<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 Overactive bladder and can you explain it in depth? [/INST] Overactive bladder (OAB) is a condition where there is a frequent feeling of needing to urinate to a degree that it negatively affects a persons life. The frequent need to urinate may occur during the day, at night, or both. If there is loss of bladder control then it is known as urge incontinence. More than 40% of people with overactive bladder have incontinence. Conversely, about 40% to 70% of urinary incontinence is due to overactive bladder. Overactive bladder is not life-threatening, but most people with the condition have problems for years.The cause of overactive bladder is unknown. Risk factors include obesity, caffeine, and constipation. Poorly controlled diabetes, poor functional mobility, and chronic pelvic pain may worsen the symptoms. People often have the symptoms for a long time before seeking treatment and the condition is sometimes identified by caregivers. Diagnosis is based on a persons signs and symptoms and requires other problems such as urinary tract infections or neurological conditions to be excluded. The amount of urine passed during each urination is relatively small. Pain while urinating suggests that there is a problem other than overactive bladder.Specific treatment is not always required. If treatment is desired pelvic floor exercises, bladder training, and other behavioral methods are initially recommended. Weight loss in those who are overweight, decreasing caffeine consumption, and drinking moderate fluids, can also have benefits. Medications, typically of the anti-muscarinic type, are only recommended if other measures are not effective. They are no more effective than behavioral methods; however, they are associated with side effects, particularly in older people. Some non-invasive electrical stimulation methods appear effective while they are in use. Injections of botulinum toxin into the bladder is another option. Urinary catheters or surgery are generally not recommended. A diary to track problems can help determine whether treatments are working.Overactive bladder is estimated to occur in 7-27% of men and 9-43% of women. It becomes more common with age. Some studies suggest that the condition is more common in women, especially when associated with loss of bladder control. Economic costs of overactive bladder were estimated in the United States at US$12.6 billion and 4.2 billion Euro in 2000.

Signs and symptoms
Overactive bladder is characterized by a group of four symptoms: urgency, urinary frequency, nocturia, and urge incontinence.  Urge incontinence is not present in the "dry" classification.Urgency is considered the hallmark symptom of OAB, but there are no clear criteria for what constitutes urgency and studies often use other criteria.  Urgency is currently defined by the International Continence Society (ICS), as of 2002, as "Sudden, compelling desire to pass urine that is difficult to defer."  The previous definition was "Strong desire to void accompanied by fear of leakage or pain."  The definition does not address the immediacy of the urge to void and has been criticized as subjective.Urinary frequency is considered abnormal if the person urinates more than eight times in a day.  This frequency is usually monitored by having the person keep a voiding diary where they record urination episodes. The number of episodes varies depending on sleep, fluid intake, medications, and up to seven is considered normal if consistent with the other factors.Nocturia is a symptom where the person complains of interrupted sleep because of an urge to void and, like the urinary frequency component, is affected by similar lifestyle and medical factors.  Individual waking events are not considered abnormal, one study in Finland established two or more voids per night as affecting quality of life.Urge incontinence is a form of urinary incontinence characterized by the involuntary loss of urine occurring for no apparent reason while feeling urinary urgency as discussed above.  Like frequency, the person can track incontinence in a diary to assist with diagnosis and management of symptoms.  Urge incontinence can also be measured with pad tests, and these are often used for research purposes.  Some people with urge incontinence also have stress incontinence and this can complicate clinical studies.It is important that the clinician and the person with overactive bladder both reach a consensus on the term, urgency. Some common phrases used to describe OAB include, When Ive got to go, Ive got to go, or When I have to go, I have to rush, because I think I will wet myself. Hence the term, fear of leakage, is an important concept to people.

Causes
The cause of OAB is unclear, and indeed there may be multiple causes. It is often associated with overactivity of the detrusor urinae muscle, a pattern of bladder muscle contraction observed during urodynamics. It is also possible that the increased contractile nature originates from within the urothelium and lamina propria, and abnormal contractions in this tissue could stimulate dysfunction in the detrusor or whole bladder.

Catheter-related irritation
If bladder spasms occur or there is no urine in the drainage bag when a catheter is in place, the catheter may be blocked by blood, thick sediment, or a kink in the catheter or drainage tubing. Sometimes spasms are caused by the catheter irritating the bladder, prostate or penis. Such spasms can be controlled with medication such as butylscopolamine, although most people eventually adjust to the irritation and the spasms go away.

Diagnosis
Diagnosis of OAB is made primarily on the persons signs and symptoms and by ruling out other possible causes such as an infection. Urodynamics, a bladder scope, and ultrasound are generally not needed. Additionally, urine culture may be done to rule out infection. The frequency/volume chart may be maintained and cystourethroscopy may be done to exclude tumor and kidney stones.  If there is an underlying metabolic or pathologic condition that explains the symptoms, the symptoms may be considered part of that disease and not OAB.Psychometrically robust self-completion questionnaires are generally recognized as a valid way of measuring a persons signs and symptoms, but there does not exist a single ideal questionnaire. These surveys can be divided into two groups: general surveys of lower urinary tract symptoms and surveys specific to overactive bladder. General questionnaires include: American Urological Association Symptom Index (AUASI), Urogenital Distress Inventory (UDI), Incontinence Impact Questionnaire (IIQ), and Bristol Female Lower Urinary Tract Symptoms (BFLUTS). Overactive bladder questionnaires include: Overactive Bladder Questionnaire (OAB-q), Urgency Questionnaire (UQ), Primary OAB Symptom Questionnaire (POSQ), and the International Consultation on Incontinence Questionnaire (ICIQ).
OAB causes similar symptoms to some other conditions such as urinary tract infection (UTI), bladder cancer, and benign prostatic hyperplasia (BPH).  Urinary tract infections often involve pain and hematuria (blood in the urine) which are typically absent in OAB.  Bladder cancer usually includes hematuria and can include pain, both not associated with OAB, and the common symptoms of OAB (urgency, frequency, and nocturia) may be absent.  BPH frequently includes symptoms at the time of voiding as well as sometimes including pain or hematuria, and all of these are not usually present in OAB. Diabetes insipidus, which causes high frequency and volume, though not necessarily urgency.

Classification
There is some controversy about the classification and diagnosis of OAB. Some sources classify overactive bladder into two different variants:  "wet" (i.e., an urgent need to urinate with involuntary leakage) or "dry" (i.e., an urgent need to urinate but no involuntary leakage). Wet variants are more common than dry variants. The distinction is not absolute; one study suggested that many classified as "dry" were actually "wet" and that people with no history of any leakage may have had other syndromes.OAB is distinct from stress urinary incontinence, but when they occur together, the condition is usually known as mixed incontinence.

Management
A recent (2019) systematic review of studies related to urinary incontinence in women found that behavioral therapy, alone or combined with other treatments, is generally more effective than any other single treatment alone. Behavioral therapy as a treatment has been used to improve or cure urgency urinary incontinence, including improving patient satisfaction.

Lifestyle
Treatment for OAB includes nonpharmacologic methods such as lifestyle modification (fluid restriction, avoidance of caffeine), bladder retraining, and pelvic floor muscle (PFM) exercise.
Timed voiding is a form of bladder training that uses biofeedback to reduce the frequency of accidents resulting from poor bladder control. This method is aimed at improving the persons control over the time, place and frequency of urination.
Timed voiding programs involve establishing a schedule for urination. To do this, a person fills in a chart of voiding and leaking. From the patterns that appear in the chart, the person can plan to empty his or her bladder before he or she would otherwise leak. Some individuals find it helpful to use a vibrating reminder watch to help them remember to use the bathroom. Vibrating watches can be set to go off at certain intervals or at specific times throughout the day, depending on the watch. Through this bladder training exercise, the person can alter their bladders schedule for storing and emptying urine.

Medications
A number of antimuscarinic drugs (e.g., darifenacin, hyoscyamine, oxybutynin, tolterodine, solifenacin, trospium, fesoterodine) are frequently used to treat overactive bladder. Long term use, however, has been linked to dementia. β3 adrenergic receptor agonists (e.g., mirabegron, vibegron), may be used, as well. However, both antimuscarinic drugs and β3 adrenergic receptor agonists constitute a second-line treatment due to the risk of side effects.Few people get complete relief with medications and all medications are no more than moderately effective.A typical person with overactive bladder may urinate 12 times per day. Medication may reduce this number by 2-3 and reduce urinary incontinence events by 1-2 per day.

