<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 Crossbite and can you explain it in depth? [/INST] Crossbite is a form of malocclusion where a tooth (or teeth) has a more buccal or lingual position (that is, the tooth is either closer to the cheek or to the tongue) than its corresponding antagonist tooth in the upper or lower dental arch. In other words, crossbite is a lateral misalignment of the dental arches.

Anterior crossbite
An anterior crossbite can be referred as negative overjet, and is typical of class III skeletal relations (prognathism).

Primary/mixed dentitions
An anterior crossbite in a child with baby teeth or mixed dentition may happen due to either dental misalignment or skeletal misalignment. Dental causes may be due to displacement of one or two teeth, where skeletal causes involve either mandibular hyperplasia, maxillary hypoplasia or combination of both.

Dental crossbite
An anterior crossbite due to dental component involves displacement of either maxillary central or lateral incisors lingual to their original erupting positions. This may happen due to delayed eruption of the primary teeth leading to permanent teeth moving lingual to their primary predecessors. This will lead to anterior crossbite where upon biting, upper teeth are behind the lower front teeth and may involve few or all frontal incisors. In this type of crossbite, the maxillary and mandibular proportions are normal to each other and to the cranial base. Another reason that may lead to a dental crossbite is crowding in the maxillary arch. Permanent teeth will tend to erupt lingual to the primary teeth in presence of crowding. Side-effects caused by dental crossbite can be increased recession on the buccal of lower incisors and higher chance of inflammation in the same area. Another term for an anterior crossbite due to dental interferences is Pseudo Class III Crossbite or Malocclusion.

Single tooth crossbite
Single tooth crossbites can occur due to uneruption of a primary teeth in a timely manner which causes permanent tooth to erupt in a different eruption pattern which is lingual to the primary tooth. Single tooth crossbites are often fixed by using a finger-spring based appliances. This type of spring can be attached to a removable appliance which is used by patient every day to correct the tooth position.

Skeletal crossbite
An anterior crossbite due to skeletal reasons will involve a deficient maxilla and a more hyperplastic or overgrown mandible. People with this type of crossbite will have dental compensation which involves proclined maxillary incisors and retroclined mandibular incisors. A proper diagnosis can be made by having a person bite into their centric relation will show mandibular incisors ahead of the maxillary incisors, which will show the skeletal discrepancy between the two jaws.

Posterior crossbite
Bjork defined posterior crossbite as a malocclusion where the buccal cusps of canine, premolar and molar of upper teeth occlude lingually to the buccal cusps of canine, premolar and molar of lower teeth. Posterior crossbite is often correlated to a narrow maxilla and upper dental arch. A posterior crossbite can be unilateral, bilateral, single-tooth or entire segment crossbite. Posterior crossbite has been reported to occur between 7–23% of the population. The most common type of posterior crossbite to occur is the unilateral crossbite which occurs in 80% to 97% of the posterior crossbite cases. Posterior crossbites also occur most commonly in primary and mixed dentition. This type of crossbite usually presents with a functional shift of the mandible towards the side of the crossbite. Posterior crossbite can occur due to either skeletal, dental or functional abnormalities. One of the common reasons for development of posterior crossbite is the size difference between maxilla and mandible, where maxilla is smaller than mandible. Posterior crossbite can result due to

Upper Airway Obstruction where people with "adenoid faces" who have trouble breathing through their nose. They have an open bite malocclusion and present with development of posterior crossbite.
Prolong digit or suckling habits which can lead to constriction of maxilla posteriorly
Prolong pacifier use (beyond age 4)

Unilateral posterior crossbite
Unilateral crossbite involves one side of the arch. The most common cause of unilateral crossbite is a narrow maxillary dental arch. This can happen due to habits such as digit sucking, prolonged use of pacifier or upper airway obstruction. Due to the discrepancy between the maxillary and mandibular arch, neuromuscular guidance of the mandible causes mandible to shift towards the side of the crossbite. This is also known as Functional mandibular shift. This shift can become structural if left untreated for a long time during growth, leading to skeletal asymmetries. Unilateral crossbites can present with following features in a child

Lower midline deviation to the crossbite side
Class 2 Subdivision relationships
Temporomandibular disorders

Treatment
A child with posterior crossbite should be treated immediately if the child shifts their mandible on closing, which is often seen in a unilateral crossbite as mentioned above. The best age to treat a child with crossbite is in their mixed dentition when their palatal sutures have not fused to each other. Palatal expansion allows more space in an arch to relieve crowding and correct posterior crossbite. The correction can include any type of palatal expanders that will expand the palate which resolves the narrow constriction of the maxilla. There are several therapies that can be used to correct a posterior crossbite: braces, Z spring or cantilever spring, quad helix, removable plates, clear aligner therapy, or a Delaire mask. The correct therapy should be decided by the orthodontist depending on the type and severity of the crossbite.
One of the keys in diagnosing the anterior crossbite due to skeletal vs dental causes is diagnosing a CR-CO shift in a patient </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 Necrotizing periodontal diseases and can you explain it in depth? [/INST] Necrotizing periodontal diseases is one of the seven categories of periodontitis as defined by the American Academy of Periodontology 1999 classification system and is one of the three classifications of periodontal diseases and conditions within the 2017 classification.
Necrotizing periodontal diseases are a type of inflammatory periodontal (gum) disease caused by bacteria (notably fusobacteria and spirochaete species). The diseases appear to represent different severities or stages of the same disease process, although this is not completely certain. These diseases usually have a sudden onset, and so the term acute is often added to the diagnosis. The mildest on the spectrum is necrotizing ulcerative gingivitis (NUG), followed by the successively more severe conditions necrotizing ulcerative periodontitis (NUP), necrotizing stomatitis and finally cancrum oris (noma), which is frequently fatal.

Necrotizing ulcerative gingivitis
Necrotizing ulcerative gingivitis, (NUG), or simply necrotizing gingivitis (NG), is a common, non-contagious infection of the gums. Acute necrotizing ulcerative gingivitis (ANUG) is the acute presentation of NUG, which is the usual course the disease takes. If improperly treated NUG may become chronic and/or recurrent. In developed countries, ANUG occurs mostly in young adults with predisposing factors such as psychological stress, sleep deprivation, poor oral hygiene, smoking, immunosuppression and/or malnutrition. In developing countries, ANUG occurs mostly in malnourished children. Due to shared predisposing factors in a population (e.g. students during a period of examinations, armed forces recruits) ANUG is known to occur in epidemic-type patterns. This has led to the popular belief that ANUG is contagious, but this is not the case. The main features of NUG are painful, bleeding gums and ulceration and necrosis of the interdental papilla. There may also be intra-oral halitosis, cervical lymphadenitis (swollen lymph nodes in the neck) and malaise. Treatment of the acute disease is by debridement and antibiotics, usually metronidazole. Poor oral hygiene and other predisposing factors may need to be corrected to prevent recurrence. ANUG is also known as trench mouth, as it was observed to occur in the mouths of front line soldiers during World War I.

Necrotizing ulcerative periodontitis
Necrotizing ulcerative periodontitis (NUP, or simply necrotizing periodontitis, NP) or acute necrotizing ulcerative periodontitis (ANUP) is where the infection leads to attachment loss (destruction of the ligaments anchoring teeth in their sockets), but involves only the gingiva, periodontal ligament and alveolar ligament </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 Fissure of the nipple 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 Xanthoma diabeticorum 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 Neuroferritinopathy and can you explain it in depth? [/INST] Neuroferritinopathy  is a genetic neurodegenerative disorder characterized by the accumulation of iron in the basal ganglia, cerebellum, and motor cortex of the human brain. Symptoms, which are extrapyramidal in nature, progress slowly and generally do not become apparent until adulthood. These symptoms include chorea, dystonia, and cognitive deficits which worsen with age.This disorder is autosomal dominant and is caused by mutations in the gene encoding the light chain subunit of the ferritin protein. Wild type ferritin functions as a buffer for iron, sequestering it and controlling its release. Thus, mutations in the light chain of ferritin result in the accumulation of iron in the brain which can be imaged using MRI. Currently, neuroferritinopathy is the only neurodegenerative disease with an iron accumulation in the brain classified as an autosomal dominant syndrome.Treatment of neuroferritinopathy is focused on managing symptoms associated with chorea and dystonia using standard medications for each. The disorder is progressive and symptoms become worse with age. Fewer than 100 cases of neuroferritinopathy have been reported since its identification in 2001. Its incidence has been largely localized to Northeast England suggesting a founder effect. Due to its genetic nature, current research is focused on therapeutic management of the symptoms caused by the disorder.

Signs and symptoms
Neuroferritinopathy has several distinguishing signs and symptoms. These fall into two categories: diagnostic findings and physically visible symptoms.

Diagnostic findings
Symptoms categorized as medically tested and diagnosed include iron accumulation in the brain, basal ganglia cavitation, and neurodegeneration. Patients who are diagnosed with neuroferritinopathy have abnormal iron accumulation in the brain within the neurons and glia of the striatum and cerebellar cortices. Along with the accumulation of iron in the brain, neuroferritinopathy typically causes severe neuronal loss as well.
Secondary symptoms may also arise. It is possible that the initial iron accumulation will cause additional neuronal damage and neuronal death. The damaged neurons may be replaced by other cells in an effort to reverse the neurodegeneration. These cells often have a higher iron content. The breakdown of the blood brain barrier may also occur due to the loss of neurons and will subsequently allow more iron to access the brain and accumulate over time.Neuroferritinopathy is mainly seen in those who have reached late adulthood and is generally seen to slowly progress throughout many decades in a lifetime with the mean age of onset being 39 years old. A loss of cognition is generally only seen with late stages of the disease. Diagnosed patients are seen to retain most of their cognitive functioning until the most progressive stages of the illness sets in.

