<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Spinal muscular atrophy and explain in detail? [/INST] Spinal muscular atrophy (SMA) is a rare neuromuscular disorder that results in the loss of motor neurons and progressive muscle wasting. It is usually diagnosed in infancy or early childhood and if left untreated it is the most common genetic cause of infant death. It may also appear later in life and then have a milder course of the disease. The common feature is progressive weakness of voluntary muscles, with arm, leg and respiratory muscles being affected first. Associated problems may include poor head control, difficulties swallowing, scoliosis, and joint contractures.The age of onset and the severity of symptoms form the basis of the traditional classification of spinal muscular atrophy into a number of types.Spinal muscular atrophy is due to an abnormality (mutation) in the SMN1 gene which encodes SMN, a protein necessary for survival of motor neurons. Loss of these neurons in the spinal cord prevents signalling between the brain and skeletal muscles. Another gene, SMN2, is considered a disease modifying gene, since usually the more the SMN2 copies, the milder is the disease course. The diagnosis of SMA is based on symptoms and confirmed by genetic testing.Usually, the mutation in the SMN1 gene is inherited from both parents in an autosomal recessive manner, although in around 2% of cases it occurs during early development (de novo). The incidence of spinal muscular atrophy worldwide varies from about 1 in 4,000 births to around 1 in 16,000 births, with 1 in 7,000 and 1 in 10,000 commonly quoted for Europe and the US respectively.Outcomes in the natural course of the disease vary from death within a few weeks after birth in the most acute cases to normal life expectancy in the protracted SMA forms. The introduction of causative treatments in 2016 has significantly improved the outcomes. Medications that target the genetic cause of the disease include nusinersen, risdiplam, and the gene therapy medication onasemnogene abeparvovec. Supportive care includes physical therapy, occupational therapy, respiratory support, nutritional support, orthopaedic interventions, and mobility support.

Classification
5q SMA is a single disease that manifests over a wide range of severity, affecting infants through adults. Before its genetics was understood, its varying manifestations were thought to be different diseases – Werdnig–Hoffmann disease when young children were affected and Kugelberg–Welander disease for late-onset cases.In 1990, it was realised that these separate diseases formed a spectrum of the same disorder. Spinal muscular atrophy was then classified into 3–5 clinical types based either on the age of symptom onset or on the maximum motor function achieved. Currently, the consensus is that the phenotype of spinal muscular atrophy spans a continuum of symptoms without clear delineation of subtypes. However, the traditional classification, outlined in the table below, is still used today both in clinical research and sometimes, controversially, as a criterion of access to therapies.

For convenience, care-focused publications classify patients into "non-sitters", "sitters" and "walkers" based on their actual functional status.
Motor development and disease progression in people with SMA is usually assessed using validated functional scales – CHOP-INTEND (The Childrens Hospital of Philadelphia Infant Test of Neuromuscular Disorders) or HINE (Hammersmith Infant Neurological Examination) in infants; and either the MFM (Motor Function Measure) or one of several variants of the HFMS (Hammersmith Functional Motor Scale) in older patients.
The eponymous label Werdnig–Hoffmann disease (sometimes misspelled with a single n) refers to the earliest clinical descriptions of childhood SMA by Johann Hoffmann and Guido Werdnig. The eponymous term Kugelberg–Welander disease named after Erik Klas Hendrik Kugelberg (1913–1983) and Lisa Welander (1909–2001), who first documented the late-onset form and distinguished it from muscular dystrophy. Very rarely used Dubowitz disease (not to be confused with Dubowitz syndrome) is named after Victor Dubowitz, an English neurologist who authored several studies on the intermediate SMA phenotype.

Signs and symptoms
The symptoms vary depending on the SMA type, the stage of the disease as well as individual factors. Signs and symptoms below are most common in the severe SMA type 0/I:
Areflexia, particularly in extremities
Overall muscle weakness, poor muscle tone, limpness or a tendency to flop
Difficulty achieving developmental milestones, difficulty sitting/standing/walking
In small children: adopting of a frog-leg position when sitting (hips abducted and knees flexed)
Loss of strength of the respiratory muscles: weak cough, weak cry (infants), accumulation of secretions in the lungs or throat, respiratory distress
Bell-shaped torso (caused by using only abdominal muscles for respiration) in severe SMA type
Fasciculations (twitching) of the tongue
Difficulty sucking or swallowing, poor feeding

