<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Silent stroke and can you explain it in depth? [/INST] A silent stroke (or asymptomatic cerebral infarction) is a stroke that does not have any outward symptoms associated with stroke, and the patient is typically unaware they have suffered a stroke. Despite not causing identifiable symptoms, a silent stroke still causes damage to the brain and places the patient at increased risk for both transient ischemic attack and major stroke in the future. In a broad study in 1998, more than 11 million people were estimated to have experienced a stroke in the United States. Approximately 770,000 of these strokes were symptomatic and 11 million were first-ever silent MRI infarcts or hemorrhages. Silent strokes typically cause lesions which are detected via the use of neuroimaging such as MRI. The risk of silent stroke increases with age but may also affect younger adults. Women appear to be at increased risk for silent stroke, with hypertension and current cigarette smoking being amongst the  predisposing factors.These types of strokes include lacunar and other ischemic strokes and minor hemorrhages. They may also include leukoaraiosis (changes in the white matter of the brain): the white matter is more susceptible to vascular blockage due to reduced amount of blood vessels as compared to the cerebral cortex. These strokes are termed "silent" because they typically affect "silent" regions of the brain that do not cause a noticeable change in an afflicted person’s motor functions such as contralateral paralysis, slurred speech, pain, or an alteration in the sense of touch. A silent stroke typically affects regions of the brain associated with various thought processes, mood regulation and cognitive functions and is a leading cause of vascular cognitive impairment and may also lead to a loss of urinary bladder control.In the Cardiovascular Health Study, a population study conducted among 3,660 adults over the age of 65. 31% showed evidence of silent stroke in neuroimaging studies utilizing MRI. These individuals were unaware they had suffered a stroke. It is estimated that silent strokes are five times more common than symptomatic stroke.A silent stroke differs from a transient ischemic attack (TIA). In TIA symptoms of stroke are exhibited which may last from a few minutes to 24 hours before resolving. A TIA is a risk factor for having a major stroke and subsequent silent strokes in the future.

Types
Ischemic stroke: occurs when a blood vessel supplying blood to the brain becomes blocked. This type of stroke accounts for approximately 87 percent of all stroke cases.
Hemorrhagic stroke: occurs when a blood vessel supplying blood to the brain becomes weakened and ruptures. Typically hemorrhagic stroke is caused by two types of weakened blood vessel: aneurysms and arteriovenous malformations (AVMs).
Lacunar infarcts (LACI) are small (0.2 to 15 mm in diameter) noncortical (does not affect cerebral cortex) infarcts caused by the occlusion of a single penetrating branch of a larger blood vessel that provides blood to the brains deep structures including the  white matter. LACIs are strongly associated with the development of white matter lesions (WML) which can be detected via the use of computerized tomography (CT scans).

Risk factors
There are various individual risk factors associated with having a silent stroke. Many of these risk factors are the same as those associated with having a major symptomatic stroke.

Acrolein: elevated levels of acrolein, a toxic metabolite produced from the polyamines spermine, spermidine and by amine oxidase serve as a marker for silent stroke, when elevated in conjunction with C-reactive protein and interleukin 6 the confidence levels in predicting a silent stroke risk increase.
Adiponectin: is a type of protein secreted by adipose cells that improves insulin sensitivity and possesses antiatherogenic properties. Lower levels of s-adiponectin are associated with ischemic stroke.
Aging: the prevalence of silent stroke rises with increasing age with a prevalence rate of over twenty percent of the elderly increasing to 30%-40% in those over the age of 70.
Anemia: children with acute anemia caused by medical conditions other than sickle cell anemia  with hemoglobin below 5.5 g/dL. are at increased risk for having a silent stroke according to a study released at American Stroke Associations International Stroke Conference 2011. The researchers suggested a thorough examination for evidence of silent stroke in all severely anemic children in order to facilitate timely intervention to ameliorate the potential brain damage.Sickle cell anemia: is an autosomal recessive genetic blood disorder caused in the gene (HBB gene) which codes for hemoglobin (Hg) and results in lowered levels. The blood cells in sickle cell disease are abnormally shaped  (sickle-shaped) and may form clots or block blood vessels. Estimates of children with sickle cell anemia who suffer strokes (with silent strokes predominating in the younger patients) range from 15%-30%. These children are at significant risk of cognitive impairment and poor educational outcomes.
Thalassemia major: is an autosomal recessive genetically inherited form of hemolytic anemia, characterized by red blood cell (hemoglobin) production abnormalities. Children with this disorder are at increased risk for silent stroke.
Atrial fibrillation (AF): atrial fibrillation (irregular heartbeat) is associated with a doubled risk for silent stroke.
Cigarette smoking: The procoagulant and atherogenic effects of smoking increase the risk for silent stroke. Smoking also has a deleterious effect on regional cerebral blood flow (rCBF). The chances of having a stroke increase with the amount of cigarettes smoked and the length of time an individual has smoked (pack years).
C-reactive protein (CRP) and Interleukin 6 (IL6): C-reactive protein is one of the plasma proteins known as  acute phase proteins (proteins whose plasma concentrations increase (or decrease) by 25% or more during inflammatory disorders) which is produced by the liver. The level of CRP rises in response to inflammation in various parts of the body including vascular inflammation. The level of CRP can rise as high as 1000-fold in response to inflammation. Other conditions that can cause marked changes in CRP levels include infection, trauma, surgery, burns, inflammatory conditions, and advanced cancer. Moderate changes can also occur after strenuous exercise, heatstroke, and childbirth. Increased levels of CRP as measured by a CRP test or the more sensitive high serum CRP (hsCRP) test have a close correlation to increased risk of silent stroke. Interleukin-6 is an interleukin (type of protein) produced by T-cells (specialized white blood cells), macrophages and endothelial cells. IL6 is also classified as a cytokine (acts in relaying information between cells). IL6 is involved in the regulation of the acute phase response to injury and infection may act as both an anti-inflammatory agent and a pro-inflammatory. Increased levels of CRP as measured by a CRP test or the more sensitive high serum CRP (hsCRP) test and elevated levels of I6 as measured by an IL6 ELISA are markers for the increased risk of silent stroke.
Diabetes mellitus: untreated or improperly managed diabetes mellitus is associated with an increased risk for silent stroke.
Hypertension: which affects up to 50 million people in the United States alone is the major treatable risk factor associated with silent strokes.
Homocysteine: elevated levels of total homocysteine (tHcy) an amino acid are an independent risk factor for silent stroke, even in healthy middle-aged adults.
Metabolic syndrome (MetS):Metabolic syndrome is a name for a group of risk factors that occur together and increase the risk for coronary artery disease, stroke, and type 2 diabetes. A higher number of these MetS risk factors the greater the chance of having a silent stroke.Polycystic ovary syndrome (PCOS): is associated with double the risk for arterial disease including silent stroke independent of the subjects Body mass index (BMI).
Sleep apnea: encompasses a heterogeneous group of sleep-related breathing disorders in which there is repeated intermittent episodes of breathing cessation or hypopnea, when breathing is shallower or slower than normal. Sleep apnea is a common finding in stroke patients but recent research suggests that it is even more prevalent in silent stroke and  chronic microvascular changes in the brain </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Ackerman syndrome and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Stimulant psychosis and can you explain it in depth? [/INST] Stimulant psychosis is a mental disorder characterized by psychotic symptoms (such as hallucinations, paranoid ideation, delusions, disorganized thinking, grossly disorganized behaviour) which involves and typically occurs following an overdose or several day binge on psychostimulants; however, it has also been reported to occur in approximately 0.1% of individuals, within the first several weeks after starting amphetamine or methylphenidate therapy. Methamphetamine psychosis, or long-term effects of stimulant use in the brain (at the molecular level), depend upon genetics and may persist for some time.The most common causative agents are substituted amphetamines, including substituted cathinones, as well as certain dopamine reuptake inhibitors such as cocaine and phenidates.

Signs and symptoms
The symptoms of stimulant psychosis vary depending on the drug ingested, but generally involve the symptoms of organic psychosis such as hallucinations, delusions, or paranoia. Other symptoms may include mania, erratic behavior, agitation and/or aggression.

