and insufficient breast emptying during the engorgement phase. This may affect only a part of the breast and is not associated with any infection. It can be treated by varying the babys feeding position and applying heat before feeding. If it happens more than once, further evaluation is needed. Milk stasis is an urgent matter for mothers who wish to breastfeed, as failure to remove milk from the breasts causes milk production to decrease and eventually stop.

Mastitis
Mastitis is an inflammation of the breast. It causes local pain (dolor), redness (rubor), swelling (tumor), and warmth (calor). Later stages of mastitis cause symptoms of systemic infection like fever and nausea. It mostly occurs 2–3 weeks after delivery but can happen at any time. Typically results from milk stasis with primary or secondary local, later systemic infection. Infectious organisms include Staphylococcus sp., Streptococcus sp. and E. coli. Continued breastfeeding, plenty of rest and adequate fluid supply is the best treatment for light cases.

Overactive let-down
Overactive let-down (OALD) is the forceful ejection of milk from the breast during breastfeeding. The forceful spray of milk can cause the baby to consume too much milk too quickly as well as to swallow air during the period of rapid swallowing following the let-down.

Raynauds of the nipple
Nipple pain can be caused by vasospasm of the nipple. In essence, blood does not flow properly to the nipple which causes the nipple to blanch. This can be caused by trauma to the nipple through early breastfeeding or candidal infection of the nipple. The pain is intense during the latch stage and in between breastfeeding sessions there is a throbbing pain when the nipple is blanched. The nipple can be massaged to help blood flow return to reduce pain, as well as avoiding cold. In some instances, heart medication, nifedipine, is used to help the blood flow return to the nipple.

Infant health problems
Infants with classic galactosemia cannot digest lactose and therefore cannot benefit from breast milk. Breastfeeding might harm the baby also if the mother has untreated pulmonary tuberculosis, is taking certain medications that suppress the immune system. has HIV, or uses potentially harmful substances such as cocaine, heroin, and amphetamines. Other than cases of acute poisoning, no environmental contaminant has been found to cause more harm to infants than lack of breastfeeding. Although heavy metals such as mercury are dispersed throughout the environment and are of concern to the nursing infant, the neurodevelopmental benefits of human milk tend to override the potential adverse effects of neurotoxicants.

Weak sucking reflex
Artificial teats (nipples) or dummies (pacifiers) can suppress the sucking reflex in infants. In addition, when a baby is put to the breast for shorter periods of time, milk production decreases. The time spent sucking by the infant on the pacifier or artificial teat reduces the time on the breast.  The CDC also currently (2022) reports that early use of pacifiers can have a negative outcome on the success of breastfeeding and they suggest that it should be delayed until breastfeeding is firmly established.

Transmission of infection
Tuberculosis
It is not safe for mothers with active, untreated tuberculosis to breastfeed until they are no longer contagious. According to the American Academy of Pediatrics 2006 Redbook: Women with tuberculosis who have been treated appropriately for 2 or more weeks and who are not considered contagious may breastfeed. Women with tuberculosis disease suspected of being contagious should refrain from breastfeeding or any other close contact with the infant because of potential transmission through respiratory tract droplets (see Tuberculosis, p 678). Mycobacterium tuberculosis rarely causes mastitis or a breast abscess, but if a breast abscess caused by M. tuberculosis is present, breastfeeding should be discontinued until the mother no longer is contagious.
In areas where BCG vaccination is the standard of care, the WHO provides treatment recommendations and advises mothers to continue breastfeeding. TBC may be congenital, or perinatally acquired through airborne droplet spread.

HIV
Research published in the Lancet has highlighted a lower risk of HIV transmission with exclusive breastfeeding by HIV positive mothers (4% risk), compared to mixed feeding (10-40% risk). Research on the timing of HIV transmission in 2000 revealed that a "substantial transmission occurs early during breastfeeding," concluding that 75% of all breast milk transmission had occurred within the first 6 months during a randomized control trial in Kenya. This research is of particular importance in developing countries where infant formula is not widely available or safe to prepare. In fact, the World Health Organization recommended breastfeeding in 1987 and 1992 for seropositive and seronegative women in areas where malnutrition and infectious diseases are the major cause of infant mortality. In 1996 UNAIDS issued a recommendation that women in developing countries consider the risks and benefits of each feeding practice on an individual level; they recommended women make an informed choice about infant feeding.  In the days before the AIDS epidemic was clearly understood, some researchers pointed to the need to increase breastfeeding rates and pointed to the risks of formula feeding, citing increased rates of marasmus and diarrhea. D Jelliffe and E Jelliffe also criticized the marketing of infant formulas by US companies to resource-poor countries, something they termed "comerciogenic malnutrition." A more recent article from 1992 describes how the health of an infant can be compromised by water, which in many resource-poor countries holds the risk of environmental pathogens that are not present in breastmilk.

Transmission of drugs and toxins
Medications
The vast majority of over the counter and prescription medicines are compatible with breastfeeding, but there are some that might be passed onto the child through the milk.

