<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 Olfactory reference syndrome and explain in detail? [/INST] Olfactory reference syndrome (ORS) is a psychiatric condition in which there is a persistent false belief and preoccupation with the idea of emitting abnormal body odors which the patient thinks are foul and offensive to other individuals. People with this condition often misinterpret others behaviors, e.g. sniffing, touching their nose or opening a window, as being referential to an unpleasant body odor which in reality is non-existent and cannot be detected by other people.This disorder is often accompanied by shame, embarrassment, significant distress, avoidance behavior, social phobia and social isolation.

Signs and symptoms
The onset of ORS may be sudden, where it usually follows after a precipitating event, or gradual.

Odor complaint
The defining feature of ORS is excessive thoughts of having offensive body odor(s) which are detectable to others. The individual may report that the odor comes from: the nose and/or mouth, i.e. halitosis (bad breath); the anus; the genitals; the skin generally; or specifically the groin, armpits or feet. The source(s) of the supposed odor may also change over time. There are also some who are unsure of the exact origin of the odor. The odor is typically reported to be continuously present. The character of the odor may be reported as similar to bodily substances, e.g. feces, flatus, urine, sweat, vomitus, semen, vaginal secretions; or alternatively it may be an unnatural, non-human or chemical odor, e.g. ammonia, detergent, rotten onions, burnt rags, candles, garbage, burning fish, medicines, old cheese. Again, the reported character of the odor complaint may change over time. Halitosis appears to be the most common manifestation of ORS, with 75% complaining of bad breath, alone or in combination with other odors. The next most common complaint was sweat (60%).Although all individuals with ORS believe they have an odor, in some cases the individual reports they cannot perceive the odor themselves. In the latter cases, the belief arises via misinterpretation of the behavior of others or with the rationale that a disorder of smell which prevents self detection of the odor (i.e. anosmia) exists. In the cases where the non-existent odor can be detected, this is usually considered as phantosmia (olfactory hallucination). Olfactory hallucination can be considered the result of the belief in an odor delusion, or the belief a result of the olfactory hallucination. In one review, the individual with ORS was unreservedly convinced that he or she could detect the odor themselves in 22% of cases, whilst in 19% there was occasional or intermittent detection and in 59% lack of self-detection was present.Some distinguish delusional and non-delusional forms of ORS. In the delusional type, there is complete conviction that the odor is real. In the non-delusional type, the individual is capable of some insight into the condition, and can recognize that the odor might not be real, and that their level of concern is excessive. Others argue that reported cases of ORS present a spectrum of different levels of insight. Since sometimes the core belief of ORS is not of delusional intensity, it is argued that considering the condition as a form of delusional disorder, as seems to occur in the DSM, is inappropriate. In one review, in 57% of cases the beliefs were fixed, held with complete conviction, and the individual could not be reassured that the odor was non existent. In 43% of cases the individual held the beliefs with less than complete conviction, and was able to varying degrees to consider the possibility that the odor was not existent.Other symptoms may be reported and are claimed to be related to the cause of the odor, such as malfunction of the anal sphincter, a skin disease, "diseased womb", stomach problems or other unknown organic disease. Excessive washing in ORS has been reported to cause the development of eczema.

Referential ideas
People with ORS misinterpret the behavior of others to be related to the imagined odor (thoughts of reference). In one review, ideas of reference were present in 74% of cases. Usually, these involve misinterpretations of comments, gestures and actions of other people such that it is believed that an offensive smell from the individual is being referred to. These thoughts of reference are more pronounced in social situations which the individual with ORS may find stressful, such as public transport, crowded lift, workplace, classroom, etc. Example behaviors which are misinterpreted include coughing, sneezing, turning of the head, opening a window, facial expressions, sniffing, touching nose, scratching head, gestures, moving away, avoiding the person, whistling. Commonly, when being in proximity to others who are talking among themselves, persons with ORS will be convinced that the conversation is about his or her odor. Even the actions of animals (e.g. barking of dogs) can be interpreted as referential to an odor. Persons with ORS may have trouble concentrating at a given task or in particular situations due to obsessive thoughts concerning body odor.

Repetitive behavior
95% of persons with ORS engage in at least one excessive hygiene, grooming or other related repetitive practice in an attempt to alleviate, mask and monitor the perceived odor. This has been described as a contrite reaction, and repetitive, counterphobic, "safety", ritual or compulsive behaviors. Despite these measures, the odor symptom is reported to still offend other people. Example ORS behaviors include: repetitive showering and other grooming behaviors, excessive tooth brushing, or tongue scraping (a treatment for halitosis), repeated smelling of oneself to check for any odor, over-frequent bathroom use, attempts to mask the odor, with excessive use of deodorants, perfumes, mouthwash, mint, chewing gum, scented candles, and soap; changing clothes (e.g. underwear), multiple times per day, frequent washing of clothes, wearing several layers of clothing, wrapping feet in plastic, wearing garments marketed as odor-reducing, eating special diets, dietary supplements (e.g. intended to reduce flatulence odor), repeatedly seeking reassurance from others that there is no odor, although the negative response is usually interpreted instead as politeness rather than truth, and avoidance behaviors such as habitually sitting at a distance from others, minimizing movement in an attempt "not to spread the odor", keeping the mouth closed and avoiding talking or talking with a hand in front of the mouth.

Functional impairment
Persons with ORS tend to develop a behavior pattern of avoidance of social activities and progressive social withdrawal. They often avoid travel, dating, relationships, break off engagements and avoid family activities. Due to shame and embarrassment, they may avoid school or work, or repeatedly change jobs and move to another town. Significant developments may occur such as loss of employment, divorce, becoming housebound, psychiatric hospitalization, and suicide attempts. According to some reports, 74% of persons with ORS avoid social situations, 47% avoid work, academic or other important activities, 40% had been housebound for at least one week because of ORS, and 31.6% had experienced psychiatric hospitalization. With regards to suicide, reports range from 43 to 68% with suicidal ideation, and 32% with a history of at least one suicide attempt. 5.6% died by suicide.

Psychiatric co-morbidity
Psychiatric co-morbidity in ORS is reported. Depression, which is often severe, may be a result of ORS, or may be pre-existing. Personality disorders, especially cluster C, and predominantly the avoidant type, may exist with ORS.   Bipolar disorder, schizophrenia, hypochondriasis, alcohol or drug abuse and obsessive compulsive disorder may also be co-morbid with ORS.

Causes
The causes of ORS are unknown. It is thought that significant negative experiences may trigger the development of ORS. These have been considered as two types: key traumatic experiences related to smell, and life stressors present when the condition developed but which were unrelated to smell. In one review, 85% of reported cases had traumatic, smell-related experiences, and 17% of cases had stress factors unrelated to smell. Reported smell-related experiences usually revolve around family members, friends, co-workers, peers or other people making comments about an odor from the person, which causes embarrassment and shame. Examples include accusation of flatulence during a religious ceremony, or being bullied for flatulence such at school, accidental urination in class, announcements about a passenger needing to use deodorant over speaker by a driver on public transport, sinusitis which caused a bad taste in the mouth, mockery about a fish odor from a finger which had been inserted into the persons vagina in the context of a sexual assault, and revulsion about menarche and brothers sexual intimacy. It has been suggested that a proportion of such reported experiences may not have been real, but rather early symptom of ORS (i.e. referential thoughts). Examples of non smell-related stressful periods include guilt due to a romantic affair, being left by a partner, violence in school, family illness when growing up (e.g. cancer), and bullying.The importance of a family history of mental illness or other conditions in ORS is unclear, because most reported cases have lacked this information. In some cases, there has been reported psychiatric and medical conditions in first degree relatives such as schizophrenia, psychosis, alcoholism, suicide, affective disorders, obsessive compulsive disorder, anxiety, paranoia, neurosis, sociopathy, and epilepsy. Sometimes more than one family member had a noteworthy condition.Neuroimaging has been used to investigate ORS. Hexamethylpropyleneamine oxime single-photon emission computed tomography (HMPAO SPECT) demonstrated hypoperfusion of the frontotemporal lobe in one case. That is to say, part of the brain was receiving insufficient blood flow. In another, functional magnetic resonance imaging was carried out while the person with ORS listened to both neutral words and emotive words. Compared to an age and sex matched healthy control subject under the same conditions, the individual with ORS showed more activation areas in the brain when listening to emotionally loaded words. This difference was described as abnormal, but less pronounced as would be observed in the brain of a person with a psychotic disorder.

