<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 Midline cervical cleft 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 Antibiotic-associated diarrhea and can you explain it in depth? [/INST] Antibiotic-associated diarrhea (AAD) results from an imbalance in the colonic microbiota caused by antibiotics. Microbiotal alteration changes carbohydrate metabolism with decreased short-chain fatty acid absorption and an osmotic diarrhea as a result </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 Atypical hemolytic uremic syndrome and can you explain it in depth? [/INST] Atypical hemolytic uremic syndrome (aHUS) is an extremely rare, life-threatening, progressive disease that frequently has a genetic component. In most cases it can be effectively controlled by interruption of the complement cascade. Particular monoclonal antibodies, discussed later in the article, have proven efficacy in many cases.
AHUS is usually caused by chronic, uncontrolled activation of the complement system, a branch of the bodys immune system that destroys and removes foreign particles.  The disease affects both children and adults and is characterized by systemic thrombotic microangiopathy (TMA), the formation of blood clots in small blood vessels throughout the body, which can lead to stroke, heart attack, kidney failure, and death. The complement system activation may be due to mutations in the complement regulatory proteins (factor H, factor I, or membrane cofactor protein), or is occasionally due to acquired neutralizing autoantibody inhibitors of these complement system components, for example anti–factor H antibodies.: 1933    Prior to availability of eculizumab (Soliris)and ravulizumab(Ultomiris), an estimated 33–40% of patients died or developed end-stage renal disease (ESRD) (despite the use of supportive care, e.g. plasmapheresis) with the first clinical bout of aHUS. Including subsequent relapses, a total of approximately two-thirds (65%) of patients died, required dialysis, or had permanent renal damage within the first year after diagnosis despite plasma exchange or plasma infusion (PE/PI).

Signs and symptoms
Clinical signs and symptoms of complement-mediated TMA can include abdominal pain, confusion, fatigue, edema (swelling), nausea/vomiting and diarrhea.  aHUS often presents with malaise and fatigue, as well as microangiopathic anemia.: 1931  However, severe abdominal pain and bloody diarrhea are unusual.: 1931   Laboratory tests may also reveal low levels of platelets (cells in the blood that aid in clotting), elevated lactate dehydrogenase (LDH, a chemical released from damaged cells, and which is therefore a marker of cellular damage), decreased haptoglobin (indicative of the breakdown of red blood cells), anemia (low red blood cell count)/schistocytes (damaged red blood cells), elevated creatinine (indicative of kidney dysfunction), and proteinuria (indicative of kidney injury). Patients with aHUS often present with an abrupt onset of systemic signs and symptoms such as acute kidney failure, hypertension (high blood pressure), myocardial infarction (heart attack), stroke, lung complications, pancreatitis (inflammation of the pancreas), liver necrosis (death of liver cells or tissue), encephalopathy (brain dysfunction), seizure, or coma. Failure of neurologic, cardiac, kidney, and gastrointestinal (GI) organs, as well as death, can occur unpredictably at any time, either very quickly or following prolonged symptomatic or asymptomatic disease progression. For example, approximately 1 in 6 patients with aHUS initially will present with proteinuria or hematuria without acute kidney failure. Patients who survive the presenting signs and symptoms endure a chronic thrombotic and inflammatory state, which puts many of them at lifelong elevated risk of sudden blood clotting, kidney failure, other severe complications and premature death.

Comorbidities
Although many patients experience aHUS as a single disease, comorbidities are common. In one study, 25% (47/191) of patients with no known family history of aHUS were found to have a coexisting disease or condition. Comorbidities in this study included malignant hypertension (30%), TMA with a history of transplant (23%), TMA associated with pregnancy (21%), glomerulopathy (17%), systemic disease such as systemic lupus erythematosus (SLE) or progressive systemic sclerosis (PSS) (6%), and malignancy (1%). The presence of mutations in complement regulatory proteins, or of disease-associated variations in the genes encoding these proteins (i.e., in most patients with comorbid conditions as well as in patients with aHUS as a single disease), suggests that deviations from the normal genetic coding of these factors could result in a genetic predisposition to TMA. Individuals so predisposed could have aHUS episodes precipitated by one of the known disease triggers (e.g., infection, pregnancy, surgery, trauma) as well as by other systemic diseases (e.g., malignant hypertension, SLE, cancer).

Mechanisms
In healthy individuals, complement is used to attack foreign substances, and the complement system is highly regulated to prevent it from damaging healthy tissues and organs. However, in most patients with aHUS, it has been demonstrated that chronic, uncontrolled, and excessive activation of complement can result from production of anti-factor H autoantibodies or from genetic mutations in any of several complement regulatory proteins (e.g., factor H, factor HR1 or HR3, membrane cofactor protein, factor I, factor B, complement C3, and thrombomodulin). This results in platelet activation, damage to endothelial cells (cells that line the blood vessels), and white blood cell activation, leading to systemic TMA, which manifests as decreased platelet count, hemolysis (breakdown of red blood cells), damage to multiple organs, and often, death.

Diagnosis
aHUS is not the only condition that causes systemic TMA, a fact that makes differential diagnosis essential. Historically, the clinical diagnosis of TMA-causing diseases was grouped into a broad category that (in addition to aHUS) included thrombotic thrombocytopenic purpura (TTP) and Shiga-toxin-producing Escherichia coli hemolytic uremic syndrome (STEC-HUS). However, it is now understood that although aHUS, STEC-HUS, and TTP have similar clinical presentations, they have distinct causes and specific tests can be conducted to differentiate these diseases. In addition, there are other conditions that can cause TMA as a secondary manifestation; these entities include systemic lupus erythematosus (SLE), malignant hypertension, progressive systemic sclerosis (PSS, also known as scleroderma), the pregnancy-associated HELLP (hemolysis, liver dysfunction, and low platelets) syndrome, and toxic drug reaction (e.g., to cocaine, cyclosporine, or tacrolimus).  Nevertheless, aHUS should be suspected in patients presenting with systemic TMA, and appropriate diagnostic work-up should be undertaken.The neurological and kidney-related signs and symptoms of aHUS overlap with those of TTP. However, unlike aHUS, TTP is primarily an autoimmune disorder in which the presence of an inhibitory autoantibody results in severe deficiency of ADAMTS13, an enzyme that cleaves von Willebrand factor (vWf), a large protein involved in blood clotting, into smaller pieces. (TTP also can be a genetic disorder characterized by mutations in the ADAMTS13 gene leading to severe ADAMTS13 deficiency. This congenital cause of ADAMTS13 deficiency is called Upshaw-Schülman syndrome.) A lab test showing ADAMTS13 activity levels of ≤5% is indicative of TTP.Similarly, the gastrointestinal (GI) signs and symptoms of aHUS overlap with those of STEC-HUS. Stool samples from patients with diarrhea or other GI symptoms should be tested for STEC and the presence of Shiga-toxin. However, a positive identification of Shiga-toxin, which is required to diagnose STEC-HUS, does not rule out aHUS. Nevertheless, in the appropriate clinical setting, a positive identification of Shiga-toxin makes aHUS very unlikely.aHUS patients report a mean timeline of  29 days for  the overall diagnosis process from first noticing symptoms to receiving an aHUS diagnosis. During which time they report their overall health state drops from 88% of patients feeling good to excellent, to 99% feeling good to very poor and a more than halving of their health status index from 3.8 (on a scale of 1 to 5) pre-illness to 1.4 at diagnosis.