Causes
Spinal muscular atrophy is caused by a genetic mutation in the SMN1 gene.Human chromosome 5 contains two nearly identical genes at location 5q13: a telomeric copy SMN1 and a centromeric copy SMN2. In healthy individuals, the SMN1 gene codes the survival of motor neuron protein (SMN) which, as its name says, plays a crucial role in survival of motor neurons. The SMN2 gene, on the other hand – due to a variation in a single nucleotide (840.C→T) – undergoes alternative splicing at the junction of intron 6 to exon 8, with only 10–20% of SMN2 transcripts coding a fully functional survival of motor neuron protein (SMN-fl) and 80–90% of transcripts resulting in a truncated protein compound (SMNΔ7) which is rapidly degraded in the cell.In individuals affected by SMA, the SMN1 gene is mutated in such a way that it is unable to correctly code the SMN protein – due to either a deletion occurring at exon 7 or to other point mutations (frequently resulting in the functional conversion of the SMN1 sequence into SMN2). Almost all people, however, have at least one functional copy of the SMN2 gene (with most having 2–4 of them) which still codes 10–20% of the usual level of the SMN protein, allowing some neurons to survive. In the long run, however, the reduced availability of the SMN protein results in gradual death of motor neuron cells in the anterior horn of spinal cord and the brain. Skeletal muscles, which all depend on these motor neurons for neural input, now have decreased innervation (also called denervation), and therefore have decreased input from the central nervous system (CNS). Decreased impulse transmission through the motor neurons leads to decreased contractile activity of the denervated muscle. Consequently, denervated muscles undergo progressive atrophy (waste away).Muscles of lower extremities are usually affected first, followed by muscles of upper extremities, spine and neck and, in more severe cases, pulmonary and mastication muscles. Proximal muscles are always affected earlier and to a greater degree than distal muscles.The severity of SMA symptoms is broadly related to how well the remaining SMN2 genes can make up for the loss of function of SMN1. This partly depends on the number of copies of the SMN2 gene present on the chromosome. Whilst healthy individuals usually carry two SMN2 gene copies, people with SMA can have anything between 1 and 5 (or more) of them; the greater the number of SMN2 copies, the milder the disease severity. Thus, most SMA type I babies have one or two SMN2 copies; people with SMA II and III usually have at least three SMN2 copies; and people with SMA IV normally have at least four of them. However, the correlation between symptom severity and SMN2 copy number is not absolute and there seem to exist other factors affecting the disease phenotype.Spinal muscular atrophy is inherited in an autosomal recessive pattern, which means that the defective gene is located on an autosome. Two copies of the defective gene – one from each parent – are required to inherit the disorder: the parents may be carriers and not personally affected. SMA seems to appear de novo (i.e., without any hereditary causes) in around 2–4% of cases.Spinal muscular atrophy affects individuals of all ethnic groups, unlike other well known autosomal recessive disorders, such as sickle cell disease and cystic fibrosis, which have significant differences in occurrence rate among ethnic groups. The overall prevalence of SMA, of all types and across all ethnic groups, is in the range of 1 per 10,000 individuals; the gene frequency is around 1:100, therefore, approximately one in 50 persons are carriers. There are no known health consequences of being a carrier. A person may learn carrier status only if ones child is affected by SMA or by having the SMN1 gene sequenced.Affected siblings usually have a very similar form of SMA. However, occurrences of different SMA types among siblings do exist – while rare, these cases might be due to additional de novo deletions of the SMN gene, not involving the NAIP gene, or the differences in SMN2 copy numbers.

Diagnosis
SMA is diagnosed using genetic testing that detects homozygous deletion of the SMN1 gene in over 95% of cases, and a compound SMN1 mutation in the remaining patients. Genetic testing is usually carried out using a blood sample, and MLPA is one of more frequently used genetic testing techniques, as it also allows establishing the number of SMN2 gene copies, which has clinical importance.Symptomatically, SMA can be diagnosed with a degree of certainty only in children with the acute form who manifest a progressive illness with paradoxical breathing, bilateral low muscle tone and absent tendon reflexes.

Early diagnosis
Early diagnosis of SMA, at the asymptomatic stage of the disease, allows for

Preimplantation testing
Preimplantation genetic diagnosis can be used to screen for SMA-affected embryos during in-vitro fertilisation.

Prenatal testing
Prenatal testing for SMA is possible through chorionic villus sampling, cell-free fetal DNA analysis and other methods.

Newborn screening
Routine newborn screening for SMA is becoming increasingly commonplace in developed countries, given the availability of causative treatments that are most effective at the asymptomatic stage of the disease. In 2018, newborn screening for SMA was added to the US list of recommended newborn screening tests and as of April 2020 it has been adopted in 39 US states. As of May 2021, SMA newborn screening has been implemented in Taiwan and is in the course of implementation in Australia, Belgium, Canada, France, Germany, Netherlands, Poland, Serbia and Slovenia. Additionally, pilot projects are being conducted in Australia, China, Italy, and Japan.

Carrier testing
Those at risk of being carriers of SMN1 deletion, and thus at risk of having offspring affected by SMA, can undergo carrier analysis using a blood or saliva sample. The American College of Obstetricians and Gynecologists recommends all people thinking of becoming pregnant be tested to see if they are a carrier. The carrier frequency of SMA is comparable to other disorders like thalassemia and in a north Indian cohort has been found to be 1 in 38. However, genetic testing will not be able to identify all individuals at risk since about 2% of cases are caused by de novo mutations and 5% of the normal population have two copies of SMN1 on the same chromosome, which makes it possible to be a carrier by having one chromosome with two copies and a second chromosome with zero copies. This situation will lead to a false negative result, as the carrier status will not be correctly detected by a traditional genetic test.

