<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 Schizoaffective disorder and can you explain it in depth? [/INST] Schizoaffective disorder (SZA, SZD or SAD) is a mental disorder characterized by abnormal thought processes and an unstable mood. This diagnosis is made when the person has symptoms of both schizophrenia (usually psychosis) and a mood disorder: either bipolar disorder or depression. The main criterion for a diagnosis of schizoaffective disorder is the presence of psychotic symptoms for at least two weeks without any mood symptoms present. Schizoaffective disorder can often be misdiagnosed when the correct diagnosis may be psychotic depression, bipolar I disorder, schizophreniform disorder, or schizophrenia. It is imperative for providers to accurately diagnose patients, as treatment and prognosis differ greatly for most of these diagnoses.There are three forms of schizoaffective disorder: bipolar (or manic) type (marked by symptoms of schizophrenia and mania), depressive type (marked by symptoms of schizophrenia and depression), and mixed type (marked by symptoms of schizophrenia, depression, and mania). Common symptoms of the disorder include hallucinations, delusions, and disorganized speech and thinking. Auditory hallucinations, or "hearing voices", are most common. The onset of symptoms usually begins in adolescence or young adulthood. On a ranking scale of symptom progression of mental health issues relating to the schizophrenic spectrum, schizoaffective disorder falls between mood disorders and schizophrenia in regards to severity, with other disorders included on the ranking as well depending on symptoms. Schizoaffective disorder and other disorders on the schizophrenic spectrum are evaluated as a psychotic disorder in the DSM-V, so the line between psychotic or not psychotic begins at a mood disorder, as being considered not psychotic, and schizoaffective disorder along with other disorders of the schizophrenia spectrum, as being considered psychotic.Genetics (researched in the field of genomics); problems with neural circuits; chronic early, and chronic or short-term current environmental stress appear to be important causal factors. No single isolated organic cause has been found, but extensive evidence exists for abnormalities in the metabolism of tetrahydrobiopterin (BH4), dopamine, and glutamic acid in people with schizophrenia, psychotic mood disorders, and schizoaffective disorder. People with schizoaffective disorder are likely to have co-occurring conditions, including anxiety disorders and substance use disorders.
While a diagnosis of schizoaffective disorder is rare in the general population, it is considered a common diagnosis among psychiatric disorders. Though schizoaffective disorder and schizophrenia are often thought of as mood disorders, DSM-V criteria classifies them as psychotic disorders. Diagnosis of schizoaffective disorder is based on DSM-V criteria as well as the presence of various symptoms such as mania, depression, and schizophrenia.

The mainstay of current treatment is antipsychotic medication combined with mood stabilizer medication or antidepressant medication, or both. There is growing concern by some researchers that antidepressants may increase psychosis, mania, and long-term mood episode cycling in the disorder. When there is risk to self or others, usually early in treatment, hospitalization may be necessary. Psychiatric rehabilitation, psychotherapy, and vocational rehabilitation are very important for recovery of higher psychosocial function. As a group, people with schizoaffective disorder that were diagnosed using DSM-IV and ICD-10 criteria (which have since been updated) have a better outcome, but have variable individual psychosocial functional outcomes compared to people with mood disorders, from worse to the same. Outcomes for people with DSM-5 diagnosed schizoaffective disorder depend on data from prospective cohort studies, which have not been completed yet. The DSM-5 diagnosis was updated because DSM-IV criteria resulted in overuse of the diagnosis; that is, DSM-IV criteria led to many patients being misdiagnosed with the disorder. DSM-IV prevalence estimates were less than one percent of the population, in the range of 0.5–0.8 percent; newer DSM-5 prevalence estimates are not yet available.

Signs and symptoms
Schizoaffective disorder is defined by mood disorder-free psychosis in the context of a long-term psychotic and mood disorder. Psychosis must meet criterion A for schizophrenia which may include delusions, hallucinations, disorganized thinking and speech or behavior and negative symptoms.  Both delusions and hallucinations are classic symptoms of psychosis.  Delusions are false beliefs which are strongly held despite evidence to the contrary.  Beliefs should not be considered delusional if they are in keeping with cultural beliefs.  Delusional beliefs may or may not reflect mood symptoms (for example, someone experiencing depression may or may not experience delusions of guilt).  Hallucinations are disturbances in perception involving any of the five senses, although auditory hallucinations (or "hearing voices") are the most common. Negative symptoms include alogia (lack of speech), blunted affect (reduced intensity of outward emotional expression), avolition (lack of motivation), and anhedonia (inability to experience pleasure).  Negative symptoms can be more lasting and more debilitating than positive symptoms of psychosis.
Mood symptoms are of mania, hypomania, mixed episode, or depression, and tend to be episodic rather than continuous.  A mixed episode represents a combination of symptoms of mania and depression at the same time.  Symptoms of mania include elevated or irritable mood, grandiosity (inflated self-esteem), agitation, risk-taking behavior, decreased need for sleep, poor concentration, rapid speech, and racing thoughts.  Symptoms of depression include low mood, apathy, changes in appetite or weight, disturbances in sleep, changes in motor activity, fatigue, guilt or feelings of worthlessness, and suicidal thinking.
DSM-5 states that if a patient only experiences psychotic symptoms during a mood episode, their diagnosis is Mood Disorder with Psychotic Features and not Schizophrenia or Schizoaffective Disorder. If the patient experiences psychotic symptoms without mood symptoms for longer than a two-week period, their diagnosis is either Schizophrenia or Schizoaffective Disorder. If mood disorder episodes are present for the majority and residual course of the illness and up until the diagnosis, the patient can be diagnosed with Schizoaffective Disorder.

Causes
A combination of genetic and environmental factors are believed to play a role in the development of schizoaffective disorder.
Genetic studies do not support the view that schizophrenia, psychotic mood disorders and schizoaffective disorder are distinct etiological entities, but rather the evidence suggests the existence of common inherited vulnerability that increases the risks for all these syndromes. Some susceptibility pathways may be specific for schizophrenia, others for bipolar disorder, and yet other mechanisms and genes may confer risk for mixed schizophrenic and affective [or mood disorder] psychoses, but there is no support from genetics for the view that these are distinct disorders with distinct etiologies and pathogenesis. Laboratory studies of putative endophenotypes, brain imaging studies, and post mortem studies shed little additional light on the validity of the schizoaffective disorder diagnosis, as most studies combine subjects with different chronic psychoses in comparison to healthy subjects.
Viewed broadly then, biological and environmental factors interact with a persons genes in ways which may increase or decrease the risk for developing schizoaffective disorder; exactly how this happens (the biological mechanism) is not yet known. Schizophrenia spectrum disorders, of which schizoaffective disorder is a part, have been increasingly linked to advanced paternal age at the time of conception, a known cause of genetic mutations. The physiology of people diagnosed with schizoaffective disorder appears to be similar, but not identical, to that of those diagnosed with schizophrenia and bipolar disorder; however, human neurophysiological function in normal brain and mental disorder syndromes is not fully understood.While there are various medications and treatment options for those with schizoaffective disorder, this disorder can affect a person for their entire lifespan. In some cases, this disorder can affect a persons ability to have a fulfilling social life and they may also have trouble forming bonds or relationships with others. Schizoaffective disorder is also more likely to occur in women and begins at a young age.

Substance use disorder
A clear causal connection between substance use and psychotic spectrum disorders, including schizoaffective disorder, has been difficult to prove. In the specific case of cannabis (marijuana), however, evidence supports a link between earlier onset of psychotic illness and cannabis use. The more often cannabis is used, particularly in early adolescence, the more likely a person is to develop a psychotic illness, with frequent use being correlated with double the risk of psychosis and schizoaffective disorder. A 2009 Yale review stated that in individuals with an established psychotic disorder, cannabinoids can exacerbate symptoms, trigger relapse, and have negative consequences on the course of the illness. While cannabis use is accepted as a contributory cause of schizoaffective disorder by many, it remains controversial, since not all young people who use cannabis later develop psychosis, but those who do use cannabis have an increased odds ratio of about 3. Certain drugs can imitate symptoms of schizophrenia (which is known to have similar symptoms to schizoaffective disorder). This is important to note when including that substance-induced psychosis should be ruled out when diagnosing patients so that patients are not misdiagnosed.

Mechanisms
Though the pathophysiology of schizoaffective disorder remains unclear, studies suggest that dopamine, norepinephrine, and serotonin may be factors in the development of the disorder.White matter and Grey Matter  reductions in the right lentiform nucleus, left superior temporal gyrus, and right precuneus, and other areas in the brain are also characteristic of schizoaffective disorder. Deformities in white matter have also been found to worsen with time in individuals with schizoaffective disorder. Due to its role in emotional regulation, researchers believe that the hippocampus is also involved in the progression of schizoaffective disorder. Specifically, psychotic disorders (such as schizoaffective disorder) have been associated with lower hippocampal volumes. Moreover, deformities in the medial and thalamic regions of the brain have been implicated as contributing factors to the disorder as well.