Cause
Substituted amphetamines
Drugs in the class of amphetamines, or substituted amphetamines, are known to induce "amphetamine psychosis" typically when chronically abused or used in high doses. In an Australian study of 309 active methamphetamine users, 18% had experienced a clinical level psychosis in the past year. Commonly abused amphetamines include methamphetamine, MDMA, 4-FA, as well as substituted cathinones like a-PVP, MDPV, and mephedrone, though a large number of other closely related compounds have been recently synthesized. Methylphenidate is sometimes incorrectly included in this class, although it is nonetheless still capable of producing stimulant psychosis.
The symptoms of amphetamine psychosis include auditory and visual hallucinations, grandiosity, delusions of persecution, and delusions of reference concurrent with both clear consciousness and prominent extreme agitation. A Japanese study of recovery from methamphetamine psychosis reported a 64% recovery rate within 10 days rising to an 82% recovery rate at 30 days after methamphetamine cessation. However it has been suggested that around 5–15% of users fail to make a complete recovery in the long term. Furthermore, even at a small dose, the psychosis can be quickly reestablished. Psychosocial stress has been found to be an independent risk factor for psychosis relapse even without further substituted amphetamine use in certain cases.The symptoms of acute amphetamine psychosis are very similar to those of the acute phase of schizophrenia although in amphetamine psychosis visual hallucinations are more common and thought disorder is rare. Amphetamine psychosis may be purely related to high drug usage, or high drug usage may trigger an underlying vulnerability to schizophrenia. There is some evidence that vulnerability to amphetamine psychosis and schizophrenia may be genetically related. Relatives of methamphetamine users with a history of amphetamine psychosis are five times more likely to have been diagnosed with schizophrenia than relatives of methamphetamine users without a history of amphetamine psychosis. The disorders are often distinguished by a rapid resolution of symptoms in amphetamine psychosis, while schizophrenia is more likely to follow a chronic course.Although rare and not formally recognized, a condition known as Amphetamine Withdrawal Psychosis (AWP) may occur upon cessation of substituted amphetamine use and, as the name implies, involves psychosis that appears on withdrawal from substituted amphetamines.  However, unlike similar disorders, in AWP, substituted amphetamines reduce rather than increase symptoms, and the psychosis or mania resolves with resumption of the previous dosing schedule.

Cocaine
Cocaine has a similar potential to induce temporary psychosis with more than half of cocaine abusers reporting at least some psychotic symptoms at some point. Typical symptoms include paranoid delusions that they are being followed and that their drug use is being watched, accompanied by hallucinations that support the delusional beliefs. Delusional parasitosis with formication ("cocaine bugs") is also a fairly common symptom.Cocaine-induced psychosis shows sensitization toward the psychotic effects of the drug. This means that psychosis becomes more severe with repeated intermittent use.

Phenidates
Methylphenidate and its analogues (such as ethylphenidate, 4F-MPH, and isopropylphenidate) share similar pharmacological profiles as other norepinephrine-dopamine reuptake inhibitors. Chronic abuse of methylphenidate has the potential to lead to psychosis. Similar psychiatric side effects have been reported in a study of ethylphenidate. No studies regarding psychosis and 4F-MPH or isopropylphenidate have been conducted, but given their high DAT binding and cellular uptake activity, the possibility of stimulant psychosis remains.

Caffeine
There is limited evidence that caffeine, in high doses or when chronically abused, may induce psychosis in normal individuals and worsen pre-existing psychosis in those diagnosed with schizophrenia.

Diagnosis
Differential diagnosis
Though less common than stimulant psychosis, stimulants such as cocaine and amphetamines as well as the dissociative drug phencyclidine (PCP, angel dust) may also cause a theorized severe and life-threatening condition known as excited delirium </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Prurigo and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Head injury and can you explain it in depth? [/INST] A head injury is any injury that results in trauma to the skull or brain. The terms traumatic brain injury and head injury are often used interchangeably in the medical literature. Because head injuries cover such a broad scope of injuries, there are many causes—including accidents, falls, physical assault, or traffic accidents—that can cause head injuries.
The number of new cases is 1.7 million in the United States each year, with about 3% of these incidents leading to death. Adults have head injuries more frequently than any age group resulting from falls, motor vehicle crashes, colliding or being struck by an object, or assaults. Children, however, may experience head injuries from accidental falls or intentional causes (such as being struck or shaken) leading to hospitalization. Acquired brain injury (ABI) is a term used to differentiate brain injuries occurring after birth from injury, from a genetic disorder, or from a congenital disorder.Unlike a broken bone where trauma to the body is obvious, head trauma can sometimes be conspicuous or inconspicuous. In the case of an open head injury, the skull is cracked and broken by an object that makes contact with the brain. This leads to bleeding. Other obvious symptoms can be neurological in nature. The person may become sleepy, behave abnormally, lose consciousness, vomit, develop a severe headache, have mismatched pupil sizes, and/or be unable to move certain parts of the body. While these symptoms happen immediately after a head injury occurs, many problems can develop later in life. Alzheimers disease, for example, is much more likely to develop in a person who has experienced a head injury.
Brain damage, which is the destruction or degeneration of brain cells, is a common occurrence in those who experience a head injury. Neurotoxicity is another cause of brain damage that typically refers to selective, chemically induced neuron/brain damage.

Classification
Head injuries include both injuries to the brain and those to other parts of the head, such as the scalp and skull. Head injuries can be closed or open. A closed (non-missile) head injury is where the dura mater remains intact. The skull can be fractured, but not necessarily. A penetrating head injury occurs when an object pierces the skull and breaches the dura mater. Brain injuries may be diffuse, occurring over a wide area, or focal, located in a small, specific area. A head injury may cause skull fracture, which may or may not be associated with injury to the brain. Some patients may have linear or depressed skull fractures. If intracranial hemorrhage occurs, a hematoma within the skull can put pressure on the brain. Types of intracranial hemorrhage include subdural, subarachnoid, extradural, and intraparenchymal hematoma. Craniotomy surgeries are used in these cases to lessen the pressure by draining off the blood.
Brain injury can occur at the site of impact, but can also be at the opposite side of the skull due to a contrecoup effect (the impact to the head can cause the brain to move within the skull, causing the brain to impact the interior of the skull opposite the head-impact). While impact on the brain at the same site of injury to the skull is the coup effect. If the impact causes the head to move, the injury may be worsened, because the brain may ricochet inside the skull causing additional impacts, or the brain may stay relatively still (due to inertia) but be hit by the moving skull (both are contrecoup injuries).
Specific problems after head injury can include

Concussion
A concussion is a form of a mild traumatic brain injury (TBI). This injury is a result due to a blow to the head that could make the persons physical, cognitive, and emotional behaviors irregular. Symptoms may include clumsiness, fatigue, confusion, nausea, blurry vision, headaches, and others. Mild concussions are associated with sequelae. Severity is measured using various concussion grading systems.
A slightly greater injury is associated with both anterograde and retrograde amnesia (inability to remember events before or after the injury). The amount of time that the amnesia is present correlates with the severity of the injury. In all cases, the patients develop post concussion syndrome, which includes memory problems, dizziness, tiredness, sickness and depression. Cerebral concussion is the most common head injury seen in children.

Intracranial bleeding
Types of intracranial hemorrhage are roughly grouped into intra-axial and extra-axial.  The hemorrhage is considered a focal brain injury; that is, it occurs in a localized spot rather than causing diffuse damage over a wider area.

Intra-axial bleeding
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.

Extra-axial bleeding
Extra-axial hemorrhage, bleeding that occurs within the skull but outside of the brain tissue, falls into three subtypes:

Epidural hemorrhage (extradural hemorrhage)  which occur between the dura mater (the outermost meninx) and the skull, is caused by trauma.  It may result from laceration of an artery, most commonly the middle meningeal artery. This is a very dangerous type of injury because the bleed is from a high-pressure system and deadly increases in intracranial pressure can result rapidly. However, it is the least common type of meningeal bleeding and is seen in 1% to 3% cases of head injury.
Patients have a loss of consciousness (LOC), then a lucid interval, then sudden deterioration (vomiting, restlessness, LOC)
Head CT shows lenticular (convex) deformity.
Subdural hemorrhage results from tearing of the bridging veins in the subdural space between the dura and arachnoid mater.
Head CT shows crescent-shaped deformity
Subarachnoid hemorrhage, which occur between the arachnoid and pia meningeal layers, like intraparenchymal hemorrhage, can result either from trauma or from ruptures of aneurysms or arteriovenous malformations.  Blood is seen layering into the brain along sulci and fissures, or filling cisterns (most often the suprasellar cistern because of the presence of the vessels of the circle of Willis and their branch points within that space). The classic presentation of subarachnoid hemorrhage is the sudden onset of a severe headache (a thunderclap headache). This can be a very dangerous entity and requires emergent neurosurgical evaluation and sometimes urgent intervention.

Cerebral contusion
Cerebral contusion is bruising of the brain tissue. The piamater is not breached in contusion in contrary to lacerations. The majority of contusions occur in the frontal and temporal lobes. Complications may include cerebral edema and transtentorial herniation. The goal of treatment should be to treat the increased intracranial pressure. The prognosis is guarded.

Diffuse axonal injury
Diffuse axonal injury, or DAI, usually occurs as the result of an acceleration or deceleration motion, not necessarily an impact. Axons are stretched and damaged when parts of the brain of differing density slide over one another. Prognoses vary widely depending on the extent of the damage.

