<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 Narcissistic personality disorder and can you explain it in depth? [/INST] Narcissistic personality disorder (NPD) is a mental disorder characterized by a life-long pattern of exaggerated feelings of self-importance, an excessive need for admiration, a diminished ability to empathize with others feelings, and interpersonally exploitative behavior. Narcissistic personality disorder is one of the sub-types of the broader category known as personality disorders. It is often comorbid with other mental disorders and associated with significant functional impairment and psychosocial disability.Personality disorders are a class of mental disorders characterized by enduring and inflexible maladaptive patterns of behavior, cognition, and inner experience, exhibited across many contexts and deviating from those accepted by any culture. These patterns develop by early adulthood, and are associated with significant distress or impairment. Criteria for diagnosing personality disorders are listed in the fifth chapter of the International Classification of Diseases (ICD) and in the American Psychiatric Associations Diagnostic and Statistical Manual of Mental Disorders (DSM).
There is no standard treatment for NPD. Its high comorbidity with other mental disorders influences treatment choice and outcomes. Psychotherapeutic treatments generally fall into two categories: psychoanalytic/psychodynamic and cognitive behavioral therapy, with growing support for integration of both in therapy. However, there is an almost complete lack of studies determining the effectiveness of treatments.

Signs and symptoms
DSM-5
The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) describes NPD as possessing at least five of the following nine criteria.
A grandiose sense of self-importance
Preoccupation with fantasies of unlimited success, power, brilliance, beauty, or ideal love
Believing that they are "special" and unique and can only be understood by, or should associate with, other special or high-status people (or institutions)
Requiring excessive admiration
A sense of entitlement (unreasonable expectations of especially favorable treatment or automatic compliance with their expectations)
Being interpersonally exploitative (taking advantage of others to achieve their own ends)
Lacking empathy (unwilling to recognize or identify with the feelings and needs of others)
Often being envious of others or believing that others are envious of them
Showing arrogant, haughty behaviors or attitudesWithin the DSM-5, NPD is a cluster B personality disorder. Individuals with cluster B personality disorders often appear dramatic, emotional, or erratic. Narcissistic personality disorder is a mental disorder characterized by a life-long pattern of exaggerated feelings of self-importance, an excessive craving for admiration, and a diminished ability to empathize with others feelings.A diagnosis of NPD, like other personality disorders, is made by a qualified healthcare professional in a clinical interview. The process of diagnosis often involves asking the client to describe people emotionally close to them, which can reveal extreme arrogance or a lack of empathy.Narcissistic personality disorder usually develops either in youth or in early adulthood. True symptoms of NPD are pervasive, apparent in varied social situations, and are rigidly consistent over time. Severe symptoms of NPD can significantly impair the persons mental capabilities to develop meaningful human relationships, such as friendship, kinship, and marriage. Generally, the symptoms of NPD also impair the persons psychological abilities to function socially, either at work or at school, or within important societal settings. The DSM-5 indicates that, in order to qualify as symptomatic of NPD, the persons manifested personality traits must substantially differ from social norms.

ICD-11 and ICD-10
In the International Statistical Classification of Diseases and Related Health Problems, 11th Edition ICD-11 of the World Health Organization (WHO), all personality disorders are diagnosed under a single title called "personality disorder". The criteria for diagnosis are mainly concerned with assessing dysfunction, distress and maladaptive behavior as opposed to attributing specific personality traits.
In the previous edition, the ICD-10, narcissistic personality disorder (NPD) is listed under the category of "other specific personality disorders". This means similarly to the ICD-11, the ICD-10 required that cases otherwise described as NPD in the DSM-5 would only need to meet a general set of diagnostic criteria.

Associated features
People with NPD exaggerate their skills, accomplishments, and their degree of intimacy with people they consider high-status. A sense of personal superiority may lead them to monopolize conversations, look down on others or to become impatient and disdainful when other persons talk about themselves. This behavior correlates to an overall worse functioning in areas of life like work and intimate romantic relationships.People with NPD have been observed to use psychosocial strategies, such as the tendency to devalue and derogate and to insult and blame other people, usually with anger and hostility towards peoples responses to their anti-social behavior. Narcissistic personalities are more likely to respond with anger or aggressiveness when presented with rejection. Because they are sensitive to perceived criticism or defeat, people with NPD are prone to feelings of shame, humiliation, and worthlessness over minor incidents of daily life and imagined, personal slights, and usually mask such feelings from people, by feigning humility, responding with outbursts of rage and defiance, or seeking revenge.The DSM-5 indicates that: "Many highly successful individuals display personality traits that might be considered narcissistic. Only when these traits are inflexible, maladaptive, and persisting, and cause significant functional impairment or subjective distress, do they constitute narcissistic personality disorder." Given the high-function sociability associated with narcissism, some people with NPD might not view such a diagnosis as a functional impairment to their lives. Although overconfidence tends to make people with NPD very ambitious, such a mindset does not necessarily lead to professional high achievement and success, because they refuse to take risks, in order to avoid failure or the appearance of failure. Moreover, the psychological inability to tolerate disagreement, contradiction, and criticism, makes it difficult for persons with NPD to work cooperatively or to maintain long-term, professional relationships with superiors and colleagues.

Differential diagnosis
The occurrence of narcissistic personality disorder presents a high rate of comorbidity with other mental disorders. People with NPD are prone to bouts of psychological depression, often to the degree that meets the clinical criteria for a co-occurring depressive disorder. NPD is associated with the occurrence of bipolar disorder and substance use disorders, especially cocaine use disorder. NPD may also be comorbid or differentiated with the occurrence of other mental disorders, including histrionic personality disorder, borderline personality disorder, antisocial personality disorder, or paranoid personality disorder. NPD should also be differentiated from mania and hypomania as these cases can also present with grandiosity, but present with different levels of functional impairment. Narcissistic personality disorder differs from self-confidence which is associated with a strong sense of self. It is common for children and adolescents to display personality traits that resemble NPD, but such occurrences are usually transient, and register below the clinical criteria for a formal diagnosis of NPD.

Subtypes
Although the DSM-5 diagnostic criteria for NPD has been viewed as homogeneous, there are a variety of subtypes used for classification of NPD. There is poor consensus on how many subtypes exist, but there is broad acceptance that there are at least two: grandiose or overt narcissism, and vulnerable or covert narcissism. However, none of the subtypes of NPD are recognized in the DSM-5 or in the ICD-11.

Grandiose/overt and vulnerable/covert
Similar to the definition of NPD in the DSM-IV, Grandiose narcissism is defined by an inflated sense of self-worth and high self-esteem, interpersonal exploitativeness, social dominance and assertiveness, shamelessness and a sense of entitlement derived from feelings of superiority or prestige.The counterpart to grandiose narcissism is vulnerable narcissism, characterized by the personality traits of defensiveness, fragility, social withdrawal, and sensitivity to criticism.

Oblivious and hypervigilant
The psychiatrist and psychoanalyst Glen Gabbard described two subtypes of NPD in 1989, later referred to as equivalent to, the grandiose and vulnerable subtypes. The first was the "oblivious" subtype of narcissist, equivalent to the grandiose subtype. It was described as being grandiose, arrogant and thick-skinned, while also exhibiting personality traits of helplessness and emotional emptiness, low self-esteem and shame. These were observed in people with NPD to be expressed as socially avoidant behavior in situations where self-presentation is difficult or impossible, leading to withdrawal from situations where social approval is not given.
The second subtype Gabbard described was termed "hypervigilant", equivalent to the vulnerable subtype. People with this subtype of NPD were described as having easily hurt feelings, an oversensitive temperament, and persistent feelings of shame.

High functioning or exhibitionist
A third subtype for classifying people with NPD, also initially theorised by Gabbard, is termed high functioning or exhibitionistic. It has been described as "high functioning narcissists [who] were grandiose, competitive, attention-seeking, and sexually provocative; they tended to show adaptive functioning and utilize their narcissistic traits to succeed."

Millons subtypes
In the study Disorders of Personality: DSM-IV-TM and Beyond (1996), Theodore Millon suggested five subtypes of NPD, although they did not identify specific treatments per subtype.

Mastersons subtypes (exhibitionist and closet)
In 1993, James F. Masterson proposed two subtypes for pathological narcissism, exhibitionist and closet. Both fail to adequately develop an age- and phase- appropriate self because of defects in the quality of psychological nurturing provided, usually by the mother. A person with exhibitionist narcissism is similar to NPD described in the DSM-IV and differs from closet narcissism in several ways. A person with closet narcissism is more likely to be described as having a deflated, inadequate self-perception and greater awareness of emptiness within. A person with exhibitionist narcissism would be described as having an inflated, grandiose self-perception with little or no conscious awareness of feelings of emptiness. Such a person would assume that their condition was normal and that others were just like them. A person with closet narcissism is described to seek constant approval from others and appears similar to those with borderline personality disorder in the need to please others. A person with exhibitionist narcissism seeks perfect admiration all the time from others.