Procedures
Various devices (Urgent PC Neuromodulation System) may also be used. Botulinum toxin A (Botox) is approved by the Food and Drug Administration in adults with neurological conditions, including multiple sclerosis and spinal cord injury. Botulinum Toxin A injections into the bladder wall can suppress involuntary bladder contractions by blocking nerve signals and may be effective for up to 9 months. The growing knowledge of pathophysiology of overactive bladder fuelled a huge amount of basic and clinical research in this field of pharmacotherapy. A surgical intervention involves the enlargement of the bladder using bowel tissues, although generally used as a last resort. This procedure can greatly enlarge urine volume in the bladder.OAB may be treated with electrical stimulation, which aims to reduce the contractions of the muscle that tenses around the bladder and causes urine to pass out of it.  There are invasive and non-invasive electrical stimulation options.  Non-invasive options include the introduction of a probe into the vagina or anus, or the insertion of an electrical probe into a nerve near the ankle with a fine needle.  These non-invasive options appear to reduce symptoms while they are in use, and are better than no treatment, or treatment with drugs, or pelvic floor muscle treatment, but the quality of evidence is low. It is unknown which electrical stimulation option works best.  Also, it is unknown whether the benefits last after treatment stops.

Prognosis
Many people with OAB symptoms had those symptoms subside within a year, with estimates as high as 39%, but most have symptoms for several years.

Epidemiology
Earlier reports estimated that about one in six adults in the United States and Europe had OAB. The number of people affected with OAB increases with age, thus it is expected that OAB will become more common in the future as the average age of people living in the developed world is increasing. However, a recent Finnish population-based survey suggested that the number of people affected had been largely overestimated due to methodological shortcomings regarding age distribution and low participation (in earlier reports). It is suspected, then, that OAB affects approximately half the number of individuals as earlier reported.The American Urological Association reports studies showing rates as low as 7% to as high as 27% in men and rates as low as 9% to 43% in women. Urge incontinence was reported as higher in women </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 Ovulation induction and can you explain it in depth? [/INST] Ovulation induction is the stimulation of ovulation by medication. It is usually used in the sense of stimulation of the development of ovarian follicles to reverse anovulation or oligoovulation.

Scope
The term ovulation induction can potentially also be used for:

Final maturation induction, in the sense of triggering oocyte release from relatively mature ovarian follicles during late follicular phase. In any case, ovarian stimulation (in the sense of stimulating the development of oocytes) is often used in conjunction with triggering oocyte release, such as for proper timing of artificial insemination.
Controlled ovarian hyperstimulation (stimulating the development of multiple follicles of the ovaries in one single cycle), has also appeared in the scope of ovulation induction. Controlled ovarian hyperstimulation is generally part of in vitro fertilization, and the aim is generally to develop multiple follicles (optimally between 11 and 14 antral follicles measuring 2–8 mm in diameter), followed by transvaginal oocyte retrieval, co-incubation, followed by embryo transfer of a maximum of two embryos at a time.
Also, where anovulation or oligovulation is secondary to another disease, the treatment for the underlying disease can be regarded as ovulation induction, by indirectly resulting in ovulation.However, this article focuses on medical ovarian stimulation, during early to mid-follicular phase, without subsequent in vitro fertilization, with the aim of developing one or two ovulatory follicles (the maximum number before recommending sexual abstinence).

Indications
Ovulation induction helps reversing anovulation or oligoovulation, that is, helping women who do not ovulate on their own regularly, such as those with polycystic ovary syndrome (PCOS).

Regimen alternatives
The main alternatives for ovulation induction medications are:

Antiestrogen, causing an inhibition of the negative feedback of estrogen on the pituitary gland, resulting in an increase in secretion of follicle-stimulating hormone. Medications in use for this effect are mainly clomifene citrate and tamoxifen (both being selective estrogen-receptor modulators), as well as letrozole (an aromatase inhibitor.
Follicle-stimulating hormone, directly stimulating the ovaries. In women with anovulation, it may be an alternative after 7 to 12 attempted cycles of antiestrogens (as evidenced by clomifene citrate), since the latter ones are less expensive and more easy to control.

Antiestrogens
Clomifene citrate
Clomifene citrate (or clomid) is the medication which is most commonly used to treat anovulation. It is a selective estrogen-receptor modulator, affecting the hypothalamic–pituitary–gonadal axis to respond as if there was an estrogen deficit in the body, in effect increasing the production of follicle-stimulating hormone. It is relatively easy and convenient to use. Clomifene appears to inhibit estrogen receptors in hypothalamus, thereby inhibiting negative feedback of estrogen on production of follicle-stimulating hormone. It may also result in direct stimulation of the hypothalamic-pituitary axis. It also has an effect on cervical mucus quality and uterine mucosa, which might affect sperm penetration and survival, hence its early administration during the menstrual cycle. Clomifene citrate is a very efficient ovulation inductor, and has a success rate of 67%. Nevertheless, it only has a 37% success rate in inducing pregnancy. This difference may be due to the anti-estrogenic effect which clomifene citrate has on the endometrium, cervical mucus, uterine blood flow, as well as the resulting decrease in the motility of the fallopian tubes and the maturation of the oocytes.

Letrozole
Letrozole has been used for ovarian stimulation by fertility doctors since 2001 because it has fewer side-effects than clomiphene and less chance of multiple gestation. A study of 150 babies following treatment with letrozole or letrozole and follicle-stimulating hormone presented at the American Society of Reproductive Medicine 2005 Conference found no difference in overall abnormalities but did find a significantly higher rate of locomotor and cardiac abnormalities among the group having taken letrozole compared to natural conception. A larger, follow-up study with 911 babies compared those born following treatment with letrozole to those born following treatment with clomiphene. That study also found no significant difference in the rate of overall abnormalities, but found that congenital cardiac anomalies was significantly higher in the clomiphene group compared to the letrozole group.
Dosage is generally 2.5 to 7.5 mg daily over 5 days. A higher dose of up to 12.5 mg per day results in increased follicular growth and a higher number of predicted ovulations, without a detrimental effect on endometrial thickness, and is considered in those who do not respond adequately to a lower dose.

Tamoxifen
Tamoxifen affects estrogen receptors in a similar fashion as clomifene citrate. It is often used in the prevention and treatment of breast cancer. It can therefore also be used to treat patients that have a reaction to clomifene citrate.

Follicle-stimulating hormone
Preparations of follicle-stimulating hormone mainly include those derived from the urine of menopausal women, as well as recombinant preparations. The recombinant preparations are more pure and more easily administered, but they are more expensive. The urinary preparations are equally effective and less expensive, but are not as convenient to administer as they are available in vials versus injection pens.

Gonadotropin-releasing hormone pump
The gonadotropin-releasing hormone pump is used to release doses in a pulsatile fashion. This hormone is synthesised by the hypothalamus and induces the secretion of follicle-stimulating hormone by the pituitary gland. Gonadotropin-releasing hormone must be delivered in a pulsatile fashion to imitate the random secretion of the hypothalamus in order to stimulate the pituitary into secreting luteinizing hormone and follicle-stimulating hormone. The gonadotropin-releasing hormone pump is the size of a cigarette box and has a small catheter. Unlike other treatments, using the gonadotropin-releasing hormone pump usually does not result in multiple pregnancies. Filicori from the University of Bologna suggests that this might be because gonadotrophins are absent when the treatment is initiated, and therefore the hormones released by the pituitary (luteinizing hormone and follicle-stimulating hormone) can still take part in the retro-control of gonadotrophin secretion, mimicking the natural cycle. This treatment can also be used for underweight and/or anorexic patients; it has also been used in certain cases of hyperprolactimenia.

National and regional usage
In the Nordic countries, letrozole is practically the standard initial regimen used for ovulation induction, since no formulation of clomifene is registered for use there.India banned the usage of letrozole in 2011, citing potential risks to infants. In 2012, an Indian parliamentary committee said that the drug controller office colluded with letrozoles makers to approve the drug for infertility in India.

Technique
Although there are many possible additional diagnostic and interventional techniques, protocols for ovulation induction generally consist of:

Determining the first day of the last menstruation, which is termed day 1. In case of amenorrhea, a period can be induced by intake of an oral progestin for 10 days.
Daily administration of the ovulation induction regimen, starting on day 3, 4, or 5, and it is usually taken for 5 days.
Sexual intercourse or artificial insemination by the time of ovulation.

Ultrasonography
During ovulation induction, it is recommended to start at a low dose and monitor the ovarian response with transvaginal ultrasound, including discernment of the number of developing follicles. Initial exam is most commonly started 4–6 days after last pill. Serial transvaginal ultrasound can reveal the size and number of developing follicles. It can also provide presumptive evidence of ovulation such as sudden collapse of the preovulatory follicle, and an increase in fluid volume in the rectouterine pouch. After ovulation, it may reveal signs of luteinization such as loss of clearly defined follicular margins and appearance of internal echoes.