Physical symptoms
Symptoms categorized as physically visible symptoms include chorea, dystonia, spasticity, and rigidity, all physical symptoms of the body associated with movement disorders. The symptoms accompanying neuroferritinopathy affecting movement are also progressive, becoming more generalized with time. Usually during the first ten years of onset of the disease only one or two limbs are directly affected.
Distinctive symptoms of neuroferritinopathy are chorea, found in 50% of diagnosed patients, dystonia, found in 43% of patients, and parkinsonism, found in 7.5% of patients. Full control of upper limbs on the body generally remains until late onset of the disease. Over time, symptoms seen in a patient can change from one side of the body to the opposite side of the body, jumping from left to right or vice versa. Another route that the physically visible symptoms have been observed to take is the appearance, disappearance, and then reappearance once more of specific symptoms.While these symptoms are the classic indicators of neuroferritinopathy, symptoms will vary from patient to patient.

Causes
Neuroferritinopathy results from abnormal brain iron accumulation. This iron accumulation is due to mutations in the FTL polypeptide, which is responsible for encoding proteins involved in iron metabolism. Neuroferritinopathy is most commonly caused by a single insertion of the nucleotide adenine into the gene for L-chain ferritin which in turn, alters the carboxyl end of the entire protein chain. However, exact location of the insertion in the exon varies by family. Neuroferritinopathy may also be caused by the insertion of two extra nucleotide bases. The insertion of bases into the L-chain ferritin gene causes the chain to lengthen and alter the sequence of the amino acids found in the gene, also known as a frameshift mutation.These mutations result in decreased iron-binding ability. The oxidative damage caused by increased iron leads to apoptosis, or programmed cell death. Accumulation of iron in the brain is extremely dangerous as excess iron catalyzes the formation of free radicals, which have damaging effects to the brain. The iron accumulation characteristic of neuroferritinopathy particularly affects the cerebellum, basal ganglia, and motor cortex regions of the brain.

Mechanism
The protein ferritin functions to sequester and release iron, acting as an iron buffering system in cells. Iron is essential to brain function in oxygen transport and cellular metabolism for example. However, careful control of iron is important as increased brain iron levels catalyze the formation of free radicals that create oxidative molecules via the Fenton Reaction. These oxidative molecules can cause oxidative brain damage. Iron that is bound to ferritin in nonreactive.Fenton Reaction
(1) Fe2+ + H2O2 → Fe3+ + HO• + OH−(2) Fe3+ + H2O2 → Fe2+ + HOO• + H+The ferritin protein is made up of heavy chain (H) and light chain (L) subunits. In neuroferritinopathy, the gene encoding the light chain is mutated. Several different mutation variations have led to diagnosis as neuroferritinopathy; all of these mutations occur in the light chain. A mutated light chain is believed to inhibit ferritins ability to effectively sequester and hold iron. Without control of iron, it is free to cause oxidative brain damage as described above.The concentration of iron in a healthy brain varies greatly from region to region. The specific regions of the brain that are associated with motor functions appear to have larger accumulations of iron than non-motor-related regions. This observation of varying iron concentrations is a possible explanation for the correlation between movement disorders and the iron imbalance within the central nervous system.

Diagnosis
Neuroferritinopathy is primarily diagnosed in older adults, specifically in adults affected by Alzheimers disease or Parkinsons disease, as iron accumulates in the brain over long periods of time. Neuroferritinopathy is diagnosed using either neuroimaging techniques, physiological tests, or genetic testing.

Classification
Neuroferritinopathy was originally described with hallmark features of neurodegeneration and iron accumulation in the brain, leading it to be classified with other neurodegeneration with brain iron accumulation (NBIA) disorders which share similar symptoms and imaging findings. Over time single-gene causes have been found for many NBIA disorders, like neuroferritinopathy. Before the availability of genetic testing, all such disorders were considered together and known as Hallervorden-Spatz syndrome, a term which is no longer used due to the Nazi party ties of the namesakes. Brain iron disorders are now divided into three categories: genetic neurodegeneration with brain iron accumulation, genetic systemic iron accumulation with neurologic features, and acquired diseases associated with iron excess or iron deficiency. Neuroferritinopathy is classified under the first category. Neuroferritinopathy is classified as a late-onset basal ganglia disease and is a dominantly inherited neurodegenerative disease. Four different alleles are responsible for neuroferritinopathy. Three arise from nucleotide insertions in the ferritin light chain (FTL) polypeptide gene while the fourth arises from a missense mutation in the FTL gene.

Neuroimaging
Neuroferritinopathy is most commonly diagnosed using MRI and other neuroimaging techniques. MRIs help identify the iron deposits in the cerebellum, basal ganglia, and motor cortex common to neuroferritinopathy. MRIs of affected individuals also show mild cerebellar and cerebral atrophy, or tissue breakdown, and gas cavity formation in the putamen. Most importantly, the MRIs show misfolded ferritin proteins and iron deposits in the glial cells of the caudate, putamen, globus pallidus, cerebral cortex, thalamus, and purkinje cells, causing neuronal death in these areas.

Physiological testing
Blood tests usually come back normal in affected individuals, so they do not serve as a reliable means of diagnosis. Blood tests can show low serum ferritin levels. However, this is unreliable as method of diagnosis, as some patients show typical serum ferritin levels even at the latest stages of neuroferritinopathy. Cerebral spinal fluid tests also are typically normal.
Ferritin aggregates found in the skin, liver, kidney, and muscle tissues may help in diagnosing neuroferritinopathy. More cytochrome c oxidase-negative fibers are also often found in the muscle biopsies of affected individuals.

Genetic testing
Genetic testing can confirm a neuroferritinopathy diagnosis. A diagnosis can be made by analyzing the protein sequences of affected individuals  and comparing them to known neuroferritinopathy sequences.

Treatment
Due to neuroferritinopathys genetic etiology, the disorder is not currently curable. Furthermore, progression of the disorder is unable to be effectively halted. Therefore, current treatment focuses on managing symptoms of the disorder.
No medication is available to treat all 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 Cholesterolosis of gallbladder 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 Spiradenoma and can you explain it in depth? [/INST] Spiradenomas (SA) are rare, benign cutaneous adnexal tumors that may progress to become their malignant counterparts, i.e. spiradenocarcinomas (SAC). Cutaneous adnexal tumors are a group of skin tumors consisting of tissues that have differentiated (i.e. matured from stem cells) towards one of the four primary adnexal structures found in normal skin: hair follicles, sebaceous sweat glands, apocrine sweat glands, and eccrine sweat glands. SA and SAC tumors were regarded as eccrine gland tumors and termed eccrine spiradenomas and eccrine spiradenocarcinomas, respectively. However, more recent studies have found them to be hair follicle tumors and commonly term them spiradenomas and spiradenocarcinomas, respectively. Further confusing the situation, SA-like and SAC-like tumors are also 1) manifestations of the inherited disorder, CYLD cutaneous syndrome (CCS), and 2) have repeatedly been confused with an entirely different tumor, adenoid cystic carcinomas of the salivary gland. Here, SA and SAC are strictly defined as sporadic hair follicle tumors that do not include the hereditary CCS spiradenomas and heridtary spiradenocarcinoms of CCS or the adenoid cystic carcinomas.
SA tumors usually occur as slow-growing, single, small, nodular lesions located in the skin of the head, neck, or trunk. SAC tumors develop from benign SA tumors or in very rare cases begin as malignant tumors. SA and SAC tumors must be distinguished from the spiradenoma and spiradenocaricnoma tumors that develop in individuals afflicted with the CYLD cutaneous syndrome. CCS is an inherited disorder that commonly involves the development of multiple but on occasion a single or few tumors that closely resemble, and may be confused with, the sporadic SA and SAC tumors described here. CCS spiradenoma and CCS spiradenocarcinoma tumors must be distinguished form the sporadic SA and SAC tumors reviewed here in order to afford genetic counseling to individuals with CCS as well as to the close family members of these individuals.Currently, SA and SAC are usually treated by complete excision making sure that no tumor cells are left behind at the surgical site. This is particularly important in SAC where the incomplete surgical removal of all tumor cells may result in recurrence of the tumor at the surgical site and/or its metastasis to the local lymph nodes draining the surgical site and/or to distant tissues. In addition to surgical resection, some cases of SAC tumors have been treated with adjuvant therapy that includes radiotherapy and/or chemotherapy. It is not clear that these adjuvant treatments improve patient prognoses. Further studies are needed to determine the best treatment(s) for localize SA, localized SAC, and, in particular, metastatic SAC tumors.

