<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 Fugue state and can you explain it in depth? [/INST] Dissociative fugue (), formerly called a fugue state or psychogenic fugue, is a mental and behavioral disorder that is classified variously as a dissociative disorder, a conversion disorder, and a somatic symptom disorder. The disorder is a rare psychiatric phenomenon characterized by reversible amnesia for ones identity, including the memories, personality, and other identifying characteristics of individuality. The state can last for days, months or longer. Dissociative fugue usually involves unplanned travel or wandering and is sometimes accompanied by the establishment of a new identity. It is a facet of dissociative amnesia, according to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5).
After recovery from a fugue state, previous memories usually return intact, and further treatment is unnecessary. An episode of fugue is not characterized as attributable to a psychiatric disorder if it can be related to the ingestion of psychotropic substances, to physical trauma, to a general medical condition or to dissociative identity disorder, delirium, or dementia. Fugues are precipitated by a series of long-term traumatic episodes. It is most commonly associated with childhood victims of sexual abuse who learn to dissociate memory of the abuse (dissociative amnesia).

Signs and symptoms
Symptoms of a dissociative fugue include mild confusion and once the fugue ends, possible depression, grief, shame, and discomfort. People have also experienced a post-fugue anger. Another symptom of the fugue state can consist of loss of ones identity.

Diagnosis
A doctor might suspect dissociative fugue when people seem confused about their identity or are puzzled about their past or when confrontations challenge their new identity or absence of one. The doctor reviews symptoms and does a physical examination to exclude physical disorders that may contribute to or cause memory loss.
Sometimes dissociative fugue cannot be diagnosed until people return to their pre-fugue identity and are distressed to find themselves in unfamiliar circumstances, sometimes with awareness of "lost time". The diagnosis is usually made retroactively when a doctor reviews the history and collects information that documents the circumstances before people left home, the travel itself, and the establishment of an alternative life.
Functional amnesia can also be situation-specific, varying from all forms and variations of traumas or generally violent experiences, with the person experiencing severe memory loss for a particular trauma. Committing homicide; experiencing or committing a violent crime such as rape or torture; experiencing combat violence; attempting suicide; and being in automobile accidents and natural disasters have all induced cases of situation-specific amnesia (Arrigo & Pezdek, 1997; Kopelman, 2002a). As Kopelman (2002a) notes, however, care must be exercised in interpreting cases of psychogenic amnesia when there are compelling motives to feign memory deficits for legal or financial reasons. However, although some fraction of psychogenic amnesia cases can be explained in this fashion, it is generally acknowledged that true cases are not uncommon. Both global and situationally specific amnesia are often distinguished from the organic amnesic syndrome, in that the capacity to store new memories and experiences remains intact. Given the very delicate and oftentimes dramatic nature of memory loss in such cases, there usually is a concerted effort to help the person recover their identity and history. This will allow the subject to be recovered sometimes spontaneously when particular cues are encountered.

Definition
The cause of the fugue state is related to dissociative amnesia, (Code 300.12 of the DSM-IV codes) which has several other subtypes: selective amnesia, generalized amnesia, continuous amnesia, and systematized amnesia, in addition to the subtype "dissociative fugue".Unlike retrograde amnesia (which is popularly referred to simply as "amnesia", the state where someone forgets events before brain damage), dissociative amnesia is not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication, DSM-IV Codes 291.1 & 292.83) or a neurological or other general medical condition (e.g., amnestic disorder due to a head trauma, DSM-IV Code 294.0). It is a complex neuropsychological process.As the person experiencing a dissociative fugue may have recently experienced the reappearance of an event or person representing an earlier life trauma, the emergence of an armoring or defensive personality seems to be for some, a logical apprehension of the situation.Therefore, the terminology "fugue state" may carry a slight linguistic distinction from "dissociative fugue", the former implying a greater degree of "motion". For the purposes of this article, then, a "fugue state" occurs while one is "acting out" a "dissociative fugue".
The DSM-IV  defines "dissociative fugue" as:

sudden, unexpected travel away from home or ones customary place of work, with inability to recall ones past
confusion about personal identity, or the assumption of a new identity
significant distress or impairmentThe Merck Manual  defines "dissociative fugue" as:

One or more episodes of amnesia in which the inability to recall some or all of ones past and either the loss of ones identity or the formation of a new identity occur with sudden, unexpected, purposeful travel away from home.In support of this definition, the Merck Manual  further defines dissociative amnesia as:

An inability to recall important personal information, usually of a traumatic or stressful nature, that is too extensive to be explained by normal forgetfulness.

Prognosis
The DSM-IV-TR states that the fugue may have a duration from days to months, and recovery is usually rapid. However, some cases may be refractory. An individual usually has only one episode.

Cases
Shirley Ardell Mason (1923–1998), also known as "Sybil", would disappear and then reappear with no recollection of what happened during the time span. She recalled "being here and then not here" and having no identity of herself; it was claimed by her psychiatrist, Cornelia Wilbur, that she also had dissociative identity disorder. Wilburs diagnosis of DID was disputed by Wilburs contemporary Herbert Spiegel.
Jody Roberts, a reporter for the Tacoma News Tribune, disappeared in 1985, only to be found 12 years later in Sitka, Alaska, living under the name of "Jane Dee Williams". While there were some initial suspicions that she had been faking amnesia, some experts have come to believe that she genuinely experienced a protracted fugue state.
David Fitzpatrick, who had dissociative fugue disorder, was profiled in the UK on Fives television series Extraordinary People. He entered a fugue state on December 4, 2005, and was working on regaining his entire lifes memories at the time of his appearance in his episode of the documentary series.
Hannah Upp, a teacher originally from Salem, Oregon, was given a diagnosis of dissociative fugue after she had disappeared from her New York home in August 2008 and was rescued from the New York Harbor 20 days later. News coverage at the time focused on her refusal to speak to detectives right after she was found  and the fact that she was seen checking her email at Apple Stores while she was missing </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 Parathyroid adenoma and can you explain it in depth? [/INST] A parathyroid adenoma is a benign tumor of the parathyroid gland. It generally causes hyperparathyroidism; there are very few reports of parathyroid adenomas that were not associated with hyperparathyroidism.A human being usually has four parathyroid glands located on the posterior surface of the thyroid in the neck. In order to maintain calcium metabolism, the parathyroid glands secrete parathyroid hormone (PTH) which stimulates the bones to release calcium and the kidneys to reabsorb it from the urine into the blood, thereby increasing its serum level. The action of calcitonin opposes PTH. When a parathyroid adenoma causes hyperparathyroidism, more parathyroid hormone is secreted, causing the calcium concentration of the blood to rise, resulting in hypercalcemia.

Signs and symptoms
The first signs of a parathyroid adenoma and the resulting primary hyperparathyroidism can include bone fractures and urinary calculi such as kidney stones.Often, a parathyroid adenoma is diagnosed by an incidental finding on blood tests that reveal high calcium levels. Patients may not be experiencing any noticeable symptoms but could be producing excessive amounts of calcium and eventually experience problems later in life if untreated. However, if symptomatic, patients can experience: pain or discomfort in the joints, muscles, and abdomen; depression and mood changes due to the hormonal imbalance.; constipation; exhaustion; and kidney damage.

Genetics
Parathyroid adenoma can be associated with overexpression of the cyclin D1 gene. It is also associated with multiple endocrine neoplasia (MEN).

Diagnosis
Hyperparathyroidism is confirmed by blood tests such as calcium and PTH levels. A specific test for parathyroid adenoma is sestamibi parathyroid scintigraphy, the sestamibi scan. This nuclear imaging technique reveals the presence and location of pathological parathyroid tissue.4DCT is used as second line investigation to diagnose parathyroid adenoma. In addition to the three dimensional imaging of a conventional CT scan, 4DCT provides imaging on the changes of iodinated contrast enhancement overtime and present them in a video format (from plain imaging to arterial to venous and delay phases). Parathyroid adenoma would show low density on non contrast image, with peak enhancement during the arterial phase, then slowly fade away until the delay phase.

Treatment
Surgery is the only cure for parathyroid adenomas. It is successful about 95% of the time </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 Cerebral venous sinus thrombosis and can you explain it in depth? [/INST] Cerebral venous sinus thrombosis (CVST), cerebral venous and sinus thrombosis or cerebral venous thrombosis (CVT), is the presence of a blood clot in the dural venous sinuses (which drain blood from the brain), the cerebral veins, or both. Symptoms may include severe headache, visual symptoms, any of the symptoms of stroke such as weakness of the face and limbs on one side of the body, and seizures, which occur in around 40% of patients.The diagnosis is usually by computed tomography (CT scan) or magnetic resonance imaging (MRI) to demonstrate obstruction of the venous sinuses. After confirmation of the diagnosis, investigations may be performed to determine the underlying cause, especially if one is not readily apparent.
Treatment is typically with anticoagulants (medications that suppress blood clotting) such as low molecular weight heparin. Rarely, thrombolysis (enzymatic destruction of the blood clot) or mechanical thrombectomy is used, although evidence for this therapy is limited. The disease may be complicated by raised intracranial pressure, which may warrant surgical intervention such as the placement of a shunt.