Tobacco smoke
If one does continue tobacco smoking after giving birth, however, it is still more beneficial to breastfeed than to completely avoid this practice altogether. There is evidence that breastfeeding offers protection against many infectious diseases, especially diarrhea. Even in babies exposed to the harmful effects of nicotine through breast milk, the likelihood of acute respiratory illness is significantly diminished when compared to infants whose mothers smoked but were formula fed.  Regardless, the benefits of breastfeeding outweigh the risks of nicotine exposure.
The main concern about smoking and breastfeeding is that infants may have smoking-induced reductions to the milk iodine content.  Smoking can adversely affect the lactation process by decreasing milk production and altering the milk composition. Smoking reduces daily milk output by roughly 250–300 mL.  Not only will this be problematic on a daily basis for not producing enough milk, it will also cause the mother to wean her baby early.  The altered milk composition also caused infants to exhibit daily behaviors such as colic and crying which can promote early weaning, again something that is not beneficial to the infant.Also, the nicotine obtained from smoking travels through a woman into her breast milk, thus giving nicotine to her child.Heavy use of cigarettes by the mother (more than 20 per day) has been shown to reduce the mothers milk supply and cause vomiting, diarrhoea, rapid heart rate, and restlessness in breastfed infants. Sudden Infant Death Syndrome (SIDS) is more common in babies exposed to a smoky environment. Breastfeeding mothers who smoke are counseled not to do so during or immediately before feeding their child, and are encouraged to seek advice to help them reduce their nicotine intake or quit.

Other substance abuse
With respect to alcohol, the American Academy of Pediatrics states that when breastfeeding, "moderation is definitely advised" and recommends waiting for 2 hours after drinking before nursing or pumping. A 2014 review found that "even in a theoretical case of binge drinking, the children would not be subjected to clinically relevant amounts of alcohol [through breastmilk]", and would have no adverse effects on children as long as drinking is "occasional".If the mother consumes too much caffeine, it can cause irritability, sleeplessness, nervousness and increased feeding in the breastfed infant </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 Hydrops fetalis and can you explain it in depth? [/INST] Hydrops foetalis or hydrops fetalis is a condition in the fetus characterized by an accumulation of fluid, or edema, in at least two fetal compartments. By comparison, hydrops allantois or hydrops amnion is an accumulation of excessive fluid in the allantoic or amniotic space, respectively.

Signs and symptoms
Locations can include the subcutaneous tissue on the scalp, the pleura (pleural effusion), the pericardium (pericardial effusion) and the abdomen (ascites). Edema is usually seen in the fetal subcutaneous tissue, sometimes leading to spontaneous abortion.  It is a prenatal form of heart failure, in which the heart is unable to satisfy demand (in most cases abnormally high) for blood flow.

Causes
Hydrops fetalis usually stems from fetal anemia, when the heart needs to pump a much greater volume of blood to deliver the same amount of oxygen. This anemia can have either an immune or non-immune cause. Non-immune hydrops can also be unrelated to anemia, for example if a fetal tumor or congenital cystic adenomatoid malformation increases the demand for blood flow. The increased demand for cardiac output leads to heart failure, and corresponding edema.

Immune pathophysiology
Erythroblastosis fetalis, also known as Rh disease, is the only immune cause of hydrops fetalis. Rh disease is a hemolytic disease of newborns. Pregnant mothers do not always have the same blood type as their child. During birth or throughout the pregnancy, the mother may be exposed to the infants blood. In the event of a pregnancy where the fetus has the Rh-D blood antigen and the mother does not, the mothers immune system will respond to the red blood cells as foreign and create antibodies against the Rh-D antigen on the fetal blood cells. Rh disease develops in the event of a second pregnancy where the mothers immune system launches an attack, via IgG, against the infants Rh-D positive blood cells. The immune response results in hemolysis of fetal red blood cells causing severe anemia.Hemolysis caused by the Rh incompatibility, causes extramedullary hematopoiesis in the fetal liver and bone marrow. The push to make more erythroblasts to help compensate with the hemolysis over works the liver causing hepatomegaly. The resulting liver dysfunction decreases albumin output which in turn decreases oncotic pressure. Consequentially, the decrease in pressure results in overall peripheral edema and ascites.Rh disease is currently an uncommon cause of immune-mediated hydrops fetalis. Due to preventative methods developed in the 1970s, the incidence of Rh disease has markedly declined. Rh disease can be prevented by administration of anti-D IgG (Rho(D) Immune Globulin) injections to RhD-negative mothers during pregnancy and/or within 72 hours of the delivery. However, a small percentage of pregnant mothers are still susceptible to Rh disease even after receiving anti-D IgG (Rho(D) Immune Globulin).