Management
The management of SMA varies based upon the severity and type. In the most severe forms (types 0/1), individuals have the greatest muscle weakness requiring prompt intervention. Whereas the least severe form (type 4/adult onset), individuals may not seek the certain aspects of care until later (decades) in life. While types of SMA and individuals among each type may differ, therefore specific aspects of an individuals care can differ.

Medication
Nusinersen (marketed as Spinraza) is used to treat spinal muscular atrophy. It is an antisense nucleotide that modifies the alternative splicing of the SMN2 gene. It is given directly to the central nervous system using an intrathecal injection. Nusinersen prolongs survival and improves motor function in infants with SMA. It was approved for use in the US in 2016, and for use in the EU in 2017.Onasemnogene abeparvovec (marketed as Zolgensma) is a gene therapy treatment which uses self-complementary adeno-associated virus type 9 (scAAV-9) as a vector to deliver the SMN1 transgene. The therapy was first approved in the US in May 2019 as an intravenous formulation for children below 24 months of age. Approval in the European Union, Japan and other countries followed, albeit often with different approval scopes.Risdiplam (marketed as Evrysdi) is a medication taken by mouth in liquid form. It is a pyridazine derivative that works by increasing the amount of functional survivor motor neuron protein produced by the SMN2 gene through modifying its splicing pattern. Risdiplam was first approved for medical use in the United States in August 2020 and has since been approved in over 30 countries.

Breathing
The respiratory system is the most common system to be affected and the complications are the leading cause of death in SMA types 0/1 and 2. SMA type 3 can have similar respiratory problems, but it is more rare. The complications that arise due to weakened intercostal muscles because of the lack of stimulation from the nerve. The diaphragm is less affected than the intercostal muscles. Once weakened, the muscles never fully recover the same functional capacity to help in breathing and coughing as well as other functions. Therefore, breathing is more difficult and pose a risk of not getting enough oxygen/shallow breathing and insufficient clearance of airway secretions. These issues more commonly occurs while asleep, when muscles are more relaxed. Swallowing muscles in the pharynx can be affected, leading to aspiration coupled with a poor coughing mechanism increases the likelihood of infection/pneumonia. Mobilizing and clearing secretions involve manual or mechanical chest physiotherapy with postural drainage, and manual or mechanical cough assistance device. To assist in breathing, Non-invasive ventilation (BiPAP) is frequently used and tracheostomy may be sometimes performed in more severe cases; both methods of ventilation prolong survival to a comparable degree, although tracheostomy prevents speech development.

Nutrition
The more severe the type of SMA, the more likely to have nutrition related health issues. Health issues can include difficulty in feeding, jaw opening, chewing and swallowing. Individuals with such difficulties can be at increase risk of over or undernutrition, failure to thrive and aspiration. Other nutritional issues, especially in individuals that are non-ambulatory (more severe types of SMA), include food not passing through the stomach quickly enough, gastric reflux, constipation, vomiting and bloating. Therein, it could be necessary in SMA type I and people with more severe type II to have a feeding tube or gastrostomy. Additionally, metabolic abnormalities resulting from SMA impair β-oxidation of fatty acids in muscles and can lead to organic acidemia and consequent muscle damage, especially when fasting. It is suggested that people with SMA, especially those with more severe forms of the disease, reduce intake of fat and avoid prolonged fasting (i.e., eat more frequently than healthy people) as well as choosing softer foods to avoid aspiration. During an acute illness, especially in children, nutritional problems may first present or can exacerbate an existing problem (example: aspiration) as well as cause other health issues such as electrolyte and blood sugar disturbances.

Orthopaedics
Skeletal problems associated with weak muscles in SMA include tight joints with limited range of movement, hip dislocations, spinal deformity, osteopenia, an increase risk of fractures and pain. Weak muscles that normally stabilize joints such as the vertebral column lead to development of kyphosis and/or scoliosis and joint contracture. Spine fusion is sometimes performed in people with SMA I/II once they reach the age of 8–10 to relieve the pressure of a deformed spine on the lungs. Furthermore, immobile individuals, posture and position on mobility devices as well as range of motion exercises, and bone strengthening can be important to prevent complications. People with SMA might also benefit greatly from various forms of physiotherapy, occupational therapy and physical therapy.Orthotic devices can be used to support the body and to aid walking. For example, orthotics such as AFOs (ankle foot orthoses) are used to stabilise the foot and to aid gait, TLSOs (thoracic lumbar sacral orthoses) are used to stabilise the torso. Assistive technologies may help in managing movement and daily activity and greatly increase the quality of life.