Diagnosis
Classification
Although the existence of ORS is generally accepted, there is some controversy as to whether it is a distinct condition or merely a part or manifestation of other psychiatric conditions, mainly due to the overlapping similarities. Similarly, there is controversy with regards how the disorder should be classified. As ORS has obsessive and compulsive features, some consider it as a type of obsessive–compulsive spectrum disorder, while others consider it an anxiety disorder due to the strong anxiety component. It is also suggested to be a type of body dysmorphic disorder or, as it involves a single delusional belief, some suggest that ORS is a monosymptomatic hypochondriacal psychosis (hypochondriacal type of delusional disorder, see monothematic delusion).The World Health Organizations 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) does not have a specific entry for ORS, or use the term, but in the "persistent delusional disorders" section, states delusions can "express a conviction that others think that they smell."ORS has also never been allocated a dedicated entry in any edition of the American Psychiatric Associations Diagnostic and Statistical Manual of Mental Disorders. In the third edition (DSM-III), ORS was mentioned under "atypical somatoform disorders". The revised third edition (DSM-III-R) mentions ORS in the text, stating that "convictions that the person emits a foul odor are one of the most common types of delusion disorder, somatic type." The fourth edition (DSM-IV), does not use the term ORS but again mentions such a condition under "delusional disorder, somatic type", stating "somatic delusions can occur in several forms. Most common are the persons conviction that he or she emits a foul odor from the skin, mouth, rectum or vagina." In the fifth edition (DSM-5), ORS again does not appear as a distinct diagnosis, but it is mentioned in relation to taijin kyōfushō (対人恐怖症, "disorder of fear of personal interaction"). The variants of taijin kyōfushō (shubo-kyofu "the phobia of a deformed body" and jikoshu-kyofu "fear of foul body odor") are listed under 300.3 (F42) "other specified obsessive compulsive and related disorders", and is about someones fear that his or her body, or its functions, is offensive to other people. There are four subtypes of taijin kyōfushō. 17% of these individuals have "the phobia of having foul body odor", the subtype termed jikoshu-kyofu. Although taijin kyōfushō has been described as a culture-bound syndrome confined to east Asia (e.g. Japan and Korea), it has been suggested that the jikoshu-kyofu variant of taijin kyōfushō is closely related or identical to ORS, and that such a condition occurs in other cultures. However, some Western sources state that jikoshu-kyofu and ORS are distinguishable because of cultural differences, i.e. Western culture being primarily concerned with individual needs, and Japanese culture primarily with the needs of the many. Hence, it is claimed that ORS mainly focuses on the affected individuals embarrassment, and jikoshu-kyofu is focused on the fear of creating embarrassment in others. In this article, jikoshu-kyofu and ORS are considered as one condition.
Synonyms for ORS, many historical, include bromidrosiphobia, olfactory phobic syndrome, chronic olfactory paranoid syndrome, autodysomophobia, delusions of bromosis, hallucinations of smell and olfactory delusional syndrome. By definition, the many terms which have been suggested in the dental literature to refer to subjective halitosis complaints (i.e. when a person complains of halitosis yet no odor is detectable clinically) can also be considered under the umbrella of ORS. Examples include halitophobia, non-genuine halitosis, delusional halitosis, pseudo-halitosis, imaginary halitosis, psychosomatic halitosis, and self halitosis.

Diagnostic criteria
Diagnostic criteria have been proposed for ORS:
Persistent (more than six months), false belief that one emits an offensive odor, which is not perceived by others. There may be degrees of insight (i.e. the belief may or may not be of delusional intensity).
This pre-occupation causes clinically significant distress (depression, anxiety, shame), social and occupational disability, or may be time-consuming (i.e. preoccupies the individual at least one hour per day).
The belief is not a symptom of schizophrenia or other psychotic disorder, and not due to the effects of medication or recreational drug abuse, or any other general medical condition.

Differential diagnosis
The differential diagnosis for ORS may be complicated as the disorder shares features with other conditions. Consequently, ORS may be misdiagnosed as another medical or psychiatric condition and vice versa.
The typical history of ORS involves a long delay while the person continues to believe there is a genuine odor. On average, a patient with ORS goes undiagnosed for about eight years. Repeated consultation with multiple different non-psychiatric medical specialists ("doctor shopping") in an attempt to have their non-existent body odor treated is frequently reported. Individuals with ORS may present to dermatologists, gastroentrologists, otolaryngologists, dentists, proctologists, and gynecologists. Despite the absence of any clinically detectable odor, physicians and surgeons may embark on unnecessary investigations (e.g. gastroscopy), and treatments, including surgery such as, among others, thoracic sympathectomy and tonsillectomy Such treatments generally have no long-term effect on the individuals belief in an odor symptom. If non-psychiatric clinicians refuse to carry out treatment on the basis that there is no real odor and offer to refer the patient to a psychologist or psychiatrist, persons with ORS typically refuse and instead seek "a better" doctor or dentist.Conversely, some have suggested that medical conditions which cause genuine odor may sometimes be misdiagnosed as ORS. There are a great many different medical conditions which are reported to potentially cause a genuine odor, and these are usually considered according to the origin of the odor, e.g. halitosis (bad breath), bromhidrosis (body odor), etc. These conditions are excluded before a diagnosis of ORS is made. Although there are many different publications on topics like halitosis, the symptom is still poorly understood and managed in practice. It is recognized that symptoms such as halitosis can be intermittent, and therefore may not be present at the time of the consultation, leading to misdiagnosis. Individuals with genuine odor symptoms may present with similar mindset and behavior to persons with ORS. For example, one otolaryngologist researcher noted "behavioral problems such as continuous occupation with oral hygiene issues, obsessive use of cosmetic breath freshening products such as mouthwashes, candies, chewing gums, and sprays, avoiding close contact with other people, and turning the head away during conversation" as part of what was termed "skunk syndrome" in patients with genuine halitosis secondary to chronic tonsillitis. Another author, writing about halitosis, noted that there are generally three types of persons that complain of halitosis: those with above-average odor, those with average or near-average odor who are oversensitive, and those with below-average or no odor who believe they have offensive breath. Therefore, in persons with genuine odor complaints, the distress and concern may typically be out of proportion to the reality of the problem. Genuine halitosis has been described as a social barrier between the individual and friends, relatives, partners and colleagues, and may negatively alter self-esteem and quality of life. Similar psychosocial problems are reported in other conditions which cause genuine odor symptoms. In the literature on halitosis, emphasis is frequently placed on multiple consultations to reduce the risk of misdiagnosis, and also asking the individual to have a reliable confidant accompany them to the consultation who can confirm the reality of the reported symptom. ORS patients are unable to provide such confidants as they have no objective odor.Various organic diseases may cause parosmias (distortion of the sense of smell). Also, since smell and taste are intimately linked senses, disorders of gustation (e.g. dysgeusia—taste dysfunction) can present as a complaint related to smell, and vice versa. These conditions, collectively termed chemosensory dysfunctions, are many and varied, and they may trigger a person to complain of an odor than is not present; however, the diagnostic criteria for ORS require the exclusion of any such causes. They include pathology of the right hemisphere of the brain, substance abuse, arteriovenous malformations in the brain, and temporal lobe epilepsy.Social anxiety disorder (SAD) and ORS have some demographic and clinical similarities. Where the social anxiety and avoidance behavior is primarily focussed on concern about body odors, ORS is a more appropriate diagnosis than avoidant personality disorder or SAD. Body dismorphic disorder (BDD) has been described as the closest diagnosis in DSM-IV to ORS as both primarily focus on bodily symptoms. The defining difference between the two is that in BDD the preoccupation is with physical appearance, not body odors. Similarly, where obsessive behaviors are directly and consistently related to body odors rather than anything else, ORS is a more appropriate diagnosis than obsessive–compulsive disorder, in which obsessions are different and multiple over time.ORS may be misdiagnosed as schizophrenia. About 13% of people with schizophrenia have olfactory hallucinations. Generally, schizophrenic hallucinations are perceived as having an imposed, external origin, while in ORS they are recognized as originating from the individual. The suggested diagnostic criteria mean that the possibility of ORS is negated by a diagnosis of schizophrenia in which persistent delusions of an offensive body odor and olfactory hallucinations are contributing features for criterion A. However, some reported ORS cases were presented as co-morbid. Indeed, some have suggested that ORS may in time transform into schizophrenia, but others state there is little evidence for this. Persons with ORS have none of the other criteria to qualify for a diagnosis of schizophrenia.It has been suggested that various special investigations may be indicated to help rule out some of the above conditions. Depending upon the case, this might include neuroimaging, thyroid and adrenal hormone tests, and analysis of body fluids (e.g. blood) with gas chromatography.

Treatment
There is no agreed treatment protocol. In most reported cases of ORS the attempted treatment was antidepressants, followed by antipsychotics and various psychotherapies. Little data are available regarding the efficacy of these treatments in ORS, but some suggest that psychotherapy yields the highest rate of response to treatment, and that antidepressants are more efficacious than antipsychotics (response rates 78%, 55% and 33% respectively). According to one review, 43% of cases which showed overall improvement required more than one treatment approach, and in only 31% did the first administered treatment lead to some improvement.Pharmacotherapies that have been used for ORS include antidepressants, (e.g. selective serotonin reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors), antipsychotics, (e.g. blonanserin, lithium, chlorpromazine), and benzodiazepines. The most common treatment used for ORS is SSRIs. Specific antidepressants that have been used include clomipramine.Psychotherapies that have been used for ORS include cognitive behavioral therapy, eye movement desensitization and reprocessing. Dunne (2015) reported a Case Study treatment of ORS using EMDR which was successful using  a trauma model formulation rather than an OCD approach.

Prognosis
When untreated, the prognosis for ORS is generally poor. It is chronic, lasting many years or even decades with worsening of symptoms rather than spontaneous remission. Transformation to another psychiatric condition is unlikely, although very rarely what appears to be ORS may later manifest into schizophrenia, psychosis, mania, or major depressive disorder. The most significant risk is suicide.
When treated, the prognosis is better. In one review, the proportion of treated ORS cases which reported various outcomes were assessed. On average, the patients were followed for 21 months (range: two weeks to ten years). With treatment, 30% recovered (i.e. no longer experienced ORS odor beliefs and thoughts of reference), 37% improved and in 33% there was a deterioration in the condition (including suicide) or no change from the pre-treatment status.