Supernumerary follicles
A cycle with supernumerary follicles is usually defined as one where there are more than two follicles >16 mm in diameter. It is generally recommended to have such cycles cancelled because of the risk of multiple pregnancy (see also the "Risks and side effects" section below). In cancelled cycles, the woman or couple should be warned of the risks in case of supernumerary follicles, and should avoid sexual intercourse or use contraception until the next menstruation. Induction of final maturation (such as done with hCG) may need to be withheld because of increased risk of ovarian hyperstimulation syndrome. The starting dose of the inducing drug should be reduced in the next cycle.Alternatives to cancelling a cycle are mainly:

Aspiration of supernumerary follicles until one or two remain.
Converting the protocol to IVF treatment with embryo transfer of up to two embryos only.
Selective fetal reduction. This alternative confers a high risk of complications.
Proceeding with any multiple pregnancy without fetal reduction, with the ensuing risk of complications. This alternative is not recommended.

Lab tests
The following laboratory tests may be used to monitor induced cycles:
Serum estradiol levels, starting 4–6 days after last pill
Adequacy of luteinizing hormone surge LH surge by urine tests 3 to 4 days after last clomifene pill
Post-coital test 1–3 days before ovulation to check whether there are at least 5 progressive sperm per HPF
Mid-luteal progesterone, with at least 10 ng/ml 7–9 days after ovulation being regarded as adequate.

Final maturation induction
Final maturation induction and release, such as by human chorionic gonadotropin (HCG or hCG) or recombinant luteinizing hormone, results in a predictable time of ovulation, with the interval from drug administration to ovulation depending on the type of drug. This avails for sexual intercourse or intrauterine insemination to conveniently be scheduled at ovulation, the most likely time to achieve pregnancy.As evidenced by clomifene-induced cycles, however, triggering oocyte release has been shown to decrease pregnancy chances compared to frequent monitoring with LH surge tests. Therefore, in such cases, triggering oocyte release is best reserved for women who require intrauterine insemination and in whom luteinizing hormone monitoring proves difficult or unreliable. It may also be used when luteinizing hormone monitoring has no shown an luteinizing hormone surge by cycle day 18 (where cycle day 1 is the first day of the preceding menstruation) and there is an ovarian follicle of over 20 mm in size.

Repeat cycles
Ovulation induction can be repeated every menstrual cycle. For clomifene, the dosage may be increased by 50-mg increments in subsequent cycles until ovulation is achieved. However, at a dosage of 200 mg, further increments are unlikely to increase pregnancy chances.It is not recommended by the manufacturer of clomifene to use it for more than 6 consecutive cycles. In women with anovulation, 7 - 12 attempted cycles of pituitary feedback regimens (as evidenced by clomifene citrate) are recommended before switching to gonadotrophins, since the latter ones are more expensive and less easy to control.It is no longer recommended to perform an ultrasound examination to exclude any significant residual ovarian enlargement before each new treatment cycle.

Risks and side effects
Ultrasound and regular hormone checks mitigate risks throughout the process. However, there are still some risks with the procedure </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 Paracentesis and can you explain it in depth? [/INST] Paracentesis (from Greek κεντάω, "to pierce") is a form of body fluid sampling procedure, generally referring to peritoneocentesis (also called laparocentesis or abdominal paracentesis) in which the peritoneal cavity is punctured by a needle to sample peritoneal fluid.The procedure is used to remove fluid from the peritoneal cavity, particularly if this cannot be achieved with medication. The most common indication is ascites that has developed in people with cirrhosis.

Indications
It is used for a number of reasons:
to relieve abdominal pressure from ascites
to diagnose spontaneous bacterial peritonitis and other infections (e.g. abdominal TB)
to diagnose metastatic cancer
to diagnose blood in peritoneal space in trauma

For ascites
The procedure is often performed in a doctors office or an outpatient clinic. In an experts hands, it is usually very safe, although there is a small risk of infection, excessive bleeding or perforating a loop of bowel. These last two risks can be minimized greatly with the use of ultrasound guidance.The patient is requested to urinate before the procedure; alternately, a Foley catheter is used to empty the bladder. The patient is positioned in the bed with the head elevated at 45–60 degrees to allow fluid to accumulate in lower abdomen. After cleaning the side of the abdomen with an antiseptic solution, the physician numbs a small area of skin and inserts a large-bore needle with a plastic sheath 2 to 5 cm (1 to 2 in) in length to reach the peritoneal (ascitic) fluid. The needle is removed, leaving the plastic sheath to allow drainage of the fluid </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 Paroxysmal nocturnal hemoglobinuria and can you explain it in depth? [/INST] Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, life-threatening disease of the blood characterized by destruction of red blood cells by the complement system, a part of the bodys innate immune system. This destructive process occurs due to deficiency of the red blood cell surface protein DAF, which normally inhibits such immune reactions. Since the complement cascade attacks the red blood cells within the blood vessels of the circulatory system, the red blood cell destruction (hemolysis) is considered an intravascular hemolytic anemia. Other key features of the disease, such as the high incidence of venous blood clot formation, are incompletely understood.PNH is the only hemolytic anemia caused by an acquired (rather than inherited) intrinsic defect in the cell membrane (deficiency of glycophosphatidylinositol or GPI) leading to the absence of protective exterior surface proteins that normally attach via a GPI anchor. It may develop on its own ("primary PNH") or in the context of other bone marrow disorders such as aplastic anemia ("secondary PNH"). Only a minority of affected people  have the telltale red urine in the morning that originally gave the condition its name.Allogeneic bone marrow transplantation is the only cure, but has significant rates of additional medical problems and death. The monoclonal antibody eculizumab reduces the need for blood transfusions and improves quality of life for those affected by PNH. Eculizumab dramatically alters the natural course of PNH, reducing symptoms and disease complications as well as improving survival to the extent that it may be equivalent to that of the general population. Eculizumab costs at least US$440,000 for a single year of treatment and has been reported as one of the worlds most expensive drugs.

Signs and symptoms
The classic sign of PNH is red discoloration of the urine due to the presence of hemoglobin  and hemosiderin from the breakdown of red blood cells. As the urine is more concentrated in the morning, this is when the color is most pronounced. This phenomenon mainly occurs in those who have the primary form of PNH, who will notice this at some point in their disease course. The remainder mainly experience the symptoms of anemia, such as tiredness, shortness of breath, and palpitations.A small proportion of patients report attacks of abdominal pain, difficulty swallowing and pain during swallowing, as well as erectile dysfunction in men; this occurs mainly when the breakdown of red blood cells is rapid, and is attributable to spasm of smooth muscle due to depletion of nitric oxide by red cell breakdown products.Forty percent of people with PNH develop thrombosis (a blood clot) at some point in their illness. This is the main cause of severe complications and death in PNH. These may develop in common sites (deep vein thrombosis of the leg and resultant pulmonary embolism when these clots break off and enter the lungs), but in PNH blood clots may also form in more unusual sites: the hepatic vein (causing Budd-Chiari syndrome), the portal vein of the liver (causing portal vein thrombosis), the superior or inferior mesenteric vein (causing mesenteric ischemia) and veins of the skin. Cerebral venous thrombosis, an uncommon form of stroke, is more common in those with PNH.

Pathophysiology
All cells have proteins attached to their membranes, often serving as a mode of communication or signaling between the cell and the surrounding environment. These signaling proteins are physically attached to the cell membrane in various ways, commonly anchored by glycolipids such as glycosyl phosphatidylinositols (GPI). PNH occurs as a result of a defect in the assembling of these glycolipid-protein structures on the surface of blood cells.The most common defective enzyme in PNH is phosphatidylinositol glycan A (PIGA), one of several enzymes needed to make GPI. The gene that codes for PIGA is located on the X chromosome, which means that only one active copy of the gene for PIGA is present in each cell (initially, females have two copies, but one is silenced through X-inactivation). A mutation in the PIGA gene can lead to the absence of GPI anchors expressed on the cell membrane. When this mutation occurs in a hematopoietic stem cell in the bone marrow, all of the cells it produces will also have the defect.Several of the proteins that anchor to GPI on the cell membrane are used to protect the cell from destruction by the complement system, and, without these anchors, the cells are more easily targeted by the complement proteins. Although red blood cells, white blood cells, and platelets are targeted by complement, red blood cells are particularly vulnerable to lysis. The complement system is part of the innate immune system and has a variety of functions, from destroying invading microorganisms by opsonization to direct destabilization by the membrane attack complex. The main proteins that protect blood cells from destruction are decay-accelerating factor (DAF/CD55), which disrupts formation of C3-convertase, and protectin (CD59/MIRL/MAC-IP), which binds the membrane attack complex and prevents C9 from binding to the cell.The symptoms of esophageal spasm, erectile dysfunction, and abdominal pain are attributed to the fact that hemoglobin released during hemolysis binds with circulating nitric oxide, a substance that is needed to relax smooth muscle. This theory is supported by the fact that these symptoms improve on administration of nitrates or sildenafil (Viagra), which improves the effect of nitric oxide on muscle cells. There is a suspicion that chronic hemolysis causing chronically depleted nitric oxide may lead to the development of pulmonary hypertension (increased pressure in the blood vessels supplying the lung), which in turn puts strain on the heart and causes heart failure.Historically, the role of sleep and night in this disease (the "nocturnal" component of the name) has been attributed to acidification of the blood at night due to relative hypoventilation and accumulation of carbon dioxide in the blood during sleep. This hypothesis has been questioned by researchers who note that not all those with PNH have increased hemolysis during sleep, so it is uncertain how important a role sleep actually plays in this disease.