Compound head injury
Overlying scalp laceration and soft tissue disruption in continuity with a skull fracture constitutes "compound head injury", and has higher rates of infection, unfavorable neurologic outcome, delayed seizures, mortality, and duration of hospital stay.

Signs and symptoms
Three categories used for classifying the severity of brain injuries are mild, moderate or severe.

Mild brain injuries
Symptoms of a mild brain injury include headaches, confusion, ringing ears, fatigue, changes in sleep patterns, mood or behavior. Other symptoms include trouble with memory, concentration, attention or thinking. Mental fatigue is a common debilitating experience and may not be linked by the patient to the original (minor) incident. Narcolepsy and sleep disorders are common misdiagnoses.

Moderate/severe brain injuries
Cognitive symptoms include confusion, aggressive, abnormal behavior, slurred speech, and coma or other disorders of consciousness. Physical symptoms include headaches that do not go away or worsen, vomiting or nausea, convulsions or seizures, abnormal dilation of the eyes, inability to awaken from sleep, weakness in the extremities and loss of coordination. In cases of severe brain injuries, the likelihood of areas with permanent disability is great, including neurocognitive deficits, delusions (often, to be specific, monothematic delusions), speech or movement problems, and intellectual disability. There may also be personality changes. The most severe cases result in coma or even persistent vegetative state.

Symptoms in children
Symptoms observed in children include changes in eating habits, persistent irritability or sadness, changes in attention, disrupted sleeping habits, or loss of interest in toys.Presentation varies according to the injury. Some patients with head trauma stabilize and other patients deteriorate. A patient may present with or without neurological deficit. Patients with concussion may have a history of seconds to minutes unconsciousness, then normal arousal. Disturbance of vision and equilibrium may also occur. Common symptoms of head injury include coma, confusion, drowsiness, personality change, seizures, nausea and vomiting, headache and a lucid interval, during which a patient appears conscious only to deteriorate later.Symptoms of skull fracture can include:

leaking cerebrospinal fluid (a clear fluid drainage from nose, mouth or ear) is strongly indicative of basilar skull fracture and the tearing of sheaths surrounding the brain, which can lead to secondary brain infection.
visible deformity or depression in the head or face; for example a sunken eye can indicate a maxillar fracture
an eye that cannot move or is deviated to one side can indicate that a broken facial bone is pinching a nerve that innervates eye muscles
wounds or bruises on the scalp or face.
Basilar skull fractures, those that occur at the base of the skull, are associated with Battles sign, a subcutaneous bleed over the mastoid, hemotympanum, and cerebrospinal fluid rhinorrhea and otorrhea.Because brain injuries can be life-threatening, even people with apparently slight injuries, with no noticeable signs or complaints, require close observation; They have a chance for severe symptoms later on. The caretakers of those patients with mild trauma who are released from the hospital are frequently advised to rouse the patient several times during the next 12 to 24 hours to assess for worsening symptoms.
The Glasgow Coma Scale (GCS) is a tool for measuring the degree of unconsciousness and is thus a useful tool for determining the severity of the injury. The Pediatric Glasgow Coma Scale is used in young children. The widely used PECARN Pediatric Head Injury/Trauma Algorithm helps physicians weigh risk-benefit of imaging in a clinical setting given multiple factors about the patient—including mechanism/location of the injury, age of the patient, and GCS score.

Location of brain damage predicts symptoms
Symptoms of brain injuries can also be influenced by the location of the injury and as a result, impairments are specific to the part of the brain affected. Lesion size is correlated with severity, recovery, and comprehension. Brain injuries often create impairment or disability that can vary greatly in severity.
Studies show there is a correlation between brain lesion and language, speech, and category-specific disorders. Wernickes aphasia is associated with anomia, unknowingly making up words (neologisms), and problems with comprehension. The symptoms of Wernickes aphasia are caused by damage to the posterior section of the superior temporal gyrus.Damage to the Brocas area typically produces symptoms like omitting functional words (agrammatism), sound production changes, dyslexia, dysgraphia, and problems with comprehension and production. Brocas aphasia is indicative of damage to the posterior inferior frontal gyrus of the brain.An impairment following damage to a region of the brain does not necessarily imply that the damaged area is wholly responsible for the cognitive process which is impaired, however. For example, in pure alexia, the ability to read is destroyed by a lesion damaging both the left visual field and the connection between the right visual field and the language areas (Brocas area and Wernickes area). However, this does not mean someone with pure alexia is incapable of comprehending speech—merely that there is no connection between their working visual cortex and language areas—as is demonstrated by the fact that pure alexics can still write, speak, and even transcribe letters without understanding their meaning. Lesions to the fusiform gyrus often result in prosopagnosia, the inability to distinguish faces and other complex objects from each other. Lesions in the amygdala would eliminate the enhanced activation seen in occipital and fusiform visual areas in response to fear with the area intact. Amygdala lesions change the functional pattern of activation to emotional stimuli in regions that are distant from the amygdala.Other lesions to the visual cortex have different effects depending on the location of the damage. Lesions to V1, for example, can cause blindsight in different areas of the brain depending on the size of the lesion and location relative to the calcarine fissure. Lesions to V4 can cause color-blindness, and bilateral lesions to MT/V5 can cause the loss of the ability to perceive motion. Lesions to the parietal lobes may result in agnosia, an inability to recognize complex objects, smells, or shapes, or amorphosynthesis, a loss of perception on the opposite side of the body.

Causes
Head injuries can be caused by a large variety of reasons. All of these causes can be put into two categories used to classify head injuries; those that occur from impact (blows) and those that occur from shaking. Common causes of head injury due to impact are motor vehicle traffic collisions, home and occupational accidents, falls, assault, and sports related accidents. Head injuries from shaking are most common amongst infants and children.According to the United States CDC, 32% of traumatic brain injuries (another, more specific, term for head injuries) are caused by falls, 10% by assaults, 16.5% by being struck by or against something, 17% by motor vehicle accidents, and 21% by other/unknown ways. In addition, the highest rate of injury is among children ages 0–14 and adults age 65 and older. Brain injuries that include brain damage can also be brought on by exposure to toxic chemicals, lack of oxygen, tumors, infections, and stroke. Possible causes of widespread brain damage include birth hypoxia, prolonged hypoxia (shortage of oxygen), poisoning by teratogens (including alcohol), infection, and neurological illness. Brain tumors can increase intracranial pressure, causing brain damage.

Diagnosis
There are a few methods used to diagnose a head injury. A healthcare professional will ask the patient questions revolving around the injury as well as questions to help determine in what ways the injury is affecting function. In addition to this hearing, vision, balance, and reflexes may also be assessed as an indicator of the severity of the injury. A non-contrast CT of the head should be performed immediately in all those who have sustained a moderate or severe head injury. A CT is an imaging technique that allows physicians to see inside the head without surgery in order to determine if there is internal bleeding or swelling in the brain.  Computed tomography (CT) has become the diagnostic modality of choice for head trauma due to its accuracy, reliability, safety, and wide availability. The changes in microcirculation, impaired auto-regulation, cerebral edema, and axonal injury start as soon as a head injury occurs and manifest as clinical, biochemical, and radiological changes. An MRI may also be conducted to determine if someone has abnormal growths or tumors in the brain or to determine if the patient has had a stroke.Glasgow Coma Scale (GCS) is the most widely used scoring system used to assess the level of severity of a brain injury. This method is based on objective observations of specific traits to determine the severity of a brain injury. It is based on three traits eye-opening, verbal response, and motor response, gauged as described below. Based on the Glasgow Coma Scale severity is classified as follows, severe brain injuries score 3–8, moderate brain injuries score 9-12 and mild score 13–15.
There are several imaging techniques that can aid in diagnosing and assessing the extent of brain damage, such as computed tomography (CT) scan, magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS), positron emission tomography (PET), single-photon emission tomography (SPECT). CT scans and MRI are the two techniques widely used and are the most effective. CT scans can show brain bleeds, fractures of the skull, fluid build up in the brain that will lead to increased cranial pressure. MRI is able to better detect smaller injuries, detect damage within the brain, diffuse axonal injury, injuries to the brainstem, posterior fossa, and subtemporal and sub frontal regions. However, patients with pacemakers, metallic implants, or other metal within their bodies are unable to have an MRI done. Typically the other imaging techniques are not used in a clinical setting because of the cost, lack of availability.