Other
Although the heart is not a matter of routine concern, a link between SMA and certain heart conditions has been suggested.Children with SMA do not differ from the general population in their behaviour; their cognitive development can be slightly faster, and certain aspects of their intelligence are above the average. Despite their disability, SMA-affected people report high degree of satisfaction from life.Palliative care in SMA has been standardised in the Consensus Statement for Standard of Care in Spinal Muscular Atrophy which has been recommended for standard adoption worldwide.

Prognosis
In the absence of pharmacological treatment, people with SMA tend to deteriorate over time. Recently, survival has increased in severe SMA patients with aggressive and proactive supportive respiratory and nutritional support.If left untreated, the majority of children diagnosed with SMA type 0 and 1 do not reach the age of 4, recurrent respiratory problems being the primary cause of death. With proper care, milder SMA type I cases (which account for approx. 10% of all SMA1 cases) live into adulthood. Long-term survival in SMA type I is not sufficiently evidenced; however, as of 2007 advances in respiratory support seem to have brought down mortality.In untreated SMA type II, the course of the disease is slower to progress and life expectancy is less than the healthy population. Death before the age of 20 is frequent, although many people with SMA live to become parents and grandparents. SMA type III has normal or near-normal life expectancy if standards of care are followed. Type IV, adult-onset SMA usually means only mobility impairment and does not affect life expectancy.

Research directions
Since the underlying genetic cause of SMA was identified in 1995, several therapeutic approaches have been proposed and investigated that primarily focus on increasing the availability of SMN protein in motor neurons. The main research directions have been as follows:

SMN1 gene replacement
Gene therapy in SMA aims at restoring the SMN1 gene function through inserting specially crafted nucleotide sequence (a SMN1 transgene) into the cell nucleus using a viral vector. This approach has been exploited by the first approved gene therapy for SMA, scAAV-9 based treatment onasemnogene abeparvovec.

SMN2 alternative splicing modulation
This approach aims at modifying the alternative splicing of the SMN2 gene to force it to code for higher percentage of full-length SMN protein. Sometimes it is also called gene conversion, because it attempts to convert the SMN2 gene functionally into SMN1 gene. It is the therapeutic mechanism of the approved medications nusinersen and risdiplam.
Branaplam is another SMN2 splicing modulator that has reached the clinical stage of development.Historically, this research direction investigated also other molecules. RG3039, also known as Quinazoline495, was a proprietary quinazoline derivative developed by Repligen and licensed to Pfizer in March 2014 which was discontinued shortly after, having only completed phase I trials. PTK-SMA1 was a proprietary small-molecule splicing modulator of the tetracyclines group developed by Paratek Pharmaceuticals and about to enter clinical development in 2013 which however never happened due to Paratek downsizing at that time. RG7800, developed by Hoffmann-La Roche, was a molecule akin to risdiplam that has undergone phase I testing but was discontinued due to animal toxicity. Early leads also included sodium orthovanadate and aclarubicin.Morpholino-type antisense oligonucleotides, with the same cellular target as nusinersen, remain a subject of research in treating SMA and other single-gene diseases, including at the University College London and at the University of Oxford.

SMN2 gene activation
This approach aims at increasing expression (activity) of the SMN2 gene, thus increasing the amount of full-length SMN protein available.

Oral salbutamol (albuterol), a popular asthma medicine, showed therapeutic potential in SMA both in vitro and in three small-scale clinical trials involving patients with SMA types 2 and 3, besides offering respiratory benefits.A few compounds initially showed promise but failed to demonstrate efficacy in clinical trials. Butyrates (sodium butyrate and sodium phenylbutyrate) held some promise in in vitro studies but a clinical trial in symptomatic people did not confirm their efficacy. Another clinical trial in pre-symptomatic types 1–2 infants was completed in 2015 but no results have been published.
Valproic acid (VPA) was used in SMA on an experimental basis in the 1990s and 2000s because in vitro research suggested its moderate effectiveness. However, it demonstrated no efficacy in achievable concentrations when subjected to a large clinical trial. It has also been proposed that it may be effective in a subset of people with SMA but its action may be suppressed by fatty acid translocase in others. Others argue it may actually aggravate SMA symptoms. It is currently not used due to the risk of severe side effects related to long-term use. A 2019 meta-analysis suggested that VPA may offer benefits, even without improving functional score.
Hydroxycarbamide (hydroxyurea) was shown effective in mouse models and subsequently commercially researched by Novo Nordisk, Denmark, but demonstrated no effect on people with SMA in subsequent clinical trials.Compounds which increased SMN2 activity in vitro but did not make it to the clinical stage include growth hormone, various histone deacetylase inhibitors, benzamide M344, hydroxamic acids (CBHA, SBHA, entinostat, panobinostat, trichostatin A, vorinostat), prolactin as well as natural polyphenol compounds like resveratrol and curcumin. Celecoxib, a p38 pathway activator, is sometimes used off-label by people with SMA based on a single animal study but such use is not backed by clinical-stage research.