Diagnosis
Blood tests in PNH show changes consistent with intravascular hemolytic anemia: low hemoglobin, raised lactate dehydrogenase, raised bilirubin (a breakdown product of hemoglobin), and decreased levels of haptoglobin; there can be raised reticulocytes (immature red cells released by the bone marrow to replace the destroyed cells) if there is no iron deficiency present. The direct antiglobulin test (DAT, or direct Coombs test) is negative, as the hemolysis of PNH is not caused by antibodies. If the PNH occurs in the setting of known (or suspected) aplastic anemia, abnormal white blood cell counts and decreased platelet counts may be seen at this. In this case, anemia may be caused by insufficient red blood cell production in addition to the hemolysis.Historically, the sucrose lysis test, in which a patients red blood cells are placed in low-ionic-strength solution and observed for hemolysis, was used for screening.  If this was positive, the Hams acid hemolysis test (after Dr Thomas Ham, who described the test in 1937) was performed for confirmation. The Ham test involves placing red blood cells in mild acid; a positive result (increased RBC fragility) indicates PNH or Congenital dyserythropoietic anemia. This is now an obsolete test for diagnosing PNH due to its low sensitivity and specificity.Today, the gold standard is flow cytometry for CD55 and CD59 on white and red blood cells.  Based on the levels of these cell proteins, erythrocytes may be classified as type I, II, or III PNH cells. Type I cells have normal levels of CD55 and CD59; type II have reduced levels; and type III have absent levels. The fluorescein-labeled proaerolysin (FLAER) test is being used more frequently to diagnose PNH.  FLAER binds selectively to the glycophosphatidylinositol anchor and is more accurate in demonstrating a deficit than simply for CD59 or CD55.

Classification
PNH is classified by the context under which it is diagnosed:
Classic PNH. Evidence of PNH in the absence of another bone marrow disorder.
PNH in the setting of another specified bone marrow disorder such as aplastic anemia and myelodysplastic syndrome (MDS).
Subclinical PNH. PNH abnormalities on flow cytometry without signs of hemolysis.

Screening
There are several groups where screening for PNH should be undertaken. These include patients with unexplained thrombosis who
are young, have thrombosis in an unusual site (e.g. intra-abdominal veins, cerebral veins, dermal veins), have any evidence of hemolysis (e.g. a raised LDH), or have a low red blood cell, white blood cell, or platelet count. Those who have a diagnosis of aplastic anemia should be screened annually.

Treatment
Acute attacks
There is disagreement as to whether steroids (such as prednisolone) can decrease the severity of hemolytic crises. Transfusion therapy may be needed; in addition to correcting significant anemia, this suppresses the production of PNH cells by the bone marrow, and indirectly the severity of the hemolysis. Iron deficiency develops with time, due to losses in urine, and may have to be treated if present. Iron therapy can result in more hemolysis as more PNH cells are produced.

Long-term
PNH is a chronic condition. In patients with only a small clone and few problems, monitoring of the flow cytometry every six months gives information on the severity and risk of potential complications. Given the high risk of thrombosis in PNH, preventive treatment with warfarin decreases the risk of thrombosis in those with a large clone (50% of white blood cells type III).Episodes of thrombosis are treated as they would in other patients, but, given that PNH is a persisting underlying cause, it is likely that treatment with warfarin or similar drugs needs to be continued long-term after an episode of thrombosis.

Eculizumab
In 2007, the drug eculizumab was approved for the treatment of PNH. Prior to eculizumab, the median life expectancy of an individual with PNH was approximately 10 years. Since that time, short and mid-term studies of patients on eculizumab demonstrate that the drug returns the patient to a normal life expectancy, improves quality of life, and decreases the need for blood transfusions.Eculizumab is controversial due to its high cost, as it is among the most expensive pharmaceuticals in the world, with a price of US$440,000 per person per year. Eculizumab is a humanized monoclonal antibody that acts as a terminal complement inhibitor </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 Patent ductus arteriosus and can you explain it in depth? [/INST] Patent ductus arteriosus (PDA) is a medical condition in which the ductus arteriosus fails to close after birth: this allows a portion of oxygenated blood from the left heart to flow back to the lungs by flowing from the aorta, which has a higher pressure, to the pulmonary artery. Symptoms are uncommon at birth and shortly thereafter, but later in the first year of life there is often the onset of an increased work of breathing and failure to gain weight at a normal rate. With time, an uncorrected PDA usually leads to pulmonary hypertension followed by right-sided heart failure.
The ductus arteriosus is a fetal blood vessel that normally closes soon after birth. In a PDA, the vessel does not close, but remains patent (open), resulting in an abnormal transmission of blood from the aorta to the pulmonary artery. PDA is common in newborns with persistent respiratory problems such as hypoxia, and has a high occurrence in premature newborns. Premature newborns are more likely to be hypoxic and have PDA due to underdevelopment of the heart and lungs.
If transposition of the great vessels is present in addition to a PDA, the PDA is not surgically closed since it is the only way that oxygenated blood can mix with deoxygenated blood. In these cases, prostaglandins are used to keep the PDA open, and NSAIDs are not administered until surgical correction of the two defects is completed.

Signs and symptoms
Common symptoms include:
dyspnea (shortness of breath)Signs include:
tachycardia (a heart rate exceeding the normal resting rate)
continuous "machine-like" (also described as "rolling-thunder" and "to-and-fro") heart murmur (usually from aorta to pulmonary artery, with higher flow during systole and lower flow during diastole)
cardiomegaly (enlarged heart, reflecting ventricular dilation and volume overload)
left subclavicular thrill
bounding pulse
widened pulse pressure
increased cardiac output
increased systolic pressure
poor growth
differential cyanosis, i.e. cyanosis of the lower extremities but not of the upper body.People with patent ductus arteriosus typically present in good health, with normal respirations and heart rate. If the PDA is moderate or large, widened pulse pressure and bounding peripheral pulses are frequently present, reflecting increased left ventricular stroke volume and diastolic run-off of blood into the (initially lower-resistance) pulmonary vascular bed. Eisenmenger physiology is pulmonary hypertension due to a left-to-right shunt. Prominent suprasternal and carotid pulsations may be noted secondary to increased left ventricular stroke volume.

Risk factors
Known risk factors include:
Preterm birth
Congenital rubella syndrome
Chromosomal abnormalities (e.g., Down syndrome)
Genetic conditions such as Loeys–Dietz syndrome (would also present with other heart defects), Wiedemann–Steiner syndrome, and CHARGE syndrome.
Fetal Alcohol Spectrum Disorder

Diagnosis
PDA is usually diagnosed using noninvasive techniques. Echocardiography (in which sound waves are used to capture the motion of the heart) and associated Doppler studies are the primary methods of detecting PDA. Electrocardiography (ECG), in which electrodes are used to record the electrical activity of the heart, is not particularly helpful as no specific rhythms or ECG patterns can be used to detect PDA.A chest X-ray may be taken, which reveals overall heart size (as a reflection of the combined mass of the cardiac chambers) and the appearance of blood flow to the lungs. A small PDA most often accompanies a normal-sized heart and normal blood flow to the lungs. A large PDA generally accompanies an enlarged cardiac silhouette and increased blood flow to the lungs.

Prevention
Some evidence suggests that intravenous NSAIDs, such as indomethacin, administration on the first day of life to all preterm infants reduces the risk of developing a PDA and the complications associated with PDA. Intravenous Indomethacin treatment in premature infants also may reduce the need for surgical intervention. Administering ibuprofen probably helps to prevent PDA and reduce the need for surgery but it also likely increases the risk of kidney complications.