Signs and symptoms
Nine in ten people with cerebral venous thrombosis have a headache; this tends to worsen over the period of several days, but may also develop suddenly (thunderclap headache).  The headache may be the only symptom. Many have symptoms of stroke: inability to move one or more limbs, weakness on one side of the face or difficulty speaking. The neurologic deficits related to central venous thromboses does not necessarily affect one side of the body or one arterial or brain territory as is more common "arterial" strokes. Bilateral 6th cranial nerve palsies may occur, causing abnormalities related to eye movement, but this is rare.40% of people have seizures, although it is more common in women who develop sinus thrombosis peripartum (in the period before and after giving birth). These are mostly seizures affecting only one part of the body and unilateral (occurring on one side), but occasionally the seizures are generalised and rarely they lead to status epilepticus (persistent or recurrent seizure activity for a long period of time).In the elderly, many of the aforementioned symptoms may not occur. Common symptoms in the elderly with this condition are otherwise unexplained changes in mental status and a depressed level of consciousness.The pressure around the brain may rise, causing papilledema (swelling of the optic disc) which may be experienced as visual obscurations. In severely raised intracranial pressure, the level of consciousness is decreased, the blood pressure rises, the heart rate falls and there is abnormal posturing.Focal neurologic deficits may occur hours to days after the headache in 50% of cases, this may present as hemiparesis (unilateral weakness) if due to infarction of the frontal or parietal lobe which are drained by the vein of Trolard. Focal deficits may also present as aphasia or confusion if the vein of Labbe (responsible for draining the temporal lobe) is affected.

Causes
Disorders that cause, or increase the risk for systemic venous thrombosis are associated with central venous thromboses. In children, head and neck infections and acute systemic illnesses are the primary cause of central venous thrombosis. Cerebral venous sinus thrombosis is more common in particular situations. 85% of people have at least one of these risk factors:
Thrombophilia, a tendency to develop blood clots due to abnormalities in coagulation, e.g. factor V Leiden, deficiency of protein C, protein S or antithrombin, or related problems
Nephrotic syndrome, a kidney problem causing protein loss in the urine
Chronic inflammatory diseases, such as inflammatory bowel disease, lupus and Behçets disease
Pregnancy and puerperium (the period after giving birth)
Particular blood disorders, especially polycythemia vera and paroxysmal nocturnal hemoglobinuria
Use of estrogen-containing forms of hormonal contraception
Meningitis and infections of the ear, nose and throat area such as mastoiditis and sinusitis
Direct injury to the venous sinuses
Medical procedures in the head and neck area
Obesity, especially in combination with oral contraceptive use
Sickle cell anemia
Dehydration, primarily in infants and children
Homocysteinemia
Homocystinuria

Diagnosis
The diagnosis may be suspected on the basis of the symptoms, for example the combination of headache, signs of raised intracranial pressure and focal neurological abnormalities, or when alternative causes of headache and neurological abnormalities, such as a subarachnoid hemorrhage, have been excluded.

Imaging
There are various neuroimaging investigations that may detect cerebral sinus thrombosis. Cerebral edema and venous infarction may be apparent on any modality, but for the detection of the thrombus itself, the most commonly used tests are computed tomography (CT) and magnetic resonance imaging (MRI), both using various types of radiocontrast to perform a venogram and visualise the veins around the brain.Computed tomography, with radiocontrast in the venous phase (CT venography or CTV), has a detection rate that in some regards exceeds that of MRI. The test involves injection into a vein (usually in the arm) of a radioopaque substance, and time is allowed for the bloodstream to carry it to the cerebral veins – at which point the scan is performed. It has a sensitivity of 75–100% (it detects 75–100% of all clots present), and a specificity of 81–100% (it would be incorrectly positive in 0–19%). In the first two weeks, the "empty delta sign" may be observed (in later stages, this sign may disappear). The empty delta sign is characterized by enhancement of the dural wall without intra-sinus enhancement.Magnetic resonance venography employs the same principles, but uses MRI as a scanning modality. MRI has the advantage of being better at detecting damage to the brain itself as a result of the increased pressure on the obstructed veins, but it is not readily available in many hospitals and the interpretation may be difficult.Cerebral angiography may demonstrate smaller clots than CT or MRI, and obstructed veins may give the "corkscrew appearance". This, however, requires puncture of the femoral artery with a sheath and advancing a thin tube through the blood vessels to the brain where radiocontrast is injected before X-ray images are obtained. It is therefore only performed if all other tests give unclear results or when other treatments may be administered during the same procedure.

D-dimer
There is an association between the D-dimer blood test and cerebral venous sinus thrombosis. This association however is not strong enough to rule out the diagnosis alone.

Further tests
In most cases, the direct cause for the cerebral sinus thrombosis is not readily apparent. Identifying a source of infection is crucial; it is common practice to screen for various forms of thrombophilia (a propensity to form blood clots).

Pathogenesis
The veins of the brain, both the superficial veins and the deep venous system, empty into the dural venous sinuses, which carry blood back to the jugular vein and thence to the heart. In cerebral venous thrombosis, blood clots usually form both in the veins of the brain and the venous sinuses. The thrombosis of the veins themselves causes venous infarction (damage to brain tissue due to a congested and therefore insufficient blood supply). This results in cerebral edema (both vasogenic and cytotoxic edema), and leads to small petechial haemorrhages that may merge into large haematomas. Thrombosis of the sinuses is the main mechanism behind the increase in intracranial pressure due to decreased resorption of cerebrospinal fluid (CSF). The condition does not typically lead to hydrocephalus, however, because there is no difference in pressure between various parts of the brain. However, those who have deep cerebral venous sinus thrombosis or oedema at basal ganglia are more prone to hydrocephalus development.Any blood clot forms due to an imbalance between coagulation (the formation of the insoluble blood protein fibrin) and fibrinolysis. The three major mechanisms for such an imbalance are enumerated in Virchows triad: alterations in normal blood flow, injury to the blood vessel wall, and alterations in the constitution of blood (hypercoagulability). Most cases of cerebral venous sinus thrombosis are due to hypercoagulability. The inflammatory response and prolonged immobilization of patients with COVID-19 may also help explain the formation of CVST.It is possible for the clot to break off and migrate (embolise) to the lungs, causing a pulmonary embolism. An analysis of earlier case reports concludes that this occurs in about 10% of cases, but has a very poor prognosis.Central venous thromboses usually involve the dural sinuses with or without involvement of the cortical veins; isolated cortical venous thromboses are extremely rare with only about 100 cases reported.

Treatment
Various studies have investigated the use of anticoagulation to suppress blood clot formation in cerebral venous sinus thrombosis. Before these trials had been conducted, there had been a concern that small areas of hemorrhage in the brain would bleed further as a result of treatment; the studies showed that this concern was unfounded. Clinical practice guidelines now recommend heparin or low molecular weight heparin in the initial treatment, followed by warfarin, provided there are no other bleeding risks that would make these treatments unsuitable. Some experts discourage the use of anticoagulation if there is extensive hemorrhage; in that case, they recommend repeating the imaging after 7–10 days. If the hemorrhage has decreased in size, anticoagulants are started, while no anticoagulants are given if there is no reduction.The duration of warfarin treatment depends on the circumstances and underlying causes of the condition. If the thrombosis developed under temporary circumstances (e.g. pregnancy), three months are regarded as sufficient. If the condition was unprovoked but there are no clear causes or a "mild" form of thrombophilia, 6 to 12 months is advised. If there is a severe underlying thrombosis disorder, warfarin treatment may need to continue indefinitely.Heparin and platelet transfusions should not be used as a treatment for any form of cerebral venous thrombosis caused by immune thrombotic thrombocytopenias including Heparin induced thrombocytopenia (HIT), auto-immune heparin induced thrombocytopenia (aHIT) or vaccine induced immune thrombotic thrombocytopenia (VITT) due to unpredictable effects of heparin on anti-platelet factor-4 antibodies (PF-4). In cases of VITT, intravenous immune globulins (IVIG) are recommended as they block the anti-PF4 antibody interaction with platelets and a non-heparin anticoagulant. In refractory cases, plasma exchange may be used.Thrombolysis (removal of the blood clot with "clot buster" medication) has been described, either systemically by injection into a vein or directly into the clot during angiography. The 2006 European Federation of Neurological Societies guideline recommends that thrombolysis is only used in people who deteriorate despite adequate treatment, and other causes of deterioration have been eliminated. It is unclear which drug and which mode of administration is the most effective. Bleeding into the brain and in other sites of the body is a major concern in the use of thrombolysis. American guidelines make no recommendation with regards to thrombolysis, stating that more research is needed.In those where a venous infarct or hemorrhage causes significant compression of surrounding brain structures, decompressive craniectomy is sometimes required. Raised intracranial pressure, if severe or threatening vision, may require therapeutic lumbar puncture (removal of excessive cerebrospinal fluid), or neurosurgical treatment (optic nerve sheath fenestration or shunting). Venous stenting is emerging as a minimally invasive, safer alternative to shunting. In certain situations, anticonvulsants may be used to try to prevent seizures. These situations include focal neurological problems (e.g. inability to move a limb) and focal changes of the brain tissue on CT or MRI scan. Evidence to support or refute the use of antiepileptic drugs as a preventive measure, however, is lacking.

Prognosis
In 2004 the first adequately large scale study on the natural history and long-term prognosis of this condition was reported; this showed that at 16 months follow-up 57.1% of people had full recovery, 29.5%/2.9%/2.2% had respectively minor/moderate/severe symptoms or impairments, and 8.3% had died. Severe impairment or death were more likely in those aged over 37 years, male, affected by coma, mental status disorder, intracerebral hemorrhage, thrombosis of the deep cerebral venous system, central nervous system infection and cancer. A subsequent systematic review of nineteen studies in 2006 showed that mortality is about 5.6% during hospitalisation and 9.4% in total, while of the survivors 88% make a total or near-total recovery. After several months, two thirds of the cases has resolution ("recanalisation") of the clot. The rate of recurrence was low (2.8%).In children with CVST the risk of death is high. Poor outcome is more likely if a child with CVST develops seizures or has evidence of venous infarction on imaging.

