<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 Interstitial granulomatous dermatitis with arthritis 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 Cross 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 Mineral deficiency 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 Congenital cataract and explain in detail? [/INST] Congenital cataracts refers to a lens opacity which is present at birth. Congenital cataracts cover a broad spectrum of severity: whereas some lens opacities do not progress and are visually insignificant, others can produce profound visual impairment.
Congenital cataracts may be unilateral or bilateral. They can be classified by morphology, presumed or defined genetic cause, presence of specific metabolic disorders, or associated ocular anomalies or systemic findings.

Signs and symptoms
Congenital cataracts occur in a variety of morphologic configurations, including lamellar, polar, sutural, coronary, cerulean, nuclear, capsular, complete, membranous.

Cause
In general, approximately one-third of congenital cataracts are a component of a more extensive syndrome or disease (e.g., cataract resulting from congenital rubella syndrome), one-third occur as an isolated inherited trait, and one-third result from undetermined causes. Metabolic diseases tend to be more commonly associated with bilateral cataracts.

Genetics
Approximately 50% of all congenital cataract cases may have a genetic cause which is quite heterogeneous </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 Intracranial hemorrhage and explain in detail? [/INST] Intracranial hemorrhage (ICH), also known as intracranial bleed, is bleeding within the skull. Subtypes are intracerebral bleeds (intraventricular bleeds and intraparenchymal bleeds), subarachnoid bleeds, epidural bleeds, and subdural bleeds. More often than not it ends in a lethal outcome.
Intracerebral bleeding affects 2.5 per 10,000 people each year.

Signs and symptoms
Intracranial hemorrhage is a serious medical emergency because the buildup of blood within the skull can lead to increases in intracranial pressure, which can crush delicate brain tissue or limit its blood supply.  Severe increases in intracranial pressure (ICP) can cause brain herniation, in which parts of the brain are squeezed past structures in the skull.

Causes
Trauma is the most common cause of intracranial hemorrhage. It can cause epidural hemorrhage, subdural hemorrhage, and subarachnoid hemorrhage. Other condition such as hemorrhagic parenchymal contusion and cerebral microhemorrhages can also be caused by trauma.Non-traumatic causes of hemorrhage includes: hypertension, cerebral amyloid angiopathy, hemorrhagic conversion of ischemic infarction, cerebral aneurysms, dural arteriovenous fistulae, cerebral venous sinus thrombosis, cerebral vasculitis and mycotic aneurysm.More than half of all cases of intracranial hemorrhage are the result of hypertension.

Diagnosis
CT scan (computed tomography) of the brain (without any iodinated contrast), is the initial imaging choice because of its high speed, good accessibility in hospitals, high sensitivity in detecting brain injuries or brain diseases, thus helping to triage patients in emergency department in a timely manner and urgent neurosurgical intervention can be administered. Examples of brain diseases that require urgent intervention are: large volume hemorrhage, brain herniation, and cerebral infarction. Other advantages of CT over MRI scan are ability to detect bony fractures, vascular injury, and cerebrospinal fluid (CSF) leak. It also does not need to screen for MRI safety of implants/foreign body especially for penetrating or blast injuries.However, MRI has higher sensitivity than CT scan for the detection of epidural hemorrhage, subdural hemorrhage, subarachnoid hemorrhage, nonhemorrhagic cortical contusions, hemorrhagic parenchymal contusions, brainstem injuries, and white matter axonal injuries. If CT scan shows normal findings, but the subject has persistent neurological symptoms, MRI is also indicated. However, MRI safety concerns on metallic foreign bodies, limited availability, longer imaging time, high sensitivity to motion, and higher cost limits the usefulness of MRI.Swirl sign on CT scan (areas of low densities with surrounding areas of high densities) is indicative of active intracranial bleeding, high chance of death within one month, and poor subjects function in three months if the subject is still alive.When ICP is increased the heart rate may be decreased.

Traumatic
Types of intracranial hemorrhage are roughly grouped into intra-axial and extra-axial. Intra-axial hemorrhage is bleeding within the brain itself, or cerebral hemorrhage. This category includes intraparenchymal hemorrhage, or bleeding within the brain tissue, and intraventricular hemorrhage, bleeding within the brains ventricles (particularly of premature infants). Intra-axial hemorrhages are more dangerous and harder to treat than extra-axial bleeds. Hemorrhagic parenchymal contusions and cerebral microhemorrhages are examples of traumatic intra-axial bleeds.Extra-axial hemorrhage, bleeding that occurs within the skull but outside of the brain tissue, falls into three subtypes: epidural hematoma, subdural hematoma, and subarachnoid hemorrhage.

Hemorrhagic parenchymal contusion
This condition most commonly occurred in those with significant head movement or head impact. It is caused by injuries of small arterial or venous vessels, causing hemorrhage within the brain parenchyma, and give rise to hyperdense lesion on CT scan. MRI is more sensitive than CT scan in detecting such small hemorrhagic contusions, with the use of gradient echo sequence. Contusions are more commonly seen in the brain parenchyma near base of the skull such as inferior frontal lobes and temporal lobes as a result of Coup contrecoup injury. Those with parenchymal contusion would require frequent follow-up imaging because such contusions may grow large enough to become hemorrhage and exerts significant mass effect on the brain.Cerebral microhemorrhages is a smaller form of hemorrhagic parenchymal contusion and are typically found in white matter. Such microhemorrhages are difficult to be detected on CT scan, but easily detected on gradient echo and susceptibility weighted imaging on MRI scan as hypointense susceptibility blooming. Such microhemorrhages are frequently associated with diffuse axonal injury and located near the grey-white matter junction.

Epidural hemorrhage
Epidural hemorrhage (extradural hemorrhage, EDH) which occur between the dura mater (the outermost meningeal layer) and the skull, is caused by trauma. It does not cross the suture lines of the skull because the superifical dural layer is attached tightly to the skull along the suture lines. Unless rarely, fracture involves the suture lines (more common in children), then epidural hematoma may cross the suture lines. As the blood accumulated in the epidural space is confined within suture lines, accumulation of additional blood will cause bulging in this space, and thus resulting in a typical "biconvex" appearance on CT scans. EDH can be due to arterial or venous rupture depending on the locations. Arterial injuries results in more rapidly growing hematoma when compared to venous injuries. At the pterion region, middle meningeal artery is most commonly affected. When fracture is crossing areas where dural venous sinuses resides, venous hemorrhage can occur such as falx cerebri, tentorium cerebelli, and vertex (where superior sagittal sinus resides). Anterior temporal EDH is usually caused by sphenoparietal sinus. Such EDH is limited and does not require surgery because its extension is confined within sphenosquamosal suture and orbital fissure. In 20 to 50% of epidural hemorrhage cases, there is a lucid interval where a person regained consciousness after being knocked unconscious and then followed by deterioration of consciousness after that.When the epidural hematoma is large enough, it will cause mass effect on contralateral brain which lead to midline, subfalcine (below the falx cerebri), and trans-tentorial (crossing tentorium cerebelli) herniations. This phenomenon can cause the subject to lose consciousness and eventually death. Therefore, large EDH requires emergent surgical clot evacuation. Embolisation of middle meningeal artery is performed if the hemorrhage is medium or small.

Subdural hemorrhage
Subdural hemorrhage (SDH) results from tearing of the bridging veins in the subdural space between the dura and arachnoid mater. It can cross the suture lines, but not across dural reflections such as falx cerebri or tentorium cerebelli. Therefore, subdural hematoma always limited to one side of the brain. Density of SDH reduces as it progresses from acute to chronic forms. However, areas with low density may not represent chronic SDH entirely as unclotted blood products that are due to active bleed can also give low density appearance on CT scans especially those with coagulopathy. Those with SDH that have same density with brain parenchyma may represent acute bleed such as those with anemia, arachnoid tear, and the mixing of hemorrhage and CSF. SDH usually have high or mixed densities during first two days of trauma, followed by isodensity at 11 days after trauma, and hypodensity after 14 days of trauma. Membranes with granulation tissue can rupture within SDH, and give high density appearance on CT scan. Over a prolonged period of time, calcifications can form. SDH can be treated with burr hole drainage, craniotomy or port system placement for blood clot evacuation, or middle meningeal artery embolisation.Subdural hematoma maybe less acute than epidural hematoma due to slower blood accumulation, but it still has the potential to cause brain herniation that may require surgical evacuation. Clinical features depend on the site of injury and severity of injury. Patients may have a history of loss of consciousness but they recover and do not relapse. Clinical onset occurs over hours. Complications include focal neurologic deficits depending on the site of hematoma and brain injury, increased intracranial pressure leading to herniation of brain and ischemia due to reduced blood supply and seizures.