Presentation
Spiradenoma tumors occur in individuals of various ages but tend to develop in middle-aged and elder adults (e.g. in a study of 27 patients, the median age at diagnosis was 62 years). However, cases have been reported in children as young as 2 years. These tumors usually present as a solitary, sometimes painful, slowly growing, 1–2 cm (i.e. centimeters), gray-to-pink nodules that lie underneath the skins epidermis in the head, neck, trunk, arms, or legs. However, these nodules have been reported to be as large as 6 cm and to occur in other hair follicle-containing cutaneious sites such as the vulva, breast, and breast nipple. Areas of the skin that do not have hair follicles (e.g. palms of the hands and soles of feet) do not develop these nodules. Less than 2% of cases present with more than one nodule; the multiple nodules in SA tend to array in a linear, blaschkoid (i.e. V-, U-, or inverted U-shaped), or zosteriform (i.e. belt- or girdle-shape tracking an area of skin served by a sensory nerve) patterns. Giant vascular eccrine spiradenomas are larger (> 2 cm) and more highly vascular variants of SA that usually develop at the same cutaneous sites as SA but have also been reported to occur in the abdomen and scrotum. No malignant giant vascular SA has been described in the literature to date (2021).A recent review of 182 cases reported that spiradenocarcinomas were diagnosed in individuals 8–89 years old (mean 57.4 years). These SAC tumors developed in SA tumors that had existed for 0–720 months (mean 168.5 months); 14.4% of individuals were diagnosed with multiple carcinoma lesions. (Multiple SAC lesions may appear as a nodule associated with smaller satellite nodules.) The lesions occurred on the trunk (32.3% of cases), limbs (31.3%), head or neck (30.7%), and genitalia (1.6%). These individuals presented with lesions that began to show abnormal growth (82.6% of cases), pain (47.7% of cases), and/or ulcerations (38.7% of cases). In earlier studies, SAC tumors were reported to varied in size with 40% being larger than 5 cm and the majority not having metastasized; the sites to which these lesions metastasized were most commonly to lymph nodes near to the SAC or, rarely, distant tissues such as the lung, liver, brain, spinal cord, bone, skin, and breast.

Pathology
As determined by the microscopic histopathological appearances of their hematoxylin and eosin-stained samples, spiradenomas are non-encapsulated nodular skin lesions that extend into the dermis. The lesions consist of a relatively disorganized and dense array of proliferating basophilic cells (i.e. cells appearing blue because of their abnormally large uptake of the hematoxylin stain). These cells are arranged as small cells with hyperchromatic nuclei and scant cytoplasm layered outside and larger cells with vesicular (i.e. vesicle-containing) nuclei layered inside of intertwining strips. Lymphocytes commonly populate these lesions. Some lesions may merge the histopathological features of spiroadenomas with those of cylindromas. Cylindromas are hair follicle tumors that consist of basal cells (i.e. small, round cells similar to those seen in the lowest layer of the skins epidermis) which are arranged in ("jigsaw-like" cylindrical patterns separated by thickened basement membranes. The cylindroma tissues may also contain disorganized, dense arrays of proliferating basophilic cells.Spiradenocarcinoma tumors almost always derive from SA tumors and have areas of SA architecture abruptly transitioning to areas of SAC architecture. The SAC component of these lesions consists of cells that, along with their nuclei and cytoplasm, vary greatly in size and shape. The cells may be rapidly proliferating, have atypical mitosis figures, and may be invading nearby neural or lymphovascular structures; they do not arrange into intertwining strips of small and large cells. High-grade SAC tissues show a more severely disturbed architecture, more marked variation in cell, nuclei, and cytoplasm sizes and shapes, and more rapidly proliferating cells than low-grade SAC tissues. SAC tumor tissues may show various other features, e.g. they may closely resemble sarcomas. In rare cases, SAC has been reported to apparently arise de novo, i.e. begin as malignant lesions.

Gene abnormalities
Studies indicate that a minority of SA and SAC cases have one of two potentially disease-causing mutations in their tumor cells: loss-of-function (i.e. gene-inactivating) mutations in the CYLD gene in 5 of 17 SA and 2 of 24 SAC cases or gain-of-function (i.e. gene-activating) mutations in the ALPK1 gene in 7 of 16 SA and 4 of 14 SAC cases. The two mutations are mutually exclusive, i.e. do not occur together in any individuals tumor(s). Both mutations result in blocking the actions pf NF-κB. NF-κB is a transcription factor which acts indirectly to stimulate the expression of various genes that trigger cell death by apoptosis and necroptosis and also inhibit cell proliferation (see CYLD genes mechanism of action). It is proposed that the blockade of NF-κBs actions prolongs cell survival, stimulates high rates of cell growth, and perhaps has other effects which contribute to the formation and/or progression of SA and SAC tumors.

Diagnosis
SA and SAC tumors have been confused with leiomyoma, angiolipoma, granular cell tumor, basal cell carcinoma, squamous cell carcinoma, metastatic adenocarcinoma, and adenoid cystic carcinoma tumors; the giant vascular SA form of these tumors has been mistaken for a hemangioma, angiolipoma, calcifying epithelioma, neuroma, malignant melanoma, angiosarcoma, vascular malformation, and venous thrombosis. CT scans, FDG-positron emission tomography, and magnetic resonance imaging to detect 1) the shape and local invasiveness of these tumors and 2) the presence of metastases and 2) the clinical presentation of individuals of these tumors often suggest the correct diagnosis. However, definitive separation of SA, SAC, and giant vascular SA from the just cited lesions requires histopathological examinations. The diagnosis of SA versus SAC tumors is often suggested by their clinical presentations, e.g. rapid enlargement or onset of pain in a long-standing SA tumor strongly suggests that it has become a SAC. Findings that a known SA or undiagnosed tumor has areas of SA histology transitioning to SAC histology (see above Pathology section) is virtually diagnostic for SAC.The sporadic SA and SAC tumors reviewed here must also be distinguished from the very similar appearing SA-like and SAC-like tumors in individuals afflicted with the CYLD cutaneous syndrome. CCS is a familial disease uniformly associated with the inheritance of inactivating mutations in the CYLD gene. Individuals with CCS commonly develop an increasingly large number of skin tumors, including SA and SAC, over time. Usually, these individuals are readily distinguished from sporadic SA and SAC by their family history of the disease and the presence of large numbers of tumors. The rare cases of CCS that present with one or a few tumors are distinguished form CCS by testing for the CYLD gene: all individuals with CCS carry a mutated CYLD gene in their tumor as well as other tissues such as blood leucocytes while individuals with sporadic SA or SAC carry the mutated CYLD gene in their tumor but not other tissues (see Genetics of CCS). It is important to afford individuals with CCS and the close family members of these individuals access to in depth genetic counselling.

Treatments
There is no consensus on the best treatment(s) for SA and SAC tumors. Further research, including meta-analysis comparisons of different treatment regimens, is needed to define the best treatment(s) for these tumors. In all cases, however, regular follow-ups of individuals with SA and SAC are strongly recommended in order to detect as early as possible: the formation of new tumors; changes in old tumors that suggest their progression to more aggressive or malignant formss; local recurrences of surgically removed tumors; and the development of local or distant metastases. One recommended follow-up strategy prescribes patients to have check-ups ever three months in the first year after treatment, every six months in the second year after treatment, and annually thereafter. Each check-up should incorporate the examination of the patients regional lymph nodes and on a case-by-case basis annual chest X-rays and liver function tests.

Spiradenomas
The currently preferred treatment for sporadic SA tumors (including giant vascular eccrine SA) in almost all cases is surgical excision. Many studies recommend wide local surgical excision of these tumors with surgical margins of ≥1 cm in order to ensure that all tumor cells are removed: local lymph node resections are usually reserved for those cases suspected of having lymph node metastases. Mohs micrographic surgery has been used as an alternative to surgical excision for the complete removal of these tumors. Since SA tumors may contain unidentified areas of malignancy and therefore have high recurrence rates, may metastasize to local lymph nodes and/or distant tissues, and can result in overall poor survival times, adjuvant radiation therapy has been used to minimize these aggressive events in SA tumors with equivocal signs of malignancy </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 Cigarette burns 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 Aniridia and can you explain it in depth? [/INST] Aniridia  is the absence of the iris, a muscular structure that opens and closes the pupil to allow light into the eye. It is also responsible for eye color. Without it the central eye appears all black. It can be congenital, in which both eyes are usually involved, or caused by a penetrant injury.  Isolated aniridia is a congenital disorder which is not limited to a defect in iris development,  but is a  panocular condition with macular and optic nerve hypoplasia, cataract,  and corneal changes. Vision may be severely compromised and the disorder is frequently associated with a number of ocular complications: nystagmus, amblyopia, buphthalmos, and cataract. Aniridia in some individuals occurs as part of a syndrome, such as WAGR syndrome (kidney nephroblastoma (Wilms tumour), genitourinary anomalies and intellectual disability), or Gillespie syndrome (cerebellar ataxia).

PAX6
The AN2 region of the short  arm of chromosome 11 (11p13) includes the PAX6 gene (named for its PAired boX status), whose gene product helps regulate a cascade of other genetic processes involved in the development of the eye (as well as other non-ocular structures).  This PAX6 gene is around 95% similar to the pax gene found in zebrafish, a creature whose ancestors diverged from human evolutionary development around 400 million years ago. Thus the PAX6 gene is  highly conserved across evolutionary  lineages.
Defects in the PAX6 gene cause aniridia-like ocular defects in mice (as well as Drosophila). Aniridia is a heterozygous disorder, meaning that only one of the two chromosome 11 copies is affected. When both copies are altered (homozygous condition), the result is a uniformly fatal condition with near complete failure of entire eye formation. In 2001, two cases of  homozygous aniridia patients were reported; the fetuses died prior to birth and had severe brain damage. In mice, homozygous small eye defect (mouse Pax-6) leads to loss of the eyes and nose and the murine fetuses sustain severe brain damage.