Malignant narcissism
Malignant narcissism, a term first coined in Erich Fromms 1964 book The Heart of Man: Its Genius for Good and Evil, is a syndrome consisting of a combination of NPD, antisocial personality disorder, and paranoid traits. A person with malignant narcissism was described as deriving higher levels of psychological gratification from accomplishments over time, suspected to worsen the disorder. Because a person with malignant narcissism becomes more involved in psychological gratification, it was suspected to be a risk factor for developing antisocial, paranoid, and schizoid personality disorders. The term malignant is added to the term narcissist to indicate that individuals with this disorder have a severe form of narcissistic disorder that is characterized also by features of paranoia, psychopathy (anti-social behaviors), aggression, and sadism.

Assessment and screening
Narcissistic Personality Inventory
Risk factors for NPD and grandiose/overt and vulnerable/covert subtypes are measured using the narcissistic personality inventory, an assessment tool originally developed in 1979, has undergone multiple iterations with new versions in 1984, 2006 and 2014. The subtype is also assessed with the pathological narcissism inventory (PNI). The PNI is a screening tool for antisocial, borderline, narcissistic personality disorders. The PNI scales exhibited significant associations with parasuicidal behavior, suicide attempts, homicidal ideation, and several aspects of psychotherapy utilization. Pathological narcissism a term for concurrent grandiose and vulnerable narcissism, which is linked to poor self-esteem, lack of empathy, feelings of shame, interpersonal distress, aggression, and significant impairments in personality functioning across both clinical and non-clinical samples. Despite the phenomenological and empirical distinction between vulnerable and grandiose narcissism, some theories suggest that grandiose narcissists also have fragile personality traits. There are a number of other assessment tools for narcissism and NPD subtypes.

Millon Clinical Multiaxial Inventory
The Millon Clinical Multiaxial Inventory (MCMI) is another diagnostic test developed by Theodore Millon. The MCMI includes a scale for narcissism. The NPI and MCMI have been found to be well correlated. Whereas the MCMI measures narcissistic personality disorder (NPD), the NPI measures narcissism as it occurs in the general population; the MCMI is a screening tool. In other words, the NPI measures "normal" narcissism; i.e., most people who score very high on the NPI do not have NPD. Indeed, the NPI does not capture any sort of narcissism taxon as would be expected if it measured NPD.A 2020 study found that females scored significantly higher on vulnerable narcissism than males, but no gender differences were found for grandiose narcissism.

Causes
Although there are no specific causes for NPD, it is described using the biopsychosocial model which describes a combination of risk factors from biological, psychological and socio-environmental factors. This includes but is not limited to genetics, neurobiology, trauma, abuse and parenting.

Genetic
Evidence suggests there is a high heritability of NPD, with a number of genetic influences indicating varying rates of heritability based on subtype. A number of twin studies historically suggested for the heritability of NPD, including personality disorders in general.

Environment
Environmental and social factors also influence development of NPD. In some people, pathological narcissism may develop from an impaired emotional attachment to primary caregivers (usually parents). That lack of psychological and emotional attachment to a parental figure can result in the childs perception of themselves as unimportant and unconnected to other people, usually, family, community and society. Typically, the child comes to believe that they have a personality defect that makes them unvalued and unwanted; overindulgent, permissive parenting or insensitive and over-controlling parenting are risk factors towards the development of NPD in a child.In Gabbards Treatments of Psychiatric Disorders (2014), the following factors are identified as promoting the development of narcissistic personality disorder:
An oversensitive temperament (individual differences of behavior) at birth
Excessive admiration that is never balanced with realistic criticism
Excessive praise for good behaviors, or excessive criticism for bad behaviors in childhood
Overindulgence and overvaluation by family or peers
Being praised by adults for perceived exceptional physical appearance or abilities
Trauma caused by psychological abuse, physical abuse or sexual abuse in childhood
Unpredictable or unreliable parental caregiving
Learning the behaviors of psychological manipulation from parents or peersMoreover, the research reported in "Modernity and Narcissistic Personality Disorders" (2014) indicates that cultural elements also influence the prevalence of NPD, because narcissistic personality traits more commonly occur in modern societies than in traditionalist conservative societies.

Pathophysiology
Studies of the occurrence of narcissistic personality disorder identified structural abnormalities in the brains of people with NPD, specifically, a lesser volume of gray matter in the left, anterior insular cortex. The results of a 2015 study associated the condition of NPD with a reduced volume of gray matter in the prefrontal cortex. The regions of the brain identified and studied – the insular cortex and the prefrontal cortex – are associated with the human emotions of empathy and compassion, and with the mental functions of cognition and emotional regulation. The neurologic findings of the studies suggest that NPD may be related to a compromised (damaged) capacity for emotional empathy and emotional regulation.

Management
Treatment for NPD is primarily psychotherapeutic; there is no clear evidence that psychopharmacological treatment is effective for NPD, although it can prove useful for treating comorbid disorders. Psychotherapeutic treatment falls into two general categories: psychoanalytic/psychodynamic and cognitive behavioral. Psychoanalytic therapies include schema therapy, transference focused psychotherapy, mentalization-based treatment and metacognitive psychotherapy. Cognitive behavioral therapies include cognitive behavioral therapy and dialectical behavior therapy. Formats also include group therapy and couples therapy. The specific choice of treatment varies based on individual presentations.Management of narcissistic personality disorder has not been well studied, however many treatments tailored to NPD exist. Therapy is complicated by the lack of treatment-seeking behavior in people with NPD, despite mental distress. Additionally, people with narcissistic personality disorders have decreased life satisfaction and lower qualities of life, irrespective of diagnosis. People with NPD often present with comorbid mental disorders, complicating diagnosis and treatment. NPD is rarely the primary reason for which people seek mental health treatment. When people with NPD enter treatment (psychologic or psychiatric), they often express seeking relief from a comorbid mental disorder,  including major depressive disorder, a substance use disorder (drug addiction), or bipolar disorder.

Prognosis
As of 2020, no treatment guidelines exist for NPD and no empirical studies have been conducted on specific NPD groups to determine efficacy for psychotherapies and pharmacology.The presence of NPD in patients undergoing psychotherapy for the treatment of other mental disorders is associated with slower treatment progress and higher dropout rates.

Epidemiology
As of 2018, overall prevalence is estimated to range from 0.8% to 6.2%. In 2008 under the DSM-IV, lifetime prevalence of NPD was estimated to be 6.2%, with 7.7% for men and 4.8% for women, with a 2015 study confirming the gender difference. In clinical settings, prevalence estimates range from 1% to 15%. The occurrence of narcissistic personality disorder presents a high rate of comorbidity with other mental disorders.

History
The term "narcissism" comes from a first century (written in the year 8 AD) book by the Roman poet Ovid. Metamorphoses Book III is a myth about two main characters, Narcissus and Echo. Narcissus is a handsome young man who spurns the advances of many potential lovers. When Narcissus rejects the nymph Echo, named this way because she was cursed to only echo the sounds that others made, the gods punish him by making him fall in love with his own reflection in a pool of water. When Narcissus discovers that the object of his love cannot love him back, he slowly pines away and dies.The concept of excessive selfishness has been recognized throughout history. In ancient Greece, the concept was understood as hubris. It is only since the late 1800s that narcissism has been defined in psychological terms:
Havelock Ellis (1898) was the first psychologist to use the term when he linked the myth to the condition in one of his patients.
Sigmund Freud (1905-1953) used the terms "narcissistic libido" in his Three Essays on the Theory of Sexuality.
Ernest Jones (1913/1951) was the first to construe extreme narcissism as a character flaw.
Robert Waelder (1925) published the first case study of narcissism. His patient was a successful scientist with an attitude of superiority, an obsession with fostering self-respect, and a lack of normal feelings of guilt. The patient was aloof and independent from others and had an inability to empathize with others situations, and was selfish sexuality. Waelders patient was also overly logical and analytical and valued abstract intellectual thought (thinking for thinkings sake) over the practical application of scientific knowledge.Narcissistic personality was first described by the psychoanalyst Robert Waelder in 1925. The term narcissistic personality disorder (NPD) was coined by Heinz Kohut in 1968. Waelders initial study has been influential in the way narcissism and the clinical disorder Narcissistic personality disorder are defined today

Freudianism and psychoanalysis
Much early history of narcissism and NPD originates from psychoanalysis. Regarding the adult neurotics sense of omnipotence, Sigmund Freud said that "this belief is a frank acknowledgement of a relic of the old megalomania of infancy"; and concluded that: "we can detect an element of megalomania in most other forms of paranoic disorder. We are justified in assuming that this megalomania is essentially of an infantile nature, and that, as development proceeds, it is sacrificed to social considerations."Narcissistic injury and narcissistic scar are terms used by Freud in the 1920s. Narcissistic wound and narcissistic blow are other, almost interchangeable, terms. When wounded in the ego, either by a real or a perceived criticism, a narcissistic persons displays of anger can be disproportionate to the nature of the criticism suffered; but typically, the actions and responses of the NPD person are deliberate and calculated. Despite occasional flare-ups of personal insecurity, the inflated self-concept of the NPD person is primarily stable.In The Psychology of Gambling (1957), Edmund Bergler considered megalomania to be a normal occurrence in the psychology of a child, a condition later reactivated in adult life, if the individual takes up gambling. In The Psychoanalytic Theory of Neurosis (1946), Otto Fenichel said that people who, in their later lives, respond with denial to their own narcissistic injury usually undergo a similar regression to the megalomania of childhood.