Management
Most head injuries are of a benign nature and require no treatment beyond analgesics such as acetaminophen. Non-steroidal painkillers such as ibuprofen are avoided since they could make any potential bleeding worse. Due to the high risk of even minor brain injuries, close monitoring for potential complications such as intracranial bleeding.  If the brain has been severely damaged by trauma, a neurosurgical evaluation may be useful.  Treatments may involve controlling elevated intracranial pressure. This can include sedation, paralytics, cerebrospinal fluid diversion. Second-line alternatives include decompressive craniectomy (Jagannathan et al. found a net 65% favorable outcomes rate in pediatric patients), barbiturate coma, hypertonic saline, and hypothermia. Although all of these methods have potential benefits, there has been no randomized study that has shown unequivocal benefit.
Clinicians will often consult clinical decision support rules such as the Canadian CT Head Rule or the New Orleans/Charity Head injury/Trauma Rule to decide if the patient needs further imaging studies or observation only. Rules like these are usually studied in depth by multiple research groups with large patient cohorts to ensure accuracy given the risk of adverse events in this area.There is a subspecialty certification available for brain injury medicine that signifies expertise in the treatment of brain injury.

Prognosis
Prognosis, or the likely progress of a disorder, depends on the nature, location, and cause of the brain damage (see Traumatic brain injury, Focal and diffuse brain injury, Primary and secondary brain injury).
In children with uncomplicated minor head injuries the risk of intracranial bleeding over the next year is rare at 2 cases per 1 million. In some cases transient neurological disturbances may occur, lasting minutes to hours. Malignant post traumatic cerebral swelling can develop unexpectedly in stable patients after an injury, as can post-traumatic seizures. Recovery in children with neurologic deficits will vary. Children with neurologic deficits who improve daily are more likely to recover, while those who are vegetative for months are less likely to improve. Most patients without deficits have full recovery. However, persons who sustain head trauma resulting in unconsciousness for an hour or more have twice the risk of developing Alzheimers disease later in life.Head injury may be associated with a neck injury. Bruises on the back or neck, neck pain, or pain radiating to the arms are signs of cervical spine injury and merit spinal immobilization via application of a cervical collar and possibly a longboard. If the neurological exam is normal this is reassuring. Reassessment is needed if there is a worsening headache, seizure, one-sided weakness, or has persistent vomiting.
To combat overuse of head CT scans yielding negative intracranial hemorrhage results, which unnecessarily exposes patients to radiation and increase time in the hospital and cost of the visit, multiple clinical decision support rules have been developed to help clinicians weigh the option to scan a patient with a head injury. Among these are the Canadian Head CT rule, the PECARN Head Injury/Trauma Algorithm, and the New Orleans/Charity Head Injury/Trauma Rule all help clinicians make these decisions using easily obtained information and noninvasive practices.
Brain injuries are very hard to predict in the outcome. Many tests and specialists are needed to determine the likelihood of the prognosis. People with minor brain damage can have debilitating side effects; not just severe brain damage has debilitating effects. The side- effects of a brain injury depend on location and the bodys response to injury. Even a mild concussion can have long term effects that may not resolve.

History
The foundation for understanding human behavior and brain injury can be attributed to the case of Phineas Gage and the famous case studies by Paul Broca. The first case study on Phineas Gages head injury is one of the most astonishing brain injuries in history. In 1848, Phineas Gage was paving way for a new railroad line when he encountered an accidental explosion of a tamping iron straight through his frontal lobe. Gage observed to be intellectually unaffected but exemplified post-injury behavioral deficits. These deficits include: becoming sporadic, disrespectful, extremely profane, and gave no regard for other workers. Gage started having seizures in February 1860, dying only four months later on May 21, 1860.Ten years later, Paul Broca examined two patients exhibiting impaired speech due to frontal lobe injuries. Brocas first patient lacked productive speech </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Frontonasal dysplasia and can you explain it in depth? [/INST] Frontonasal dysplasia (FND) is a congenital malformation of the midface.
For the diagnosis of FND, a patient should present at least two of the following characteristics: hypertelorism (an increased distance between the eyes), a wide nasal root, vertical midline cleft of the nose and/or upper lip, cleft of the wings of the nose, malformed nasal tip, encephalocele (an opening of the skull with protrusion of the brain) or V-shaped hair pattern on the forehead.
The cause of FND remains unknown. FND seems to be sporadic (random) and multiple environmental factors are suggested as possible causes for the syndrome. However, in some families multiple cases of FND were reported, which suggests a genetic cause of FND.

Classification
There are multiple classification systems for FND. None of these classification systems have unraveled any genetic factors as the cause of FND. Yet, all of them are very valuable in determining the prognosis of an individual. In the subheadings below, the most common classifications will be explained.

Sedano classification
This is a classification based on the embryological cause of FND.

De Myer
This classification is based on the morphologic characteristics of FND, that describes a variety of phenotypesBoth of these classifications are further described in table 1. This table originates from the article ‘Acromelic frontonasal dysplasia: further delineation of a subtype with brain malformations and polydactyly (Toriello syndrome), Verloes et al.

Signs and symptoms
Midfacial malformations can be subdivided into two different groups. One group with hypertelorism, this includes FND. The other with hypotelorism (a decreased distance between the eyes), this includes holoprosencephaly (failure of development of the forebrain). In addition, a craniofacial cleft can be classified using the Tessier classification. Each of the clefts is numbered from 0 to 14. The 15 different types of clefts are then subdivided into 4 groups, based on their anatomical position in the face: midline clefts, paramedian clefts, orbital clefts and lateral clefts. FND is a midline cleft, classified as Tessier 0/14.
Besides this, the additional anomalies seen in FND can be subdivided by region. None of these anomalies are specific for the syndrome of FND, but they do occur more often in patients with FND than in the population. The anomalies that may be present are:

Nasal: mild anomalies to nostrils that are far apart and a broad nasal root, a notch or cleft of the nose and accessory nasal tags.
Ocular: narrowed eye slits, almond shaped eyes, epicanthal folds (extra eyelid tissue), epibulbar dermoids (benign tumors of the eye), upper eyelid colombas (full thickness upper eyelid defects), microphthalmos (one or two small eyes), congenital cataract and degeneration of the eye with retinal detachment.
Facial: telecanthus (an increased distance between the corners of the eye), a median cleft of the upper lip and/or palatum, and a V-shaped hairline.
Others: polydactyly (an excess of fingers or toes), syndactyly (fused fingers or toes), brachydactyly (short fingers and/or toes), clinodactyly (bending of the fifth fingers towards the fourth fingers), preauricular skin tags, an absent tragus, low set ears, deafness, small frontal sinuses, mental retardation, encephalocele (protrusion of the brain), spina bifida (split spine), meningoencephalocele (protrusion of both meninges), umbilical hernia, cryptorchidism (absence of one or two testes) and possibly cardiac anomalies.The clefts of the face that are present in FND are vertical clefts. These can differ in severity. When they are less severe, they often present with hypertelorism and normal brain development.
Mental retardation is more likely when the hypertelorism is more severe or when extracephalic anomalies occur.

Cause
Embryogenesis
Midline facial clefts are one of the symptoms in FND. These defects develop in the early stages of embryological development. This is around the 19th to 21st day of pregnancy. The cause of the defect is failure of the mesodermal migration. The mesoderm is one of the germ layers (a collection of cells that have the same embryological origin). As a result of this failure, a midline facial cleft is formed.Another symptom of FND is the V-shaped hairline. In the normal situation, hair growth surrounding the eyes is inhibited. However, in FND this suppression is prevented in the midline by the increased inter-ocular distance. This causes the so-called widow’s peak (a V-shaped hairline) in FND patients.Very early in embryogenesis, the face and neck develop. This development continues until adolescence. Organs develop out of primordia (tissue in its earliest recognizable stage of development). The developmental processes of the face and jaw structures originate from different primordia:

Unpaired frontonasal process
Paired nasomedial and nasolateral processes
Paired maxillary processes and mandibular processes

The formation of the frontonasal process is the result of a complex signaling system which begins with the synthesis of retinoic acid (a vitamin A metabolite). This is needed to set up the facial ectodermal zone. This zone makes signaling molecules that stimulate the cell proliferation of the frontonasal process. A midfacial defect will occur if this signaling pathway is disrupted. It is suggested that the absence of this pathway will lead to the formation of a gap, and that when the pathway is working too hard, excessive tissue will be formed. FND consists of various nasal malformations that result from excessive tissue in the frontonasal process, which results in hypertelorism and a broad nasal bridge.Between the 4th and 8th week of pregnancy, the nasomedial and maxillary processes will fuse to form the upper lip and jaw. A failure of the fusion between the maxillary and nasomedial processes results in a cleft lip. A median cleft lip is the result of a failed fusion between the two nasomedial processes.
The palate is formed between the 6th and 10th week of pregnancy. The primordia of the palate are the lateral palatine processes and median palatine processes. A failure of the fusion between the median and lateral palatine processes results in a cleft palate.

Genetics
There is still some discussion on whether FND is sporadic or genetic. The majority of FND cases are sporadic. Yet, some studies describe families with multiple members with FND. Gene mutations are likely to play an important role in the cause. Unfortunately, the genetic cause for most types of FND remains undetermined.