Diagnosis
Psychosis as a symptom of a psychiatric disorder is first and foremost a diagnosis of exclusion. So a new-onset episode of psychosis cannot be considered to be a symptom of a psychiatric disorder until other relevant and known medical causes of psychosis are excluded, or ruled out. Many clinicians improperly perform, or entirely miss this step, introducing avoidable diagnostic error and misdiagnosis.An initial assessment includes a comprehensive history and physical examination. Although no biological laboratory tests exist which confirm schizoaffective disorder, biological tests should be performed to exclude psychosis associated with or caused by substance use, medications, toxins or poisons, surgical complications, or other medical illnesses. Since non-medical mental health practitioners are not trained to exclude medical causes of psychosis, people experiencing psychosis should be referred to an emergency department or hospital.
Delirium should be ruled out, which can be distinguished by visual hallucinations, acute onset and fluctuating level of consciousness, indicating other underlying factors which includes medical illnesses. Excluding medical illnesses associated with psychosis is performed by using blood tests to measure:

Thyroid-stimulating hormone to exclude hypo- or hyperthyroidism,
Basic electrolytes and serum calcium to rule out a metabolic disturbance,
Full blood count including ESR to rule out a systemic infection or chronic disease, and
Serology to exclude syphilis or HIV infection.Other investigations which may be performed include:

EEG to exclude epilepsy, and an
MRI or CT scan of the head to exclude brain lesions.Blood tests are not usually repeated for relapse in people with an established diagnosis of schizoaffective disorder, unless there is a specific medical indication. These may include serum BSL if olanzapine has previously been prescribed, thyroid function if lithium has previously been taken to rule out hypothyroidism, liver function tests if chlorpromazine has been prescribed, CPK levels to exclude neuroleptic malignant syndrome, and a urinalysis and serum toxicology screening if substance use is suspected. Assessment and treatment may be done on an outpatient basis; admission to an inpatient facility is considered if there is a risk to self or others.
Because psychosis may be precipitated or exacerbated by common classes of psychiatric medications, such as antidepressants, ADHD stimulant medications, and sleep medications, prescribed medication-induced psychosis should be ruled out, particularly for first-episode psychosis. This is an essential step to reduce diagnostic error and to evaluate potential medication sources of further patient harm. Regarding prescribed medication sources of patient harm, Yale School of Medicine Professor of Psychiatry Malcolm B. Bowers, Jr, MD wrote:
Illicit drugs arent the only ones that precipitate psychosis or mania—prescribed drugs can too, and in particular, some psychiatric drugs. We investigated this and found that about 1 in 12 psychotic or manic patients in an inpatient psychiatric facility are there due to antidepressant-induced psychosis or mania. Thats unfortunate for the field [of psychiatry] and disastrous for some of our patients.
It is important to be understood here. I want to call attention to the fact that some persons with a family history of even the subtler forms of bipolar disorder or psychosis are more vulnerable than others to the mania- or psychosis-inducing potential of antidepressants, stimulants and sleeping medications. While Im not making a blanket statement against these medications, I am urging caution in their use. I believe [clinicians] should ask patients and their families whether there is a family history of bipolar disorder or psychosis before prescribing these medications. Most patients and their families dont know the answer when they are first asked, so time should be allowed for the patient to ask family or relatives, between the session when asked by [the clinician] and a follow-up session. This may increase the wait for a medication slightly, but because some patients are vulnerable, this is a necessary step for [the clinician] to take. I believe that psychiatry as a field has not emphasized this point sufficiently. As a result, some patients have been harmed by the very treatments that were supposed to help them; or to the disgrace of psychiatry, harmed and then misdiagnosed.
Substance-induced psychosis should also be ruled out. Both substance- and medication-induced psychosis can be excluded to a high level of certainty while the person is psychotic, typically in an emergency department, using both a

Broad spectrum urine toxicology screening, and a
Full serum toxicology screening (of the blood).Some dietary supplements may also induce psychosis or mania, but cannot be ruled out with laboratory tests. So a psychotic persons family, partner, or friends should be asked whether he or she is currently taking any dietary supplements.Common mistakes made when diagnosing psychotic patients include:
Not properly excluding delirium,
Missing a toxic psychosis by not screening for substances and medications,
Not appreciating medical abnormalities (e.g., vital signs),
Not obtaining a medical history and family history,
Indiscriminate screening without an organizing framework,
Not asking family or others about dietary supplements,
Premature diagnostic closure, and
Not revisiting or questioning the initial diagnostic impression of primary psychiatric disorder.Schizoaffective disorder can only be diagnosed among those who have undergone a clinical evaluation with a psychiatrist. The criterion includes mental and physical symptoms such as, hallucinations or delusions, and depressive episodes. There are also links to bad hygiene and a troubled social life for those with schizoaffective disorder. Research has failed to conclusively demonstrate a positive relationship between schizoaffective disorder and substance abuse. There are several theorized causations for the onset of Schizoaffective disorder, including, genetics, general brain function, like chemistry, and structure, and stress.Only after these relevant and known causes of psychosis have been ruled out can a psychiatric differential diagnosis be made. A mental health clinician will incorporate family history, observation of a psychotic persons behavior while the person is experiencing active symptoms, to begin a psychiatric differential diagnosis. Diagnosis also includes self-reported experiences, as well as behavioral abnormalities reported by family members, friends, or significant others. Mistakes in this stage include:

Not screening for dissociative disorders. Dissociative identity disorder and psychotic symptoms in schizoaffective disorder have considerable overlap, yet a different overall treatment approach.

DSM-5 criteria
The most widely used criteria for diagnosing schizoaffective disorder are from the American Psychiatric Associations Diagnostic and Statistical Manual of Mental Disorders-5.The DSM-IV schizoaffective disorder definition was plagued by problems of being inconsistently (or unreliably) used on patients; when the diagnosis is made, it does not stay with most patients over time, and it has questionable diagnostic validity (that is, it does not describe a distinct disorder, nor predict any particular outcome). These problems have been slightly reduced (or "modestly improved") in the DSM-5 according to Carpenter.When psychotic symptoms are confined to an episode of mania or depression (with or without mixed features), the diagnosis is that of a “psychotic” mood disorder, namely either psychotic bipolar disorder or psychotic major depression. Only when psychotic states persist in a sustained fashion for two weeks or longer without concurrent affective symptoms is the diagnosis schizoaffective disorder, schizophreniform disorder or schizophrenia.The second cardinal guideline in the DSM-5 diagnosis of schizoaffective disorder is one of timeframe.

DSM-5 requires two episodes of psychosis (whereas DSM-IV needed only one) to qualify for the schizoaffective disorder diagnosis. As such, it is no longer an "episode diagnosis." The new schizoaffective framework looks at the time from "the [first episode of] psychosis up to the current episode [of psychosis], rather than only defining a single episode with [co-occurring] psychotic and mood syndromes." Specifically, one of the episodes of psychosis must last a minimum of two weeks without mood disorder symptoms, but the person may be mildly to moderately depressed while psychotic. The other period of psychosis "requires the overlap of mood [disorder] symptoms with psychotic symptoms to be conspicuous" and last for a greater portion of the disorder.These two changes are intended by the DSM-5 workgroup to accomplish two goals:
Increase the diagnosis consistency (or reliability) when it is used;
Significantly decrease the overall use of the schizoaffective disorder diagnosis.If the schizoaffective diagnosis is used less often, other diagnoses (like psychotic mood disorders and schizophrenia) are likely to be used more often; but this is hypothetical until real-world data arrive. Validity problems with the diagnosis remain and await further work in the fields of psychiatric genetics, neuroimaging, and cognitive science that includes the overlapping fields of cognitive, affective, and social neuroscience, which may change the way schizoaffective disorder is conceptualized and defined in future versions of the DSM and ICD.

Comorbidities
Schizoaffective disorder shares a high level of comorbidity with other psychiatric disorders, specifically  anxiety disorders, depression, and bipolar disorder. Individuals with schizoaffective disorder are also often diagnosed with substance abuse disorder, usually relating to tobacco, marijuana, or alcohol. Health care providers indicate the importance of assessing for co-occurring substance use disorders, as multiple diagnoses not only potentially increase negative symptomology, but may also adversely affect the treatment of schizoaffective disorder.

Types
One of three types of schizoaffective disorder may be noted in a diagnosis based on the mood component of the disorder:
Bipolar type, when the disturbance includes manic episodes, hypomania, or mixed episodes—major depressive episodes also typically occur;
Depressive type, when the disturbance includes major depressive episodes exclusively—that is, without manic, hypomanic, or mixed episodes.
Mixed type, when the disturbance includes both manic and depressive symptoms, but psychotic symptoms exist separately from bipolar disorder.

Problems with DSM-IV schizoaffective disorder
The American Psychiatric Associations DSM-IV criteria for schizoaffective disorder persisted for 19 years (1994–2013). Clinicians adequately trained in diagnosis used the schizoaffective diagnosis too often, largely because the criteria were poorly defined, ambiguous, and hard to use (or poorly operationalized). Poorly trained clinicians used the diagnosis without making necessary exclusions of common causes of psychosis, including some prescribed psychiatric medications. Specialty books written by experts on schizoaffective disorder have existed for over eight years before DSM-5 describing the overuse of the diagnosis.Carpenter and the DSM-5 schizoaffective disorders workgroup analyzed data made available to them in 2009, and reported in May 2013 that:
a recent review of psychotic disorders from large private insurance and Medicare databases in the U.S. found that the diagnosis of DSM-IV schizoaffective disorder was used for about a third of cases with non-affective psychotic disorders. Hence, this unreliable and poorly defined diagnosis is clearly overused.
As stated above, the DSM-IV schizoaffective disorder diagnosis is very inconsistently used or unreliable. A diagnosis is unreliable when several different mental health professionals observing the same individual make different diagnoses excessively. Even when a structured DSM-IV diagnostic interview and best estimate procedures were made by experts in the field that included information from family informants and prior clinical records, reliability was still poor for the DSM-IV schizoaffective diagnosis.The DSM-IV schizoaffective diagnosis is not stable over time either. An initial diagnosis of schizoaffective disorder during time spent at a psychiatric inpatient facility was stable at 6-month and 24-month follow ups for only 36% of patients. By comparison, diagnostic stability was 92% for schizophrenia, 83% for bipolar disorder and 74% for major depression. Most patients diagnosed with DSM-IV schizoaffective disorder are later diagnosed with a different disorder, and that disorder is more stable over time than the DSM-IV schizoaffective disorder diagnosis.In April 2009, Carpenter and the DSM-5 schizoaffective disorder workgroup reported that they were "developing new criteria for schizoaffective disorder to improve reliability and face validity," and were "determining whether the dimensional assessment of mood [would] justify a recommendation to drop schizoaffective disorder as a diagnostic category." Speaking to an audience at the May 2009 annual conference of the American Psychiatric Association, Carpenter said:
We had hoped to get rid of schizoaffective [disorder] as a diagnostic category [in the DSM-5] because we dont think its [a] valid [scientific entity] and we dont think its reliable. On the other hand, we think its absolutely indispensable to clinical practice.
A major reason why DSM-IV schizoaffective disorder was indispensable to clinical practice is because it offered clinicians a diagnosis for patients with psychosis in the context of mood disorder whose clinical picture, at the time diagnosed, appeared different from DSM-IV "schizophrenia" or "mood disorder with psychotic features".
But DSM-IV schizoaffective disorder carries an unnecessarily worse prognosis than a "mood disorder with psychotic features" diagnosis, because long-term data revealed that a significant proportion of DSM-IV schizoaffective disorder patients had 15-year outcomes indistinguishable from patients with mood disorders with or without psychotic features, even though the clinical picture at the time of first diagnosis looked different from both schizophrenia and mood disorders.These problems with the DSM-IV schizoaffective disorder definition result in most people the diagnosis is used on being misdiagnosed; furthermore, outcome studies done 10 years after the diagnosis was released showed that the group of patients defined by the DSM-IV and ICD-10 schizoaffective diagnosis had significantly better outcomes than predicted, so the diagnosis carries a misleading and unnecessarily poor prognosis. The DSM-IV criteria for schizoaffective disorder will continue to be used on U.S. board examinations in psychiatry through the end of 2014; established practitioners may continue to use the problematic DSM-IV definition much further into the future also.