Treatment
Plasma exchange/infusion
Although plasma exchange/infusion (PE/PI) is frequently used, there are no controlled trials of its safety or efficacy in aHUS. Even though PE/PI often partially controls some of the hematological manifestations of aHUS in some patients, its effectiveness has not been demonstrated in terms of inducing total disease remission.  PE/PI is associated with significant safety risks, including risk of infection, allergic reactions, thrombosis, loss of vascular access, and poor quality of life. Importantly, terminal complement activation has been shown to be chronically present on the surface of platelets in patients with aHUS who appear to be clinically well while receiving chronic PE/PI.Guidelines issued by the European Paediatric Study Group for HUS recommend rapid administration of plasma exchange or plasma infusion (PE/PI), intensively administered daily for 5 days and then with reducing frequency. However, the American Society for Apheresis offers a "weak" recommendation for plasma exchange to treat aHUS, due to the "low" or "very low" quality of evidence supporting its use. Although some patients experienced improvements in red blood cell and platelet counts, plasma therapies generally did not result in full remission.

Monoclonal antibody therapy
Eculizumab (Soliris) appears to be useful for atypical hemolytic uremic syndrome (aHUS). In September 2011 the U.S. Food and Drug Administration (FDA) approved it as an orphan drug to treat people with aHUS. This approval was based on two small prospective trials of 17 people and 20 people. In the UK, NICE issued guidance on the use of Eculizumab for treating aHUS, based on five evidence sources, including those used by the FDA No randomised controlled trials were identified. All prospective studies were phase 2, open‑label, non‑randomised, single‑arm studies that included patients with different clinical baseline characteristics. The prospective studies lasted 26 weeks; however, patients were allowed to continue treatment with eculizumab in a long‑term extension study.Ravulizumab-cwvz (Ultomiris) is a second generation monoclonal antibody for aHUS made by Alexion pharmaceuticals, Inc. The target of ravulizumab-cwvz is the same eculizumab (Soliris) with changes to the structure of the antibody resulting in a longer serum half life and therefore reduced dosing regimen.

Dialysis
Patients with aHUS who have ESRD are generally consigned to lifelong dialysis, which carries a 5-year survival rate of 34–38%, with infections accounting for 14% of deaths. These patients also remain at ongoing risk of non-kidney systemic complications of the disease.

Kidney transplantation
Despite its history of use in patients with aHUS, kidney transplantation does not address the continued and uncontrolled complement activation that leads to progressive, systemic TMA. As many as 90% of patients with aHUS and who are not treated with Soliris or Ultomiris, experience TMA in the transplanted organ, leading to transplant failure. Patients who have undergone kidney transplantation are still at continued risk of neurological, gastrointestinal, and cardiovascular complications and, importantly, premature mortality. Following kidney transplantation, the ongoing, uncontrolled, chronic complement activation associated with aHUS causes graft loss in 66% of children and 55% of adults, as well as continued inflammatory and TMA insult to other organs. Combined liver-kidney transplantation is only available to very few patients, due to the limited supply of solid organs. In addition, there is a substantial near-term risk of mortality, which many physicians and patients consider excessive. In recent years, some transplant centers have begun to administer eculizumab to patients with TMA who receive a kidney transplant. This strategy has been effective in preventing TMA recurrences in these patients.

Terminal complement inhibition
Patients using either eculizumab or ravulizumab for the treatment of aHUS showed improvements in kidney function even avoiding dialysis and minimizing death. Markers of disease activity in the blood also had a great improvement. However, the only available evidence has substantial bias and low quality and therefore there should be careful considerations for futures studies in treatment duration, adverse outcomes and risk of disease recurrence associated with this treatment.

Historical Prognosis
Prior to the use of monoclonal antibodies(e.g., Soliris, Ultomiris) patients with aHUS had an extremely poor prognosis. Among those with the most commonly identified aHUS genetic mutation, the proportion of patients experiencing negative outcomes (e.g., need for dialysis, permanent kidney damage, death) within the first year rose to 70% </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 Scarlet fever and can you explain it in depth? [/INST] Scarlet fever is an infectious disease resulting from a group A streptococcus (group A strep) infection, also known as Streptococcus pyogenes. The signs and symptoms include a sore throat, fever, headaches, swollen lymph nodes, and a characteristic rash. The rash is red and feels like sandpaper and the tongue may be red and bumpy. It most commonly affects children between five and 15 years of age.Scarlet fever affects a small number of people who have strep throat or streptococcal skin infections. The bacteria are usually spread by people coughing or sneezing. It can also be spread when a person touches an object that has the bacteria on it and then touches their mouth or nose. The characteristic rash is due to the erythrogenic toxin, a substance produced by some types of the bacterium. The diagnosis is typically confirmed by culturing the throat.There is no vaccine for scarlet fever. Prevention is by frequent handwashing, not sharing personal items, and staying away from other people when sick. The disease is treatable with antibiotics, which prevent most complications. Outcomes with scarlet fever are typically good if treated. Long-term complications as a result of scarlet fever include kidney disease, rheumatic heart disease, and arthritis. In the early 20th century, before antibiotics were available, it was a leading cause of death in children. An antitoxin was produced before antibiotics; however, it was never made in sufficient quantities, and could not be used to treat any other disease as antibiotics can.There have been signs of antibiotic resistance, and there have been recent outbreaks in Hong Kong in 2011 and in the UK in 2014, with occurrence rising 68% in the UK in the four years up to 2018. Research published in October 2020 has shown that infection of the bacterium by three viruses has led to stronger strains of the bacterium.

Signs and symptoms
Rash which has a characteristic appearance, spreading pattern, and desquamating process e.g.
"Strawberry tongue":

The tongue initially has a white coating on it, while the papillae of the tongue are swollen and reddened. The protrusion of the red papillae through the white coating gives the tongue a "white strawberry" appearance.
A few days later (following the desquamating process, or the shedding of the tissue which created the white coating), the whiteness disappears, and the red and enlarged papillae give the tongue the "red strawberry" appearance. The symptomatic appearance of the tongue is part of the rash that is characteristic of scarlet fever.
Pastias lines
Lines of petechiae, which appear as pink/red areas located in arm pits and elbow pits
Vomiting and abdominal pain

Strep throat
Typical signs and symptoms of streptococcal pharyngitis (also known as strep throat):
Sore throat, painful swallowing
Fever – typically over 39 °C (102.2 °F)
Fatigue
Enlarged and reddened tonsils with yellow or white exudates present (this is typically an exudative pharyngitis)
Enlarged and tender lymph nodes usually located on the front of the neckThe following signs will usually be absent: cough, hoarseness, runny nose, diarrhea, and conjunctivitis. Such symptoms indicate what is more likely a viral infection.

Rash
The rash begins 1–2 days following the onset of symptoms caused by the strep pharyngitis (sore throat, fever, fatigue). This characteristic rash has been denoted as "scarlatiniform", and it appears as a diffuse redness of the skin with small papules, or bumps, which resemble goose bumps. These bumps are what give the characteristic sandpaper texture to the rash. The reddened skin will blanch when pressure is applied to it. The skin may feel itchy, but it will not be painful. The rash generally starts at the flexion of the elbow and other surfaces. It appears next on the trunk and gradually spreads out to the arms and legs. The palms, soles and face are usually left uninvolved by the rash. The face, however, is usually flushed, most prominently in the cheeks, with a ring of paleness around the mouth. After the rash spreads, it becomes more pronounced in creases in the skin, such as the skin folds in the inguinal and axillary regions of the body. Also in those areas, Pastias Lines may appear: petechiae arranged in a linear pattern. Within 1 week of onset, the rash begins to fade followed by a longer process of desquamation, or shedding of the outer layer of skin. This lasts several weeks. The desquamation process usually begins on the face and progresses downward on the body. After the desquamation, the skin will be left with a sunburned appearance.

Mouth
The streptococcal pharyngitis, which is the usual presentation of scarlet fever in combination with the characteristic rash, commonly involves the tonsils. The tonsils will appear swollen and reddened. The palate and uvula are also commonly affected by the infection. The involvement of the soft palate can be seen as tiny red and round spots known as Forchheimer spots.