Epidemiology
Cases have been reported from many different countries around the world </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 Noonan syndrome with multiple lentigines and explain in detail? [/INST] Noonan syndrome with multiple lentigines (NSML) which is part of a group called Ras/MAPK pathway syndromes, is a rare autosomal dominant, multisystem disease caused by a mutation in the protein tyrosine phosphatase, non-receptor type 11 gene (PTPN11). The disease is a complex of features, mostly involving the skin, skeletal and cardiovascular systems, which may or may not be present in all patients. The nature of how the mutation causes each of the conditions symptoms is not well known; however, research is ongoing. It is a RASopathy.
Noonan syndrome with multiple lentigines is caused by a different missense mutation of the same gene. Noonan syndrome is fairly common (1:1,000 to 1:2,500 live births), and neurofibromatosis 1 (which was once thought to be related to NSML) is also common (1:3500); however, no epidemiological data exists for NSML.

Signs and symptoms
An alternative name of the condition, LEOPARD syndrome, is a mnemonic, originally coined in 1969, as the condition is characterized by some of the following seven conditions, the first letters of which spell LEOPARD, along with the characteristic "freckling" of the skin, caused by the lentigines that is reminiscent of the large cat.

Lentigines — Reddish-brown to dark brown macules (surface skin lesion) generally occurring in a high number (10,000+) over a large portion of the skin, at times higher than 80% coverage. These can even appear inside the mouth (buccal), or on the surface of the eye (scleral). These have irregular borders and range in size from 1 mm in diameter to café-au-lait spots, several centimeters in diameter. Also, some areas of vitiligo-like hypopigmentation may be observed.
Electrocardiographic conduction abnormalities: Generally observed on an electrocardiograph as a bundle branch block.
Ocular hypertelorism: Wideset eyes, which lead to a similar facial resemblance between patients. Facial abnormalities are the second highest occurring symptom after the lentigines. Abnormalities also include: broad nasal root, prognathism (protruding lower jaw), or low-set, possibly rotated, ears.
Pulmonary stenosis: Narrowing of the pulmonary artery as it exits the heart. Other cardiac abnormalities may be present, including aortic stenosis, or mitral valve prolapse.
Abnormal genitalia: usually cryptorchidism (retention of testicles in body) or monorchism (single testicle). In female patients, this presents as missing or single ovaries, much harder by nature to detect. Ultrasound imaging is performed at regular intervals, from the age of 1 year, to determine if ovaries are present.
Retarded growth: Slow, or stunted growth. Most newborns with this syndrome are of normal birth weight and length, but will often slow within the first year.
Deafness: Sensorineural (nerve deafness).The presence of all of these hallmarks is not needed for a diagnosis. A clinical diagnosis is considered made when, with lentigines present there are 2 other symptoms observed, such as ECG abnormalities and ocular hypertelorism, or without lentigines, 3 of the above conditions are present, with a first-degree relative (i.e. parent, child, sibling) with a clinical diagnosis.
Additional dermatologic abnormalities (axillary freckling, localized hypopigmentation, interdigital webbing, hyperelastic skin)
Mild mental retardation is observed in about 30% of those affected by the syndrome
Nystagmus (involuntary eye movements), seizures, or hyposmia (reduced ability to smell) has been documented in a few patients
In 2004, a patient was reported with recurrent upper extremity aneurysms that required surgical repairs.
In 2006, a NSML patient was reported with acute myelogenous leukemia.Due to the rarity of the syndrome itself, it is hard to determine whether certain additional diseases are actually part of the syndrome. With a base population of possibly less than one thousand individuals, one or two outlying cases can skew the statistical population very quickly.

Pathophysiology
In the two predominant mutations of NSML (Y279C and T468M) the mutations cause a loss of catalytic activity of the SHP2 protein (the gene product of the PTPN11 gene), which is a previously unrecognized behavior for this class of mutations. This interferes with growth factor and related signalling. While further research confirms this mechanism, additional research is needed to determine how this relates to all of the observed effects of NSML.

Diagnosis
The presence of the disease can be confirmed with a genetic test. In a study of 10 infants with clinical indications of NSML prior to their first birthday, 8 (80%) patients were confirmed to have the suspected mutation. An additional patient with the suspected mutation was subsequently found to have NF1, following evaluation of the mother.There are 5 identified allelic variants responsible for NSML. Y279C, T468M, A461T, G464A, and Q510P which seems to be a unique familial mutation, in that all other variants are caused by transition errors, rather than transversion.

Treatment
It is suggested that, once diagnosed, individuals be routinely followed by a cardiologist, endocrinologist, dermatologist, and other appropriate specialties as symptoms present.
It is recommended that those with the syndrome who are capable of having children seek genetic counseling before deciding to have children. As the syndrome presents frequently as a forme fruste (incomplete, or unusual form) variant, an examination of all family members must be undertaken. As an autosomal dominant trait there is a fifty percent chance with each child that they will also be born with the syndrome. Although fully penetrant, since the syndrome has variable expressivity, one generation may have a mild expression of the syndrome, while the next may be profoundly affected.
Once a decision to have children is made, and the couple conceives, the fetus is monitored during the pregnancy for cardiac evaluation. If a gross cardiac malformation is found, parents receive counseling on continuing with the pregnancy.
Other management is routine care as symptoms present:
For those with endocrine issues (low levels of thyrotopin [a pituitary hormone responsible for regulating thyroid hormones], follicle stimulating hormone) drug therapy is recommended.
For those who are disturbed by the appearance of lentigines, cryosurgery may be beneficial </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 Pelvis justo major and explain in detail? [/INST] Pelvis justo major (also called "Giant Pelvis") is a rare condition of the adult female pelvis where the pelvis flairs above the Iliopectineal line. It is 1.5 or more times larger than an average pelvis in every direction and is at least 42 cm (16.5 inches) biiliac width. Even though this condition is classified as a congenital abnormality, it is not a medical disease or abnormality of the pelvis (as the pelvis is a true gynecoid shape, only larger).
Women with this condition, at the time of delivery, may have a precipitous birth. There is virtually no resistance of the huge pelvic opening to the size of a newborn so only the soft parts resist the birth. With a huge Justo Major Pelvis, there is no pelvic bone "molding" of the fetal head. With the average pelvic size (2/3 or less Justo Major size) the usual pelvic molding process slows the birth, resulting in a slow and gradual stretching of the vaginal opening for primiparous women. When a huge Justo Major Pelvis allows such an extremely rapid vaginal birth, there can be tears of the perineal soft tissues. At the time of delivery the strong uterine contractions and maternal bearing down almost instantly overwhelm the integrity of a tightened and previously unstretched vaginal orifice </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 Measles and explain in detail? [/INST] Measles is a highly contagious infectious disease caused by measles virus. Symptoms usually develop 10–12 days after exposure to an infected person and last 7–10 days. Initial symptoms typically include fever, often greater than 40 °C (104 °F), cough, runny nose, and inflamed eyes. Small white spots known as Kopliks spots may form inside the mouth two or three days after the start of symptoms. A red, flat rash which usually starts on the face and then spreads to the rest of the body typically begins three to five days after the start of symptoms. Common complications include diarrhea (in 8% of cases), middle ear infection (7%), and pneumonia (6%). These occur in part due to measles-induced immunosuppression. Less commonly seizures, blindness, or inflammation of the brain may occur. Other names include morbilli, rubeola, red measles, and English measles. Both rubella, also known as German measles, and roseola are different diseases caused by unrelated viruses.Measles is an airborne disease which spreads easily from one person to the next through the coughs and sneezes of infected people. It may also be spread through direct contact with mouth or nasal secretions. It is extremely contagious: nine out of ten people who are not immune and share living space with an infected person will be infected. Furthermore, measless reproductive number estimates vary beyond the frequently cited range of 12 to 18. The NIH quote this 2017 paper saying: "[a] review in 2017 identified feasible measles R0 values of 3.7–203.3". People are infectious to others from four days before to four days after the start of the rash. While often regarded as a childhood illness, it can affect people of any age. Most people do not get the disease more than once. Testing for the measles virus in suspected cases is important for public health efforts. Measles is not known to occur in other animals.Once a person has become infected, no specific treatment is available, although supportive care may improve outcomes. Such care may include oral rehydration solution (slightly sweet and salty fluids), healthy food, and medications to control the fever. Antibiotics should be prescribed if secondary bacterial infections such as ear infections or pneumonia occur. Vitamin A supplementation is also recommended for children. Among cases reported in the U.S. between 1985 and 1992, death occurred in only 0.2% of cases, but may be up to 10% in people with malnutrition. Most of those who die from the infection are less than five years old.The measles vaccine is effective at preventing the disease, is exceptionally safe, and is often delivered in combination with other vaccines. Vaccination resulted in an 80% decrease in deaths from measles between 2000 and 2017, with about 85% of children worldwide having received their first dose as of 2017.
Measles affects about 20 million people a year, primarily in the developing areas of Africa and Asia. It is one of the leading vaccine-preventable disease causes of death. In 1980, 2.6 million people died from measles, and in 1990, 545,000 died due to the disease; by 2014, global vaccination programs had reduced the number of deaths from measles to 73,000. Despite these trends, rates of disease and deaths increased from 2017 to 2019 due to a decrease in immunization.