Types
Aniridia may be broadly divided  into hereditary and sporadic forms </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 Monostotic fibrous 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 Obsessive–compulsive personality disorder and can you explain it in depth? [/INST] Obsessive–compulsive personality disorder (OCPD) is a cluster C personality disorder marked by an excessive need for orderliness and neatness. Symptoms are usually present by the time a person reaches adulthood, and are visible in a variety of situations. The cause of OCPD is thought to involve a combination of genetic and environmental factors, namely problems with attachment.This is a distinct disorder from obsessive–compulsive disorder (OCD), and the relation between the two is contentious. Some studies have found high comorbidity rates between the two disorders but others have shown little comorbidity. Both disorders may share outside similarities, such as rigid and ritual-like behaviors. Attitudes toward these behaviors differ between people affected with either of the disorders: for people with OCD, these behaviors are egodystonic, unwanted and involuntary, being the product of anxiety-inducing and involuntary thoughts. On the other hand, for people with OCPD, they are egosyntonic; the person perceives them as rational and wanted, being the result of, for example, strong adherence to routines, a desire for control, or a need for perfection. OCPD is highly comorbid with other personality disorders, autism spectrum, eating disorders, anxiety, mood disorders, and substance use disorders.The disorder is the most common personality disorder in the United States, and is diagnosed twice as often in males as in females, however, there is evidence to suggest the prevalence between men and women is equal.

Signs and symptoms
Obsessive–compulsive personality disorder (OCPD) is marked by an excessive obsession with rules, lists, schedules, and order; a need for perfectionism that interferes with efficiency and the ability to complete tasks; a devotion to productivity that hinders interpersonal relationships and leisure time; rigidity and zealousness on matters of morality and ethics; an inability to delegate responsibilities or work to others; restricted functioning in interpersonal relationships; restricted expression of emotion and affect; and a need for control over ones environment and self.Some of OCPDs symptoms are persistent and stable, whilst others are unstable. The obsession with perfectionism, reluctance to delegate tasks to others, and rigidity and stubbornness are stable symptoms. On the other hand, the symptoms that were most likely to change over time were the miserly spending style and the excessive devotion to productivity. This discrepancy in the stability of symptoms may lead to mixed results in terms of the course of the disorder, with some studies showing a remission rate of 58% after a 12-month period, whilst others suggesting that the symptoms are stable and may worsen with age.

Attention to order and perfection
People with OCPD tend to be obsessed with controlling their environments; to satisfy this need for control, they become preoccupied with trivial details, lists, procedures, rules, and schedules.This preoccupation with details and rules makes the person unable to delegate tasks and responsibilities to other people unless they submit to their exact way of completing a task because they believe that there is only one correct way of doing something. They stubbornly insist that a task or job must be completed their way, and only their way, and may micromanage people when they are assigned a group task. They are frustrated when other people suggest alternative methods. A person with this disorder may reject help even when they desperately need it as they believe that only they can do something correctly.People with OCPD are obsessed with maintaining perfection. The perfectionism and the extremely high standards that they establish are to their detriment and may cause delays and failures to complete objectives and tasks.  Every mistake is thought of as a major catastrophe that will soil their reputation for life. For example, a person may write an essay for a college, and then believe that it fell short of "perfection", so they continue rewriting it until they miss the deadline. They may never complete the essay due to the self-imposed high standards. They are unaware that other people may become frustrated and annoyed by the repeated delays and hassles that this behavior causes. Work relationships may then become a source of tension.

Devotion to productivity
Individuals with OCPD devote themselves to work and productivity at the expense of interpersonal relationships and recreation. Economic necessity, such as poverty, cannot account for this behavior. They may believe that they do not have sufficient time to relax because they have to prioritize their work above all. They may refuse to spend time with friends and family because of that. They may find it difficult to go on a vacation, and even if they book a vacation, they may keep postponing it until it never happens. They may feel uncomfortable when they do go on a vacation and will take something along with them so they can work. They choose hobbies that are organized and structured, and they approach them as a serious task requiring work to perfect. The devotion to productivity in OCPD, however, is distinct from work addiction. OCPD is controlled and egosyntonic, whereas work addiction is uncontrolled and egodystonic, and the affected person may display signs of withdrawal.

Rigidity
Individuals with OCPD are overconscientious, scrupulous and rigid, and inflexible on matters of morality, ethics and other areas of life. They may force themselves and others to follow rigid moral principles and strict standards of performance. They are self-critical and harsh about their mistakes. These symptoms should not be accounted for or caused by a persons culture or religion. Their view of the world is polarised and dichotomous; there is no grey area between what is right and what is wrong. Whenever this dichotomous view of the world cannot be applied to a situation, this causes internal conflict as the persons perfectionist tendencies are challenged.People with this disorder are so obsessed with doing everything the "right and correct" way that they have a hard time understanding and appreciating the ideas, beliefs, and values of other people, and are reluctant to change their views, especially on matters of morality and politics.

Restricted emotions and interpersonal functioning
Individuals with this disorder may display little affection and warmth; their relationships and speech tend to have a formal and professional approach, and not much affection is expressed even to loved ones, such as greeting or hugging a significant other at an airport or train station.They are extremely careful in their interpersonal interactions. They have little spontaneity when interacting with others, and ensure that their speech follows rigid and austere standards by excessively scrutinising it. They filter their speech for embarrassing or imperfect articulation, and they have a low bar for what they consider to be such. They lower their bar even further when they are communicating with their superiors or with a person of high status. Communication becomes a time-consuming and exhausting effort, and they start avoiding it altogether. Others regard them as cold and detached as a result.Their need for restricting affection is a defense mechanism used to control their emotions.  They may expunge emotions from their memories and organize them as a library of facts and data; the memories are intellectualized and rationalized, not experiences that they can feel. This helps them avoid unexpected emotions and feelings and allows them to remain in control. They view self-exploration as a waste of time and have a patronising attitude towards emotional people.

Interpersonal control
Individuals with OCPD are at one extreme of the conscientiousness continuum. While conscientiousness is a desirable trait generally, its extreme presentation for those with OCPD leads to interpersonal problems. OCPD individuals present as over-controlled and this extends to the relationships they have with other people. Individuals with OCPD are referential to authority and rules. OCPD individuals may therefore punish those who violate their strict standards. The inability to accept differences in belief or behaviors from others often leads to high conflict and controlling relationships with coworkers, spouses, and children.

Cause
The cause of OCPD is thought to involve a combination of genetic and environmental factors. There is clear evidence to support the theory that OCPD is genetically inherited, however, the relevance and impact of genetic factors vary with studies placing it somewhere between 27% and 78%.Other studies have found links between attachment theory and the development of OCPD. According to this hypothesis, those with OCPD have never developed a secure attachment style, had overbearing parents, were shown little care, and were unable to develop empathetically and emotionally.

Diagnosis
DSM-5
The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, a widely used manual for diagnosing mental disorders, places obsessive-compulsive personality disorder under section II, under the "personality disorders" chapter, and defines it as: "a pervasive pattern of preoccupation with orderliness, perfectionism, and mental and interpersonal control, at the expense of flexibility, openness, and efficiency, beginning by early adulthood and present in a variety of contexts". A diagnosis of OCPD is only received when four out of the eight criteria are met.The eight criteria of OCPD described in the DSM-5 (of which four are required to be present in a patient for a diagnosis) are:

Preoccupation with details
Perfectionism interfering with task completion
Rigidity and stubbornness
Reluctance to delegate
Excessive conscientiousness and pedantry (excessive concern with minor details and rules)
Workaholic behavior
Miserliness (excessive desire to save money)
Unable to discard worn-out or worthless objectsThe list of criteria for the ICD-10 is similar, but does not include the last three criteria in the above list, and additionally includes the symptoms "intrusive thoughts" and "excessive doubt and caution" as criteria for diagnosis.

Alternative model for diagnosis
The DSM-5 also includes an alternative set of diagnostic criteria as per the dimensional model of conceptualizing personality disorders. Under the proposed set of criteria, a person only receives a diagnosis when there is an impairment in two out of four areas of ones personality functioning, and when there are three out of four pathological traits, one of which must be rigid perfectionism.
The patient must also meet the general criteria C through G for a personality disorder, which state that the traits and symptoms being displayed by the patient must be stable and unchanging over time with an onset of at least adolescence or early adulthood, visible in a variety of situations, not caused by another mental disorder, not caused by a substance or medical condition, and abnormal in comparison to a persons developmental stage and culture/religion.