Subarachnoid hemorrhage
A subarachnoid hemorrhage (SAH) is bleeding into the subarachnoid space—the area between the arachnoid membrane and the pia mater surrounding the brain. Trauma can also cause SAH when the arteries and veins coursing through the subarachnoid space are ruptured. It is usually located at the cerebral sulci near the vertex of the head and spare the basal cisterns on CT scan. Severe trauma can cause SAH in all parts of the brain. When the SAH volume is large, rarely it can cause cerebral infarction a few days after trauma due to arterial vasospasm. Although CT scan is performed more often than MRI to detect SAH, MRI is more sensitive than CT in this aspect. SAH shows hyperintense signal of Fluid-attenuated inversion recovery (FLAIR) sequence and blooming artifact on susceptibility weighted imaging (SWI).Computed tomography angiography (CT angiography) or Magnetic resonance angiography (MR angiography) should be done if fracture involves the carotid canal, because in such cases, posttraumatic vasospasm can occur, thus cutting blood supply to the brain. Besides, intracranial hemorrhage that are atypical for trauma should also be investigated further with CT or MR angiography to look for other causes of intracranial bleeds apart from trauma causes. Such atypical patterns includes: isolated SAH in the basal cisterns, isolated large-volume SAH in the Sylvian fissure, and isolated SAH in the anterior interhemispheric fissure. These cases warrants investigations to look for aneurysms that can cause such bleeding.

Non-traumatic
Hypertensive bleed
Intracranial bleed in hypertensive subjects usually occurs at 50 to 60 years of life with 30 to 50% chance of death. Such hemorrhages are typically located in the basal ganglia, cerebellum, or occipital lobes. Other location such as bleed within the cerebral cortex and intracranial bleed in people younger than 50 years should prompt further investigations on other causes of bleed such as brain tumour or cerebral arteriovenous malformation. The bleed can be very small without any significant effect on surrounding brain or large hemorrhage that exerts mass effecct on adjacent brain. Follow up CT scan is recommended. Those with extension of bleed into the ventricular system, expansion of bleeding, or increasing cerebral oedema on CT scan gives poorer prognosis. CT angiography (CTA) of brain can be performed to investigate the source of bleeding. An image during the delayed phase of the CTA may be taken to look for pooling of contrast that signifies active bleeding (known as "Spot sign"). Presence of "Spot sign" signifies poor clinical outcome for the subject.

Cerebral amyloid angiopathy
Cerebral amyloid angiopathy (CAA) is the deposition of Amyloid beta peptide protein within the brain. Accumulation of such peptide proteins within the walls of the arteries can cause weakening of the walls and causes microhemorrhages, SAH within the cerebral sulci or large cerebral intraparenchymal bleed. SAH in CAA can be differentiated from vasculitis by its presentations. SAH in CAA usually occurs in those who age more than 60 years, temporary motor and sensory deficits, and intracranial bleed in white matter adjacent to cerebral cortex. Basal ganglia, posterior fossa, and brainstem are spared. Boston criteria is used to determine the likelihood of a cerebral hemorrhage due to CAA. Definitive diagnosis of CAA is by performing brain biopsyCT scan may show hyperdense intra-axial hemorrhage in the subcortical region. Diffuse white matter hypodensities in both cerebral hemispheres may represents microangiopathic changes. On MRI these lesions will be presented as blooming artifact on gradient echo and susceptibility weighted imaging.

Hemorrhagic conversion of ishemic infarction
43% of those with infarcted brain tissue will develop hemorrhagic conversion. Risk of hemorrhagic is further increased with recanalisation of veins or arteries. Several types of hemorrhages can occur such as petechial hemorrhages around the infarcted margin (HI1), confluent petechial hemorrhages within the infarcted tissue (HI2), hematoma occupying less than 30% of the infarcted tissue (PH1), hematoma involving greater than 30% of infarcted tissue with small mass effect (PH2), and hematoma involving greater than 30% of the infarcted tissue with significant mass effect. However, only PH2 is clinically significant. Those who has infarction should be monitored frequently with CT brains to access hemorrhagic conversions or worsening vasogenic oedema that may require neurosurgical decompression. Dual energy CT scan maybe useful to differentiate the high densities caused by reperfusion hemorrhage (bleeding after endovascular stroke treatment) and high density due to iodinated contrast administered during cerebral angiography.

Cerebral aneurysm
Besides from head injury, it may occur spontaneously, usually from a ruptured cerebral aneurysm (focal outpouchings with weakened walls on the arteries on the brain surface that are prone to rupture). Symptoms of SAH include a severe headache with a rapid onset (thunderclap headache), vomiting, confusion or a lowered level of consciousness, and sometimes seizures. CT scan has 100% sensitivity of detecting SAH at 6 to 24 hours after symptoms onset. The diagnosis is generally confirmed with a CT scan of the head. If CT scan is normal but SAH is still strongly suspected, lumbar puncture can be done at six to twelfth hours after the onset of headache. This is determine the presence of blood within the cerebrospinal fluid (CSF). Those with SAH will have blood and bilirubin within CSF because of degradation red blood cells. Meanwhile, those who has blood within CSF due to traumatic lumbar puncture will not have bilirubin within CSF.  SAH is generally located within basal cisterns, extends diffusely to all subarachnoid spaces (cerebral sulci) or into the ventricular system, or brain parenchyma. Modified Fisher scale is used to describe the volume and distribution of SAH, just predicting the probability of cerebral artery vasospasm after SAH.Treatment is by prompt neurosurgery or radiologically guided interventions with medications and other treatments to help prevent recurrence of the bleeding and complications. Since the 1990s, many aneurysms are treated by a minimal invasive procedure known as endovascular coiling, which is carried out by instrumentation through large blood vessels. However, this procedure has higher recurrence rates than the more invasive craniotomy with clipping.

Cerebral ateriovenous malformation
Cerebral ateriovenous malformation (Cerebral AVM) is characterised by abnormal shunting between cerebral arteries and veins without going through capillaries. Instead the blood goes through a collection of small vessels from arteries to veins. These collection of abnormal small vessels is termed as "nidus". This condition happens in 0.1% of the population has a risk of 2 to 4% per year for intracranial bleeding. Once ruptured, it results in intraparenchymal hemorrhage, intraventricular hemorrhage and SAH. Rupture of cerebral AVM often occurs in young people and children. Cerebral AVM can be diagnosed by computed tomography angiography (CTA) brain, magnetic resonance angiography (MRA) brain, or digital subtraction angiography (DSA). DSA is important to determine whether there is nidal or perinidal aneurysm.

Dural arteriovenous fistulae
Dural arteriovenous fistulae (DAVF) is the direct connection between dural or cerebral arteries with dural venous sinuses or cortical veins. It accounts for 10 to 15% of intracranial arteriovenous shunts. DAVF lacks a nidus. Signs and symptoms of DAVF are: headache, tinnitus, neurological deficits involving cranial nerves, and increased intracranial pressure. DAVF once ruptured, will produce intraparenchymal hemorrhage or SAH. Increase in number of vessels near dural venous sinuses as seen on CTA is suggestive of DVAF. 4DCT may increase the sensitivity of detecting DAVF. In MRI scans, susceptibility weighted imaging (SWI) and arterial spin labelling sequences (labelling protons in blood without the use of contrast media to determine blood flow) are useful in evaluating DAVF. The patterns of draining veins from the fistula determines the risk of DAVF rupture. Increased pressure within the dural venous sinuses causes backpressure into the cortical veins, thus making cortical veins more prone to rupture. The risk of hemorrhage is graded by Cognard and Borden grading systems. These grading systems are based upon the DSA.

Cortical venous/cerebral venous sinus thrombosis
Dural venous sinus thrombosis (DVST) and cortical venous thrombosis (CVT) commonly presents with headache, increased intracranial pressure, or seizures. DVST is more common than CVT. DVST are frequently caused by infections in the skull base, dehydration, thrombophilia, meningioma, and other dural tumours. On CT scans, brain parenchymal hemorrhage that does not confined to specific arterial territory along with hyperdense appearance on dural venous sinuses raises the suspicion of DVST. Further evaluation with CT venography, MR venography, and post gadolinium MRI provides accurate diagnosis of venous thrombosis and follow-up after treatment. These studies demonstrate thrombus as filling defect or lack of signal.

Vasculitis/vasculopathy
Those with vasculitis may be presented with headache, behavioural changes, neurological deficits, or intracranial bleeding. Sulcal SAH is the most common form of intracranial bleed caused by vasculitis. On CT scans, sulcal SAH is seen as hyperdensity within the cerebral sulcus, while on MRI, it is seen as hyperintensity on FLAIR sequence, and hypointensity on GRE/SWI sequence. DSA is important in making the diagnosis of vasculitis or vasculopathy.