Epidemiology
Cerebral venous sinus thrombosis is rare, with an estimated 3-4 cases per million annual incidence in adults. While it may occur in all age groups, it is most common in the third decade. 75% are female. Given that older studies show no difference in incidence between men and women, it has been suggested that the use of oral contraceptives in women is behind the disparity between the sexes. A 1995 report from Saudi Arabia found a substantially larger incidence at 7 cases per 100,000; this was attributed to the fact that Behçets disease, which increases risk of CVST, is more common in the Middle East.A 1973 report found that CVST could be found on autopsy (examination of the body after death) in nine percent of all people. Many of these were elderly and had neurological symptoms in the period leading up to their death, and many developed concomitant heart failure. An estimated 0.3% incidence of CVST in patients infected with SARS-CoV-2.In children, a Canadian study reported in 2001 that CVST occurs in 6.7 per million annually. 43% occur in the newborn (less than one month old), and a further 10% in the first year of life. Of the newborn, 84% were already ill, mostly from complications after childbirth and dehydration.

History
The first description of thrombosis of the cerebral veins and sinuses is attributed to the French physician Ribes, who in 1825 observed thrombosis of the sagittal sinus and cerebral veins in a man who had had seizures and delirium. Until the second half of the 20th century it remained a diagnosis generally made after death. In the 1940s, reports by Dr Charles Symonds and others allowed for the clinical diagnosis of cerebral venous thrombosis, using characteristic signs and symptoms and results of lumbar puncture.Improvements on the diagnosis of cerebral venous sinus thrombosis in life were made with the introduction of venography in 1951, which also aided in the distinction from idiopathic intracranial hypertension, which has similar presenting signs and symptoms in many cases.The British gynecologist Stansfield is credited with the introduction, in 1942, of the just recently introduced anticoagulant heparin in the treatment of CVST in 1942. Clinical trials in the 1990s finally resolved the concern about using anticoagulants in most cases of CVST.

COVID-19 vaccine
In March 2021, the European Medicines Agency (EMA) announced that out of the around 20 million people who had received the Oxford–AstraZeneca COVID-19 vaccine, general blood clotting rates were normal, but that it had identified seven cases of disseminated intravascular coagulation, and eighteen cases of cerebral venous sinus thrombosis. It had been proposed that inadvertent injection of COVID-19 vaccine into deltoid muscle vasculature may result in vaccine distribution to distant tissues that may be causing these rare adverse reactions. A causal link with the vaccine, however, had not been proven, but the EMA decided to conduct further analysis and to inform recipients of the remote possibility of such rare syndromes </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 Purpura fulminans and can you explain it in depth? [/INST] Purpura fulminans is an acute, often fatal, thrombotic disorder which manifests as blood spots, bruising and discolouration of the skin resulting from coagulation in small blood vessels within the skin and rapidly leads to skin necrosis and disseminated intravascular coagulation.

Causes
Purpura fulminans is caused by defects in the protein C anticoagulant pathway. Identification of the cause of purpura fulminans often depends on the patients age and circumstances of presentation.

Congenital protein C deficiency
Congenital (inherited) defects in protein C activity are autosomal dominant and may be partial or severe loss of function. Hundreds of natural mutations of the protein C gene (PROC) have been identified.

Acquired protein C deficiency
Acquired protein C deficiency is caused by either depletion of available protein C in plasma or decreased protein C synthesis (caused by administration of vitamin K antagonists, severe liver failure or complications of prematurity).

Severe acute sepsis
Purpura fulminans is a presenting feature of severe acute sepsis, such as Neisseria meningitidis, Streptococcus pneumoniae, Group A and B Streptococci, and less commonly with Haemophilus influenzae, Staphylococcus aureus, or Plasmodium falciparum (malaria) infections, particularly in individuals with asplenia.

Combination of sepsis and partial congenital defect
In some cases, a combination of sepsis and a partial congenital defect in the protein C anticoagulant pathway initiates purpura fulminans.

Unknown
In rare instances, purpura fulminans is an autoimmune manifestation against protein C or protein S after normally benign infections, such as chicken pox. Sometimes purpura fulminans has unknown cause.

Pathophysiology
Regardless of the underlying cause of purpura fulminans, the mechanism of disease is similar with deficiency in protein C concentration or decrease in protein C activity which promotes blood clotting (thrombosis).In cases of severe sepsis, there is widespread activation of the acute systemic inflammatory response, including activation of the coagulation and complement pathways, as well as endothelial dysfunction. Activated protein C helps regulate the systemic inflammatory response. During sepsis, signalling by the inflammatory cytokines, interleukin-1 and tumour necrosis factor, mediate altered protein transcription in the systemic inflammatory response, resulting in decreased synthesis of the regulatory proteins antithrombin, protein C and protein S, with increased synthesis of prothrombotic proteins Factor VIII, von Willebrand factor, and fibrinogen. Activated protein C binds to endothelial protein C receptor and subsequently cleaves the endothelial cell protease activated receptor-1, not only altering coagulation profiles but down-regulating pro-inflammatory and pro-apoptotic mediators, up-regulation of anti-inflammatory and anti-apoptotic pathways and stabilization of the endothelial cell barrier functions.Systemic coagulation activation may lead to depletion of circulating coagulation factors and platelets, which subsequently lead to bleeding. In early purpura fulminans, lesion progression correlates with the histological appearance of blockage of small skin blood vessels with blood clots causing capillary dilation and congestion with red blood cells. In later stage lesions, there is irreversible endothelial ischaemic injury with extravasation of blood cells into the dermis and gangrenous necrosis, sometimes with secondary infection.The depletion of anticoagulant and anti-inflammatory proteins, in particular, protein C and its co-factor, protein S, may also promote thrombus formation, inhibit fibrinolysis and lead to further activation of the inflammatory pathways.

Diagnosis
Early purpura fulminans lesions look similar to traumatic skin bleeds or purpuric rashes, such as immune thrombocytopenic purpura or thrombotic thrombocytopenic purpura; however, purpura fulminans will rapidly progress to necrosis whereas other purpuric rashes do not. In most cases, differential diagnoses may be distinguished from purpura fulminans by other clinical and laboratory findings.The initial appearance of purpura fulminans lesions is of well-demarcated erythaamatous lesions which progress rapidly to develop irregular central areas of blue-black haemorrhagic necrosis. Advancing areas of necrosis are often surrounded by a thin border of erythaema that fades into adjacent unaffected skin. Haemorrhage into the necrotic skin causes purpura fulminans lesions to become painful, dark and raised, sometimes with vesicle or blister (bulla) formation.The distribution of purpura fulminans lesions may be different according to the underlying pathogenesis. Purpura fulminans in severe sepsis typically develops in the distal extremities and progresses proximally or appears as a generalised or diffuse rash affecting the whole body surface. In cases of severe inheritable protein C deficiency, purpura fulminans with disseminated intravascular coagulation manifests within a few hours or days after birth.

Laboratory investigations
The cardinal features of purpura investigations are the same as those of disseminated intravascular coagulation: prolonged plasma clotting times, thrombocytopenia, reduced plasma fibrinogen concentration, increased plasma fibrin-degradation products and occasionally microangiopathic haemolysis.

Prevention
For people who have severe congenital protein C deficiency, protein C replacement therapies are available, which is indicated and approved for use in the United States and Europe for the prevention of purpura fulminans. Protein C replacement is often in combination with anticoagulation therapy of injectable low molecular weight heparin or oral warfarin. Before initiating warfarin therapy, a few days of therapeutic heparin may be administered to prevent warfarin necrosis and other progressive or recurrent thrombotic complications.

Complications of prevention
The amount of fresh frozen plasma required to reverse disseminated intravascular coagulation associated with purpura fulminans may lead to complications of fluid overload and death, especially in neonates, such as transfusion-related acute lung injury. Exposure to multiple plasma donors over time increases the cumulative risk for transfusion-associated viral infection and allergic reaction to donor proteins found in fresh frozen plasma.Allergic reactions and alloantibody formation are also potential complications, as with any protein replacement therapy.Concomitant warfarin therapy in subjects with congenital protein C deficiency is associated with an increased risk of warfarin skin necrosis.

Treatment
Early stage sepsis-associated purpura fulminans may be reversible with quick therapeutic intervention. Treatment is mainly removing the underlying cause and degree of clotting abnormalities and with supportive treatment (antibiotics, volume expansion, tissue oxygenation, etc.). Thus, treatment includes aggressive management of the septic state.Purpura fulminans with disseminated intravascular coagulation should be urgently treated with fresh frozen plasma (10–20 mL/kg every 8–12 hours) and/or protein C concentrate to replace pro-coagulant and anticoagulant plasma proteins that have been depleted by the disseminated intravascular coagulation process.Protein C in plasma in the steady state has a half life of 6- to 10-hour, therefore, patients with severe protein C deficiency and presenting with purpura fulminans can be treated acutely with an initial bolus of protein C concentrate 100 IU/kg followed by 50 IU /kg  every 6 hours </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 Monteggia fracture and can you explain it in depth? [/INST] The Monteggia fracture is a fracture of the proximal third of the ulna with dislocation of the proximal head of the radius. It is named after Giovanni Battista Monteggia.