SMN stabilisation
SMN stabilisation aims at stabilising the SMNΔ7 protein, the short-lived defective protein coded by the SMN2 gene, so that it is able to sustain neuronal cells.No compounds have been taken forward to the clinical stage. Aminoglycosides showed capability to increase SMN protein availability in two studies. Indoprofen offered some promise in vitro.

Neuroprotection
Neuroprotective drugs aim at enabling the survival of motor neurons even with low levels of SMN protein.

Olesoxime was a proprietary neuroprotective compound developed by the French company Trophos, later acquired by Hoffmann-La Roche, which showed stabilising effect in a phase-II clinical trial involving people with SMA types 2 and 3. Its development was discontinued in 2018 in view of competition from nusinersen and underwhelming data from an open-label extension trial.Of clinically studied compounds which did not show efficacy, thyrotropin-releasing hormone (TRH) held some promise in an open-label uncontrolled clinical trial but did not prove effective in a subsequent double-blind placebo-controlled trial </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Vasculitic neuropathy and explain in detail? [/INST] Vasculitic neuropathy is a peripheral neuropathic disease. In a vasculitic neuropathy  there is damage to the vessels that supply blood to the nerves. It can be as part of a systemic problem or can exist as a single-organ issue only affecting the peripheral nervous system (PNS). It is diagnosed with the use of electrophysiological testing, blood tests, nerve biopsy and clinical examination. It is a serious medical condition that can cause prolonged morbidity and disability and generally requires treatment. Treatment depends on the type but it is mostly with corticosteroids or immunomodulating therapies.

Types
There are three main categories of vasculitic neuropathies: primary, secondary and non-systemic.

Primary systemic vasculitic neuropathy
Some patients with systemic vasculitis will have their multi-organ disease spread to the peripheral nervous system; this is primary vasculitic neuropathy. Some examples of systemic vasculitic disease are: IgA vasculitis, Hypocomplementemic urticarial vasculitis, polyarteritis nodosa (PAN) and anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides such as granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA) and microscopic polyangiitis (MPA).

Vasculitic neuropathy secondary to other disease
Some patients with a non-vasculitic systemic disease or another illness such as infection or malignancy can subsequently develop vasculitic neuropathy as a direct consequence of the former illness; this is secondary vasculitic neuropathy. Some examples of such illness which can cause vasculitic neuropathy are:
Connective tissue diseases: rheumatoid arthritis, systemic lupus erythematosus, primary sjögrens, dermatomyositis.
Infectious diseases: hepatitis B, hepatitis C, human immunodeficiency virus (HIV), cytomegalovirus, lyme disease, human T-cell-lymphotrophic virus-I, parvovirus B19.
Malignancy.
Drugs (amphetamines, sympathomimetics, cocaine, etc.)
Vaccinations.

Non-systemic vasculitic neuropathy
Non-systemic vasculitic neuropathy (NSVN) is a diagnosis of elimination </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Lenz microphthalmia syndrome and explain in detail? [/INST] Lenz microphthalmia syndrome is a very rare inherited disorder characterized by abnormal smallness of one or both eyes (microphthalmos) sometimes with droopy eyelids (blepharoptosis), resulting in visual impairment or blindness. Eye problems may include coloboma, microcornea, and glaucoma </s>


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Odontogenic cyst and explain in detail? [/INST] Odontogenic cyst are a group of jaw cysts that are formed from tissues involved in odontogenesis (tooth development). Odontogenic cysts are closed sacs, and have a distinct membrane derived from rests of odontogenic epithelium. It may contain air, fluids, or semi-solid material. Intra-bony cysts are most common in the jaws, because the mandible and maxilla are the only bones with epithelial components. That odontogenic epithelium is critical in normal tooth development. However, epithelial rests may be the origin for the cyst lining later.
Not all oral cysts are odontogenic cyst. For example, mucous cyst of the oral mucosa and nasolabial duct cyst are not of odontogenic origin.
In addition, there are several conditions with so-called (radiographic) pseudocystic appearance in jaws; ranging from anatomic variants such as Stafne static bone cyst, to the aggressive aneurysmal bone cyst.

Classification
I. Cysts of the jaws
A. Epithelial-lined cysts
1. Developmental origin
(a) Odontogenic
i. Gingival cyst of infants
ii. Odontogenic keratocyst
iii. Dentigerous cyst
iv. Eruption cyst
v. Gingival cyst of adults
vi. Developmental lateral periodontal cyst
vii. Botryoid odontogenic cyst
viii. Glandular odontogenic cyst
ix. Calcifying odontogenic cyst
(b) Non-odontogenic
i. Midpalatal raphé cyst of infants
ii. Nasopalatine duct cyst
iii. Nasolabial cyst
2. Inflammatory origin
i. Radicular cyst, apical and lateral
ii. Residual cyst
iii. Paradental cyst and juvenile paradental cyst
iv. Inflammatory collateral cyst
B. Non-epithelial-lined cysts
1. Solitary bone cyst
2. Aneurysmal bone cyst
II. Cysts associated with the maxillary antrum
1. Mucocele
2. Retention cyst
3. Pseudocyst
4. Postoperative maxillary cyst
III. Cysts of the soft tissues of the mouth, face and neck
1. Dermoid and epidermoid cysts
2. Lymphoepithelial (branchial) cyst
3. Thyroglossal duct cyst
4. Anterior median lingual cyst (intralingual cyst of foregut origin)
5. Oral cysts with gastric or intestinal epithelium (oral alimentary tract cyst)
6. Cystic hygroma
7. Nasopharyngeal cyst
8 </s>