DSM-5 research directions
The new schizoaffective disorder criteria continue to have questionable diagnostic validity. Questionable diagnostic validity does not doubt that people with symptoms of psychosis and mood disorder need treatment—psychosis and mood disorder must be treated. Instead, questionable diagnostic validity means there are unresolved problems with the way the DSM-5 categorizes and defines schizoaffective disorder.

A core concept in modern psychiatry since DSM-III was released in 1980, is the categorical separation of mood disorders from schizophrenia, known as the Kraepelinian dichotomy. Emil Kraepelin introduced the idea that schizophrenia was separate from mood disorders after observing patients with symptoms of psychosis and mood disorder, over a century ago, in 1898. This was a time before genetics were known and before any treatments existed for mental illness. The Kraepelinian dichotomy was not used for DSM-I and DSM-II because both manuals were influenced by the dominant psychodynamic psychiatry of the time, but the designers of DSM-III wanted to use more scientific and biological definitions. Consequently, they looked to psychiatrys history and decided to use the Kraepelinian dichotomy as a foundation for the classification system.
The Kraepelinian dichotomy continues to be used in DSM-5 despite having been challenged by data from modern psychiatric genetics for over eight years, and there is now evidence of a significant overlap in the genetics of schizophrenia and bipolar disorder. According to this genetic evidence, the Kraepelinian categorical separation of mood disorders from schizophrenia at the foundation of the current classification and diagnostic system is a mistaken false dichotomy.The dichotomy at the foundation of the current system forms the basis for a convoluted schizoaffective disorder definition in DSM-IV that resulted in excessive misdiagnosis. Real life schizoaffective disorder patients have significant and enduring symptoms that bridge what are incorrectly assumed to be categorically separate disorders, schizophrenia and bipolar disorder. People with psychotic depression, bipolar disorder with a history of psychosis, and schizophrenia with mood symptoms also have symptoms that bridge psychosis and mood disorders. The categorical diagnostic manuals do not reflect reality in their separation of psychosis (via the schizophrenia diagnosis) from mood disorder, nor do they currently emphasize the actual overlap found in real-life patients. Thus, they are likely to continue to introduce either-or conceptual and diagnostic error, by way of confirmation bias into clinicians mindsets, hindering accurate assessment and treatment.The new definition continues the lack of parsimony of the old definition. Simpler, clearer, and more usable definitions of the diagnosis were supported by certain members of the DSM-5 workgroup (see next paragraph); these were debated but deemed premature, because more "research [is] needed to establish a new classification system of equal or greater validity" to the existing system. Because of DSM-5s continuing problematic categorical foundation, schizoaffective disorders conceptual and diagnostic validity remains doubtful. After enough research is completed and data exists, future diagnostic advances will need to either eliminate and replace, or soften and bridge, the hard categorical separation of mood disorders from schizophrenia; most likely using a spectrum or dimensional approach to diagnosis.More parsimonious definitions than the current one were considered by Carpenter and the DSM-5 workgroup:
One option for the DSM-5 would have been to remove the schizoaffective disorder category and to add affective [or mood] symptoms [that is, mania, hypomania, mixed episode, or depression] as a dimension to schizophrenia and schizophreniform disorder or to define a single category for the co-occurrence of psychosis and mood symptoms. This option was extensively debated but ultimately deemed to be premature in the absence of sufficient clinical and theoretical validating data justifying such a … reconceptualization. Additionally, there appeared to be no practical way to introduce affect [or mood] dimensions covering the entire course of illness, that would capture the current concept of periods of psychosis related and unrelated to mood episodes.
[N]o valid biomarkers or laboratory measures have emerged to distinguish between affective psychosis [or psychotic mood disorders] and schizophrenia. To the contrary, the idea of a dichotomy between these types of conditions has proven naïve. [T]he admixture of "schizophrenic" and affective [or mood] symptoms is a feature of many, or even most, cases with severe mental illness. Most presenting symptoms of psychosis have little validity in determining diagnosis, prognosis, or treatment response in psychosis. [U]ltimately a more … dimensional approach [to assessment and treatment] will be required.
The field of psychiatry has begun to question its assumptions and analyze its data in order to merge closer with evidence-based medicine. The removal of the "episode diagnosis", and the addition of two episodes of psychosis, as qualifications for the DSM-5 schizoaffective diagnosis, may improve the diagnosis consistency over DSM-IV for research purposes, where diagnostic criteria are by necessity followed exactingly. But the new definition remains long, unwieldy, and perhaps still not very useful for community clinicians—with two psychoses, one for two weeks minimum and without mood disorder (but the person can be mildly or moderately depressed) and the other with significant mood disorder and psychosis lasting for most of the time, and with lasting mood symptoms for most of the residual portion of the illness. Community clinicians used the previous definition "for about a third of cases with non-affective psychotic disorders." Non-affective psychotic disorders are, by definition, not schizoaffective disorder. For clinicians to make such sizeable errors of misdiagnosis may imply systemic problems with the schizoaffective disorder diagnosis itself. Already, at least one expert believes the new schizoaffective definition has not gone far enough to solve the previous definitions problems.From a scientific standpoint, modern clinical psychiatry is still a very young, underdeveloped medical specialty because its target organ, the human brain, is not yet well understood. The human brains neural circuits, for example, are just beginning to be mapped by modern neuroscience in the Human Connectome Project and CLARITY. Clinical psychiatry, furthermore, has begun to understand and acknowledge its current limitations—but further steps by the field are required to significantly reduce misdiagnosis and patient harm; this is crucial both for responsible patient care and to retain public trust. Looking forward, a paradigm shift is needed in psychiatric research to address unanswered questions about schizoaffective disorder. The dimensional Research Domain Criteria project currently being developed by the U.S. National Institutes of Mental Health, may be the specific problem solving framework psychiatry needs to develop a more scientifically mature understanding of schizoaffective disorder as well as all other mental disorders.

Treatment
The primary treatment of schizoaffective disorder is medication, with improved outcomes using combined long-term psychological and social supports. Hospitalization may occur for severe episodes either voluntarily or (if mental health legislation allows it) involuntarily. Long-term hospitalization is uncommon since deinstitutionalization started in the 1950s, although it still occurs. Community support services including drop-in centers, visits by members of a community mental health team, supported employment and support groups are common. Evidence indicates that regular exercise has a positive effect on the physical and mental health of those with schizoaffective disorder.Because of the heterogeneous symptomology associated with schizoaffective disorder, it is common for patients to be misdiagnosed. Many people are either diagnosed with depression, schizophrenia, or bipolar disorder instead of schizoaffective disorder. Because of the broad range of symptoms of Schizoaffective disorder, patients are often misdiagnosed in a clinical setting. In fact, almost 39% of people are misdiagnosed when it comes to psychiatric disorders.While various medications and treatment options exist for those diagnosed with schizoaffective disorder, symptoms may continue to impact a person for their entire lifespan.Schizoaffective disorder can affect a persons ability to experience a fulfilling social life and they may also exhibit difficulty forming bonds or relationships with others. Schizoaffective disorder is more likely to occur in women and symptoms begin manifesting at a young age.

