<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 Myopathy, X-linked, with excessive autophagy and explain in detail? [/INST] X-linked myopathy with excessive autophagy (XMEA) is a rare childhood onset disease characterized by slow progressive vacuolation and atrophy of skeletal muscle. There is no known cardiac or intellectual involvement.

Presentation
The incidence of this disease is not precisely known but it is considered to be rare (< 1/106 population). It has been reported in 15 families to date mostly from Canada, Finland and France.This disease usually presents between the ages of 5 to 10 years old. The usual picture is with weakness involving the upper legs and affects activities such as running and climbing stairs. As the condition progresses, patients tend to experience weakness in their lower legs and arms. Some remain able to walk in advanced age, while others require assistance in adulthood.

Genetics
This disorder is inherited in a recessive X linked fashion. As a result, males are much more commonly affected than females. It is due to a mutation in VMA21 gene - the human homolog of the yeast Vma21p protein </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 Cutaneous horn and explain in detail? [/INST] Cutaneous horns, also known by the Latin name cornu cutaneum, are unusual keratinous skin tumors with the appearance of horns, or sometimes of wood or coral. Formally, this is a clinical diagnosis for a "conical projection above the surface of the skin." They are usually small and localized but can, in very rare cases, be much larger. Although often benign, they can also be malignant or premalignant.

Signs and symptoms
The lesion at the base of the keratin mound is benign in the majority of cases. Malignancy is present in up to 20% of cases, with squamous-cell carcinoma being the most common type. The incidence of squamous-cell carcinoma increases to 37% when the cutaneous horn is present on the penis.
Tenderness at the base of the lesion often suggests the presence of a possible underlying squamous-cell carcinoma.

Cause
The cause of cutaneous horns is still unknown, but it is believed that exposure to radiation can trigger the condition. This is evidenced by a higher rate of cases occurring on the face and hands, areas that are often exposed to sunlight. Other cases have reported cutaneous horns arising from burn scars. As with many other wart-like skin conditions, a link to the HPV virus family, especially the HPV-2 subtype has been suggested.

Diagnosis
Cutaneous horn usually arises due to an underlying epidermal lesion, the most common being verruca vulgaris (wart), actinic keratosis (a potentially pre-malignant lesion of dysplastic keratinocytes), or squamous cell carcinoma (a form of skin cancer). These can look essentially identical clinically. The only reliable way to diagnose which type of lesion is present under the horn is to biopsy the lesion and have it microscopically examined by a pathologist (or dermatologist).

Treatments
As the horn is composed of keratin, the same material found in fingernails, the horn can usually be removed with a sterile razor. However, the underlying condition will still need to be treated. Treatments vary, but they can include surgery, radiation therapy, and chemotherapy.

Notable cases
Zhang Ruifang, aged 101 (as of 2010), living in Linlou Village, Henan province, China, has grown a cutaneous horn on her forehead, resembling what those who have examined her and her family call "Devils Horns." Notably, this growth has expanded to reach a total of 6 centimeters in length.  Another is forming on the opposite side of her forehead.
Liang Xiuzhen, aged 87 (as of 2015) living in Guiyan village in Ziyang City, Sichuan province, China, grew a 13 cm (5.1") pointed horn from her forehead, earning her the nickname "Unicorn Woman".
Huang Yuanfan, aged 84 (living in Ziyuan, China).
Shyam Lal Yadav, aged 74 (living in Madhya Pradesh, India).
Madame Dimanche, called Widow Sunday, a French woman living in Paris in the early 19th century, grew a 24.9 cm (9.8") horn from her forehead in six years from the age of 76 before it was successfully removed by French surgeon Br </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 Lecithin cholesterol acyltransferase deficiency and explain in detail? [/INST] Lecithin cholesterol acyltransferase deficiency is a disorder of lipoprotein metabolism. The disease has two forms: Familial LCAT deficiency, in which there is complete LCAT deficiency, and Fish-eye disease, in which there is a partial deficiency.Lecithin cholesterol acyltransferase catalyzes the formation of cholesterol esters in lipoproteins.

Signs and symptoms
Symptoms of the familial form include visual impairment caused by diffuse corneal opacities, target cell hemolytic anemia, and kidney failure. Less common symptoms include atherosclerosis, hepatomegaly (enlarged liver), splenomegaly (enlarged spleen), and enlarged lymph nodes.Fish-eye disease is less severe and most commonly presents with impaired vision due to corneal opacification. It rarely presents with other findings, although, atherosclerosis, hepatomegaly, splenomegaly, and lymphadenopathy can occur. Carlson and Philipson found that the disease was named so because the cornea of the eye was so opaque or cloudy with dots of cholesterol that it resembled a boiled fish.If an individual only carries one copy of the mutated gene, they typically do not show symptoms.

Pathophysiology
A deficiency of LCAT causes accumulation of unesterified cholesterol in certain body tissues. Cholesterol effluxes from cells as free cholesterol and is transported in HDL as esterified cholesterol. LCAT is the enzyme that esterifies the free cholesterol on HDL to cholesterol ester and allows the maturation of HDL. LCAT deficiency does not allow for HDL maturation resulting in its rapid catabolism of circulating apolipoprotein A1 and apolipoprotein A2. The remaining form of HDL resembles nascent HDL.The LCAT glycoprotein produces lysophosphatidylcholine and cholesterol ester and binds to lipoproteins after being secreted by the liver. Usually the enzyme produced is responsible for cholesterol ester formation and high density lipoprotein (HDL) metabolism, but in fish-eye disease the enzyme cannot esterify, or make the acid into an alkyl, cholesterol in HDL particles </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 Micropsia and explain in detail? [/INST] Micropsia is a condition affecting human visual perception in which objects are perceived to be smaller than they actually are. Micropsia can be caused by optical factors (such as wearing glasses), by distortion of images in the eye (such as optically, via swelling of the cornea or from changes in the shape of the retina such as from retinal edema, macular degeneration, or central serous retinopathy), by changes in the brain (such as from traumatic brain injury, epilepsy, migraines, prescription drugs, and illicit drugs), and from psychological factors. Dissociative phenomena are linked with micropsia, which may be the result of brain-lateralization disturbance.Micropsia is also commonly reported when the eyes are fixating at (convergence), or focusing at (accommodation), a distance closer than that of the object in accord with Emmerts law. Specific types of micropsia include hemimicropsia, a form of micropsia that is localized to one half of the visual field and can be caused by brain lesions in one of the cerebral hemispheres.
Related visual distortion conditions include macropsia, a less common condition with the reverse effect, and Alice in Wonderland syndrome, a condition that has symptoms that can include both micropsia and macropsia.

Signs and symptoms
Micropsia causes affected individuals to perceive objects as being smaller or more distant than they actually are.The majority of individuals with micropsia are aware that their perceptions do not mimic reality. Many can imagine the actual sizes of objects and distances between objects. It is common for patients with micropsia to be able to indicate true size and distance despite their inability to perceive objects as they actually are. One specific patient was able to indicate the dimensions of specific objects with her hands. She was also able to estimate the distances between two objects and between an object and herself. She succeeded in indicating horizontal, vertical, and 45 degree positions and did not find it difficult to search for an object in a cluttered drawer, indicating that her figure-ground discrimination was intact despite having micropsia.Individuals experiencing hemimicropsia often complain that objects in their left or right visual field appear to be shrunken or compressed. They may also have difficulty appreciating the symmetry of pictures. When drawing, patients often have a tendency to compensate for their perceptual asymmetry by drawing the left or right half of objects slightly larger than the other. In a case of one person with hemimicropsia asked to draw six symmetrical objects, the size of the picture on the left half was on average 16% larger than the corresponding right half.

Diagnosis
EEG testing can diagnose patients with medial temporal lobe epilepsy. Epileptiform abnormalities including spikes and sharp waves in the medial temporal lobe of the brain can diagnose this condition, which can in turn be the cause of an epileptic patients micropsia.The Amsler grid test can be used to diagnose macular degeneration. For this test, patients are asked to look at a grid, and distortions or blank spots in the patients central field of vision can be detected. A positive diagnosis of macular degeneration may account for a patients micropsia.A controlled size comparison task can be employed to evaluate objectively whether a person is experiencing hemimicropsia. For each trial, a pair of horizontally aligned circles is presented on a computer screen, and the person being tested is asked to decide which circle is larger. After a set of trials, the overall pattern of responses should display a normal distance effect where the more similar the two circles, the higher the number of errors. This test is able to effectively diagnose micropsia and confirm which hemisphere is being distorted.Due to the large range of causes that lead to micropsia, diagnosis varies among cases. Computed tomography (CT) and magnetic resonance imaging (MRI) may find lesions and hypodense areas in the temporal and occipital lobes. MRI and CT techniques are able to rule out lesions as the cause for micropsia, but are not sufficient to diagnose the most common causes.

Definition
Micropsia is the most common visual distortion, or dysmetropsia. It is categorized as an illusion in the positive phenomena grouping of abnormal visual distortions.
Convergence-accommodative micropsia is a physiologic phenomenon in which an object appears smaller as it approaches the subject.
Psychogenic micropsia can present itself in individuals with certain psychiatric disorders.
Retinal micropsia is characterized by an increase in the distance between retinal photoreceptors and is associated with decreased visual acuity.
Cerebral micropsia is a rare form of micropsia that can arise in children with chronic migraines.
Hemimicropsia is a type of cerebral micropsia that occurs within one half of the visual field.