Frontorhiny
The cause of frontorhiny is a mutation in the ALX3 gene. ALX3 is essential for normal facial development. Different mutations can occur in the ALX3 gene, but they all lead to the same effect: severe or complete loss of protein functionality. The ALX3 mutation never occurs in a person without frontorhiny.

Acromelic frontonasal dysostosis
Acromelic frontonasal dysostosis is caused by a heterozygous mutation in the ZSWIM6 gene. It is thought that acromelic frontonasal dysostosis occurs due to an abnormality in the Sonic Hedgehog (SSH) signaling pathway. This pathway plays an important role in developing the midline central nervous system/craniofrontofacial region and the limbs. Hence, it is plausible that an error in the SSH pathway causes acromelic frontonasal dysostosis, because this syndrome not only shows abnormalities in the midfacial region, but also in the limbs and CNS.

Diagnostics
The main diagnostic tools for evaluating FND are X-rays and CT-scans of the skull. These tools could display any possible intracranial pathology in FND. For example, CT can be used to reveal widening of nasal bones. Diagnostics are mainly used before reconstructive surgery, for proper planning and preparation.Prenatally, various features of FND (such as hypertelorism) can be recognized using ultrasound techniques. However, only three cases of FND have been diagnosed based on a prenatal ultrasound.Other conditions may also show symptoms of FND. For example, there are other syndromes  that also represent with hypertelorism. Furthermore, disorders like an intracranial cyst can affect the frontonasal region, which can lead to symptoms similar to FND. Therefore, other options should always be considered in the differential diagnosis.

Types
Pai syndrome
The Pai Syndrome is a rare subtype of frontonasal dysplasia. It is a triad of developmental defects of the face, comprising midline cleft of the upper lip, nasal and facial skin polyps and central nervous system lipomas. When all the cases are compared, a difference in severity of the midline cleft of the upper lip can be seen. The mild form presents with just a gap between the upper teeth. The severe group presents with a complete cleft of the upper lip and alveolar ridge.Nervous system lipomas are rare congenital benign tumors of the central nervous system, mostly located in the medial line and especially in the corpus callosum. Generally, patients with these lipomas present with strokes. However, patients with the Pai syndrome don’t. That is why it is suggested that isolated nervous system lipomas have a different embryological origin than the lipomas present in the Pai syndrome. The treatment of CNS lipomas mainly consists of observation and follow up.Skin lipomas occur relatively often in the normal population. However, facial and nasal lipomas are rare, especially in childhood. However, the Pai syndrome often present with facial and nasal polyps. These skin lipomas are benign, and are therefore more a cosmetic problem than a functional problem.
The skin lipomas can develop on different parts of the face. The most common place is the nose. Other common places are the forehead, the conjunctivae and the frenulum linguae. The amount of skin lipomas is not related to the severity of the midline clefting.Patients with the Pai syndrome have a normal neuropsychological development.
Until today there is no known cause for the Pai syndrome.
The large variety in phenotypes make the Pai syndrome difficult to diagnose. Thus the incidence of Pai syndrome seems to be underestimated.

Acromelic frontonasal dysplasia (AFND)
Acromelic frontonasal dysplasia is a rare subtype of FND. It has an autosomal dominant inheritance. Acromelic frontonasal dysplasia is associated with central nervous system malformations and limb defects including a clubfoot, an underdeveloped shin-bone, and preaxial polydactyly of the feet. Preaxial polydactyly is a condition in which there are too many toes on the side of the big toe. The phenotype of AFND is severe: a type Ia DeMyer and a Sedano type D. In contrast to the other subtypes of FND, AFND has a relatively high frequency of underlying malformations of the brain.

Frontorhiny
Frontorhiny is another subtype of FND. It consists of multiple characteristics. Patient are characterized by: hypertelorism, a wide nasal bridge, a split nasal tip, a broad columella (strip of skin running from the tip of the nose to the upper lip), widely separated narrow nostrils, a long philtrum (vertical groove on the upper lip) and two-sided nasal swellings.Frontorhiny is one of the two subtypes of FND where a genetic mutation has been determined. The mutation has an autosomal recessive inheritance pattern. The syndrome is often seen in siblings and, most of the time, parents are carriers. See Genetics.

Craniofrontonasal dysplasia
Craniofrontonasal dysplasia (CFND) is a rare type of FND with X linked inheritance. Multiple features are characteristic for CFND such as craniosynostosis of the coronal sutures (prematurely closed cranial sutures), dry frizzy curled hair, splitting of the nails and facial asymmetry.There is a large variety in phenotype. Women present with a more severe phenotype than men. Females characteristically have FND, craniosynostosis and additional small malformations. Males are usually more mildly affected, presenting with only hypertelorism. The gene that causes CFND is called EFNB1 and is located on the X chromosome. A hypothesis for the more severe outcome in females is based on X-inactivation, which leads to mosaicism. As a result, patients have less functional cells, generating abnormal tissue boundaries, termed "cellular interference". This process almost never occurs in males, as they have less mutagenic material in their genes. EFBN1 also has an important function in males. As the syndrome has an X-linked inheritance pattern, there is no man-to-man inheritance.

Oculoauriculofrontonasal syndrome
OAFNS is a combination of FND and oculo-auriculo-vertebral spectrum (OAVS).The diagnosis of OAVS is based on the following facial characteristics: microtia (underdeveloped external ear), preauricular tags, facial asymmetry, mandibular hypoplasia and epibulbar lipodermoids (benign tumor of the eye which consists of adipose and fibrous tissue).
There still remains discussion about the classification and the minimal amount of characteristics.  When someone presents with FND and the characteristics of OAVS, the diagnosis OAFNS may be made.As the incidence of OAFNS is unknown, there are probably a lot of children with mild phenotypes that aren’t being diagnosed as being OAFNS.The cause of OAFNS is unknown, but there are some theories about the genesis. Autosomal recessive inheritance is suggested because of a case with two affected siblings  and a case with consanguineous parents. However, another study shows that it is more plausible that OAFNS is sporadic.
It is known that maternal diabetes plays a role in developing malformations of craniofacial structures and in OAVS. Therefore, it is suggested as a cause of OAFNS. Folate deficiency is also suggested as possible mechanism.Low-dose CT protocols should be considered in diagnosing children with OAFNS.

Treatment
Because newborns can breathe only through their nose, the main goal of postnatal treatment is to establish a proper airway. Primary surgical treatment of FND can already be performed at the age of 6 months, but most surgeons wait for the children to reach the age of 6 to 8 years. This decision is made because then the neurocranium and orbits have developed to 90% of their eventual form. Furthermore, the dental placement in the jaw has been finalized around this age.

Facial bipartition with median faciotomy
To correct the rather prominent hypertelorism, wide nasal root and midline cleft in FND, a facial bipartition can be performed. This surgery is preferred to periorbital box-osteotomy because deformities are corrected with a better aesthetic result.During the operation, the orbits are disconnected from the skull and the base of the skull. However, they remain attached to the upper jaw. Part of the forehead in the centre of the face is removed (median faciotomy) in the process. Then, the orbits are rotated internally, to correct the hypertelorism. Often, a new nasal bone will have to be interpositioned, using a bone transplant.
Complications of this procedure are: bleeding, meningitis, cerebrospinal fluid leakage and blindness.

Rhinoplasty
Structural nasal deformities are corrected during or shortly after the facial bipartition surgery </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Flagellant and can you explain it in depth? [/INST] Flagellants are practitioners of a form of mortification of the flesh by whipping their skin with various instruments of penance. Many Christian confraternities of penitents have flagellants, who beat themselves, both in the privacy of their dwellings and in public processions, in order to repent of sins and share in the Passion of Jesus.In the 14th century, a movement within Western Christianity known as Flagellantism became popular and adherents "began beating their flesh in a public penitential ritual in response to war, famine, plague and fear engendered by millenarianism." Though this movement withered away, the practices of public repentance and promoting peace were adopted by the flagellants in Christian, especially Roman Catholic, confraternities of penitents that exist to the present-day.

History
Flagellation (from Latin flagellare, to whip) was quite a common practice amongst the more fervently religious throughout antiquity.
Christianity has formed a permanent tradition surrounding the doctrine of mortification of the flesh, ranging from self-denial, wearing hairshirts and chains, fasting and self-flagellation using the discipline. Those who practice self-flagellation claim that St. Paul’s statement in the Bible ‘I chastise my body’ refers to self-inflicted bodily scourging (1 Corinthians 9:27). There are prominent Christians who have practiced self-flagellation. Martin Luther, the Protestant Reformer, self-flagellated among other ascetic practices during his early years as an Augustinian monk (although he later condemned such practices). Likewise, the Congregationalist writer Sarah Osborn also practiced self-flagellation in order "to remind her of her continued sin, depravity, and vileness in the eyes of God". It became "quite common" for members of the Tractarian movement within the Anglican Communion to practice self-flagellation using a discipline.Historically speaking, in the 11th century, Peter Damian, a Benedictine Christian monk in the Roman Catholic tradition, taught that spirituality should manifest itself in physical discipline; he admonished those who sought to follow Christ to practice self-flagellation for the duration of the time it takes one to recite forty Psalms, increasing the number of flagellations on holy days of the liturgical calendar. For Damian, only those who shared in the sufferings of Christ could be saved. Throughout Christian history, the mortification of the flesh, wherein one denies themselves physical pleasures, has been commonly followed by members of the clergy, especially in Christian monasteries and convents; the 11th-century Dominicus Loricatus repeated the entire Psalter twenty times in one week, accompanying each psalm with a hundred lash-strokes to his back. The distinction of the Flagellants was to take this self-mortification into the cities and other public spaces as a demonstration of piety.