Treatment
Symptomatic PDA can be treated with both surgical and non-surgical methods.

Conservative
Neonates without adverse symptoms may simply be monitored as outpatients.

Surgery
Surgically, the DA may be closed by ligation (though support in premature infants is mixed). This can either be performed manually and be tied shut, or with intravascular coils or plugs that leads to formation of a thrombus in the DA.Devices developed by Franz Freudenthal block the blood vessel with woven structures of nitinol wire.Newer procedures performed effectively in older, bigger children include catheter PDA occlusion and video-assisted thoracoscopic PDA clipping.

Prostaglandin inhibitors
Because prostaglandin E2 is responsible for keeping the DA open, NSAIDs (which can inhibit prostaglandin synthesis) such as indomethacin or a special form of ibuprofen have been used to initiate PDA closure. Findings from a 2015 systematic review concluded that, for closure of a PDA in preterm and/or low birth weight infants, ibuprofen is as effective as indomethacin </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Head lice infestation and can you explain it in depth? [/INST] Head lice infestation, also known as pediculosis capitis, is the infection of the head hair and scalp by the head louse (Pediculus humanus capitis). Itching from lice bites is common. During a persons first infection, the itch may not develop for up to six weeks. If a person is infected again, symptoms may begin much more quickly. The itch may cause problems with sleeping. Generally, however, it is not a serious condition. While head lice appear to spread some other diseases in Africa, they do not appear to do so in Europe or North America.Head lice are spread by direct contact with the hair of someone who is infected. The cause of head lice infestations in children is not related to cleanliness. Other animals, such as cats and dogs, do not play a role in transmission. Head lice feed only on human blood and are only able to survive on human head hair. When adults, they are about 2 to 3 mm long. When not attached to a human, they are unable to live beyond three days. Humans can also become infected with two other lice – the body louse and the crab louse. To make the diagnosis, live lice must be found. Using a comb can help with detection. Empty eggshells (known as nits) are not sufficient for the diagnosis.Possible treatments include: combing the hair frequently with a fine tooth comb or shaving the head completely. A number of topical medications are also effective, including malathion, ivermectin, and dimethicone. Dimethicone, which is a silicone oil, is often preferred due to the low risk of side effects. Pyrethroids such as permethrin have been commonly used; however, they have become less effective due to increasing pesticide resistance. There is little evidence for alternative medicines.Head-lice infestations are common, especially in children. In Europe, they infect between 1 and 20% of different groups of people. In the United States, between 6 and 12 million children are infected a year. They occur more often in girls than boys. It has been suggested that historically, head lice infection were beneficial, as they protected against the more dangerous body louse. Infestations may cause stigmatization of the infected individual.

Epidemiology
Reliable data describing the usual incidence of infestation in the general public, in the average school community, or during specific times of the year are lacking.
The number of cases of human louse infestations (or pediculosis) has increased worldwide since the mid-1960s, reaching hundreds of millions annually. It is estimated between 1 and 20% of specific groups in Europe are infected.Despite improvements in medical treatment and prevention of human diseases during the 20th century, head louse infestation remains stubbornly prevalent. In 1997, 80% of American elementary schools reported at least one outbreak of lice. Lice infestation during that same period was more prevalent than chickenpox.About 6–12 million children between the ages of 3 and 11 are treated annually for head lice in the United States alone. High levels of louse infestations have also been reported from all over the world, including Israel, Denmark, Sweden, U.K., France, and Australia.The United Kingdoms National Health Service report that lice have no preference for any type of hair be it clean, dirty, or short. The number of children per family, the sharing of beds and closets, hair washing habits, local customs and social contacts, healthcare in a particular area (e.g. school), and socioeconomic status were found to be factors in head louse infestation in Iran. Other studies found no relationship between frequency of brushing or shampooing. The California Department of Public Health indicates that chronic head lice infestation may be a sign of socioeconomic or family problems. Children between 4 and 13 years of age are the most frequently infested group. In the U.S., African-American children have lower rates of infestation.Head lice (Pediculus humanus capitis) infestation is most frequent on children aged 3–10 and their families. Females get head lice twice as often as males, and infestation in persons of Afro-Caribbean or other black descent could be rare due to difference in hair shape or width. But these children may have nits that hatch and the live lice could be transferred by head contact to other children.

Signs and symptoms
Head lice are generally uncomfortable, but typically do not constitute a serious condition. The most common symptom is itching of the head, which normally worsens 3 to 4 weeks after the initial infestation. The bite reaction is very mild, and it can be rarely seen between the hairs. Bites can be seen, especially in the neck of long-haired individuals when the hair is pushed aside. Swelling of the local lymph nodes and fever are rare. Itching may cause skin breakdown and uncommonly result in a bacterial infection. Many individuals do not experience symptoms. Itching may take 2–6 weeks to develop upon first infestation, and sooner in subsequent infestations.In Ethiopia, head lice appear to be able to spread louse-born epidemic typhus and Bartonella quintana. In Europe, the head lice do not appear to carry these infections.

Transmission
Head lice spreads through direct contact of the head of an infested person with the head of a non-infested person. The presence of live lice indicates an active infestation while the presence of nits indicates a past or currently inactive infection with the potential to become active. Head lice do not leap or spring as a means to transfer to their hosts; instead, they move by crawling. Transmission by indirect contact (e.g. sharing bedding, clothing, headwear, the same comb) is much less common. The cause of head lice infestations is not related to cleanliness. Neither hair length nor how often the hair is brushed affects the risk of infection. Pets are not vectors for head lice.Other lice that infest humans are the body louse and the crab louse (aka pubic lice). The claws of these three species are adapted to attach to specific hair diameters. Pubic lice are most often spread by sexual contact with an infested person. Body lice can be found on clothing and they are not known to burrow into the skin.

Diagnosis
The condition is diagnosed by finding live lice and unhatched eggs in the hair. Finding empty eggs is not enough. Dandruff, lint, sand,  hair casts, and dried hairspray, can be mistaken for eggs and nits. This is made easier by using a magnifying glass or running a comb through the childs wet hair, the latter of which is the most assured method of diagnosis and can be used to monitor treatment. In questionable cases, a child can be referred to a health professional. However, head lice infestation is commonly overdiagnosed, with extinct infestations being mistaken for active ones. Infestations are only considered extinct if nits are more than 0.25 inches away from the scalp and nymphs and adult lice are absent. As a result, lice-killing treatments are more often used on non-infested than infested children. The use of a louse comb is the most effective way to detect living lice. With both methods, special attention should be paid to the area near the ears and the nape of the neck. The use of a magnifying glass to examine the material collected between the teeth of the comb could prevent misdiagnosis.The presence of nits alone, however, is not an accurate indicator of an active head louse infestation. Generally, white nits are empty egg casings, while brown nits may still contain viable louse larva. One way of determining the nit is to squeeze it between two fingernails; it gives a characteristic snapping pop sound as the egg bursts. Children with nits on their hair have a 35–40% chance of also being infested with living lice and eggs. If lice are detected, the entire family needs to be checked (especially children up to the age of 13 years) with a louse comb, and only those who are infested with living lice should be treated. As long as no living lice are detected, the child should be considered negative for head louse infestation. Accordingly, a child should be treated with a pediculicide only when living lice are detected on their hair (not because he/she has louse eggs/nits on the hair and not because the scalp is itchy).

Prevention
Examination of the childs head at regular intervals using a louse comb allows the diagnosis of louse infestation at an early stage. Early diagnosis makes treatment easier and reduces the possibility of infesting others. In times and areas when louse infestations are common, weekly examinations of children, especially those 4–15 years old, carried out by their parents, will aid control. Additional examinations are necessary if the child came in contact with infested individuals, if the child frequently scratches his/her head, or if nits suddenly appear on the childs hair.
Clothes, towels, bedding, combs, and brushes, which came in contact with the infested individual, can be disinfected either by leaving them outside for at least two days or by washing them at 60 °C (140 °F) for 30 minutes. This is because adult lice can survive only one to two days without a blood meal and are highly dependent on human body warmth.

Treatment
There are a number of treatments effective for head lice. These methods include combs, shaving, medical creams, and hot air. Medical creams usually require two treatments a week apart. Head lice are not justification to keep children home from school as the risk of spread is low.

Mechanical measures
Wet combing (mechanical removal of lice through combing wet hair) can be used as treatment measure for those who are too young for pediculicide treatment, which is intended for 6 years of age or older. Wet combing a few times a day for a few weeks may also get rid of the infestation in half of people.  This requires the use of a special lice comb with extra fine teeth. This is the recommended method for infants and women who are pregnant. Shaving the head can also effectively treat lice.
Another treatment is the use of heated air applied by a hair dryer. This can be of special use in the early stages of an infestation, since it has very high mortality for eggs.