Differential diagnosis
Of all of the visual distortions, micropsia has the largest variety of causes.

Migraines
Micropsia can occur during the aura phase of a migraine attack, a phase that often precedes the onset of a headache and is commonly characterized by visual disturbances. Micropsia, along with hemianopsia, quadrantopsia, scotoma, phosphene, teicopsia, metamorphopsia, macropsia, teleopsia, diplopia, dischromatopsia, and hallucination disturbances, is a type of aura that occurs immediately before or during the onset of a migraine headache. The symptom usually occurs less than thirty minutes before the migraine headache begins and lasts for five to twenty minutes. Only 10-20% of children with migraine headaches experience auras. Visual auras such as micropsia are most common in children with migraines.

Seizures
The most frequent neurological origin of micropsia is a result of temporal lobe seizures. These seizures affect the entire visual field of the patient. More rarely, micropsia can be part of purely visual seizures. This in turn only affects one half of the visual field and is accompanied by other cerebral visual disturbances. The most common cause of seizures which produce perceptual disturbances such as micropsia and macropsia is medial temporal lobe epilepsy in which the seizures originate in the amygdala-hippocampus complex. Micropsia often occurs as an aura signalling a seizure in patients with medial temporal lobe epilepsy. Most auras last for a very short period, ranging from a few seconds to a few minutes.

Drug use
Micropsia can result from the action of mescaline and other hallucinogenic drugs. Although drug-induced changes in perception usually subside as the chemical leaves the body, long-term cocaine use can result in the chronic residual effect of micropsia. Micropsia can be a symptom of Hallucinogen Persisting Perception Disorder, or HPPD, in which a person can experience hallucinogenic flashbacks long after ingesting a hallucinogen. A majority of these flashbacks are visual distortions which include micropsia, and 15-80% of hallucinogen users may experience these flashbacks. Micropsia can also be a rare side effect of zolpidem, a prescription medication used to temporarily treat insomnia.

Psychological factors
Psychiatric patients may experience micropsia in an attempt to distance themselves from situations involving conflict. Micropsia may also be a symptom of psychological conditions in which patients visualize people as small objects as a way to control others in response to their insecurities and feelings of weakness. In some adults who experienced loneliness as children, micropsia may arise as a mirror of prior feelings of separation from people and objects.

Epstein-Barr virus infection
Micropsia can be caused by swelling of the cornea due to infection by the Epstein-Barr virus (EBV) and can therefore present as an initial symptom of EBV mononucleosis, a disease caused by Epstein-Barr virus infection.

Retinal edema
Micropsia can result from retinal edema causing a dislocation of the receptor cells. Photoreceptor misalignment seems to occur following the surgical re-attachment for macula-off rhegmatogenous retinal detachment. After surgery, patients may experience micropsia as a result of larger photoreceptor separation by edematous fluid.

Macular degeneration
Macular degeneration typically produces micropsia due to the swelling or bulging of the macula, an oval-shaped yellow spot near the center of the retina in the human eye. The main factors leading to this disease are age, smoking, heredity, and obesity. Some studies show that consuming spinach or collard greens five times a week cuts the risk of macular degeneration by 43%.

Central serous chorioretinopathy
CSCR is a disease in which a serous detachment of the neurosensory retina occurs over an area of leakage from the choriocapillaris through the retinal pigment epithelium (RPE). The most common symptoms that result from the disease are a deterioration of visual acuity and micropsia.

Brain lesions
Micropsia is sometimes seen in individuals with brain infarctions. The damaged side of the brain conveys size information that contradicts the size information conveyed by the other side of the brain. This causes a contradiction to arise between the true perception of an objects size and the smaller perception of the object, and micropsic bias ultimately causes the individual to experience micropsia. Lesions affecting other parts of the extracerebral visual pathways can also cause micropsia.

Treatment
Treatment varies for micropsia due to the large number of different causes for the condition.Treatments involving the occlusion of one eye and the use of a prism fitted over an eyeglass lens have both been shown to provide relief from micropsia.Micropsia that is induced by macular degeneration can be treated in several ways. A study called AREDS (age-related eye disease study) determined that taking dietary supplements containing high-dose antioxidants and zinc produced significant benefits with regard to disease progression. This study was the first ever to prove that dietary supplements can alter the natural progression and complications of a disease state. Laser treatments also look promising but are still in clinical stages.

Epidemiology
Episodes of micropsia or macropsia occur in 9% of adolescents.10-35% of those with migraines experience auras, with 88% of these patients experiencing both visual auras (which include micropsia) and neurological auras.Micropsia seems to be slightly more common in boys than in girls among children who experience migraines.Approximately 80% of temporal lobe seizures produce auras that may lead to micropsia or macropsia. They are a common feature of simple partial seizures and usually precede complex partial seizures of temporal lobe origin.Central Serous Chorioretinopathy (CSCR) which can produce micropsia predominantly affects persons between the ages of 20 and 50. Women appear to be affected more than men by a factor of almost 3 to 1.

Society and culture
Comparison with Alices Adventures in Wonderland
Alice in Wonderland Syndrome, a neurological condition associated with both micropsia and macropsia, is named after Lewis Carrolls famous 19th century novel Alices Adventures in Wonderland </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 Primary progressive aphasia and explain in detail? [/INST] Primary progressive aphasia (PPA) is a type of neurological syndrome in which language capabilities slowly and progressively become impaired. As with other types of aphasia, the symptoms that accompany PPA depend on what parts of the left hemisphere are significantly damaged. However, unlike most other aphasias, PPA results from continuous deterioration in brain tissue, which leads to early symptoms being far less detrimental than later symptoms. Those with PPA slowly lose the ability to speak, write, read, and generally comprehend language. Eventually, almost every patient becomes mute and completely loses the ability to understand both written and spoken language. Although it was first described as solely impairment of language capabilities while other mental functions remain intact, it is now recognized that many, if not most of those with PPA experience impairment of memory, short-term memory formation and loss of executive functions. It was first described as a distinct syndrome by M.‑Marsel Mesulam in 1982. Primary progressive aphasias have a clinical and pathological overlap with the frontotemporal lobar degeneration (FTLD) spectrum of disorders and Alzheimers disease. However, PPA is not considered synonymous to Alzheimers disease due to the fact that, unlike those affected by Alzheimers disease, those with PPA are generally able to maintain the ability to care for themselves, remain employed, and pursue interests and hobbies. Moreover, in diseases such as Alzheimers disease, Picks disease, and Creutzfeldt-Jakob disease, progressive deterioration of comprehension and production of language is just one of the many possible types of mental deterioration, such as the progressive decline of memory, motor skills, reasoning, awareness, and visuospatial skills.

Causes
Currently, the specific causes for PPA and other degenerative brain disease similar to PPA are unknown. Autopsies have revealed a variety of brain abnormalities in people who had PPA. These autopsies, as well as imaging techniques such as CT scans, MRI, EEG, single photon emission computed tomography (SPECT), and positron emission tomography (PET), have generally revealed abnormalities to be almost exclusively in the left hemisphere.

Risk factors
There have been no large epidemiological studies on the incidence and prevalence of the PPA variants. Though it most likely has been underestimated, onset of PPA has been found to occur in the sixth or seventh decade.There are no known environmental risk factors for the progressive aphasias. However, one observational, retrospective study suggested that vasectomy could be a risk factor for PPA in men. These results have yet to be replicated or demonstrated by prospective studies.PPA is not considered a hereditary disease. However, relatives of a person with any form of frontotemporal lobar degeneration, including PPA, are at slightly greater risk of developing PPA or another form of the condition. In a quarter of patients diagnosed with PPA, there is a family history of PPA or one of the other disorders in the FTLD spectrum of disorders. It has been found that genetic predisposition varies among the different PPA variants, with PNFA being more commonly familial in nature than LPA or SD.The most convincing genetic basis of PPA has been found to be a mutation in the GRN gene. Most patients with observed GRN mutations present clinical features of PNFA, but the phenotype can be atypical.

Diagnosis
Diagnostic criteria
The following diagnosis criteria were defined by Mesulam:
As opposed to having followed trauma to the brain, a patient must show an insidious onset and a gradual progression of aphasia, defined as a disorder of sentence and/or word usage, affecting the production and comprehension of speech.
The disorder in question must be the only determinant on functional impairment in the activities of the patients daily living.
On the basis of diagnostic procedures, the disorder in question must be unequivocally attributed to a neurodegenerative process.Whether or not PPA and other aphasias are the only source of cognitive impairment in a patient is often difficult to assess because: 1) as with other neurologically degenerative diseases, such as Alzheimers disease, there are currently no reliable non-invasive diagnostic tests for aphasias, and thus neuropsychological assessments are the only tool physicians have for diagnosing patients; and 2) aphasias often affect other, non-language portions of these neuropsychological tests, such as those specific for memory.