Variable presentations
The features of scarlet fever can differ depending on the age and race of the person. Children less than 5 years old can have atypical presentations. Children less than 3 years old can present with nasal congestion and a lower grade fever. Infants may present with symptoms of increased irritability and decreased appetite.Children who have darker skin can have a different presentation, as the redness of the skin involved in the rash and the ring of paleness around the mouth can be less obvious. Suspicion based on accompanying symptoms and diagnostic studies are important in these cases.

Course
Following exposure to streptococcus, onset of symptoms occur 12 hours to 7 days later. These may include fever, fatigue, and sore throat. The characteristic scarlatiniform rash appears 12–48 hours later. During the first few days of the rash development and rapid generalization, the Pastias Lines and strawberry tongue are also present. The rash starts fading within 3–4 days, followed by the desquamation of the rash, which lasts several weeks to a month. If the case of scarlet fever is uncomplicated, recovery from the fever and clinical symptoms, other than the process of desquamation, occurs in 5–10 days.

Complications
The complications, which can arise from scarlet fever when left untreated or inadequately treated, can be divided into two categories: suppurative and nonsuppurative.Suppurative complications: These are rare complications that arise either from direct spread to structures that are close to the primary site of infection, or spread through the lymphatic system or blood. In the first case, scarlet fever may spread to the pharynx. Possible problems from this method of spread include peritonsillar or retropharyngeal abscesses, cellulitis, mastoiditis or sinusitis.In the second case, the streptococcal infection may spread through the lymphatic system or the blood to areas of the body further away from the pharynx. A few examples of the many complications that can arise from those methods of spread include endocarditis, pneumonia, or meningitis.Nonsuppurative complications: These complications arise from certain subtypes of group A streptococci that cause an autoimmune response in the body through what has been termed molecular mimicry. In these cases, the antibodies which the persons immune system developed to attack the group A streptococci are also able to attack the persons own tissues. The following complications result, depending on which tissues in the persons body are targeted by those antibodies.
Acute rheumatic fever: This is a complication that results 2–6 weeks after a group A streptococcal infection of the upper respiratory tract. It presents in developing countries, where antibiotic treatment of streptococcal infections is less common, as a febrile illness with several clinical manifestations, which are organized into what is called the Jones criteria. These criteria include arthritis, carditis, neurological issues, and skin findings. Diagnosis also depends on evidence of a prior group A streptococcal infection in the upper respiratory tract (as seen in streptococcal pharyngitis and scarlet fever). The carditis is the result of the immunologic response targeting the persons heart tissue, and it is the most serious sequelae that develops from acute rheumatic fever. When this involvement of the heart tissue occurs, it is called rheumatic heart disease. In most cases of rheumatic heart disease, the mitral valve is affected, ultimately leading to mitral stenosis. The link to rheumatic fever and heart disease is a particular concern in Australia, because of the high prevalence of these diseases in Aboriginal and Torres Strait Islander communities.
Poststreptococcal glomerulonephritis: This is inflammation of the kidney, which presents 1–2 weeks after a group A streptococcal pharyngitis. It can also develop after an episode of Impetigo or any group A streptococcal infection in the skin (this differs from acute rheumatic fever which only follows group A streptococcal pharyngitis). It is the result of the autoimmune response to the streptococcal infection affecting part of the kidney. Persons present with what is called acute nephritic syndrome, in which they have high blood pressure, swelling, and urinary abnormalities. Urinary abnormalities include blood and protein found in the urine, as well as less urine production overall.
Poststreptococcal reactive arthritis: The presentation of arthritis after a recent episode of group A streptococcal pharyngitis raises suspicion for acute rheumatic fever, since it is one of the Jones criteria for that separate complication. But, when the arthritis is an isolated symptom, it is referred to as poststreptococcal reactive arthritis. This arthritis can involve a variety of joints throughout the body, unlike the arthritis of acute rheumatic fever, which primarily affects larger joints such as the knee joints. It can present less than 10 days after the group A streptococcal pharyngitis.

Cause
Strep throat spreads by close contact among people, via respiratory droplets (for example, saliva or nasal discharge). A person in close contact with another person infected with group A streptococcal pharyngitis has a 35% chance of becoming infected. One in ten children who are infected with group A streptococcal pharyngitis will develop scarlet fever.

Pathophysiology
The rash of scarlet fever, which is what differentiates this disease from an isolated group A strep pharyngitis (or strep throat), is caused by specific strains of group A streptococcus which produce a pyrogenic exotoxin, mainly responsible for the skin manifestation of the infection. These toxin-producing strains cause scarlet fever in people who do not already have antitoxin antibodies. Streptococcal pyrogenic exotoxins A, B, and C (speA, speB, and speC) have been identified. The pyrogenic exotoxins are also called erythrogenic toxins and cause the erythematous rash of scarlet fever. The strains of group A streptococcus that cause scarlet fever need specific bacteriophages for there to be pyrogenic exotoxin production. Specifically, bacteriophage T12 is responsible for the production of speA. Streptococcal Pyrogenic Exotoxin A, speA, is the one which is most commonly associated with cases of scarlet fever which are complicated by the immune-mediated sequelae acute rheumatic fever and post-streptococcal glomerulonephritis.These toxins are also known as "superantigens" because they are able to cause an extensive immune response within the body through activation of some of the main cells responsible for the persons immune system. The body responds to these toxins by making antibodies to those specific toxins. However, those antibodies do not completely protect the person from future group A streptococcal infections, because there are 12 different pyrogenic exotoxins possible.

Microbiology
The disease is caused by secretion of pyrogenic exotoxins by the infecting Streptococcus bacteria. Streptococcal pyrogenic exotoxin A (speA) is probably the best studied of these toxins. It is carried by the bacteriophage T12 which integrates into the streptococcal genome from where the toxin is transcribed. The phage itself integrates into a serine tRNA gene on the chromosome.The T12 virus itself has not been placed into a taxon by the International Committee on Taxonomy of Viruses. It has a double-stranded DNA genome and on morphological grounds appears to be a member of the Siphoviridae.The speA gene was cloned and sequenced in 1986. It is 753 base pairs in length and encodes a 29.244 kiloDalton (kDa) protein. The protein contains a putative 30-
amino-acid signal peptide; removal of the signal sequence gives a predicted molecular weight of 25.787 kDa for the secreted protein. Both a promoter and a ribosome binding site (Shine-Dalgarno sequence) are present upstream of the gene. A transcriptional terminator is located 69 bases downstream from the translational termination codon. The carboxy terminal portion of the protein exhibits extensive homology with the carboxy terminus of Staphylococcus aureus enterotoxins B and C1.Streptococcal phages other than T12 may also carry the speA gene.

Diagnosis
Although the presentation of scarlet fever can be clinically diagnosed, further testing may be required to distinguish it from other illnesses. Also, history of a recent exposure to someone with strep throat can be useful in diagnosis. There are two methods used to confirm suspicion of scarlet fever; rapid antigen detection test and throat culture.The rapid antigen detection test is a very specific test but not very sensitive. This means that if the result is positive (indicating that the group A strep antigen was detected and therefore confirming that the person has a group A strep pharyngitis), then it is appropriate to treat the people with scarlet fever with antibiotics. But, if the rapid antigen detection test is negative (indicating that they do not have group A strep pharyngitis), then a throat culture is required to confirm, as the first test could have yielded a false negative result. In the early 21st century, the throat culture is the current "gold standard" for diagnosis.Serologic testing seeks evidence of the antibodies that the body produces against the streptococcal infection, including antistreptolysin-O and antideoxyribonuclease B. It takes the body 2–3 weeks to make these antibodies, so this type of testing is not useful for diagnosing a current infection. But, it is useful when assessing a person who may have one of the complications from a previous streptococcal infection.Throat cultures done after antibiotic therapy can show if the infection has been removed. These throat swabs, however, are not indicated, because up to 25% of properly treated individuals can continue to carry the streptococcal infection while being asymptomatic.