Therapy
Psychosocial treatments have been found to improve outcomes related to schizoaffective disorder.  Supportive psychotherapy and cognitive behavioral therapy are both helpful. Intensive case management (ICM) has been shown to reduce hospitalizations, improve adherence to treatment, and improve social functioning. With ICM, clients are assigned a case manager responsible for coordination of care and assisting clients to access supports to address needs in multiple areas related to well-being, including housing.
Psychiatric/psychosocial rehabilitation is often a component of schizoaffective disorder treatment. This rehabilitation method focuses on solving community integration problems such as obtaining and keeping housing and increasing involvement in positive social groups. It also focuses on improving and increasing activities of daily living; increasing daily healthy habits and decreasing unhealthy behaviors, thereby significantly improving quality of life. Psychiatric rehabilitation may also focus on vocational rehabilitation. Evidence suggests that cognition-based approaches may be able to improve work and social functioning.Psychiatric rehabilitation consists of eight main areas:

Psychiatric (symptom reduction and management)
Health and Medical (maintaining consistency of care)
Housing (safe environments)
Basic living skills (hygiene, meals [including increasing healthy food intake and reducing processed food intake], safety, planning and chores)
Social (relationships, family boundaries, communication and integration of client into the community)
Education and vocation (coping skills, motivation and suitable goals chosen by client)
Finance (personal budget)
Community and legal (resources)

Medication
Antipsychotic medication is usually required both for acute treatment and the prevention of relapse. There is no single antipsychotic of choice in treating schizoaffective disorder, but atypical antipsychotics may be considered due to their mood-stabilizing abilities. To date, paliperidone (Invega) is the only antipsychotic with FDA approval for the treatment of schizoaffective disorder. Other antipsychotics may be prescribed to further alleviate psychotic symptoms.Though not approved for treatment use by the FDA, research suggests that Clozapine may also be effective in treating schizoaffective disorder, particularly in those resistant to initial medication. Clozapine is an atypical antipsychotic that is recognized as being particularly effective when other antipsychotic agents have failed. When combined with cognitive therapy, Clozapine has been found to decrease positive and negative symptoms of psychosis at a higher rate in schizoaffective individuals. Clozapine has also been associated with a decreased risk of suicide in patients with schizoaffective disorder and a history of suicidality. Despite this, clozapine treatment may be ineffective for some patients, particularly in those that are already drug-resistant.The management of the bipolar type of schizoaffective disorder is similar to the treatment of bipolar disorder, with the goal of preventing mood episodes and cycling. Lithium or anticonvulsant mood stabilizers such as valproic acid, carbamazepine, and lamotrigine are prescribed in combination with an antipsychotic.Antidepressants have also been used to treat schizoaffective disorder. Though they may be useful in treating the depressive subtype of the disorder, research suggests that antidepressants are far less effective in treatment than antipsychotics and mood stabilizers.Some research has supported the efficacy of anxiolytics in treating schizoaffective disorder, though general findings on their effectiveness in treating schizoaffective disorder remain inconclusive. Due to the severe negative outcomes associated with many anti-anxiety drugs, many researchers have cautioned against their long term use in treatment.

Electroconvulsive therapy
Electroconvulsive therapy (ECT) may be considered for patients with schizoaffective disorder experiencing severe depression or severe psychotic symptoms that have not responded to treatment with antipsychotics.

Epidemiology
Compared to depression, schizophrenia, and bipolar disorder, schizoaffective disorder is less commonly diagnosed. Schizoaffective disorder is estimated to occur in 0.3 to 0.8 percent of people at some point in their life. 30% of cases occur between the ages of 25 and 35. It is more common in women than men; however, this is because of the high concentration of women in the depressive subcategory, whereas the bipolar subtype has a roughly even gender distribution. Children are less likely to be diagnosed with this disorder, as the onset presents itself in adolescence or young adulthood.

History
The term schizoaffective psychosis was introduced by the American psychiatrist Jacob Kasanin in 1933 to describe an episodic psychotic illness with predominant affective symptoms, that was thought at the time to be a good-prognosis schizophrenia. Kasanins concept of the illness was influenced by the psychoanalytic teachings of Adolf Meyer and Kasanin postulated that schizoaffective psychosis was caused by "emotional conflicts" of a "mainly sexual nature" and that psychoanalysis "would help prevent the recurrence of such attacks." He based his description on a case study of nine individuals.

Other psychiatrists, before and after Kasanin, have made scientific observations of schizoaffective disorder based on assumptions of a biological and genetic cause of the illness. In 1863, German psychiatrist Karl Kahlbaum (1828–1899) described schizoaffective disorders as a separate group in his vesania typica circularis. Kahlbaum distinguished between cross-sectional and longitudinal observations.  In 1920, psychiatrist Emil Kraepelin (1856–1926) observed a "great number" of cases that had characteristics of both groups of psychoses that he originally posited were two distinct and separate illnesses, dementia praecox (now called schizophrenia) and manic depressive insanity (now called bipolar disorders and recurrent depression).Kraepelin acknowledged that "there are many overlaps in this area," that is, the area between schizophrenia and mood disorders. In 1959, psychiatrist Kurt Schneider (1887–1967) began to further refine conceptualizations of the different forms that schizoaffective disorders can take since he observed "concurrent and sequential types". (The concurrent type of illness he referred to is a longitudinal course of illness with episodes of mood disorder and psychosis occurring predominantly at the same time [now called psychotic mood disorders or affective psychosis]; while his sequential type refers to a longitudinal course predominantly marked by alternating mood and psychotic episodes.) Schneider described schizoaffective disorders as "cases in-between" the traditional Kraepelinian dichotomy of schizophrenia and mood disorders.The historical clinical observation that schizoaffective disorder is an overlap of schizophrenia and mood disorders is explained by genes for both illnesses being present in individuals with schizoaffective disorder; specifically, recent research shows that schizophrenia and mood disorders share common genes and polygenic variations.

Schizoaffective disorder was included as a subtype of schizophrenia in DSM-I and DSM-II, though research showed a schizophrenic cluster of symptoms in individuals with a family history of mood disorders whose illness course, other symptoms and treatment outcome were otherwise more akin to bipolar disorder than to schizophrenia </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 Macrocheilia 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 Spinal stenosis and can you explain it in depth? [/INST] Spinal stenosis is an abnormal narrowing of the spinal canal or neural foramen that results in pressure on the spinal cord or nerve roots. Symptoms may include pain, numbness, or weakness in the arms or legs. Symptoms are typically gradual in onset and improve with leaning forward. Severe symptoms may include loss of bladder control, loss of bowel control, or sexual dysfunction.Causes may include osteoarthritis, rheumatoid arthritis, spinal tumors, trauma, Pagets disease of the bone, scoliosis, spondylolisthesis, and the genetic condition achondroplasia. It can be classified by the part of the spine affected into cervical, thoracic, and lumbar stenosis. Lumbar stenosis is the most common, followed by cervical stenosis. Diagnosis is generally based on symptoms and medical imaging.Treatment may involve medications, bracing, or surgery. Medications may include NSAIDs, acetaminophen, or steroid injections. Stretching and strengthening exercises may also be useful. Limiting certain activities may be recommended. Surgery is typically only done if other treatments are not effective, with the usual procedure being a decompressive laminectomy.Spinal stenosis occurs in as many as 8% of people. It occurs most commonly in people over the age of 50. Males and females are affected equally often. The first modern description of the condition is from 1803 by Antoine Portal, and there is evidence of the condition dating back to Ancient Egypt.

Types
The most common forms are lumbar spinal stenosis, at the level of the lower back, and cervical spinal stenosis, which are at the level of the neck. Thoracic spinal stenosis, at the level of the mid-back, is much less common.In lumbar stenosis, the spinal nerve roots in the lower back are compressed which can lead to symptoms of sciatica (tingling, weakness, or numbness that radiates from the low back and into the buttocks and legs).Cervical spinal stenosis can be far more dangerous by compressing the spinal cord. Cervical canal stenosis may lead to myelopathy, a serious condition causing symptoms including major body weakness and paralysis. Such severe spinal stenosis symptoms are virtually absent in  lumbar stenosis, however, as the spinal cord terminates at the top end of the adult lumbar spine, with only nerve roots (cauda equina) continuing further down. Cervical spinal stenosis is a condition involving narrowing of the spinal canal at the level of the neck. It is frequently due to chronic degeneration, but may also be congenital or traumatic. Treatment frequently is surgical.

Signs and symptoms
Common
Standing discomfort (94%)
Discomfort/pain, in shoulder, arm, hand (78%)
Bilateral symptoms (68%)
Numbness at or below the level of involvement  (63%)
Weakness at or below the level of involvement  (43%)
Pain or weakness in buttock / thigh only (8%)
Pain or weakness below the knee (3%)

Neurological disorders
Cervical (spondylotic) myelopathy, a syndrome caused by compression of the cervical spinal cord which is associated with "numb and clumsy hands", imbalance,   loss of bladder and bowel control, and weakness that can progress to paralysis.
Pinched nerve, causing numbness.
Intermittent neurogenic claudication characterized by lower limb numbness, weakness, diffuse or radicular leg pain associated with paresthesia (bilaterally), weakness and/or heaviness in buttocks radiating into lower extremities with walking or prolonged standing. Symptoms occur with extension of spine and are relieved with spine flexion. Minimal to zero symptoms when seated or supine.
Radiculopathy (with or without radicular pain) neurologic condition—nerve root dysfunction causes objective signs such as weakness, loss of sensation and of reflex.
Cauda equina syndrome - Lower extremity pain, weakness, numbness that may involve perineum and buttocks, associated with bladder and bowel dysfunction.
Lower back pain due to degenerative disc or joint changes.

Causes
Aging
Any of the factors below may cause the spaces in the spine to narrow.

Spinal ligaments can thicken (ligamenta flava)
Bone spurs develop on the bone and into the spinal canal or foraminal openings
Intervertebral discs may bulge or herniate into the canal or foraminal openings
Degenerative disc disease causes narrowing of the spaces.
Facet joints break down
Facet joints may hypertrophy
Compression fractures of the spine, which are common in osteoporosis
Synovial cysts form on the facet joints causing compression of the spinal sac of nerves (thecal sac)

Arthritis
Osteoarthritis
Rheumatoid arthritis—much less common cause of spinal problems

Congenital
Spinal canal is too small at birth
Structural deformities of the vertebrae may cause narrowing of the spinal canal.

Instability of the spine
A vertebra slips forward on another (spondylolisthesis)

Trauma
Accidents and injuries may dislocate the spine and the spinal canal or cause burst fractures that yield fragments of bone that go through the canal.
Patients with cervical myelopathy caused by narrowing of the spinal canal are at higher risks of acute spinal cord injury if involved in accidents.

Tumors
Irregular growths of soft tissue will cause inflammation.
Growth of tissue into the canal pressing on nerves, the sac of nerves, or the spinal cord.