Non-immune pathophysiology
Severe anemia leads to hyperdynamic circulation, which means high-output cardiac failure causes the blood to circulate rapidly. The excessive pumping of blood causes the left side of the heart to fail leading to pulmonary edema. The build up of fluid in the lungs increases the pressure in the lungs leading to vasoconstriction. The coupled vasoconstriction and pulmonary hypertension causes the right side of the heart to fail which in turn, increases the venous hydrostatic pressure in the body. The summation of these effects ultimately leads to peripheral edema and ascites. All in all, the left side failure of the heart will lead to pulmonary edema whereas right side failure will lead to peripheral edema and ascites </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 Trachonychia 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 Paraumbilical hernia and can you explain it in depth? [/INST] A paraumbilical (or umbilical) hernia is a hole in the connective tissue of the abdominal wall in the midline with close approximation to the umbilicus. If the hole is large enough there can be protrusion of the abdominal contents, including omental fat and/or bowel </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 Status marmoratus 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 Smouldering myeloma 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 Tricho–dento–osseous syndrome and can you explain it in depth? [/INST] Tricho–dento–osseous syndrome (TDO) is a rare, systemic, autosomal dominant genetic disorder that causes defects in hair, teeth, and bones respectively. This disease is present at birth. TDO has been shown to occur in areas of close geographic proximity and within families; most recent documented cases are in Virginia, Tennessee, and North Carolina. The cause of this disease is a mutation in the DLX3 (distal-less 3) gene, which controls hair follicle differentiation and induction of bone formation. All patients with TDO have two co-existing conditions called enamel hypoplasia and taurodontism in which the abnormal growth patterns of the teeth result in severe external and internal defects. The hair defects are characterized as being rough, course, with profuse shedding. Hair is curly and kinky at infancy but later straightens. Dental defects are characterized by dark-yellow/brownish colored teeth, thin and/or possibly pitted enamel, that is malformed. The teeth can also look normal in color, but also have a physical impression of extreme fragility and thinness in appearance. Additionally, severe underbites where the top and bottom teeth fail to correctly align may be present; it is common for the affected individual to have a larger, more pronounced lower jaw and longer bones. The physical deformities that TDO causes become more noticeable with age, and emotional support for the family as well as the affected individual is frequently recommended. Adequate treatment for TDO is a team based approach, mostly involving physical therapists, dentists, and oromaxillofacial surgeons. Genetic counseling is also recommended.

Signs and symptoms
Hair and bone abnormalities
Hair abnormalities are very prominent in majority of the cases of TDO. Kinky/curly hair that is unusually dry and easily sheds is present at birth. In 80% of cases, the hair has a more relaxed appearance by adolescence. The presence of this hair texture type is a defining characteristic between a diagnosis of TDO verses amelogenesis imperfecta with hypomaturation. Additionally, in TDO the nails are usually abnormally thin, brittle, and split frequently. Cranial deficiencies are marked by the presence of having a long skull relative to its width, or protrusive foreheads due to increased thickness of the cranial bones and premature closing of the associated sutures in the skull. The long bones in the body (arms, legs) are also abnormally long and tend to fracture very easily. Osteosclerosis, commonly seen in TDO cases is characterized by an increase in bone density, affecting the skull and the mastoid process located behind the jawbone on the skull, as well as a shortened ramus seen in people with TDO. There are no known pathological problems associated with hair and bone changes in people with this disease. Changes in the long bones tend to appear later in development, but changes in the teeth appear once the teeth being to form, called primary dentition. The hair and bone abnormalities are evaluated radiographically during initial diagnosis, and visually during the course of the disease. Radiographic exams may be repeated if there is suspect of fracture.

Oral abnormalities
In the oral cavity 100% of people diagnosed with TDO have taurodontism which is characterized by vertically enlarged pulp chambers at the expense of the roots of the teeth; the floor of the pulp chamber and furcation is moved apically down. This is due to the failure of the Hertwig epithelial root sheath which maps the shape of the forming tooth roots during active differentiation. Amelogenesis imperfecta, an abnormal formation of the enamel or external layer of the crown of the tooth, may also be present where the tooth enamel may be thin or absent. There are several clinical subsets of amelogenesis imperfecta, but common to TDO is the hypoplastic-hypomaturation subtype; the hypomaturation-hypoplastic is less common in individuals with TDO. The difference between the 2 dominant subtypes is the changes seen in the enamel matrix, and the phenotypic type that predominates. The hypoplastic-hypomaturation type of amelogenesis imperfecta with TDO occurs where the tooth enamel depicts a generalized pitted pattern, with open contacts between the teeth as well as an open bite. A smaller number of cases are of the hypomaturation-hypoplastic case type, in which the enamel structure is softer due to the under maturation of ameloblasts during development. Mandibular prognathism also called a severe underbite, is also a prominent feature in TDO. Prognathism defects are diagnosed based the level of severity that this condition interferes with being able to chew or speak properly.Due to improper tooth development, TDO patients have high rates of dental caries causing dental abscess. The under maturation of the enamel causes the tooth structure to be softer, and more susceptible to the effects of bruxism due to abnormalities in skeletal development. The oral abnormalities are evaluated by radiographs and visual examination. Oral radiographs are frequently repeated due to the high incidence of infection due to abnormal biting patterns seen in TDO cases.