Causes
Mechanisms include:

Fall outstretched hand with the forearm in excessive pronation (hyper-pronation injury).  The ulna fractures in the proximal one-third of the shaft due to extreme dislocation </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 Malignant triton tumor 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 Drug overdose and can you explain it in depth? [/INST] A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended. Typically it is used for cases when a risk to health will potentially result. An overdose may result in a toxic state or death.

Classification
The word "overdose" implies that there is a common safe dosage and usage for the drug; therefore, the term is commonly applied only to drugs, not poisons, even though many poisons as well are harmless at a low enough dosage. Drug overdose is sometimes used as a means to commit suicide, as the result of intentional or unintentional misuse of medication. Intentional misuse leading to overdose can include using prescribed or non-prescribed drugs in excessive quantities in an attempt to produce euphoria.
Usage of illicit drugs, in large quantities, or after a period of drug abstinence can also induce overdose. Cocaine users who inject intravenously can easily overdose accidentally, as the margin between a pleasurable drug sensation and an overdose is small. Unintentional misuse can include errors in dosage caused by failure to read or understand product labels. Accidental overdoses may also be the result of over-prescription, failure to recognize a drugs active ingredient or unwitting ingestion by children. A common unintentional overdose in young children involves multivitamins containing iron.
The term overdose is often misused as a descriptor for adverse drug reactions or negative drug interactions due to mixing multiple drugs simultaneously.

Signs and symptoms
Signs and symptoms of an overdose vary depending on the drug or exposure to toxins. The symptoms can often be divided into differing toxidromes. This can help one determine what class of drug or toxin is causing the difficulties.
Symptoms of opioid overdoses include slow breathing, heart rate and pulse. Opioid overdoses can also cause pinpoint pupils, and blue lips and nails due to low levels of oxygen in the blood. A person experiencing an opioid overdose might also have muscle spasms, seizures and decreased consciousness. A person experiencing an opiate overdose usually will not wake up even if their name is called or if they are shaken vigorously.

Causes
The drugs or toxins that are most frequently involved in overdose and death (grouped by ICD-10):

Added flavoring
Masking undesired taste may impair judgement of the potency, which is a factor in overdosing. For example, lean is usually created as a drinkable mixture, the cough syrup is combined with soft drinks, especially fruit-flavored drinks such as Sprite, Mountain Dew or Fanta, and is typically served in a foam cup. A hard candy, usually a Jolly Rancher, may be added to give the mixture a sweeter flavor.

Diagnosis
The substance that has been taken may often be determined by asking the person. However, if they will not, or cannot, due to an altered level of consciousness, provide this information, a search of the home or questioning of friends and family may be helpful.
Examination for toxidromes, drug testing, or laboratory test may be helpful. Other laboratory test such as glucose, urea and electrolytes, paracetamol levels and salicylate levels are typically done. Negative drug-drug interactions have sometimes been misdiagnosed as an acute drug overdose, occasionally leading to the assumption of suicide.

Prevention
The distribution of naloxone to injection drug users and other opioid drug users decreases the risk of death from overdose. The Centers for Disease Control and Prevention (CDC) estimates that U.S. programs for drug users and their caregivers prescribing take-home doses of naloxone and training on its utilization are estimated to have prevented 10,000 opioid overdose deaths. Healthcare institution-based naloxone prescription programs have also helped reduce rates of opioid overdose in the U.S. state of North Carolina, and have been replicated in the U.S. military. Nevertheless, scale-up of healthcare-based opioid overdose interventions is limited by providers insufficient knowledge and negative attitudes towards prescribing take-home naloxone to prevent opioid overdose. Programs training police and fire personnel in opioid overdose response using naloxone have also shown promise in the U.S.Supervised injection sites (also known as overdose prevention centers) have been used to help prevent drug overdoses by offering opioid reversal medications such as naloxone, medical assistance and treatment options. They also provide clean needles to help prevent the spread of diseases like HIV/AIDS and hepatitis.

Management
Stabilization of the persons airway, breathing, and circulation (ABCs) is the initial treatment of an overdose. Ventilation is considered when there is a low respiratory rate or when blood gases show the person to be hypoxic. Monitoring of the patient should continue before and throughout the treatment process, with particular attention to temperature, pulse, respiratory rate, blood pressure, urine output, electrocardiography (ECG) and O2 saturation. Poison control centers and medical toxicologists are available in many areas to provide guidance in overdoses both to physicians and to the general public.

Antidotes
Specific antidotes are available for certain overdoses. For example, naloxone is the antidote for opiates such as heroin or morphine. Similarly, benzodiazepine overdoses may be effectively reversed with flumazenil. As a nonspecific antidote, activated charcoal is frequently recommended if available within one hour of the ingestion and the ingestion is significant. Gastric lavage, syrup of ipecac, and whole bowel irrigation are rarely used.

Epidemiology and statistics
1,015,060  US residents died from drug overdoses from 1968 to 2019. 22 people out of every 100,000 died from drug overdoses in 2019 in the US. From 1999 to Feb 2019 in the United States, more than 770,000 people have died from drug overdoses.In the US around 107,300 people died in the 12-month period ending January 31, 2022, at a rate of 294 deaths per day. 70,630 people died from drug overdoses in 2019. The U.S. drug overdose death rate has gone from 2.5 per 100,000 people in 1968 to 21.5 per 100,000 in 2019.The National Center for Health Statistics reports that 19,250 people died of accidental poisoning in the U.S. in the year 2004 (eight deaths per 100,000 population).In 2008 testimony before a Senate subcommittee, Leonard J. Paulozzi, a medical epidemiologist at the Centers for Disease Control and Prevention said that in 2005 more than 22,000 American people died due to overdoses, and the number is growing rapidly </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 Double aortic arch and can you explain it in depth? [/INST] Double aortic arch  is a relatively rare congenital cardiovascular malformation.  DAA is an anomaly of the aortic arch in which two aortic arches  form a complete vascular ring that can compress the trachea and/or esophagus.   Most commonly there is a larger (dominant) right arch behind and a smaller (hypoplastic) left aortic arch in front of the trachea/esophagus. The two arches join to form the descending aorta which is usually on the left side (but may be right-sided or in the midline).  In some cases the end of the smaller left aortic arch closes (left atretic arch) and the vascular tissue becomes a fibrous cord. Although in these cases a complete ring of two patent aortic arches is not present, the term ‘vascular ring’ is the accepted generic term even in these anomalies.
The symptoms are related to the compression of the trachea, esophagus or both by the complete vascular ring. Diagnosis can often be suspected or made by chest x-ray, barium esophagram, or echocardiography. Computed tomography (CT) or magnetic resonance imaging (MRI) show the relationship of the aortic arches to the trachea and esophagus and also the degree of tracheal narrowing. Bronchoscopy can be useful in internally assessing the degree of tracheomalacia. Treatment is surgical and is indicated in all symptomatic patients. In the current era the risk of mortality or significant morbidity after surgical division of the lesser arch is low. However, the preoperative degree of tracheomalacia has an important impact on postoperative recovery. In certain patients it may take several months (up to 1–2 years) for the obstructive respiratory symptoms (wheezing) to disappear.

Signs and symptoms
Symptoms are caused by vascular compression of the airway, esophagus or both. Presentation is often within the first month (neonatal period) and usually within the first 6 months of life. Starting at birth an inspiratory and expiratory stridor (high pitch noise from turbulent airflow in trachea) may be present often in combination with an expiratory wheeze. The severity of the stridor may depend on the patient’s body position. It can be worse when the baby is lying on their back rather than their side. Sometimes the stridor can be relieved by extending the neck (lifting the chin up). Parents may notice that the baby’s cry is hoarse and the breathing noisy. Frequently a persistent cough is present. When the airway obstruction is significant there may be episodes of severe cyanosis (“blue baby”) that can lead to unconsciousness. Recurrent respiratory infections are common and secondary pulmonary secretions can further increase the airway obstruction.Secondary to compression of the esophagus babies often feed poorly. They may have difficulties in swallowing liquids with choking or regurgitating and increased respiratory obstruction during feeding. Older patients might refuse to take solid food, although most infants with severe symptoms nowadays are operated upon before they are offered solid food.Occasionally patients with double aortic arches present late (during later childhood or adulthood). Symptoms may mimic asthma.

Causes
Little is known regarding the exact causes of aortic arch anomalies. However, the association with chromosome 22q11 deletion (DiGeorge Syndrome) implies that a genetic component is likely in certain cases. Esophageal atresia also occurs in some patients with double aortic arch.