Diagnosis
The diagnosis of spinal stenosis involves a complete evaluation of the spine. The process usually begins with a medical history and physical examination. X-ray and MRI scans are typically used to determine the extent and location of the nerve compression.

Medical history
The medical history is the most important aspect of the examination as it will tell the physician about subjective symptoms, possible causes for spinal stenosis, and other possible causes of back pain.

Physical examination
The physical examination of a patient with spinal stenosis will give the physician information about exactly where nerve compression is occurring. Some important factors that should be investigated are any areas of sensory abnormalities, numbness, irregular reflexes, and any muscular weakness.

MRI
MRI has become the most frequently used study to diagnose spinal stenosis. The MRI uses electromagnetic signals to produce images of the spine. MRIs are helpful because they show more structures, including nerves, muscles, and ligaments, than seen on X-rays or CT scans. MRIs are helpful at showing exactly what is causing spinal nerve compression.

Myelography
In CT myelography, spinal tap is performed in the low back with dye injected into the spinal fluid. X-rays are performed followed by a CT scan of the spine to help see narrowing of the spinal canal.
This is a very effective study in cases of lateral recess stenosis.  It is also necessary for patients in which MRI is contraindicated, such as those with implanted pacemakers.

Red flags
Fever
Nocturnal pain
Gait disturbance
Structural deformity
Unexplained weight loss
Previous carcinoma
Severe pain upon lying down
Recent trauma with suspicious fracture
Presence of severe or progressive neurologic deficit

Treatments
Treatment options are either surgical or non-surgical. Overall evidence is inconclusive whether non-surgical or surgical treatment is the better for lumbar spinal stenosis.

Non-surgical treatments
The effectiveness of non-surgical treatments is unclear as they have not been well studied.
Education about the course of the condition and how to relieve symptoms
Medicines to relieve pain and inflammation, such as acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs)
Exercise, to maintain or achieve overall good health, aerobic exercise, such as riding a stationary bicycle, which allows for a forward lean, walking, or swimming can relieve symptoms
Weight loss, to relieve symptoms and slow progression of the stenosis
Physical therapy to support self-care. Also may give instructs on stretching and strength exercises that may lead to a decrease in pain and other symptoms.
Lumbar epidural steroid or anesthetic injections have low quality evidence to support their use.

Surgery
Lumbar decompressive laminectomy: This involves removing the roof of bone overlying the spinal canal and thickened ligaments in order to decompress the nerves and sac of nerves. 70-90% of people have good results.
Interlaminar implant:  This is a non-fusion U-shaped device that is placed between two bones in the lower back that maintains motion in the spine and keeps the spine stable after a lumbar decompressive surgery. The U-shaped device maintains height between the bones in the spine so nerves can exit freely and extend to lower extremities.
Surgery for cervical myelopathy is either conducted from the front or from the back, depending on several factors such as where the compression occurs and how the cervical spine is aligned.
Anterior cervical discectomy and fusion: A surgical treatment of nerve root or spinal cord compression by decompressing the spinal cord and nerve roots of the cervical spine with a discectomy in order to stabilize the corresponding vertebrae.
Posterior approaches seek to generate space around the spinal cord by removing parts of the posterior elements of the spine. Techniques include laminectomy, laminectomy and fusion, and laminoplasty.Decompression plus fusion appears no better than decompression alone, while spinal spacers appears better than decompression plus fusion but not better than decompression alone </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 Liver disease and can you explain it in depth? [/INST] Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common.

Signs and symptoms
Some of the signs and symptoms of a liver disease are the following:

Jaundice
Confusion and altered consciousness caused by hepatic encephalopathy.
Thrombocytopenia and coagulopathy.
Risk of bleeding symptoms particularly taking place in gastrointestinal tract

Liver diseases
There are more than a hundred different liver diseases. Some of the most common are:
Fascioliasis, a parasitic infection of liver caused by a liver fluke of the genus Fasciola, mostly Fasciola hepatica.
Hepatitis, inflammation of the liver, is caused by various viruses (viral hepatitis) also by some liver toxins (e.g. alcoholic hepatitis), autoimmunity (autoimmune hepatitis) or hereditary conditions.
Alcoholic liver disease is a hepatic manifestation of alcohol overconsumption, including fatty liver disease, alcoholic hepatitis, and cirrhosis. Analogous terms such as "drug-induced" or "toxic" liver disease are also used to refer to disorders caused by various drugs.
Fatty liver disease (hepatic steatosis) is a reversible condition where large vacuoles of triglyceride fat accumulate in liver cells. Non-alcoholic fatty liver disease is a spectrum of disease associated with obesity and metabolic syndrome.
Hereditary diseases that cause damage to the liver include hemochromatosis, involving accumulation of iron in the body, and Wilsons disease. Liver damage is also a clinical feature of alpha 1-antitrypsin deficiency and glycogen storage disease type II.
In transthyretin-related hereditary amyloidosis, the liver produces a mutated transthyretin protein which has severe neurodegenerative or cardiopathic effects. Liver transplantation can be curative.
Gilberts syndrome, a genetic disorder of bilirubin metabolism found in a small percent of the population, can cause mild jaundice.
Cirrhosis is the formation of fibrous tissue (fibrosis) in the place of liver cells that have died due to a variety of causes, including viral hepatitis, alcohol overconsumption, and other forms of liver toxicity. Cirrhosis causes chronic liver failure.
Primary liver cancer most commonly manifests as hepatocellular carcinoma or cholangiocarcinoma; rarer forms include angiosarcoma and hemangiosarcoma of the liver. (Many liver malignancies are secondary lesions that have metastasized from primary cancers in the gastrointestinal tract and other organs, such as the kidneys, lungs.)
Primary biliary cirrhosis is a serious autoimmune disease of the bile capillaries.
Primary sclerosing cholangitis is a serious chronic inflammatory disease of the bile duct, which is believed to be autoimmune in origin.
Budd–Chiari syndrome is the clinical picture caused by occlusion of the hepatic vein.

Mechanisms
Liver diseases can develop through several mechanisms:

DNA damage
One general mechanism, increased DNA damage, is shared by some of the major liver diseases, including infection by hepatitis B virus or hepatitis C virus, heavy alcohol consumption, and obesity.Viral infection by hepatitis B virus, or hepatitis C virus causes an increase of reactive oxygen species.  The increase in intracellular reactive oxygen species is about 10,000-fold with chronic hepatitis B virus infection and 100,000-fold following hepatitis C virus infection. This increase in reactive oxygen species causes inflammation and more than 20 types of DNA damage.  Oxidative DNA damage is mutagenic and also causes epigenetic alterations at the sites of DNA repair.  Epigenetic alterations and mutations affect the cellular machinery that may cause the cell to replicate at a higher rate or result in the cell avoiding apoptosis, and thus contribute to liver disease.  By the time accumulating epigenetic and mutational changes eventually cause hepatocellular carcinoma, epigenetic alterations appear to have an even larger role in carcinogenesis than mutations.  Only one gene, TP53, is mutated in more than 20% of liver cancers while 41 genes each have hypermethylated promoters (repressing gene expression) in more than 20% of liver cancers.Alcohol consumption in excess causes a build-up of acetaldehyde. Acetaldehyde and free radicals generated by metabolizing alcohol induce DNA damage and oxidative stress.  In addition, activation of neutrophils in alcoholic liver disease contributes to the pathogenesis of hepatocellular damage by releasing reactive oxygen species (which can damage DNA).  The level of oxidative stress and acetaldehyde-induced DNA adducts due to alcohol consumption does not appear sufficient to cause increased mutagenesis.  However, as reviewed by Nishida et al., alcohol exposure, causing oxidative DNA damage (which is repairable), can result in epigenetic alterations at the sites of DNA repair.  Alcohol-induced epigenetic alterations of gene expression appear to lead to liver injury and ultimately carcinoma.Obesity is associated with a higher risk of primary liver cancer.  As shown with mice, obese mice are prone to liver cancer, likely due to two factors.  Obese mice have increased pro-inflammatory cytokines. Obese mice also have higher levels of deoxycholic acid, a product of bile acid alteration by certain gut microbes, and these microbes are increased with obesity.  The excess deoxycholic acid causes DNA damage and inflammation in the liver, which, in turn, can lead to liver cancer.

Other relevant aspects
Several liver diseases are due to viral infection. Viral hepatitides such as Hepatitis B virus and Hepatitis C virus can be vertically transmitted during birth via contact with infected blood. According to a 2012 NICE publication, "about 85% of hepatitis B infections in newborns become chronic". In occult cases, Hepatitis B virus is present by hepatitis B virus DNA, but testing for HBsAg is negative. High consumption of alcohol can lead to several forms of liver disease including alcoholic hepatitis, alcoholic fatty liver disease, cirrhosis, and liver cancer. In the earlier stages of alcoholic liver disease, fat builds up in the livers cells due to increased creation of triglycerides and fatty acids and a decreased ability to break down fatty acids. Progression of the disease can lead to liver inflammation from the excess fat in the liver. Scarring in the liver often occurs as the body attempts to heal and extensive scarring can lead to the development of cirrhosis in more advanced stages of the disease. Approximately 3–10% of individuals with cirrhosis develop a form of liver cancer known as hepatocellular carcinoma. According to Tilg, et al., gut microbiome could very well have an effect, be involved in the pathophysiology, on the various types of liver disease which an individual may encounter. Insight into the exact causes and mechanisms mediating pathophysiology of the liver is quickly progressing due to the introduction new technological approaches like Single cell sequencing and kinome profiling

Air pollutants
Particulate matter or carbon black are common pollutants. They have a direct toxic effect on the liver; cause inflammation of liver caused by and thereby impact lipid metabolism and fatty liver disease; and can translocate from the lungs to the liver.Because particulate matter and carbon black are very diverse and each has different toxicodynamics, detailed mechanisms of translocation are not clear.  Water-soluble fractions of particulate matter are the most important part of translocation to the liver, through extrapulmonary circulation. When particulate matter gets into the bloodstream, it combines with immune cells and stimulates innate immune responses. Pro-inflammatory cytokines are released and cause disease progression.