Cause
TDO is caused by autosomal dominant mutations in the DLX gene family. Known mutations include a 4-basepair deletion in exon 3 of DLX3 on chromosome 17q21, causing a frameshift mutation.

Pathogenesis
DLX3 plays numerous significant roles during osseous, connective tissue, and dermal cell differentiation. It is expressed in the placenta and is important for embryonic development of hard bone tissue in the teeth, skull, and long bones such as in the arms and legs. During normal tooth development, DLX3 is predominantly expressed in the inner tooth enamel epithelium. In TDO cases, DLX3 is expressed in the outer enamel epithelium and leads to the abnormally thin enamel observed in the disease, which leads to tooth attrition and is most often the cause of dental abscess seen in TDO persons.
DLX3 in TDO is also responsible for upper cranial thickness, calvaria, osteosclerosis of the long bones, long narrow head (dolichocephaly), abnormally thin brittle nails, and premature closing of fibrous joints. Consequently, 95% of people with TDO that are 16 years old or younger show skeletal abnormalities before full maturation takes place.Lack of mastoid pneumatization by mastoid cells occurs in 82% of the cases and is rarely prevalent outside of TDO diagnosis. Mastoid pneumatization occurs at about 6 months of ages and acts to minimize pressure fluctuations in the Eustachian tubes of the ear. The mastoid lies posterior to the lower jawbone (mandible) and distal to the ear. The Eustachian tube connects the middle ear to the back of the nose, and acts to create a specific pressure in the ear canal that causes vibrations to the eardrum; if adequate pressure is not attained, muffled, dull hearing results. In addition to the mastoid pneumatization assisting the Eustachian tubes for normal hearing, lack of mastoid pneumatization causes inflammation of the ear, general irritation, and does not allow enough air in to assist with mucus flowing out. It is not completely understood why gene mutations occur, but it is known that genetic mutations that cause disease are acquired from either or both parents at fertilization.

Diagnosis
TDO is diagnosed by radiographic imaging, physical characteristics of the disease, and genetic testing. Radiographs such as cephalometric analysis or panoramic radiograph are used to detect skeletal abnormalities in TDO cases; these radiographs along with the phenotypic effects of the disease are often enough evidence for proper diagnosis. In TDO, radiologic imaging almost always shows evidence of hardening of bone tissue (sclerosis), lesions on the bone structures surrounding the teeth due to decay or trauma, or hard tissue mass. The radiographic testing is non-invasive, and involves the patient to be able to sit or stand in front of the radiographic device with their mouth closed and lips relaxed for approximately one minute. Oral abnormalities are diagnosed by a visual dental examination. A normal oral evaluation would show no signs of broken or fractured teeth, attrition of tooth enamel, no spacing between teeth, no soft tissue mass or sign of dental abscess, and a bite relationship where the mandibular (bottom) teeth interdigitate within a normal plane of 1-2mm behind and underneath the maxillary (top) teeth.

Overlapping diseases
It is phenotypically difficult to diagnose between TDO and Amelogenesis imperfecta of the hypomaturation-hypoplasia type with taurodontism (AIHHT) as they are very closely linked phenotypically during adulthood, and the only distinguishing characteristic is found during genetic analysis by Polymerase Chain Reaction (PCR) amplification. This type of test in diagnosis of TDO is only used during research or if there is a concern of genetic issue to a particular individual whose family member has been diagnosed with TDO.

Prevention
Preventive maintenance therapy for the oral effects of TDO involve frequent dental cleanings, professional application of desensitizing medication, diet counseling, and oral hygiene instructions in proper home care and maintenance; medicated dental rinses and toothpastes are also prescribed as people with TDO are more prone to oral hard tissue disease and early tooth loss. If restorative dentistry is performed without orthodontics to correct the protrusion of the lower jaw, a dental night guard worn at bedtimes on the upper or lower teeth to protect them from the effects of grinding may be recommended.In extreme cases, tooth loss is inevitable, and the patient will consult with a prosthodontist to determine tooth replacement options such as dental implants, or partial dentures. There is no cure for TDO, but managing its oral and systemic affects is key to having the most favorable outcome from the disease. As the person affected by TDO ages, increased bone fractures may occur. The person with TDO should watch for any pimple like masses on the gum tissue, pain or soreness in the teeth and gums, broken or chipped teeth, feeling of water in the ear or severe pain in the extremities which could indicate fracture.

Treatment
The hair, teeth, and skeletal side effects of TDO are lifelong, and treatment is used to manage those effects. A person with TDO has the same life expectancy as a person without TDO. There are no cures or medications used to treat systemic effects of TDO, but medications for the frequent ear and dental infections can be used to manage its symptoms. A team based approach between dental specialists, oral and maxillofacial surgeons, and physicians is necessary for treating the systemic effects and improves the prognosis </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 Embryonal rhabdomyosarcoma and can you explain it in depth? [/INST] Embryonal rhabdomyosarcoma (EMRS) is a rare histological form of cancer in the connective tissue wherein the mesenchymally-derived malignant cells resemble the primitive developing skeletal muscle of the embryo. It is the most common soft tissue sarcoma occurring in children. Embryonal rhabdomyosarcoma is also known as PAX-fusion negative or Fusion-Negative rhabdomyosarcoma, as tumors of this subtype are unified by their lack of a PAX3-FOXO1 fusion oncogene (or other PAX fusions seen in alveolar rhabdomyosarcoma). Fusion status refers to the presence or absence of a fusion gene, which is a gene formed from joining two different genes together through DNA rearrangements. These types of tumors are classified as embryonal rhabdomyosarcoma "because of their remarkable resemblance to developing embryonic and fetal skeletal muscle."