Mycotic aneurysm
It is arterial outpouchings arise from distal cerebral arteries. These are pseudoaneurysm, caused by thrombus clogging the distal arteries, which results in inflammation and small tears at the site of occlusion. These inflammation and thrombis can caused by infective endocarditis, artificial heart valve or other heart problems. Similar to vasculitis, rupture of mycotic aneurysm also causes SAH in cerebral sulci, mostly located in the vertex. If mycotic aneurysm is located more proximally, it will produce diffuse SAH pattern. CTA or MRA would produce focal outpouching or increase in diameter of the vessel. Meanwhile, GRE/SWI MRI sequence would produce focal hypointensity. Small mycotic aneurysms are difficult to be seen on CT or MRI. Thus, DSA is useful in identifying these lesions.

Management
For those who is already on blood thinners such as aspirin or clopidogrel for prevention of myocardial infarction or stroke, traumatic intracranial hemorrhage should prompt the use of platelet function assays (PFA-100) to assess the effect of these antiplalelet agents </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 Pretibial myxedema 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 Psychotic depression and explain in detail? [/INST] Psychotic depression, also known as depressive psychosis, is a major depressive episode that is accompanied by psychotic symptoms. It can occur in the context of bipolar disorder or major depressive disorder. It can be difficult to distinguish from schizoaffective disorder, a diagnosis that requires the presence of psychotic symptoms for at least two weeks without any mood symptoms present. Unipolar psychotic depression requires that the psychotic features occur only during episodes of major depression. Diagnosis using the DSM-5 involves meeting the criteria for a major depressive episode, along with the criteria for "mood-congruent or mood-incongruent psychotic features" specifier.

Signs and symptoms
Individuals with psychotic depression experience the symptoms of a major depressive episode, along with one or more psychotic symptoms, including delusions and/or hallucinations. Delusions can be classified as mood congruent or incongruent, depending on whether or not the nature of the delusions is in keeping with the individuals mood state. Common themes of mood congruent delusions include guilt, persecution, punishment, personal inadequacy, or disease. Half of patients experience more than one kind of delusion. Delusions occur without hallucinations in about one-half to two-thirds of patients with psychotic depression. Hallucinations can be auditory, visual, olfactory (smell), or haptic (touch), and are congruent with delusional material. Affect is sad, not flat. Severe anhedonia, loss of interest, and psychomotor retardation are typically present.

Cause
Psychotic symptoms tend to develop after an individual has already had several episodes of depression without psychosis. However, once psychotic symptoms have emerged, they tend to reappear with each future depressive episode. The prognosis for psychotic depression is not considered to be as poor as for schizoaffective disorders or primary psychotic disorders. Still, those who have experienced a depressive episode with psychotic features have an increased risk of relapse and suicide compared to those without psychotic features, and they tend to have more pronounced sleep abnormalities.Family members of those who have experienced psychotic depression are at increased risk for both psychotic depression and schizophrenia.Most patients with psychotic depression report having an initial episode between the ages of 20 and 40. As with other depressive episodes, psychotic depression tends to be episodic, with symptoms lasting for a certain amount of time and then subsiding. While psychotic depression can be chronic (lasting more than 2 years), most depressive episodes last less than 24 months. A study conducted by Kathleen S. Bingham found that patients receiving appropriate treatment for psychotic depression went into "remission". They reported a quality of life similar to that of people without PD.

Pathophysiology
There are a number of biological features that may distinguish psychotic depression from non-psychotic depression. The most significant difference may be the presence of an abnormality in the hypothalamic pituitary adrenal axis (HPA). The HPA axis appears to be dysregulated in psychotic depression, with dexamethasone suppression tests demonstrating higher levels of cortisol following dexamethasone administration (i.e. lower cortisol suppression). Those with psychotic depression also have higher ventricular-brain ratios than those with non-psychotic depression.

Diagnosis
Differential diagnosis
Psychotic symptoms are often missed in psychotic depression, either because patients do not think their symptoms are abnormal or they attempt to conceal their symptoms from others. On the other hand, psychotic depression may be confused with schizoaffective disorder. Due to overlapping symptoms, differential diagnosis includes also dissociative disorders.

Treatment
Several treatment guidelines recommend pharmaceutical treatments that include either the combination of a second-generation antidepressant and atypical antipsychotic or tricyclic antidepressant monotherapy or electroconvulsive therapy (ECT) as the first-line treatment for unipolar psychotic depression.There is no evidence for or against the use of mifepristone.

Combined antidepressant and antipsychotic medications
There is some evidence indicating that combination therapy with an antidepressant plus an antipsychotic is more effective in treating psychotic depression than either antidepressant treatment alone or placebo </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 Angel-shaped phalango-epiphyseal dysplasia and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Renal glycosuria 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 Radicular pain 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 Prurigo gestationis 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 Pyomyositis and explain in detail? [/INST] Pyomyositis is a bacterial infection of the skeletal muscles which results in an abscess. Pyomyositis is most common in tropical areas but can also occur in temperate zones.

Diagnosis
Diagnosis is done via the following manner:
Pus discharge culture and sensitivity
X ray of the part to rule out osteomyelitis
Creatinine phosphokinase (more than 50,000 units)
MRI is useful
Ultrasound guided aspiration

Treatment
The abscesses within the muscle must be drained surgically (not all patient require surgery if there is no abscess) </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 Tooth pathology and explain in detail? [/INST] Tooth pathology is any condition of the teeth that can be congenital or acquired. Sometimes a congenital tooth diseases are called tooth abnormalities. These are among the most common diseases in humans The prevention, diagnosis, treatment and rehabilitation of these diseases are the base to the dentistry profession, in which are dentists and dental hygienists, and its sub-specialties, such as oral medicine, oral and maxillofacial surgery, and endodontics. Tooth pathology is usually separated from other types of dental issues, including enamel hypoplasia and tooth wear.

Examples
Congenital
Anodontia

Acquired
Dental caries—Dental caries are known as cavities or tooth decay Bacteria in the mouth use foods that contain sugar or starch to produce acids which eat away at the tooth’s structure causing destruction to the enamel of the teeth. Meanwhile, the minerals in saliva (calcium and phosphate) together with fluoride are repairing the enamel </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 Dipygus 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 Paroophoron 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 Sanfilippo syndrome and explain in detail? [/INST] Sanfilippo syndrome, also known as mucopolysaccharidosis type III (MPS III), is a rare autosomal recessive lysosomal storage disease that primarily affects the brain and spinal cord. It is caused by a buildup of large sugar molecules called glycosaminoglycans (AKA GAGs, or mucopolysaccharides) in the bodys lysosomes.
Affected children generally do not show any signs or symptoms at birth, although some early indicators can be respiratory issues at birth, large head size, and umbilical hernia. In early childhood, they begin to develop developmental disability and loss of previously learned skills. In later stages of the disorder, they may develop seizures and movement disorders. Patients with Sanfilippo syndrome usually live into adolescence or early adulthood.

Signs and symptoms
The disease manifests in young children. Symptoms usually begin to appear between two and six years of age. Affected infants appear normal, although some mild facial dysmorphism may be noticeable. Of all of the MPS diseases, Sanfilippo syndrome produces the fewest physical abnormalities.
After an initial symptom-free interval, patients usually present with a slowing of development and/or behavioral problems, followed by progressive intellectual decline resulting in severe dementia and progressive motor disease. Acquisition of speech is often slow and incomplete.The disease progresses to increasing behavioral disturbance including temper tantrums, hyperactivity, destructiveness, aggressive behavior, pica, difficulties with toilet training, and sleep disturbance. As affected children initially have normal muscle strength and mobility, the behavioral disturbances may be difficult to manage. The disordered sleep in particular presents a significant problem to care providers.In the final phase of the illness, children become increasingly immobile and unresponsive, often require wheelchairs, and develop swallowing difficulties and seizures. The life-span of an affected child does not usually extend beyond late teens to early twenties.Individuals with MPS type III tend to have mild skeletal abnormalities; osteonecrosis of the femoral head may be present in patients with the severe form. Optic nerve atrophy, deafness, and otitis can be seen in moderate to severe individuals. Other characteristics include coarse facial features, thick lips, synophrys, and stiff joints.It is difficult to clinically distinguish differences among the four types of Sanfilippo syndrome. However, type A is usually the most severe subtype, characterized by earliest onset, rapid clinical progression with severe symptoms, and short survival. The median age of death for children afflicted with type A is 15.4 ± 4.1 years.It is important that simple and treatable conditions such as ear infections and toothaches not be overlooked because of behavior problems that make examination difficult. Children with MPS type III often have an increased tolerance to pain. Bumps, bruises, or ear infections that would be painful for other children often go unnoticed in children with MPS type III. Some children with MPS type III may have a blood-clotting problem during and after surgery.

Genetics
Mutations in four different genes can lead to Sanfilippo syndrome. This disorder is inherited in an autosomal recessive pattern. People with two working copies of the gene are unaffected. People with one working copy are genetic carriers of Sanfilippo syndrome. They have no symptoms but may pass down the defective gene to their children. People with two defective copies will suffer from Sanfilippo syndrome.