Medications
There are many medications which can kill lice. Dimethicone is between 70 and 97% effective with a low rate of side effects, and thus is seen as the preferred treatment. It works by physical means and there is no evidence of pesticide resistance. Ivermectin is around 80% effective, but can cause local skin irritation. Malathion has an effectiveness around 90%, but theres the possibility of toxicity. Pyrethroids such as permethrin, while commonly used, have lower rates of effectiveness due to the resistance among lice. Effectiveness varies from 10 to 80%, depending on the population studied. Medications within a lotion appear to work better than those within a shampoo. Benzyl alcohol appears effective but it is unclear if it is better than standard treatments. Abametapir was approved for medical use in the United States in July 2020.Resistance to several commonly used treatments is increasing worldwide, with patterns of resistance varying by region. Head lice have demonstrated resistance to permethrin, malathion, phenothrin, and carbaryl in several countries around the world. A previous method used to delay resistance included utilizing a rotating list of recommended insecticides by health authorities. The mosaic model is the current recommendation, in which it is advised to use one product for a treatment course, followed by a different insecticide from another substance class if the first treatment fails.

Home Remedies
Tea tree oil has been promoted as a treatment for head lice; however, there is no clear evidence of its effectiveness. A 2012 review of head lice treatment recommended against the use of tea tree oil for children because it could cause skin irritation or allergic reactions, because of contraindications, and because of a lack of knowledge about the oils safety and effectiveness. Other home remedies, such as putting vinegar, isopropyl alcohol, olive oil, mayonnaise, or melted butter under a shower cap, have been disproven. The CDC states that swimming has no effect on drowning lice, and can decrease the effectiveness of some treatments.

Environment
After treatment, people are often instructed to wash all bedding and vacuum all areas the head may have been, such as car seats, coat hoods, and sofas, but this is not always necessary, since adult lice will die within 2 days without a blood meal, and newly hatched lice die within minutes of hatching. Combs and brushes may be deloused in boiling water for 5–10 minutes. Items may also be frozen for 24 hours well below the freezing point of water to ensure that ice crystals form within the cells of the lice.

Outbreak Management
In addition to environmental management, an outbreak of head lice infestation requires synchronous treatment of all who are infested and evaluation of those who have been exposed or are suspected to have head lice. Synchronous ovoidal dimethicone treatment has been shown to successfully manage and terminate outbreaks, and a single treatment is likely sufficient </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 Pediculosis corporis and can you explain it in depth? [/INST] Pediculosis corporis is a cutaneous condition caused by body lice (specifically Pediculus humanus humanus) that lay their eggs in the seams of clothing.: 447

Signs and symptoms
Body lice are a nuisance in themselves and cause intense itching. They are also vectors (transmitters) of other diseases and can spread epidemic typhus, trench fever, and louse-borne relapsing fever.

Risk factors
Body lice are spread through prolonged direct physical contact with a person who has them or through contact with articles such as clothing, beds, bed linens, or towels that have been in contact with an infested person. In the United States, body lice infestations are rare, typically found mainly in homeless transient populations who do not have access to bathing and regular changes of clean clothes. Infestation is unlikely to persist on anyone who bathes regularly and who has at least weekly access to freshly laundered clothing and bedding.Although louse-borne (epidemic) typhus is no longer widespread, outbreaks of this disease still occur during times of war, civil unrest, natural or man-made disasters, and in prisons where people live together in unsanitary conditions </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 Pediculosis pubis and can you explain it in depth? [/INST] Pediculosis pubis (also known as "crabs" and "pubic lice") is an infestation by the pubic louse, Pthirus pubis, a wingless insect which feeds on blood and lays its eggs (nits) on mainly pubic hair. Less commonly, hair near the anus, armpit, beard, eyebrows, moustache, and eyelashes may be involved. It is usually acquired during sex, but can be spread via bedding, clothing and towels, and is more common in crowded conditions where there is close contact between people.The main symptom is an intense itch in the groin, particularly at night. There may be some grey-blue discolouration at the feeding site, and eggs and lice may be visible. Scratch marks, crusting and scarring may be seen, and there may be signs of secondary bacterial infection.Diagnosis is by visualising the nits or live lice, either directly or with a magnifying glass. Investigations for other sexually transmitted infections (STIs) are usually performed.First line treatment usually contains permethrin and is available over the counter. Two rounds of treatment at least a week apart are usually required to kill newly hatched nymphs. Washing bedding and clothing in hot water kills the lice, and transmission can be prevented by avoiding sexual contact until no signs of infestation exist. Eggs may be removed by combing pubic hair with a comb dipped in vinegar. Sexual partners should be evaluated and treated.Infestation with pubic lice is found in all parts of the world and occurs in all ethnic groups and all levels of society. Worldwide, the condition affects about 2% of the population.

Definition
Pediculosis pubis is an infestation by the pubic louse, Pthirus pubis, a wingless insect which feeds on blood and lays its eggs (nits) on mainly pubic hair. Less commonly, hair near the anus, armpit, beard, eyebrows, moustache, and eyelashes may be involved. Although the presence of pubic lice are associated with the presence of other sexually transmitted diseases, pubic lice do not spread infectious diseases.

Signs and symptoms
The onset of symptoms is typically three weeks after the first infestation of lice and is mainly an intense itch in the pubic area and groin, particularly at night, resulting from an allergic reaction to the saliva of feeding lice. In some infestations, a characteristic grey-blue or slate coloration macule appears (maculae caeruleae) at the feeding site, which may last for days. Nits or live lice may be seen crawling on the skin. Louse droppings may be noticed as a black powder in the underwear.Scratch marks, crusting, scarring, rust-colored faecal material, blood stained underwear and secondary bacterial infection may sometimes be seen. Large lymph nodes in the groin and armpits may be felt. Some people with pubic lice infestation may not have any symptoms.

Causes
Spread
Pubic lice are usually transmitted from one person to another during vaginal, oral or anal sex, whether a condom is used or not. One sexual encounter with an infected person carries a high risk of catching pubic lice. In some circumstances transmission can occur through kissing and hugging, and less likely via bedding, clothing and towels. The lice spread more easily in crowded conditions where the distance between people is close, allowing the lice to crawl from one person to another.Infestation on the eyebrows or eyelashes of a child may indicate sexual exposure or abuse.

Characteristics and life cycle
Pubic lice (Pthirus pubis) have three stages: the egg (also called a nit), the nymph, and the adult. They can be hard to see and are found firmly attached to the hair shaft. They are oval and usually yellow to white. Pubic lice nits take about 6–10 days to hatch. The nymph is an immature louse that hatches from the nit (egg). A nymph looks like an adult pubic louse but it is smaller. Pubic lice nymphs take about 2–3 weeks after hatching to mature into adults capable of reproducing. To live, a nymph must feed on blood. The adult pubic louse resembles a miniature crab when viewed through a strong magnifying glass. Pubic lice have six legs; their two front legs are very large and look like the pincher claws of a crab—thus the nickname "crabs". Pubic lice are tan to grayish-white in color. Females lay nits and are usually larger than males. To live, lice must feed on blood. If the louse falls off a person, it dies within 1–2 days. Eggs (nits) are laid on a hair shaft. Females will lay approximately 30 eggs during their 3–4 week life span. Eggs hatch after about a week and become nymphs, which look like smaller versions of the adults. The nymphs undergo three molts before becoming adults. Adults are 1.5–2.0 mm long and flattened. They are much broader in comparison to head and body lice. Adults are found only on the human host and require human blood to survive. Pubic lice are transmitted from person to person most-commonly via sexual contact, although fomites (bedding, clothing) may play a minor role in their transmission.

Diagnosis
Diagnosis is made by carefully looking at the pubic hair for nits, young lice and adult lice. Lice and nits can be removed either with forceps or by cutting the infested hair with scissors (with the exception of an infestation of the eye area). A magnifying glass, dermatoscope or a stereo-microscope can be used for identification. Testing for other sexually transmitted infections is recommended in those who are infested with pubic lice.

Treatment
Pubic lice can be treated at home. Available treatments may vary from country to country and include mainly permethrin-containing creams and lotions applied to cool dry skin.Treatment with medication is combined with combing pubic hair with a fine-toothed comb after applying vinegar directly to skin or dipping the comb in vinegar, to remove nits. It is recommended to wash bedding, clothing and towels in hot water or preferably in a washing machine at 50°C or higher. When this is not possible, the clothing can be stored in a sealed plastic bag for at least three days. Re-infestation can be prevented by wearing clean underwear at the start of treatment and after completing treatment. Shaving the affected hair is not essential.