Narcissistic supply
Narcissistic supply was a concept introduced by Otto Fenichel in 1938, to describe a type of admiration, interpersonal support, or sustenance drawn by an individual from his or her environment and essential to their self-esteem. The term is typically used in a negative sense, describing a pathological or excessive need for attention or admiration in codependents and the orally fixated, that does not take into account the feelings, opinions, or preferences of other people.

Narcissistic rage
The term narcissistic rage was a concept introduced by Heinz Kohut in 1972. Narcissistic rage was theorised as a reaction to a perceived threat to a narcissists self-esteem or self-worth. Narcissistic rage occurs on a continuum from aloofness, to expressions of mild irritation or annoyance, to serious outbursts, including violent attacks.Narcissistic rage reactions are not necessarily limited to NPD. They may also be seen in catatonic, paranoid delusion, and depressive episodes. It was later suggested that narcissistic people have two layers of rage; the first layer of rage being directed constant anger towards someone else, with the second layer being self-deprecating.

Object relations
In the second half of the 20th century, in contrast to Freuds perspective of megalomania as an obstacle to psychoanalysis, in the US and UK Kleinian psychologists used the object relations theory to re-evaluate megalomania as a defence mechanism. This Kleinian therapeutic approach built upon Heinz Kohuts view of narcissistic megalomania as an aspect of normal mental development, by contrast with Otto Kernbergs consideration of such grandiosity as a pathological distortion of normal psychological development.To the extent that people are pathologically narcissistic, the person with NPD can be a self-absorbed individual who passes blame by psychological projection and is intolerant of contradictory views and opinions; is apathetic towards the emotional, mental, and psychological needs of other people; and is indifferent to the negative effects of their behaviors, whilst insisting that people should see them as an ideal person. The merging of the terms "inflated self-concept" and "actual self" is evident in later research on the grandiosity component of narcissistic personality disorder, along with incorporating the defence mechanisms of idealization and devaluation and of denial.

Comparison to other personality disorders
NPD shares properties with borderline personality disorder, including social stigma, unclear causes and prevalence rates. In a 2020 study, it was argued that NPD is following a similar historical trend to borderline personality disorder: "In the past three decades, enormous progress has been made to elucidate the psychopathology, longitudinal course, and effective treatment for BPD. NPD, which remains as similarly stigmatized and poorly understood as BPD once was, now carries the potential for a new wave of investigation and treatment development."However, NPD also shares some commonality with the now discredited "multiple personality disorder" (MPD) personality constellation in popular culture and clinical lore. MPD received a high level of mainstream media attention the 1980s, followed by a nearly complete removal from public discourse within the following two decades; this was in part due to thorough debunking many of its propositions and the evident societal harm created by its entry into the legal defence realm. Similar to MPD, NPD has been the subject of high levels of preoccupation in social and popular media forums, without a firm empirical basis despite over a century of description in clinical lore. The NPD label may be misused colloquially and clinically to disparage a target for the purpose of buttressing ones own self-esteem, or other motives that are detrimental for the person receiving the label. Finally, the rise in popular interest in NPD is not accompanied by hypothesized increases in narcissism among recent generations despite widespread assumptions to the contrary.

Controversy
The extent of controversy about narcissism was on display when the committee on personality disorders for the 5th Edition (2013) of the Diagnostic and Statistical Manual of Mental Disorders recommended the removal of Narcissistic Personality from the manual. A contentious three-year debate unfolded in the clinical community with one of the sharpest critics being John Gunderson, who led the DSM personality disorders committee for the 4th edition of the manual.The American Psychiatric Associations (APA) formulation, description, and definition of narcissistic personality disorder, as published in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Ed., Text Revision (DSM-IV-TR, 2000), was criticised by clinicians as inadequately describing the range and complexity of the personality disorder that is NPD. That it is excessively focused upon "the narcissistic individuals external, symptomatic, or social interpersonal patterns – at the expense of ... internal complexity and individual suffering", which reduced the clinical utility of the NPD definition in the DSM-IV-TR.In revising the diagnostic criteria for personality disorders, the work group for the list of "Personality and Personality Disorders" proposed the elimination of narcissistic personality disorder (NPD) as a distinct entry in the DSM-5, and thus replaced a categorical approach to NPD with a dimensional approach, which is based upon the severity of the dysfunctional-personality-trait domains. Clinicians critical of the DSM-5 revision characterized the new diagnostic system as an "unwieldy conglomeration of disparate models that cannot happily coexist", which is of limited usefulness in clinical practice. Despite the reintroduction of the NPD entry, the APAs re-formulation, re-description, and re-definition of NPD, towards a dimensional view based upon personality traits, remains in the list of personality disorders of the DSM-5.
A 2011 study concluded that narcissism should be conceived as personality dimensions pertinent to the full range of personality disorders, rather than as a distinct diagnostic category. In a 2012 literature review about NPD, the researchers concluded that narcissistic personality disorder "shows nosological inconsistency, and that its consideration as a trait domain needed further research would be strongly beneficial to the field." In a 2018 latent structure analysis, results suggested that the DSM-5 NPD criteria fail to distinguish some aspects of narcissism relevant to diagnosis of NPD and subclinical narcissism.

In popular culture
Game of Thrones series and television adaptation of George R </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 Hypoglycemia and can you explain it in depth? [/INST] Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipples triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose below 70 mg/dL (3.9 mmol/L), symptoms associated with hypoglycemia, and resolution of symptoms when blood sugar returns to normal. Hypoglycemia may result in headache, tiredness, clumsiness, trouble talking, confusion, fast heart rate, sweating, shakiness, nervousness, hunger, loss of consciousness, seizures, or death. Symptoms typically come on quickly.The most common cause of hypoglycemia is medications used to treat diabetes such as insulin, sulfonylureas, and biguanides. Risk is greater in diabetics who have eaten less than usual, recently exercised, or consumed alcohol. Other causes of hypoglycemia include severe illness, sepsis, kidney failure, liver disease, hormone deficiency, tumors such as insulinomas or non-B cell tumors, inborn errors of metabolism, several medications, and alcohol. Low blood sugar may occur in otherwise healthy newborns who have not eaten for a few hours.Hypoglycemia is treated by eating a sugary food or drink, for example glucose tabs or gel, apple juice, soda, or candy. The person must be conscious and able to swallow. The goal is to consume 10-20 grams of a carbohydrate to raise blood glucose levels to a minimum of 70 mg/dL (3.9 mmol/L). If a person is not able to take food by mouth, glucagon by injection or in the nose may help. The treatment of hypoglycemia unrelated to diabetes includes treating the underlying problem.Among people with diabetes, prevention starts with learning the signs and symptoms of hypoglycemia. Diabetes medications, like insulin, sulfonylureas, and biguanides can also be adjusted or stopped to prevent hypoglycemia. Frequent and routine blood glucose testing is recommended. Some may find continuous glucose monitors with insulin pumps to be helpful in the management of diabetes and prevention of hypoglycemia.

Definition
Blood sugar levels naturally fluctuate throughout the day, however hypoglycemia, also called low blood sugar or low blood glucose, is when blood sugar levels drop below 70 mg/dL (3.9 mmol/L).Blood sugar levels are generally maintained between 70 and 110 mg/dL (3.9-6.1 mmol/L). Although 70 mg/dL (3.9 mmol/L) is the lower limit of normal glucose, symptoms of hypoglycemia usually do not occur until 55 mg/dL (3.0 mmol/L) or lower. The blood glucose level at which symptoms of hypoglycemia develop in someone with several prior episodes of hypoglycemia may be even lower.

Whipples triad
The symptoms of low blood sugar alone are not specific enough to characterize a hypoglycemic episode. A single blood sugar reading below 70 mg/dL is also not specific enough characterize a hypoglycemic episode. Whipples triad is a set of three conditions that need to be met in order to accurately characterize a hypoglycemic episode.The three conditions are the following:

The signs and symptoms of hypoglycemia are present (see section below on Signs and Symptoms)
A low blood glucose measurement is present, typically less than 70 mg/dL (3.9 mmol/L)
The signs and symptoms of hypoglycemia resolve after blood glucose levels have returned to normal

Age
The biggest difference in blood glucose levels between the adult and pediatric population occurs in newborns during the first 48 hours of life. After the first 48 hours of life, the Pediatric Endocrine Society cites that there is little difference in blood glucose level and the use of glucose between adults and children. During the 48 hour neonatal period, the neonate adjusts glucagon and epinephrine levels following birth, which may cause temporary hypoglycemia. As a result, there has been difficulty in developing guidelines on interpretation and treatment of low blood glucose in neonates aged less than 48 hours. Following a data review, the Pediatric Endocrine Society concluded that neonates aged less than 48 hours begin to respond to hypoglycemia at serum glucose levels of 55–65 mg/dL (3.0-3.6 mmol/L). This is contrasted by the value in adults, children, and older infants, which is approximately 80–85 mg/dL (4.4-4.7 mmol/L).In children who are aged greater than 48 hours, serum glucose on average ranges from 70 to 100 mg/dL (3.9-5.5 mmol/L), similar to adults. Whipples triad is used to identify hypoglycemia in children who can communicate their symptoms.