Signs and symptoms
Symptoms typically begin 10–14 days after exposure. The classic symptoms include a four-day fever (the 4 Ds) and the three Cs—cough, coryza (head cold, fever, sneezing), and conjunctivitis (red eyes)—along with a maculopapular rash. Fever is common and typically lasts for about one week; the fever seen with measles is often as high as  40 °C (104 °F).Kopliks spots seen inside the mouth are diagnostic for measles, but are temporary and therefore rarely seen. Koplik spots are small white spots that are commonly seen on the inside of the cheeks opposite the molars. They appear as "grains of salt on a reddish background." Recognizing these spots before a person reaches their maximum infectiousness can help reduce the spread of the disease.The characteristic measles rash is classically described as a generalized red maculopapular rash that begins several days after the fever starts. It starts on the back of the ears and, after a few hours, spreads to the head and neck before spreading to cover most of the body, often causing itching. The measles rash appears two to four days after the initial symptoms and lasts for up to eight days. The rash is said to "stain", changing color from red to dark brown, before disappearing. Overall, measles usually resolves after about three weeks.People who have been vaccinated against measles but have incomplete protective immunity may experience a form of modified measles. Modified measles is characterized by a prolonged incubation period, milder, and less characteristic symptoms (sparse and discrete rash of short duration).

Complications
Complications of measles are relatively common, ranging from mild ones such as diarrhea to serious ones such as pneumonia (either direct viral pneumonia or secondary bacterial pneumonia), laryngotracheobronchitis (croup) (either direct viral laryngotracheobronchitis or secondary bacterial bronchitis), otitis media, acute brain inflammation (and very rarely subacute sclerosing panencephalitis), and corneal ulceration (leading to corneal scarring).In addition, measles can suppress the immune system for weeks to months, and this can contribute to bacterial superinfections such as otitis media and bacterial pneumonia. Two months after recovery there is a 11–73% decrease in the number of antibodies against other bacteria and viruses.The death rate in the 1920s was around 30% for measles pneumonia. People who are at high risk for complications are infants and children aged less than 5 years; adults aged over 20 years; pregnant women; people with compromised immune systems, such as from leukemia, HIV infection or innate immunodeficiency; and those who are malnourished or have vitamin A deficiency.  Complications are usually more severe in adults. Between 1987 and 2000, the case fatality rate across the United States was three deaths per 1,000 cases attributable to measles, or 0.3%. In underdeveloped nations with high rates of malnutrition and poor healthcare, fatality rates have been as high as 28%. In immunocompromised persons (e.g., people with AIDS) the fatality rate is approximately 30%.Even in previously healthy children, measles can cause serious illness requiring hospitalization. One out of every 1,000 measles cases progresses to acute encephalitis, which often results in permanent brain damage. One to three out of every 1,000 children who become infected with measles will die from respiratory and neurological complications.

Cause
Measles is caused by the measles virus, a single-stranded, negative-sense, enveloped RNA virus of the genus Morbillivirus within the family Paramyxoviridae.The virus is highly contagious and is spread by coughing and sneezing via close personal contact or direct contact with secretions. Measles is the most contagious transmissible virus known. It remains infective for up to two hours in that airspace or nearby surfaces. Measles is so contagious that if one person has it, 90% of non-immune people who have close contact with them (e.g., household members) will also become infected. Humans are the only natural hosts of the virus, and no other animal reservoirs are known to exist, although mountain gorillas are believed to be susceptible to the disease.
Risk factors for measles virus infection include immunodeficiency caused by HIV or AIDS, immunosuppression following receipt of an organ or a stem cell transplant, alkylating agents, or corticosteroid therapy, regardless of immunization status; travel to areas where measles commonly occurs or contact with travelers from such an area; and the loss of passive, inherited antibodies before the age of routine immunization.

Pathophysiology
Once the measles virus gets onto the mucosa, it infects the epithelial cells in the trachea or bronchi. Measles virus uses a protein on its surface called hemagglutinin (H protein), to bind to a target receptor on the host cell, which could be CD46, which is expressed on all nucleated human cells, CD150, aka signaling lymphocyte activation molecule or SLAM, which is found on immune cells like B or T cells, and antigen-presenting cells, or nectin-4, a cellular adhesion molecule. Once bound, the fusion, or F protein helps the virus fuse with the membrane and ultimately get inside the cell.As the virus is a single-stranded negative-sense RNA virus, it includes the enzyme RNA-dependent RNA polymerase (RdRp) which is used to transcribe its genome into a positive-sense mRNA strand.After entering a cell, it is ready to be translated into viral proteins, wrapped in the cells lipid envelope, and sent out of the cell as a newly made virus. Within days, the measles virus spreads through local tissue and is picked up by dendritic cells and alveolar macrophages, and carried from that local tissue in the lungs to the local lymph nodes. From there it continues to spread, eventually getting into the blood and spreading to more lung tissue, as well as other organs like the intestines and the brain. Functional impairment of the infected dendritic cells by the measles virus is thought to contribute to measles-induced immunosuppression.

Diagnosis
Typically, clinical diagnosis begins with the onset of fever and malaise about 10 days after exposure to the measles virus, followed by the emergence of cough, coryza, and conjunctivitis that worsen in severity over 4 days of appearing. Observation of Kopliks spots is also diagnostic. Other possible condition that can result in these symptoms include parvovirus, dengue fever, Kawasaki disease, and scarlet fever. Laboratory confirmation is however strongly recommended.

Laboratory testing
Laboratory diagnosis of measles can be done with confirmation of positive measles IgM antibodies or detection of measles virus RNA from throat, nasal or urine specimen by using the reverse transcription polymerase chain reaction assay. This method is particularly useful to confirm cases when the IgM antibodies results are inconclusive. For people unable to have their blood drawn, saliva can be collected for salivary measles-specific IgA testing. Salivary tests used to diagnose measles involve collecting a saliva sample and testing for the presence of measles antibodies. This method is not ideal, as saliva contains many other fluids and proteins which may make it difficult to collect samples and detect measles antibodies. Saliva also contains 800 times fewer antibodies than blood samples do, which makes salivary testing additionally difficult. Positive contact with other people known to have measles adds evidence to the diagnosis.

Prevention
Mothers who are immune to measles pass antibodies to their children while they are still in the womb, especially if the mother acquired immunity through infection rather than vaccination. Such antibodies will usually give newborn infants some immunity against measles, but these antibodies are gradually lost over the course of the first nine months of life. Infants under one year of age whose maternal anti-measles antibodies have disappeared become susceptible to infection with the measles virus.In developed countries, it is recommended that children be immunized against measles at 12 months, generally as part of a three-part MMR vaccine (measles, mumps, and rubella). The vaccine is generally not given before this age because such infants respond inadequately to the vaccine due to an immature immune system. A second dose of the vaccine is usually given to children between the ages of four and five, to increase rates of immunity. Measles vaccines have been given to over a billion people. Vaccination rates have been high enough to make measles relatively uncommon. Adverse reactions to vaccination are rare, with fever and pain at the injection site being the most common. Life-threatening adverse reactions occur in less than one per million vaccinations (<0.0001%).In developing countries where measles is common, the World Health Organization (WHO) recommends two doses of vaccine be given, at six and nine months of age. The vaccine should be given whether the child is HIV-infected or not. The vaccine is less effective in HIV-infected infants than in the general population, but early treatment with antiretroviral drugs can increase its effectiveness. Measles vaccination programs are often used to deliver other child health interventions as well, such as bed nets to protect against malaria, antiparasite medicine and vitamin A supplements, and so contribute to the reduction of child deaths from other causes.The Advisory Committee on Immunization Practices (ACIP) recommends that all adult international travelers who do not have positive evidence of previous measles immunity receive two doses of MMR vaccine before traveling, although birth before 1957 is presumptive evidence of immunity. Those born in the United States before 1957 are likely to have been naturally infected with measles virus and generally need not be considered susceptible.There have been false claims of an association between the measles vaccine and autism; this incorrect concern has reduced the rate of vaccination and increased the number of cases of measles where immunization rates became too low to maintain herd immunity. Additionally, there have been false claims that measles infection protects against cancer.Administration of the MMR vaccine may prevent measles after exposure to the virus (post-exposure prophylaxis). Post-exposure prophylaxis guidelines are specific to jurisdiction and population. Passive immunization against measles by an intramuscular injection of antibodies could be effective up to the seventh day after exposure. Compared to no treatment, the risk of measles infection is reduced by 83%, and the risk of death by measles is reduced by 76%. However, the effectiveness of passive immunization in comparison to active measles vaccine is not clear.The MMR vaccine is 95% effective for preventing measles after one dose if the vaccine is given to a child who is 12 months or older; if a second dose of the MMR vaccine is given, it will provide immunity in 99% of children.There is no evidence that the measles vaccine virus can be transmitted to other persons.

Treatment
There is no specific antiviral treatment if measles develops. Instead the medications are generally aimed at treating superinfections, maintaining good hydration with adequate fluids, and pain relief. Some groups, like young children and the severely malnourished, are also given vitamin A, which acts as an immunomodulator that boosts the antibody responses to measles and decreases the risk of serious complications.