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Parathyroid hormone and explain in detail? [/INST] Parathyroid hormone (PTH), also called parathormone or parathyrin,  is a peptide hormone secreted by the parathyroid glands that regulates the serum calcium concentration through its effects on bone, kidney, and intestine.PTH influences bone remodeling, which is an ongoing process in which bone tissue is alternately resorbed and rebuilt over time.  PTH is secreted in response to low blood serum calcium (Ca2+) levels.  PTH indirectly stimulates osteoclast activity within the bone matrix (osteon), in an effort to release more ionic calcium (Ca2+) into the blood to elevate a low serum calcium level.  The bones act as a (metaphorical) "bank of calcium" from which the body can make "withdrawals" as needed to keep the amount of calcium in the blood at appropriate levels despite the ever-present challenges of metabolism, stress, and nutritional variations. PTH is "a key that unlocks the bank vault" to remove the calcium.
PTH is secreted primarily by the chief cells of the parathyroid glands. The gene for PTH is located on chromosome 11. It is a polypeptide containing 84 amino acids, which is a prohormone. It has a molecular mass around 9500 Da. Its action is opposed by the hormone calcitonin.
There are two types of PTH receptors. Parathyroid hormone 1 receptors, activated by the 34 N-terminal amino acids of PTH, are present at high levels on the cells of bone and kidney. Parathyroid hormone 2 receptors are present at high levels on the cells of central nervous system, pancreas, testes, and placenta. The half-life of PTH is about 4 minutes.Disorders that yield too little or too much PTH, such as hypoparathyroidism, hyperparathyroidism, and paraneoplastic syndromes can cause bone disease, hypocalcemia, and hypercalcemia.

Structure
hPTH-(1-84) crystallizes as a slightly bent, long, helical dimer. The extended helical conformation of hPTH-(1-84) is the likely bioactive conformation. The N-terminal fragment 1-34 of parathyroid hormone (PTH) has been crystallized and the structure has been refined to 0.9 Å resolution.

Function
Regulation of serum calcium
Parathyroid hormone regulates serum calcium through its effects on bone, kidney, and the intestine:In bone, PTH enhances the release of calcium from the large reservoir contained in the bones. Bone resorption is the normal destruction of bone by osteoclasts, which are indirectly stimulated by PTH. Stimulation is indirect since osteoclasts do not have a receptor for PTH; rather, PTH binds to osteoblasts, the cells responsible for creating bone. Binding stimulates osteoblasts to increase their expression of RANKL and inhibits their secretion of osteoprotegerin (OPG). Free OPG competitively binds to RANKL as a decoy receptor, preventing RANKL from interacting with RANK, a receptor for RANKL. The binding of RANKL to RANK (facilitated by the decreased amount of OPG available for binding the excess RANKL) stimulates osteoclast precursors, which are of a monocyte lineage, to fuse. The resulting multinucleated cells are osteoclasts, which ultimately mediate bone resorption. Estrogen also regulates this pathway through its effects on PTH. Estrogen suppresses T cell TNF production by regulating T cell differentiation and activity in the bone marrow, thymus, and peripheral lymphoid organs. In the bone marrow, estrogen downregulates the proliferation of hematopoietic stem cells through an IL-7 dependent mechanism.In the kidney, around 250 mmol of calcium ions are filtered into the glomerular filtrate per day. Most of this (245 mmol/d) is reabsorbed from the tubular fluid, leaving about 5 mmol/d to be excreted in the urine. This reabsorption occurs throughout the tubule (most, 60-70%, of it in the proximal tubule), except in the thin segment of the loop of Henle. Circulating parathyroid hormone only influences the reabsorption that occurs in the distal tubules and the renal collecting ducts (but see Footnote). A more important effect of PTH on the kidney is, however, its inhibition of the reabsorption of phosphate (HPO42−) from the tubular fluid, resulting in a decrease in the plasma phosphate concentration.  Phosphate ions form water-insoluble salts with calcium. Thus, a decrease in the phosphate concentration of the  blood plasma (for a given total calcium concentration) increases the amount of calcium that is ionized. A third important effect of PTH on the kidney is its stimulation of the conversion of 25-hydroxy vitamin D into 1,25-dihydroxy vitamin D (calcitriol), which is released into the circulation. This latter form of vitamin D is the active hormone which stimulates calcium uptake from the intestine.Via the kidney, PTH enhances the absorption of calcium in the intestine by increasing the production of activated vitamin D. Vitamin D activation occurs in the kidney. PTH up-regulates 25-hydroxyvitamin D3 1-alpha-hydroxylase, the enzyme responsible for 1-alpha hydroxylation of 25-hydroxy vitamin D, converting vitamin D to its active form (1,25-dihydroxy vitamin D). This activated form of vitamin D increases the absorption of calcium (as Ca2+ ions) by the intestine via calbindin.
PTH was one of the first hormones to be shown to use the G-protein adenylyl cyclase second messenger system.