Classification
Embryonal rhabdomyosarcoma is the more common of the two major sub-types of rhabdomyosarcoma. ERMS accounts for 60% to 70% of rhabdomyosarcoma, the other being alveolar rhabdomyosarcoma (ARMS), also known as PAX-fusion positive or Fusion Positive rhabdomyosarcoma. Most often, ERMS is found in children during ages 0 to 5 years old, however ERMS can develop throughout any stage of life. Embryonal rhabdomyosarcoma can be further divided into three  subcategories: the botryoid, spindle cell, and not-otherwise-specified (NOS). These two subtypes of rhabdomyosarcoma, ERMS and ARMS, also are caused by different genetic mutation pathways.The Horn-Enterline classification uses morphologic characteristics to divide rhabdomyosarcoma into the embryonal, alveolar, botryoid, and pleomorphic subtypes. However, due to recent advancements in molecular genetics, the genetic and epigenetic factors contributing to these morphological differences have been more closely examined. As a result, the World Health Organization currently takes into account both molecular genetics and morphology to classify rhabdomyosarcoma into the embryonal, alveolar, spindle cell/sclerosing, and pleomorphic subtypes.When examining Embroynal Rhabdomyosarcoma tumors vs. Alveolar Rhabdomyosarcoma tumors, a 2013 study had discovered that there were more rates of mutation in ERMS tumors. The study had use whole genome sequencing to sequence the DNA from 16 RMS tumors and found that RAS pathway mutations tend to be more associated with intermediate and high risk embryonal Rhabdomyosarcoma. Additionally, Embryonal Rhabdomyosarcoma tends to be more common in males versus females, with an occurrence of 1.4:1.

Histology
Embryonal rhabdomyosarcoma has been informally classified as a "small round blue cell tumor" because of the characteristic microscopic appearance of its cells after histological staining with hematoxylin and eosin. Histologically, embryonal rhabdomyosarcoma commonly presents as alternating loose and dense patches of cells, including round cell and spindle cell components. The heterogenous structure resembles striated muscle at various embryonal developmental stages.

Location
Embryonal rhabdomyosarcoma can develop in soft tissues throughout the body, however, it is commonly found in the "head and neck area or in the genital or urinary organs"  The botryoid variant of ERMS occurs in mucosal-lined organs such as the common bile duct, bladder, and vagina. The etymology for this variant name comes from "grape clusters", referring to the gross appearance of grape-like masses.

Epidemiology of RMS
RMS has a higher incidence of affecting males compared to females. Embryonal rhabdomyosarcoma is the most common in young children but there has been report of a second age peak in adolescence years.

United States
As the most common form of soft tissue sarcoma, RMS affects around 4.5 people per million individuals under the age of 20 in the United States. From 1975 to 2005 in the United States, there is a lower incidence rate of rhabdomyosarcoma and better 5-year survival rates in Native Indian/Alaskan Native/Asian/Pacific Islander children compared to white or black children; however, Native Indian/Alaskan Native/Asian/Pacific Islander make up only 6.5% of the total population studied.

Global
The incidence of RMS in Europe is similar to that of the United States, while the incidence in some parts of Asia is half of the United States.

Etiology
Embryonal rhabdomyosarcoma results from copy number alterations as well as mutations in the RAS pathway. Genomic patterns associated with ERMS include the gains in chromosomes 8, 2, 11, 12, 13, and/or 20 and losses in chromosomes 10 and 15. Another common genomic alteration is loss of heterozygosity at chromosome 11p, the short arm of chromosome 11. It is believed that some of the identifying genetic mutations that can cause ERMS include p53 loss, RAS pathway activation, MYOD1 mutations. Patients in the fusion-negative group had different genetic mutation profiles than those in the fusion-positive group.Focusing on the fusion negative population, it was shown that the most fusion-negative tumors were caused by RAS isoform mutations. Approximately 50% of ERMS is associated with RAS mutations, with NRAS mutations more common in adolescent cases and HRAS and KRAS mutations occurring in 70% of infant cases. Embryonal rhabdomyosarcoma is commonly driven by a mutation in the RAS family of proto-oncogenes, creating a powerful signal which is now known to promote tumor growth by preventing muscle lineage progression by blocking expression of the transcription factor myogenin. Inhibition of this signaling pathway with a cancer medication, trametinib, has been recently shown to overcome this differentiation block and reduce tumor progression in animal models of embryonal rhabdomyosarcoma.Tumor suppressor gene mutations, such as TP53 mutations, were shown in about 13% in the mutations and MYOD1 mutations were seen in about 3% of the mutations. Tumor suppressors signal the cell to stop the cell cycle and start apoptosis, known as programmed cell death, when the cell senses damage or irregular cell cycle growth patterns. Approximately 10% of ERMS cases include a loss of function mutation at TP53, which results in anaplasia, poor cellular differentiation that can be identified through nuclei that are larger and darker-colored than normal. An international study of more than 600 people with RMS showed worst outcomes in cases with anaplasia, regardless of fusion-status.