Diagnosis
Prenatal diagnosis (fetal ultrasound):
Today the diagnosis of double aortic arch can be obtained in-utero in experienced centers. Scheduled repair soon after birth in symptomatic patients can relieve tracheal compression early and therefore potentially prevent the development of severe tracheomalacia.
Chest X-ray:
Plain chest x-rays of patients with double aortic arch may appear normal (often) or show a dominant right aortic arch or two aortic arches . There might be evidence of tracheal deviation and/or compression. Sometimes patients present with radiologic findings of pneumonia.
Barium swallow (esophagraphy):
Historically the esophagram used to be the gold standard for diagnosis of double aortic arch. In patients with double aortic arch the esophagus shows left- and right-sided indentations from the vascular compression. Due to the blood-pressure related movement of the aorta and the two arches, moving images of the barium-filled esophagus can demonstrate the typical pulsatile nature of the obstruction. The indentation from a dominant right arch is usually deeper and higher compared to the dent from the left arch.
Bronchoscopy:
Although bronchoscopy is not routinely done in patients with suspected or confirmed double aortic arch, it can visualize sites and severity of pulsatile tracheal compression.
Echocardiography:
In babies under the age of 12 months, echocardiography is considered to be sensitive and specific in making the diagnosis of double aortic arch when both arches are open. Non-perfused elements of other types of vascular rings (e.g. left arch with atretic (closed) end) or the ligamentum arteriosum might be difficult to visualize by echocardiography.
Computed tomography (CT):
Computed tomography after application of contrast media is usually diagnostically accurate. It shows the relationship of the arches to the trachea and bronchi.
Magnetic resonance imaging (MRI):
Magnetic resonance imaging provides excellent images of the trachea and surrounding vascular structures and has the advantage of not using radiation for imaging compared to Computed tomography.
Cardiac catherization/aortography:
Today patients with double aortic arch usually only undergo cardiac catherization to evaluate the hemodynamics and anatomy of associated congenital cardiac defects. Through a catheter in the ascending aorta contrast media is injected and the resulting aortography may be used to delineate the anatomy of the double aortic arch including sites of narrowing in the left aortic arch. Aortography can also be used to visualize the origin of all head and arm vessels originating from the two arches.

Classification
Double aortic arch is a subtype of complete vascular ring. There are three types of double aortic arch:

Right dominant arch (about 70% of surgical cases)
Balanced or codominant (about 5%): both arches are of equal size
Left dominant (about 25%)Double aortic arch with right dominant arch:
Normally there is only one (left) aortic arch. In patients with double aortic arch the ascending aorta arises normally from the left ventricle but then divides into two arches, a left and a right aortic arch which join posteriorly to become the descending aorta.
The smaller left arch passes anteriorly and to the left of the trachea in the usual position. It is often joined by the ligamentum arteriosum (or patent ductus arteriosus) where it forms the descending aorta. The left arch gives first origin to the left common carotid artery and then the left subclavian artery.
The right aortic arch is completing the vascular ring by passing to the right and then behind the esophagus and trachea to join the usually left-sided descending aorta. The first vessel coming off the right arch is usually the right common carotid artery followed by the right subclavian artery.
Double aortic arch with left dominant arch:
In this less common condition, as the name indicates, the left arch is the larger of the two aortic arches. The origins of the arm and head vessels are identical to the anatomy of double aortic arch with right dominant arch
Balanced or codominant double aortic arch:
In this rare condition both aortic arches are of the same diameter.

Treatment
Surgical correction is indicated in all double aortic arch patients with obstructive symptoms (stridor, wheezing, pulmonary infections, poor feeding with choking). If symptoms are absent a conservative approach (watchful waiting) can be reasonable. Children with very mild symptoms may outgrow their symptoms but need regular follow-up.

Anesthesia and intraoperative monitoring
The procedure is performed in general anesthesia. It is useful to place pulse oximeter probes on both hands and one foot so that test occlusion of one arch or its branches will allow confirmation of the anatomy. In addition blood pressure cuffs should also be placed on one leg and both arms to confirm the absence of a pressure gradient when the intended point of division of the lesser arch is temporarily occluded with forceps.

Open division of vascular ring
Isolated double aortic arch without associated intracardiac defects is a vascular anomaly that can be corrected without the support of cardiopulmonary bypass.For surgical division of the narrower left aortic arch in a typical double arch patient with a dominant right arch, the patient is placed on the right side. After prepping and draping of the left chest a posterolateral thoracotomy is performed. The chest cavity is entered between the fourth and fifth rib (fourth intercostal space, as in the operation for patent ductus arteriosus or coarctation). After pulling the left lung aside, the layer (mediastinal pleura) above the left arch is incised and the left arch and the ligamentum arteriosum are dissected out and separated from the surrounding structures. The ligamentum is divided and two vascular clamps are placed on the junction of the left arch with the descending aorta. After division the two aortic ends are oversewn with 2 running layers of non-absorbable sutures. The end of the left arch is now further dissected from the mediastinal tissues for relief of any remaining constricting mechanism. The medial surface of the descending aorta and the distal end are also carefully dissected away from the esophagus. Additional relief can be obtained by stitching the lateral wall of the aorta to the adjacent rib to pull it away from the esophagus.After insertion of a chest tube to prevent hemothorax and/or pneumothorax, the fourth and fifth rib are approximated by an absorbable suture. The surgery is completed by closure of the left thoracotomy wound in layers.In most centers, the mortality risk for surgery is between zero and 2%.  A specific risk of open surgical repair of double aortic arch is injury to the recurrent laryngeal nerve, which can cause vocal cord paralysis. Injury to the lymphatic system can lead to postoperative chylothorax. Additional risks include lung injury, bleeding with the need for blood transfusions and wound infection.

Postoperative care
After the surgery, some patients require intubation and mechanical ventilation for several days to allow adequate tracheal toilet, but most patients can have the tubes removed soon after the surgery. The obstructive airway symptoms may be worse in the first postoperative weeks. Only a few patients have immediate relief of stridor, but many obtain immediate relief of problems with swallowing (dysphagia). After extubation, it might be necessary to maintain positive airway pressure by appropriate flows of a humidified oxygen/air mixture.

Epidemiology
Complete vascular rings represent about 0.5-1% of all congenital cardiovascular malformations </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 Lelis syndrome and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Plantar wart and can you explain it in depth? [/INST] A plantar wart, or verruca, is a wart occurring on the bottom of the foot or toes. Its color is typically similar to that of the skin. Small black dots often occur on the surface. One or more may occur in an area. They may result in pain with pressure such that walking is difficult.They are caused by the human papillomavirus (HPV). A break in the skin is required for infection to occur. Risk factors include use of communal showers, having had prior warts, and poor immune function. Diagnosis is typically based on symptoms.Treatment is only needed if it is causing symptoms. This may include salicylic acid, cryotherapy, chemo-based fluorouracil or bleomycin, and surgical removal. The skin atop the lesion should generally be removed before treatment. In about a third to two-thirds of cases, they go away without specific treatment, but this may take a few years. Plantar warts are common. Children and young adults are most often affected.

Signs and symptoms
Their colors are typically similar to that of the nearby skin. Small, black dots may occur on their surfaces. One or more may occur in an area. They may result in pain with pressure such that walking may be difficult.

Cause
Plantar warts are benign epithelial tumors generally caused by infection by human papillomavirus types 1, 2, 4, 60, or 63, but have also been caused by types 57, 65, 66, and 156. These types are classified as clinical (visible symptoms). The virus attacks compromised skin through direct contact,  possibly entering through tiny cuts and abrasions in the stratum corneum (outermost layer of skin). After infection, warts may not become visible for several weeks or months. Because of pressure on the sole of the foot or finger, the wart is pushed inward and a layer of hard skin may form over the wart. A plantar wart can be painful if left untreated.Warts may spread through autoinoculation, by infecting nearby skin, or by contaminated walking surfaces. They may fuse or develop into clusters called mosaic warts.

Diagnosis
A plantar wart is a small lesion that appears on the surface of the skin and typically resembles a cauliflower, with tiny black petechiae (tiny hemorrhages under the skin) in the center. Pinpoint bleeding may occur when these are scratched. Plantar warts occur on the soles of feet and toes. They may be painful when standing or walking.Plantar warts are often similar to calluses or corns, but can be differentiated by close observation of skin striations. Feet are covered in friction ridges, which are akin to fingerprints of the feet. Friction ridges are disrupted by plantar warts; if the lesion is not a plantar wart, the striations continue across the top layer of the skin. Plantar warts tend to be painful on application of pressure from either side of the lesion rather than direct pressure, unlike calluses (which tend to be painful on direct pressure, instead).

Prevention
HPV is spread by direct and indirect contact from an infected host. Avoiding direct contact with contaminated surfaces such as communal changing rooms and shower floors and benches, avoiding sharing of shoes and socks and avoiding contact with warts on other parts of the body and on the bodies of others may help reduce the spread of infection. Infection is less common among adults than children.As all warts are contagious, precautions should be taken to avoid spreading them. Recommendations include:

Cover them with an adhesive bandage while swimming
Wear latex swimming socks
Wear flip-flops when using communal showers
Do not share towels.Plantar warts are not prevented by inoculation with HPV vaccines because the warts are caused by different strains of HPV </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 Jacobsen syndrome and can you explain it in depth? [/INST] Jacobsen syndrome is a rare chromosomal disorder resulting from deletion of genes from chromosome 11 that includes band 11q24.1. It is a congenital disorder. Since the deletion takes place on the q arm of chromosome 11, it is also called 11q terminal deletion disorder. The deletion may range from 5 million to 16 million deleted DNA base pairs. The severity of symptoms depends on the number of deletions; the more deletions there are, the more severe the symptoms are likely to be.
People with Jacobsen syndrome have serious intellectual disabilities, dysmorphic features, delayed development and a variety of physical problems including heart defects. Research shows that almost 88.5% of people with Jacobsen syndrome have a bleeding disorder called Paris-Trousseau syndrome.Jacobsen syndrome is catastrophic in 1 out of every 5 cases, with children usually dying within the first 2 years of life due to heart complications.