Differential diagnosis
Viral exanthem: Viral infections are often accompanied by a rash which can be described as morbilliform or maculopapular. This type of rash is accompanied by a prodromal period of cough and runny nose in addition to a fever, indicative of a viral process.
Allergic or contact dermatitis: The erythematous appearance of the skin will be in a more localized distribution rather than the diffuse and generalized rash seen in scarlet fever.
Drug eruption: These are potential side effects of taking certain drugs such as penicillin. The reddened maculopapular rash which results can be itchy and be accompanied by a fever.
Kawasaki disease: Children with this disease also present a strawberry tongue and undergo a desquamative process on their palms and soles. However, these children tend to be younger than 5 years old, their fever lasts longer (at least five days), and they have additional clinical criteria (including signs such as conjunctival redness and cracked lips), which can help distinguish this from scarlet fever.
Toxic shock syndrome: Both streptococcal and staphylococcal bacteria can cause this syndrome. Clinical manifestations include diffuse rash and desquamation of the palms and soles. It can be distinguished from scarlet fever by low blood pressure, lack of sandpaper texture for the rash, and multi-organ system involvement.
Staphylococcal scalded skin syndrome: This is a disease that occurs primarily in young children due to a toxin-producing strain of the bacteria Staphylococcus aureus. The abrupt start of the fever and diffused sunburned appearance of the rash can resemble scarlet fever. However, this rash is associated with tenderness and large blister formation. These blisters easily pop, followed by causing the skin to peel.
Staphylococcal scarlet fever: The rash is identical to the streptococcal scarlet fever in distribution and texture, but the skin affected by the rash will be tender.

Prevention
One method is long-term use of antibiotics to prevent future group A streptococcal infections. This method is only indicated for people who have had complications like recurrent attacks of acute rheumatic fever or rheumatic heart disease. Antibiotics are limited in their ability to prevent these infections since there are a variety of subtypes of group A streptococci that can cause the infection.The vaccine approach has a greater likelihood of effectively preventing group A streptococcal infections because vaccine formulations can target multiple subtypes of the bacteria. A vaccine developed by George and Gladys Dick in 1924 was discontinued due to poor efficacy and the introduction of antibiotics. Difficulties in vaccine development include the considerable strain variety of group A streptococci present in the environment and the amount of time and number of people needed for appropriate trials for safety and efficacy of any potential vaccine. There have been several attempts to create a vaccine in the past few decades. These vaccines, which are still in the development phase, expose the person to proteins present on the surface of the group A streptococci to activate an immune response that will prepare the person to fight and prevent future infections.There used to be a diphtheria scarlet fever vaccine. It was, however, found not to be effective. This product was discontinued by the end of World War II.

Treatment
Antibiotics to combat the streptococcal infection are the mainstay of treatment for scarlet fever. Prompt administration of appropriate antibiotics decreases the length of illness. Peeling of the outer layer of skin, however, will happen despite treatment. One of the main goals of treatment is to prevent the child from developing one of the suppurative or nonsuppurative complications, especially acute rheumatic fever. As long as antibiotics are started within nine days, it is very unlikely for the child to develop acute rheumatic fever. Antibiotic therapy has not been shown to prevent the development of post-streptococcal glomerulonephritis. Another important reason for prompt treatment with antibiotics is the ability to prevent transmission of the infection between children. An infected individual is most likely to pass on the infection to another person during the first 2 weeks. A child is no longer contagious (able to pass the infection to another child) after 24 hours of antibiotics.The antibiotic of choice is Penicillin V which is taken by mouth. In countries without a liquid Penicillin V product, children unable to take tablets can be given amoxicillin which comes in a liquid form and is equally effective. Duration of treatment is 10 days. Benzathine penicillin G can be given as a one time intramuscular injection as another alternative if swallowing pills is not possible. If the person is allergic to the family of antibiotics which both penicillin and amoxicillin are a part of (beta-lactam antibiotics), a first generation cephalosporin is used. Cephalosporin antibiotics, however, can still cause adverse reactions in people whose allergic reaction to penicillin is a Type 1 Hypersensitivity reaction. In those cases it is appropriate to choose clindamycin or erythromycin instead. Tonsillectomy, although once a reasonable treatment for recurrent streptococcal pharyngitis, is not indicated, as a person can still be infected with group A streptococcus without their tonsils.

Antibiotic resistance and resurgence
A drug-resistant strain of scarlet fever, resistant to macrolide antibiotics such as erythromycin, but retaining drug-sensitivity to beta-lactam antibiotics such as penicillin, emerged in Hong Kong in 2011, accounting for at least two deaths in that city—the first such in over a decade. About 60% of circulating strains of the group A streptococcus that cause scarlet fever in Hong Kong are resistant to macrolide antibiotics, says Professor Kwok-yung Yuen, head of Hong Kong Universitys microbiology department. Previously, observed resistance rates had been 10–30%; the increase is likely the result of overuse of macrolide antibiotics in recent years.There was also an outbreak in the UK in 2014, and the National Health Service reported a 68% increase in the number of S. pyogenes identified in laboratory reports between 2014 and 2018.New research published in October 2020 in the journal that the bacterium appears to be getting more robust after being infected with viruses, specifically the North-East Asian serotype M12 (emm12) (group A Streptococcus, GAS). They found three new genes, acquired from viruses, leading to the development of "superantigens" targeting white blood cells, leading to a more virulent strain of the bacterium.A vaccine that will protect against the 180 to 200 types of bacteria causing the disease has been worked on for over 20 years, but as of 2020 a safe one had not yet been developed.

Epidemiology
Scarlet fever occurs equally in both males and females. Children are most commonly infected, typically between 5–15 years old. Although streptococcal infections can happen at any time of year, infection rates peak in the winter and spring months, typically in colder climates.The morbidity and mortality of scarlet fever has declined since the 18th and 19th century when there were epidemics caused by this disease. Around 1900 the mortality rate in multiple places reached 25%. The improvement in prognosis can be attributed to the use of penicillin in the treatment of this disease. The frequency of scarlet fever cases has also been declining over the past century. There have been several reported outbreaks of the disease in various countries in the past decade. The reason for these recent increases remains unclear in the medical community. Between 2013 and 2016 population rates of scarlet fever in England increased from 8.2 to 33.2 per 100,000 and hospital admissions for scarlet fever increased by 97%.

History
It is unclear when a description of this disease was first recorded. Hippocrates, writing around 400 BC, described the condition of a person with a reddened skin and fever.The first unambiguous description of the disease in the medical literature appeared in the 1553 book De Tumoribus praeter Naturam by the Sicilian anatomist and physician Giovanni Filippo Ingrassia, where he referred to it as rossalia. He also made a point to distinguish that this presentation had different characteristics from measles. It was redescribed by Johann Weyer during an epidemic in lower Germany between 1564 and 1565; he referred to it as scarlatina anginosa. The first unequivocal description of scarlet fever appeared in a book by Joannes Coyttarus of Poitiers, De febre purpura epidemiale et contagiosa libri duo, which was published in 1578 in Paris. Daniel Sennert of Wittenberg described the classical scarlatinal desquamation in 1572 and was also the first to describe the early arthritis, scarlatinal dropsy, and ascites associated with the disease.In 1675 the term that has been commonly used to refer to scarlet fever, "scarlatina", was written by Thomas Sydenham, an English physician.