Classification
In 2011, the classification of primary progressive aphasia was updated to include three clinical variants. Patients must first be diagnosed with PPA, and then divided into variants based on speech production features, repetition, single- word and syntax comprehension, confrontation naming, semantic knowledge, and reading/spelling. In the classical Mesulam criteria for primary progressive aphasia, there are two variants: a non-fluent type progressive nonfluent aphasia (PNFA) and a fluent type semantic dementia (SD).  A third variant of primary progressive aphasia, logopenic progressive aphasia (LPA) was then added, and is an atypical form of Alzheimers disease. For PNFA, The core criteria for diagnosis includes agrammatism and slow, and labored speech. Inconsistent speech sound errors are also very common, including distortions, deletions, and insertions. In terms of comprehension, there are deficits in syntax and sentence comprehension due to grammatical complexity, but single- word and object comprehension is relatively maintained. The second variant, SD, presents with deficits in single-word and object comprehension. Naming impairments can be severe, specially for low-frequency objects, and can eventually lead to a more widespread semantic memory deficiency over time. The ability to read and write can also be impaired if there are irregularities between pronunciation and spelling. However, repetition and motor speech is relatively preserved. The logopenic variant involves impairments in word retrieval, sentence repetition, and phonological paraphasias, comparable to conduction aphasia. Compared to the semantic variant, single word comprehension and naming is spared, however, sentence comprehension presents difficulty because of length and grammatical complexity. Speech will include incomplete words, hesitations preceding content words, and repetition. However, these PPA subtypes differ from similar aphasias, as these subtypes do not occur acutely following trauma to the brain, such as following a stroke, due to differing functional and structural neuroanatomical patterns of involvement and the progressive nature of the disease.

Treatment
Due to the progressive, continuous nature of the disease, improvement over time seldom occurs in patients with PPA as it often does in patients with aphasias caused by trauma to the brain.In terms of medical approaches to treating PPA, there are currently no drugs specifically used for patients with PPA, nor are there any specifically designed interventions for PPA. A large reason for this is the limited research that has been done on this disease. However, in some cases, patients with PPA are prescribed the same drugs Alzheimers patients are normally prescribed.The primary approach to treating PPA has been with behavioral treatment, with the hope that these methods can provide new ways for patients to communicate in order to compensate for their deteriorated abilities.  Speech therapy can assist an individual with strategies to overcome difficulties.  There are three very broad categories of therapy interventions for aphasia: restorative therapy approaches, compensatory therapy approaches, and social therapy approaches. Rapid and sustained improvement in speech and dementia in a patient with primary progressive aphasia utilizing off-label perispinal etanercept, an anti-TNF treatment strategy also used for Alzheimers, has been reported. A video depicting the patients improvement was published in conjunction with the print article. These findings have not been independently replicated and remain controversial.

History
M.-Marsel Mesulam coined the term primary progressive aphasia.

See also
References
Further reading
Amici S, Ogar J, Brambati SM,  et al. (Dec 2007). "Performance in specific language tasks correlates with regional volume changes in progressive aphasia". Cognitive & Behavioral Neurology. 20 (4): 203–11. doi:10.1097/WNN.0b013e31815e6265. PMID 18091068. S2CID 18090918.
Gliebus G (March 2010). "Primary progressive aphasia: clinical, imaging, and neuropathological findings". Am J Alzheimers Dis Other Demen. 25 (2): 125–7. doi:10.1177/1533317509356691. PMID 20124255. S2CID 29195502.
Henry ML, Beeson PM, Alexander GE, Rapcsak SZ (February 2012). "Written language impairments in primary progressive aphasia: a reflection of damage to central semantic and phonological processes". J Cogn Neurosci. 24 (2): 261–75. doi:10.1162/jocn_a_00153. PMC 3307525. PMID 22004048.
Henry ML, Gorno-Tempini ML (December 2010). "The logopenic variant of primary progressive aphasia". Current Opinion in Neurology. 23 (6): 633–7. doi:10.1097/WCO.0b013e32833fb93e. PMC 3201824. PMID 20852419.
Reilly J, Rodriguez AD, Lamy M, Neils-Strunjas J (2010). "Cognition, language, and clinical pathological features of non-Alzheimers dementias: an overview". J Commun Disord </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 Coffin–Lowry syndrome and explain in detail? [/INST] Coffin–Lowry syndrome is a genetic disorder that is X-linked dominant and which causes severe mental problems sometimes associated with abnormalities of growth, cardiac abnormalities, kyphoscoliosis, as well as auditory and visual abnormalities.

Presentation
Symptoms of disease are more severe in males, who are generally diagnosed in early childhood. Children with CLS display cognitive disabilities of varying severity. Additional neuromuscular features include sleep apnea, muscular spasticity, progressive loss of muscle strength and tone leading to paraplegia or partial paralysis. Affected individuals are at elevated risk of stroke. Some patients experience stimulus-induced drop attacks (SIDAs, temporary paralytic episodes without loss of consciousness), triggered by unpredictable environmental stimuli (touch, scents, sounds, etc.). SIDA episodes become more frequent as the disease progresses, and become frequent around adolescence in males. Additional clinical physical features include small, soft hands with tapered fingers. Distinct facial architecture such as a flattened nose, widely separated and downward sloping eyes, a prominent forehead, and a wide mouth with large lips are reported as coincident facial features in patients with the disorder. Some individuals experience hearing loss. Others display kyphoscoliosis (multidirectional curvature of the spine) which can lead to difficulty with breathing and/or pulmonary hypertension. Cardiorespiratory complications may arise, which is why it is recommended that CLS patients undergo regular monitoring for spinal irregularities. Physical exams, CT imaging and X-ray imaging are standard methods of assessment.

Causes
The syndrome is caused by mutations in the RPS6KA3 gene. This gene is located on the short arm of the X chromosome (Xp22.2). The RPS6KA3 gene makes a protein that is involved with signaling within cells.  Researchers believe that this protein helps control the activity of other genes and plays an important role in the brain. The protein is involved in cell signaling pathways that are required for learning, the formation of long-term memories, and the survival of nerve cells. The protein RSK2 which is encoded by the RPS6KA3 gene is a kinase which phosphorylates some substrates like CREB and histone H3.  RSK2 is involved at the distal end of the Ras/MAPK signaling pathway. Mutations in the RPS6KA3 disturb the function of the protein, but it is unclear how a lack of this protein causes the signs and symptoms of Coffin–Lowry syndrome.  At this time more than 120 mutations have been found. Some people with the features of Coffin–Lowry syndrome do not have identified mutations in the RPS6KA3 gene. In these cases, the cause of the condition is unknown.This condition is inherited in an X-linked dominant pattern. A condition is considered X-linked if the gene that causes the disorder is located on the X chromosome (one of the two sex chromosomes). The inheritance is dominant if one copy of the altered gene is sufficient to cause the condition.A majority of boys with Coffin–Lowry syndrome have no history of the condition in their families. These cases are caused by new mutations in the RPS6KA3 gene (de novo mutations). A new mutation means that neither parent has the altered gene, but the affected individual could pass it on to his children.

Genetics
Coffin–Lowry syndrome is an X-linked disorder resulting from loss-of-function mutations in the RPS6KA3 gene, which encodes RSK2 (ribosomal S6 kinase 2). Multiple mutations have been identified in RPS6KA3 that can give rise to the disorder, including missense mutations, nonsense mutations, insertions and deletions. Individuals with CLS rarely have affected parents, suggesting that most incidents arise from de novo mutations in the germline. The lack of an inheritance pattern may be due to the fact that affected individuals are unlikely to parent children. In 20–30% of cases, however, there is a family history of disease. In these cases, the disorder is typically inherited from the maternal parent. Because RPS6KA3 is located on the X chromosome, males (who possess only one copy of the X chromosome) display more severe symptoms than females. Affected females usually possess one mutated copy of the RPS6KA3 gene and one wild type copy. Random inactivation of one copy of the X chromosome in females mitigates the impact of possessing a mutant allele. Occasionally females are born with two mutated alleles. In these cases the symptoms are as severe as in males with the disease.

Cell physiology
Mutations in the RPS6KA3 gene can result in expression of an RSK2 protein (ribosomal S6 kinase 2) with reduced or absent kinase function. RSK2 is a downstream component of the MAPK (mitogen-activated protein kinase) cascade that is itself a kinase. RSK2 phosphorylates cellular proteins (including histone H3, and CREB), which regulate eukaryotic gene expression. In individuals with Coffin–Lowry syndrome, phosphorylation of transcriptional regulators is reduced due to the weakened activity of RSK2 kinase activity. RSK2 is normally activated by the ERK MAP kinase. Mutated RSK2 may be deficient for activation by ERK, or its kinase activity may be reduced despite activation by ERK. The most common mutation in RPS6KA3 is an early stop codon that fails to produce a functional protein, indicating that disease etiology most likely arises from loss-of-function effects. Substitution mutations (which alter a single amino acid) have also been shown to give rise to the disease. RSK2 is  highly expressed in the brain, specifically in the neocortex, hippocampus, and Purkinje cells, all of which are involved in cognitive function and behavior. There is some experimental evidence that RSK2 regulates synaptic transmission and plasticity in neuronal cell types.