Differential diagnosis
Other conditions that may present similarly to hypoglycemia include the following:

Alcohol or drug intoxication
Cardiac arrhythmia
Valvular heart disease
Postprandial syndrome
Hyperthyroidism
Pheochromocytoma
Post-gastric bypass hypoglycemia
Generalized anxiety disorder
Surreptitious insulin use
Lab or blood draw error (lack of antiglycolytic agent in collection tube or during processing)

Signs and symptoms
Hypoglycemic symptoms are divided into two main categories. The first category is symptoms caused by low glucose in the brain, called neuroglycopenic symptoms. The second category of symptoms is caused by the bodys reaction to low glucose in the brain, called adrenergic symptoms.
Everyone experiences different symptoms of hypoglycemia, so someone with hypoglycemia may not have all of the symptoms listed above. Symptoms also tend to have quick onset. It is important to quickly obtain a blood glucose measurement in someone presenting with symptoms of hypoglycemia to properly identify the hypoglycemic episode.

Pathophysiology
Glucose is the main source of energy for the brain, and a number of mechanisms are in place to prevent hypoglycemia and protect energy supply to the brain. The body can adjust insulin production and release, adjust glucose production by the liver, and adjust glucose use by the body. The body naturally produces the hormone insulin, in an organ called the pancreas. Insulin helps to regulate the amount of glucose in the body, especially after meals. Glucagon is another hormone involved in regulating blood glucose levels, and can be thought of as the opposite of insulin. Glucagon helps to increase blood glucose levels, especially in states of hunger.When blood sugar levels fall to the low-normal range, the first line of defense against hypoglycemia is decreasing insulin release by the pancreas. This drop in insulin allows the liver to increase glycogenolysis. Glycogenolysis is the process of glycogen breakdown that results in the production of glucose. Glycogen can be thought of as the inactive, storage form of glucose. Decreased insulin also allows for increased gluconeogenesis in the liver and kidneys. Gluconeogenesis is the process of glucose production from non-carbohydrate sources, supplied from muscles and fat.Once blood glucose levels fall out of the normal range, additional protective mechanisms work to prevent hypoglycemia. The pancreas is signaled to release glucagon, a hormone that increases glucose production by the liver and kidneys, and increases muscle and fat breakdown to supply gluconeogenesis. If increased glucagon does not raise blood sugar levels to normal, the adrenal glands release epinephrine. Epinephrine works to also increase gluconeogenesis and glycogenolysis, while also decreasing the use of glucose by organs, protecting the brains glucose supply.After hypoglycemia has been prolonged, cortisol and growth hormone are released to continue gluconeogenesis and glycogenolysis, while also preventing the use of glucose by other organs. The effects of cortisol and growth hormone are far less effective than epinephrine. In a state of hypoglycemia, the brain also signals a sense of hunger and drives the person to eat, in an attempt to increase glucose.

Causes
Hypoglycemia is most common in those with diabetes treated by insulin, glinides, and sulfonylureas. Hypoglycemia is rare in those without diabetes, because there are many regulatory mechanisms in place to appropriately balance glucose, insulin, and glucagon. Please refer to Pathophysiology section (above) for more information on glucose, insulin, and glucagon.

Diabetics
Medications
The most common cause of hypoglycemia in diabetics is medications used to treat diabetes such as insulin, sulfonylureas, and biguanides. This is often due to excessive doses or poorly timed doses. Sometimes diabetics may take insulin in anticipation of a meal or snack, and missing or forgetting that meal will lead to hypoglycemia. This is due to increased insulin without the presence of glucose from the planned meal.

Hypoglycemic unawareness
Recurrent episodes of hypoglycemia can lead to hypoglycemic unawareness, or the decreased ability to recognize hypoglycemia. As diabetics experience more episodes of hypoglycemia, the blood glucose level which triggers symptoms of hypoglycemia decreases. In other words, people without hypoglycemic unawareness experience symptoms of hypoglycemia at a blood glucose of about 55 mg/dL (3.0 mmol/L). Those with hypoglycemic unawareness experience the symptoms of hypoglycemia at far lower levels of blood glucose. This is dangerous for a number of reasons. The hypoglycemic person not only gains awareness of hypoglycemia at very low blood glucose levels, but they also require high levels of carbohydrates or glucagon to recover their blood glucose to normal levels. These individuals are also at far greater risk of severe hypoglycemia.While the exact cause of hypoglycemic unawarenss is still under research, it is thought that these individuals progressively begin to develop fewer adrenergic-type symptoms, resulting in the loss of  neuroglycopenic-type symptoms. Neuroglycopenic symptoms are caused by low glucose in the brain, and can result in tiredness, confusion, difficulty with speech, seizures, and loss of consciousness. Adrenergic symptoms are caused by the bodys reaction to low glucose in the brain, and can result in fast heart rate, sweating, nervousness, and hunger. See section above on Signs and Symptoms for further explanation of neuroglycopenic symptoms and adrenergic symptoms.
In terms of epidemiology, hypoglycemic unawarenss occurs in 20-40% of type 1 diabetics.

Other causes
Other causes of hypoglycemia in diabetics include the following:

Fasting, whether it be a planned fast or overnight fast, as there is a long period of time without glucose intake
Exercising more than usual as it leads to more use of glucose, especially by the muscles
Drinking alcohol, especially when combined with diabetic medications, as alcohol inhibits glucose production
Kidney disease, as insulin cannot be cleared out of circulation well

Non-diabetics
Serious illness
Serious illness may result in low blood sugar. Severe disease of many organ systems can cause hypoglycemia as a secondary problem. Hypoglycemia is especially common in those in the intensive care unit or those in whom food and drink is withheld as a part of their treatment plan.Sepsis, a common cause of hypoglycemia in serious illness, can lead to hypoglycemia through many ways. In a state of sepsis, the body uses large amounts of glucose for energy. Glucose use is further increased by cytokine production. Cytokines are a protein produced by the body in a state of stress, particularly when fighting an infection. Cytokines may inhibit glucose production, further decreasing the bodys energy stores. Finally, the liver and kidneys are sites of glucose production, and in a state of sepsis those organs may not receive enough oxygen, leading to decreased glucose production due to organ damage.Other causes of serious illness that may cause hypoglycemia include liver failure and kidney failure. The liver is the main site of glucose production in the body, and any liver failure or damage will lead to decreased glucose production. While the kidneys are also sites of glucose production, their failure of glucose production is not significant enough to cause hypoglycemia . Instead, the kidneys are responsible for removing insulin from the body, and when this function is impaired in kidney failure, the insulin stays in circulation longer, leading to hypoglycemia.

Drugs
A number of medications have been identified which may cause hypoglycemia, through a variety of ways. Moderate quality evidence implicates the non-steroidal anti-inflammatory drug indomethacin and the anti-malarial quinine. Low quality evidence implicates lithium, used for bipolar disorder. Finally, very low quality evidence implicates a number of hypertension medications including angiotensin converting enzyme inhibitors (also called ACE-inhibitors), angiotensin receptor blockers (also called ARBs), and β-adrenergic blockers (also called beta blockers). Other medications with very low quality evidence include the antibiotics levofloxacin and trimethoprim-sulfamethoxazole, progesterone blocker mifepristone, anti-arrhythmic disopyramide, anti-coagulant heparin, and chemotherapeutic mercaptopurine.If a person without diabetes accidentally takes medications that are traditionally used to treat diabetes, this may also cause hypoglycemia. These medications include insulin, glinides, and sulfonylureas. This may occur through medical errors in a healthcare setting or through pharmacy errors, also called iatrogenic hypoglycemia.

Surreptitious insulin use
When individuals take insulin without needing it, to purposefully induce hypoglycemia, this is referred to as surreptitious insulin use or factitious hypoglycemia. Some people may use insulin to induce weight loss, whereas for others this may be due to malingering or factitious disorder, which is a psychiatric disorder. Demographics affected by factitious hypoglycemia include women aged 30–40, particularly those with diabetes, relatives with diabetes, healthcare workers, or those with history of a psychiatric disorder. The classic way to identify surreptitious insulin use is through blood work revealing high insulin levels with low C-peptide and proinsulin.

Alcohol misuse
The production of glucose is blocked by alcohol. In those who misuse alcohol, hypoglycemia may be brought on by a several-day alcohol binge associated with little to no food intake. The cause of hypoglycemia is multifactorial, where glycogen becomes depleted in a state of starvation. Glycogen stores are then unable to be repleted due to the lack of food intake, all compounded the inhibition of glucose production by alcohol.