In 1827, Richard Bright was the first to recognize the involvement of the renal system in scarlet fever.The association between streptococci and disease was first described in 1874 by Theodor Billroth, discussing people with skin infections. Billroth also coined the genus name Streptococcus. In 1884 Friedrich Julius Rosenbach edited the name to its current one, Streptococcus pyogenes, after further looking at the bacteria in the skin lesions. The organism was first cultured in 1883 by the German surgeon Friedrich Fehleisen from erysipelas lesions.Also in 1884, the German physician Friedrich Loeffler was the first to show the presence of streptococci in the throats of people with scarlet fever. Because not all people with pharyngeal streptococci developed scarlet fever, these findings remained controversial for some time. The association between streptococci and scarlet fever was confirmed by Alphonse Dochez and George and Gladys Dick in the early 1900s.Also in 1884, the worlds first convalescent home for people with scarlet fever was opened at Brockley Hill, Stanmore, founded by Mary Wardell.Nil Filatov (in 1895) and Clement Dukes (in 1894) described an exanthematous disease which they thought was a form of rubella, but in 1900, Dukes described it as a separate illness which came to be known as Dukes disease, Filatovs disease, or fourth disease. However, in 1979, Keith Powell identified it as in fact the same illness as the form of scarlet fever which is caused by staphylococcal exotoxin and is known as staphylococcal scalded skin syndrome.Scarlet fever serum from horses blood was used in the treatment of children beginning in 1900 and reduced mortality rates significantly.In 1906, the Austrian pediatrician Clemens von Pirquet postulated that disease-causing immune complexes were responsible for the nephritis that followed scarlet fever.Bacteriophages were discovered in 1915 by Frederick Twort. His work was overlooked and bacteriophages were later rediscovered by Felix dHerelle in 1917. The specific association of scarlet fever with the group A streptococci had to await the development of Lancefields streptococcal grouping scheme in the 1920s. George and Gladys Dick showed that cell-free filtrates could induce the erythematous reaction characteristic of scarlet fever, proving that this reaction was due to a toxin </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 Hyphema and can you explain it in depth? [/INST] Hyphema is a condition that occurs when blood enters the front (anterior) chamber of the eye between the iris and the cornea. People usually first notice a loss of vision or decrease in vision. The eye may also appear to have a reddish tinge, or it may appear as a small pool of blood at the bottom of the iris or in the cornea. A traumatic hyphema is caused by a hit to the eye from a projected object or a blow to the eye. A hyphema can also occur spontaneously.

Presentation
A decrease in vision or a loss of vision is often the first sign of a hyphema. People with microhyphema may have slightly blurred or normal vision. A person with a full hyphema may not be able to see at all (complete loss of vision). The persons vision may improve over time as the blood moves by gravity lower in the anterior chamber of the eye, between the iris and the cornea. In many people, the vision will improve, however some people may have other injuries related to trauma to the eye or complications related to the hyphema. A microhyphema, where red blood cells are hanging in the anterior chamber of the eye, is less severe. A layered hyphema when fresh blood is seen lower in the anterior chamber is moderately severe. A full hyphema (total hyphema), when blood fills up the chamber completely, is the most severe.

Complications
While the vast majority of hyphemas resolve on their own without issue, sometimes complications occur. Traumatic hyphema may lead to increased intraocular pressure (IOP), peripheral anterior synechiae, atrophy of the optic nerve, staining of the cornea with blood, re-bleeding, and impaired accommodation.Secondary hemorrhage, or rebleeding of the hyphema, is thought to worsen outcomes in terms of visual function and lead to complications such as glaucoma, corneal staining, optic atrophy, or vision loss. Rebleeding occurs in 4–35% of hyphema cases and is a risk factor for glaucoma. Young children with traumatic hyphema are at an increased risk of developing amblyopia, an irreversible condition.

Causes
Hyphemas are frequently caused by injury, and may partially or completely block vision. The most common causes of hyphema are intraocular surgery, blunt trauma, and lacerating trauma.  Hyphemas may also occur spontaneously, without any inciting trauma.  Spontaneous hyphemas are usually caused by the abnormal growth of blood vessels (neovascularization), tumors of the eye (retinoblastoma or iris melanoma), uveitis, or vascular anomalies (juvenile xanthogranuloma). Additional causes of spontaneous hyphema include: rubeosis iridis, myotonic dystrophy, leukemia, hemophilia, and von Willebrand disease.  Conditions or medications that cause thinning of the blood, such as aspirin, warfarin, or drinking alcohol may also cause hyphema. Source of bleeding in hyphema with blunt trauma to eye is circulus iridis major artery.

Treatment
The main goals of treatment are to decrease the risk of re-bleeding within the eye, corneal blood staining, and atrophy of the optic nerve. Small hyphemas can usually be treated on an outpatient basis. There is little evidence that most of the commonly used treatments for hyphema (antifibrinolytic agents [oral and systemic aminocaproic acid, tranexamic acid, and aminomethylbenzoic acid], corticosteroids [systemic and topical], cycloplegics, miotics, aspirin, conjugated estrogens, traditional Chinese medicine, monocular versus bilateral patching, elevation of the head, and bed rest) are effective at improving visual acuity after two weeks </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 Mild cognitive impairment and can you explain it in depth? [/INST] Mild cognitive impairment (MCI) is a neurocognitive disorder which involves cognitive impairments beyond those expected based on an individuals age and education but which are not significant enough to interfere with instrumental activities of daily living. MCI may occur as a transitional stage between normal aging and dementia, especially Alzheimers disease. It includes both memory and non-memory impairments. The cause of the disorder remains unclear, as well as both its prevention and treatment, with some 50 percent of people diagnosed with it going on to develop Alzheimers disease within five years.  The diagnosis can also serve as an early indicator for other types of dementia, although MCI may remain stable or even remit.Mild cognitive impairment has been relisted as mild neurocognitive disorder in DSM-5, and in ICD-11, the latter effective on the 1st of January 2022.

Classification
MCI can present with a variety of symptoms, but is divided generally into two types.Amnestic MCI (aMCI) is mild cognitive impairment with memory loss as the predominant symptom; aMCI is frequently seen as a prodromal stage of Alzheimers disease. Studies suggest that these individuals tend to progress to probable Alzheimers disease at a rate of approximately 10% to 15% per year. It is possible that being diagnosed with cognitive decline may serve as an indicator of MCI.Nonamnestic MCI (naMCI) is mild cognitive impairment in which impairments in domains other than memory (for example, language, visuospatial, executive) are more prominent. It may be further divided as nonamnestic single- or multiple-domain MCI, and these individuals are believed to be more likely to convert to other dementias (for example, dementia with Lewy bodies).The International Classification of Diseases classifies MCI as a "mental and behavioural disorder."

Causes
Mild cognitive impairment (MCI) may be caused due to alteration in the brain triggered during early stages of Alzheimers disease or other forms of dementia. Exact causes of MCI are unknown. It is controversial whether MCI even should be identified as a disorder.Risk factors of both dementia and MCI are considered to be the same: these are aging, genetic (heredity) cause of Alzheimers or other dementia, and cardiovascular disease.Individuals with MCI have increased oxidative damage in their nuclear and mitochondrial brain DNA.

Diagnosis
The diagnosis of MCI requires considerable clinical judgement, and as such a comprehensive clinical assessment including clinical observation, neuroimaging, blood tests and neuropsychological testing are best in order to rule out an alternate diagnosis.
MCI is diagnosed when there is:
Evidence of memory impairment
Preservation of general cognitive and functional abilities
Absence of diagnosed dementia

Neuropathology
Although amnestic MCI patients may not meet criteria for Alzheimers disease, patients may be in a transitional stage of evolving Alzheimers disease.Magnetic resonance imaging can observe deterioration, including progressive loss of gray matter in the brain, from mild cognitive impairment to full-blown Alzheimer disease.  A technique known as PiB PET imaging is used to show the sites and shapes of beta amyloid deposits in living subjects using a 11C tracer that binds selectively to such deposits.