Mechanism
Glycosaminoglycans (GAGs) are chains of sugar molecules. They are found in the extracellular matrix and the cell membrane, or stored in the secretory granules. GAGs are stored in the cell lysosome, and are degraded by enzymes such as glycosidases, sulfatases, and acetyltransferases. Deficiency in these enzymes lead to the four subtypes of MPS III.

Diagnosis
Sanfilippo syndrome types A, B, C, and D are considered to be clinically indistinguishable, although mutations in different genes are responsible for each disease. The following discussion is therefore applicable to all four conditions.A urinalysis can show elevated levels of heparan sulfate in the urine. All four types of Sanfilippo syndrome show increased levels of GAGs in the urine; however, this is less true of Sanfilippo syndrome than other MPS disorders. Additionally, urinary GAG levels are higher in infants and toddlers than in older children. In order to avoid a false negative urine test due to dilution, it is important that a urine sample be taken first thing in the morning.The diagnosis may be confirmed by enzyme assay of skin fibroblasts and white blood cells. The enzyme assay is considered to be the most credible diagnostic tool because it detects whether or not the enzymes that are normally present in the cellular pathway that is responsible for breaking down heparan sulfate are present or not, thereby providing a definitive answer. This test is also ideal for younger patients in which collecting a viable urine sample is difficult or impossible. Another diagnostic tool can be gene sequencing. However, if the genetic mutation they carry has never been seen or recorded, the patient would receive a false negative.Prenatal diagnosis is possible by chorionic villus sampling or amniocentesis.

Treatments
Treatment remains largely supportive. The behavioral disturbances of MPS-III respond poorly to medication. If an early diagnosis is made, bone marrow replacement may be beneficial. Although the missing enzyme can be manufactured and given intravenously, it cannot penetrate the blood–brain barrier and therefore cannot treat the neurological manifestations of the disease. Along with many other lysosomal storage diseases, MPS-III exists as a model of a monogenetic disease involving the central nervous system.Several promising therapies are in development. The French company Lysogene is conducting a phase II/III clinical trial of a gene therapy-based treatment. Other potential therapies include chemical modification of deficient enzymes to allow them to penetrate the blood–brain barrier, stabilisation of abnormal but active enzyme to prevent its degradation, and implantation of stem cells strongly expressing the missing enzyme. For any future treatment to be successful, it must be administered as early as possible. Currently MPS-III is mainly diagnosed clinically, by which stage it is probably too late for any treatment to be very effective. Neonatal screening programs would provide the earliest possible diagnosis.The flavonoid genistein decreases the accumulation of GAGs. In vitro, animal studies and clinical experiments suggest that the symptoms of the disease may be alleviated by an adequate dose of genistein. Despite its reported beneficial properties, genistein also has toxic side effects.Several support and research groups have been established to speed the development of new treatments for Sanfilippo syndrome.Participants in the first-ever "Caregiver Preference Study for Sanfilippo Syndrome" advocated for clinical trials that shift focus from primary cognitive outcomes to other multisystem endpoints, and perceptions of non-curative therapies revealed a preference for treatment options that stop or slow the disorder progression to maintain the child’s current function to ensure quality of life; thus, parents express high risk tolerance and a desire for broader inclusion criteria for trials.

Prognosis
According to a study of patients with Sanfilippo syndrome, the median life expectancy varies depending on the subtype. In Sanfilippo syndrome type A, the mean age at death (± standard deviation) was 15.22 ± 4.22 years. For type B, it was 18.91 ± 7.33 years, and for type C it was 23.43 ± 9.47 years. The mean life expectancy for type A has increased since the 1970s.

Epidemiology
Incidence of Sanfilippo syndrome varies geographically, with approximately 1 case per 280,000 live births in Northern Ireland, 1 per 66,000 in Australia, and 1 per 50,000 in the Netherlands.The Australian study estimated the following incidence for each subtype of Sanfilippo syndrome:

History
The condition is named after Sylvester Sanfilippo, the pediatrician who first described the disease in 1963.

Caregiver impact
Caregivers for children with Sanfilippo syndrome face a unique set of challenges because of the diseases complex nature. There is little understanding among clinicians of the family experience of caring for patients with Sanfilippo and how a caregivers experiences change and evolve as patients age </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 Tillaux fracture 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 L1 syndrome and explain in detail? [/INST] L1 syndrome is a group of mild to severe X-linked recessive disorders that share a common genetic basis. The spectrum of L1 syndrome disorders includes X-linked complicated corpus callosum dysgenesis, spastic paraplegia 1, MASA syndrome, and X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS). It is also called L1CAM syndrome (for the disorders causative gene) and CRASH syndrome, an acronym for its primary clinical features: corpus callosum hypoplasia, retardation (intellectual disability), adducted thumbs, spasticity, and hydrocephalus.L1 syndrome can be caused by different variants in L1CAM, the gene that provides the information that allows the body to produce L1 cell adhesion molecule (sometimes called the L1 protein).  The L1 cell adhesion molecule is a surface protein found on the surface of all neurons. It allows neurons to bind to one another and create synapses (connections where information is passed on from the axons of one neuron to the dendrites and cell body of another). As a result, L1 cell adhesion molecule is essential for the structural development of the brain and contributes to the ability to think, move, and develop memories. The type and severity of L1CAM variant causing L1 syndrome in a particular person is directly related to the severity of symptoms and functional impairment that they experience.There is no cure for L1 syndrome, and prognosis is often poor. Life expectancy for people with L1 syndrome can vary dramatically depending on the severity of the condition, with some dying shortly after birth and others reaching adulthood. Treatment for people with L1 syndrome is supportive and aims to improve quality of life and minimize functional impairment.

Signs and symptoms
L1 syndrome presents as a spectrum ranging from mild to severe features. There is a genotype -phenotype correlation across the L1 spectrum, meaning that the specific genetic variant causing an L1-spectrum disorder in a patient determines the severity of the L1 syndrome in that patient. Patients with truncating (loss-of-function) variants in L1CAM, which prevent the full synthesis of L1 (protein) experience more severe features than patients with missense variants in L1CAM, which may result in an abnormal protein but do not prevent its synthesis. Illustrating this difference in L1 syndrome severity, up to 50% of infants born with L1 syndrome caused by a truncating mutation will die before the age of 3 years despite provision of best available medical treatment. In comparison, roughly 10% of infants born with L1 syndrome caused by a missense mutation will die before the age of 3 years.Despite its presentation on a continuous spectrum, L1 syndrome is loosely divided into four discrete phenotypes.

Societal Implications Based on Symptoms
People diagnosed with L1 syndrome often experience issues with respect to societal roles and interactions due to the severe physical and mental disabilities associated with the disorder. These issues can vary depending on the symptoms that manifest in a specific individual and the severity of those symptoms, which is ultimately determined based on where the individual is situated on the L1 syndrome spectrum.Spasticity is one of the most common signs of L1 syndrome and is seen in all four major clinical phenotypes. It is characterized as the continuous contraction of certain muscles, leading to muscle stiffness which can interfere with normal movement and speech. In three of the major phenotypes (except HSAS), this spasticity is presented as spastic paraplegia, where the muscles of the lower limbs are stiff and continuously contracted. This spastic paraplegia often manifests itself as a gait (walking motion) disorder, specifically shuffling gait in MASA syndrome patients, which acts as a source of impairment and stress due to postural instability, and leads to poor quality of life and increased mortality.Aphasia is also a common disorder, especially in people with MASA syndrome (a disorder on the L1 syndrome spectrum) and describes a range of language impairments with respect to syntax (structure), semantics (meaning), phonology (sound), morphology (structure), and/or pragmatics in language comprehension or expression. People with aphasia, as well as their family members, often experience a poor quality of life due to the social isolation and depression caused by this language impairment and therefore may seek therapy to enable functional and socially relevant communication. Therapy services to address aphasia in MASA syndrome patients include one-on-one sessions with a clinician, group therapy, or even computer-based therapy, which is becoming more popular given its accessibility.Intellectual disabilities also contribute to the social difficulties faced by people with L1 syndrome, and can range from mild to severe depending on the persons location on the L1 syndrome spectrum. People with mild intellectual disability usually have an IQ around 50-70 (100 is the average) and are slower in all developmental areas, but they have no unusual physical characteristics and are able to blend in socially. Moderate intellectual disability characteristics include being able to maintain self-care with some support from other, travel to familiar places in the community, communicate in simple ways, and having an IQ around 35–50. Severe intellectual disability is often seen in people with X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS) (on the L1 syndrome spectrum) and has several key characteristics including: the ability to understand speech but otherwise having very limited communication skills; the ability to learn daily routines and simple self-care, but need direct supervision in social settings and need family support to live in a supervised home setting. Depending on the severity of the intellectual disability, people with L1 syndrome will have varying levels of difficulty in adapting to their social environments and may need considerable support from others to complete day-to-day tasks.