Signs and symptoms
Almost all children with Jacobsen syndrome have intellectual disabilities, which range from mild to moderate depending upon the number of the deletions of genes from the chromosome. Most have delayed development, including delayed speech, motor disabilities and lack of coordination, which makes simple activities like sitting, standing and walking difficult. Most children eventually start speaking, but in cases with severe intellectual disability language use is highly restricted.They have distinctive facial features like:

Small head (microcephaly)
Pointed forehead (trigonocephaly)
Small ears which are low-set
Widely-spaced eyes (hypertelorism)
Droopy eyelids (ptosis)
Broad nasal bridge
Abnormally thin upper lips
Downturned corners of the mouth
Excess skin covering in the inner corner of eyes (epicanthal folds)Some children also experience behavioural problems like distractibility, hyperactivity, impaired communication and social skills, which qualifies them for a diagnosis of ASD and ADHD. Heart defects are very common in children with Jacobsen syndrome. 88.5% of people with the disorder have Paris-Trousseau syndrome, which is a bleeding disorder and causes a lifelong risk of abnormal bleeding and bruising due to dysfunction in the platelets. Other symptoms may include eye problems, ear and sinus infections, hearing problems, bone deformities, growth hormone deficiency, gastrointestinal problems, kidney malfunctions, etc.

Cause
Jacobsen syndrome is caused by deletion of genetic material from the long arm of chromosome 11. The size of deletion may vary across patients, but the deletion always occurs at the end terminal of the q arm of chromosome 11. There are three ways in which the deletion could occur:
de novo deletion- this is a random event that occurred during the formation of the sperm or the egg or during the cell division in the embryonic stage, where genes from chromosome 11 get deleted.Imbalanced translocation- in this case, a parent with balanced translocation or other types of chromosomal rearrangement can pass on these genes to their children which further results in an imbalanced translocation. The affected children have deletions on chromosome 11 as well as some extra genetic material from another chromosome.Ring chromosome 11- in this case genetic material from both long and short arm of the chromosome get deleted, and the remaining part joins and forms a ring like structure. Here the affected person would have symptoms associated with both 11q and 11p deletion.

Genetics
If de novo deletion occurs then both the parents have normal chromosomes, and chances that another child will have the deletion decline. Very few cases have been found in which the deletion has been present in mosaic form (where some of the cells have deletion on chromosome 11 and some do not, and the symptoms are less severe) in one of the parents, which increases the risk of having another child with Jacobsen syndrome. When the childs chromosomal abnormality occurs due to one of the parents balanced translocation, the chances of another child having the abnormality is high.

Diagnosis
Diagnosing Jacobsen syndrome can be difficult in some cases because it is a rare chromosomal disorder. There are a variety of tests that can be carried out, like karyotypes, cardiac echocardiograms, a renal sonogram, a platelet count, blood counts, a brain imaging study. Genetic testing can be carried out for diagnosis. Here chromosomes are stained to give a barcode like appearance and studied under the microscope, which reveals the broken and deleted genes. The condition can also be diagnosed early in the prenatal stage if there are any abnormalities seen in the ultrasound. A simple assessment of the symptoms can be done to diagnose the syndrome. A thorough physical examination could be carried out to assess the symptoms.

Treatment
There has been no treatment discovered for Jacobsen syndrome to date, but the symptoms can be treated. 56% of children with Jacobsen syndrome have congenital heart problems; to keep them in check, a baseline evaluation can be made by a paediatric cardiologist by carrying out an electrocardiogram or echocardiogram. Any problems that are found can be treated then.Monthly CBT may help ease bleeding disorders. Consecutively, platelet transfusion and ddAVP can be carried out. Medication that interferes with platelet count should be avoided, and oral contraceptive therapy may be considered for women with heavy bleeding during menses.An evaluation by a neuropsychologist or a behaviour specialist like a psychiatrist or psychologist can be performed, including brain imaging like MRI or ERP. Later, as deemed appropriate, intervention programs can be carried through. Music therapy is very beneficial for language development. According to the age, vision and hearing tests can aid in fixing problems related cognition </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 Anisocoria and can you explain it in depth? [/INST] Anisocoria is a condition characterized by an unequal size of the eyes pupils. Affecting up to 20% of the population, anisocoria is often entirely harmless, but can be a sign of more serious medical problems.

Causes
Anisocoria is a common condition, defined by a difference of 0.4 mm or more between the  sizes of the pupils of the eyes.Anisocoria has various causes:
Physiological anisocoria: About 20% of population has a slight difference in pupil size which is known as physiological anisocoria. In this condition, the difference between pupils is usually less than 1 mm.
Horners syndrome
Mechanical anisocoria: Occasionally previous trauma, eye surgery, or inflammation (uveitis, angle closure glaucoma) can lead to adhesions between the iris and the lens.
Adie tonic pupil: Tonic pupil is usually an isolated benign entity, presenting in young women. It may be associated with loss of deep tendon reflex (Adies syndrome). Tonic pupil is characterized by delayed dilation of iris especially after near stimulus, segmental iris constriction, and sensitivity of pupil to a weak solution of pilocarpine.
Oculomotor nerve palsy: Ischemia, intracranial aneurysm, demyelinating diseases (e.g., multiple sclerosis), head trauma, and brain tumors are the most common causes of oculomotor nerve palsy in adults. In ischemic lesions of the oculomotor nerve, pupillary function is usually spared whereas in compressive lesions the pupil is involved.
Pharmacological agents with anticholinergic or sympathomimetic properties will cause anisocoria, particularly if instilled in one eye.  Some examples of pharmacological agents which may affect the pupils include pilocarpine, cocaine, tropicamide, MDMA, dextromethorphan, and ergolines. Alkaloids present in plants of the genera Brugmansia and Datura, such as scopolamine, may also induce anisocoria.
Migraines

Diagnosis
Causes of anisocoria range from benign (normal) to life-threatening conditions.
Clinically, it is important to establish whether anisocoria is more apparent in dim or bright light to clarify if the larger pupil or smaller pupil is the abnormal one.

Anisocoria which is worsened (greater asymmetry between the pupils) in the dark suggests the small pupil (which should dilate in dark conditions) is the abnormal pupil and suggests Horners syndrome or mechanical anisocoria. In Horners syndrome sympathetic nerve fibers have a defect, therefore the pupil of the involved eye will not dilate in darkness. If the smaller pupil dilates in response to instillation of apraclonidine eye drops, this suggests Horners syndrome is present.
Anisocoria which is greater in bright light suggests the larger pupil (which should constrict in bright conditions) is the abnormal pupil. This may suggest Adie tonic pupil, pharmacologic dilation, oculomotor nerve palsy, or damaged iris.A relative afferent pupillary defect (RAPD) also known as a Marcus Gunn pupil does not cause anisocoria.
Some of the causes of anisocoria are
life-threatening, including Horners syndrome (which may be due to carotid artery dissection) and oculomotor nerve palsy (due to a brain aneurysm, uncal herniation, or head trauma).
If the examiner is unsure whether the abnormal pupil is the constricted or dilated one, and if a one-sided drooping of the eyelid is present then the abnormally sized pupil can be presumed to be the one on the side of the ptosis. This is because Horners syndrome and oculomotor nerve lesions both cause ptosis.
Anisocoria is usually a benign finding, unaccompanied by other symptoms (physiological anisocoria) </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 Querulant and can you explain it in depth? [/INST] In the legal profession and courts, a querulant  (from the Latin querulus - "complaining") is a person who obsessively feels wronged, particularly about minor causes of action. In particular the term is used for those who repeatedly petition authorities or pursue legal actions based on manifestly unfounded grounds. These applications include in particular complaints about petty offenses.
Querulant behavior is to be distinguished from either the obsessive pursuit of justice regarding major injustices, or the proportionate, reasonable, pursuit of justice regarding minor grievances. According to Mullen and Lester, the life of the querulant individual becomes consumed by their personal pursuit of justice in relation to minor grievances.

Use in psychiatry
In psychiatry, the terms querulous paranoia (Kraepelin, 1904) and litigious paranoia have been used to describe a paranoid condition which manifested itself in querulant behavior. The concept had, until 2004, disappeared from the psychiatric literature; largely because it had been misused to stigmatise the behavior of people seeking the resolution of valid grievances.  It also appears in ICD-10, under its Latin name Paranoia querulans, in section F22.8, "Other persistent delusional disorders".

Frequency
According to Lester et al. querulous behavior remains common, as shown in petitions to the courts and complaints organizations. They state that "persistent complainants’ pursuit of vindication and retribution fits badly with complaints systems established to deliver reparation and compensation [and that these] complainants damaged the financial and social fabric of their own lives and frightened those dealing with their claims."

See also
Idée fixe
Monomania
Persecutory delusion
Vexatious litigation

References
External links

Blaney, Paul H.; Millon, Theodore (20 November 2008). Oxford Textbook of Psychopathology. Oxford University Press. ISBN 978-0-19-988836-8.
Lee, Kyoungmi; Kim, Hakkyun; Vohs, Kathleen D </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 Accelerated idioventricular rhythm and can you explain it in depth? [/INST] Accelerated idioventricular rhythm is a ventricular rhythm with a rate of between 40 and 120 beats per minute. Idioventricular means “relating to or affecting the cardiac ventricle alone” and refers to any ectopic ventricular arrhythmia.  Accelerated idioventricular arrhythmias are distinguished from ventricular rhythms with rates less than 40 (ventricular escape) and those faster than 120 (ventricular tachycardia). Though some other references limit to between 60 and 100 beats per minute.  It is also referred to as AIVR and "slow ventricular tachycardia."
It can be present at birth. However, it is more commonly associated with reperfusion after myocardial injury </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 Empty sella syndrome and can you explain it in depth? [/INST] Empty sella syndrome is the condition when the pituitary gland shrinks or becomes flattened, filling the sella turcica  with cerebrospinal fluid instead of the normal pituitary. It can be discovered as part of the diagnostic workup of pituitary disorders, or as an incidental finding when imaging the brain.