Treatment
As of January 2018, there are no USFDA-approved medications for the treatment of mild cognitive impairment.  Moreover, as of January 2018, there is no high-quality evidence that supports the efficacy of any pharmaceutical drugs or dietary supplements for improving cognitive symptoms in individuals with mild cognitive impairment. A moderate amount of high-quality evidence supports the efficacy of regular physical exercise for improving cognitive symptoms in individuals with MCI. The clinical trials that established the efficacy of exercise therapy for MCI involved twice weekly exercise over a period of six months. A small amount of high-quality evidence supports the efficacy of cognitive training for improving some measures of cognitive function in individuals with mild cognitive impairment.  Due to the heterogeneity among studies which assessed the effect of cognitive training in individuals with MCI, there are no particular cognitive training interventions that have been found to provide greater symptomatic benefits for MCI relative to other forms of cognitive training.The American Academy of Neurologys (AAN) clinical practice guideline on mild cognitive impairment from January 2018 stated that clinicians should identify modifiable risk factors in individuals with MCI, assess functional impairments, provide treatment for any behavioral or neuropsychiatric symptoms, and monitor the individuals cognitive status over time. It also stated that medications which cause cognitive impairment should be discontinued or avoided if possible </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 Mood disorder and can you explain it in depth? [/INST] A mood disorder, also known as an affective disorder, is any of a group of conditions of mental and behavioral disorder where a disturbance in the persons mood is the main underlying feature. The classification is in the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Classification of Diseases (ICD).
Mood disorders fall into seven groups, including; abnormally elevated mood, such as mania or hypomania; depressed mood, of which the best-known and most researched is major depressive disorder (MDD) (alternatively known as clinical depression, unipolar depression, or major depression); and moods which cycle between mania and depression, known as bipolar disorder (BD) (formerly known as manic depression). There are several sub-types of depressive disorders or psychiatric syndromes featuring less severe symptoms such as dysthymic disorder (similar to MDD, but longer lasting and more persistent, though often milder) and cyclothymic disorder (similar to but milder than BD).In some cases, more than one mood disorder can be present in an individual, like bipolar disorder and depressive disorder. If a mood disorder and schizophrenia are both present in an individual, this is known as schizoaffective disorder. Mood disorders may also be substance induced, or occur in response to a medical condition.
English psychiatrist Henry Maudsley proposed an overarching category of affective disorder. The term was then replaced by mood disorder, as the latter term refers to the underlying or longitudinal emotional state, whereas the former refers to the external expression observed by others.

Classification
Depressive disorders
Major depressive disorder (MDD), commonly called major depression, unipolar depression, or clinical depression, wherein a person has one or more major depressive episodes. After a single episode, Major Depressive Disorder (single episode) would be diagnosed. After more than one episode, the diagnosis becomes Major Depressive Disorder (Recurrent). Depression without periods of mania is sometimes referred to as unipolar depression because the mood remains at the bottom "pole" and does not climb to the higher, manic "pole" as in bipolar disorder.Individuals with a major depressive episode or major depressive disorder are at increased risk for suicide. Seeking help and treatment from a health professional dramatically reduces the individuals risk for suicide. Studies have demonstrated that asking if a depressed friend or family member has thought of committing suicide is an effective way of identifying those at risk, and it does not "plant" the idea or increase an individuals risk for suicide in any way. Epidemiological studies carried out in Europe suggest that, at this moment, roughly 8.5 percent of the worlds population have a depressive disorder. No age group seems to be exempt from depression, and studies have found that depression appears in infants as young as 6 months old who have been separated from their mothers.Depressive disorder is frequent in primary care and general hospital practice but is often undetected.  Unrecognized depressive disorder may slow recovery and worsen prognosis in physical illness, therefore it is important that all doctors be able to recognize the condition, treat the less severe cases, and identify those requiring specialist care.Diagnosticians recognize several subtypes or course specifiers:Atypical depression (AD) is characterized by mood reactivity (paradoxical anhedonia) and positivity,  significant weight gain or increased appetite ("comfort eating"), excessive sleep or somnolence (hypersomnia), a sensation of heaviness in limbs known as leaden paralysis, and significant social impairment as a consequence of hypersensitivity to perceived interpersonal rejection. Difficulties in measuring this subtype have led to questions of its validity and prevalence.Melancholic depression is characterized by a loss of pleasure (anhedonia) in most or all activities, a failure of reactivity to pleasurable stimuli, a quality of depressed mood more pronounced than that of grief or loss, a worsening of symptoms in the morning hours, early-morning waking, psychomotor retardation, excessive weight loss (not to be confused with anorexia nervosa), or excessive guilt.Psychotic major depression (PMD), or simply psychotic depression, is the term for a major depressive episode, in particular of melancholic nature, wherein the patient experiences psychotic symptoms such as delusions or, less commonly, hallucinations. These are most commonly mood-congruent (content coincident with depressive themes).Catatonic depression is a rare and severe form of major depression involving disturbances of motor behavior and other symptoms. Here, the person is mute and almost stuporose, and either is immobile or exhibits purposeless or even bizarre movements. Catatonic symptoms can also occur in schizophrenia or a manic episode, or can be due to neuroleptic malignant syndrome.Postpartum depression (PPD) is listed as a course specifier in DSM-IV-TR; it refers to the intense, sustained and sometimes disabling depression experienced by women after giving birth. Postpartum depression, which affects 10–15% of women, typically sets in within three months of labor, and lasts as long as three months. It is quite common for women to experience a short-term feeling of tiredness and sadness in the first few weeks after giving birth; however, postpartum depression is different because it can cause significant hardship and impaired functioning at home, work, or school as well as, possibly, difficulty in relationships with family members, spouses, or friends, or even problems bonding with the newborn. In the treatment of postpartum major depressive disorders and other unipolar depressions in women who are breastfeeding, nortriptyline, paroxetine (Paxil), and sertraline (Zoloft) are in general considered to be the preferred medications. Women with personal or family histories of mood disorders are at particularly high risk of developing postpartum depression.Premenstrual dysphoric disorder (PMDD) is a severe and disabling form of premenstrual syndrome affecting 3–8% of menstruating women. The disorder consists of a "cluster of affective, behavioral and somatic symptoms" that recur monthly during the luteal phase of the menstrual cycle. PMDD was added to the list of depressive disorders in the Diagnostic and Statistical Manual of Mental Disorders in 2013. The exact pathogenesis of the disorder is still unclear and is an active research topic. Treatment of PMDD relies largely on antidepressants that modulate serotonin levels in the brain via serotonin reuptake inhibitors as well as ovulation suppression using contraception.Seasonal affective disorder (SAD), also known as "winter depression" or "winter blues", is a specifier. Some people have a seasonal pattern, with depressive episodes coming on in the autumn or winter, and resolving in spring. The diagnosis is made if at least two episodes have occurred in colder months with none at other times over a two-year period or longer. It is commonly hypothesised that people who live at higher latitudes tend to have less sunlight exposure in the winter and therefore experience higher rates of SAD, but the epidemiological support for this proposition is not strong (and latitude is not the only determinant of the amount of sunlight reaching the eyes in winter). It is said that this disorder can be treated by light therapy. SAD is also more prevalent in people who are younger and typically affects more females than males.Dysthymia is a condition related to unipolar depression, where the same physical and cognitive problems are evident, but they are not as severe and tend to last longer (usually at least 2 years). The treatment of dysthymia is largely the same as for major depression, including antidepressant medications and psychotherapy.Double depression can be defined as a fairly depressed mood (dysthymia) that lasts for at least two years and is punctuated by periods of major depression.Unspecified Depressive Disorder is designated by the code 311 for depressive disorders. In the DSM-5, Unspecified Depressive Disorder encompasses symptoms that are characteristic of depressive disorders and cause significant impairment in functioning, but do not meet the criteria for the diagnosis of any specified depressive disorders. In the DSM-IV, this was called Depressive Disorder Not Otherwise Specified.Depressive personality disorder (DPD) is a controversial psychiatric diagnosis that denotes a personality disorder with depressive features. Originally included in the DSM-II, depressive personality disorder was removed from the DSM-III and DSM-III-R. Recently, it has been reconsidered for reinstatement as a diagnosis. Depressive personality disorder is currently described in Appendix B in the DSM-IV-TR as worthy of further study.Recurrent brief depression (RBD), distinguished from major depressive disorder primarily by differences in duration. People with RBD have depressive episodes about once per month, with individual episodes lasting less than two weeks and typically less than 2–3 days. Diagnosis of RBD requires that the episodes occur over the span of at least one year and, in female patients, independently of the menstrual cycle. People with clinical depression can develop RBD, and vice versa, and both illnesses have similar risks.Minor depressive disorder, or simply minor depression, which refers to a depression that does not meet full criteria for major depression but in which at least two symptoms are present for two weeks.