Diagnosis
Affected individuals are often short in stature. Behavioral symptoms include aggression and depression, but these may be secondary to the emotional consequences of significant physical disabilities associated with the disorder.Coffin–Lowry patients may be affected by chewing and swallowing difficulties, for which there are diagnostic assessments. Among these are the Videofluoroscopic Swallowing Evaluation (VFSE), the Karaduman Chewing Performance Scale, and the Penetration Aspiration Scale (PAS) which is used to evaluate accidental aspiration of food particles. The Pediatric Assessment Tool (PEDI-EAT-10) also includes measurement of severity of dysphagia (difficulty in swallowing). Molecular genetic testing can be used to confirm the genetic diagnosis of Coffin–Lowry syndrome or to assess pregnancy risk in affected families.Symptoms table:

Generally symptoms listed as "rare" are common in more severe cases.

Imaging studies
X-ray and neuroimaging studies may be helpful in confirming a diagnosis of Coffin–Lowry syndrome. Decreased ribosomal S6 kinase activity in cultured fibroblast or transformed lymphoblast cells from a male indicates Coffin–Lowry syndrome. Studies of enzyme activity can not be used to diagnose an affected female.Molecular genetic testing on a blood specimen or cells from a cheek swab is available to identify mutations in the RSK2 gene. This testing can be used to confirm but not rule out the diagnosis of Coffin–Lowry syndrome because not all affected individuals have a detectable mutation.

Treatment
There is no cure for Coffin–Lowry syndrome. Clinical objectives are centered on symptom management. Because stimulus-induced drop attacks (SIDAs) can result in physical harm to patients with the disorder, the use of medication to prevent or reduce the number of SIDA episodes is a safety priority. Physical precautionary measures have also been used to protect patients from injury, including the use of a helmet or a wheelchair. Because sudden excitement or fright can trigger a SIDA episode it is important to minimize exposure to startling stimuli. Medications prescribed include benzodiazepines (tranquilizers used to treat anxiety), valproate (used to manage epilepsy and bipolar disorder), and selective serotonin reuptake inhibitors (SSRIs) (used to treat major depression). When affected individuals display aggressive or destructive behavior that could harm themselves or others, the antipsychotic medication risperidone may eventually be prescribed. It is recommended that spinal development be monitored regularly by X-ray and physical exams. Echocardiograms are recommended every 5–10 years to assess cardiac function and development. Families are encouraged to receive genetic counseling in order to understand and prepare to provide care for children affected by Coffin–Lowry syndrome.

Prognosis
Lifespan may be significantly shortened in males with Coffin–Lowry syndrome. Patients may survive into their late twenties, but generally die young due to cardiac, respiratory, and post-operative complications. The progression of reduced cardiac functioning over time may necessitate surgical procedures to counteract mitral valve dysfunction, congenital heart disease, patent ductus arteriosus, and ventricular hypertrophy. Kyphoscoliosis may worsen over time and contribute to these pathologies.

Epidemiology
The prevalence of CLS is uncertain due to the rarity of the disease, but CLS is estimated to affect between 1 in 50,000 and 1 in 100,000 people. Prenatal testing is available to test for CLS of an offspring if a family member has been diagnosed with CLS.

History
Coffin–Lowry was first described by Grange S. Coffin (b. 1923) in 1966 and independently by Robert Brian Lowry (b. 1932) in 1971. Dr. Temtamy showed that the cases represented a single syndrome in 1975.In 1972, Peter G. Procopis and B </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 Transverse nasal crease 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 Aniseikonia and explain in detail? [/INST] Aniseikonia is an ocular condition where there is a significant difference in the perceived size of images. It can occur as an overall difference between the two eyes, or as a difference in a particular meridian. If the ocular image size in both eyes are equal, the condition is known as iseikonia.

Symptoms and signs
Up to 7% difference in image size is well tolerated. If magnification difference becomes excessive the effect can cause diplopia, suppression, disorientation, eyestrain, headache, and dizziness and balance disorders. Asthenopic symptoms alone may occur even if image size difference is less than 7%.

Causes
Retinal image size is determined by many factors. The size and position of the object being viewed affects the characteristics of the light entering the system. Corrective lenses affect these characteristics and are used commonly to correct refractive error. The optics of the eye including its refractive power and axial length also play a major role in retinal image size.Aniseikonia can occur naturally or be induced by the correction of a refractive error, usually anisometropia (having significantly different refractive errors between each eye) or antimetropia (being myopic (nearsighted) in one eye and hyperopic (farsighted) in the other.) Meridional aniseikonia occurs when these refractive differences only occur in one meridian (see astigmatism).
One cause of significant anisometropia and subsequent aniseikonia has been aphakia. Aphakic patients do not have a crystalline lens. The crystalline lens is often removed because of opacities called cataracts. The absence of this lens left the patient highly hyperopic (farsighted) in that eye.  For some patients the removal was only performed on one eye, resulting in the anisometropia / aniseikonia. Today, this is rarely a problem because when the lens is removed in cataract surgery, an intraocular lens, or IOL is left in its place.Retinal aniseikonia occur due to forward displacement, stretching or edema of retina.

Diagnosis
A way to demonstrate aniseikonia is to hold a near target (e.g., a pen or a finger) approximately 6 inches directly in front of one eye.  The person then closes one eye, and then the other.  The person should notice that the target appears larger to the eye that it is directly in front of.  When this object is viewed with both eyes, it is seen with a small amount of aniseikonia.  The principles behind this demonstration are relative distance magnification (closer objects appear larger) and asymmetrical convergence (the target is not an equal distance from each eye).

Treatment
Optical aniseikonia due to anisometropia can be corrected by spectacles, contact lenses or refractive corneal surgeries.Spectacle correction is done by changing the optical magnification properties of the auxiliary optics (corrective lenses). The optical magnification properties of spectacle lenses can be adjusted by changing parameters like the base curve, vertex distance, and center thickness.  Magnification size matched lenses that are used to correct aniseikonia are known as iseikonic lenses.Contact lenses may also provide less difference in retinal image size. Wider and better field of vision is another benefit of contact lens use </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 Pulp stone and explain in detail? [/INST] Pulp stones (also denticles or endoliths) are nodular, calcified masses appearing in either or both the coronal and root portion of the pulp organ in teeth. Pulp stones are not painful unless they impinge on nerves.
They are classified:
A) On the basis of structure
1) True pulp stones: formed of dentin by odontoblasts
2) False pulp stones: formed by mineralization of degenerating pulp cells, often in a concentric patternB) On the basis of location
1) Free: entirely surrounded by pulp tissue
2) Adherent: partly fused with dentin
3) Embedded: entirely surrounded by dentin

Introduction
Pulp stones are discrete calcifications found in the pulp chamber of the tooth which may undergo changes to become diffuse pulp calcifications such as dystrophic calcification.  They are usually noticed by radiographic examination and appeared as round or ovoid radiopaque lesions. Clinically, a tooth with a pulp stone has normal appearance like any other tooth. The number of pulp stones in a single tooth may vary from 1 to 12 or more, with varying sizes from minute particles to large masses which tend to occlude the pulpal space. It is reported that pulp stones are more commonly found in the coronal region of pulp, albeit also found in the radicular pulp.It is believed that pulp stones develop around a central nidus of pulp tissue, for instance collagen fibril, ground substance and necrotic cell remnants. Initial calcification occurs around the central nidus and extends outward with regular calcified material in a concentric or radial manner.

Etiology
The pulp calcifications can arise due to:

pulp degeneration
increasing age
circulatory disturbances within the pulp
long standing local irritants such as dental caries, pulp-capping procedures, healed tooth fractures, tooth injury restorations and periodontal diseases
orthodontic tooth movements
transplantation of teeth
traumaIt is shown that pulp stone occurring in adolescents is significantly associated with carious and/or restored teeth, which suggests a causative relationship of chronic pulp irritation to pulp stone formation. A defence reaction in the pulpodentinal complex may be triggered by caries and microleakage around restorations which lead to pulp calcifications. The formation of pulp stone may have a similar mechanism as the tertiary dentine formation near the irritated odontoblasts. Apart from that, with aging, the pulp decreases in size due to the deposition of secondary or tertiary dentine. This subsequently results in favourable conditions for the formation of pulpal calcifications.
The other reported etiologic factors also include:

idiopathic factors
consumption of fluoride supplements
hypervitaminosis D
a possible genetic predisposition such as dentinogenesis imperfecta and dentinal dysplasia

Types/classification
Pulp stones can be classified based on different location and structure. Based on location, they can classified into free, embedded and adherent pulp stones. Free pulp stones are found within the pulp tissue and is the most common encounter. The size vary from 50μm in diameter to several millimetres and may occlude the entire pulp chamber. Embedded pulp stone is fully embedded in dentine and most commonly found in the apical portion of the root. Adherent pulp stones are attached to the wall of pulp space but not fully enclosed by dentine.
Structurally, pulp stones can be classified as true and false pulp stones. True pulp stones are made up of dentine that is lined by odontoblast. True pulp stones are quite rare. On the other hand, false pulp stones are made up of concentric layers of mineralised tissue around blood thrombi, collagen fibres, or dying and dead cells.