Regulation of serum phosphate
PTH reduces the reabsorption of phosphate from the proximal tubule of the kidney, which means more phosphate is excreted through the urine.
However, PTH enhances the uptake of phosphate from the intestine and bones into the blood. In the bone, slightly more calcium than phosphate is released from the breakdown of bone. In the intestines, absorption of both calcium and phosphate is mediated by an increase in activated vitamin D. The absorption of phosphate is not as dependent on vitamin D as is that of calcium. The end result of PTH release is a small net drop in the serum concentration of phosphate.

Vitamin D synthesis
PTH upregulates the activity of 1-α-hydroxylase enzyme, which converts 25-hydroxycholecalciferol, the major circulating form of inactive vitamin D, into 1,25-dihydroxycholecalciferol, the active form of vitamin D, in the kidney.

Interactive pathway map
Regulation of PTH secretion
Secretion of parathyroid hormone is determined chiefly by serum ionized calcium concentration through negative feedback. Parathyroid cells express calcium-sensing receptors on the cell surface. PTH is secreted when [Ca2+] is decreased (calcitonin is secreted when serum calcium levels are elevated). The G-protein-coupled calcium receptors bind extracellular calcium and may be found on the surface on a wide variety of cells distributed in the brain, heart, skin, stomach, C cells, and other tissues.  In the parathyroid gland, high concentrations of extracellular calcium result in activation of the Gq G-protein coupled cascade through the action of phospholipase C.  This hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) to liberate intracellular messengers IP3 and diacylglycerol (DAG).  Ultimately, these two messengers result in a release of calcium from intracellular stores into the cytoplasmic space.  Hence a high extracellular calcium concentration leads to an increase in the cytoplasmic calcium concentration.  In contrast to the mechanism that most secretory cells use, this high cytoplasmic calcium concentration inhibits the fusion of vesicles containing granules of preformed PTH with the membrane of the parathyroid cell, and thus inhibits release of PTH.
In the parathyroids, magnesium serves this role in stimulus-secretion coupling. A mild decrease in serum magnesium levels stimulates the reabsorptive activity PTH has on the kidneys. Severe hypomagnesemia inhibits PTH secretion and also causes resistance to PTH, leading to a form of hypoparathyroidism that is reversible.

Stimulators
Decreased serum [Ca2+].
Mild decreases in serum [Mg2+].
An increase in serum phosphate (increased phosphate causes it to complex with serum calcium,  forming calcium phosphate, which reduces stimulation of Ca-sensitive receptors (CaSr) that do not sense calcium phosphate, triggering an increase in PTH).
Adrenaline
Histamine

Inhibitors
Increased serum [Ca2+].
Severe decreases in serum [Mg2+], which also produces symptoms of hypoparathyroidism (such as hypocalcemia).
Calcitriol
Increase in serum phosphate. Fibroblast growth factor-23 (FGF23) is produced in osteoblasts (from bone) in response to increases in serum phosphate (Pi). It binds to the fibroblast growth factor receptor of the parathyroid and suppresses PTH release. This may seem contradictory because PTH actually helps rid the blood of phosphates but it is also causes release of phosphate into the blood from bone resorption. FGF23 inhibits PTH and then takes its place helping inhibit re-absorption of phosphate in the kidney without the phosphate releasing effect on bones.

Disorders
Hyperparathyroidism, the presence of excessive amounts of parathyroid hormone in the blood, occurs in two very distinct sets of circumstances </s>


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


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Flail chest and explain in detail? [/INST] Flail chest is a life-threatening medical condition that occurs when a segment of the rib cage breaks due to trauma and becomes detached from the rest of the chest wall. Two of the symptoms of flail chest are chest pain and shortness of breath.It occurs when multiple adjacent ribs are broken in multiple places, separating a segment, so a part of the chest wall moves independently. The number of ribs that must be broken varies by differing definitions: some sources say at least two adjacent ribs are broken in at least two places, some require three or more ribs in two or more places. The flail segment moves in the opposite direction to the rest of the chest wall: because of the ambient pressure in comparison to the pressure inside the lungs, it goes in while the rest of the chest is moving out, and vice versa. This so-called "paradoxical breathing" is painful and increases the work involved in breathing.
Flail chest is usually accompanied by a pulmonary contusion, a bruise of the lung tissue that can interfere with blood oxygenation. Often, it is the contusion, not the flail segment, that is the main cause of respiratory problems in people with both injuries.Surgery to fix the fractures appears to result in better outcomes.