Bipolar disorders
Bipolar disorder (BD) (also called "manic depression" or "manic-depressive disorder"), an unstable emotional condition characterized by cycles of abnormal, persistent high mood (mania) and low mood (depression), which was formerly known as "manic depression" (and in some cases rapid cycling, mixed states, and psychotic symptoms). Subtypes include:Bipolar I is distinguished by the presence or history of one or more manic episodes or mixed episodes with or without major depressive episodes. A depressive episode is not required for the diagnosis of Bipolar I Disorder, but depressive episodes are usually part of the course of the illness.
Bipolar II consisting of recurrent intermittent hypomanic and depressive episodes or mixed episodes.
Cyclothymia is a form of bipolar disorder, consisting of recurrent hypomanic and dysthymic episodes, but no full manic episodes or full major depressive episodes.
Bipolar disorder not otherwise specified (BD-NOS), sometimes called "sub-threshold" bipolar, indicates that the patient has some symptoms in the bipolar spectrum (e.g., manic and depressive symptoms) but does not fully qualify for any of the three formal bipolar DSM-IV diagnoses mentioned above.
It is estimated that roughly 1% of the adult population has bipolar I, a further 1% has bipolar II or cyclothymia, and somewhere between 2% and 5% percent have "sub-threshold" forms of bipolar disorder. Furthermore, the possibility of getting bipolar disorder when one parent is diagnosed with it is 15–30%. Risk, when both parents have it, is 50–75%. Also, while with bipolar siblings the risk is 15–25%, with identical twins it is about 70%.A minority of people with bipolar disorder have high creativity, artistry or a particular gifted talent. Before the mania phase becomes too extreme, its energy, ambition, enthusiasm and grandiosity often bring people with this type of mood disorder lifes masterpieces.

Substance-induced
A mood disorder can be classified as substance-induced if its etiology can be traced to the direct physiologic effects of a psychoactive drug or other chemical substance, or if the development of the mood disorder occurred contemporaneously with substance intoxication or withdrawal. Also, an individual may have a mood disorder coexisting with a substance abuse disorder. Substance-induced mood disorders can have features of a manic, hypomanic, mixed, or depressive episode. Most substances can induce a variety of mood disorders. For example, stimulants such as amphetamine, methamphetamine, and cocaine can cause manic, hypomanic, mixed, and depressive episodes.

Alcohol-induced
High rates of major depressive disorder occur in heavy drinkers and those with alcoholism. Controversy has previously surrounded whether those who abused alcohol and developed depression were self-medicating their pre-existing depression. Recent research has concluded that, while this may be true in some cases, alcohol misuse directly causes the development of depression in a significant number of heavy drinkers. Participants studied were also assessed during stressful events in their lives and measured on a Feeling Bad Scale. Likewise, they were also assessed on their affiliation with  deviant  peers, unemployment, and their partners substance use and criminal offending. High rates of suicide also occur in those who have alcohol-related problems. It is usually possible to differentiate between alcohol-related depression and depression that is not related to alcohol intake by taking a careful history of the patient. Depression and other mental health problems associated with alcohol misuse may be due to distortion of brain chemistry, as they tend to improve on their own after a period of abstinence.

Benzodiazepine-induced
Benzodiazepines, such as alprazolam, clonazepam, lorazepam and diazepam, can cause both depression and mania.Benzodiazepines are a class of medication commonly used to treat anxiety, panic attacks and insomnia, and are also commonly misused and abused. Those with anxiety, panic and sleep problems commonly have negative emotions and thoughts, depression, suicidal ideations, and often have comorbid depressive disorders. While the anxiolytic and hypnotic effects of benzodiazepines disappear as tolerance develops, depression and impulsivity with high suicidal risk commonly persist. These symptoms are "often interpreted as an exacerbation or as a natural evolution of previous disorders and the chronic use of sedatives is overlooked". Benzodiazepines do not prevent the development of depression, can exacerbate preexisting depression, can cause depression in those with no history of it, and can lead to suicide attempts. Risk factors for suicide and suicide attempts while using benzodiazepines include high dose prescriptions (even in those not misusing the medications), benzodiazepine intoxication, and underlying depression.The long-term use of benzodiazepines may have a similar effect on the brain as alcohol, and are also implicated in depression. As with alcohol, the effects of benzodiazepine on neurochemistry, such as decreased levels of serotonin and norepinephrine, are believed to be responsible for the increased depression. Additionally, benzodiazepines can indirectly worsen mood by worsening sleep (i.e., benzodiazepine-induced sleep disorder). Like alcohol, benzodiazepines can put people to sleep but, while asleep, they disrupt sleep architecture: decreasing sleep time, delaying time to REM sleep, and decreasing deep sleep (the most restorative part of sleep for both energy and mood). Just as some antidepressants can cause or worsen anxiety in some patients due to being activating, benzodiazepines can cause or worsen depression due to being a central nervous system depressant—worsening thinking, concentration and problem solving (i.e., benzodiazepine-induced neurocognitive disorder). However, unlike antidepressants, in which the activating effects usually improve with continued treatment, benzodiazepine-induced depression is unlikely to improve until after stopping the medication.In a long-term follow-up study of patients dependent on benzodiazepines, it was found that 10 people (20%) had taken drug overdoses while on chronic benzodiazepine medication despite only two people ever having had any pre-existing depressive disorder. A year after a gradual withdrawal program, no patients had taken any further overdoses.Just as with intoxication and chronic use, benzodiazepine withdrawal can also cause depression. While benzodiazepine-induced depressive disorder may be exacerbated immediately after discontinuation of benzodiazepines, evidence suggests that mood significantly improves after the acute withdrawal period to levels better than during use. Depression resulting from withdrawal from benzodiazepines usually subsides after a few months but in some cases may persist for 6–12 months.

Due to another medical condition
"Mood disorder due to a general medical condition" is used to describe manic or depressive episodes which occur secondary to a medical condition. There are many medical conditions that can trigger mood episodes, including neurological disorders (e.g. dementias), metabolic disorders (e.g. electrolyte disturbances), gastrointestinal diseases (e.g. cirrhosis), endocrine disease (e.g. thyroid abnormalities), cardiovascular disease (e.g. heart attack), pulmonary disease (e.g. chronic obstructive pulmonary disease), cancer, and autoimmune diseases (e.g. multiple sclerosis).

Not otherwise specified
Mood disorder not otherwise specified (MD-NOS) is a mood disorder that is impairing but does not fit in with any of the other officially specified diagnoses. In the DSM-IV MD-NOS is described as "any mood disorder that does not meet the criteria for a specific disorder." MD-NOS is not used as a clinical description but as a statistical concept for filing purposes. The diagnosis of MD-NOS does not exist in the DSM-5, however the diagnoses of unspecified depressive disorder and unspecified bipolar disorder are in the DSM-5.Most cases of MD-NOS represent hybrids between mood and anxiety disorders, such as mixed anxiety-depressive disorder or atypical depression. An example of an instance of MD-NOS is being in minor depression frequently during various intervals, such as once every month or once in three days. There is a risk for MD-NOS not to get noticed, and for that reason not to get treated.