Diagnosis
A number  of liver function tests are available to test the proper function of the liver. These test for the presence of enzymes in blood that are normally most abundant in liver tissue, metabolites or products. serum proteins, serum albumin, serum globulin, alanine transaminase, aspartate transaminase, prothrombin time, partial thromboplastin time.Imaging tests such as transient elastography, ultrasound and magnetic resonance imaging can be used to show the liver tissue and the bile ducts. Liver biopsy can be performed to examine liver tissue to distinguish between various conditions; tests such as elastography may reduce the need for biopsy in some situations.In liver disease, prothrombin time is longer than usual </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 Mittelschmerz and can you explain it in depth? [/INST] Mittelschmerz (German: "middle pain") is a colloquial term for "ovulation pain" or "midcycle pain". About 20% of women experience mittelschmerz, some every cycle, some intermittently.

Signs and symptoms
Mittelschmerz is characterized by lower abdominal and pelvic pain that occurs roughly midway through a womans menstrual cycle. The pain can appear suddenly and usually subsides within hours, although it may sometimes last two or three days. In some cases it can last up to the following cycle. In some women, the mittelschmerz is localized enough so that they can tell which of their two ovaries provided the egg in a given month.  Because ovulation occurs on a random ovary each cycle, the pain may switch sides or stay on the same side from one cycle to another.

Other ovulation symptoms
Women may notice other physical symptoms associated with their mittelschmerz, during or near ovulation.  The most common sign is the appearance of fertile cervical mucus in the days leading up to ovulation.  Cervical mucus is one of the primary signs used by various fertility awareness methods.  Other symptoms are sometimes called secondary fertility signs to distinguish from the three primary signs.
Mid-cycle or ovulatory bleeding is thought to result from the sudden drop in estrogen that occurs just before ovulation.  This drop in hormones can trigger withdrawal bleeding in the same way that switching from active to placebo birth control pills does.  The rise in hormones that occurs after ovulation prevents such mid-cycle spotting from becoming as heavy or long lasting as a typical menstruation.  Spotting is more common in longer cycles.
A womans vulva may swell just prior to ovulation, especially the side on which ovulation will occur.
One of the groin lymph nodes (on the side on which ovulation will occur) will swell to about the size of a pea, and may become tender.

Causes
Mittelschmerz is believed to have a variety of causes:

Follicular swelling: The swelling of follicles in the ovaries prior to ovulation </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 Intestinal capillariasis 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 Dural tear and can you explain it in depth? [/INST] Dural tear is a tear occurring in the dura mater of the brain. It is usually caused as a result of trauma or as a complication following surgery.

Diagnosis
In case of head injury, a dural tear is likely in case of a depressed skull fracture. A burr hole is made through the normal skull near the fractured portion, and Adsons elevator is introduced. Underlying dura is separated carefully from the overlying depressed bone fragments. The dura that is now visible is carefully examined to exclude any dural tear.

Treatment
The whole extent of the dural tear is exposed by removing the overlying skull. The ragged edges of the tear are excised. However, care should be taken not to excise too much dura as it may increase the chances for spread of infection into the subarachnoid space </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 Flatulence and can you explain it in depth? [/INST] Flatulence, in humans, is the expulsion of gas from the intestines via the anus, commonly referred to as farting. "Flatus" is the medical word for gas generated in the stomach or bowels. A proportion of intestinal gas may be swallowed environmental air, and hence flatus is not entirely generated in the stomach or bowels. The scientific study of this area of medicine is termed flatology.Flatus is brought to the rectum and pressurized by muscles in the intestines. It is normal to pass flatus ("to fart"), though volume and frequency vary greatly among individuals. It is also normal for intestinal gas to have a feculent or unpleasant odor, which may be intense. The noise commonly associated with flatulence ("blowing a raspberry") is produced by the anus and buttocks, which act together in a manner similar to that of an embouchure. Both the sound and odor are sources of embarrassment, annoyance or amusement (flatulence humor).
There are several general symptoms related to intestinal gas: pain, bloating and abdominal distension, excessive flatus volume, excessive flatus odor, and gas incontinence. Furthermore, eructation (colloquially known as "burping") is sometimes included under the topic of flatulence. When excessive or malodorous, flatus can be a sign of a health disorder, such as irritable bowel syndrome, celiac disease or lactose intolerance.

Terminology
Non-medical definitions of the term include "the uncomfortable condition of having gas in the stomach and bowels", or "a state of excessive gas in the alimentary canal". These definitions highlight that many people consider "bloating", abdominal distension or increased volume of intestinal gas, to be synonymous with the term flatulence (although this is technically inaccurate).
Colloquially, flatulence may be referred to as "farting", "pumping", "trumping", "blowing off", "pooting", "passing gas", "breaking wind", "backfiring", or simply (in American English) "gas" or (British English) "wind". Derived terms include vaginal flatulence, otherwise known as a queef.

Signs and symptoms
Generally speaking, there are four different types of complaints that relate to intestinal gas, which may present individually or in combination.

Bloating and pain
Patients may complain of bloating as abdominal distension, discomfort and pain from "trapped wind". In the past, functional bowel disorders such as irritable bowel syndrome that produced symptoms of bloating were attributed to increased production of intestinal gas.
However, three significant pieces of evidence refute this theory. First, in normal subjects, even very high rates of gas infusion into the small intestine (30 mL/min) is tolerated without complaints of pain or bloating and harmlessly passed as flatus per rectum. Secondly, studies aiming to quantify the total volume of gas produced by patients with irritable bowel syndrome (some including gas emitted from the mouth by eructation) have consistently failed to demonstrate increased volumes compared to healthy subjects. The proportion of hydrogen produced may be increased in some patients with irritable bowel syndrome, but this does not affect the total volume. Thirdly, the volume of flatus produced by patients with irritable bowel syndrome who have pain and abdominal distension would be tolerated in normal subjects without any complaints of pain.
Patients who complain of bloating frequently can be shown to have objective increases in abdominal girth, often increased throughout the day and then resolving during sleep. The increase in girth combined with the fact that the total volume of flatus is not increased led to studies aiming to image the distribution of intestinal gas in patients with bloating. They found that gas was not distributed normally in these patients: there was segmental gas pooling and focal distension. In conclusion, abdominal distension, pain and bloating symptoms are the result of abnormal intestinal gas dynamics rather than increased flatus production.

Excessive volume
The normal range of volumes of flatus in normal individuals varies hugely (476–1,491 mL/24 h). All intestinal gas is either swallowed environmental air, present intrinsically in foods and beverages, or the result of gut fermentation.
Swallowing small amounts of air occurs while eating and drinking. This is emitted from the mouth by eructation (burping) and is normal. Excessive swallowing of environmental air is called aerophagia, and has been shown in a few case reports to be responsible for increased flatus volume. This is, however, considered a rare cause of increased flatus volume. Gases contained in food and beverages are likewise emitted largely through eructation, e.g., carbonated beverages.
Endogenously produced intestinal gases make up 74 percent of flatus in normal subjects. The volume of gas produced is partially dependent upon the composition of the intestinal microbiota, which is normally very resistant to change, but is also very different in different individuals. Some patients are predisposed to increased endogenous gas production by virtue of their gut microbiota composition. The greatest concentration of gut bacteria is in the colon, while the small intestine is normally nearly sterile. Fermentation occurs when unabsorbed food residues arrive in the colon.
Therefore, even more than the composition of the microbiota, diet is the primary factor that dictates the volume of flatus produced. Diets that aim to reduce the amount of undigested fermentable food residues arriving in the colon have been shown to significantly reduce the volume of flatus produced. Again, increased volume of intestinal gas will not cause bloating and pain in normal subjects. Abnormal intestinal gas dynamics will create pain, distension, and bloating, regardless of whether there is high or low total flatus volume.

Odor
Although flatus possesses an odor, this may be abnormally increased in some patients and cause social distress to the patient. Increased odor of flatus presents a distinct clinical issue from other complaints related to intestinal gas. Some patients may exhibit over-sensitivity to bad flatus odor, and in extreme forms, olfactory reference syndrome may be diagnosed. Recent informal research found a correlation between flatus odor and both loudness and humidity content.

Incontinence of flatus
"Gas incontinence" could be defined as loss of voluntary control over the passage of flatus. It is a recognised subtype of faecal incontinence, and is usually related to minor disruptions of the continence mechanisms. Some consider gas incontinence to be the first, sometimes only, symptom of faecal incontinence.

Cause
Intestinal gas is composed of varying quantities of exogenous sources and endogenous sources. The exogenous gases are swallowed (aerophagia) when eating or drinking or increased swallowing during times of excessive salivation (as might occur when nauseated or as the result of gastroesophageal reflux disease). The endogenous gases are produced either as a by-product of digesting certain types of food, or of incomplete digestion, as is the case during steatorrhea. Anything that causes food to be incompletely digested by the stomach or small intestine may cause flatulence when the material arrives in the large intestine, due to fermentation by yeast or prokaryotes normally or abnormally present in the gastrointestinal tract.
Flatulence-producing foods are typically high in certain polysaccharides, especially oligosaccharides such as inulin. Those foods include beans, lentils, dairy products, onions, garlic, spring onions, leeks, turnips, swedes, radishes, sweet potatoes, potatoes, cashews, Jerusalem artichokes, oats, wheat, and yeast in breads. Cauliflower, broccoli, cabbage, Brussels sprouts and other cruciferous vegetables that belong to the genus Brassica are commonly reputed to not only increase flatulence, but to increase the pungency of the flatus.In beans, endogenous gases seem to arise from complex oligosaccharides (carbohydrates) that are particularly resistant to digestion by mammals, but are readily digestible by microorganisms (methane-producing archaea; Methanobrevibacter smithii) that inhabit the digestive tract. These oligosaccharides pass through the small intestine largely unchanged, and when they reach the large intestine, bacteria ferment them, producing copious amounts of flatus.When excessive or malodorous, flatus can be a sign of a health disorder, such as irritable bowel syndrome, celiac disease, non-celiac gluten sensitivity or lactose intolerance. It can also be caused by certain medicines, such as ibuprofen, laxatives, antifungal medicines or statins. Some infections, such as giardiasis, are also associated with flatulence.Interest in the causes of flatulence was spurred by high-altitude flight and human spaceflight; the low atmospheric pressure, confined conditions, and stresses peculiar to those endeavours were cause for concern. In the field of mountaineering, the phenomenon of high altitude flatus expulsion was first recorded over two hundred years ago.