Hormone deficiency
Children with primary adrenal failure, also called Addisons disease, may experience hypoglycemia after long periods of fasting. Addisons disease is associated with chronically low levels of the stress hormone cortisol, which leads to decreased glucose production.Hypopituitarism, leading to decreased growth hormone, is another cause of hypoglycemia in children, particularly with long periods of fasting or increased exercise.

Inborn errors of metabolism
Briefly, inborn errors of metabolism are a group rare of genetic disorders that are associated with the improper breakdown or storage of proteins, carbohydrates, or fatty acids. Inborn errors of metabolism may cause infant hypoglycemia, and much less commonly adult hypoglycemia. Disorders that are related to the breakdown of glycogen, called glycogen storage diseases, may cause hypoglycemia. Normally, breakdown of glycogen leads to increased glucose levels, particularly in a fasting state. In glycogen storage diseases however, glycogen cannot be properly broken-down, leading to inappropriately decreased glucose levels in a fasting state, and thus hypoglycemia. The glycogen storage diseases associated with hypoglycemia include type 0, type I, type III, and type IV, as well as Fanconi syndrome.

Insulinomas
A primary B-cell tumor, such as an insulinoma, is associated with hypoglycemia. This is a tumor located in the pancreas. An insulinoma produces insulin, which in turn decreases glucose levels, causing hypoglycemia. Normal regulatory mechanisms are not in place, which prevent insulin levels from falling during states of low blood glucose. During an episode of hypoglycemia, plasma insulin, C-peptide, and proinsulin will be inappropriately high.

Non-B cell tumors
Hypoglycemia may occur in people with non-B cell tumors such as hepatomas, adrenocorticoid carcinomas, and carcinoid tumors. These tumors lead to a state of increased insulin, specifically increased insulin-like growth factor II, which decreases glucose levels.

Post-gastric bypass postprandial hypoglycemia
The Roux-en-Y gastric bypass, is a weight-loss surgery performed on the stomach, and has been associated with hypoglycemia, called post-gastric bypass postprandial hypoglycemia. Although the entire mechanism of hypoglycemia following this surgery is not fully understood, it is thought that meals cause very high levels of glucagon-like peptide-1 (also called GLP-1), a hormone that increases insulin, causing glucose levels to drop.

Autoimmune hypoglycemia
Antibodies can be formed against insulin, leading to autoimmune hypoglycemia. Antibodies are immune cells produced by the body, that normally attack bacteria and viruses, but sometimes can attack normal human cells, leading to an autoimmune disorder. In autoimmune hypoglycemia, there are two possible mechanisms. In one instance, antibodies bind to insulin following its release associated with a meal, resulting in insulin being non-functional. At a later time, the antibodies fall off insulin, causing insulin to be functional again leading late hypoglycemia after a meal, called late postprandial hypoglycemia. Another mechanism causing hypoglycemia is due to antibodies formed against insulin receptors, called insulin receptor antibodies. The antibodies attach to insulin receptors and prevent insulin breakdown, or degradation, leading to inappropriately high insulin levels and low glucose levels.

Neonatal hypoglycemia
Low blood sugar may occur in healthy neonates aged less than 48 hours who have not eaten for a few hours. During the 48 hour neonatal period, the neonate adjusts glucagon and epinephrine levels following birth, which may trigger transient hypoglycemia. In children who are aged greater than 48 hours, serum glucose on average ranges from 70 to 100 mg/dL (3.9-5.5 mmol/L), similar to adults, with hypoglycemia being far less common.

Diagnostic approach
The most reliable method of identifying hypoglycemia is through identifying Whipples triad. The components of Whipples triad are a blood sugar level below 70 mg/dL (3.9 mmol/L), symptoms related to low blood sugar, and improvement of symptoms when blood sugar is restored to normal. Identifying Whipples triad in a patient helps to avoid unnecessary diagnostic testing and decreases healthcare costs.In those with a history of diabetes treated with insulin, glinides, or sulfonylurea, who demonstrate Whipples triad, it is reasonable to assume the cause of hypoglycemia is due to insulin, glinides, or sulfonylurea use. In those without a history of diabetes with hypoglycemia, further diagnostic testing is necessary to identify the cause. Testing, during an episode of hypoglycemia, should include the following:

Plasma glucose level, not point-of-care measurement
Insulin level
C-peptide level
Proinsulin level
Beta-hydroxybutyrate level
Oral hypoglycemic agent screen
Response of blood glucose level to glucagon
Insulin antibodiesIf necessary, a diagnostic hypoglycemic episode can be produced in an inpatient or outpatient setting. This is called a diagnostic fast, in which a patient undergoes an observed fast to cause a hypoglyemic episode, allowing for appropriate blood work to be drawn. In some, the hypoglycemic episode may be reproduced simply after a mixed meal, whereas in others a fast may last up to 72 hours.In those with a suspected insulinoma, imaging is the most reliable diagnostic technique, including ultrasound, computed tomography imaging (also called CT imaging), and magnetic resonsance imaging (also called MRI).

Treatment
After hypoglycemia in a person is identified, rapid treatment is necessary and can be life-saving. The main goal of treatment is to raise blood glucose back to normal levels, which is done through various ways of administering glucose, depending on the severity of the hypoglycemia, what is on-hand to treat, and who is administering the treatment. A general rule used by the American Diabetes Association is the "15-15 Rule," which suggests consuming or administering 15 grams of a carbohydrate, followed by a 15-minute wait and re-measurement of blood glucose level to assess if blood glucose has returned to normal levels.

Self-treatment
If an individual recognizes the symptoms of hypoglycemia coming on, blood sugar should promptly be measured, and a sugary food or drink should be consumed. The person must be conscious and able to swallow. The goal is to consume 10-20 grams of a carbohydrate to raise blood glucose levels to a minimum of 70 mg/dL (3.9 mmol/L).Examples of products to consume are:

Glucose tabs or gel (refer to instructions on packet)
Juice containing sugar like apple, grape, or cranberry juice, 4 ounces or 1/2 cup
Soda or a soft-drink, 4 ounces or 1/2 cup (not diet soda)
Candy
Table sugar or honey, 1 tablespoonImprovement in blood sugar levels and symptoms are expected to occur in 15–20 minutes, at which point blood sugar should be measured again. If the repeat blood sugar level is not above 70 mg/dL (3.9 mmol/L), consume another 10-20 grams of a carbohydrate and remeasure blood sugar levels after 15–20 minutes. Repeat until blood glucose levels have returned to normal levels. The greatest improvements in blood glucose will be seen if the carbohydrate chewed or drunk, and then swallowed. This results in the greatest bioavaliablity of glucose, meaning the greatest amount of glucose enters the body producing the best possible improvements in blood glucose levels. The second best way to consume a carbohydrate it to allow it to dissolve under the tongue, also referred to as sublingual administration. For example, a hard candy can be dissolved under the tongue, however the best improvements in blood glucose will occur if the hard candy is chewed and crushed, then swallowed.After correcting blood glucose levels, people may consume a full meal within one hour in order to replenish glycogen stores.

Education
Family, friends, and co-workers of a person with diabetes may provide life-saving treatment in the case of a hypoglycemic episode It is important for these people to receive training on how to recognize hypoglycemia, what foods to help the hypoglycemic eat, how to administer injectable or intra-nasal glucagon, and how use a glucose meter.

Treatment by family, friends, or co-workers
Family, friends, and co-workers of those with hypoglycemia are often first to identify hypoglycemic episodes, and may offer help. Upon recognizing the signs and symptoms of hypoglycemia in a diabetic, a blood sugar level should first be measured using a glucose meter. If blood glucose is below 70 mg/dL (3.9 mmol/L), treatment will depend on whether the person is conscious and can swallow safely. If the person is conscious and able to swallow, the family, friend, or co-worker can help the hypoglycemic consume 10-20 grams of a carbohydrate to raise blood glucose levels to a minimum of 70 mg/dL (3.9 mmol/L). Improvement in blood sugar level and symptoms is expected to occur in 15–20 minutes, at which point blood sugar is measured again. If the repeat blood sugar level is not above 70 mg/dL (3.9 mmol/L), the hypoglycemic should consume another 10-20 grams of a carbohydrate and with remeasurement of blood sugar levels after 15–20 minutes. Repeat until blood glucose levels have returned to normal levels, or call emergency services for further assistance.If the person is unconscious, a glucagon kit may be used to treat severe hypoglycemia, which delivers glucagon either by injection into a muscle or through nasal inhalation. In the United States, glucacon kits are available by prescription for diabetic patients to carry in case of an episode of severe hypoglycemia. Emergency services should be called for further assistance.

Treatment by medical professionals
In a healthcare setting, treatment depends on the severity of symptoms and intravenous access. If a patient is conscious and able to swallow safely, food or drink may be administered, as well as glucose tabs or gel. In those with intravenous access, 25 grams of 50% dextrose is commonly administered. When there is no intravenous access, intramuscular or intra-nasal glucagon may be administered.