First line
At first, treatment is usually with topical permethrin 1% cream, which can be bought over the counter without a prescription. It is applied to the areas affected by pubic lice and washed off after 10 minutes. Brands of permethrin include Lyclear, available in the UK as a creme rinse or dermal cream at 5% strengths.
In the US, permethrin may be familiar as NIX, Actin and ElimiteAn alternative is the combination of pyrethrins and piperonyl butoxide, in a topical application, which include the brands Licide, and A-200, Pronto and RID shampoos. These medications are safe and effective when used exactly according to the instructions in the package or on the label. To kill newly hatched lice, both treatments can be repeated within the following seven to ten days.European guidelines state alternatives to permethrin as including either the application of 0.2% phenothrin (washed off after two hours), or 0.5% malathion lotions (washed off after 12 hours). The CDC states alternatives as topical 0.5% malathion or oral ivermectin.

Other treatments
Lindane is still used in a shampoo form in some non-European countries. Its licence was withdrawn by the European Medicines Agency in 2008. It may be considered as a last resort in some people who show resistance to other treatments, but is not recommended to be used for a second round of treatment. Lindane is not recommended in pregnant and breastfeeding women, children under the age of two years, and people who have extensive dermatitis </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 Pellagra and can you explain it in depth? [/INST] Pellagra  is a disease caused by a lack of the vitamin niacin (vitamin B3). Symptoms include inflamed skin, diarrhea, dementia, and sores in the mouth. Areas of the skin exposed to either sunlight or friction are typically affected first. Over time affected skin may become darker, stiffen, peel, or bleed.There are two main types of pellagra, primary and secondary. Primary pellagra is due to a diet that does not contain enough niacin and tryptophan. Secondary pellagra is due to a poor ability to use the niacin within the diet. This can occur as a result of alcoholism, long-term diarrhea, carcinoid syndrome, Hartnup disease, and a number of medications such as isoniazid. Diagnosis is typically based on symptoms and may be assisted by urine testing.Treatment is with either niacin or nicotinamide supplementation. Improvements typically begin within a couple of days. General improvements in diet are also frequently recommended. Decreasing sun exposure via sunscreen and proper clothing is important while the skin heals. Without treatment death may occur. The disease occurs most commonly in the developing world, often as a disease of poverty associated with malnutrition, specifically sub-Saharan Africa.

Signs and symptoms
The classic symptoms of pellagra are diarrhea, dermatitis, dementia, and death ("the four Ds").
A more comprehensive list of symptoms includes:

Sensitivity to sunlight
Dermatitis (characteristic "broad collar" rash known as casal collar)
Hair loss
Swelling
Smooth, beefy red glossitis (tongue inflammation)
Trouble sleeping
Weakness
Mental confusion or aggression
Ataxia (lack of coordination), paralysis of extremities, peripheral neuritis (nerve damage)
Diarrhea
Dilated cardiomyopathy (enlarged, weakened heart)
Eventually dementiaJ. Frostigs and Tom Spies—according to Cleary and Cleary—described more specific psychological symptoms of pellagra as:

Psychosensory disturbances (impressions as being painful, annoying bright lights, odors intolerance causing nausea and vomiting, dizziness after sudden movements),
Psychomotor disturbances (restlessness, tense and a desire to quarrel, increased preparedness for motor action), as well as
Emotional disturbancesIndependently of clinical symptoms, blood level of tryptophan or urinary metabolites such as 2-pyridone/N-methylniacinamide ratio <2 or NAD/NADP ratio in red blood cells can diagnose pellagra. The diagnosis is confirmed by rapid improvements in symptoms after doses of niacin (250–500 mg/day) or niacin enriched food.

Pathophysiology
Pellagra can develop according to several mechanisms, classically as a result of niacin (vitamin B3) deficiency, which results in decreased nicotinamide adenine dinucleotide (NAD). Since NAD and its phosphorylated NADP form are cofactors required in many body processes, the pathological impact of pellagra is broad and results in death if not treated.
The first mechanism is simple dietary lack of niacin. Second, it may result from deficiency of tryptophan, an essential amino acid found in meat, poultry, fish, eggs, and peanuts that the body uses to make niacin. Third, it may be caused by excess leucine, as it inhibits quinolinate phosphoribosyl transferase (QPRT) and inhibits the formation of niacin or nicotinic acid to nicotinamide mononucleotide (NMN) causing pellagra like symptoms to occur.Some conditions can prevent the absorption of dietary niacin or tryptophan and lead to pellagra. Inflammation of the jejunum or ileum can prevent nutrient absorption, leading to pellagra, and this can in turn be caused by Crohns disease. Gastroenterostomy can also cause pellagra. Chronic alcoholism can also cause poor absorption which combines with a diet already low in niacin and tryptophan to produce pellagra. Hartnup disease is a genetic disorder that reduces tryptophan absorption, leading to pellagra.
Alterations in protein metabolism may also produce pellagra-like symptoms. An example is carcinoid syndrome, a disease in which neuroendocrine tumors along the GI tract use tryptophan as the source for serotonin production, which limits the available tryptophan for niacin synthesis. In normal patients, only one percent of dietary tryptophan is converted to serotonin; however, in patients with carcinoid syndrome, this value may increase to 70%.  Carcinoid syndrome thus may produce niacin deficiency and clinical manifestations of pellagra.  Anti-tuberculosis medication tends to bind to vitamin B6 and reduce niacin synthesis, since B6 (pyridoxine) is a required cofactor in the tryptophan-to-niacin reaction.
Several therapeutic drugs can provoke pellagra.  These include the antibiotics isoniazid, which decreases available B6 by binding to it and making it inactive, so it cannot be used in niacin synthesis, and chloramphenicol; the anti-cancer agent fluorouracil; and the immunosuppressant mercaptopurine.

Treatment
If untreated, pellagra can kill within four or five years. Treatment is with nicotinamide, which has the same vitamin function as niacin and a similar chemical structure, but has lower toxicity. The frequency and amount of nicotinamide administered depends on the degree to which the condition has progressed.

Epidemiology
Pellagra can be common in people who obtain most of their food energy from corn, notably rural South America, where maize is a staple food. If maize is not nixtamalized, it is a poor source of tryptophan, as well as niacin. Nixtamalization corrects the niacin deficiency, and is a common practice in Native American cultures that grow corn, but most especially in Mexico and the countries of Central America. Following the corn cycle, the symptoms usually appear during spring, increase in the summer due to greater sun exposure, and return the following spring. Indeed, pellagra was once endemic in the poorer states of the U.S. South, such as Mississippi and Alabama, where its cyclical appearance in the spring after meat-heavy winter diets led to it being known as "spring sickness" (particularly when it appeared among more vulnerable children), as well as among the residents of jails and orphanages as studied by Dr. Joseph Goldberger.Pellagra is common in Africa, Indonesia, and China. In affluent societies, a majority of patients with clinical pellagra are poor, homeless, alcohol-dependent, or psychiatric patients who refuse food. Pellagra was common among prisoners of Soviet labor camps (the Gulags).  In addition, pellagra, as a micronutrient deficiency disease, frequently affects populations of refugees and other displaced people due to their unique, long-term residential circumstances and dependence on food aid. Refugees typically rely on limited sources of niacin provided to them, often peanuts (which, in Africa, may be supplied in place of local groundnut staples, such as the Bambara or Hausa groundnut); the instability in the nutritional content and distribution of food aid can be the cause of pellagra in displaced populations. In the 2000s, there were outbreaks in countries such as Angola, Zimbabwe and Nepal. In Angola specifically, recent reports show a similar incidence of pellagra since 2002, with clinical pellagra in 0.3% of women and 0.2% of children and niacin deficiency in 29.4% of women and 6% of children related to high untreated corn consumption.In other countries such as the Netherlands and Denmark, even with sufficient intake of niacin, cases have been reported. In this case, deficiency might happen not just because of poverty or malnutrition but secondary to alcoholism, drug interaction (psychotropic, cytostatic, tuberculostatic or analgesics), HIV, vitamin B2 and B6 deficiency, or malabsorption syndromes such as Hartnup disease and carcinoid tumors.