Medications
Treatment is supportive, with ibuprofen or paracetamol (acetaminophen) to reduce fever and pain and, if required, a fast-acting medication to dilate the airways for cough. As for aspirin, some research has suggested a correlation between children who take aspirin and the development of Reye syndrome.The use of vitamin A during treatment is recommended to decrease the risk of blindness; however, it does not prevent or cure the disease.  A systematic review of trials into its use found no reduction in overall mortality, but two doses (200 000 IU) of vitamin A was shown to reduce mortality for measles in children younger than two years of age. It is unclear if zinc supplementation in children with measles affects outcomes as it has not been sufficiently studied. There are no adequate studies on whether Chinese medicinal herbs are effective.

Prognosis
Most people survive measles, though in some cases, complications may occur. About 1 in 4 individuals will be hospitalized and 1–2 in 1000 will die. Complications are more likely in children under age 5 and adults over age 20. Pneumonia is the most common fatal complication of measles infection and accounts for 56-86% of measles-related deaths.Possible consequences of measles virus infection include laryngotracheobronchitis, sensorineural hearing loss, and—in about 1 in 10,000 to 1 in 300,000 cases—panencephalitis, which is usually fatal. Acute measles encephalitis is another serious risk of measles virus infection. It typically occurs two days to one week after the measles rash breaks out and begins with very high fever, severe headache, convulsions and altered mentation. A person with measles encephalitis may become comatose, and death or brain injury may occur.For people having had measles, it is rare to ever have a symptomatic reinfection.The measles virus can deplete previously acquired immune memory by killing cells that make antibodies, and thus weakens the immune system which can cause deaths from other diseases. Suppression of the immune system by measles lasts about two years and has been epidemiologically implicated in up to 90% of childhood deaths in third world countries, and historically may have caused rather more deaths in the United States, the UK and Denmark than were directly caused by measles. Although the measles vaccine contains an attenuated strain, it does not deplete immune memory.

Epidemiology
Measles is extremely infectious and its continued circulation in a community depends on the generation of susceptible hosts by birth of children. In communities that generate insufficient new hosts the disease will die out. This concept was first recognized in measles by Bartlett in 1957, who referred to the minimum number supporting measles as the critical community size (CCS). Analysis of outbreaks in island communities suggested that the CCS for measles is around 250,000. To achieve herd immunity, more than 95% of the community must be vaccinated due to the ease with which measles is transmitted from person to person.In 2011, the WHO estimated that 158,000 deaths were caused by measles. This is down from 630,000 deaths in 1990. As of 2018, measles remains a leading cause of vaccine-preventable deaths in the world. In developed countries the mortality rate is lower, for example in England and Wales from 2007 to 2017 death occurred between two and three cases out of 10,000. In children one to three cases out of every 1,000 die in the United States (0.1–0.2%). In populations with high levels of malnutrition and a lack of adequate healthcare, mortality can be as high as 10%. In cases with complications, the rate may rise to 20–30%. In 2012, the number of deaths due to measles was 78% lower than in 2000 due to increased rates of immunization among UN member states.
Even in countries where vaccination has been introduced, rates may remain high. Measles is a leading cause of vaccine-preventable childhood mortality. Worldwide, the fatality rate has been significantly reduced by a vaccination campaign led by partners in the Measles Initiative: the American Red Cross, the United States CDC, the United Nations Foundation, UNICEF and the WHO. Globally, measles fell 60% from an estimated 873,000 deaths in 1999 to 345,000 in 2005. Estimates for 2008 indicate deaths fell further to 164,000 globally, with 77% of the remaining measles deaths in 2008 occurring within the Southeast Asian region. There were 142,300 measles related deaths globally in 2018, of which most cases were reported from African and eastern Mediterranean regions. These estimates were slightly higher than that of 2017, when 124,000 deaths were reported due to measles infection globally.In 2000, the WHO established the Global Measles and Rubella Laboratory Network (GMRLN) to provide laboratory surveillance for measles, rubella, and congenital rubella syndrome. Data from 2016 to 2018 show that the most frequently detected measles virus genotypes are decreasing, suggesting that increasing global population immunity has decreased the number of chains of transmission.Cases reported in the first three months of 2019, were 300% higher than in the first three months of 2018, with outbreaks in every region of the world, even in countries with high overall vaccination coverage where it spread among clusters of unvaccinated people. The numbers of reported cases as of mid-November is over 413,000 globally, with an additional 250,000 cases in DRC (as reported through their national system), similar to the increasing trends of infection reported in the earlier months of 2019, compared to 2018. In 2019, the total number of cases worldwide climbed to 869,770. The number of cases reported for 2020 is lower compare to 2019. According to the WHO, the COVID-19 pandemic hindered vaccination campaigns in at least 68 countries, including in countries that were experiencing outbreaks, which caused increased risk of additional cases.

Europe
In England and Wales, though deaths from measles were uncommon, they averaged about 500 per year in the 1940s. Deaths diminished with the improvement of medical care in the 1950s but the incidence of the disease did not retreat until vaccination was introduced in the late 1960s. Wider coverage was achieved in the 1980s with the measles, mumps and rubella, MMR vaccine.In 2013–14, there were almost 10,000 cases in 30 European countries. Most cases occurred in unvaccinated individuals and over 90% of cases occurred in Germany, Italy, Netherlands, Romania, and United Kingdom. Between October 2014 and March 2015, a measles outbreak in the German capital of Berlin resulted in at least 782 cases. In 2017, numbers continued to increase in Europe to 21,315 cases, with 35 deaths. In preliminary figures for 2018, reported cases in the region increased 3-fold to 82,596 in 47 countries, with 72 deaths; Ukraine had the most cases (53,218), with the highest incidence rates being in Ukraine (1209 cases per million), Serbia (579), Georgia (564) and Albania (500). The previous year (2017) saw an estimated measles vaccine coverage of 95% for the first dose and 90% for the second dose in the region, the latter figure being the highest-ever estimated second-dose coverage.In 2019, the United Kingdom, Albania, the Czech Republic, and Greece lost their measles-free status due to ongoing and prolonged spread of the disease in these countries. In the first 6 months of 2019, 90,000 cases occurred in Europe.

Americas
As a result of widespread vaccination, the disease was declared eliminated from the Americas in 2016. However, there were cases again in 2017, 2018, 2019, and 2020 in this region.

United States
In the United States, measles affected approximately 3,000 people per million in the 1960s before the vaccine was available. With consistent widespread childhood vaccination, this figure fell to 13 cases per million by the 1980s, and to about 1 case per million by 2000.In 1991, an outbreak of measles in Philadelphia was centered at the Faith Tabernacle Congregation, a faith healing church that actively discouraged parishioners from vaccinating their children. Over 1400 people were infected with measles and nine children died.Before immunization in the United States, between three and four million cases occurred each year. The United States was declared free of circulating measles in 2000, with 911 cases from 2001 to 2011. In 2014 the CDC said endemic measles, rubella, and congenital rubella syndrome had not returned to the United States. Occasional measles outbreaks persist, however, because of cases imported from abroad, of which more than half are the result of unvaccinated U.S. residents who are infected abroad and infect others upon return to the United States. The CDC continues to recommend measles vaccination throughout the population to prevent outbreaks like these.In 2014, an outbreak was initiated in Ohio when two unvaccinated Amish men harboring asymptomatic measles returned to the United States from missionary work in the Philippines. Their return to a community with low vaccination rates led to an outbreak that rose to include a total of 383 cases across nine counties. Of the 383 cases, 340 (89%) occurred in unvaccinated individuals.From 4 January, to 2 April 2015, there were 159 cases of measles reported to the CDC. Of those 159 cases, 111 (70%) were determined to have come from an earlier exposure in late December 2014. This outbreak was believed to have originated from the Disneyland theme park in California. The Disneyland outbreak was held responsible for the infection of 147 people in seven U.S. states as well as Mexico and Canada, the majority of which were either unvaccinated or had unknown vaccination status. Of the cases 48% were unvaccinated and 38% were unsure of their vaccination status. The initial exposure to the virus was never identified.In 2015, a U.S. woman in Washington state died of pneumonia, as a result of measles. She was the first fatality in the U.S. from measles since 2003. The woman had been vaccinated for measles and was taking immunosuppressive drugs for another condition. The drugs suppressed the womans immunity to measles, and the woman became infected with measles; she did not develop a rash, but contracted pneumonia, which caused her death.In June 2017, the Maine Health and Environmental Testing Laboratory confirmed a case of measles in Franklin County. This instance marks the first case of measles in 20 years for the state of Maine. In 2018 one case occurred in Portland, Oregon, with 500 people exposed; 40 of them lacked immunity to the virus and were being monitored by county health officials as of 2 July 2018. There were 273 cases of measles reported throughout the United States in 2018, including an outbreak in Brooklyn with more than 200 reported cases from October 2018 to February 2019. The outbreak was tied with population density of the Orthodox Jewish community, with the initial exposure from an unvaccinated child that caught measles while visiting Israel.A resurgence of measles occurred during 2019, which has been generally tied to parents choosing not to have their children vaccinated as most of the reported cases have occurred in people 19 years old or younger. Cases were first reported in Washington state in January, with an outbreak of at least 58 confirmed cases most within Clark County, which has a higher rate of vaccination exemptions compared to the rest of the state; nearly one in four kindergartners in Clark did not receive vaccinations, according to state data. This led Washington state governor Jay Inslee to declare a state of emergency, and the states congress to introduce legislation to disallow vaccination exemption for personal or philosophical reasons. In April 2019, New York Mayor Bill de Blasio declared a public health emergency because of "a huge spike" in cases of measles where there were 285 cases centred on the Orthodox Jewish areas of Brooklyn in 2018, while there were only two cases in 2017. There were 168 more in neighboring Rockland County. Other outbreaks have included Santa Cruz County and Butte County in California, and the states of New Jersey and Michigan. As of April 2019, there have been 695 cases of measles reported in 22 states. This is the highest number of measles cases since it was declared eradicated in 2000. From 1 January, to 31 December 2019, 1,282 individual cases of measles were confirmed in 31 states. This is the greatest number of cases reported in the U.S. since 1992. Of the 1,282 cases, 128 of the people who got measles were hospitalized, and 61 reported having complications, including pneumonia and encephalitis.