Signs and symptoms
If there are symptoms, people with empty sella syndrome can have headaches and vision loss. Additional symptoms would be associated with hypopituitarism.
Additional symptoms are as follows:
Abnormality of the middle ear ossicles
Cryptorchidism
Dolichocephaly
Arnold-Chiari type I malformation
Meningocele
Patent ductus arteriosus
Muscular hypotonia
Platybasia

Cause
The cause of this condition is divided into primary and secondary, as follows:

The cause of this condition in terms of secondary empty sella syndrome happens when a tumor or surgery damages the gland, this is an acquired manner of the condition.
~70% of patients with idiopathic intracranial hypertension will have empty sella on MRI
The cause of primary empty sella syndrome is a congenital defect (diaphragma sellae)

Mechanism
The normal mechanism of the pituitary gland sees that it controls the hormonal system, which therefore has an effect on growth, sexual development, and adrenocortical function. The gland is divided into anterior and posterior.Its pathophysiology is such that individuals affected with the condition can have cerebrospinal fluid build-up, which in turn causes intracranial pressure leading to headaches for the individual.

Diagnosis
The diagnosis of empty sella syndrome, done via examination (and test), may be linked to early onset of puberty, growth hormone deficiency, or pituitary gland dysfunction (at an early age). Additionally there is:

CT scan
MRI scans

Classification
There are two types of empty sella syndrome: primary and secondary.

Primary empty sella syndrome occurs when a small anatomical defect above the pituitary gland increases pressure in the sella turcica and causes the gland to flatten out along the interior walls of the sella turcica cavity. Primary empty sella syndrome is associated with obesity and increase in intracranial pressure in women. In most cases, especially in people with primary empty sella syndrome, there are no symptoms and it does not affect life expectancy or health </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 Microcytic anemia and can you explain it in depth? [/INST] Microcytic anaemia is any of several types of anaemia characterized by small red blood cells (called microcytes). The normal mean corpuscular volume (abbreviated to MCV on full blood count results, and also known as mean cell volume) is approximately 80–100 fL. When the MCV is <80 fL, the red cells are described as microcytic and when >100 fL, macrocytic (the latter occurs in macrocytic anemia). The MCV is the average red blood cell size.
In microcytic anaemia, the red blood cells (erythrocytes) contain less hemoglobin and are usually also hypochromic, meaning that the red blood cells appear paler than usual. This can be reflected by a low mean corpuscular hemoglobin concentration (MCHC), a measure representing the amount of hemoglobin per unit volume of fluid inside the cell; normally about 320–360 g/L or 32–36 g/dL. Typically, therefore, anemia of this category is described as "microcytic, hypochromic anaemia".

Causes
Typical causes of microcytic anemia include:

Childhood
Iron deficiency anemia by far the most common cause of anemia in general and of microcytic anemia in particular
Thalassemia
Adulthood
Iron deficiency anemia
Thalassemia
Anemia of chronic diseaseRare hereditary causes of microcytic anemia include sideroblastic anemia and other X-linked anemias, hereditary hypotransferrinemia, hereditary aceruloplasminemia, erythropoietic protoporphyria, iron-refractory iron deficiency anemia, and other thalassemic mutations (such as hemoglobin E and hemoglobin Lepore syndrome).Rare acquired causes of microcytic anemia include lead poisoning, zinc deficiency, copper deficiency, alcohol, and certain medications.Other causes that are typically thought of as causing normocytic anemia or macrocytic anemia must also be considered, as the presence of two or more causes of anemia can distort the typical picture.

Iron Deficiency Anemia
Nearly half of all anemia cases are due to iron deficiency as it is the most common nutritional disorder. Although it is a common nutritional disorder, most causes of iron deficiency anemia (IDA) are due to blood loss. It is also more common to occur among children and females who are menstruating but can occur to any individual of any age. As well as a low MCV, diagnostic criteria includes low serum ferritin levels and transferrin saturation may also be used. Non-pharmacological measures to treat IDA include increasing sources of dietary iron, especially from heme sources such are liver, seafood, and red meats. However, these measures often take a great deal of time longer to replete iron stores compared to pharmacological agents such as iron supplements which are the mainstay of treatment. Pharmacological agents may also be required in cases where deficiency is more severe, in cases where iron loss exceeds dietary intake, and in individuals who follow a plant-based diet as non-heme sources often have lower bioavailability. When oral iron supplements are used, they should be taken on an empty stomach to increase absorption This might increase the risk of side effects however, such as nausea and epigastric pain.

Anemia of Chronic Disease
Anemia of chronic disease (ACD) is the second most common cause of anemia after IDA. It usually occurs in individuals that have chronic inflammation due to a medical condition. Both diagnosis and treatment can be difficult as there may be an overlap with iron deficiency and thus it is a diagnosis of exclusion. Since ACD is caused by an underlying disorder, complete resolution of the condition is unlikely and we focus on controlling the inflammatory disorder rather than treating the ACD itself. Potential inflammatory conditions that can cause ACD are pulmonary tuberculosis, rheumatoid arthritis, and malignancies among many others.

Thalassemia
Thalassemia is an inherited condition that has variants in alpha or beta globin genes that result in lower levels of globin chains required to make hemoglobin, resulting in alpha thalassemia or beta thalassemia, respectively. Diagnosis is made by DNA analysis for alpha thalassemia and hemoglobin analysis for beta thalassemia. Management of thalassemia involves chronic transfusions that maintain a hemoglobin level that reduces symptoms of anemia as well as suppresses extramedullary hematopoiesis which can lead to multiple morbidities. Folic acid supplements are also recommended for some cases of thalassemia.

Evaluation and Diagnosis
In theory, the three most common microcytic anemias (iron deficiency anemia, anemia of chronic disease, and thalassemia) can be differentiated by their red blood cell (RBC) morphologies </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 Salpingitis isthmica nodosa 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 Iodine deficiency and can you explain it in depth? [/INST] Iodine deficiency is a lack of the trace element iodine, an essential nutrient in the diet. It may result in metabolic problems such as goiter, sometimes as an endemic goiter as well as congenital iodine deficiency syndrome due to untreated congenital hypothyroidism, which results in developmental delays and other health problems. Iodine deficiency is an important global health issue, especially for fertile and pregnant women. It is also a preventable cause of intellectual disability.
Iodine is an essential dietary mineral for neurodevelopment among children. The thyroid hormones thyroxine and triiodothyronine contain iodine. In areas where there is little iodine in the diet, typically remote inland areas where no marine foods are eaten, iodine deficiency is common. It is also common in mountainous regions of the world where food is grown in iodine-poor soil.
Prevention includes adding small amounts of iodine to table salt, a product known as iodized salt. Iodine compounds have also been added to other foodstuffs, such as flour, water and milk, in areas of deficiency. Seafood is also a well known source of iodine.In the U.S., the use of iodine has decreased over concerns of overdoses since mid-20th century, and the iodine antagonists bromine, perchlorate and fluoride have become more ubiquitous. In particular, around 1980 the practice of using potassium iodate as dough conditioner in bread and baked goods was gradually replaced by the use of other conditioning agents such as bromide.Iodine deficiency resulting in goiter occurs in 187 million people globally as of 2010 (2.7% of the population). It resulted in 2700 deaths in 2013, up from 2100 deaths in 1990.

Signs and symptoms
Goiter
A low amount of thyroxine (one of the two thyroid hormones) in the blood, due to lack of dietary iodine to make it, gives rise to high levels of thyroid stimulating hormone (TSH), which stimulates the thyroid gland to increase many biochemical processes; the cellular growth and proliferation can result in the characteristic swelling or hyperplasia of the thyroid gland, or goiter. In mild iodine deficiency, levels of triiodothyronine (T3) may be elevated in the presence of low levels of levothyroxine, as the body converts more of the levothyroxine to triiodothyronine as a compensation. Some such patients may have a goiter, without an elevated TSH. The introduction of iodized salt since the early 1900s has eliminated this condition in many affluent countries; however, in Australia, New Zealand, and several European countries, iodine deficiency is a significant public health problem. It is more common in developing countries. Public health initiatives to lower the risk of cardiovascular disease have resulted in lower discretionary salt use at the table. Additionally, there is a trend towards consuming more processed foods in western countries. The noniodized salt used in these foods means that people are less likely to obtain iodine from adding salt during cooking.
Goiter is said to be endemic when the prevalence in a population is > 5%, and in most cases goiter can be treated with iodine supplementation. If goiter is untreated for around five years, however, iodine supplementation or thyroxine treatment may not reduce the size of the thyroid gland because the thyroid is permanently damaged.

Congenital iodine deficiency syndrome
Congenital iodine deficiency syndrome, previously known as cretinism, is a condition associated with iodine deficiency and goiter, commonly characterised by mental deficiency, deafness, squint, disorders of stance and gait and stunted growth due to hypothyroidism. Paracelsus was the first to point out the relation between goitrous parents and their mentally disabled children.As a result of restricted diet, isolation, intermarriage, etc., as well as low iodine content in their food, children often had peculiar stunted bodies and retarded mental faculties, a condition later known to be associated with thyroid hormone deficiency. Diderot, in his 1754 Encyclopédie, described these patients as "crétins". In French, the term "crétin des Alpes" also became current, since the condition was observed in remote valleys of the Alps in particular. The word cretin appeared in English in 1779.
While reporting recent progress towards overcoming iodine-deficiency disorders worldwide, The Lancet noted: "According to World Health Organization, in 2007, nearly 2 billion individuals had insufficient iodine intake, a third being of school age." A conclusion was made that the single most preventable cause of intellectual disability is that of iodine deficiency.