Histopathology
Histologically, there are two types of stones: (1) stones with regular calcifications (2) stones with irregular calcifications.  For regular calcification, the pulp stones are smooth, round or ovoid with concentric laminations. It is commonly found in the coronal pulp. As for irregular calcifications without laminations, pulp stones may have the shape of rods or leaves and the surface is rough. It is more common in the radicular pulp. Pulp stones with regular calcification grow in size by addition of collagen fibrils to their surface, whereas the irregular type of pulp stones are formed by calcification of pre-existing collagen fibres.
Pulp stones may also form around epithelial cells such as remnants of Hertwigs epithelial root sheath. It is presumed that epithelial remnants are able to induce adjacent mesenchymal stem cells to differentiate into odontoblasts.

Associations
A pilot study was done with patients with cardiovascular disease (CVD) and it shows increased incidence of pulp stones in teeth with patients with CVD compared to healthy patients without CVD.  There are also researchers which suggest the link between pulpal calcification and carotid artery calcification, despite not having a strong proof  on this correlation </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 Microdontia and explain in detail? [/INST] Microdontia is a condition in which one or more teeth appear smaller than normal. In the generalized form, all teeth are involved. In the localized form, only a few teeth are involved. The most common teeth affected are the upper lateral incisors and third molars.
Teeth affected by microdontia may also have abnormal shape, and the abnormal size may affect the whole tooth, or only a part of the tooth.

Definition
Males tend to have larger teeth than females, and tooth size also varies by race. Abnormal tooth size is defined by some as when the dimensions are more than 2 standard deviations from the average. Microdontia is when the teeth are abnormally small, and macrodontia is when the teeth are abnormally large.

Classification
There are 3 types of microdontia:

True generalized
All the teeth are smaller than the normal size. True generalized microdontia is very rare, and occurs in pituitary dwarfism. Due to decreased levels of growth hormone the teeth fail to develop to a normal size.

Relative generalized
All the teeth are normal size but appear smaller relative to enlarged jaws </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 Refractory cytopenia with multilineage 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 Medulloepithelioma and explain in detail? [/INST] Medulloepithelioma is a rare, primitive, fast-growing brain tumour thought to stem from cells of the embryonic medullary cavity. Tumours originating in the ciliary body of the eye are referred to as embryonal medulloepitheliomas, or diktyomas.A highly malignant undifferentiated primitive neuroepithelial tumour of children, medulloepithelioma may contain bone, cartilage, skeletal muscle, and tends to metastasize extracranially.

Signs and symptoms
Medulloepithelioma have been reported to occur in the cerebral hemispheres, brainstem, cerebellum, and peripheral sites.Due to rapid growth of the tumour, patients typically present with increased intracranial pressure, seizures, and focal neurologic signs.

Diagnosis
Imaging studies such as Computerized Tomography (CT) and Magnetic Resonance Imaging (MRI) can aid diagnosis. Medulloepithelioma appears isodense or hypodense with variable heterogeneity and calcification on non-contrast CT scan, and enhances with contrast. This radiographical finding is consistent with a primitive neuroectodermal tumour, especially in children </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 Metastatic calcification 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 Hereditary breast–ovarian cancer syndrome and explain in detail? [/INST] Hereditary breast–ovarian cancer syndromes (HBOC) are cancer syndromes that produce higher than normal levels of breast cancer, ovarian cancer and additional cancers in genetically related families (either one individual had both, or several individuals in the pedigree had one or the other disease). It accounts for 90% of the hereditary cancers. The hereditary factors may be proven or suspected to cause the pattern of breast and ovarian cancer occurrences in the family. The name HBOC may be misleading because it implies that this genetic susceptibility to cancer is mainly in women. In reality, both sexes have the same rates of gene mutations and HBOC can predispose to other cancers including prostate cancer and pancreatic cancer. For this reason, the term "King syndrome" has recently come into use </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 Punctate epithelial erosions 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 Retinitis pigmentosa and explain in detail? [/INST] Retinitis pigmentosa (RP) is a genetic disorder of the eyes that causes loss of vision. Symptoms include trouble seeing at night and decreasing peripheral vision (side and upper or lower visual field). As peripheral vision worsens, people may experience "tunnel vision". Complete blindness is uncommon. Onset of symptoms is generally gradual and often begins in childhood.Retinitis pigmentosa is generally inherited from one or both parents or rarely it can be newly evolved from a miscoding during DNA division. It is caused by genetic miscoding of proteins in one of more than 300 genes involved. The underlying mechanism involves the progressive loss of rod photoreceptor cells that line the retina of the eyeball. The rod cells secrete a neuroprotective substance (Rod-derived cone viability factor, RdCVF) that protects the cone cells from apoptosis (cell death).  However, when the rod cells die, this substance is no longer provided. This is generally followed by the loss of cone photoreceptor cells. Diagnosis is by eye examination of the retina finding dark pigment deposits caused by the rupture of the underlying retinal pigmented epithelial cells, given that these cells contain a pigment known as melanin. Other supportive testing may include the electroretinogram (ERG), visual field testing (VFT), ocular coherence tomography (OCT) and DNA testing to determine the gene responsible for a persons particular type of RP (now called Inherited Retinal Dystrophy (IRD).There is currently no cure for retinitis pigmentosa. Efforts to manage the problem may include the use of low vision aids, portable lighting, or orientation and mobility training. Vitamin A palmitate supplements may be useful to slow worsening. A visual prosthesis may be an option in certain people with severe disease.Currently there is only one FDA-approved gene therapy that is commercially available to RP patients with Leber congenital amaurosis type 2. It replaces the miscoded RPE65 protein that is produced within the retinal pigmented epithelium. It has been found to effectively work in about 50% of the patients who receive the therapy. The earlier the child receives the RPE65 therapy the better the chances for a positive outcome. There are many other therapies being researched at this time with the goal of being approved in the next few years.
It is estimated to affect 1 in 4,000 people.

Signs and symptoms
The initial retinal degenerative symptoms of retinitis pigmentosa are characterized by decreased night vision (nyctalopia) and the loss of the mid-peripheral visual field. The rod photoreceptor cells, which are responsible for low-light vision and are orientated mainly in the retinal periphery, are the retinal processes affected first during non-syndromic (without other conditions) forms of this disease. Visual decline progresses relatively quickly to the far peripheral field, eventually extending into the central visual field as tunnel vision increases. Visual acuity and color vision can become compromised due to accompanying loss of the cone photoreceptor cells, which are responsible for color vision, visual acuity, and sight in the central visual field. The progression of disease occurs in both eyes in a similar but not identical pattern.
A variety of indirect symptoms characterize retinitis pigmentosa along with the direct effects of the initial rod photoreceptor degeneration and later cone photoreceptor decline. Phenomena such as photophobia, which describes the event in which light is perceived as an intense glare, and photopsia, the presence of blinking, swirling or shimmering lights spontaneously occurring within the visual field, often manifest during the later stages of RP. Findings related to RP have often been characterized in the fundus (back layer) of the eye as the "ophthalmic triad". This includes the development of (1) a mottled appearance of the retina and retinal pigment epithelium (RPE) that gives the same visual appearance of Bone Spicule patterns (but are not Bone Spicules), (2) a waxy yellow appearance of the optic disk, and (3) the attenuation of blood vessels in size and Arterial/Venous ratio as they enter and exit the Optic Disk of the retina and transverse it.Non-syndromic RP (RP appears alone without other co-morbidities) usually presents a variety of the following symptoms:
Night blindness
Tunnel vision (due to loss of peripheral vision)
Latticework vision(due to patchy loss of peripheral vision)

loss of depth perception
Photopsia (Spontaneously occurring flashes/blinking/swirling/shimmering lights)
Photophobia (aversion to bright lights)
Development of the appearance of melanin pigment in a bone spicule pattern in the fundus (not bone tissue)
Slow adjustment from dark to light environments and vice versa
Blurring of vision
Poor color separation
Loss of central vision is the last to go, because this is a disease of the rods and not the cones which are the highest in number in the Central Vision (Macula and Fovea)
Eventual blindness (legally defined as 20 degrees or less in the best seeing eye or visual acuity of 20/200 or worse. Majority of patients do not go totally Blind, they quite often retain limited non-functional vision.

Causes
RP may be:
(1) non-syndromic, that is, it occurs alone, without any other clinical findings,
(2) syndromic, with other neurosensory disorders, developmental abnormalities, or complex clinical findings, or
(3) secondary to other systemic diseases.
RP combined with deafness (congenital or progressive) is called Usher syndrome.
Alports syndrome is associated with RP and an abnormal glomerular-basement membrane leading to nephrotic syndrome. It is inherited as X-linked dominant.
RP combined with ophthalmoplegia, dysphagia, ataxia, and cardiac conduction defects is seen in the mitochondrial DNA disorder Kearns–Sayre syndrome (also known as Ragged Red Fiber Myopathy)
RP combined with retardation, peripheral neuropathy, acanthotic (spiked) RBCs, ataxia, steatorrhea, and absence of VLDL is seen in abetalipoproteinemia.
RP is seen clinically in association with several other rare genetic disorders (including muscular dystrophy and chronic granulomatous disease) as part of McLeod syndrome. This is an X-linked recessive phenotype characterized by a complete absence of XK cell surface proteins, and therefore markedly reduced expression of all Kell red blood cell antigens. For transfusion purposes, these patients are considered completely incompatible with all normal and K0/K0 donors.
RP associated with hypogonadism, and developmental delay with an autosomal recessive inheritance pattern is seen with Bardet–Biedl syndromeOther conditions include neurosyphilis, toxoplasmosis and Refsums disease.