Predisposing Conditions
Genetic conditions such as Gorlin syndrome, neurofibromatosis type 1, Beckwith-Wiedemann syndrome, Li-Fraumeni syndrome, Noonan syndrome, Costello syndrome, and DICER1 syndrome have been shown to predispose individuals to embryonal rhabdomyosarcoma. Risk factors associated with embryonal rhabdomyosarcoma include cigarette smoking, older age of birth parent, x-ray exposure, and maternal drug use. Of note, the development of Noonan syndrome, Costello syndrome, and neurofibromatosis type 1 are RASopathies, associated with mutations in the RAS cell signaling pathway. ERMS caused by genetically inherited mutations is cannot be morphologically distinguished from spontaneously acquired ERMS.

Diagnosis
Rhabdomyosarcoma is diagnosed through the presence of embryonic myogenesis, or skeletal muscle formation, which can be identified through morphological examination as well as assays containing myogenic markers. Immunohistochemical assays use protein expression to determine the fusion status of the growth, differentiating fusion-negative rhabdomyosarcoma from fusion-positive  rhabdomyosarcoma. In the recent years, there has been a shift to use molecular classification over histological classification as histology alone does not predict the fusion type of rhabdomyosarcoma. The performance of molecular genetic tests as well as matching the genotypic result to the clinical presentation are necessary to confirm the diagnosis of rhabdomyosarcoma as well as identify a subtype.

Immunochemistry
Fusion-status is determined through the expression of certain proteins that indicate muscle differentiation, or immunomarkers, although the specific assay panel used for diagnosis depends on the tumor morphology. These immunomarkers include desmin, muscle-specific actin, Myogenin, and MyoD1, the latter two being transcription factors that are involved in muscle differentiation. Embryonal rhabdomyosarcoma can be classified by its lack of PAX3–FOXO1 or PAX7–FOXO1 gene fusions, but approximately 20% of alveolar rhabdomyosarcomas are also determined to be fusion-negative. However, it is suggested that these "fusion-negative" ARMS may be a misclassification of embryonal rhabdomyosarcomas with predominantly dense morphology. The World Health Organization recommends considering "fusion-negative" ARMS as a "primitive form of ERMS". In either case, "fusion-negative" alveolar rhabdomyosarcoma have similar clinical presentation and outcome as embryonal rhabdomyosarcoma, thus risk stratification, prognosis, and treatment intensity of rhabdomyosarcoma are now determined by fusion-status instead of histological classification.

Imaging
After a physical exam, formal diagnosis of RMS in adult patients requires a computed tomography (CT) scan, which can assess the areas affected and to delineate the tumor. In children, physicians may opt for magnetic resonance imaging (MRI) to limit radiation exposure in younger populations. In the majority of individuals diagnosed with rhabdomyosarcoma, more than half are diagnosed before the age of 10.

Prognosis
The prognosis for rhabdomyosarcoma has improved greatly in recent decades, with over 70% of people surviving for five years after diagnosis. The combined use of radiotherapy and surgery has significantly reduced the mortality rates compared to patients who did not undergo any radiotherpay or chemotherapy treatments. Embryonal rhabdomyosarcoma is generally associated with better prognosis than alveolar rhabdomyosarcoma, with a 5-year survival prognosis of 82% and 53%, respectively. This may be due to the more aggressive and metastatic nature of ARMS that can be attributed to its PAX3–FOXO1 or PAX7–FOXO1 gene fusions. Nevertheless, some embryonal rhabdomyosarcoma patients with a rare Leu122Arg mutation in MYOD1 gene have a very poor outcome. In two different studies, none of the subjects with the MYOD1 mutation survived.  Tumors due to this mutation commonly manifest in the head and neck area, causing the mutated protein to behave like an oncogene.There have not been many studies linking the genetic profile and clinical outcome of ERMS. However in "A Report From an International Consortium", the authors analyzed patient data from the Childrens Oncology Group (COG) and European paediatric Soft tissue sarcoma Study Group (EpSSG), hoping to identify and analyze any relationship between clinical outcomes and genetic mutations. The study comprised of 641 patients with sufficient data to analyze.Contrary to previous research, the findings of this study suggest that having RAS isoform mutations did not necessarily equate to a poor development of the disease. However, a pattern was found between the RAS isoform mutation seen and ones stage in life; HRAS isoform in infants, KRAS isoform in toddlers, and NRAS isoform in adolescence. This clinical study also found similar results as previous studies with the correlation of TP53 mutations and clinical outcome. TP53 mutations tended to result in a worsening development and clinical outcome of the disease. Although MYOD1 mutations make up a small percentage of ERMS, these mutations have been seen to have a negative prognosis and more studies should be conducted to understand how to treat the clinical condition of this specific mutation.