Brazil
The spread of measles had been interrupted in Brazil in 2016, with the last known case twelve months earlier. This last case was in the state of Ceará.Brazil won a measles elimination certificate by the Pan American Health Organization in 2016, but the Ministry of Health has proclaimed that the country has struggled to keep this certificate, since two outbreaks had already been identified in 2018, one in the state of Amazonas and another one in Roraima, in addition to cases in other states (Rio de Janeiro, Rio Grande do Sul, Pará, São Paulo and Rondônia), totaling 1053 confirmed cases until 1 August 2018. In these outbreaks, and in most other cases, the contagion was related to the importation of the virus, especially from Venezuela.  This was confirmed by the genotype of the virus (D8) that was identified, which is the same that circulates in Venezuela.

Southeast Asia
In the Vietnamese measles epidemic in spring of 2014, an estimated 8,500 measles cases were reported as of 19 April, with 114 fatalities; as of 30 May, 21,639 suspected measles cases had been reported, with 142 measles-related fatalities. In the Naga Self-Administered Zone in a remote northern region of Myanmar, at least 40 children died during a measles outbreak in August 2016 that was probably caused by lack of vaccination in an area of poor health infrastructure. Following the 2019 Philippines measles outbreak, 23,563 measles cases have been reported in the country with 338 fatalities. A measles outbreak also happened among the Malaysian Orang Asli sub-group of Batek people in the state of Kelantan from May 2019, causing the deaths of 15 from the tribe.

South Pacific
A measles outbreak in New Zealand has 2193 confirmed cases and two deaths. A measles outbreak in Tonga has 612 cases of measles.

Samoa
A measles outbreak in Samoa in late 2019 has over 5,700 cases of measles and 83 deaths, out of a Samoan population of 200,000. Over three percent of the population were infected, and a state of emergency was declared from 17 November to 7 December. A vaccination campaign brought the measles vaccination rate from 31 to 34% in 2018 to an estimated 94% of the eligible population in December 2019.

Africa
The Democratic Republic of the Congo and Madagascar have reported the highest numbers of cases in 2019. However, cases have decreased in Madagascar as a result of nationwide emergency measles vaccine campaigns. As of August 2019 outbreaks were occurring in Angola, Cameroon, Chad, Nigeria, South Sudan and Sudan.

Madagascar
An outbreak of measles in 2018 has resulted in 118,000 cases and 1,688 deaths. This followed outbreaks of bubonic and pneumonic plague in 2017 (2575 cases, 221 deaths) and 2014 (263 confirmed cases, 71 deaths).

Democratic Republic of Congo
An outbreak of measles with nearly 5,000 deaths and 250,000 infections occurred in 2019, after the disease spread to all the provinces in the country. Most deaths were among children under five years of age. The World Health Organization (WHO) has reported this as the worlds largest and fastest-moving epidemic.

History
Measles is of zoonotic origin, having evolved from rinderpest, which infects cattle. A precursor of the measles began causing infections in humans as early as the 4th century BC or as late as after AD 500. The Antonine Plague of AD 165–180 has been speculated to have been measles, but the actual cause of this plague is unknown and smallpox is a more likely cause. The first systematic description of measles, and its distinction from smallpox and chickenpox, is credited to the Persian physician Muhammad ibn Zakariya al-Razi (860–932), who published The Book of Smallpox and Measles. At the time of Razis book, it is believed that outbreaks were still limited and that the virus was not fully adapted to humans. Sometime between AD 1100 and 1200, the measles virus fully diverged from rinderpest, becoming a distinct virus that infects humans. This agrees with the observation that measles requires a susceptible population of >500,000 to sustain an epidemic, a situation that occurred in historic times following the growth of medieval European cities.

Measles is an endemic disease, meaning it has been continually present in a community and many people develop resistance. In populations not exposed to measles, exposure to the new disease can be devastating. In 1529, a measles outbreak in Cuba killed two-thirds of those indigenous people who had previously survived smallpox. Two years later, measles was responsible for the deaths of half the population of Honduras, and it has ravaged Mexico, Central America, and the Inca civilization.Between roughly 1855 and 2005, measles is estimated to have killed about 200 million people worldwide.The 1846 measles outbreak in the Faroe Islands was unusual for being well-studied.  Measles had not been seen on the islands for 60 years, so almost no residents had any acquired immunity.  Three-quarters of the residents got sick, and more than 100 (1–2%) died from it before the epidemic burned itself out. Peter Ludvig Panum observed the outbreak and determined that measles was spread through direct contact of contagious people with people who had never had measles.Measles killed 20 percent of Hawaiis population in the 1850s. In 1875, measles killed over 40,000 Fijians, approximately one-third of the population. In the 19th century, the disease killed more than half of the Great Andamanese population. Seven to eight million children are thought to have died from measles each year before the vaccine was introduced.In 1914, a statistician for the Prudential Insurance Company estimated from a survey of 22 countries that 1% of all deaths in the temperate zone were caused by measles. He observed also that 1–6% of cases of measles ended fatally, the difference depending on age (0–3 being the worst), social conditions (e.g. overcrowded tenements) and pre-existing health conditions.In 1954, the virus causing the disease was isolated from a 13-year-old boy from the United States, David Edmonston, and adapted and propagated on chick embryo tissue culture. The World Health Organization recognizes eight clades, named A, B, C, D, E, F, G, and H. Twenty-three strains of the measles virus have been identified and designated within these clades. While at Merck, Maurice Hilleman developed the first successful vaccine.  Licensed vaccines to prevent the disease became available in 1963. An improved measles vaccine became available in 1968. Measles as an endemic disease was eliminated from the United States in 2000, but continues to be reintroduced by international travelers. In 2019 there were at least 1,241 cases of measles in the United States distributed across 31 states, with over three quarters in New York.

Society and culture
German anti-vaccination campaigner and HIV/AIDS denialist Stefan Lanka posed a challenge on his website in 2011, offering a sum of €100,000 for anyone who could scientifically prove that measles is caused by a virus and determine the diameter of the virus </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 Hypothenar hammer syndrome 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 Keratoacanthoma and explain in detail? [/INST] Keratoacanthoma (KA) is a common low-grade (unlikely to metastasize or invade) rapidly-growing skin tumour that is believed to originate from the hair follicle (pilosebaceous unit) and can resemble squamous cell carcinoma.The defining characteristic of a keratoacanthoma is that it is dome-shaped, symmetrical, surrounded by a smooth wall of inflamed skin, and capped with keratin scales and debris. It grows rapidly, reaching a large size within days or weeks, and if untreated for months will almost always starve itself of nourishment, necrose (die), slough, and heal with scarring. Keratoacanthoma is commonly found on sun-exposed skin, often face, forearms and hands. It is rarely found at a mucocutaneous junction or on mucous membranes.Keratoacanthoma may be difficult to distinguish visually from a skin cancer. Under the microscope, keratoacanthoma very closely resembles squamous cell carcinoma. In order to differentiate between the two, almost the entire structure needs to be removed and examined. While some pathologists classify keratoacanthoma as a distinct entity and not a malignancy, about 6% of clinical and histological keratoacanthomas do progress to invasive and aggressive squamous cell cancers; some pathologists may label KA as "well-differentiated squamous cell carcinoma, keratoacanthoma variant", and prompt definitive surgery may be recommended.

Classification
Frequently reported and reclassified over the last century, keratoacanthoma can be divided into various subtypes and despite being considered benign, their unpredictable behaviour has warranted the same attention as with squamous cell carcinoma.Keratoacanthomas may be divided into the following types:: 763–764 : 643–646
Giant keratoacanthomas are a variant of keratoacanthoma, which may reach dimensions of several centimeters.: 763
Keratoacanthoma centrifugum marginatum is a cutaneous condition, a variant of keratoacanthomas, which is characterized by multiple tumors growing in a localized area.: 763 : 645
Multiple keratoacanthomas (also known as "Ferguson–Smith syndrome," "Ferguson-Smith type of multiple self-healing keratoacanthomas,") is a cutaneous condition, a variant of keratoacanthomas, which is characterized by the appearance of multiple, sometimes hundreds of keratoacanthomas.: 763 : 644
A solitary keratoacanthoma (also known as "Subungual keratoacanthoma") is a benign, but rapidly growing, locally aggressive tumor which sometimes occur in the nail apparatus.: 667, 764 : 644
Generalized eruptive keratoacanthoma (also known as "Generalized eruptive keratoacanthoma of Grzybowski") is a cutaneous condition, a variant of keratoacanthomas, characterized by hundreds to thousands of tiny follicular keratotic papules over the entire body.: 763  : 645  Treatments are not successful for many people with generalized eruptive keratoacanthoma. Use of emollients and anti-itch medications can ease some symptoms. Improvement or complete resolutions of the condition has occurred with the application of the following medications: acitretin, isotretinoin, fluorouracil, methotrexate, cyclophosphamide.