Differential diagnosis
There are several mental disorders in the DSM-5 that are listed as differential diagnoses for OCPD. They are as follows:

Obsessive–compulsive disorder. OCD and OCPD have a similar name which may cause confusion; however, OCD can be easily distinguished from OCPD: OCPD is not characterized by true obsessions or compulsions.
Hoarding disorder.  A diagnosis of hoarding disorder is only considered when the hoarding behavior exhibited is causing severe impairment in the functioning of the person, such as an inability to access rooms in a house due to excessive hoarding.
Narcissistic personality disorder.  Individuals with a narcissistic personality disorder usually believe that they have achieved perfection (especially compared to other people) and cannot get better, whereas those with OCPD do not believe that they have achieved perfection, and are self-critical. Those with NPD tend to be stingy and lack generosity; however, they are usually generous when spending on themselves, unlike those with OCPD who hoard money and are miserly on themselves and others.
Antisocial personality disorder.  Similarly, individuals with antisocial personality disorder are not generous, but miserly around others, although they usually over-indulge themselves and are sometimes reckless in spending.
Schizoid personality disorder.  Schizoid personality disorder and obsessive-compulsive personality disorder may both display restricted affectivity and coldness; however, in OCPD, this is usually due to a controlling attitude, whereas, in SPD, it occurs due to a lack of ability to experience emotion and display affection.
Other personality traits.  Obsessive-compulsive personality traits may be particularly useful and helpful, especially in productive environments. Only when these traits become extreme, maladaptive, and cause clinically significant impairment in several aspects of ones life should a diagnosis of OCPD be considered.
Personality change due to another medical condition.  Obsessive–compulsive personality disorder must be differentiated from a personality change due to a medical condition, which affects the central nervous system, and may cause changes in behavior and traits.
Substance use disorders. Substance use may cause the advent of obsessive-compulsive traits. It is necessary that this is distinguished from underlying and persistent behavior, which must occur when a person is not under influence of a substance.

ICD-10
The World Health Organizations ICD-10 uses the term anankastic personality disorder (F60.5). At least four of the following must be present:

Feelings of doubt
Perfectionism
Excessive conscientiousness
Checking and preoccupation with details
Stubbornness
Caution
Rigidity
Insistent and unwelcome thoughts or impulses that do not attain the severity of an obsessive-compulsive disorder.

Millons subtypes
In his book, Personality Disorders in Modern Life, Theodore Millon describes 5 types of obsessive–compulsive personality disorder, which he shortened to compulsive personality disorder.

Comorbidity
Obsessive–compulsive disorder
OCPD is often confused with obsessive-compulsive disorder (OCD). Despite the similar names, they are two distinct disorders. Some OCPD individuals do have OCD, and the two can be found in the same family, sometimes along with eating disorders.The rate of comorbidity of OCPD in patients with OCD is estimated to be around 15–28%. However, due to the addition of the hoarding disorder diagnosis in the DSM-5, and studies showing that hoarding may not be a symptom of OCPD, the true rate of comorbidity may be much lower.There is significant similarity in the symptoms of OCD and OCPD, which can lead to complexity in distinguishing them clinically. For example, perfectionism is an OCPD criterion and a symptom of OCD if it involves the need for tidiness, symmetry, and organization. Hoarding is also considered both a compulsion found in OCD and a criterion for OCPD in the DSM-5. Even though OCD and OCPD are seemingly separate disorders there are obvious redundancies between the two concerning several symptoms.Regardless of similarities between the OCPD criteria and the obsessions and compulsions found in OCD, there are discrete qualitative dissimilarities between these disorders, predominantly in the functional part of symptoms. Unlike OCPD, OCD is described as invasive, and stressful. Time-consuming obsessions and habits are aimed at reducing obsession-related stress. OCD symptoms are at times regarded as egodystonic because they are experienced as alien and repulsive to the person. Therefore, there is a greater mental anxiety associated with OCD.In contrast, the symptoms seen in OCPD, although repetitive, are not linked with repulsive thoughts, images, or urges. OCPD characteristics and behaviors are known as ego-syntonic, as people with this disorder view them as suitable and correct. On the other hand, the main features of perfectionism and inflexibility can result in considerable suffering in an individual with OCPD as a result of the associated need for control.The presence of OCPD in patients with OCD has been linked to a worse prognosis of OCD, especially when cognitive behavioral therapy was used. This may be due to the ego-syntonic nature of OCPD which may lead to the obsessions becoming aligned with ones personal values. In contrast, the trait of perfectionism may improve the outcome of treatment as patients are likely to complete homework assigned to them with determination. The findings with regards to pharmacological treatment has also been mixed, with some studies showing a lower reception to SRIs in OCD patients with comorbid OCPD, with others showing no relationship.Comorbidity between OCD and OCPD has been linked to a more severe presentation of symptoms, a younger age of onset, more significant impairment in functioning, poorer insight, and higher comorbidity of depression and anxiety.

Autism spectrum disorder
There are considerable similarities and overlap between autism spectrum disorder (ASD) and OCPD, such as list-making, inflexible adherence to rules, and obsessive aspects of ASD, although the latter may be distinguished from OCPD especially regarding affective behaviors, worse social skills, difficulties with Theory of Mind and intense intellectual interests, e.g. an ability to recall every aspect of a hobby. A 2009 study involving adult autistic people found that 32% of those diagnosed with ASD met the diagnostic requirements for a comorbid OCPD diagnosis.

Eating disorders
Perfectionism has been linked with Anorexia Nervosa in research for decades. A researcher in 1949 described the behavior of the average "anorexic girl" as being "rigid" and "hyperconscious", observing a tendency to "[n]eatness, meticulosity, and a mulish stubbornness not amenable to reason [which] make her a rank perfectionist". So common are such traits as perfectionism and rigidity among anorectics, that they have been referred to in clinical literature as "classical childhood features of patients with anorexia nervosa" or classical premorbid personality descriptors of anorexia nervosa".Regardless of the prevalence of the full-fledged OCPD among eating disordered samples, the presence of this personality disorder or its traits, such as perfectionism, has been found to be positively correlated with a range of complications in eating disorders and a negative outcome, as opposed to impulsive features—those linked with histrionic personality disorder, for example—which predict a better outcome from treatment. OCPD predicts more severe symptoms of Anorexia Nervosa, and worse remission rates, however, OCPD and perfectionistic traits predicted a higher acceptance of treatment, which was defined as undergoing 5 weeks of treatment.People with Anorexia Nervosa who exercise excessively display a higher prevalence of several OCPD traits when compared to their counterparts who did not exercise excessively. The traits included self-imposed perfectionism, and the childhood OCPD traits of being rule-bound and cautious. It may be that people with OCPD traits are more likely to use exercise alongside restricting food intake in order to mitigate fears of increased weight, reduce anxiety, or reduce obsessions related to weight gain. Samples that had the childhood traits of rigidity, extreme cautiousness, and perfectionism endured more severe food restriction and higher levels of exercise and underwent longer periods of underweight status. It may be that OCPD traits are an indicator of a more severe manifestation of AN which is harder to treat.

Gambling Disorder
A majority of those with lifelong gambling disorder have some sort of personality disorder, and the most common personality disorder amongst them is obsessive compulsive personality disorder. OCPD has a strong comorbidity with individuals who have gambling disorder. A study of data collected in the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions looked at pathological gambling and psychiatric conditions as defined by the DSM-IV. Of the surveyed population consistent with gambling disorder, 60.8% also had a personality disorder, with OCPD appearing most frequently at 30%. About 300,000 U.S citizens have both a gambling disorder and obsessive compulsive personality disorder; and yet, there is little research on the comorbidity of the two disorders. Those with gambling disorders and OCPD do, indeed, exhibit different behavioral patterns than those with gambling disorders alone. More research on the relationship between the disorders is thought to help uncover causes and develop treatments for patients.

Mental Fatigue
Recently, in 2020, the connection between mental fatigue and OCPD was published for the first time, even though mental fatigue has been previously associated with identified characteristics of OCPD such as workaholic behavior and perfectionism.

Other disorders and conditions
A diagnosis of OCPD is common with anxiety disorders, substance use disorders, and mood disorders. OCPD is also highly comorbid with Cluster A personality disorders,[4]
especially paranoid and schizotypal personality disorders.OCPD is also linked to hypochondriasis, with some studies estimating a rate of co-occurrence as high as 55.7%.Moreover, OCPD has been found to be very common among some medical conditions, including Parkinsons disease and the hypermobile subtype of Ehler-Danlos syndrome. The latter may be explained by the need for control that arises from musculoskeletal problems and the associated features that arise early in life, whilst the former can be explained by dysfunctions in the fronto-basal ganglia circuitry.

Treatment
The best-validated treatment for OCPD is cognitive therapy (CT) or cognitive behavioral therapy (CBT), with studies showing an improvement in areas of personality impairment, and reduced levels of anxiety and depression. Group CBT is also associated with an increase in extraversion and agreeableness and reduced neuroticism.  Interpersonal psychotherapy has been linked to even better results when it came to reducing depressive symptoms.

Epidemiology
Estimates for the prevalence of OCPD in the general population are 3%, making it the most common personality disorder. Current evidence is inconclusive as to whether OCPD is more common in men than women, or in equal rates among sexes. It is estimated to occur in 8.7% of psychiatric outpatient settings.A study of data collected in the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions looked specifically for seven personality disorders as defined by the DSM-IV. The study concluded the most prevalent personality disorder of the surveys population to be OCPD, at 7.88%. This study also concluded there were no gender differences in prevalence and that OCPD was not a predicter of disability.