Fibrocystic breast changes
There is preliminary evidence that iodine deficiency enhances the sensitivity of breast tissue to estrogen. In rats treated with estradiol, iodine deficiency has been shown to lead to changes similar to benign breast changes that are reversible by increased iodine in the diet. In a few studies, iodine supplementation had beneficial effects (such as reducing the presence of breast cyst, fibrous tissue plaques and breast pain) in women with fibrocystic breast changes.Protective effects of iodine on breast cancer have been postulated from epidemiologic evidence and described in animal models. In view of the antiproliferative properties of iodine in breast tissue, molecular iodine supplementation has been suggested as an adjuvant in breast cancer therapy.

Risk factors
Following is a list of potential risk factors that may lead to iodine deficiency:
Low dietary iodine
Selenium deficiency
Pregnancy
Exposure to radiation
Increased intake/plasma levels of goitrogens, such as calcium
Sex (higher occurrence in women)
Smoking tobacco
Alcohol (reduced prevalence in users)
Oral contraceptives (reduced prevalence in users)
Perchlorates
Thiocyanates
Age (for different types of iodine deficiency at different ages)

Pathophysiology
Iodine accounts for 65% of the molecular weight of T4 and 59% of T3.  There is a total of 15–20 mg of iodine in the human body, primarily concentrated in thyroid tissue and hormones. Thirty percent of iodine is distributed in other tissues, including the mammary glands, eyes, gastric mucosa, choroid plexus, arterial walls, the cervix, and salivary glands. In the cells of these tissues, iodide enters directly by sodium-iodide symporter (NIS).

Venturi S, Guidi A, Venturi M (1996). "[Extrathyroid iodine deficiency disorders: what is the real iodine requirement?]"". Le Basi Razionali della Terapia. 16: 267–275.
Pellerin P (1961). "La tecnique dautoradiographie anatomique a la temperature de lazote liquide". Path Biol. 232 (9): 233–252.

Diagnosis
The diagnostic workup of a suspected iodine deficiency includes signs and symptoms as well as possible risk factors mentioned above. A 24-hour urine iodine collection is a useful medical test, as approximately 90% of ingested iodine is excreted in the urine. For the standardized 24-hour test, a 50 mg iodine load is given first, and 90% of this load is expected to be recovered in the urine of the following 24 hours. Recovery of less than 90% is taken to mean high retention, that is, iodine deficiency. The recovery may, however, be well less than 90% during pregnancy, and an intake of goitrogens can alter the test results.If a 24-hour urine collection is not practical, a random urine iodine-to-creatinine ratio can alternatively be used. However, the 24-hour test is found to be more reliable.A general idea of whether a deficiency exists can be determined through a functional iodine test in the form of an iodine skin test. In this test, the skin is painted with an iodine solution: if the iodine patch disappears quickly, this is taken as a sign of iodine deficiency. However, no accepted norms exist on the expected time interval for the patch to disappear, and in persons with dark skin color the disappearance of the patch may be difficult to assess. If a urine test is taken shortly after, the results may be altered due to the iodine absorbed previously in a skin test.

Treatment
Iodine deficiency is treated by ingestion of iodine salts, such as found in food supplements. Mild cases may be treated by using iodized salt in daily food consumption, or drinking more milk, or eating egg yolks, and saltwater fish.  For a salt and/or animal product restricted diet, sea vegetables (kelp, hijiki, dulse, nori (found in sushi)) may be incorporated regularly into a diet as a good source of iodine.The recommended daily intake of iodine for adult women is 150–300 µg for maintenance of normal thyroid function; for men, it is somewhat less at 150 µg.Nonetheless, there is a lack of evidence on iodine fortification in foods, beverages, condiments, or seasonings other than salt in preventing goiter or improving physical development. On the other hand, such a measure may increase iodine concentration in urine.However, too high iodine intake, for example due to overdosage of iodine supplements, can have toxic side effects. It can lead to hyperthyroidism and consequently high blood levels of thyroid hormones (hyperthyroxinemia). In case of extremely high single-dose iodine intake, typically a short-term suppression of thyroid function (Plummer effect and Wolff–Chaikoff effect) occurs. Persons with pre-existing thyroid disease, elderly persons, fetuses and neonates, and patients with other risk factors are at a higher risk of experiencing iodine-induced thyroid abnormalities. In particular, in persons with goiter due to iodine deficiency or with altered thyroid function, a form of hyperthyroidism called Jod-Basedow phenomenon can be triggered even at small or single iodine dosages, for example as a side effect of administration of iodine-containing contrast agents. In some cases, excessive iodine contributes to a risk of autoimmune thyroid diseases (Hashimotos thyroiditis and Graves disease).
Different experts in nutrition advise different amounts of iodine supplementation.  Supplementation is typically in a product which contains roughly half iodine and half iodide (a popular product used and sold for decades is “Iodoral®” which contains 5 mg of Iodine and 7.5 mg of Iodide).
On low side there is Kara Fitzgerald recommending less than 1,100 mcg per day (except when treating some medical conditions), she considers long term dosage of 40,000 mcg per day “excessive”.  In the middle we have Dr. Alan Gaby who considers a “moderately high dose” to be 3,000 to 6,000 mcg per day.   On the higher end we have Dr. David Brownstein, Dr. Jorge Flechas, Dr. Guy Abraham, Dr. Alan Roby and Dr. Jonathan Wright who recommend 6,000 mcg to 50,000 mcg per day.

Prognosis
With iodine supplementation, goiters caused by iodine deficiency decrease in size in very young children and pregnant women. Generally, however, long-standing goiters caused by iodine deficiency respond with only small amounts of shrinkage after iodine supplementation, and patients are at risk for developing hyperthyroidism.Being pregnant while iodine-deficient additionally carries the risk of causing congenital iodine deficiency syndrome in the newborn. This disease can only be managed by lifelong administration of thyroxine (T4).

Epidemiology
Iodine deficiency resulting in goiter occurs in 187 million people globally as of 2010 (2.7% of the population). Certain areas of the world, due to natural deficiency and unavailability of iodine, are severely affected by iodine deficiency, which affects approximately two billion people worldwide. It is particularly common in the Western Pacific, South-East Asia and Africa. Among other nations affected by iodine deficiency, China and Kazakhstan have begun taking action, while Russia has not. Successful campaigns for the adoption of the use of iodized salt require education of salt producers and sellers and a communication campaign directed at the public. The cost of adding iodine to salt is negligible—"Only a few cents a ton."Iodine deficiency has largely been confined to the developing world for several generations, but reductions in salt consumption and changes in dairy processing practices eliminating the use of iodine-based disinfectants have led to increasing prevalence of the condition in Australia and New Zealand in recent years.  A proposal to mandate the use of iodized salt in most commercial breadmaking was adopted in Australia in October 2009. In a study of the United Kingdom published in 2011, almost 70% of test subjects were found to be iodine deficient. The studys authors suggested an investigation regarding "evidence-based recommendations for iodine supplementation".Micronutrient deficiencies, including iodine deficiency, impair the development of intelligence. Lacking iodine during human development causes a fall, in average, of 12 intelligence quotient (IQ) points in China. A study of U.S. military data collected during the First and Second World Wars found that the introduction of salt iodization in the U.S. in the 1920s resulted in an increase in IQ, by approximately one standard deviation, for the quarter of the U.S. population most deficient in iodine, explaining about "one decades worth of the upward trend in IQ" in the U.S. (i.e., the Flynn effect). The same study documented "a large increase in thyroid-related deaths following the countrywide adoption of iodized salt, which affected mostly older individuals in localities with high prevalence of iodine deficiency".In iodine-deficient or mildly iodine-deficient areas of Europe, iodine deficiency is frequent during pregnancy despite the widespread use of iodised salt, posing risks to the neurodevelopment of foetuses. In one study performed in a mildly iodine-deficient area, iodine deficiency was found to be present in more than half of breastfeeding women; in contrast, the majority of their newborns had iodine excess, mostly due to neonatal exposure to iodine-containing disinfectants. A 2014 meta-analysis found that iodine supplementation "improves some maternal thyroid indices and may benefit aspects of cognitive function in school-age children, even in marginally iodine-deficient areas".

Deficient populations
In areas where there is little iodine in the diet, typically remote inland areas and semi-arid equatorial climates where no marine foods are eaten, iodine deficiency gives rise to hypothyroidism, symptoms of which are extreme fatigue, goiter, mental slowing, depression, weight gain, and low basal body temperatures.Iodine deficiency is the leading cause of preventable mental retardation, a result which occurs primarily when babies or small children are rendered hypothyroidic by a lack of the element. The addition of iodine to table salt has largely eliminated this problem in the wealthier nations, but as of March 2006, iodine deficiency remained a serious public health problem in the developing world.Iodine deficiency is also a problem in certain areas of Europe. In Germany it has been estimated to cause a billion dollars in health care costs per year. A modelling analysis suggests universal iodine supplementation for pregnant women in England may save £199 (2013 UK pounds) to the health service per pregnant woman and save £4476 per pregnant woman in societal costs.Iodine deficiency was previously a common disease in Norway, because the content of iodine in the drinking water was low.  Before 1950 goiter was a widespread disease caused by iodine deficiency. Up to 80 per cent of the population were affected in inland areas </s>