Causes
Meta-analyses show that high scores on the personality domain neuroticism are a strong predictor for the development of mood disorders. A number of authors have also suggested that mood disorders are an evolutionary adaptation (see also evolutionary psychiatry). A low or depressed mood can increase an individuals ability to cope with situations in which the effort to pursue a major goal could result in danger, loss, or wasted effort. In such situations, low motivation may give an advantage by inhibiting certain actions. This theory helps to explain why negative life incidents precede depression in around 80 percent of cases, and why they so often strike people during their peak reproductive years. These characteristics would be difficult to understand if depression were a dysfunction.A depressed mood is a predictable response to certain types of life occurrences, such as loss of status, divorce, or death of a child or spouse. These are events that signal a loss of reproductive ability or potential, or that did so in humans ancestral environment. A depressed mood can be seen as an adaptive response, in the sense that it causes an individual to turn away from the earlier (and reproductively unsuccessful) modes of behavior.A depressed mood is common during illnesses, such as influenza. It has been argued that this is an evolved mechanism that assists the individual in recovering by limiting their physical activity. The occurrence of low-level depression during the winter months, or seasonal affective disorder, may have been adaptive in the past, by limiting physical activity at times when food was scarce. It is argued that humans have retained the instinct to experience low mood during the winter months, even if the availability of food is no longer determined by the weather.Much of what is known about the genetic influence of clinical depression is based upon research that has been done with identical twins. Identical twins have exactly the same genetic code. It has been found that when one identical twin becomes depressed the other will also develop clinical depression approximately 76% of the time. When identical twins are raised apart from each other, they will both become depressed about 67% of the time. Because both twins become depressed at such a high rate, the implication is that there is a strong genetic influence. If it happened that when one twin becomes clinically depressed the other always develops depression, then clinical depression would likely be entirely genetic.Bipolar disorder is also considered a mood disorder and it is hypothesized that it might be caused by mitochondrial dysfunction.

Sex differences
Mood disorders, specifically stress-related mood disorders such as anxiety and depression, have been shown to have differing rates of diagnosis based on sex. In the United States, women are two times more likely than men to be diagnosed with a stress-related mood disorder. Underlying these sex differences, studies have shown a dysregulation of stress-responsive neuroendocrine function causing an increase in the likelihood of developing these affective disorders. Overactivation of the hypothalamic-pituitary-adrenal (HPA) axis could provide potential insight into how these sex differences arise. Neuropeptide corticotropin-releasing factor (CRF) is released from the paraventricular nucleus (PVN) of the hypothalamus, stimulating adrenocorticotropic hormone (ACTH) release into the blood stream. From here ACTH triggers the release of glucocorticoids such as cortisol from the adrenal cortex. Cortisol, known as the main stress hormone, creates a negative feedback loop back to the hypothalamus to deactivate the stress response. When a constant stressor is present, the HPA axis remains overactivated and cortisol is constantly produced. This chronic stress is associated with sustained CRF release, resulting in the increased production of anxiety- and depressive-like behaviors and serving as a potential mechanism for differences in prevalence between men and women.

Diagnosis
DSM-5
The DSM-5, released in May 2013, separates the mood disorder chapter from the DSM-TR-IV into two sections: Depressive and related disorders and bipolar and related disorders. Bipolar disorders fall in between depressive disorders and schizophrenia spectrum and related disorders "in recognition of their place as a bridge between the two diagnostic classes in terms of symptomatology, family history and genetics" (Ref. 1, p 123). Bipolar disorders underwent a few changes in the DSM-5, most notably the addition of more specific symptomology related to hypomanic and mixed manic states. Depressive disorders underwent the most changes, the addition of three new disorders: disruptive mood dysregulation disorder, persistent depressive disorder (previously dysthymia), and premenstrual dysphoric disorder (previously in appendix B, the section for disorders needing further research). Disruptive mood dysregulation disorder is meant as a diagnosis for children and adolescents who would normally be diagnosed with bipolar disorder as a way to limit the bipolar diagnosis in this age cohort. Major depressive disorder (MDD) also underwent a notable change, in that the bereavement clause has been removed. Those previously exempt from a diagnosis of MDD due to bereavement are now candidates for the MDD diagnosis.

Treatment
There are different types of treatments available for mood disorders, such as therapy and medications. Behaviour therapy, cognitive behaviour therapy and interpersonal therapy have all shown to be potentially beneficial in depression. Major depressive disorder medications usually include antidepressants; a combination of antidepressants and cognitive behavioral therapy has shown to be more effective than one treatment alone. Bipolar disorder medications can consist of antipsychotics, mood stabilizers, anticonvulsants and/or lithium. Lithium specifically has been proven to reduce suicide and all causes of mortality in people with mood disorders. If mitochondrial dysfunction or mitochondrial diseases are the cause of mood disorders like bipolar disorder, then it has been hypothesized that N-acetyl-cysteine (NAC), acetyl-L-carnitine (ALCAR), S-adenosylmethionine (SAMe), coenzyme Q10 (CoQ10), alpha-lipoic acid (ALA), creatine monohydrate (CM), and melatonin could be potential treatment options. In determining treatment, there are many types of depression scales that are used. One of the depression scales is a self-report scale called Beck Depression Inventory (BDI). Another scale is the Hamilton Depression Rating Scale (HAMD). HAMD is a clinical rating scale in which the patient is rated based on clinician observation. The Center for Epidemiologic Studies Depression Scale (CES-D) is a scale for depression symptoms that applies to the general population. This scale is typically used in research and not for self-reports. The PHQ-9 which stands for Patient-Health Questionnaire-9 questions, is a self-report as well. Finally, the Mood Disorder Questionnaire (MDQ) evaluates bipolar disorder.

Epidemiology
According to a substantial number of epidemiology studies conducted, women are twice as likely to develop certain mood disorders, such as major depression.  Although there is an equal number of men and women diagnosed with bipolar II disorder, women have a slightly higher frequency of the disorder.The prevalence of depressive symptoms has increased over the years with recent generations reporting a 6% increase in symptoms of depression compared to individuals from older generations.In 2011, mood disorders were the most common reason for hospitalization among children aged 1–17 years in the United States, with approximately 112,000 stays. Mood disorders were top principal diagnosis for Medicaid super-utilizers in the United States in 2012. Further, a study of 18 States found that mood disorders accounted for the highest number of hospital readmissions among Medicaid patients and the uninsured, with 41,600 Medicaid patients and 12,200 uninsured patients being readmitted within 30 days of their index stay—a readmission rate of 19.8 per 100 admissions and 12.7 per 100 admissions, respectively. In 2012, mood and other behavioral health disorders were the most common diagnoses for Medicaid-covered and uninsured hospital stays in the United States (6.1% of Medicaid stays and 5.2% of uninsured stays).A study conducted in 1988 to 1994 amongst young American adults involved a selection of demographic and health characteristics. A population-based sample of 8,602 men and women ages 17–39 years participated. Lifetime prevalence were estimated based on six mood measures:

major depressive episode (MDE) 8.6%,
major depressive disorder with severity (MDE-s) 7.7%,
dysthymia 6.2%,
MDE-s with dysthymia 3.4%,
any bipolar disorder 1.6%, and
any mood disorder 11.5%.

Research
Kay Redfield Jamison and others have explored the possible links between mood disorders – especially bipolar disorder – and creativity. It has been proposed that a "ruminating personality type may contribute to both [mood disorders] and art."Jane Collingwood notes an Oregon State University study that

"looked at the occupational status of a large group of typical patients and found that those with bipolar illness appear to be disproportionately concentrated in the most creative occupational category. They also found that the likelihood of engaging in creative activities on the job is significantly higher for bipolar than nonbipolar workers".In Liz Patereks article "Bipolar Disorder and the Creative Mind" she wrote

"Memory and creativity are related to mania. Clinical studies have shown that those in a manic state will rhyme, find synonyms, and use alliteration more than controls. This mental fluidity could contribute to an increase in creativity. Moreover, mania creates increases in productivity and energy. Those in a manic state are more emotionally sensitive and show less inhibition about attitudes, which could create greater expression. Studies performed at Harvard looked into the amount of original thinking in solving creative tasks. Bipolar individuals, whose disorder was not severe, tended to show greater degrees of creativity".The relationship between depression and creativity appears to be especially strong among poets.

See also
Personality disorder

References
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