Other treatments
While the treatment of hypoglycemia is typically managed with carbohydrate consumption, glucagon injection, or dextrose administration, there are some other treatments available. Medications like diazoxide and octreotide decrease insulin levels, increasing blood glucose levels. Dasiglucagon was approved for medical use in the United States in March 2021, to treat severe hypoglycemia. Dasiglucagon (brand name Zegalogue) is unique because it is glucagon in a prefilled syringe or auto-injector pen, as opposed to traditional glucagon kits that require mixing powdered glucagon with a liquid.The soft drink Lucozade has been used for hypoglycemia in the United Kingdom, but it has recently replaced much of its glucose with artificial sweeteners, which do not treat hypoglycemia.

Prevention
Diabetics
The prevention of hypoglycemia depends on the cause. In those with diabetes treated by insulin, glinides, or sulfonylurea, the prevention of hypoglycemia has a large focus on patient education and medication adjustments. The foundation of diabetes education is learning how to recognize the signs and symptoms of hypoglycemia, as well as learning how to act quickly to prevent worsening of an episode. Another cornerstone of prevention is strong self-monitoring of blood glucose, with consistent and frequent measurements. Research has shown that patients with type 1 diabetes who use continuous glucose monitoring systems with insulin pumps significantly improve blood glucose control. Insulin pumps help to prevent high glucose spikes, and help prevent inappropriate insulin dosing. Continuous glucose monitors can sound alarms when blood glucose is too low or too high, especially helping those with nocturnal hypoglycemia or hypoglycemic unawareness. In terms of medication adjustments, medication doses and timing can be adjusted in order to prevent hypoglycemia, or a medication can be stopped altogether.

Non-diabetics
In those with hypoglycemia who do not have diabetes, there are a number of preventative measures dependent on the cause. Hypoglycemia caused by hormonal dysfunction like lack of cortisol in Addisons disease or lack of growth hormone in hypopituitarism can be prevented with appropriate hormone replacement. The hypoglycemic episodes associated with non-B cell tumors can be decreased following surgical removal of the tumor, as well as following radiotherapy or chemotherapy to reduce the size of the tumor. In some cases, those with non-B cell tumors may have hormone therapy with growth hormone, glucocorticoid, or octreotide to also lessen hypoglycemic episodes. Post-gastric bypass hypoglycemia can be prevented by eating smaller, more frequent meals, avoiding sugar-filled foods, as well as medical treatment with an alpha-glucosidase inhibitor, diazoxide, or octreotide.Some causes of hypoglycemia require treatment of the underlying cause to best prevent hypoglycemia. This is the case for insulinomas which often require surgical removal of the tumor in order for hypoglycemia to remit. In patients who cannot undergo surgery for removal of the insulinoma, diazoxide or octreotide may be used.

Epidemiology
Hypoglycemia is common in people with type 1 diabetes, and in people with type 2 diabetes taking insulin, glinides, or sulfonylurea. It is estimated that type 1 diabetics experience two mild, symptomatic episodes of hypoglycemia per week. Additionally, people with type 1 diabetes have at least one severe hypoglyemic episode per year, requiring treatment assistance. In terms of mortality, hypoglycemia causes death in 6-10% of type 1 diabetics.In those with type 2 diabetes, hypoglycemia is less common compared to type 1 diabetics, because medications that treat type 2 diabetes like metformin, glitazones, alpha-glucosidase inhibitors, glucagon-like peptide 1 agonists, and dipeptidyl peptidase IV inhibitors, do not cause hypoglycemia. Hypoglycemia is common in type 2 diabetics who take insulin, glinides, or sulfonylurea. Insulin use remains a key risk factor in developing hypoglycemia, regardless of diabetes type.

History
Hypoglycemia was first discovered by James Collip when he was working with Frederick Banting on purifying insulin in 1922.  Collip was asked to develop an assay to measure the activity of insulin </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 Alexander disease and can you explain it in depth? [/INST] Alexander disease is a very rare autosomal dominant leukodystrophy, which are neurological conditions caused by anomalies in the myelin which protects nerve fibers in the brain. The most common type is the infantile form that usually begins during the first 2 years of life. Symptoms include mental and physical developmental delays, followed by the loss of developmental milestones, an abnormal increase in head size and seizures. The juvenile form of Alexander disease has an onset between the ages of 2 and 13 years. These children may have excessive vomiting, difficulty swallowing and speaking, poor coordination, and loss of motor control. Adult-onset forms of Alexander disease are less common. The symptoms sometimes mimic those of Parkinson’s disease or multiple sclerosis, or may present primarily as a psychiatric disorder.
According to the National Institute of Neurological Disorders and Stroke, the destruction of white matter is accompanied by the formation of Rosenthal fibers—abnormal clumps of protein that accumulate in astrocytes in the brain.
The disease occurs in both males and females, and no ethnic, racial, geographic or cultural/economic differences are seen in its distribution. Alexander disease is a progressive and often fatal disease.

Presentation
Delays in development of some physical, psychological and behavioral skills; progressive enlargement of the head (macrocephaly), seizures, spasticity, and in some cases also hydrocephalus, idiopathic intracranial hypertension, and dementia.

Cause
Alexander disease is a genetic disorder affecting the midbrain and cerebellum of the central nervous system. It is caused by mutations in the gene for glial fibrillary acidic protein (GFAP) that maps to chromosome 17q21. It is inherited in an autosomal dominant manner, such that the child of a parent with the disease has a 50% chance of inheriting the condition, if the parent is heterozygotic. However, most cases arise de novo as the result of sporadic mutations.Alexander disease belongs to leukodystrophies, a group of diseases that affect the growth or development of the myelin sheath. The destruction of white matter in the brain is accompanied by the formation of fibrous, eosinophilic deposits known as Rosenthal fibers. Rosenthal fibers appear not to be present in healthy people, but occur in specific diseases, like some forms of cancer, Alzheimer’s, Parkinson’s, Huntington’s, and ALS. The Rosenthal fibers found in Alexander disease do not share the distribution or concentration of other diseases and disorders.

Pathology
Alexander disease causes the gradual loss of bodily functions and the ability to talk. It also causes an overload of long-chain fatty acids in the brain, which destroy the myelin sheath. The cause of Alexander disease is a mutation in the gene encoding GFAP.A CT scan shows:

Decreased density of white matter
Frontal lobe predominance
Dilated lateral ventricles may present

Diagnosis
Detecting the signs of Alexander disease is possible with magnetic resonance imaging (MRI), which looks for specific changes in the brain that may be tell-tale signs for the disease. It is even possible to detect adult-onset Alexander disease with MRI. Alexander disease may also be revealed by genetic testing for its known cause. A rough diagnosis may also be made through revealing of clinical symptoms, including enlarged head size, along with radiological studies, and negative tests for other leukodystrophies.

Treatment
No cure or standard procedure for treatment is known, although a University of Wisconsin study shows promise with gene editing of the astrocytes. A phase III clinical trial of an antisense therapy, sponsored by Ionis Pharmaceuticals, began in 2021. A bone marrow transplant has been attempted on a child, but it made no improvement. Hydrocephalus may be seen in younger patients and can be relieved with surgery or by implanting a shunt to relieve pressure.

Prognosis
The prognosis is generally poor. With early onset, death usually occurs within 10 years from the onset of symptoms. Individuals with the infantile form usually die before the age of seven. Usually, the later the disease occurs, the slower its course.

Prevalence
Its occurrence is very rare. The infantile form occurs from birth to 2 years of 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 Podoconiosis and can you explain it in depth? [/INST] Podoconiosis, also known as nonfilarial elephantiasis, is a disease of the lymphatic vessels of the lower extremities that is caused by chronic exposure to irritant soils. It is the second most common cause of tropical lymphedema after lymphatic filariasis, and it is characterized by prominent swelling of the lower extremities, which leads to disfigurement and disability. Methods of prevention include wearing shoes and using floor coverings. Mainstays of treatment include daily foot hygiene, compression bandaging, and when warranted, surgery of overlying nodules.

Signs and symptoms
Podoconiosis causes bilateral yet asymmetrical leg swelling with overlying firm nodules. Early on, symptoms may include itching, tingling, widening of the forefoot, and swelling which then progress to soft edema, skin fibrosis, papillomatosis, and nodule formation resembling moss, giving rise to the diseases alternate name of "mossy foot" in some regions of the world.  As with other forms of tropical lymphedema, chronic disease can lead to rigid toes, ulceration, and bacterial superinfection. During acute episodes of adenolymphangitis, patients may develops fevers, extremity warmth, redness, and pain. These episodes are extremely debilitating and account for many days of activity and productivity loss each year.

Psychological consequences
As a result of its appearance, podoconiosis can cause social stigmatization and discrimination. People with podoconiosis also report a lower quality of life than people in  similar neighborhood circumstances except without podoconiosis and also higher levels of mental distress and depression.