X-linked hydrocephalus with stenosis of the aqueduct of Sylvius
X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS) is the most severe phenotype on the L1 spectrum and is predominantly known for its major feature: profound hydrocephalus, typically beginning before birth. Due to its prenatal onset (i.e. before the bones of the skull have fused together), hydrocephalus associated with HSAS results in progressive macrocephaly (abnormal enlargement of the skull) due to markedly increased intracranial pressure. The signs and symptoms of hydrocephalus can vary depending on severity and age of onset, however irritability (due to pain) and vomiting are common amongst infants with the condition. Without treatment, congenital hydrocephalus can be fatal in infancy. In less severe cases of untreated hydrocephalus, a child may progress beyond infancy but often experiences nausea and vomiting, missed developmental milestones (both physical and cognitive/social), diplopia (double vision), and papilledema (swelling of the optic disc) which can progress to permanent visual impairment due to increased intracranial pressure if definitive treatment is withheld. Neurological damage, caused by both hydrocephalus and poor neuronal development because of defects in the L1 cell adhesion molecule, results in nearly all people with HSAS experiencing severe intellectual disability.People living with HSAS will also frequently experience spasticity, a condition causing some muscles to be continuously contracted, thereby causing stiffness of the body and challenges with walking and speaking. Spasticity is also known to cause difficulty in performing activities of daily living such as bathing and showering, dressing, and self-feeding.Despite HSAS frequently being considered an isolated disorder of the central nervous system, its genetic basis also causes musculoskeletal defects that result in more than half of males with HSAS displaying thumbs that are adducted (clasped, or brought inwards towards the palm). Specifically, this abnormal presentation of the hand is due to congenital malformations in the extensor pollicis brevis and/or extensor pollicis longus muscle of forearm.

MASA syndrome
MASA syndrome is named after its four principle features: mental retardation, adducted thumbs (clasped, or brought inwards towards the palm), shuffling gait, and aphasia (a language disability affecting the comprehension and production of speech as well as reading and writing abilities).

Diagnosis
A healthcare provider, usually a medical geneticist (a physician with special training in diagnosing and managing genetic disorders) can provide a clinical diagnosis of L1 syndrome by examining a patient and ordering certain imaging studies, however the presence of L1 syndrome can only be confirmed when a molecular diagnosis has been made through genetic testing.Often, the diagnostic odyssey for a person with L1 syndrome begins prenatally (before they are born) when prenatal ultrasounds reveal non-specific brain abnormalities, ventriculomegaly, or a non-existent or underdeveloped corpus callosum. Fetuses with X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS) will typically have hydrocephalus severe enough to be discovered upon routine fetal ultrasound as early as 18–20 weeks gestation. After birth, in the presence of suggestive features (such as macrocephaly), hydrocephalus can be confirmed with noninvasive imaging including head magnetic resonance imaging, computed tomography, or ultrasound showing ventriculomegaly, or direct measurement of intracranial pressure through invasive techniques such as lumbar puncture. Further, the spasticity found in patients with HSAS can be easily demonstrated by examining the deep tendon reflexes and the extensor plantar reflex (which will both be abnormally brisk and strong due to damage to the cortex and internal capsule of the brain).

There are various types of genetic testing that can be used to confirm an L1 syndrome diagnosis in a patient. After birth, genetic tests carry a low-risk of physical complications and are minimally-painful: for the patient, the process requires a small amount of blood being drawn from the arm using a needle. However, prenatal genetic testing carries significant risks for both the fetus and mother due to the need to remove genetic material from the fetus while it is still in utero. In order to conduct prenatal genetic testing, the mother and fetus must undergo either amniocentesis (the surgical puncturing of the amniotic sac, which holds the fetus in the womb) or, less frequently, chorionic villus sampling. Amniocentesis provides a sample of amniotic fluid that can be used to screen for sequence variants or chromosomal variants, whereas samples obtained through chorionic villus sampling can only be used to detect major chromosomal abnormalities (such as trisomy 21), making chorionic villous sampling less relevant in the context of diagnosing L1 syndrome (which is often caused by sequence variants). Amniocentesis (typically performed between 15 and 18 weeks of pregnancy) has a 1% risk of complications for mother and fetus, including miscarriage, while chorionic villus sampling (typically performed between 10 and 12 weeks of pregnancy) has a 2% risk of complications including miscarriage. Mothers carrying a fetus with suspected L1 syndrome will often elect to undergo amniocentesis despite its risk, rather than waiting to pursue lower-risk genetic testing after their child is born, because prenatal diagnostic results can inform considerations to terminate the pregnancy.For any child born with multiple physical abnormalities, the first-line diagnostic test is chromosomal microarray.

Management
To know the extent of the disease and the required needs of an individual diagnosed with L1 syndrome, some tests are recommended, including: Head imaging study, Complete neurologic evaluation, Developmental evaluation, Evaluation for Hirschsprung disease if there is a history of constipation, Consultation with a clinical geneticist and/or genetic counselor </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 Hutchinsons teeth 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 Vertiginous epilepsy and explain in detail? [/INST] Vertiginous epilepsy is infrequently the first symptom of a seizure, characterized by a feeling of vertigo.  When it occurs, there is a sensation of rotation or movement that lasts for a few seconds before full seizure activity. While the specific causes of this disease are speculative there are several methods for diagnosis, the most important being the patients recall of episodes.  Most times, those diagnosed with vertiginous seizures are left to self-manage their symptoms or are able to use anti-epileptic medication to dampen the severity of their symptoms.Vertiginous epilepsy has also been referred to as epileptic vertigo, vestibular epilepsy, vestibular seizures, and vestibulogenic seizures in different cases, but vertiginous epilepsy is the preferred term.

Signs and Symptoms
The signs of vertiginous epilepsy often occur without a change in the subject’s consciousness so that they are still aware while experiencing the symptoms. It is often described as a sudden onset of feeling like one is turning in one direction, typically lasting several seconds. Although subjects are aware during an episode, they often cannot remember specific details due to disorientation, discomfort, and/or partial cognitive impairment. This sensation of rotational movement in the visual and auditory planes is also known as a vertiginous aura (symptom), which can precede a seizure or may constitute a seizure itself.  Auras are a “portion of the seizure that occur before consciousness is lost and for which memory is retained afterwards.” Auras can be focused in different regions of the brain and can thus affect different functions. Some such symptoms that may accompany vertiginous epilepsy include:

Auditory hallucination
Cognitive impairment
Motor activity
Ictal behavior
Limbic aurasMany people tend to mistake dizziness as vertigo, and although they sound similar, dizziness is not considered a symptom of vertiginous epilepsy. Dizziness is the sensation of imbalance or floating, impending loss of consciousness, and/or confusion.   This is different from vertigo which is characterized by the illusion of rotational movement  caused by the “conflict between the signals sent to the brain by balance- and position-sensing systems of the body”.

Mechanism
Although a specific cause has not been identified to always induce vertiginous epilepsy there have been a number of supported hypotheses to how these seizures come about, the most common being traumatic injury to the head.  Other causes include tumor or cancers in the brain, stroke with loss of blood flow to the brain, and infection.  A less tested hypothesis that some believe may play a larger role in determining who is affected by this disease is a genetic mutation that predisposes the subject for vertiginous epilepsy. This hypothesis is supported by occurrences of vertiginous epilepsy in those with a family history of epilepsy.

Vertiginous epilepsies are included in the category of the partial epilepsy in which abnormal electrical activity in the brain is localized.  With current research, it is presumed that the most likely cause to produce vertigo are epilepsies occurring in the lateral temporal lobe.   These abnormal electrical activities can either originate from within the temporal lobe or may propagate from an epilepsy in a neighboring region of the brain.  Epilepsies in the parietal and occipital lobes commonly propagate into the temporal lobe inducing a vertiginous state.   This electrical propagation across the brain explains why so many different symptoms may be associated with the vertiginous seizure.  The strength of the electrical signal and its direction of propagation in the brain will also determine which associated symptoms are noticeable.

Diagnosis
The most important factor in diagnosing a patient with vertiginous epilepsy is the subject’s detailed description of the episode.   However, due to the associated symptoms of the syndrome a subject may have difficulty remembering the specifics of the experience.   This makes it difficult for a physician to confirm the diagnosis with absolute certainty. A questionnaire may be used to help patients, especially children, describe their symptoms. Clinicians may also consult family members for assistance in diagnosis, relying on their observations to help understand the episodes.  In addition to the description of the event, neurological, physical and hematologic examinations are completed to assist in diagnosis. For proper diagnosis, an otological exam (examination of the ear) should also be completed to rule out disorders of the inner ear, which could also be responsible for manifestations of vertigo. This may include an audiological assessment and vestibular function test. During diagnosis, history-taking is essential in determining possible causes of vertiginous epilepsy as well as tracking the progress of the disorder over time.Other means used in diagnosis of vertiginous epilepsy include:

Electroencephalography (EEG)
Magnetic resonance imaging (MRI)
Positron emission tomography (PET)
Neuropsychological testingThe EEG measures electrical activity in the brain, allowing a physician to identify any unusual patterns.  While EEGs are good for identifying abnormal brain activity is it not helpful in localizing where the seizure originates because they spread so quickly across the brain.  MRIs are used to look for masses or lesions in the temporal lobe of the brain, indicating possible tumors or cancer as the cause of the seizures.  When using a PET scan, a physician is looking to detect abnormal blood flow and glucose metabolism in the brain, which is visible between seizures, to indicate the region of origin.