Flagellantism
Flagellantism was a 14th-century movement, consisting of penitents in the Catholic Church. It began as a Christian pilgrimage and was later condemned by the Catholic Church as heretical. The followers were noted for including public flagellation in their rituals. This was a common practice during the Black Death, or the Great Plague.

Spread in the 14th century
The first recorded incident was in Central Italy in Perugia, in 1259, the year after severe crop damage and famine throughout Europe. From Perugia the phenomenon seemed to spread across Northern Italy and into Austria. Other incidents are recorded in 1296, 1333-34 (the Doves), notably at the time of the Black Death (1349), and 1399. The practice peaked during the Black Death. Spontaneously Flagellant groups arose across Northern and Central Europe in 1349, including in England.Initially the Catholic Church tolerated the Flagellants and individual monks and priests joined in the early movements. By the 14th century, the Church was less tolerant and the rapid spread of the movement was alarming. Clement VI officially condemned them in a bull of October 20, 1349 and instructed Church leaders to suppress the Flagellants. This position was reinforced in 1372 by Gregory XI who associated the Flagellants with other heretical groups, notably the Beghards, and instructed inquisitors to eradicate them. They were accused of heresies including doubting the need for the sacraments, denying ordinary ecclesiastical jurisdiction and claiming to work miracles. In 1392, a sect of Flagellants and Beghards, consisting of peasants, were found throughout Swabia and Wurzburg. The papal inquisitor imposed the penance of preaching and joining a crusade against the Ottoman Turks.The Inquisition was active against any revival of the movement in the 15th century, but action against the flagellants was often taken by the local princes. In 1414, 80–90 followers of Konrad Schmid were burned in Thuringia, in Germany, even though they had recanted. Three hundred were burnt in one day in 1416, also in Thuringia. Other trials where the accused were condemned as Flagellants were recorded as late as the 1480s. The practice of flagellation within the bounds of the Catholic Church continued as an accepted form of penance.
Rulers like Catherine de Medici and Frances King Henry III supported Flagellants but Henry IV banned them. Flagellant orders like Hermanos Penitentes (Spanish Penitential Brothers) also appeared in colonial Spanish America, even against the specific orders of Church authorities.

In Italy
The first recorded cases of mass popular flagellation occurred in Perugia, in 1259. The prime cause of the Perugia episode is unclear, but it followed an outbreak of an epidemic and chroniclers report how mania spread throughout almost all the people of the city. Thousands of citizens gathered in great processions, singing and with crosses and banners, they marched throughout the city whipping themselves. It is reported that surprising acts of charity and repentance accompanied the marchers. However, one chronicler noted that anyone who did not join in the flagellation was accused of being in league with the devil. They also killed Jews and priests who opposed them. Marvin Harris links them to the Messianic preaching of Gioacchino da Fiore.
Similar processions occurred across Northern Italy, with groups up to 10,000 strong  processing in Modena, Bologna, Reggio and Parma. Although certain city authorities refused the Flagellant processions entry.
A similar movement arose again in 1399, again in Northern Italy in the form of the White Penitents or Bianchi movement. This rising is said to have been started by a peasant who saw a vision. The movement became known as the laudesi from their constant hymn singing. At its peak, a group of over 15,000 adherents gathered in Modena and marched to Rome, but the movement rapidly faded when one of its leaders was burned at the stake by order of Boniface IX.

In Germany
The German and Low Countries movement, the Brothers of the Cross, is particularly well documented - they wore white robes and marched across Germany in 33.5 day campaigns (each day referred to a year of Jesuss earthly life) of penance, only stopping in any one place for no more than a day. They established their camps in fields near towns and held their rituals twice a day. The ritual began with the reading of a letter, claimed to have been delivered by an angel and justifying the Flagellants activities. Next, the followers would fall to their knees and scourge themselves, gesturing with their free hands to indicate their sin and striking themselves rhythmically to songs, known as Geisslerlieder, until blood flowed. Sometimes the blood was soaked up in rags and treated as a holy relic. Originally members were required to receive permission to join from their spouses and to prove that they could pay for their food. However, some towns began to notice that sometimes Flagellants brought plague to towns where it had not yet surfaced. Therefore, later they were denied entry. They responded with increased physical penance.

Modern flagellants
Christianity
Roman Catholicism
Modern processions of hooded Flagellants are still a feature of various Mediterranean Christian countries, mainly in Spain, Italy and some former colonies, usually every year during Lent. They also occur in the Philippines during Holy Week.
For example, in the comune of Guardia Sanframondi in Campania, Italy, such parades are organized once every seven years. In Italy, members of the Flagellant movement were called disciplinati, while laudesi never practiced flagellation, but met together in their own chapel to sing laudi (canticles) in honour of the Blessed Virgin, but which gradually assumed a dramatic form and grew into a theatrical form known as rappresentazioni sacre. A play in the Roman dialect of the 14th century, edited by Vattasso (Studi e Testi, no. 4, p. 53), explicitly bears the title lauda.
Some Roman Catholics in Philippines practice flagellation as a form of devout worship, sometimes in addition to self-crucifixion.

Los hermanos penitentes
In English, "the penitent brothers." This is a semi-secret society of flagellants among the Hispanic Roman Catholics of Colorado and New Mexico.

Other religions
Unrelated practices exist in non-Christian traditions, including actual flagellation amongst some Shiites (commemorating the martyrdom of Husayn ibn Ali AS).

See also
Algolagnia
Ashura, Tatbir
Dancing mania
Flagellation
Monty Python and the Holy Grail, which includes a scene of monks striking themselves on the forehead repeatedly with boards while chanting the missal passage Pie Jesu.
Khlysts (Imperial Russia)
Penitentes (New Mexico)
Self-harm
The Seventh Seal
Redemptive suffering
La Cercha
Nine Emperor Gods Festival. Also referred to as the Phuket Vegetarian Festival, it is famous for its ritualised acts of flagellation, self-wounding, and trance-like ecstasies, as well as its vegetarian food-based fasting.

References
Sources
Aberth, John (2010). From the Brink of the Apocalypse: Confronting Famine, War, Plague and Death in the Later Middle Ages (2nd ed.). Routledge.
Cohn, Norman (1970). The Pursuit of the Millennium: Revolutionary Millenarians and Mystical Anarchists of the Middle Ages. Oxford University Press. ISBN 0-19-500456-6.
Lea, Henry Charles (1922). A History of the Inquisition. Vol </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Cohen syndrome and can you explain it in depth? [/INST] Cohen syndrome (also known as Pepper syndrome or Cervenka syndrome) is a very rare autosomal recessive genetic disorder with varied expression, characterised by obesity, intellectual disability, distinct craniofacial abnormalities and potential ocular dysfunction.

Signs and symptoms
Genetics
This syndrome is caused by pathogenic variants (mutations) in the VPS13B gene at chromosomal locus 8q22. It has an autosomal recessive transmission with variable expression. Variants in VSP13B also cause Mirhosseini–Holmes–Walton syndrome, which is now considered to be the same entity as Cohen syndrome

Diagnosis
Cohen syndrome is diagnosed by clinical examination but is often difficult due to variation in expression. Ocular complications, though rare, are listed as optic atrophy, microphthalmia, pigmentary chorioretinitis, hemeralopia (decreased vision in bright light), myopia, strabismus, nystagmus and iris/retinal coloboma.General appearance is obesity with thin/elongated arms and legs. micrognathia, short philtrum and high vaulted palate are common. Variable intellectual disability with occasional seizure and deafness also is characteristic of Cohen syndrome.

Management
Some of the symptoms of Cohen syndrome can be addressed through early intervention with medical specialists. Those who have this disease may benefit from early exposure to speech, physical, and occupational therapy to correct symptoms such as joint overflexibility, developmental delays, hypotonia, and motor clumsiness. Diagnosis may potentially be delayed due to the lack of a definitive molecular test as well as the clinical variability of published case reports.Glasses are beneficial to those who have severe nearsightedness, whereas individuals with retinal degeneration need training for the visually impaired, which is usually more beneficial when this is addressed at a young age </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Masked depression and can you explain it in depth? [/INST] Masked depression (MD) was a proposed form of atypical depression in which somatic symptoms or behavioural disturbances dominate the clinical picture and disguise the underlying affective disorder. The concept is not currently supported by the mental health profession.