Genetics
Retinitis pigmentosa (RP) is one of the most common forms of inherited retinal degeneration.There are multiple genes that code for proteins needed in the visual pathway, when mutated, they can cause the retinitis pigmentosa phenotype. Inheritance patterns of RP have been identified as autosomal dominant, autosomal recessive, X-linked, and maternally (mitochondrially) acquired, and are dependent on the specific RP gene mutations present in the parental generation.  (Of note, Autosomal Dominant RP Type 11 (PRPF-31) can be inherited as a genotype only, because of incomplete penetrance, thus coded for in the DNA but, does not manifest the disease as a phenotype.)  In 1989, a mutation of the gene for rhodopsin, a pigment that plays an essential part in the visual transduction cascade enabling vision in low-light conditions, was identified. The rhodopsin gene encodes a principal protein of photoreceptor outer segments. Mutations in this gene most commonly presents as missense mutations or misfolding of the rhodopsin protein, and most frequently follow autosomal dominant inheritance patterns. Since the discovery of the rhodopsin gene, more than 100 RHO mutations have been identified, accounting for 15% of all types of retinal degeneration, and approximately 25% of autosomal dominant forms of RP.Over 100 mutations have been reported to date in the opsin gene associated with the RP since the Pro23His mutation in the intradiscal domain of the protein was first reported in 1990. These mutations are found throughout the opsin gene and are distributed along the three domains of the protein (the intradiscal, transmembrane, and cytoplasmic domains). One of the main biochemical causes of RP in the case of rhodopsin mutations is protein misfolding, and the disruption of molecular chaperones. It was found that the mutation of codon 23 in the rhodopsin gene, in which proline is changed to histidine, accounts for the largest fraction of rhodopsin mutations in the United States. Several other studies have reported various codon mutations associated with retinitis pigmentosa, including Thr58Arg, Pro347Leu, Pro347Ser, as well as deletion of Ile-255. In 2000, a rare mutation in codon 23 was reported causing autosomal dominant retinitis pigmentosa, in which proline changed to alanine. However, this study showed that the retinal dystrophy associated with this mutation was characteristically mild in presentation and course. Furthermore, there was greater preservation in electroretinography amplitudes than the more prevalent Pro23His mutation.Autosomal recessive inheritance patterns of RP have been identified in at least 45 genes. This means that two unaffected individuals who are carriers of the same RP-inducing gene mutation in diallelic form can produce offspring with the RP phenotype. A mutation on the USH2A gene is known to cause 10-15% of a syndromic form of RP known as Ushers Syndrome when inherited in an autosomal recessive fashion.Mutations in four pre-mRNA splicing factors are known to cause autosomal dominant retinitis pigmentosa. These are PRPF3 (human PRPF3 is HPRPF3; also PRP3), PRPF8, PRPF31 and PAP1. These factors are ubiquitously expressed and it is proposed that defects in a ubiquitous factor (a protein expressed everywhere) should only cause disease in the retina because the retinal photoreceptor cells have a far greater requirement for protein processing (rhodopsin) than any other cell type.The somatic, or X-linked inheritance patterns of RP are currently identified with the mutations of six genes, the most common occurring at specific loci in the RPGR and RP2 genes.Types include:

Pathophysiology
A variety of retinal molecular pathway defects have been matched to multiple known RP gene mutations. Mutations in the rhodopsin gene (RHO), which is responsible for the majority of autosomal-dominantly inherited RP cases, disrupts the rhodopsin protein essential for translating light into decipherable electrical signals within the phototransduction cascade of the central nervous system. Defects in the activity of this G-protein-coupled receptor are classified into distinct classes that depend on the specific folding abnormality and the resulting molecular pathway defects. The Class I mutant proteins activity is compromised as specific point mutations in the protein-coding amino acid sequence affect the pigment proteins transport to the outer segment of the eye, where the phototransduction cascade is localized. Additionally, the misfolding of Class II rhodopsin gene mutations disrupts the proteins conjunction with 11-cis-retinal to induce proper chromophore formation. Additional mutants in this pigment-encoding gene affect protein stability, disrupt mRNA integrity post-translationally, and affect the activation rates of transducin and opsin optical proteins.Additionally, animal models suggest that the retinal pigment epithelium fails to phagocytose the outer rod segment discs that have been shed, leading to an accumulation of outer rod segment debris. In mice that are homozygous recessive for retinal degeneration mutation, rod photoreceptors stop developing and undergo degeneration before cellular maturation completes. A defect in cGMP-phosphodiesterase has also been documented; this leads to toxic levels of cGMP.

Diagnosis
An accurate diagnosis of retinitis pigmentosa relies on the documentation of the progressive loss of photoreceptor cell function, confirmed by a combination of visual field and visual acuity tests, fundus and optical coherence imagery, and electroretinography (ERG).Visual field and acuity tests measure and compare the size of the patients field of vision and the clarity of their visual perception with the standard visual measurements associated with healthy 20/20 vision. Clinical diagnostic features indicative of retinitis pigmentosa include a substantially small and progressively decreasing visual area in the visual field test, and compromised levels of clarity measured during the visual acuity test. Additionally, optical tomography such as fundus and retinal (optical coherence) imagery provide further diagnostic tools when determining an RP diagnosis. Photographing the back of the dilated eye allows the confirmation of bone spicule accumulation in the fundus, which presents during the later stages of RP retinal degeneration. Combined with cross-sectional imagery of optical coherence tomography, which provides clues into photoreceptor thickness, retinal layer morphology, and retinal pigment epithelium physiology, fundus imagery can help determine the state of RP progression.While visual field and acuity test results combined with retinal imagery support the diagnosis of retinitis pigmentosa, additional testing is necessary to confirm other pathological features of this disease. Electroretinography (ERG) confirms the RP diagnosis by evaluating functional aspects associated with photoreceptor degeneration, and can detect physiological abnormalities before the initial manifestation of symptoms. An electrode lens is applied to the eye as photoreceptor response to varying degrees of quick light pulses is measured. Patients exhibiting the retinitis pigmentosa phenotype would show decreased or delayed electrical response in the rod photoreceptors, as well as possibly compromised cone photoreceptor cell response.
The patients family history is also considered when determining a diagnosis due to the genetic mode of inheritance of retinitis pigmentosa. At least 35 different genes or loci are known to cause "nonsyndromic RP" (RP that is not the result of another disease or part of a wider syndrome). Indications of the RP mutation type can be determine through DNA testing, which is available on a clinical basis for:

RLBP1 (autosomal recessive, Bothnia type RP)
RP1 (autosomal dominant, RP1)
RHO (autosomal dominant, RP4)
RDS (autosomal dominant, RP7)
PRPF8 (autosomal dominant, RP13)
PRPF3 (autosomal dominant, RP18)
CRB1 (autosomal recessive, RP12)
ABCA4 (autosomal recessive, RP19)
RPE65 (autosomal recessive, RP20)For all other genes (e.g. DHDDS), molecular genetic testing is available on a research basis only.
RP can be inherited in an autosomal dominant, autosomal recessive, X-linked or Y-linked manner. X-linked RP can be either recessive, affecting primarily only males, or dominant, affecting both males and females, although males are usually more mildly affected. Some digenic (controlled by two genes) and mitochondrial forms have also been described.
Genetic counseling depends on an accurate diagnosis, determination of the mode of inheritance in each family, and results of molecular genetic testing.

Treatment
There is currently no cure for retinitis pigmentosa, but the efficacy and safety of various prospective treatments are currently being evaluated. The efficiency of various supplements, such as vitamin A, DHA, NAC, and lutein, in delaying disease progression remains an unresolved, yet prospective treatment option. Clinical trials investigating optic prosthetic devices, gene therapy mechanisms, and retinal sheet transplantations are active areas of study in the partial restoration of vision in retinitis pigmentosa patients.

Stalling of disease
Studies have demonstrated the delay of rod photoreceptor degeneration by the daily intake of 15000 IU (equivalent to 4.5 mg) of vitamin A palmitate; thus, stalling disease progression in some patients. Recent investigations have shown that proper vitamin A supplementation can postpone blindness by up to 10 years (by reducing the 10% loss pa to 8.3% pa) in some patients in certain stages of the disease.

Bone marrow derived stem cells (BMSC)
MD Stem Cells, a clinical research company using autologous bone marrow derived stem cells (BMSC) in the treatment of retinal and optic nerve disease, published results from the Retinitis Pigmentosa cohort within their ongoing NIH registered Stem Cell Ophthalmology Study II (SCOTS2) clinical trial (NCT 03011541). Outcomes were encouraging with 45.5% of eyes showing an average of 7.9 lines of improvement (40.9% LogMAR improvement over baseline) and 45.5% of eyes showing stable acuity over the follow up. Results were statistically significant(p=0.016). Retinitis Pigmentosa continues to be treated and evaluated in the study.