Mechanism
Production, composition, and odor
Flatus (intestinal gas) is mostly produced as a byproduct of bacterial fermentation in the gastrointestinal (GI) tract, especially the colon. There are reports of aerophagia (excessive air swallowing) causing excessive intestinal gas, but this is considered rare.Over 99% of the volume of flatus is composed of odorless gases. These include oxygen, nitrogen, carbon dioxide, hydrogen and methane. Nitrogen is not produced in the gut, but a component of environmental air. Patients who have excessive intestinal gas that is mostly composed of nitrogen have aerophagia. Hydrogen, carbon dioxide and methane are all produced in the gut and contribute 74% of the volume of flatus in normal subjects. Methane and hydrogen are flammable, and so flatus can be ignited if it contains adequate amounts of these components.Not all humans produce flatus that contains methane. For example, in one study of the faeces of nine adults, only five of the samples contained archaea capable of producing methane. The prevalence of methane over hydrogen in human flatus may correlate with obesity, constipation and irritable bowel syndrome, as archaea that oxidise hydrogen into methane promote the metabolisms ability to absorb fatty acids from food.The remaining trace (<1% volume) compounds contribute to the odor of flatus. Historically, compounds such as indole, skatole, ammonia and short chain fatty acids were thought to cause the odor of flatus. More recent evidence proves that the major contribution to the odor of flatus comes from a combination of volatile sulfur compounds. Hydrogen sulfide, methyl mercaptan (also known as methanethiol), dimethyl sulfide, dimethyl disulfide and dimethyl trisulfide are present in flatus. The benzopyrrole volatiles indole and skatole have an odor of mothballs,  and therefore probably do not contribute greatly to the characteristic odor of flatus.
In one study, hydrogen sulfide concentration was shown to correlate convincingly with perceived bad odor of flatus, followed by methyl mercaptan and dimethyl sulfide. This is supported by the fact that hydrogen sulfide may be the most abundant volatile sulfur compound present. These results were generated from subjects who were eating a diet high in pinto beans to stimulate flatus production.
Others report that methyl mercaptan was the greatest contributor to the odor of flatus in patients not under any specific dietary alterations. It has now been demonstrated that methyl mercaptan, dimethyl sulfide, and hydrogen sulfide (described as decomposing vegetables, unpleasantly sweet/wild radish and rotten eggs respectively) are all present in human flatus in concentrations above their smell perception thresholds.It is recognized that increased dietary sulfur-containing amino acids significantly increases the odor of flatus. It is therefore likely that the odor of flatus is created by a combination of volatile sulfur compounds, with minimal contribution from non-sulfur volatiles. This odor can also be caused by the presence of large numbers of microflora bacteria or the presence of faeces in the rectum. Diets high in protein, especially sulfur-containing amino acids, have been demonstrated to significantly increase the odor of flatus.

Volume and intestinal gas dynamics
Normal flatus volume is 476 to 1491 mL per 24 hours. This variability between individuals is greatly dependent upon diet. Similarly, the number of flatus episodes per day is variable; the normal range is given as 8–20 per day. The volume of flatus associated with each flatulence event again varies (5–375 mL). The volume of the first flatulence upon waking in the morning is significantly larger than those during the day. This may be due to buildup of intestinal gas in the colon during sleep, the peak in peristaltic activity in the first few hours after waking or the strong prokinetic effect of rectal distension on the rate of transit of intestinal gas. It is now known that gas is moved along the gut independently of solids and liquids, and this transit is more efficient in the erect position compared to when supine. It is thought that large volumes of intestinal gas present low resistance, and can be propelled by subtle changes in gut tone, capacitance and proximal contraction and distal relaxation. This process is thought not to affect solid and liquid intra-lumenal contents.Researchers investigating the role of sensory nerve endings in the anal canal did not find them to be essential for retaining fluids in the anus, and instead speculate that their role may be to distinguish between flatus and faeces, thereby helping detect a need to defecate or to signal the end of defecation.The sound varies depending on the tightness of the sphincter muscle and velocity of the gas being propelled, as well as other factors, such as water and body fat. The auditory pitch (sound) of the flatulence outburst can also be affected by the anal embouchure. Among humans, flatulence occasionally happens accidentally, such as incidentally to coughing or sneezing or during orgasm; on other occasions, flatulence can be voluntarily elicited by tensing the rectum or "bearing down" on stomach or bowel muscles and subsequently relaxing the anal sphincter, resulting in the expulsion of flatus.

Management
Since problems involving intestinal gas present as different (but sometimes combined) complaints, the management is cause-related.

Pain and bloating
While not affecting the production of the gases themselves, surfactants (agents that lower surface tension) can reduce the disagreeable sensations associated with flatulence, by aiding the dissolution of the gases into liquid and solid faecal matter. Preparations containing simethicone reportedly operate by promoting the coalescence of smaller bubbles into larger ones more easily passed from the body, either by burping or flatulence. Such preparations do not decrease the total amount of gas generated in or passed from the colon, but make the bubbles larger and thereby allowing them to be passed more easily.Other drugs including prokinetics, lubiprostone, antibiotics and probiotics are also used to treat bloating in patients with functional bowel disorders such as irritable bowel syndrome, and there is some evidence that these measures may reduce symptoms.A flexible tube, inserted into the rectum, can be used to collect intestinal gas in a flatus bag. This method is occasionally needed in a hospital setting, when the patient is unable to pass gas normally.

Volume
One method of reducing the volume of flatus produced is dietary modification, reducing the amount of fermentable carbohydrates. This is the theory behind diets such as the low-FODMAP diet (a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, alcohols, and polyols).Most starches, including potatoes, corn, noodles, and wheat, produce gas as they are broken down in the large intestine. Intestinal gas can be reduced by fermenting the beans, and making them less gas-inducing, or by cooking them in the liquor from a previous batch. For example, the fermented bean product miso is less likely to produce as much intestinal gas. Some legumes also stand up to prolonged cooking, which can help break down the oligosaccharides into simple sugars. Fermentative lactic acid bacteria such as Lactobacillus casei and Lactobacillus plantarum reduce flatulence in the human intestinal tract.Probiotics (live yogurt, kefir, etc.) are reputed to reduce flatulence when used to restore balance to the normal intestinal flora. Live (bioactive) yogurt contains, among other lactic bacteria, Lactobacillus acidophilus, which may be useful in reducing flatulence. L. acidophilus may make the intestinal environment more acidic, supporting a natural balance of the fermentative processes. L. acidophilus is available in supplements. Prebiotics, which generally are non-digestible oligosaccharides, such as fructooligosaccharide, generally increase flatulence in a similar way as described for lactose intolerance.
Digestive enzyme supplements may significantly reduce the amount of flatulence caused by some components of foods not being digested by the body and thereby promoting the action of microbes in the small and large intestines. It has been suggested that alpha-galactosidase enzymes, which can digest certain complex sugars, are effective in reducing the volume and frequency of flatus. The enzymes alpha-galactosidase, lactase, amylase, lipase, protease, cellulase, glucoamylase, invertase, malt diastase, pectinase, and bromelain are available, either individually or in combination blends, in commercial products.
The antibiotic rifaximin, often used to treat diarrhea caused by the microorganism E. coli, may reduce both the production of intestinal gas and the frequency of flatus events.

Odor
Bismuth
The odor created by flatulence is commonly treated with bismuth subgallate, available over-the-counter in the US as Devrom. Bismuth subgallate is commonly used by individuals who have had ostomy surgery, bariatric surgery, faecal incontinence and irritable bowel syndrome. Bismuth subsalicylate is a compound that binds hydrogen sulfide, and one study reported a dose of 524 mg four times a day for 3–7 days bismuth subsalicylate yielded a >95% reduction in faecal hydrogen sulfide release in both humans and rats.
Another bismuth compound, bismuth subnitrate was also shown to bind to hydrogen sulfide. Another study showed that bismuth acted synergistically with various antibiotics to inhibit sulfate-reducing gut bacteria and sulfide production. Some authors proposed a theory that hydrogen sulfide was involved in the development of ulcerative colitis and that bismuth might be helpful in the management of this condition. However, bismuth administration in rats did not prevent them from developing ulcerative colitis despite reduced hydrogen sulfide production. Also, evidence suggests that colonic hydrogen sulfide is largely present in bound forms, probably sulfides of iron and other metals. Rarely, serious bismuth toxicity may occur with higher doses. Activated charcoal
Despite being an ancient treatment for various digestive complaints, activated charcoal did not produce reduction in both the total flatus volume nor the release of sulfur-containing gasses, and there was no reduction in abdominal symptoms (after 0.52 g activated charcoal four times a day for one week). The authors suggested that saturation of charcoal binding sites during its passage through the gut was the reason for this. A further study concluded that activated charcoal (4 g) does not influence gas formation in vitro or in vivo. Other authors reported that activated charcoal was effective. A study in 8 dogs concluded activated charcoal (unknown oral dose) reduced hydrogen sulfide levels by 71%. In combination with yucca schidigera, and zinc acetate, this was increased to an 86% reduction in hydrogen sulfide, although flatus volume and number was unchanged. An early study reported activated charcoal (unknown oral dose) prevented a large increase in the number of flatus events and increased breath hydrogen concentrations that normally occur following a gas-producing meal.Garments and external devices
In 1998, Chester "Buck" Weimer of Pueblo, Colorado, received a patent for the first undergarment that contained a replaceable charcoal filter. The undergarments are air-tight and provide a pocketed escape hole in which a charcoal filter can be inserted. In 2001 Weimer received the Ig Nobel Prize for Biology for his invention.A similar product was released in 2002, but rather than an entire undergarment, consumers are able to purchase an insert similar to a pantiliner that contains activated charcoal. The inventors, Myra and Brian Conant of Mililani, Hawaii, still claim on their website to have discovered the undergarment product in 2002 (four years after Chester Weimer filed for a patent for his product), but state that their tests "concluded" that they should release an insert instead.