Management
There is no real way to prevent against vertiginous episodes out of the means of managing the disease. As head trauma is a major cause for vertiginous epilepsy, protecting the head from injury is an easy way to avoid possible onset of these seizures.  With recent advances in science it is also possible for an individual to receive genetic screening, but this only tells if the subject is predisposed to developing the condition and will not aid in preventing the disease.There are a range of ways to manage vertiginous epilepsy depending on the severity of the seizures.  For simple partial seizures medical treatment is not always necessary. To the comfort of the patient, someone ailed with this disease may be able to lead a relatively normal life with vertiginous seizures.  If, however, the seizures become too much to handle, antiepileptic medication can be administered as the first line of treatment. There are several different types of medication on the market to deter epileptic episodes but there is no support to show that one medication is more effective than another. In fact, research has shown that simple partial seizures do not usually respond well to medication, leaving the patient to self-manage their symptoms. A third option for treatment, used only in extreme cases when seizure symptoms disrupt daily life, is surgery wherein the surgeon will remove the epileptic region.

Epidemiology
Vertiginous epilepsy onset can happen between the ages of 4–50, although typically symptoms will begin occurring in adolescence or young adulthood.  Research studies have shown no inclination for this disease between sexes.

History
Caloric reflex testing was developed and used for testing vestibular function of deaf children and in diagnosis of childhood vertigo. A man named Barany (1902) published the first monograph on vestibular nystagmus that recognized the clinical usefulness of caloric responses. Baranys theory of production of the vestibulo-ocular reflex in caloric testing remains as the accepted explanation along with the description of nystagmus created by rotation in both adults and infants </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 Spinocerebellar ataxia type 6 and explain in detail? [/INST] Spinocerebellar ataxia type 6 (SCA6) is a rare, late-onset, autosomal dominant disorder, which, like other types of SCA, is characterized by dysarthria, oculomotor disorders, peripheral neuropathy, and ataxia of the gait, stance, and limbs due to cerebellar dysfunction. Unlike other types, SCA 6 is not fatal.  This cerebellar function is permanent and progressive, differentiating it from episodic ataxia type 2 (EA2) where said dysfunction is episodic. In some SCA6 families, some members show these classic signs of SCA6 while others show signs more similar to EA2, suggesting that there is some phenotypic overlap between the two disorders. SCA6 is caused by mutations in CACNA1A, a gene encoding a calcium channel α subunit. These mutations tend to be trinucleotide repeats of CAG, leading to the production of mutant proteins containing stretches of 20 or more consecutive glutamine residues; these proteins have an increased tendency to form intracellular agglomerations.  Unlike many other polyglutamine expansion disorders expansion length is not a determining factor for the age that symptoms present.

Signs and symptoms
SCA6 is typified by progressive and permanent cerebellar dysfunction. These cerebellar signs include ataxia and dysarthria, likely caused by cerebellar atrophy. Prior to diagnosis and the onset of major symptoms, patients often report a feeling of "wooziness" and momentary imbalance when turning corners or making rapid movements. The age at which symptoms first occur varies widely, from age 19 to 71, but is typically between 43 and 52. Other major signs of SCA6 are the loss of vibratory and proprioceptive sensation and nystagmus.While most patients present with these severe progressive symptoms, others, sometimes within the same family, display episodic non-progressive symptoms more similar to episodic ataxia. Still others present with symptoms common to both SCA6 and familial hemiplegic migraine.

Pathophysiology
Most cases of SCA6 are a result of CAG repeat expansion beyond the normal range, i.e., more than 19 repeats, in the Cav2.1 calcium channel encoding gene CACNA1A. This gene has two splice forms, "Q-type" and "P-type", and the polyglutamine coding CAG expansion occurs in the P-type splice form. This form is expressed heavily in the cerebellum where it is localized in Purkinje cells. In Purkinje cells from SCA6 patients, mutant Cav2.1 proteins form ovular intracellular inclusions, or aggregations, similar in many ways to those seen in other polyglutamine expansion disorders such as Huntingtons disease. In cell culture models of the disease, this leads to early apoptotic cell death.Mutant channels that are able to traffic properly to the membrane have a negatively shifted voltage-dependence of inactivation. The result of this is that the channels are active for a shorter amount of time and, consequently, cell excitability is decreased.There are also a number of point mutations resulting in patients with phenotypes reminiscent of episodic ataxia and SCA6 (C271Y, G293R and R1664Q) or familial hemiplegic migraine and SCA6 (R583Q and I1710T). C287Y and G293R are both located in the pore region of domain 1 and are present in a single family each </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 Erotic asphyxiation and explain in detail? [/INST] Erotic asphyxiation (variously called asphyxiophilia, hypoxyphilia or breath control play) is the intentional restriction of oxygen to the brain for the purposes of sexual arousal. The term autoerotic asphyxiation is used when the act is done by a person to themselves. Colloquially, a person engaging in the activity is sometimes called a gasper. Erotic asphyxiation can lead to accidental death due to asphyxia.
The erotic interest in asphyxiation is classified as a paraphilia in the Diagnostic and Statistical Manual of the American Psychiatric Association.

Physiology
Concerning hallucinogenic states brought about by chronic hypoxia, Dr. E. L. Lloyd notes that they may be similar to the hallucinations experienced by climbers at altitude. He further notes that no such state occurs in hypoxia brought about by sudden aircraft decompression at altitude. These findings suggest to him that they do not arrive purely from a lack of oxygen. Upon examining the studies on hypoxia he found that "abnormalities in the cerebral neurochemistry involving one or more of the interconnected neurotransmitters, dopamine, serotonin, and beta-endorphin had been reported in all the conditions associated with hallucinations."

History
Historically, the practice of autoerotic asphyxiation has been documented since the early 17th century. It was first used as a treatment for erectile dysfunction. The idea for this most likely came from subjects who were executed by hanging. Observers at public hangings noted that male victims developed an erection, sometimes remaining after death (a death erection), and occasionally ejaculated when being hanged.

Practice
Various methods are used to achieve the level of oxygen depletion needed, such as a hanging, suffocation with a plastic bag over the head, self-strangulation such as with a ligature, gas or volatile solvents, chest compression, or some combination of these. Complicated devices (such as hydraulics) are sometimes used to produce the desired effects. The practice can be dangerous even if performed with care and has resulted in a significant number of accidental deaths. Uva (1995) writes "Estimates of the mortality rate of autoerotic asphyxia range from 250 to 1000 deaths per year in the United States." Cases have also been reported in Scandinavia and Germany. Swedish police reported in 1994 that the number of autoerotic asphyxiation fatalities in the Stockholm area (c. 1.7 million inhabitants) were at least five annually, but the number of unrecorded cases was assumed to be high. Autoerotic asphyxiation may often be mistaken for suicide, which is a major cause of death in teenagers.

Accidental death
Deaths often occur when the loss of consciousness caused by partial asphyxia leads to loss of control over the means of strangulation, resulting in continued asphyxia and death. While often asphyxiophilia is incorporated into sex with a partner, others enjoy this behaviour by themselves, making it potentially more difficult to get out of dangerous situations.In some fatality cases, the body of the asphyxiophilic individual is discovered naked or with genitalia in hand, with pornographic material or sex toys present, or with evidence of having orgasmed prior to death. Bodies found at the scene of an accidental death often show evidence of other paraphilic activities, such as fetishistic cross-dressing and masochism. In cases involving teenagers at home, families may disturb the scene by "sanitizing" it, removing evidence of paraphilic activity. This can have the consequence of making the death appear to be a deliberate suicide, rather than an accident.The great majority of known erotic asphyxial deaths are male; among all known cases in Ontario and Alberta from 1974 to 1987, only 1 out of 117 cases was female. Some individual cases of women with erotic asphyxia have been reported </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 Preauricular sinus and cyst and explain in detail? [/INST] Preauricular sinuses and preauricular cysts are two common congenital malformations.  Each involves the external ear. The difference between them is that a cyst does not connect with the skin, but a sinus does </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 Congenital pulmonary airway malformation and explain in detail? [/INST] Congenital pulmonary airway malformation (CPAM), formerly known as congenital cystic adenomatoid malformation (CCAM), is a congenital disorder of the lung similar to bronchopulmonary sequestration. In CPAM, usually an entire lobe of lung is replaced by a non-working cystic piece of abnormal lung tissue. This abnormal tissue will never function as normal lung tissue. The underlying cause for CPAM is unknown. It occurs in approximately 1 in every 30,000 pregnancies.In most cases the outcome of a fetus with CPAM is very good. In rare cases, the cystic mass grows so large as to limit the growth of the surrounding lung and cause pressure against the heart. In these situations, the CPAM can be life-threatening for the fetus. CPAM can be separated into five types, based on clinical and pathologic features. CPAM type 1 is the most common, with large cysts and a good prognosis.  CPAM type 2 (with medium-sized cysts) often has a poor prognosis, owing to its frequent association with other significant anomalies. Other types are rare.