Argus retinal prosthesis
The Argus retinal prosthesis became the first approved treatment for the disease in February 2011, and is currently available in Germany, France, Italy, and the UK. Interim results on 30 patients long term trials were published in 2012. The Argus II retinal implant has also received market approval in the US. The device may help adults with RP who have lost the ability to perceive shapes and movement to be more mobile and to perform day-to-day activities. In June 2013, twelve hospitals in the US announced they would soon accept consultation for patients with RP in preparation for the launch of Argus II later that year. The Alpha-IMS is a subretinal implant involving the surgical implantation of a small image-recording chip beneath the optic fovea. Measures of visual improvements from Alpha-IMS studies require the demonstration of the devices safety before proceeding with clinical trials and granting market approval.

Gene therapy
The goal of gene therapy studies is to virally supplement retinal cells expressing mutant genes associated with the retinitis pigmentosa phenotype with healthy forms of the gene; thus, allowing the repair and proper functioning of retinal photoreceptor cells in response to the instructions associated with the inserted healthy gene. Clinical trials investigating the insertion of the healthy RPE65 gene in retinas expressing the LCA2 retinitis pigmentosa phenotype measured modest improvements in vision; however, the degradation of retinal photoreceptors continued at the disease-related rate. Likely, gene therapy may preserve remaining healthy retinal cells while failing to repair the earlier accumulation of damage in already diseased photoreceptor cells. Response to gene therapy would theoretically benefit young patients exhibiting the shortest progression of photoreceptor decline; thus, correlating to a higher possibility of cell rescue via the healthy inserted gene.

Drugs
Drug named Disulfiram has shown reversing of the disease in rats.

Prognosis
The progressive nature of and lack of a definitive cure for retinitis pigmentosa contribute to the inevitably discouraging outlook for patients with this disease. While complete blindness is rare, the persons visual acuity and visual field will continue to decline as initial rod photoreceptor and later cone photoreceptor degradation proceeds.Studies indicate that children carrying the disease genotype benefit from presymptomatic counseling in order to prepare for the physical and social implications associated with progressive vision loss. While the psychological prognosis can be slightly alleviated with active counseling the physical implications and progression of the disease depend largely on the age of initial symptom manifestation and the rate of photoreceptor degradation, rather than access to prospective treatments. Corrective visual aids and personalized vision therapy provided by Low Vision Specialists may help patients correct slight disturbances in visual acuity and optimize their remaining visual field. Support groups, vision insurance, and lifestyle therapy are additional useful tools for those managing progressive visual decline.

Epidemiology
Retinitis pigmentosa is the leading cause of inherited blindness, with approximately 1/4,000 individuals experiencing the non-syndromic form of their disease within their lifetime. It is estimated that 1.5 million people worldwide are currently affected. Early onset RP occurs within the first few years of life and is typically associated with syndromic disease forms, while late onset RP emerges from early to mid-adulthood.
Autosomal dominant and recessive forms of retinitis pigmentosa affect both male and female populations equally; however, the less frequent X-linked form of the disease affects male recipients of the X-linked mutation, while females usually remain unaffected carriers of the RP trait. The X-linked forms of the disease are considered severe, and typically lead to complete blindness during later stages. In rare occasions, a dominant form of the X-linked gene mutation will affect both males and females equally.Due to the genetic inheritance patterns of RP, many isolate populations exhibit higher disease frequencies or increased prevalence of a specific RP mutation. Pre-existing or emerging mutations that contribute to rod photoreceptor degeneration in retinitis pigmentosa are passed down through familial lines; thus, allowing certain RP cases to be concentrated to specific geographical regions with an ancestral history of the disease. Several hereditary studies have been performed to determine the varying prevalence rates in Maine (USA), Birmingham (England), Switzerland (affects 1/7000), Denmark (affects 1/2500), and Norway </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 Metabolic acidosis and explain in detail? [/INST] Metabolic acidosis is a serious electrolyte disorder characterized by an imbalance in the bodys acid-base balance. Metabolic acidosis has three main root causes: increased acid production, loss of bicarbonate, and a reduced ability of the kidneys to excrete excess acids. Metabolic acidosis can lead to acidemia, which is defined as arterial blood pH that is lower than 7.35. Acidemia and acidosis are not mutually exclusive – pH and hydrogen ion concentrations also depend on the coexistence of other acid-base disorders; therefore, pH levels in people with metabolic acidosis can range from low to high.
Acute metabolic acidosis, lasting from minutes to several days, often occurs during serious illnesses or hospitalizations, and is generally caused when the body produces an excess amount of organic acids (ketoacids in ketoacidosis, or lactic acid in lactic acidosis). A state of chronic metabolic acidosis, lasting several weeks to years, can be the result of impaired kidney function (chronic kidney disease) and/or bicarbonate wasting. The adverse effects of acute versus chronic metabolic acidosis also differ, with acute metabolic acidosis impacting the cardiovascular system in hospital settings, and chronic metabolic acidosis affecting muscles, bones, kidney and cardiovascular health.

Signs and symptoms
Acute metabolic acidosis
Symptoms are not specific, and diagnosis can be difficult unless patients present with clear indications for arterial blood gas sampling. Symptoms may include palpitations, headache, altered mental status such as severe anxiety due to hypoxia, decreased visual acuity, nausea, vomiting, abdominal pain, altered appetite and weight gain, muscle weakness, bone pain, and joint pain. People with acute metabolic acidosis may exhibit deep, rapid breathing called Kussmaul respirations which is classically associated with diabetic ketoacidosis. Rapid deep breaths increase the amount of carbon dioxide exhaled, thus lowering the serum carbon dioxide levels, resulting in some degree of compensation. Overcompensation via respiratory alkalosis to form an alkalemia does not occur.
Extreme acidemia can also lead to neurological and cardiac complications:

Neurological: lethargy, stupor, coma, seizures
Cardiac: Abnormal heart rhythms (e.g., ventricular tachycardia) and decreased response to epinephrine, both leading to low blood pressurePhysical examination can occasionally reveal signs of the disease, but is often otherwise normal. Cranial nerve abnormalities are reported in ethylene glycol poisoning, and retinal edema can be a sign of methanol intoxication.

Chronic metabolic acidosis
Chronic metabolic acidosis has non-specific clinical symptoms but can be readily diagnosed by testing serum bicarbonate levels in patients with Chronic Kidney Disease (CKD) as part of a comprehensive metabolic panel. Patients with CKD Stages G3-G5 should be routinely screened for metabolic acidosis.

Diagnostic approach and causes
Metabolic acidosis is defined as a reduced serum pH, and an abnormal serum bicarbonate concentration of <22 mEq/L, below the normal range of 22 to 29 mEq/L. However, if a patient has other coexisting acid-base disorders, the pH level may be low, normal or high in the setting of metabolic acidosis. In the absence of chronic respiratory alkalosis, metabolic acidosis can be clinically diagnosed by measuring serum bicarbonate levels in the blood, which is generally a standard component of blood panels. Imperatively, when weighing a metabolic acidosis diagnosis, the change in serum bicarbonate levels over time should be considered; if baseline bicarbonate results are unknown, a single set of values may be misinterpreted.

Causes
Generally, metabolic acidosis occurs when the body produces too much acid (e.g., lactic acidosis, see below section), there is a loss of bicarbonate from the blood, or when the kidneys are not removing enough acid from the body.
Chronic metabolic acidosis is most often caused by a decreased capacity of the kidneys to excrete excess acids through renal ammoniagenesis. The typical Western diet generates 75-100 mEq of acid daily, and individuals with normal kidney function increase the production of ammonia to get rid of this dietary acid. As kidney function declines, the tubules lose the ability to excrete excess acid, and this results in buffering of acid using serum bicarbonate, as well as bone and muscle stores.There are many causes of acute metabolic acidosis, and thus it is helpful to group them by the presence or absence of a normal anion gap.
Increased anion gap
Causes of increased anion gap include:

Lactic acidosis
Ketoacidosis (e.g., Diabetic, alcoholic, or starvation)
Chronic kidney failure
Transient 5-oxoprolinemia due to long-term ingestion of high-doses of acetaminophen (often seen with sepsis, liver failure, kidney failure, or malnutrition)
Intoxication:
Salicylates, methanol, ethylene glycol
Organic acids, paraldehyde, ethanol, formaldehyde
Carbon monoxide, cyanide, ibuprofen, metformin
Propylene glycol (metabolized to L and D-lactate and is often found in infusions for certain intravenous medications used in the intensive care unit)
Massive rhabdomyolysis
Isoniazid, iron, phenelzine, tranylcypromine, valproic acid, verapamil
Topiramate
SulfatesNormal anion gap
Causes of normal anion gap include
Inorganic acid addition
Infusion/ingestion of HCl, NH4Cl
Gastrointestinal base loss
Diarrhea
Small bowel fistula/drainage
Surgical diversion of urine into gut loops
Renal base loss/acid retention:
Proximal renal tubular acidosis
Distal renal tubular acidosisHyperalimentation
Addison disease
Acetazolamide
Spironolactone
Saline infusionTo distinguish between the main types of metabolic acidosis, a clinical tool called the anion gap is considered very useful. It is calculated by subtracting the sum of the chloride and bicarbonate levels from the sum of the sodium and potassium levels.
As sodium is the main extracellular cation, and chloride and bicarbonate are the main anions, the result should reflect the remaining anions. Normally, this concentration is about 8–16 mmol/L (12±4). An elevated anion gap (i.e. > 16 mmol/L) can indicate particular types of metabolic acidosis, such as types caused by certain poisons, lactate acidosis, and ketoacidosis. It is important to note that the anion gap can be spuriously normal in sampling errors of the sodium level, e.g. in extreme hypertriglyceridemia. The anion gap can also be increased due to relatively low levels of cations other than sodium and potassium (e.g. calcium or magnesium).As a differential diagnosis is made, other tests may be necessary, including toxicological screening and imaging of the kidneys, along with testing of electrolytes (including chloride), glucose, kidney function, and a full blood count. Urinalysis can reveal acidity (salicylate poisoning) or alkalinity (renal tubular acidosis type I). In addition, it can show ketones in ketoacidosis. It is also important to differentiate between acidosis-induced hyperventilation and asthma; otherwise, treatment could lead to inappropriate bronchodilation.