Tumor Location
Tumor location plays an important role as RMS located in the parameningeal area, retroperitonium, pelvic, vulva, uterus, vagina, or trunk area genereally have poor prognosis. The anatomical position of parameningeal RMS makes it difficult to completely resect the entire tumor via surgery and may lead to tumor recurrence. Additionally, imaging that shows a tumor greater than 5 cm, presence of metastases, or positive lymph node status can indicate poor prognosis. People that have more distant tumors — tumors that have spread to distant parts away from the primary site — have higher mortality rate when compared to people with only localized tumors.

Age of Diagnosis
In a 2020 case study of 464 adolescents aged 0–19 years diagnosed with rhabdomyosarcoma between 1988 to 2016, children who were diagnosed between ages 5–9 years had the most promising prognosis. In contrast, infants less than 1 years old had the worst outcome, which may be associated to the lower doses of chemotherapy and radiotherapy administered and naive immune system.

Treatment
Treatment for embryonal rhabdomyosarcoma involves the use of combination therapy consisting of chemotherapy, surgery, and/or radiation therapy. In order to create an optimal treatment plan for the individual, therapy is often based upon risk stratigication (low, intermediate, or high risk) based off of individuals disease stage, size of tumor, progression of disease, surgery resection, age at diagnosis, and site of tumor. In the US, a combination of Vincristine, Actinomycin D, and cyclophosphamide are often the chemotherapeutics used to treat rhabdomyosarcoma. In contrast, the regimen in Europe utilizes Vincristine, Actinomycin D, and ifosfamide.  When the US and European regimen were studied side by side, the two regimens were comparable in terms of efficacy outcomes. Radiation therapy continues to be an integral component of rhabdomyosarcoma treatment, however, the long-term safety and treatment related complications remain a concern. Advancement in the use of radiation therapy includes using three-dimensional conformal radiation therapy (3D-CRT) to create a three-dimensional image of tumor so providers can determine the dose of radiation per patient while limiting radiation exposure to normal tissues. Techniques such as multi-field optimization (MFP) allows for more precise distribution of proton beams.

Treatment Plan
The first line of treatment for most people is surgery or resection of the tumor(s). The surgery involves removing the primary tumor and any tissue that may be infected with cancer cells. Resection of the tumor tends to be more favorable in cancers that have not yet metastisized. In the case that the tumor cannot be removed, the cancer can be treated with a combination of radiation and chemotherapy instead. In the majority of people, the surgery cannot remove all traces of the cancer and chemotherapy/radiation will be required as further treatment to eradicate any remaining cancer.
Chemotherapy is given in the US as a medication regimen abbreviated VAC, consisting of Vincristine, Actinomycin D, and Cyclophosphamide. The chemotherapy works to kill all the remaining cancer cells and to stop future growth of any possible cancerous cells. Safety concerns regarding the long term effects of chemotherapy remains a concern. Side effects of the VAC regimen include nausea, vomiting, liver damage, and immune system suppression </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 Abfraction and can you explain it in depth? [/INST] Abfraction is a theoretical concept explaining a loss of tooth structure not caused by tooth decay (non-carious cervical lesions). It is suggested that these lesions are caused by forces placed on the teeth during biting, eating, chewing and grinding; the enamel, especially at the cementoenamel junction (CEJ), undergoes large amounts of stress, causing micro fractures and tooth tissue loss. Abfraction appears to be a modern condition, with examples of non-carious cervical lesions in the archaeological record typically caused by other factors.

Definition
Abfraction is a form of non-carious tooth tissue loss that occurs along the gingival margin. In other words, abfraction is a mechanical loss of tooth structure that is not caused by tooth decay, located along the gum line. There is theoretical evidence to support the concept of abfraction, but little experimental evidence exists.The term abfraction was first published in 1991 in a journal article dedicated to distinguishing the lesion. The article was titled "Abfractions: A New Classification of Hard Tissue Lesions of Teeth"  by John O. Grippo. This article introduced the definition of abfraction as a "pathologic loss of hard tissue tooth substance caused by bio mechanical loading forces". This article was the first to establish abfraction as a  new form of lesion, differing from abrasion, attrition, and erosion.Tooth tissue is gradually weakened causing tissue loss through fracture and chipping or successively worn away leaving a non-carious lesion on the tooth surface. These lesions occur in both the dentine and enamel of the tooth. These lesions generally occur around the cervical areas of the dentition.