History
In 1908, Sigmund Freud named what is now known as obsessive–compulsive or anankastic personality disorder "anal retentive character". He identified the main strands of the personality type as a preoccupation with orderliness, parsimony (frugality), and obstinacy (rigidity and stubbornness). The concept fits his theory of psychosexual development. Freud believed that the anal retentive character faced difficulties regulating the control of defecation, leading to repercussions by the parents, and it is the latter that would cause the anal retentive character.Aubrey Lewis, in his 1936 book Problems of Obsessional Illness, suggests that anal-erotic characteristics are found in patients without obsessive thoughts, and proposed two types of obsessional personality, one melancholy and stubborn, the other uncertain and indecisive.In the book Contributions to the theory of the anal character, Karl Abraham noted that the core feature of the anal character is being perfectionistic, and he believed that these traits will help an individual in becoming industrious and productive, whilst hindering their social and interpersonal functioning, such as working with others.OCPD was included in the first edition of the Diagnostic and Statistical Manual of Mental Disorders in 1952 by the American Psychiatric Association under the name "compulsive personality". It was defined as a chronic and excessive preoccupation with adherence to rules and standards of conscience </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 Endolymphatic sac tumor and can you explain it in depth? [/INST] An endolymphatic sac tumor (ELST) is a very uncommon papillary epithelial neoplasm arising within the endolymphatic sac or endolymphatic duct. This tumor shows a very high association with Von Hippel–Lindau syndrome (VHL).

Classification
The ELST has been referred to as adenocarcinoma of endolymphatic sac, Heffner tumor, papillary adenomatous tumor, aggressive papillary adenoma, invasive papillary cystadenoma, and papillary tumor of temporal bone. However, these names are not encouraged as they do not accurately classify the current understanding of the tumor.

Signs and symptoms
Patients with ELST may present clinically with progressive or fluctuating, one sided sensorineural hearing loss which may mimick Ménières disease due to the development of tumor associated endolymphatic hydrops. Patients may also experience tinnitus, vertigo, and loss of vestibular function (ataxia). Alternatively, symptom onset may be sudden, due to intralabyrinthine hemorrhage. Patients may also present with other symptoms related to von Hippel–Lindau syndrome in other anatomic sites, which will result in imaging evaluation of the head.

Imaging findings
Imaging studies help to identify the tumor and the specific anatomic site of involvement. Magnetic resonance images show a hyperintensity (hypervascularity) of a heterogeneous mass by T1 weighted images. Computed tomography shows a multilocular, lytic destructive temporal bone mass, centered on the vestibular aqueduct (between internal auditory canal and sigmoid sinus).

Pathogenesis
The von Hippel–Lindau tumor suppressor gene generally has a germline mutation. This suppressor gene is also called elongin binding protein and G7 protein. The VHL protein is involved in up-regulation of hypoxic response via the [[hypoxia inducible factor [HIF]-1 alpha]]. Mutations generally prevent the production of any functional VHL protein or result in a change of structure of VHL protein. This genetic disorder shows an autosomal dominant inheritance pattern, with about 20% of patients possessing a new mutation. There are usually several other tumors which are part of the syndrome, including tumors of the central nervous system, kidneys, pancreas, adrenal glands, epididymis, broad ligament, along with the endolymphatic sac. The vast majority of patients with an endolymphatic sac tumor have von Hippel-Lindau syndrome.

Pathology findings
Tumors range from several millimeters up to 10 cm, with larger tumors more frequently seen in older patients. If the tumor is bilateral, it is almost always seen in a VHL patient. The tumor destroys the mastoid air spaces and extends into the middle ear and/or posterior cranial fossa.

The microscopic appearance shows an unencapsulated, destructive growth, remodeling and invading bone. The tumor is arranged as simple, broad, non-complex papillary projections without large cystic spaces. The spaces are often fluid filled, have extravasated erythrocytes and/or inspissated material. The cells are cuboidal, usually single layered along the papillary structures, showing indistinct cell borders. The nuclei are round and hyperchromatic.

Immunohistochemistry
The neoplastic cells are reactive with keratin, CK7, and Epithelial membrane antigen, but negative with TTF-1 and CK20.

Cytogenetics
The germline mutations of VHL tumor suppressor gene will be found on 3p25-26 (short arm  of chromosome 3), usually between base pair 10,158,318 to 10,168,761.

Differential diagnosis
The clinical and pathology differential are different. From a pathology perspective, an endolymphatic sac tumor needs to be separated from metastatic renal cell carcinoma, metastatic thyroid papillary carcinoma, middle ear adenoma, paraganglioma, choroid plexus papilloma, middle ear adenocarcinoma, and ceruminous adenoma.

Management
Wide excision is the treatment of choice, although attempting to preserve hearing. Based on the anatomic site, it is difficult to completely remove, and so while there is a good prognosis, recurrences or persistence may be seen. There is no metastatic potential. Patients who succumb to the disease, usually do so because of other tumors within the von Hippel-Lindau complex rather than from this tumor. Surgery is the primary treatment modality, but in some rare instances adjuvant radiation therapy may be used.

Epidemiology
This is a very rare tumor, since only about 1 in 35,000 to 40,000 people have VHL, of whom about 10% have endolymphatic sac tumors </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 Phoenix abscess and can you explain it in depth? [/INST] A phoenix abscess is an acute exacerbation of a chronic periapical lesion. It is a dental abscess that can occur immediately following root canal treatment. Another cause is due to untreated necrotic pulp (chronic apical periodontitis). It is also the result of inadequate debridement during the endodontic procedure. Risk of occurrence of a phoenix abscess is minimised by correct identification and instrumentation of the entire root canal, ensuring no missed anatomy.
Treatment involves repeating the endodontic treatment with improved debridement, or tooth extraction. Antibiotics might be indicated to control a spreading or systemic infection.

Causes
Phoenix abscesses are believed to be due to a changing internal environment of the root canal system during the instrumentation stage of root canal treatment, causing a sudden worsening of the symptoms of chronic periradicular periodontitis. This instrumentation is thought to stimulate the residual microbes in the root canal space to cause an inflammatory reaction. These microbes are predominantly facultative anaerobic gram-positive bacteria, such as Streptococcus, Enterococcus and Actinomyces species. Another cause of a phoenix abscess is a decrease in a patients resistance to these bacteria and their products.

Signs & Symptoms
Clinical Features
PainA common clinical feature is exacerbated and exaggerated pain. There may or may not be associated with pus & suppuration. The signs & symptoms are similar to that of an acute periradicular abscess, but with a periradicular radiolucency present as well.
Loss of VitalityThe problematic tooth will have a non-vital pulp with no previous 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 Hypodontia and can you explain it in depth? [/INST] Hypodontia is defined as the developmental absence of one or more teeth excluding the third molars.  It is one of the most common dental anomalies, and can have a negative impact on function, and also appearance. It rarely occurs in primary teeth (also known as deciduous, milk, first and baby teeth) and the most commonly affected are the adult second premolars and the upper lateral incisors. It usually occurs as part of a syndrome that involves other abnormalities and requires multidisciplinary treatment.
The phenomenon can be subdivided into the following according to the number of teeth concerned:

Hypodontia: one to six missing teeth excluding the third molars
Oligodontia: six or more missing permanent teeth excluding the third molars
Anodontia: complete absence of teeth

Signs and symptoms
Typically, all baby teeth will be present by the age of three. As for all adult teeth, they erupt between the ages 6 to 14, with the exception of the third molar, also known as the wisdom teeth which normally erupt between 17 and 25 years of age. If the tooth has yet to erupt by an appropriate age, panoramic x-rays are taken.

Dental features
Microdontia may be present in one or more of the other teeth. This means that the teeth appear smaller than normal, may be observed in both the primary and permanent dentition. This condition can be genetically-linked and in severe cases, may present themselves in the form of ectodermal dysplasia, cleft lip or palate or Down Syndrome. A delay in tooth development may also serve as an indication, whereby the absence of an adult successor slows down the normal resorption of the roots of the baby teeth, which is the progressive loss of parts of the tooth.
Misplaced (ectopic) positioning of the adult teeth may be discovered upon examination or a radiograph. One of the consequences may be an adult tooth intercepting with a baby tooth, causing premature loss or wrong positioning. This can be due to either the absence of neighboring teeth acting as a guide during eruption or the lack of space in the jaw for them to erupt into because of malocclusion.

Skeletal features
Several studies have discovered that anteriorly missing teeth can accompany retrognathic maxilla, also known as an underbite, prognathic mandible, where the lower jaw protrudes out more than normal, and smaller posterior cranial base length. Occurrence of hypodontia can be associated with reduced anterior lower facial height and lip protrusion. This can be linked to lower maxillary to mandibular plane angles.
A more acute mandibular angle and flatter chin may develop as a result. These characteristics become more prominent as the condition becomes progressively severe, particularly when more than one tooth is missing.

Other dental and radiographic features
Data derived from principal component analysis of radiographic images show that children with mild hypodontia may display significant increase of the interincisal angle and decrease in the maxillary and mandibular incisor angles.
Cephalometric tracing is commonly used to study a patients dentofacial proportions in the craniofacial complex. This can aid in predicting growth changes, allowing dentists, especially orthodontists, to develop a suitable treatment plan. Coupled with that, findings consistent among individuals include:

Anterior hypodontia associated with hyper divergent craniofacial pattern;
A tendency toward a class III malocclusion identified in maxillary hypodontia, and;
Reduced lower posterior facial height in children with posterior and mandibular hypodontia.