Pathophysiology
Compensatory mechanisms
Metabolic acidosis is characterized by a low concentration of bicarbonate (HCO−3), which can happen with increased generation of acids (such as ketoacids or lactic acid), excess loss of HCO−3 by the kidneys or gastrointestinal tract, or an inability to generate sufficient HCO−3. Thus demonstrating the importance of maintaining balance between acids and bases in the body for maintaining optimal functioning of organs, tissues and cells.
The body regulates the acidity of the blood by four buffering mechanisms.

Bicarbonate buffering system
Intracellular buffering by absorption of hydrogen atoms by various molecules, including proteins, phosphates and carbonate in bone.
Respiratory compensation. Hyperventilation will cause more carbon dioxide to be removed from the body and thereby increases pH.
Kidney compensation

Buffer
The decreased bicarbonate that distinguishes metabolic acidosis is therefore due to two separate processes: the buffer (from water and carbon dioxide) and additional renal generation. The buffer reactions are:

            H

              +

          +

            HCO

              3

              −

                      ↽

                      −

                      −

                      ⇀

            H

              2

            CO

              3

                      ↽

                      −

                      −

                      ⇀

            CO

              2

          +

            H

              2

          O

    {\displaystyle {\ce {H+ + HCO3- <=> H2CO3 <=> CO2 + H2O}}}
  The Henderson-Hasselbalch equation mathematically describes the relationship between blood pH and the components of the bicarbonate buffering system:

          pH

        =

            pK

            a

        +

            L
            o
            g

              [

                  HCO

                  3

                  −

              ]

              [

                  CO

                  2

              ]

    {\displaystyle {\text{pH}}={\text{pK}}_{a}+\mathop {\mathrm {Log} } {\frac {\left[{\text{HCO}}_{3}^{-}\right]}{\left[{\text{CO}}_{2}\right]}}}

Using Henrys law, we can say that [CO2] = 0.03 × PaCO2
(PaCO2 is the pressure of CO2 in arterial blood)
Adding the other normal values, we get

          pH

        =
        6.1
        +

            L
            o
            g

          [

              24

                0.03
                ×
                40

          ]

    {\displaystyle {\text{pH}}=6.1+\mathop {\mathrm {Log} } \left[{\frac {24}{0.03\times 40}}\right]}

        =
        6.1
        +
        1.3

    {\displaystyle =6.1+1.3}

        =
        7.4

    {\displaystyle =7.4}

Consequences
Acute Metabolic Acidosis
Acute Metabolic Acidosis most often occurs during hospitalizations, and acute critical illnesses. It is often associated with poor prognosis, with a mortality rate as high as 57% if the pH remains untreated at 7.20. At lower pH levels, acute metabolic acidosis can lead to impaired circulation and end organ function.

Chronic Metabolic Acidosis
Chronic metabolic acidosis commonly occurs in people with Chronic Kidney Disease with an eGFR of less than 45 ml/min/1.73m2, most often with mild to moderate severity; however, metabolic acidosis can manifest earlier on in the course of Chronic Kidney Disease. Multiple animal and human studies have shown that metabolic acidosis in Chronic Kidney Disease, given its chronic nature, has a profound adverse impact on cellular function, overall contributing to high morbidities in patients.
The most adverse consequences of chronic metabolic acidosis in people with Chronic Kidney Disease and in particular, for those who have end-stage renal disease (ESRD), are detrimental changes to the bones and muscles. Acid buffering leads to loss of bone density, resulting in an increased risk of bone fractures, renal osteodystrophy, and bone disease; as well, increased protein catabolism leads to muscle wasting. Furthermore, metabolic acidosis in Chronic Kidney Disease is also associated with a reduction in eGFR; it is both a complication of Chronic Kidney Disease, as well as an underlying cause of Chronic Kidney Disease progression.

Treatment
Treatment of metabolic acidosis depends on the underlying cause, and should target reversing the main process. When considering course of treatment, it is important to distinguish between acute versus chronic forms.

Acute Metabolic Acidosis
Bicarbonate therapy is generally administered In patients with severe acute acidemia (pH < 7.11), or with less severe acidemia (pH 7.1-7.2) who have severe acute kidney injury </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 Placental site nodule 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 Spondylosis and explain in detail? [/INST] Spondylosis is the degeneration of the vertebral column from any cause. In the more narrow sense it refers to spinal osteoarthritis, the age-related wear and tear of the spinal column, which is the most common cause of spondylosis. The degenerative process in osteoarthritis chiefly affects the vertebral bodies, the neural foramina and the facet joints (facet syndrome). If severe, it may cause pressure on the spinal cord or nerve roots with subsequent sensory or motor disturbances, such as pain, paresthesia, imbalance, and muscle weakness in the limbs.
When the space between two adjacent vertebrae narrows, compression of a nerve root emerging from the spinal cord may result in radiculopathy (sensory and motor disturbances, such as severe pain in the neck, shoulder, arm, back, or leg, accompanied by muscle weakness).  Less commonly, direct pressure on the spinal cord (typically in the cervical spine) may result in myelopathy, characterized by global weakness, gait dysfunction, loss of balance, and loss of bowel or bladder control. The patient may experience shocks (paresthesia) in hands and legs because of nerve compression and lack of blood flow. If vertebrae of the neck are involved it is labelled cervical spondylosis. Lower back spondylosis is labeled lumbar spondylosis. The term is from Ancient Greek σπόνδυλος spóndylos, "a vertebra", in plural "vertebrae – the backbone".

Signs and symptoms
Complications
A rare but severe complication of this disease is vertebrobasilar insufficiency. This is a result of the vertebral artery becoming occluded as it passes up in the transverse foramen. The spinal joints become stiff in cervical spondylosis. Thus the chondrocytes which maintain the disc become deprived of nutrition and die. Secondary osteophytes may cause stenosis for spinal nerves, manifesting as radiculopathy.

Causes
Spondylosis is caused from years of constant abnormal pressure, caused by joint subluxation, stress induced by sports, acute and/or repetitive trauma, or poor posture, being placed on the vertebrae and the discs between them.  The abnormal stress causes the body to form new bone in order to compensate for the new weight distribution.  This abnormal weight bearing from bone displacement will cause spondylosis to occur.  Poor postures and loss of the normal spinal curves can lead to spondylosis as well.  Spondylosis can affect a person at any age; however, older people are more susceptible.

Diagnosis
There are multiple techniques used in the diagnosis of spondylosis, these are;

Cervical Compression Test, a variant of Spurlings test, is performed by laterally flexing the patients head and placing downward pressure on it. Neck or shoulder pain on the ipsilateral side (i.e., the side to which the head is flexed) indicates a positive result for this test. A positive test result is not necessarily a positive result for spondylosis and as such additional testing is required.
Lhermitte sign: feeling of electrical shock with patient neck flexion
Reduced range of motion of the neck, the most frequent objective finding on physical examination
MRI and CT scans are helpful for pain diagnosis but generally are not definitive and must be considered together with physical examinations and history.

Treatment
Many of the treatments for cervical spondylosis have not been subjected to rigorous, controlled trials. Surgery is advocated for cervical radiculopathy in patients who have intractable pain, progressive symptoms, or weakness that fails to improve with conservative therapy. Surgical indications for cervical spondylosis with myelopathy (CSM) remain somewhat controversial, but "most clinicians recommend operative therapy over conservative therapy for moderate-to-severe myelopathy" (Baron, M. E.).
Physical therapy may be effective for restoring range of motion, flexibility and core strengthening. Decompressive therapies (i.e., manual mobilization, mechanical traction) may also help alleviate pain. However, physical therapy and osteopathy cannot "cure" the degeneration, and some people view that strong compliance with postural modification is necessary to realize maximum benefit from decompression, adjustments and flexibility rehabilitation.

Surgery
Current surgical procedures used to treat spondylosis aim to alleviate the signs and symptoms of the disease by decreasing pressure in the spinal canal (decompression surgery) and/or by controlling spine movement (fusion surgery).Decompression surgery: The vertebral column can be operated on from both an anterior and posterior approach. The approach varies depending on the site and cause of root compression. Commonly, osteophytes and portions of intervertebral disc are removed.Fusion surgery: Performed when there is evidence of spinal instability or mal-alignment </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 Xanthoma and explain in detail? [/INST]  </s>