Pathophysiology
According to the World Health Organization "Evidence suggests that podoconiosis is the result of a genetically determined abnormal inflammatory reaction to mineral particles in irritant red clay soils derived from volcanic deposits".The pathophysiology of podoconiosis is a combination of genetic susceptibility, possibly through associations with HLA-DQA1, HLA-DQB1, and HLA-DRB1 variants, and a cumulative exposure to irritant soil. In susceptible individuals, irritant soil particles penetrate the feet and collect in lymphatic vessels. Over time, chronic inflammation within the lymphatic vessels leads to fibrosis and occlusion.

Diagnosis
Differential diagnosis
The differential diagnosis for podoconiosis includes other causes of tropical lymphedema, such as filariasis or leprosy, and mycetoma pedis.While filariasis is generally unilateral, podoconiosis affects the legs bilaterally albeit asymmetrically and in an ascending manner. Podoconiosis very rarely affects the groin while filariasis frequently involves the groin: a high ratio of lymphoedema/hydrocele cases in an area suggests podoconiosis as the dominant cause of lymphedema. In some cases, the history and clinical presentation alone are unable to differentiate between the two causes of tropical lymphedema. Local epidemiology can also be a clue to diagnosis, as podoconiosis is typically found in higher altitude areas with volcanic soils while filariasis is common in low-lying areas where mosquitos are prevalent. Blood smears for identification of microfilariae and antigen detection techniques can be helpful in the diagnosis of lymphatic filariasis.Lepromatous lymphedema can also mimic podoconiosis clinically, but the former will have loss of sensation in the toes and feet, thickened nerves, and trophic ulcers. Other causes of lymphedema include Kaposi sarcoma, mycetoma, and elephantiasis nostras verrucosa.

Prevention
Elimination of podoconiosis relies on prevention with widespread shoe implementation, stringent foot hygiene, and floor coverings. Community-based initiatives are crucial to achieving elimination of this disease. In Ethiopia, The Mossy Foot Treatment and Prevention Association (now Mossy Foot International) works to transform patients into community podoconiosis agents who in turn visit patients, teach basic treatment techniques such as foot hygiene, and educate families about the disease. This model has been adapted by several other non-government groups as they have started programs in other regions of Ethiopia.

Treatment
The cornerstone of prevention and treatment of podoconiosis is avoidance of exposure to irritant soils.  Wearing shoes in the presence of irritant soils is the primary method of exposure reduction.  In Rwanda, a country of high disease prevalence, the government has banned walking barefoot in public, in order to prevent podoconiosis and other soil-borne diseases. Increasing the availability of footwear must be coupled with education on the benefits of wearing shoes as cultural influences, such as barefoot traditions, can hinder widespread use of footwear.Once the disease has developed, rigorous foot hygiene including daily washing with soap and water, application of an emollient, and nightly elevation of the affected extremity has been shown to reduce frequency of acute attacks.  Nodules will not resolve with these conservative measures, although surgical removal of the nodules can be performed.

Epidemiology
Podoconiosis is most frequently seen in the highland areas of Africa, India, and Central America.  The highest prevalence is seen in Uganda, Tanzania, Kenya, Rwanda, Burundi, Sudan, and Ethiopia. A recent review has summarized the global distribution of podoconiosis.  In some areas of Ethiopia, the prevalence is as high as 4%.  The incidence of podoconiosis increases with age, likely due to cumulative exposure to irritant soil.  It is very rare to see podoconiosis in the 0–5 year old age group, and the incidence rapidly rises from 6 to 20 years of age, with the highest prevalence after 45 years of age.  Podoconiosis is most commonly seen in higher altitude areas with volcanic soil, and it is estimated to affect 4 million people worldwide. Productivity losses associated with the disease are significant </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 Allergic transfusion reaction and can you explain it in depth? [/INST] An allergic transfusion reaction is when a blood transfusion results in allergic reaction. It is among the most common transfusion reactions to occur.  Reported rates depend on the degree of active surveillance versus passing reporting to the blood bank. Overall, they are estimated to complicate up to 3% of all transfusions.  The incidence of allergic transfusion reactions is associated with the amount of plasma in the product. More than 90% of these reactions occur during transfusion.

Signs and symptoms
Cause
Allergic reactions from blood transfusion may occur from the presence of allergy-causing antigens within the donors blood, or transfusion of antibodies from a donor who has allergies, followed by antigen exposure.An allergic transfusion reaction is a type of transfusion reaction that is defined according to the Center for Disease Control (CDC)  as:

Diagnosis
An allergic transfusion reaction is diagnosed if two or more of the following occur within 4 hours of cessation of transfusion:

A probable diagnosis results if any one of the following occurring within 4 hours of cessation of transfusion:
The UK hemovigilance reporting system (SHOT), has classified allergic reactions in to mild, moderate and severe. Reactions can occur that have features of both allergic and febrile reactions.

Mild
A rash, urticaria, or flushing

Moderate
Wheeze (bronchospasm) or angioedema but blood pressure normal and no respiratory compromise </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 Vitreous touch 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 Cold urticaria and can you explain it in depth? [/INST] Cold urticaria (essentially meaning cold hives) is a disorder in large red welts called hives (urticaria) form on the skin after exposure to a cold stimulus. The hives are usually itchy and often the hands and feet will become itchy and swollen as well. Hives vary in size from about 7 mm in diameter to as big as about 27 mm or larger.
This disorder, or perhaps two disorders with the same clinical manifestations, can be inherited (familial cold urticaria) or acquired (primary acquired cold urticaria). The acquired form is most likely to begin between ages 18 and 25, although it can occur as early as 5 years old in some cases. Life-threatening risks include suffocation resulting from swollen tissue (pharyngeal angioedema) induced by cold foods or beverages, drowning after shock from swimming in cold water, and anaphylactic shock.

Types
Cold urticaria may be divided into the following types:

Primary cold contact urticaria
Primary cold contact urticaria is a cutaneous condition characterized by wheals, and occurs in rainy, windy weather, and after swimming in cold water and after contact with cold objects, including ice cubes.

Secondary cold contact urticaria
Secondary cold contact urticaria is a cutaneous condition characterized by wheals, due to serum abnormalities such as cryoglobulinemia or cryofibrinogenemia are extremely rare, and are then associated with other manifestations such as Raynauds phenomenon or purpura.

Reflex cold urticaria
Reflex cold urticaria is a cutaneous condition in which generalized cooling of the body induces widespread welting.

Familial cold urticaria
Familial cold urticaria (also properly known as familial cold autoinflammatory syndrome, FCAS) is an autosomal dominant condition characterized by rash, conjunctivitis, fever/chills and arthralgias elicited by exposure to cold - sometimes temperatures below 22 °C (72 °F).It has been mapped to CIAS1 and is a slightly milder member of the disease family including Muckle–Wells syndrome and NOMID. It is rare and is estimated as having a prevalence of 1 per million people and mainly affects Americans and Europeans.FCAS is one of the cryopyrin-associated periodic syndromes (CAPS) caused by mutations in the CIAS1/NALP3 (aka NLRP3) gene at location 1q44.The effect of FCAS on the quality of life of patients is far reaching. A survey of patients in the United States in 2008 found that "[t]o cope with their underlying disease and to try to avoid symptomatic, painful, flares patients reported limiting their work, school, family, and social activities. Seventy-eight percent of survey participants described an impact of the disease on their work, including absenteeism and impaired job advancement; frequently, they quit their job as a consequence of their disease".Treatment using anakinra (Kineret) has been shown effective for FCAS, although this does mean daily injections of the immunosuppressant into an area such as the lower abdomen. The monoclonal antibody canakinumab (Ilaris) is also used.

Signs and symptoms
When the body is exposed to the cold in individuals affected by the condition, hives appear and the skin in the affected area typically becomes itchy. Hives result from dilation of capillaries which allow fluid to flow out into the surrounding tissue which is the epidermis. They resolve when the body absorbs this fluid. The border of a hive is described as polycyclic, or made up of many circles, and changes as fluid leaks out and then is absorbed. Pressing on a hive causes the skin to blanch (turn pale as blood flow is interrupted), distinguishing it from a bruise or papule.
Hives may appear immediately or after a delay.  Hives can last for a few minutes or a few days, and vary from person to person. Also, a burning sensation occurs. A serious reaction is most likely to occur for patients where the hives occur with less than 3 minutes of exposure (during a cold test).

Cause
The hives are a histamine reaction in response to cold stimuli, including a drastic drop in temperature, cold air, and cold water. There are many causes for cold hives, most are idiopathic (meaning they have no known cause). Some rare conditions can cause cold hives, and it can be useful to test for these conditions if the cold hives are in any way unusual.
Scientists from the USA National Institutes of Health have identified a genetic mutation in three unrelated families that causes a rare immune disorder characterized by excessive and impaired immune function: immune deficiency, autoimmunity, inflammatory skin disorders and cold-induced hives (cold urticaria).

"The mutation discovered occurs in a gene for phospholipase C-gamma2 (PLCG2), an enzyme involved in the activation of immune cells. The investigators have named the condition PLCG2-associated antibody deficiency and immune dysregulation, or PLAID."