Clinical manifestations
Somatic manifestations of MD are distinguished by an extreme diversity: 110  and include headaches, back pain, abdominal pain etc. Pathological behaviour masking depression may take the form of compulsive gambling, compulsive work, changes in arousal or orgasmic function, decreased libido or, on the contrary, impulsive sexual behaviour, alcoholism, or drug addiction.

Dispute about the concept
MD has been variously described as "depression sine [without] depression", "latent" depression, "vegetative depression", "hidden" or "masked" depression, "larvate" or "somatisation depression", "depressive equivalents" etc. Most investigators, especially those in the German-speaking countries, assumed masked depression (German: die larvierte Depression) to be endogenous depression. The term was largely used in the 1970s and 1980s, but at the end of the 20th century there was a decline in interest in the study of masked depression </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Mitochondrial DNA depletion syndrome and can you explain it in depth? [/INST] Mitochondrial DNA depletion syndrome (MDS or MDDS), or Alpers disease, is any of a group of autosomal recessive disorders that cause a significant drop in mitochondrial DNA in affected tissues. Symptoms can be any combination of myopathic, hepatopathic, or encephalomyopathic. These syndromes affect tissue in the muscle, liver, or both the muscle and brain, respectively. The condition is typically fatal in infancy and early childhood, though some have survived to their teenage years with the myopathic variant and some have survived into adulthood with the SUCLA2 encephalomyopathic variant. There is currently no curative treatment for any form of MDDS, though some preliminary treatments have shown a reduction in symptoms.

Signs and symptoms
All forms of MDDS are very rare.  MDDS causes a wide range of symptoms, which can appear in newborns, infants, children, or adults, depending on the class of MDDS; within each class symptoms are also diverse.In MDDS associated with mutations in TK2, infants generally develop normally, but by around two years of age, symptoms of general muscle weakness (called "hypotonia"), tiredness, lack of stamina, and difficulty feeding begin to appear.  Some toddlers start to lose control of the muscles in their face, mouth, and throat, and may have difficulty swallowing.  Motor skills that had been learned may be lost, but generally the functioning of the brain and ability to think are not affected.In MDDS associated with mutations in SUCLA2 or SUCLG1 that primarily affect the brain and muscle, hypotonia generally arises in infants before they are 6 months old, their muscles begin wasting away, and there is delay in psychomotor learning (learning basic skills like walking, talking, and intentional, coordinated movement).  The spine often begins to curve (scoliosis or kyphosis), and the child often has abnormal movements (dystonia, athetosis or chorea), difficulty feeding, acid reflux, hearing loss, stunted growth, and difficulty breathing that can lead to frequent lung infections.  Sometime epilepsy develops.In MDDS associated with mutations in RRM2B that primarily affect the brain and muscle, there is again hypotonia in the first months, symptoms of lactic acidosis like nausea, vomiting, and rapid deep breathing, failure to thrive including the head remaining small, delay or regression in moving, and hearing loss.  Many body systems are affected. The Charlie Gard case was associated with this sub form of the disease.In MDDS associated with mutations in DGUOK that primarily affect the brain and the liver, there are two forms. There is an early-onset form in which symptoms arise from problems in many organs in the first week of life, especially symptoms of lactic acidosis as well as low blood sugar. Within weeks of birth they can develop liver failure and the associated jaundice and abdominal swelling, and many neurological problems including developmental delays and regression, and uncontrolled eye movement.  Rarely within this class of already rare diseases, symptoms only relating to liver disease emerge later in infancy or in childhood.In MDDS associated with mutations in MPV17 that primarily affect the brain and the liver, the symptoms are similar to those caused by DGUOK and also emerge shortly after birth, generally with fewer and less severe neurological problems. There is a subset of people of Navajo descent who develop Navajo neurohepatopathy, who in addition to these symptoms also have easily broken bones that do not cause pain, deformed hands or feet, and problems with their corneas.In MDDS associated with mutations in POLG that primarily affect the brain and the liver, the symptoms are very diverse and can emerge anytime from shortly after birth to old age. The  first signs of the disease, which include intractable seizures and failure to meet meaningful developmental milestones, usually occur in infancy, after the first year of life, but sometimes as late as the fifth year. Primary symptoms of the disease are developmental delay, progressive intellectual disability, hypotonia (low muscle tone), spasticity (stiffness of the limbs) possibly leading to quadriplegia, and progressive dementia. Seizures may include epilepsia partialis continua, a type of seizure that consists of repeated myoclonic (muscle) jerks. Optic atrophy may also occur, often leading to blindness. Hearing loss may also occur. Additionally, although physical signs of chronic liver dysfunction may not be present, many people experience liver impairment leading to liver failure.In MDDS associated with mutations in PEO1/C10orf2 that primarily affect the brain and the liver, symptoms emerge shortly after birth or in early infancy, with hypotonia, symptoms of lactic acidosis, enlarged liver, feeding problems, lack of growth, and delay of psychomotor skills.  Neurologically, development is slowed or stopped, and epilepsy emerges, as do sensory problems like loss of eye control and deafness, and neuromuscular problems like a lack of reflexes, muscular atrophy, and twitching, and epilepsy.In MDDS associated with mutations in the genes associated with mutations in ECGF1/TYMP  that primarily affects the brain and the gastrointestinal tract, symptoms can emerge any time in the first fifty years of life; most often they emerge before the person turns 20.   Weight loss is common as is a lack of the ability of the stomach and intestines to automatically expand and contract and thus move through it (called gastrointestinal motility) – this leads to feeling full after eating only small amounts of food, nausea, acid reflux,  All affected individuals develop weight loss and progressive gastrointestinal dysmotility manifesting as early satiety, nausea, diarrhea, vomiting, and stomach pain and swelling.  People also develop neuropathy, with weakness and tingling.  There are often eye problems, and intellectual disability.

Causes
MDDS is caused by mutations that may be inherited from the parents or may form spontaneously during development of the fetus.  MDDS is associated with mutations in the genes TK2, SUCLA2, RRM2B, DGUOK, POLG, TYMP, SUCLG1,  and TWNK.Myopathic MDS is strongly correlated to a variety of mutations in the gene TK2, seeing a reduction of TK2 activity to less than 32% in people with MDS found with the mutation. Because TK2 plays a key role in the mitochondrial salvage pathways of several deoxyribonucleoside triphosphates (dNTPs), a lowered activity would lead to less cycling of nucleotides. This lack of nucleotide recycling is detrimental since the mitochondria cannot synthesize entirely new deoxynucleotides, and the inner membrane of the mitochondria prevents the negatively charged nucleotides of the cytosol from entering.The SUCLA2 gene codes for the beta-subunit of SCS-A. This enzyme catalyzes the synthesis of succinate and coenzyme A into succinyl-CoA, but is also associated with the complex formed by nucleoside diphosphate kinase (NDPK) in the last step of the dNTP salvage pathway.The RRM2B gene, which is expressed in the cell nucleus, codes for one of two versions of the R2 subunit of ribonucleotide reductase, which generates nucleotide precursors required for DNA replication by reducing ribonucleoside diphosphates to deoxyribonucleoside diphosphates.  The version of R2 encoded by RRM2B is induced by TP53, and is required for normal DNA repair and mtDNA synthesis in non-proliferating cells.  The other form of R2 is expressed only in dividing cells.The DGUOK gene encodes for mitochondrial deoxyguanosine kinase (dGK), which catalyzes the phosphorylation of deoxyribonucleosides into nucleotides. POLG encodes for the catalytic subunit pol γA, which is part of mitochondrial DNA polymerase.Other causes are mutations of thymidine phosphorylase (TyMP), succinate-CoA ligase, alpha sub unit (SUCLG1) and TWNK (also known as PEO1 and C10orf2).

Diagnosis
MDDS is diagnosed based on systemic symptoms presenting in infants, followed by a clinical examination and laboratory tests (for example, high lactate levels are common) medical imaging, and usually is finally confirmed and formally identified by genetic testing.

Classification
MDDS are a group of genetic disorders that share a common pathology — a lack of functioning DNA in mitochondria. There are generally four classes of MDDS:
a form that primarily affects muscle associated with mutations in the TK2 gene;
a form that primarily affects the brain and muscle associated with mutations in the genes SUCLA2, SUCLG1, or RRM2B;
a form that primarily affects the brain and the liver associated with mutations in DGUOK, MPV17, POLG, or TWNK (also called PEO1); and
a form that primarily affects the brain and the gastrointestinal tract associated with mutations in ECGF1 (also called TYMP).