Associated anomalies
Reduction in coronal or radical dimensions
Retained primary teeth
Ectopic canine eruption
Abnormal morphology such as peg-shaped maxillary lateral incisors and taurodontism, characterized by an enlarged tooth body and roots that are reduced in size
Extracted teeth

Cause
Several theories regarding the aetiology of hypodontia have been proposed in existing literature. There have been various theories mostly looking into genetic and environmental aspects and how they may both be involved. However, the exact cause remains unclear. The extent of individual influences of genetic and environmental factors is still widely debated.Theories regarding the mechanism through which hypodontia occurs can be categorised into evolutional or anatomical.Preliminary studies focused on an evolutionary approach which suggested shortening of the intermaxillary complex and thus shorter arches may contribute to a decrease in number of teeth. This was also suggested in 1945 by Dahlberg using Butlers Field Theory that focused on evolution and development of mammalian teeth into human dentition in an attempt to analyse different of agenesis. In each jaw, four morphological sites were identified (incisors, canines, premolars and molars). The tooth at the end of each region was less genetically stable and hence more prone to absence. In contrast, the tooth most mesial in each region seemed to be more genetically stable. A subsequent theory hypothesised the teeth at the end of each region were possibly "vestigial bodies" that became obsolete during the evolutionary process. At present, it has been theorised that evolutionary change is working to decrease the human dentition by the loss of an incisor, premolar and molar in each quadrant. According to Vastardis (2000), the size of jaws and number of teeth seem to decrease along with human evolution.Theories focusing on anatomical principle, hypothesised that specific areas of the dental lamina are especially prone to environmental effects during tooth maturation. Svinhufvud et al. (1988) suggested that teeth that were more prone to absence developed in areas of initial fusion of the jaw. For instance, maxillary lateral incisors originate where the lateral maxillae and medial nasal bone processes fuse. In contrast, Kjaer et al. (1994) suggested regions where innervation developed were more sensitive than areas of fusion. Commonly affected regions were found to undergo innervation last, this might imply the developmental relationship between nerve and hard tissue. It is thought to be local nerve development that affects tooth agenesis rather than global development, as brainstem anomalies have not been seen to affect tooth development.Presently, the role of polygenic and environmental factors on hypodontia is recognised in most theories.

Environmental factors
Environmental factors can be classified into two main groups, invasive and non-invasive. These factors act additively or independently, ultimately affecting positioning and physical development of the tooth.Invasive environmental factors potentially affect tooth development and positioning leading to hypodontia and impaction. Examples include jaw fractures, surgical procedures and extraction of the preceding deciduous tooth. Treatment such as irradiation has been shown to have severe effects on developing teeth. In a smaller capacity, chemotherapy was also found to have a similar effect. Thalidomide (N-phthaloylglutamine) was also discovered to have a causative effect on mothers who took the drug during pregnancy, resulting in congenitally missing teeth in their children. A link was found between systemic diseases, endocrine disruption (i.e. idiopathic hypoparathyroidism and pseudohypoparathyroidism) and ectodermal dysplasia. However, a definite etiological relationship has yet to be established. Examples of infections include rubella and candida. Exposure to PCBs (such as dioxin), allergies, and toxic epidermal necrolysis folloeing a drug reaction may also be contributing factors.
In a recent study assessing environmental risk factors for hypodontia, it was established that maternal smoking does play a causative role in hypodontia. Passive smoking and caffeine were also assessed but showed no statistical significance.The Journal of the American Dental Association published preliminary data suggesting a statistical association between hypodontia of the permanent teeth and epithelial ovarian cancer (EOC). The study shows that women with EOC are 8.1 times more likely to have hypodontia than are women without EOC. The suggestion therefore is that hypodontia can serve as a "marker" for potential risk of EOC in women.

Genetics
Genetic causes also involve the genes MSX1 and PAX9.Genetic associations for selective tooth agenesis ("STHAG") include:

Failure of tooth formation due to disturbances during the early stages of development could be the cause of congenital missing teeth; this is also known as tooth agenesis. A variety of studies show that missing teeth are commonly associated with genetic and environmental factors. Some literature also shows that a combination of both factors may contribute to the occurrence of hypodontia.Most craniofacial characteristics are influenced by both genetic and environmental factors through complex interactions. The variable expressivity of traits can be either completely genetically determined, environmentally determined, or both. That genetics plays an important role in hypodontia is shown in many different cases. There are hundreds of genes expressed and involved in regulating tooth morphogenesis. Although a single gene defect may contribute to hypodontia, more studies propose that hypodontia is the result of one or more points of closely linked genetic mutations, or polygenic defects.The pattern of congenitally missing teeth seen in monozygotic twins is different, suggesting an underlying epigenetic factor, which may be due to the simultaneous occurrence of two anomalies. This multifactorial aetiology involves environmental factors which trigger the genetic anomalies, resulting in the occurrence of dental agenesis. Common environmental factors include infection, trauma and drugs which predispose to the condition. In hereditary cases, evidence of dental germ developing after surrounding tissues have closed the space required for development may be a large contributing factor, as well as such genetic disorders as Down syndrome, ectodermal dysplasia, cleidocranial dysplasia, and cleft lip and cleft palate.

MSX1
MSX1 (muscle segment homeobox 1) is involved in condensation of ectomesenchyme in the tooth germ. Among the members of homeobox genes, MSX1 and MSX2 are crucial in mediating direct epithelial-mesenchymal interactions during tooth development by expressing in regions of condensing ectomesenchyme in the tooth germ. MSX1 mutations have been identified as a contributing factor in missing second premolars, third molars, and a small percentage of first molars. MSX1 is less likely to cause anterior agenesis.Heterozygous mutations in PAX9 (paired box gene 9) could arrest tooth morphogenesis as it plays a role of transcription the gene expressed in tooth mesenchyme at the bud stage during tooth development. A study showed that single nucleotide polymorphisms in PAX9 were highly associated with missing upper lateral incisors.

AXIN2
The AXIN2 (AXIS inhibition protein 2) gene is a negative regulator of the Wnt signalling pathway, which is important in regulating cell fate, proliferation, differentiation and apoptosis. Its polymorphic variant may be associated with hypodontia such as missing lower incisors or in a more severe form of agenesis like oligontia (lack of six or more permanent teeth).

EDA
EDA provides instructions for making a protein called ectodysplasin A. It encodes transmembrane protein that is part of TNF (tumour necrosis factor) family of ligands. EDA gene defects cause ectodermal dysplasia, which is also known as X-linked hypohidrotic ectodermal dysplasia. Common dental features of ectodermal dysplasia are multiple missing teeth and microdontia.PAX9 and TGFA are involved in regulating between MSX1 and PAX9, causing hypodontia of the molars.Hypodontia can be found in isolated cases too. The familiar or sporadic type of isolations are more frequently reported than the syndromic type. Isolated cases of autosomal dominant, autosomal recessive, or X-linked inheritance patterns may have an impact on the isolation conditions in expressing variation of both penetration and expressivity of traits. Mutations in MSX, PAX9 and TGFA genes are known to cause congenitally missing teeth in some racial groups.

Research
In the 1960s and 1970s, several studies were conducted sponsored by the U.S. Atomic Energy Commission, with the aim of finding a link between genetics and hypodontia.

Impact
There are numerous studies and research reports on the prevalence, aetiology, and treatment of hypodontia and the dentoskeletal effect of hypodontia. A few studies have investigated Oral Health-related Quality of Life (OHRQoL) in individuals with hypodontia and provided some evidence that hypodotia may have an impact on quality of life.

Psychosocial
Cosmetic dentistry has become more notable and prevalent in modern society. Interpersonal relationships and perceived qualities, such as intelligence, friendliness, social class, and popularity can be affected by dentofacial appearance. Some studies have shown that the extent of complaints made by patients was associated with the severity of the condition and the number of missing permanent teeth.Meta-analyses and theoretical reviews have demonstrated that attractive children are seen by others as more intelligent and exhibit more positive social behaviour and traits, other than receiving much more positive treatment than their less attractive counterparts. Therefore, a divergence from perceived ideal dentofacial aesthetic, particularly in children, might adversely affect self-esteem and self-confidence besides attracting mockery from peers.It is therefore reasonable to theorize that deviations from "normal" or "ideal" dentofacial aesthetic could be destructive to an individuals psychosocial and emotional well-being, which brings upon some psychosocial distress in that individual as a result of their condition.

Functional
Individuals with hypodontia tend to have deeper bites and spaces. Further deepening of the bite can also be seen on individuals with missing posterior teeth. Apart from that, hypodontia may lead to non-working interferences, poor gingival contours and over-eruptions of the opposing teeth.It has been found that individuals with hypodontia experience more difficulty during mastication or functioning movements due to smaller occlusal table available. A recent cross-sectional study showed that hypodontia patients have more difficulties in chewing, especially if the deciduous teeth associated with the missing permanent teeth had been exfoliated. Despite currently limited evidence to support this statement, it is plausible that hypodontia may pose functional limitations, which eventually affect that individuals general well-being and quality of life.Hypodontia can indeed pose limitations on the chewing ability of a patient. The condition can be associated with split in the upper lips – a condition known as oral cleft. Hypodontia can have impacts on speech, aesthetics and function of muscles in the mouth. As a result, hypodontia can have negative impacts on the quality of life, although the condition can be well managed and treated by dentists and orthodontists. To manage the condition, the patient will need to have long-term orthodontic treatment.

Financial
Patient with hypodontia requires careful treatment plan due to complex case in order to ensure the best treatment outcomes. Such treatment plans require multi-disciplinary approach, which usually come at a financial cost to both patient and possibly their family. Due to this reason, a team consists of different dental specialties is involved in the patient care.