Cause
Keratoacanthomas usually occurs in older individuals </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 Achilles bursitis 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 Spondylo-ocular syndrome 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 Acatalasia and explain in detail? [/INST] Acatalasia  is an autosomal recessive peroxisomal disorder caused by absent or very low levels of the enzyme catalase </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 Nasodigitoacoustic syndrome and explain in detail? [/INST] Nasodigitoacoustic syndrome, also called Keipert syndrome, is a rare congenital syndrome first described by J.A. Keipert and colleagues in 1973. The syndrome is characterized by a misshaped nose, broad thumbs and halluces (the big toes), brachydactyly,  sensorineural hearing loss, facial features such as hypertelorism (unusually wide-set eyes), and developmental delay.
It is believed to be inherited in an X-linked recessive manner, which means a genetic mutation causing the disorder is located on the X chromosome, and while two copies of the mutated gene must be inherited for a female to be born with the disorder, just one copy is sufficient to cause a male to be born with the disorder. Nasodigitoacoustic syndrome is likely caused by a mutated gene located on the X chromosome between positions Xq22.2–q28.
The incidence of the syndrome has not been determined, but it is considered to affect less than 200,000 people in the United States, and no greater than 1 per 2,000 in Europe. It is similar to Keutel, Muenke, Rubinstein and Teunissen–Cremers syndrome.

Characteristics
Nasodigitoacoustic syndrome is congenital and is characterized by a number of nasal, facial and cranial features. These include a broad and high, sometimes depressed nasal bridge (top of the nose, between the eyes) and a flattened nasal tip. This can give the nose a shortened, arch-like appearance. Hypertelorism (unusually wide-set eyes), prominent frontal bones and supraorbital ridge (the eyebrow ridge), bilateral epicanthic folds (an extra flap of skin over the eyelids), a broad forehead and an overall enlarged head circumference have also been observed. A bulging of the upper lip with an exaggerated cupids bow shape, and maxillary hypoplasia (underdevelopment of the upper jaw) with retraction have also been reported.Several anomalies affecting the digits (fingers and toes) have been observed with the syndrome. A broadening of the thumbs and big toes (halluces) was reported in two brothers. The broadening was apparent in all distal phalanges of the fingers, although the pinkies were unaffected yet appeared to be clinodactylic (warped, or bent toward the other fingers). Additional reports described this broadness of the thumbs and big toes, with brachydactyly (shortness) in the distal phalanges of the other digits except the pinkies in affected individuals. On X-rays of a two-year-old boy with the disorder, the brachydactyly was shown to be caused by shortening of epiphyses (joint-ends) of the distal phalanges. The broadness and brachydactyly of the big toes in particular may give them a stunted, rounded and stub-like appearance.The auditory, or "acoustic" abnormalities observed with the syndrome include sensorineural hearing loss and hoarseness. Two affected Turkish brothers with a mild form of this hearing loss, and a hoarse voice were reported. A laryngoscopic examination of both brothers revealed swelling of the vocal cords, and a malformed epiglottis. Sensorineural-associated hearing impairment and hoarseness was also observed in a 10-year-old girl and her father, and in a number of other cases.Other characteristics seen with the syndrome include developmental delay, growth retardation, pulmonary stenosis (an obstruction of blood-flow from the right ventricle of the heart to the pulmonary artery) with associated dyspnea (shortness of breath), and renal agenesis (failure of the kidneys to develop during the fetal period). Undescended testes, hyperactivity and aggressive behavior have also been noted.

Genetics
Nasodigitoacoustic syndrome is thought to be caused by a mutation in a gene on the X chromosome. A 2007 study concluded, based on analysis of microsatellite markers (small gene sequences found in common among individuals having the same ethnicity, ancestry or genetic disease) of the family described by Keipert, that this gene was likely located on the long arm of the X chromosome between positions Xq22.2–q28. This is not definitive, however, and no specific gene has been named.The syndrome is strongly believed to be inherited in an X-linked recessive manner. When a female carries a mutated gene on one of her two copies of the X chromosome, there is a 50% chance of passing the mutation on to her children. Much like her, a daughter inheriting this mutation will be a carrier, but will not herself have the associated disease. However, a son who inherits the mutation will have the disease; this is because males have only one copy of the X chromosome and therefore could only express the disease mutation.
This form of inheritance for Nasodigitoacoustic syndrome is not yet absolute, though, as a girl has been reported with the disorder. It is suggested that further analysis is needed for the inheritance to be formally established.The mutations causing this syndrome have been mapped to the glypican 4 (GPC4) gene. This gene is located on the long arm of chromosome X (Xq26.2).

Diagnosis
The constellation of anomalies seen with nasodigitoacoustic syndrome result in a distinct diagnosis. The diagnostic criteria for the disorder are broad distal phalanges of the thumbs and big toes, accompanied by a broad and shortened nose, sensorineural hearing loss and developmental delay, with predominant occurrence in males.

Classification
Nasodigitoacoustic syndrome is similar to several syndromes that share its features. Brachydactyly of the distal phalanges, sensorineural deafness and pulmonary stenosis are common with Keutel syndrome. In Muenke syndrome, developmental delay, distal brachydactyly and sensorineural hearing loss are reported; features of Teunissen-Cremers syndrome include nasal aberrations and broadness of the thumbs and big toes, also with brachydactyly. Broad thumbs and big toes are primary characteristics of Rubinstein syndrome.

Management
A number of features found with nasodigitoacoustic syndrome can be managed or treated. Sensorineural hearing loss in humans may be caused by a loss of hair cells (sensory receptors in the inner ear that are associated with hearing). This can be hereditary and/or within a syndrome, as is the case with nasodigitoacoustic syndrome, or attributed to infections such as viruses. For the management of sensorineural hearing loss, hearing aids have been used. Treatments, depending upon the cause and severity, may include a pharmacological approach (i.e., the use of certain steroids), or surgical intervention, like a cochlear implant.Pulmonary, or pulmonic stenosis is an often congenital narrowing of the pulmonary valve; it can be present in nasodigitoacoustic-affected infants. Treatment of this cardiac abnormality can require surgery, or non-surgical procedures like balloon valvuloplasty (widening the valve with a balloon catheter).

History and epidemiology
The syndrome was initially described in 1973 by James A. Keipert and associates. They reported of two brothers with broad distal phalanges, sensorineural hearing loss, and facial features consistent with what would become known as Keipert or "nasodigitoacoustic" syndrome. Although no specific rate of incidence has been determined, the syndrome is considered a rare disease by both the Office of Rare Diseases (ORDR) at the National Institutes of Health, and Orphanet. This suggests, respectively, that nasodigitoacoustic syndrome affects less than 200,000 people in the U.S., or affects no greater than 1 per 2,000 people in Europe.

References
Publications
Gorlin, R. J.; Toriello, H </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 Lethal arthrogryposis with anterior horn cell disease 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 Persistent fetal circulation and explain in detail? [/INST] Persistent fetal circulation is a condition caused by a failure in the systemic circulation and pulmonary circulation to convert from the antenatal circulation pattern to the "normal" pattern. Infants experience a high mean arterial pulmonary artery pressure and a high afterload at the right ventricle. This means that the heart is working against higher pressures, which makes it more difficult for the heart to pump blood.In a fetus, there is high pulmonary vascular resistance (PVR) and low pulmonary blood flow as the fetus does not use the lungs for oxygen transfer, but instead relies on the placenta for oxygen. When the baby is born, the lungs are needed for oxygen transfer and need high blood flow which is encouraged by low PVR. The failure of the circulatory system of the newborn to adapt to these changes by lowering PVR leads to persistent fetal circulation. The newborn is therefore born with elevated PVR, which leads to pulmonary hypertension. Because of this, the condition is also widely known as persistent pulmonary hypertension of the newborn (PPHN). This condition can be either acute or chronic, and is associated with significant morbidity and mortality.

Presentation
Complications
PPHN can range from mild to severe disease. In the most severe form, infants experience severe hypoxemia resulting in cardiac and pulmonary complications. As a result of low oxygen levels, infants with PPHN are at an increased risk of developing complications, such as asphyxia, chronic lung disease, neurodevelopment issues, and death.Nosocomial infections are another type of complication that may contribute to mortality in someone with PPHN. If the newborn acquires an infection while hospitalized, this could result in deterioration of the condition even after days of improvement.

Pathophysiology
Typically, a fetus experiences pulmonary hypertension in utero since it is relying on the placenta for oxygen rather than its lungs. When the fetus is born, it is no longer attached to the placenta and must use the lungs to receive oxygen. To facilitate this change from fetus to newborn, the baby must change from a state of high PVR to low PVR, allowing for increased blood flow to circulate throughout the body. This inability of the newborn to adapt to these changes is caused by various processes, such as:

Normal vascular anatomy with functional vasoconstriction: This has a good prognosis, as it is reversible.  Causes include hypoxia, meconium aspiration, and respiratory distress syndrome. Left untreated, this can lead to hypoxic respiratory failure (HRF).
Decreased diameter of pulmonary vessels with hypertrophy of vessel walls: This has a poor prognosis, as it is a fixed abnormality. Causes include post-term pregnancy, placental insufficiency, and NSAID use by the mother.
Decreased size of pulmonary vascular bed: This has a poor prognosis, as it is a fixed abnormality.  It is caused by space occupying lesions such as pleural effusions and diaphragmatic hernias.
Functional obstruction of pulmonary blood flow: This has a good prognosis if it is reversible. Causes include polycythemia and hyperfibrinogenemia.