Treatment
There are no treatments for MDDS, but some of the symptoms can be managed.  For survivors living with MDDS, there are drugs to control epilepsy, and physical therapy can help with muscle control </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Mycosis fungoides and can you explain it in depth? [/INST] Mycosis fungoides, also known as Alibert-Bazin syndrome or granuloma fungoides, is the most common form of cutaneous T-cell lymphoma. It generally affects the skin, but may progress internally over time. Symptoms include rash, tumors, skin lesions, and itchy skin.
While the cause remains unclear, most cases are not hereditary. Most cases are in people over 20 years of age, and it is more common in men than women. Treatment options include sunlight exposure, ultraviolet light, topical corticosteroids, chemotherapy, and radiotherapy.

Signs and symptoms
The symptoms of mycosis fungoides are categorized into three clinical stages: the patch stage, the plaque stage, and the tumour stage. The patch stage is defined by flat, reddish patches of varying sizes that may have a wrinkled appearance. They can also look yellowish in people with darker skin. The plaque stage follows the patch stage of mycosis fungoides. It is characterized by the presence of raised lesions that appear reddish-brown; in darker skin tones, plaques may have a greyish or silver appearance. Both patch and plaque stages are considered early-stage mycosis fungoides. The tumour stage typically shows large irregular lumps. Tumours can develop form plaques or normal skin in any region of the body, including the face and head regions.The symptoms displayed are progressive, with early stages consisting of lesions presented as scaly patches. Lesions often initially develop on the trunk of the body in places that are rarely exposed to the sun, such as the buttocks. These lesions can start as insignificant patches and may remain undiagnosed for up to a decade. Hypopigmentation (when the skin is lighter than normal) of lesions are less common but can be found in children, adolescents and/or dark-skinned individuals.The advanced stage of mycosis fungoides is characterized by generalized erythroderma (red rash covering most of the body) with severe pruritus (itching) and scaling. Itching (Pruritus) is the most commonly reported symptom of people experiencing mycosis fungoides with up to 88% of people reporting varying intensities of pruritus that typically worsens as the disease progresses. Those that experience intense pruritus commonly indicate that it negatively affects their quality of life emotionally, functionally and physically.Mycosis fungoides (MF) and Sézary syndrome (SS) are related conditions with the same type of cancer t-lymphocytes that initially grow in different body compartments. SS cells are mainly found in the blood, whereas MF typically involves the skin. In advanced stages of MF, the cancer cells move from the skin into the blood stream and other organs, and is referred to as  "leukemic mycosis fungoides", :Sézary syndrome preceded by mycosis fungoides", or "secondary mycosis fungoides".

Cause
Mycosis fungoides is caused by abnormal white blood cells (T-lymphocytes). These abnormal cells have a preference for localizing and proliferating uncontrolled in the outer layer of the skin (epidermis). The abnormal cells may later involve other organs such as the lymph nodes. It is hypothesized that the genetic mutations in these cancer cells lead to increased growth and escape from programmed cell death.Additionally, the disease is an unusual expression of CD4 T cells, a part of the immune system. These T cells are skin-associated, meaning they are biochemically and biologically most related to the skin, in a dynamic manner.  Mycosis fungoides is the most common type of cutaneous T-cell lymphoma (CTCL), but there are many other types of CTCL that have nothing to do with mycosis fungoides and these disorders are treated differently.

Diagnosis
Diagnosis often requires a combination of clinical and pathological studies. Diagnosis is sometimes difficult because the early phases of the disease often resemble inflammatory dermatoses (such as eczema, psoriasis, lichenoid dermatoses including lichen planus, vitiligo, and chronic cutaneous lupus erythematosus), as well as other cutaneous lymphomas. Several biopsies are recommended, as the key microscopic features are often absent in early MF, and a complete diagnosis requires a combination of clinical and histological study. Furthermore, long periods of treatment can alter the biopsy findings, making it difficult to distinguish from other inflammatory dermatoses. Childhood Mycosis fungoides (MF) makes up 0.5% to 7.0% of cases. Although data on childhood MF is limited, a 2021 systematic review observed that there is a significant delay in the diagnosis of childhood MF which may negatively affect a child’s prognosis. Notably, most pediatric persons with MF present with early-stage disease.

Histology
The criteria for the disease are established on the skin biopsy by the presence of the following:
Presence of cancer cells with twisted contours (cerebriform nuclei)
In the patch and plaque stages, the cancer cells are seen in the epidermis (the most superficial layer of skin). This is referred to as epidermotropism.
Pautriers microabcesses, aggregates of four or more atypical lymphocytes arranged in the epidermis. Pautrier microabcesses are characteristic of mycosis fungoides but are generally absent.
In the tumour stage, the cancer cells move into the dermis (the deeper layer of skin)
Large cell transformation, where clonally identical lymphocytes in the lesion exhibit hypertrophy. In transformed cells, presence of the CD30 receptor is associated with improved survivalTo stage the disease, various tests may be ordered, to assess nodes, blood and internal organs, but most patients present with disease apparently confined to the skin, as patches (flat spots) and plaques (slightly raised or wrinkled spots).
Peripheral smear will often show buttock cells.

Staging
Traditionally, mycosis fungoides has been divided into three stages: premycotic, mycotic and tumorous. The premycotic stage clinically presents as an erythematous (red), itchy, scaly lesion. Microscopic appearance is non-diagnostic and represented by chronic nonspecific dermatosis associated with psoriasiform changes in epidermis.In the mycotic stage, infiltrative plaques appear and biopsy shows a polymorphous inflammatory infiltrate in the dermis that contains small numbers of frankly atypical lymphoid cells. These cells may line up individually along the epidermal basal layer. The latter finding if unaccompanied by spongiosis is highly suggestive of mycosis fungoides. In the tumorous stage a dense infiltrate of medium-sized lymphocytes with cerebriform nuclei expands the dermis.
Accurate staging of mycosis fungoides is essential to determine appropriate treatment and prognosis. Staging is based on the tumor, node, metastasis, blood (TNMB) classification proposed by the Mycosis Fungoides Cooperative Group and revised by the International Society for Cutaneous Lymphomas/European Organization of Research and Treatment of Cancer. This staging system examines the extent of skin involvement (T), presence of lymph node (N), visceral disease (M), and presence of Sezary cells in the peripheral blood (B).Most patients with mycosis fungoides have early-stage disease (Stage IA-IIA) at the time of their initial diagnosis. People with early stage disease that is primarily confined to the skin have a favorable prognosis. People with advanced stage (Stage IIB-IVB) are often refractory to treatment and have an unfavorable prognosis. Treatment options for people with advanced stage disease are designed to reduce tumor burden, delay disease progression, and preserve quality of life.

Treatment
The most commonly recommended first-line treatment for mycosis fungoides is psoralen plus ultraviolet A (PUVA therapy). PUVA is a photochemotherapy that involves topical or oral administration of the photosensitizing drug psoralen followed by skin exposure to ultraviolet radiation. Systemic treatments of mycosis fungoides often lead to resistance; as such, additional treatment options are often necessary in advanced disease.Other treatments that have been suggested, however, larger and more extensive research is needed to identify effective treatment strategies for this disease. Suggested treatments include light therapy, ultraviolet light (mainly NB-UVB 312 nm), topical steroids, topical and systemic chemotherapies, local superficial radiotherapy, the histone deacetylase inhibitor vorinostat, total skin electron radiation, photopheresis, systemic therapies (e.g. retinoids, rexinoids), and biological therapies (e.g. interferons). Treatments are often used in combination. Due to the possible adverse effects of treatment options in early disease it is recommended to begin therapy with topical and skin-directed treatments before progressing to more systemic therapies. In 2010, the U.S. Food and Drug Administration granted orphan drug designation for naloxone lotion, a topical opioid receptor competitive antagonist used as a treatment for pruritus in cutaneous T-cell lymphoma. Mogamulizumab is a CCR4 monoclonal antibody which has been shown to improve progression-free survival. It was approved by the US FDA in 2018 for use in people with relapsed or refractory mycosis fungoides or Sézary disease.There is no evidence to support the use of acitretin or extracorporeal photopheresis (ECP: a type of phototherapy) for treating people with mycosis fungoides. There is also no evidence to support the combination treatment of PUVA and intralesional IFN-α or PUVA and bexarotene.

Children
Treatment for adults and children with mycosis fungoides often differs because of the safety profiles of modalities. Narrowband UV-B is commonly considered for children, as opposed to Psoralen with UV-A, mechlorethamine hydrochloride, or oral bexarotene, which is often used in adults.

Prognosis
A 1999 US-based study of people with CLLs medical records observed a 5-year relative survival rate of 77%, and a 10-year relative survival rate of 69%. After 11 years, the observed relative survival rate remained around 66% </s>


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<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Collagen disease and can you explain it in depth? [/INST]  </s>