Management
Hypodontia is a condition that can present in various ways with differing severities. This results in a wide range of treatment methods available. Those affected should be allowed to consider and select the most suitable option for themselves. Early diagnosis of hypodontia is critical for treatment success. The treatment of hypodontia involves specialists in departments such as oral and maxillofacial surgery, operative dentistry, pediatric dentistry, orthodontics and prosthodontics.Before determining a treatment plan, the following should be determined:

Evaluate the number of teeth missing
The size and number of remaining teeth in both arches
Malocclusion
Facial profile
Bone volume
Age: Definitive treatment for hypodontia only commences once all permanent teeth erupt, or upon the completion of orthodontic treatment
Primary teeth condition
Patients motivation towards treatmentTraditionally, the management of hypodontia has involved replacing missing teeth. By replacing the missing teeth, it can prevent neighbouring teeth tilting or drifting and also prevents the overeruption of opposing teeth which could then impact on occlusion and temporo-mandibular joint dysfunction and impact the patients susceptibility to gum disease, tooth wear and tooth fractures. However, studies have suggested that a stable occlusion can be achieved even with a shortened arch of 10 occluding pairs of teeth. The findings support the concept that a healthy and stable occlusion can exist despite missing teeth as long as an acceptable number of teeth are in occlusion. However, this management technique may not be suitable for those with gum disease, parafunctioning activity (tooth grinding or clenching) or malocclusion.It should also be noted that spaces within the dental arch should be monitored, especially in younger patients, as teeth are more likely to drift, tilt or over-erupt. To do this, study models and clinical photographs could be taken in order to record baseline records. If tooth movement was to occur, another form of management may be required depending on the severity and nature.The following below are the methods used to manage hypodontia:

Accept spacing
This is a method suitable to individuals if the space from a missing tooth is not deemed to be an aesthetic concern. Appearance may not be a problem in some cases, for example, when spacing present behind the canines may not be particularly visible, depending on the individual.

Management of retained primary teeth
When there is a case of hypodontia of the permanent premolar teeth, the primary molar teeth would often remain in the mouth beyond the time they are meant to be lost. Therefore, with a presence of healthy primary teeth in the absence of a permanent successor, retaining the primary teeth can be a feasible management of hypodontia.
The primary molars present also functions as a space maintainer, prevent alveolar bone resorption and delays future prosthodontic space replacement by acting as a semi permanent solution going into adulthood Previous studies also shown a good prognosis of retained primary molars going into adulthood. However, leaving the primary teeth in place may run the risk of tooth infraocclusion where the occlusal surface is below that of adjacent teeth.Despite this, the retention of primary teeth, particularly molars, are more susceptible to occlusal wear, over-eruption of opposing teeth and the loss of inter-occlusal space.

Orthodontic space closure
Orthodontic space closure is a way of using orthodontics in order to close spaces in the mouth where the teeth are missing. The ideal age for definitive orthodontic treatment is early adolescence but it is important to consider the patients age, severity of hypodontia, patient expectations and their commitment to treatment. It can be an option for hypodontia management in the case of missing maxillary lateral incisors through the reshaping, and mesial re-positioning of the adjacent canine. This management is indicated in hypodontia cases of Class I molar relationship with severe crowding in the mandibular anterior region where the extraction of lower premolar leads to a predictable outcome, and Class II molar relationship in the absence of crowding and protrusion of the mandibular anterior dentition.When moving the canine into the space of the lateral incisor, the dimensions of the canine, root position and gingival position differ from a lateral incisor and therefore preparation of the canine is necessary in order for it to mimic the incisor. This may involve:

Reduction of the incisal tip and addition of composite on the incisal edge to create a straight contour and a rounded disto-incisal corner
Reduction of the mesial and distal surfaces to reduce the width of the tooth
Flattening of the labial surface to reduce bulbosity. However, removal of enamel by expose the darker coloured dentine and therefore further restoration may be required.
Preparation of the palatal surface of the canine to reduce its bulk.The use of veneers can also be used instead of composite however, these are more expensive and more time-consuming.
There have been several studies which showed the advantages of orthodontic space closure without prosthodontic space replacements. The main advantage mentioned is the early completion of the treatment during early adolescence and the long lasting result of the treatment outcome. In individuals with a high smile line, the mesial re-positioning of canine maintains the normal soft tissue architecture is important in maintaining the aesthetic appearance. This option also negates the risks and costs that comes with prosthodontic treatment and the impression that there is no missing tooth.Some factors need to be considered when making a decision whether to undergo space closure. These include facial profile, size and dimension of canine, the shade of colour of the teeth and the gingival contour and height. Group function occlusion is usually present as a result of the mesial movement of the canine. In order to maintain the stability of the closed space, direct-bonded lingual retainers are usually required.

Orthodontic space opening prior to prosthodontic treatment
The need for orthodontic space opening prior to prosthodontic management depends on the amount of edentulous space available in relation to adjacent teeth, occlusion and aesthetic concerns. To determine the amount of space needed, three methods in the literature can be used which are the golden proportion, the Bolton Analysis and comparing the edentulous space with the contralateral tooth size if present.Space opening and prosthodontic treatment is indicated where there is a Class I molar relationships in the absence of malocclusion Class III molar relationships presenting with a concave facial profile. However, the alteration in appearance during orthodontic treatment (e.g. creating diastema for placement of prostheses) before the filling up the space, although temporary, can negatively impact the oral health-related quality of life in adolescents.

Removable partial dentures
Removable partial dentures are known to be an effective interim method for maintaining functional and aesthetic demands in a growing patient, where definitive fixed restorations are not suitable yet. Removable dentures act as a space maintainer and also prevent the migration of adjacent or opposing teeth, thereby preserving the face height. They are also easy to adjust or add on to in the event of further tooth eruption. However, it may be difficult for young individuals to adhere with wearing removable dentures, due to their bulk. Some patients also find the idea of dentures functionally and socially unacceptable, making them unwilling to comply. Removable prosthetic devices are also known to cause damage to the remaining teeth if worn over a long period of time.

Conventional crown and bridgework
Fixed restorative options are generally preferred over removable ones.
Resin-bonded bridges: Due to its minimal preparation required, this method of replacing teeth is more suited to young adults. It is a definitive restoration with the ability to fill up one or two tooth spaces. Research has reflected a survival rate of 80% over a period of 6 years or longer, and that cantilever resin-bonded bridges are at least as good as conventional fixed-fixed bridges. Restoring teeth with this method can only be done after orthodontic treatment and will need an element of retention to ensure that tooth contacts are not misplaced.
Conventional bridges: Teeth tend to be prepared for conventional bridgework if there are large restorations present, thus being more commonly done on adult patients with hypodontia. Treatment with conventional bridgework will require significant reduction of tooth structure, which will put the tooth at risk of biological damage i.e. loss of vitality. This risk is especially high in young patients with large pulp chambers.

Tooth autotransplantation
Autotransplantation involves the removal of a tooth from one socket and relocating to another socket in the same individual. If done successfully, it is able to ensure stable alveolar bone volume as there is continuous stimulation of the periodontal ligament.

Implant supported tooth replacement
Placing dental implants has proven to be a predictable and reliable method of treating hypodontia, along with bringing excellent aesthetic results. Implant placement should be delayed until jaw growth in an individual is complete. One limitation of implant placement would be the need for a sufficient amount of bone volume, which if not met, may affect the positioning of the implant. However, bone grafting can be carried out to overcome this.

Epidemiology
Hypodontia is less common in the primary dentition, with reported prevalence rates ranging from 0.5% in the Icelandic population to 2.4% in the Japanese population </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 Vaginal vault 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 Krukenberg tumor and can you explain it in depth? [/INST] A Krukenberg tumor refers to a malignancy in the ovary that metastasized from a primary site, classically the gastrointestinal tract, although it can arise in other tissues such as the breast. Gastric adenocarcinoma, especially at the pylorus, is the most common source. Krukenberg tumors are often (over 80%) found in both ovaries, consistent with its metastatic nature.

Signs and symptoms
Krukenberg tumors often come to the attention when they cause abdominal or pelvic pain, bloating, ascites, or pain during sexual intercourse. Krukenberg tumors can occasionally provoke a reaction of the ovarian stroma which leads to hormone production, that results in vaginal bleeding, a change in menstrual habits, or hirsutism, or occasionally virilization as a main symptom. In rare cases the disease can manifest with hydronephrosis and hydroureter.All these symptoms are non-specific and can also arise with a range of problems other than cancer, and a diagnosis can only be made following confirmatory investigations such as computed tomography (CT) scans, laparotomy and/or a biopsy of the ovary.

Cause and incidence
Krukenberg tumors can be seen in all age groups, with an average age of 45 years. In most countries, cancer that has metastasized to the ovary accounts for only about 1 to 2% of ovarian cancer; in the remainder, the ovary itself is the primary cancer site. However, in Japan they represent a much higher percentage of malignancies in the ovary (almost 20%) due to the increased prevalence of gastric cancer.Krukenberg tumors account for about 15% of metastatic cancers that initially appear to have arisen in the ovary, and as such is less common than metastasis arising from ovarian epithelial and germ-cell tumors.In people who have had nongynecologic malignancy, approximately 20% of adnexal masses are malignant, and 60% of these are Krukenberg tumors.

Pathogenesis
There has been debate over the exact mechanism of metastasis of the tumor cells from the stomach, appendix or colon to the ovaries </s>