Signs and symptoms
Abfraction lesions will generally occur in the region on the tooth where the greatest tensile stress is located. In statements such as these there is no comment on whether the lesions occur above or below the CEJ. One theory suggests that the abfraction lesions will only form above the CEJ. However, it is assumed that the abfraction lesions will occur anywhere in the cervical areas of affected teeth. It is important to note that studies supporting this configuration of abfraction lesions also state that when there is more than one abnormally large tensile stress on a tooth two or more abfraction lesions can result on the one surface.When looking at abfraction lesions there are generally three shapes in which they appear, appearing as either wedge, saucer or mixed patterns. Wedge and saucer shaped lesions are the most common, whereas mixed lesions are less frequently identified in the oral cavity. In reference to figure 1, wedge shaped lesions have the sharpest internal line angles and saucer/mixed shaped lesions are either smooth internally, or a variety.
Clinically, people with abfraction lesions can also present with tooth sensitivity in the associated areas. This occurs because as the abfraction lesions appear, dentine/cementum is exposed. The dentine and cementum are less dense than tooth enamel and therefore more susceptible to sensation from thermal/mechanical sources.

Causes
As abfraction is still a controversial theory there are various ideas on what causes the lesions. Because of this controversy the true causes of abfraction also remain disputable. Researchers have proposed that abfraction is caused by forces on the tooth from the teeth touching together, occlusal forces, when chewing and swallowing. These lead to a concentration of stress and flexion at the area where the enamel and cementum meet (CEJ).  This theoretical stress concentration and flexion over time causes the bonds in the enamel of the tooth to break down and either fracture or be worn away from other stressors such as erosion or abrasion. The people who initially proposed the theory of abfraction believe the occlusal forces alone cause the lesions without requiring the added abrasive components such as toothbrush and paste or erosion.If teeth come together in a non-ideal bite the researchers state that this would create further stress in areas on the teeth. Teeth that come together too soon or come under more load than they are designed for could lead to abfraction lesions. The impacts of restorations on the chewing surfaces of the teeth being the incorrect height has also been raised as another factor adding to the stress at the CEJ.Further research has shown that the normal occlusal forces from chewing and swallowing are not sufficient to cause the stress and flexion required to cause abfraction lesions. However, these studies have shown that the forces are sufficient in a person who grinds their teeth (bruxism). Several studies have suggested that it is more common among those who grind their teeth,  as the forces are greater and of longer duration.  Yet further studies have shown that these lesions do not always appear in people with bruxism and others without bruxism have these lesions.There are other researchers who would state that occlusal forces have nothing to do with the lesions along the CEJ and that it is the result of abrasion from toothbrush with toothpaste that causes these lesions.Being theoretical in nature there is more than one idea on how abfraction presents clinically in the mouth. One theory of its clinical features suggests that the lesions only form above the cementoenamel junction (CEJ) (which is where the enamel and cementum meet on a tooth). If this is kept in mind, it serves as a platform for it to be distinguished from other non-carious lesions, such as tooth-brush abrasion.

Treatment
Treatment of abfraction lesions can be difficult due to the many possible causes. To provide the best treatment option the dental clinician must determine the level of activity and predict possible progression of the lesion.  A No.12 scalpel is carefully used by the dental clinician to make a small indentation on the lesion, this is then closely monitored for changes. Loss of a scratch mark signifies that the lesion is active and progressing.
It is usually recommended when an abfraction lesion is less than 1 millimeter, monitoring at regular intervals is a sufficient treatment option. If there are concerns around aesthetics or clinical consequences such as dentinal hypersensitivity, a dental restoration (white filling) may be a suitable treatment option.
Aside from restoring the lesion, it is equally important to remove any other possible causative factors.
Adjustments to the biting surfaces of the teeth alter the way the upper and lower teeth come together, this may assist by redirecting the occlusal load. The aim of this is to redirect the force of the load to the long axis of the tooth, therefore removing the stress on the lesion. This can also be achieved by altering the tooth surfaces such as cuspal inclines, reducing heavy contacts and removing premature contacts. If bruxism is deemed a contributing factor an occlusal splint can be an effective treatment for eliminating the irregular forces placed on the tooth.

Controversy
Abfraction has been a controversial subject since its creation in 1991. This is due to the clinical presentation of the tooth loss, which often presents in a manner similar to that of abrasion or erosion. The major reasoning behind the controversy is the similarity of abfraction to other non carious lesions and the prevalence of multiple theories to potentially explain the lesion. One of the most prevalent theories is called "the theory of non-carious cervical lesions" which suggests that tooth flexion, occurring due to occlusion factors, impacts on the vulnerable area near the cementoenamel junction. This theory is not widely accepted among the professional community as it suggests that the only factor is occlusion. Many researchers argue that this is inaccurate as they contend that the abfraction lesion is a multifactorial (has many causative factors) lesion with other factors such as abrasion or erosion. This controversy around the causative factors, along with the recency of the lesion classification, are some of the reasons why many dental clinicians are looking at the lesion with some scepticism. More research is needed to fully clear up the controversy surrounding the abfraction lesion.

See also
Tooth wear
Abrasion
Attrition
Bruxism
Erosion

References

Summit, James B., J. William Robbins, and Richard S. Schwartz </s>