Diagnosis
To help with diagnosis, the clinician can watch out for predisposing factors, such as: birth asphyxia, meconium aspiration, use of NSAIDs (non steroidal anti-inflammatory drugs) and SSRIs (selective serotonin reuptake inhibitors)  by the mother, and early onset sepsis or pneumonia. To diagnose a fetus with pulmonary hypertension, PVR must be higher than systemic vascular resistance, resulting in high afterload and decreased systemic blood flow. This causes a significant decrease in oxygen concentration, which clinically manifests as insufficient blood flow to the lower body, while there is adequate circulation to the head and right side of the body. Other echocardiographic findings in PPHN include right ventricular hypertrophy, deviation of the ventricular septum, tricuspid regurgitation, and shunting at the patent foramen ovale.Other clinical signs that may signify PPHN are respiratory distress, partial pressure of oxygen greater than 100 mg and elevated partial pressure of carbon dioxide. A gradient of 10% or more in oxygenation saturation between simultaneous preductal and postductal arterial blood gas values in absence of structural heart disease documents persistent fetal circulation. Since this may be a sign of other conditions, persistent fetal circulation must also be characterized by enlargement of right and left ventricles often confirmed through a definitive ECG.Persistent fetal circulation in neonates can be reversible or irreversible depending on the classified etiology listed above. If related to pulmonary disorders, the amount of lung damage dictates whether or not treatment is efficacious in reversing newborn lung insufficiency. Other causes for acute pulmonary hypertension include: infection, endocrine disorders, and drug injury.Examples of cases with newborns who with sustained fetal circulation are pulmonary hypoplasia and genetic abnormalities.

Treatment
Treatment aims to increase the amount of oxygen in the blood and reverse any causes of hypoxia as well as gain adequate perfusion.Common treatments include:
Oxygen therapy
Mechanical ventilation
Pulmonary vasodilators
Nitrous Oxide Inhalation (iNO)
Sildenafil
Milrinone
GlucocorticoidsThe therapies available to manage PPHN include high frequency ventilation, surfactant instillation, pulmonary vasodilators, and extracorporeal membrane oxygenation.iNO is the preferred medication for PPHN due to its ability to more selectively cause pulmonary vasodilation in comparison to intravenous vasodilators. While this medication decreases the need for extracorporeal membrane oxygenation or extracorporeal life support, it has not been shown to reduce mortality. Intravenous sildenafil has been shown to have similar efficacy and is becoming more commonly used as treatment for PPHN.Assessment of the efficacy of these treatments includes chest radiographs and arterial blood gases. Signs of inefficacious treatments include prolonged capillary filling time, low pulse volume, low blood pressure, and sustained metabolic acidosis.In addition to treating the direct effects of this condition, other management strategies are implemented concurrently to stabilize the newborn.These include, but are not limited to nutritional support, reduction of stressful environment, gentle sedation, monitoring/treating acidosis and establishing normal systemic blood pressure.Challenges in developing countries:
PPHN has been seen more frequently in developing countries or resource-poor areas, though it occurs across the globe. Treating this condition often involves large interdisciplinary teams, which is not always possible in developing countries </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 Eosinophilic pustular folliculitis of infancy 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 Hyperglycinemia 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 Olivopontocerebellar atrophy and explain in detail? [/INST] Olivopontocerebellar atrophy (OPCA) is the degeneration of neurons in specific areas of the brain – the cerebellum, pons, and inferior olivary nucleus. OPCA is present in several neurodegenerative syndromes, including inherited and non-inherited forms of ataxia (such as the hereditary spinocerebellar ataxia known as Machado–Joseph disease) and multiple system atrophy (MSA), with which it is primarily associated.OPCA  may also be found in the brains of individuals with prion disorders and inherited metabolic diseases.  The characteristic areas of brain damage that indicate OPCA can be seen by imaging the brain using CT scans or MRI studies.The term was originally coined by Joseph Jules Dejerine and André Thomas.

Signs and symptoms
OPCA is characterized by progressive cerebellar ataxia, leading to clumsiness in body movements, veering from midline when walking, wide-based stance, and falls without signs of paralysis or weakness. Clinical presentation can vary greatly between patients, but mostly affects speech, balance and walking.  Other possible neurological problems include spasmodic dysphonia, hypertonia, hyperreflexia, rigidity, dysarthria, dysphagia and neck dystonic posture.

Cause
Olivopontocerebellar atrophy is hereditary, but has an unknown genetic basis </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 Adenoma and explain in detail? [/INST] An adenoma is a benign tumor of epithelial tissue with glandular origin, glandular characteristics, or both. Adenomas can grow from many glandular organs, including the adrenal glands, pituitary gland, thyroid, prostate, and others. Some adenomas grow from epithelial tissue in nonglandular areas but express glandular tissue structure (as can happen in familial polyposis coli). Although adenomas are benign, they should be treated as pre-cancerous. Over time adenomas may transform to become malignant, at which point they are called adenocarcinomas. Most adenomas do not transform. However, even though benign, they have the potential to cause serious health complications by compressing other structures (mass effect) and by producing large amounts of hormones in an unregulated, non-feedback-dependent manner (causing paraneoplastic syndromes). Some adenomas are too small to be seen macroscopically but can still cause clinical symptoms.

Histopathology
Adenoma is a benign tumor of glandular tissue, such as the mucosa of stomach, small intestine, and colon, in which tumor cells form glands or gland like structures.
In hollow organs (digestive tract), the adenoma grows into the lumen - adenomatous polyp or polypoid adenoma. Depending on the type of the insertion base, adenoma may be pedunculated (lobular head with a long slender stalk) or sessile (broad base).
The adenomatous proliferation is characterized by different degrees of cell dysplasia (atypia or loss of normal differentiation of epithelium) irregular cells with hyperchromatic nuclei, stratified or pseudostratified nuclei, nucleolus, decreased mucosecretion, and mitosis. The architecture may be tubular, villous, or tubulo-villous. Basement membrane and muscularis mucosae are intact.

Locations
Colon
Adenomas of the colon, also called adenomatous polyps, are quite prevalent. They are found commonly at colonoscopy. They are removed because of their tendency to become malignant and to lead to colon cancer.
Ashkenazi Jews have a 6% higher risk rate of getting adenomas, and then colon cancer, than do the general population, so it is important that they have regular actual colonoscopies, and specifically none of the less invasive diagnostic methods.

Renal
This is a tumor that is most often small and asymptomatic, and is derived from renal tubules. It may be a precursor lesion to renal carcinoma.

Adrenal
Adrenal adenomas are common, and are often found on the abdomen, usually not as the focus of investigation; they are usually incidental findings. About one in 10,000 is malignant. Thus, a biopsy is rarely called for, especially if the lesion is homogeneous and smaller than 3 centimeters. Follow-up images in three to six months can confirm the stability of the growth.
While some adrenal adenomas do not secrete hormones at all, often some secrete cortisol, causing Cushings syndrome, aldosterone causing Conns syndrome, or androgens causing hyperandrogenism.

Thyroid
About one in 10 people is found to have solitary thyroid nodules. Investigation is required because a small percentage of these is malignant. Biopsy usually confirms the growth to be an adenoma, but, sometimes, excision at surgery is required, especially when the cells found at biopsy are of the follicular type.

Pituitary
Pituitary adenomas are seen in 10% of neurological patients. A lot of them remain undiagnosed. Treatment is usually surgical, to which patients generally respond well. The most common subtype, prolactinoma, is seen more often in women, and is frequently diagnosed during pregnancy as the hormone progesterone increases its growth. Medical therapy with cabergoline or bromocriptine generally suppresses prolactinomas; progesterone antagonist therapy has not proven to be successful.

Parathyroid
An adenoma of a parathyroid gland may secrete inappropriately high amounts of parathyroid hormone and thereby cause primary hyperparathyroidism.

Liver
Hepatic adenomas are a rare benign tumour of the liver, which may present with hepatomegaly or other symptoms.

Breast
Breast adenomas are called fibroadenomas.  They are often very small and difficult to detect.  Often there are no symptoms.  Treatments can include a needle biopsy, and/or removal.

Appendix
Adenomas can also appear in the appendix.  The condition is extremely rare.  The most common version is called cystadenoma.  They are usually discovered in the course of examination of the tissue following an appendectomy.  If the appendix has ruptured and a tumor is present, this presents challenges, especially if malignant cells have formed and thus spread to the abdomen.

Bronchial
Bronchial adenomas are adenomas in the bronchi. They may cause carcinoid syndrome, a type of paraneoplastic syndrome.

Sebaceous
A sebaceous adenoma is a cutaneous condition characterized by a slow-growing tumour usually presenting as a pink, flesh-coloured, or yellow papule or nodule.

Salivary glands
Most salivary gland tumors are benign – that is, they are not cancer and will not spread to other parts of the body. These tumors are almost never life-threatening.
There are many types of benign salivary gland tumors, with names such as adenomas, oncocytomas, Warthin tumors, and benign mixed tumors (also known as pleomorphic adenomas).
Benign tumors are almost always cured by surgery. Very rarely, they may become cancer if left untreated for a long time or if they are not completely removed and grow back. Its not clear exactly how benign tumors become cancers </s>