Signs and symptoms
Two of the symptoms of flail chest are chest pain and shortness of breath.The characteristic paradoxical motion of the flail segment occurs due to pressure changes associated with respiration that the rib cage normally resists:

During normal inspiration, the diaphragm contracts and intercostal muscles pull the rib cage out. Pressure in the thorax decreases below atmospheric pressure, and air rushes in through the trachea. The flail segment will be pulled in with the decrease in pressure while the rest of the rib cage expands.
During normal expiration, the diaphragm and intercostal muscles relax increasing internal pressure, allowing the abdominal organs to push air upwards and out of the thorax. However, a flail segment will also be pushed out while the rest of the rib cage contracts.Paradoxical motion is a late sign of flail segment; therefore, an absence of paradoxical motion does not mean the patient does not have a flail segment.
The constant motion of the ribs in the flail segment at the site of the fracture is extremely painful, and, untreated, the sharp broken edges of the ribs are likely to eventually puncture the pleural sac and lung, possibly causing a pneumothorax. The concern about "mediastinal flutter" (the shift of the mediastinum with paradoxical diaphragm movement) does not appear to be merited. Pulmonary contusions are commonly associated with flail chest and that can lead to respiratory failure. This is due to the paradoxical motions of the chest wall from the fragments interrupting normal breathing and chest movement. Typical paradoxical motion is associated with stiff lungs, which requires extra work for normal breathing, and increased lung resistance, which makes air flow difficult. The respiratory failure from the flail chest requires mechanical ventilation and a longer stay in an intensive care unit. It is the damage to the lungs from the flail segment that is life-threatening.

Causes
The most common causes of flail chest injuries are vehicle collisions, which account for 76% of flail chest injuries. Another main cause of flail chest injuries is falling.  This mainly occurs in the elderly, who are more impacted by the falls as a result of their weak and frail bones, unlike their younger counterparts who can fall without being impacted as severely. Falls account for 14% of flail chest injuries.Flail chest typically occurs when three or more adjacent ribs are fractured in two or more places, allowing that segment of the thoracic wall to displace and move independently of the rest of the chest wall. Flail chest can also occur when ribs are fractured proximally in conjunction with disarticulation of costal cartilages distally. For the condition to occur, generally there must be a significant force applied over a large surface of the thorax to create the multiple anterior and posterior rib fractures. Rollover and crushing injuries most commonly break ribs at only one point, whereas for flail chest to occur a significant impact is required, breaking the ribs in two or more places. This can be caused by forceful accidents such as the aforementioned vehicle collisions or significant falls. In the elderly, it can be caused by deterioration of bone, although rare. In children, the majority of flail chest injuries result from common blunt force traumas or metabolic bone diseases, including a group of genetic disorders known as osteogenesis imperfecta.

Diagnosis
Diagnosis is by physical examination performed by a physician. The diagnosis may be assisted or confirmed by use of medical imaging with either plain X ray or CT scan.

Treatment
Treatment of the flail chest initially follows the principles of advanced trauma life support. Further treatment includes:

Good pain management includes early regional anesthesia (e.g. intercostal blocks or erector spinae plane blocks) and avoiding opioid pain medication as much as possible. This allows much better ventilation, with improved tidal volume, and increased blood oxygenation.
Positive pressure ventilation, meticulously adjusting the ventilator settings to avoid pulmonary barotrauma.
Chest tubes as required.
Adjustment of position to make the person most comfortable and provide relief of pain.
Aggressive pulmonary toiletA person may be intubated with a double lumen tracheal tube. In a double lumen endotracheal tube, each lumen may be connected to a different ventilator. Usually one side of the chest is affected more than the other, so each lung may require drastically different pressures and flows to adequately ventilate.
Surgical fixation can help in significantly reducing the duration of ventilatory support and in conserving the pulmonary function.
Surgical intervention has also been shown to reduce the need for tracheostomy, reduces the time spent in the intensive care unit following a traumatic flail chest injury and could reduce the risk of acquiring pneumonia after such an event.

Physiotherapy
In order to begin a rehabilitation program for a flail chest it is important to treat the persons pain so they are able to perform the proper exercises. Due to the underlying conditions that the flail segment has caused onto the respiratory system, chest physiotherapy is important to reduce further complications.  Proper positioning of the body is key, including postural alignment for proper drainage of mucous secretions.  The therapy will consist of a variety of postural positioning and changes in order to increase normal breathing.  Along with postural repositioning, a variety of breathing exercises are also very important in order to allow the chest wall to reposition itself back to normal conditions.  Breathing exercises will also include coughing procedures.  Furthermore, range of motion exercises are given to reduce the atrophy of the musculature </s>