Diagnosis
Diagnosis is typically obtained by an allergist or other licensed practitioner performing a cold test. During the cold test, a piece of ice is placed inside a thin plastic bag and held against the forearm, typically for 3–4 minutes. A positive result is a specific looking mark of raised red hives. The hives may be the shape of the ice, or it may radiate from the contact area of the ice. However, while these techniques assist in diagnosis, they do not provide information about temperature and stimulation time thresholds at which patients will start to develop symptoms, which is essential because it can establish disease severity and monitor the effectiveness of treatment.

Management
Management largely consists of avoiding exposures that could trigger a reaction and taking medicine to manage the reaction </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 Toxic oil syndrome and can you explain it in depth? [/INST] Toxic oil syndrome
(TOS) or simply toxic syndrome (Spanish: síndrome del aceite tóxico or síndrome tóxico) is a musculoskeletal disease. A 1981 outbreak in Spain which affected about 20,000 people, with over 300 dying within a few months and a few thousand remaining disabled, is thought to have been caused by contaminated colza (rapeseed) oil.  It was unique because of its size, the novelty of the clinical condition, and the complexity of its aetiology. Its first appearance was as a lung disease, with unusual features, though the symptoms initially resembled a lung infection. The disease appeared to be restricted to certain geographical localities, and several members of a family could be affected, even while their neighbours had no symptoms. Following the acute phase, a range of other chronic symptoms was apparent.

Alternative mechanisms
The conclusion of the Joint WHO/CISAT Scientific Committee for the Toxic Oil Syndrome from 2002, that oil was the cause for TOS, is based only on epidemiological evidence, since up to now, experimental studies performed in a variety of laboratory animals have failed to reproduce the symptoms of human TOS. None of the in vivo or in vitro studies performed with toxic-oil-specific components, such as fatty acid anilides, and esters of 3-(N-phenylamino)-1,2-propanediol (abbreviated as PAP), have provided evidence that these markers are causally involved in the pathogenesis of TOS.Specifically, three possible causative agents of TOS are PAP (3-(N-phenylamino)-1,2-propanediol), the 1,2-dioleoyl ester of PAP (abbreviated OOPAP), and the 3-oleoyl ester of PAP (abbreviated OPAP) </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 Tumoral calcinosis and can you explain it in depth? [/INST] Tumoral calcinosis is a rare condition in which there is calcium deposition in the soft tissue in periarticular location, around joints, outside the joint capsule. They are frequently (0.5–3%) seen in patients undergoing renal dialysis. Clinically also known as hyperphosphatemic familial tumoral calcinosis (HFTC), is often caused by genetic mutations in genes that regulate phosphate physiology in the body (leading to too much phosphate (hyperphosphatemia)). Best described genes that harbour mutations in humans are FGF-23, Klotho (KL), or GALNT3. A zebrafish animal model with reduced GALNT3 expression also showed HFTC-like phenotype, indicating an evolutionary conserved mechanism that is involved in developing tumoral calcinosis.

Clinical features
The name indicates calcinosis (calcium deposition) which resembles tumor (like a new growth). They are not true neoplasms – they dont have dividing cells </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 Duplicated ureter and can you explain it in depth? [/INST] Duplicated ureter or Duplex Collecting System is a congenital condition in which the ureteric bud, the embryological origin of the ureter, splits (or arises twice), resulting in two ureters draining a single kidney. It is the most common renal abnormality, occurring in approximately 1% of the population.

Pathophysiology
Ureteral development begins in the human fetus around the 4th week of embryonic development </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 Post-thrombotic syndrome and can you explain it in depth? [/INST] Post-thrombotic syndrome (PTS), also called postphlebitic syndrome and venous stress disorder is a medical condition that may occur as a long-term complication of deep vein thrombosis (DVT).

Signs and symptoms
Signs and symptoms of PTS in the leg may include:
pain (aching or cramping)
heaviness
itching or tingling
swelling (edema)
varicose veins
brownish or reddish skin discoloration
ulcerThese signs and symptoms may vary among patients and over time. With PTS, these symptoms typically are worse after walking or standing for long periods of time and improve with resting or elevating the leg.PTS lowers a persons quality of life after DVT, specifically with regards to physical and psychological symptoms and limitations in daily activities.

Cause
Despite outgoing research, the cause of PTS is not entirely clear. Inflammation is thought to play a role as well as damage to the venous valves from the thrombus itself. This valvular incompetence combined with persistent venous obstruction from thrombus increases the pressure in veins and capillaries. Venous hypertension induces a rupture of small superficial veins, subcutaneous hemorrhage and an increase of tissue permeability. That is manifested by pain, swelling, discoloration, and even ulceration.

Risk factors
The following factors increase the risk of developing PTS:
age > 65
proximal DVT
a second DVT in same leg as first DVT (recurrent ipsilateral DVT)
persistent DVT symptoms 1  month after DVT diagnosis
obesity
poor quality of anticoagulation control (i.e. dose too low) during the first 3 months of treatment

Diagnosis
When physicians find a DVT in the clinical history of their patients, a postthrombotic syndrome is possible if the patients have suggestive symptoms. Ultrasonography for deep venous thrombosis must be performed to evaluate the situation: the degree of obstruction by clots, the location of these clots, and the detection of deep and/or superficial venous insufficiency. Since signs and symptoms of DVT and PTS may be quite similar, a diagnosis of PTS should be delayed for 3–6 months after DVT diagnosis so an appropriate diagnosis can be made.

Prevention
Prevention of PTS begins with prevention of initial and recurrent DVT </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 Phlegmasia cerulea dolens and can you explain it in depth? [/INST] Phlegmasia cerulea dolens (PCD) (literally: painful blue inflammation), not to be confused with preceding phlegmasia alba dolens, is an uncommon severe form of lower extremity deep venous thrombosis (DVT) that obstructs blood outflow from a vein. Upper extremity PCD is less common, occurring in under 10% of all cases. PCD results from extensive thrombotic occlusion (blockage by a thrombus) of extremity veins, most commonly an "iliofemoral" DVT of the iliac vein and/or common femoral vein. It is a medical emergency requiring immediate evaluation and treatment.

Symptoms and signs
Primary symptoms
It is characterized by progressive lower extremity edema distal to the thigh, tight shiny skin, cyanosis (inadequate blood oxygenation), petechiae or purpura, and sudden severe pain of the affected limb in proportion to the level of venous blockage.  Patients often have difficulty walking. Blisters, bullae, paresthesias, and motor weakness may develop in severe cases, along with gangrene in ~50% of cases. Distal pulses are palpable early on but may diminish over time, and doppler signal can be usually heard throughout disease progression </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 Colorectal adenoma 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 Fuchs heterochromic iridocyclitis and can you explain it in depth? [/INST] Fuchs heterochromic iridocyclitis (FHI) is a chronic unilateral uveitis appearing with the triad of heterochromia, predisposition to cataract and glaucoma, and keratitic precipitates on the posterior corneal surface </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 Beckers nevus and can you explain it in depth? [/INST] Beckers nevus (also known as "Beckers melanosis", "Beckers pigmentary hamartoma", "nevoid melanosis", and "pigmented hairy epidermal nevus") is a benign skin disorder predominantly affecting males.: 687  The nevus can be present at birth, but more often shows up around puberty. It generally first appears as an irregular pigmentation (melanosis or hyperpigmentation) on the torso or upper arm (though other areas of the  body can be affected), and gradually enlarges irregularly, becoming thickened and often hairy (hypertrichosis).  The nevus is due to an overgrowth of the epidermis, pigment cells (melanocytes), and hair follicles. This form of nevus was first documented in 1948 by American dermatologist Samuel William Becker (1894–1964).

Clinical information
Medical knowledge and documentation of this disorder is poor, likely due to a combination of factors including recent discovery, low prevalence, and the more or less aesthetic nature of the effects of the skin disorder.  Thus the pathophysiology of Beckers nevus remains unclear.  While it is generally considered an acquired rather than congenital disorder, there exists at least one case report documenting what researchers claim is a congenital Beckers nevus with genetic association: a 16-month-old boy with a hyperpigmented lesion on his right shoulder whose father has a similar lesion on his right shoulder.

Prevalence
The most extensive study to date, a 1981 survey of nearly 20,000 French males aged 17 to 26, served to disprove many commonly held beliefs about the disorder </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 Darwins tubercle and can you explain it in depth? [/INST] Darwins tubercle (or auricular tubercle) is a congenital ear condition which often presents as a thickening on the helix at the junction of the upper and middle thirds.

History
This atavistic feature is so called because its description was first published by Charles Darwin in the opening pages of The Descent of Man, and Selection in Relation to Sex, as evidence of a vestigial feature indicating common ancestry among primates which have pointy ears. However, Darwin himself named it the Woolnerian tip, after Thomas Woolner, a British sculptor who had depicted it in one of his sculptures and had first theorised that it was an atavistic feature.

Prevalence
The feature is present in approximately 10.4% of the Spanish adult population, 40% of adults in India, and 58% of Swedish school children </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 Nummular keratitis 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 Middle cerebral artery 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 Periorbital cellulitis and can you explain it in depth? [/INST]  </s>