Incontinence
Flatus incontinence where there is involuntary passage of gas, is a type of faecal incontinence, and is managed similarly.

Society and culture
In many cultures, flatulence in public is regarded as embarrassing, but, depending on context, may also be considered humorous. People will often strain to hold in the passing of gas when in polite company, or position themselves to silence or conceal the passing of gas. In other cultures, it may be no more embarrassing than coughing.
While the act of passing flatus in some cultures is generally considered to be an unfortunate occurrence in public settings, flatulence may, in casual circumstances and especially among children, be used as either a humorous supplement to a joke ("pull my finger"), or as a comic activity in and of itself. The social acceptability of flatulence-based humour in entertainment and the mass media varies over the course of time and between cultures. A sufficient number of entertainers have performed using their flatus to lead to the coining of the term flatulist. The whoopee cushion is a joking device invented in the early 20th century for simulating a fart. In 2008, a farting application for the iPhone earned nearly $10,000 in one day.A farting game named Touch Wood was documented by John Gregory Bourke in the 1890s. It existed under the name of Safety in the 20th century in the U.S., and has been found being played in 2011.In January 2011, the Malawi Minister of Justice, George Chaponda, said that Air Fouling Legislation would make public "farting" illegal in his country. When reporting the story, the media satirised Chapondas statement with punning headlines. Later, the minister withdrew his statement.

Environmental impact
Flatulence is often blamed as a significant source of greenhouse gases, owing to the erroneous belief that the methane released by livestock is in the flatus. While livestock account for around 20% of global methane emissions, 90–95% of that is released by exhaling or burping. In cows, gas and burps are produced by methane-generating microbes called methanogens, that live inside the cows digestive system. Proposals for reducing methane production in cows include the feeding of supplements such as oregano and seaweed, and the genetic engineering of gut biome microbes to produce less methane.Since New Zealand produces large amounts of agricultural products, it is in the unique position of having high methane emissions from livestock compared to other greenhouse gas sources. The New Zealand government is a signatory to the Kyoto Protocol and therefore attempts are being made to reduce greenhouse emissions. To achieve this, an agricultural emissions research levy was proposed, which promptly became known as a "fart tax" or "flatulence tax". It encountered opposition from farmers, farming lobby groups and opposition politicians.

Entertainment
Historical comment on the ability to fart at will is observed as early as Saint Augustines The City of God (5th century A.D.). Augustine mentions men who "have such command of their bowels, that they can break wind continuously at will, so as to produce the effect of singing". Intentional passing of gas and its use as entertainment for others appear to have been somewhat well known in pre-modern Europe, according to mentions of it in medieval and later literature, including Rabelais.
Le Pétomane ("the Fartomaniac") was a famous French performer in the 19th century who, as well as many professional farters before him, did flatulence impressions and held shows. The performer Mr. Methane carries on le Pétomanes tradition today. Also, a 2002 fiction film Thunderpants revolves around a boy named Patrick Smash who has an ongoing flatulence problem from the time of his birth.Since the 1970s, farting has increasingly been featured in film, especially comedies such as Blazing Saddles and Scooby-Doo.

Religion
In Islam, flatulence, if audible or odorous, invalidates wudu (ritual purity).

Personal experiences
People find other peoples flatus unpleasant, but are unfazed by, and may even enjoy, the scent of their own. While there has been little research carried out upon the subject, some speculative guesses have been made as to why this might be so. For example, one explanation for this phenomenon is that people are very familiar with the scent of their own flatus, and that survival in nature may depend on the detection of and reaction to foreign scents.

See also
References
Citations
General and cited references
Allen, V. (2007). On Farting: Language and Laughter in the Middle Ages. Palgrave MacMillan. ISBN 978-0-312-23493-5.
Bolin, T. D. & Stanton, R. (1997). Wind Breaks. Allen & Unwin. ISBN 978-1-86448-321-5.
Dawson, Jim (1999). Who Cut the Cheese?: A Cultural History of the Fart. Ten Speed Press. ISBN 1-58008-011-1.
Dawson, Jim (2006). Blame it on the Dog: A Modern History of the Fart. Ten Speed Press. ISBN 1-58008-751-5.
Franklin, Benjamin (2003).  Japikse, Carl (ed.). Fart Proudly ((Reprint) ed.). Frog Ltd/Blue Snake </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 Worry and can you explain it in depth? [/INST] Worry refers to the thoughts, images, emotions, and actions of a negative nature in a repetitive, uncontrollable manner that results from a proactive cognitive risk analysis made to avoid or solve anticipated potential threats and their potential consequences.

Introduction
Psychologically, worry is part of
Perseverative Cognition (a collective term for continuous thinking about negative events in the past or in the future). As an emotion "worry" is experienced from anxiety or concern about a real or imagined issue, often personal issues such as health or finances, or external broader issues such as environmental pollution, social structure or technological change. It is a natural response to anticipated future problems. Excessive worry is a primary diagnostic feature of generalized anxiety disorder, but also is pervasive in other psychological disorders, like schizophrenia. Most people experience short-lived periods of worry in their lives without incident; indeed, a mild amount of worrying have positive effects, if it prompts people to take precautions (e.g., fastening their seat belt or buying insurance) or avoid risky behaviors (e.g., angering dangerous animals, or binge drinking), but with excessive worrisome people they overestimate future dangers in their assessments and in its extremities tend to magnify the situation as a dead end which results stress. Overestimation happens because analytic resources are a combination of external locus of control, personal experience and belief fallacies. Chronically worried individuals are also more likely to lack confidence in their problem solving ability, perceive problems as threats, become easily frustrated when dealing with a problem, and are pessimistic about the outcome of problem-solving efforts.Seriously anxious people find it difficult to control their worry and typically experience symptoms like restlessness, fatigue, difficulty in concentrating, irritability, muscle tension and sleep disturbance.

Theories
Avoidance model
The avoidance model of worry (AMW) theorizes that worry is a verbal linguistic, thought based activity, which arises as an attempt to inhibit vivid mental imagery and associated somatic and emotional activation. This inhibition precludes the emotional processing of fear that is theoretically necessary for successful habituation and extinction of feared stimuli. Worry is reinforced as a coping technique due to the fact that most worries never actually occur, leaving the worrier with a feeling of having successfully controlled the feared situation, without the unpleasant sensations associated with exposure. Noteworthy, studies also show that visual worry, i.e. worrying that occurs in visual modality, is also associated with increased anxiety and other psychopathology symptoms.

Cognitive model
This model explains pathological worry to be an interaction between involuntary (bottom-up) processes, such as habitual biases in attention and interpretation favoring threat content, and voluntary (top-down) processes, such as attentional control. Emotional processing biases influence the probability of threat representations into the awareness as intruding negative or positive thoughts. At a pre-conscious level, these processes influence the competition among mental representations in which some correspond to the assertive power of worry with impaired cognitive process and others to the preventive power of worry with attentional control or exhaustive vigilance. The biases determine threatening degree and nature of worry content the worrier attempts to resolve the perceived threat and the redirection of anticipations, responses and coping in such situations.There are some who respond to mental representations in an uncertain or ambiguous state in regard to the stressful or upsetting event. In this state the worrier is held in a perpetual state of worry. This is because availability of an overwhelming number(maybe 2 or 3, depending upon the worry-prone individual) of possibilities of outcomes which can be generated, it puts the worrier in a threatening crisis and they focus their attentional control voluntarily on the potential negative outcomes, whereas others engage in a constructive problem solving manner and in a benign approach rather than to engage with heightened anticipation on the possible negative outcome.

Philosophical perspectives
Greek thinkers such as stoic philosopher Epictetus and Seneca advised against worry. Albert Ellis, the creator of Rational Emotive Behavior Therapy, was inspired by the Stoics’ therapeutic ideas.

Religious perspectives
The biblical word used in Hebrew for worry (Hebrew: דָּאַג, daag) regards worry as a combined form of fear and sorrow which affects nephesh, the totality of our being. The bible takes a fortitude-strengthening approach regarding worrying e.g. Psalm 94:

In the multitude of my anxieties within me, your comforts delight my soul.In the New Testament, the Gospel of Matthew encourages:

And can any of you by worrying add a single hour to your span of life? ... So do not worry about tomorrow, for tomorrow will bring worries of its own. Today’s trouble is enough for today.The Greek word used for worry in Matthew is merimnaō, which means to be anxious about, or to be troubled with cares.
St. Paul writes to the Philippian church, "There is no need to worry" and in the pastoral epistles, 2 Timothy 1:7 emboldens:

For God did not give us a spirit of cowardice, but rather a spirit of power and of love and of self-discipline.Similarly James 1:2-4 motivates to face trials of any kind with joy, because they produce endurance (strength and courage). Further Saint Peter reveals his understanding of healthy living in Second Peter 1:3,5–7:

We have a sure hope .. </s>