Signs and symptoms
Three quarters of affected patients are asymptomatic. However, 25% develop cyanosis, pneumothorax, and show signs of increased breathing difficulty (tachypnoea and intercostal retractions).At examination, they may show hyper-resonance at percussion, diminished vesicular murmur and an asymmetrical thorax.

Cause
The cause of CPAM is unknown.

Diagnosis
CPAMs are often identified during routine prenatal ultrasonography. Identifying characteristics on the sonogram include: an echogenic (bright) mass appearing in the chest of the fetus, displacement of the heart from its normal position, a flat or everted (pushed downward) diaphragm, or the absence of visible lung tissue.CPAMs are classified into three different types based largely on their gross appearance.  Type I has a large (>2 cm) multiloculated cysts.  Type II has smaller uniform cysts.  Type III is not grossly cystic, referred to as the "adenomatoid" type.  Microscopically, the lesions are not true cysts, but communicate with the surrounding parenchyma. Some lesions have an abnormal connection to a blood vessel from an aorta and are referred to as "hybrid lesions."

Imaging
The earliest point at which a CPAM can be detected is by prenatal ultrasound. The classic description is of an echogenic lung mass that gradually disappears over subsequent ultrasounds. The disappearance is due to the malformation becoming filled with fluid over the course of the gestation, allowing the ultrasound waves to penetrate it more easily and rendering it invisible on sonographic imaging. When a CPAM is rapidly growing, either solid or with a dominant cyst, they have a higher incidence of developing venous outflow obstruction, cardiac failure and ultimately hydrops fetalis. If hydrops is not present, the fetus has a 95% chance of survival. When hydrops is present, risk of fetal demise is much greater without in utero surgery to correct the pathophysiology. The greatest period of growth is during the end of the second trimester, between 20–26 weeks.A measure of mass volume divided by head circumference, termed cystic adenomatoid malformation volume ratio (CVR) has been developed to predict the risk of hydrops. The lung mass volume is determined using the formula (length × width × anteroposterior diameter ÷ 2), divided by head circumference. With a CVR greater than 1.6 being considered high risk. Fetuses with a CVR less than 1.6 and without a dominant cyst have less than a 3% risk of hydrops. After delivery, if the patient is symptomatic, resection is mandated. If the infant is asymptomatic, the need for resection is a subject of debate, though it is usually recommended. Development of recurrent infections, rhabdomyosarcoma, adenocarcinomas in situ within the lung malformation have been reported.

Treatment
In most cases, a fetus with CPAM is closely monitored during pregnancy and the CPAM is removed via surgery after birth. Most babies with a CPAM are born without complication and are monitored during the first few months.  Many patients have surgery, typically before their first birthday, because of the risk of recurrent lung infections associated with CPAMs.  Some pediatric surgeons can safely remove these lesions using very tiny incisions using minimally invasive surgical techniques (thoracoscopy) </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 Enteritis and explain in detail? [/INST] Enteritis is inflammation of the small intestine. It is most commonly caused by food or drink contaminated with pathogenic microbes, such as serratia, but may have other causes such as NSAIDs, radiation therapy as well as autoimmune conditions like Crohns disease and celiac disease. Symptoms include abdominal pain, cramping, diarrhea, dehydration, and fever. Related diseases of the gastrointestinal system include inflammation of the stomach and large intestine.

Duodenitis, jejunitis and ileitis are subtypes of enteritis which are localised to a specific part of the small intestine. Inflammation of both the stomach and small intestine is referred to as gastroenteritis.

Signs and symptoms
Signs and symptoms of enteritis are highly variable and vary based on the specific cause and other factors such as individual variance and stage of disease.
Symptoms may include abdominal pain, cramping, diarrhea, dehydration, fever, nausea, vomiting and weight loss.

Causes
Autoimmune
Crohns disease – also known as regional enteritis, it can occur along any surface of the gastrointestinal tract. In 40% of cases, it is limited to the small intestine.Coeliac disease – caused by an autoimmune reaction to gluten by genetically predisposed individuals.Eosinophilic enteropathy – a condition where eosinophils build up in the gastrointestinal tract and blood vessels, leading to polyp formation, necrosis, inflammation and ulcers. It is most commonly seen in patients with a history of atopy, however is overall relatively uncommon.

Infectious enteritis
In Germany, 90% of cases of infectious enteritis are caused by four pathogens, Norovirus, Rotavirus, Campylobacter and Salmonella. Other common causes of infectious enteritis include bacteria such as Shigella and E. coli, as well as viruses such as adenovirus, astrovirus and calicivirus. Other less common pathogens include Bacillus cereus, Clostridium perfringens, Clostridium difficile and Staphylococcus aureus.Campylobacter jejuni  is one of the most common sources of infectious enteritis, and the most common bacterial pathogen found in 2 year old and smaller children with diarrhoea. It has been linked to consumption of contaminated water and food, most commonly poultry and milk. The disease tends to be less severe in developing countries, due to the constant exposure which people have with the antigen in the environment, leading to early development of antibodies.Rotavirus is responsible for infecting 140 million people and causing 1 million deaths each year, mostly in children younger than 5 years. This makes it the most common cause of severe childhood diarrhoea and diarrhea-related deaths in the world. It selectively targets mature enterocytes in the small intestine, causing malabsorption, as well as inducing secretion of water. It has also been observed to cause villus ischemia, and increase intestinal motility. The net result of these changes is induced diarrhoea.
Enteritis necroticans is an often fatal illness, caused by β-toxin of Clostridium perfringens. This causes inflammation and segments of necrosis throughout the gastrointestinal tract. It is most common in developing countries, however has also been documented in post-World War II Germany. Risk factors for enteritis necroticans include decreased trypsin activity, which prevent intestinal degradation of the toxin, and reduced intestinal motility, which increases likelihood of toxin accumulation.

Vascular disease
Ischemic enteritis is uncommon compared to ischemic colitis due to the highly vascularised nature of the small intestine, allowing for sufficient blood flow in most situations. It develops due to circulatory shock of mesenteric vessels in the absence of major vessel occlusion, often associated with an underlying condition such as hypertension, arrhythmia or diabetes. Thus it has been considered to be associated with atherosclerosis. Surgical treatment is usually required due to the likelihood of stenosis or complete occlusion of the small intestine. Ischemic damage can range from mucosal infarction, which is limited only to the mucosa; mural infarction of the mucosa and underlying submucosa; to transmural infarction of the full thickness of the gastrointestinal wall. Mucosal and mural infarcts in and of themselves may not be fatal, however may progress further to a transmural infarct </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 Nitrogen dioxide poisoning and explain in detail? [/INST] Nitrogen dioxide poisoning is the illness resulting from the toxic effect of nitrogen dioxide (NO2). It usually occurs after the inhalation of the gas beyond the threshold limit value.
Nitrogen dioxide is reddish-brown with a very harsh smell at high concentrations, at lower concentrations it is colorless but may still have a harsh odour. Nitrogen dioxide poisoning depends on the duration, frequency, and intensity of exposure.
Nitrogen dioxide is an irritant of the mucous membrane linked with another air pollutant that causes pulmonary diseases such as obstructive lung disease, asthma, chronic obstructive pulmonary disease and sometimes acute exacerbation of COPD and in fatal cases, deaths.
Its poor solubility in water enhances its passage and its ability to pass through the moist oral mucosa of the respiratory tract.
Like most toxic gases, the dose inhaled determines the toxicity on the respiratory tract. Occupational exposures constitute the highest risk of toxicity and domestic exposure is uncommon. Prolonged exposure to low concentration of the gas may have lethal effects, as can short-term exposure to high concentrations like chlorine gas poisoning. It is one of the major air pollutants capable of causing severe health hazards such as coronary artery disease as well as stroke.
Nitrogen dioxide is often released into the environment as a byproduct of fuel combustion but rarely released by spontaneous combustion. Known sources of nitrogen dioxide gas poisoning include automobile exhaust and power stations.
The toxicity may also result from non-combustible sources such as the one released from anaerobic fermentation of food grains and anaerobic digestion of biodegradable waste.The World Health Organization (WHO) developed a global recommendation limiting exposures to less than 20 parts per billion for chronic exposure and value less 100 ppb for one hour for acute exposure, using nitrogen dioxide as a marker for other pollutants from fuel combustion.
There is a significant association between indoor NO2 levels and increased respiratory symptoms such as wheeze, chest tightness and severity of infections among children with asthma.
Historically, some cities in the United States including Chicago and Los Angeles have higher levels of nitrogen dioxide than the EPA maximum exposure limits of 100 ppb for a one-hour exposure and less than 53 ppb for chronic exposure.

Signs and symptoms
Nitrogen dioxide poisoning is harmful to all forms of life just like chlorine gas poisoning and carbon monoxide poisoning. It is easily absorbed through the lungs and its inhalation can result in heart failure and sometimes death in severe cases.
Individuals and races may differ in nitrogen dioxide tolerance level and individual tolerance level for the gas may be altered by several factors, such as metabolic rate, barometric pressure, and hematological disorders but significant exposure may result in fatal conditions that could lead to shorter lifespan due to heart failure.

Acute poisoning
Exposure to high level of nitrogen dioxide may lead to inflammation of the mucous membrane and the lower and upper respiratory tracts.
The symptoms of acute nitrogen dioxide poisoning is non-specific and have a semblance with ammonia gas poisoning, chlorine gas poisoning, and carbon monoxide poisoning. The symptoms also resembles that of pneumonia or viral infection and other inhalational injuries but common symptoms includes rhinitis wheezing or coughing, conjunctivitis, headache, throat irritation and dyspnea which may progress to nasal fissures, ulcerations, or perforation.
The patient is usually ill-appearing and presents with hypoxemia coupled with shallow rapid breathing.
Therapy is supportive and includes removal from further nitrogen dioxide exposure.
Systemic symptoms include fever and anorexia. Electrocardiography and chest radiography can help in revealing diffuse, bilateral alveolar infiltrates.
Chest radiography may be used in diagnosis and the baseline could be established with pulmonary function testing.
There is no specific laboratory diagnostic test for acute nitrogen dioxide poisoning but analysis of arterial blood gas level,
methemoglobin level, complete blood count, glucose test, lactate threshold measurement and r peripheral blood smear may be helpful in the diagnosis of nitrogen dioxide poisoning.
The determination of nitrogen dioxide in urine or tissue does not establish the diagnosis, and there are technical and interpretive problems with these tests.

Chronic poisoning
Prolonged exposure to high levels of nitrogen dioxide can have an inflammatory effect that principally targets the respiratory tracts leading to chronic nitrogen dioxide poisoning which can occur within days or weeks after the threshold limit value is excessively exceeded.This condition causes fever, rapid breathing coupled with rapid heart rate, labored breathing and severe shortness of breath. Other effects include diaphoresis, chest pain, and persistent dry cough, all of which may result in weight loss, anorexia and may also lead to right-side heart enlargement and heart disease in advanced cases.
Prolonged exposure to relatively low levels of nitrogen (II) oxide may cause persistent headaches and nausea.
Like chlorine gas poisoning, symptoms usually resolve themselves upon removal from further nitrogen dioxide exposure, unless there had been an episode of severe acute poisoning.
Treatment and management vary with symptoms. Patients are often observed for hypoxemia for a minimum of 12 hours if there are no initial symptoms and if the patient is hypoxemic, oxygen may be administered but high-dose steroids are recommended for patients with pulmonary manifestations. Patients may also be hospitalized for 12 to 24 hours or longer for observation if the gaseous exchange is impaired.
In a case where gaseous exchange is impaired, mechanical ventilation and intubation may be necessary and if bronchiolitis obliterans develop within 2 to 6 weeks of nitrogen dioxide exposure, corticosteroid therapy or anticholinergic medications may be required for 6 to 12 months to lower the body overreaction to nitrogen dioxide gas.

Cause
Occupational exposures constitute the highest risk of toxicity and it is often high for farmers especially those that deal with food grains. It is equally high for firefighters and military personnel, especially those officers that deal in explosives. The risk is also high for arc welders, traffic officers, aerospace staffs and miners as well as those people whose occupations are connected with the nitric acid. Silo-fillers disease is a consequence of exposure to nitrogen dioxide poisoning by farmers dealing with silos. Food grains such as corn and millet, as well as grasses such as alfalfa and some other plant material, produces nitrogen dioxide within hours due to anaerobic fermentation. The threshold concentrations of nitrogen dioxide are often attained within 1 to 2 days and begin to decline gradually after 10 to 14 days but if the silos is well sealed, the gas may remain in there for weeks. Heavily fertilized silage, particularly the ones produced from immature plants, generate a higher concentration of the gas within the silo.
Nitrogen dioxide is about 1.5 times heavier than air and during silage storage, nitrogen dioxide remains in the silage material.
Improper ventilation may result in exposure during the leveling of the silage.

Pathophysiology
Nitrogen dioxide is sparingly soluble in water and on inhalation, it diffuses into the lung and slowly hydrolyzes to nitrous and nitric acid which causes pulmonary edema and pneumonitis leading to the inflammation of the bronchioles and pulmonary alveolus resulting from lipid peroxidation and oxidative stress.
Mucous membrane is primarily affected along with type I pneumocyte and the respiratory epithelium. The generation of free radicals from lipid peroxidation results in irritation of the bronchioles and alveoli that causes rapid destruction of the respiratory epithelial cells.
The overall reaction results in the release of fluid that causes pulmonary edema.Nitrogen dioxide poisoning may alter macrophage activity and immune function leading to susceptibility of the body to a wide range of infections, and overexposure to the gas may also lead to methemoglobinemia, a disorder characterized by a higher than normal level of methemoglobin (metHb, i.e., ferric [Fe3+] rather than ferrous [Fe2+] haemoglobin) in the blood.
Methemoglobinemia prevents the binding of oxygen to haemoglobin causing oxygen depletion that could lead to severe hypoxia.If nitrogen dioxide poisoning is untreated,  fibrous granulation tissue is likely to develop within the alveolar ducts, tiny ducts that connect the respiratory bronchioles to alveolar sacs, each of which contains a collection of alveoli (small mucus-lined pouches made of flattened epithelial cells). The overall reaction may cause an obstructive lung disease. Meanwhile, proliferative bronchiolitis is a secondary effect of nitrogen dioxide poisoning.

Epidemiology
The EPA have some regulations and guidelines for monitoring nitrogen dioxide levels. Historically, some states in the U.S including Chicago, Northeast corridor and L.A have had high levels of nitrogen dioxide.
In 2006, the WHO estimated that over 2 million deaths result annually from air pollution in which nitrogen dioxide constitute one of the pollutants. While over 50% of the disease that results from these pollutants are common in developing countries and the effects in developed countries is also significant. An EPA survey in the U.S. suggests that 16 percent of United States housing units are sited close to an airport, highway or railroad increasing in the United States the exposure risk of approximately 48 million people.
A feasibility study of the ozone formed from the oxidation of nitrogen dioxide in ambient air reported by the WHO suggested that daily deaths of 1 to 2% is attributed to exposure to ozone concentration above 47.3 ppb and exposure above 75.7ppb is attributed to 3 to 5% increase in daily mortality. A level of 114 ppb was attributed to 5 to 9% increase daily mortality.
Silo fillers disease is pervasive during the harvest seasons of food grains.In May 2015, the National Green Tribunal directed Delhi and other states in India to ban diesel vehicles over 10 years old as a measure to reduce nitrogen dioxide emission that may result in nitrogen dioxide poisoning. In 2008, the report of United Kingdom Committee on the Medical Effects of Air Pollutants (COMEAP) suggested that air pollution is the cause of about 29,000 deaths in UK. The WHO urban air quality database estimated Delhis mean annual PM 10 levels in 2010 as 286 μg /m3 and London as 23 μg /m3. In 2014, the database estimated Delhis annual mean PM 2.5 particulate matter levels in 2013 as 156 μg /m3 whereas, London have only 8 μg /m3 in 2010 but the nitrogen dioxide in London breach the European Unions standard. In 2013, the annual mean nitrogen dioxide level in London was estimated as 58 μg /m3 but the save and "threshold limit value" is 40 μg /m3. In March 2015, Brussels took the United Kingdom into court for breaching emissions limits of nitrogen dioxide at its coal-fired Aberthaw power stations in Wales. The plant operated  under a permit allowing emissions of 1200 mg/Nm3, which is more than twice the 5 mg/Nm3 limit specified in the EUs large combustion plant directive.

Prognosis
Generally, long-term prognosis is helpful to survival of initial exposure to nitrogen dioxide. Some cases of nitrogen dioxide poisoning resolves with no observable symptoms and patient may be determined by pulmonary function testing. If chronic exposure causes lung damage, it could take several days or months for the pulmonary function to improve </s>