History
Native American cultivators who first domesticated corn (maize) prepared it by nixtamalization, in which the grain is treated with a solution of alkali such as lime. Nixtamalization makes the niacin nutritionally available and prevents pellagra. When maize was cultivated worldwide, and eaten as a staple without nixtamalization, pellagra became common.
Pellagra was first described for its dermatological effect in Spain in 1735 by Gaspar Casal. He explained that the disease causes dermatitis in exposed skin areas such as hands, feet and neck and that the origin of the disease is poor diet and atmospheric influences. His work published in 1762 by his friend Juan Sevillano was titled Historia Natural y Medicina del Principado de Asturias or Natural and Medical History of the Principality of Asturias (1762). This led to the disease being known as "Asturian leprosy", and it is recognized as the first modern pathological description of a syndrome. It was an endemic disease in northern Italy, where it was named, from Lombard, as "pell agra" (agra = holly-like or serum-like; pell = skin) by Francesco Frapolli of Milan. With pellagra affecting over 100,000 people in Italy by the 1880s, debates raged as to how to classify the disease (as a form of scurvy, elephantiasis or as something new), and over its causation. In the 19th century, Roussel started a campaign in France to restrict consumption of maize and eradicated the disease in France, but it remained endemic in many rural areas of Europe. Because pellagra outbreaks occurred in regions where maize was a dominant food crop, the most convincing hypothesis during the late 19thcentury, as espoused by Cesare Lombroso, was that the maize either carried a toxic substance or was a carrier of disease. Louis Sambon, an Anglo-Italian doctor working at the London School of Tropical Medicine, was convinced that pellagra was carried by an insect, along the lines of malaria. Later, the lack of pellagra outbreaks in Mesoamerica, where maize is a major food crop, led researchers to investigate processing techniques in that region.

Pellagra was studied mostly in Europe until the late 19th century when it became epidemic especially in the southern United States. In the early 1900s, pellagra reached epidemic proportions in the American South. Between 1906 and 1940 more than 3 million Americans were affected by pellagra with more than 100,000 deaths, yet the epidemic resolved itself right after dietary niacin fortification. Pellagra deaths in South Carolina numbered 1,306 during the first ten months of 1915; 100,000 Southerners were affected in 1916. At this time, the scientific community held that pellagra was probably caused by a germ or some unknown toxin in corn. The Spartanburg Pellagra Hospital in Spartanburg, South Carolina, was the nations first facility dedicated to discovering the cause of pellagra. It was established in 1914 with a special Congressional appropriation to the U.S. Public Health Service (PHS) and set up primarily for research. In 1915, Dr. Joseph Goldberger, assigned to study pellagra by the Surgeon General of the United States, showed it was linked to diet by observing the outbreaks of pellagra in orphanages and mental hospitals.  Goldberger noted that children between the ages of 6 and 12 (but not older or younger children at the orphanages) and patients at the mental hospitals (but not doctors or nurses) were the ones who seemed most susceptible to pellagra. Goldberger theorized that a lack of meat, milk, eggs, and legumes made those particular populations susceptible to pellagra.  By modifying the diet served in these institutions with "a marked increase in the fresh animal and the leguminous protein foods," Goldberger was able to show that pellagra could be prevented. By 1926, Goldberger established that a diet that included these foods, or a small amount of brewers yeast, prevented pellagra.
Goldberger experimented on 11 prisoners (one was dismissed because of prostatitis). Before the experiment, the prisoners were eating the prison fare fed to all inmates at Rankin Prison Farm in Mississippi. Goldberger started feeding them a restricted diet of grits, syrup, mush, biscuits, cabbage, sweet potatoes, rice, collards, and coffee with sugar (no milk). Healthy white male volunteers were selected as the typical skin lesions were easier to see in Caucasians and this population was felt to be those least susceptible to the disease, and thus provide the strongest evidence that the disease was caused by a nutritional deficiency. Subjects experienced mild, but typical cognitive and gastrointestinal symptoms, and within five months of this cereal-based diet, 6 of the 11 subjects broke out in the skin lesions that are necessary for a definitive diagnosis of pellagra. The lesions appeared first on the scrotum. Goldberger was not given the opportunity to experimentally reverse the effects of diet-induced pellagra as the prisoners were released shortly after the diagnoses of pellagra were confirmed. In the 1920s, he connected pellagra to the corn-based diets of rural areas rather than infection as contemporary medical opinion would suggest. Goldberger believed that the root cause of pellagra amongst Southern farmers was limited diet resulting from poverty, and that social and land reform would cure epidemic pellagra. His reform efforts were not realized, but crop diversification in the Southern United States, and the accompanying improvement in diet, dramatically reduced the risk of pellagra. Goldberger is remembered as the "unsung hero of American clinical epidemiology". Though he identified that a missing nutritional element was responsible for pellagra, he did not discover the specific vitamin responsible.
In 1937, Conrad Elvehjem, a biochemistry professor at the University of Wisconsin-Madison, showed that the vitamin niacin cured pellagra (manifested as black tongue) in dogs. Later studies by Dr. Tom Spies, Marion Blankenhorn, and Clark Cooper established that niacin also cured pellagra in humans, for which Time Magazine dubbed them its 1938 Men of the Year in comprehensive science.Research conducted between 1900 and 1950 found the number of cases of women with pellagra was consistently double the number of cases of affected men. This is thought to be due to the inhibitory effect of estrogen on the conversion of the amino acid tryptophan to niacin. Some researchers of the time gave a few explanations regarding the difference.Gillman and Gillman related skeletal tissue and pellagra in their research in South Africans. They provide some of the best evidence for skeletal manifestations of pellagra and the reaction of bone in malnutrition. They claimed radiological studies of adult pellagrins demonstrated marked osteoporosis. A negative mineral balance in pellagrins was noted, which indicated active mobilization and excretion of endogenous mineral substances, and undoubtedly impacted the turnover of bone. Extensive dental caries were present in over half of pellagra patients. In most cases, caries were associated with "severe gingival retraction, sepsis, exposure of cementum, and loosening of teeth".

Etymology
The word pellagra comes from the Lombard words "pell" (skin) and "agra" (fem. sour).

United States
Pellagra was first reported in 1902 in the United States, and has "caused more deaths than any other nutrition-related disease in American history", reaching epidemic proportions in the American South during the early 1900s. Poverty and consumption of corn were the most frequently observed risk factors, but the exact cause was not known, until groundbreaking work by Joseph Goldberger. A 2017 National Bureau of Economic Research paper explored the role of cotton production in the emergence of disease; one prominent theory is that "widespread cotton production had displaced local production of niacin-rich foods and driven poor Southern farmers and mill workers to consume milled Midwestern corn, which was relatively cheap but also devoid of the niacin necessary to prevent pellagra." The study provided evidence in favor of the theory: there were lower pellagra rates in areas where farmers had been forced to abandon cotton production (a highly profitable crop) in favor of food crops (less profitable crops) due to boll weevil infestation of cotton crops (which occurred randomly).The whole dried corn kernel contains a nutritious germ and a thin seed coat that provides some fiber. There are two important considerations for using ground whole-grain corn.

The germ contains oil that is exposed by grinding, thus whole-grain cornmeal and grits turn rancid quickly at room temperature and should be refrigerated.
Whole-grain cornmeal and grits require extended cooking times as seen in the following cooking directions for whole-grain grits:"Place the grits in a pan and cover them with water. Allow the grits to settle a full minute, tilt the pan, and skim off and discard the chaff and hulls with a fine tea strainer. Cook the grits for 50 minutes if the grits were soaked overnight or else 90 minutes if not."
Most of the niacin in mature cereal grains is present as niacytin, which is niacin bound up in a complex with hemicellulose which is nutritionally unavailable. In mature corn this may be up to 90% of the total niacin content. The preparation method of nixtamalization using the whole dried corn kernel made this niacin nutritionally available and reduced the chance of developing pellagra. Niacytin is concentrated in the aleurone and germ layers which are removed by milling. The milling and degerming of corn in the preparation of cornmeal became feasible with the development of the Beall degerminator, which was originally patented in 1901 and was used to separate the grit from the germ in corn processing. However, this process of degermination reduces the niacin content of the cornmeal.
Casimir Funk, who helped elucidate the role of thiamin in the etiology of beriberi, was an early investigator of the problem of pellagra </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 Pemphigus vulgaris and can you explain it in depth? [/INST] Pemphigus vulgaris is a rare chronic blistering skin disease and the most common form of pemphigus. Pemphigus was derived from the Greek word pemphix, meaning blister. It is classified as a type II hypersensitivity reaction in which antibodies are formed against desmosomes, components of the skin that function to keep certain layers of skin bound to each other.  As desmosomes are attacked, the layers of skin separate and the clinical picture resembles a blister. These blisters are due to acantholysis, or breaking apart of intercellular connections through an autoantibody-mediated response. Over time the condition inevitably progresses without treatment: lesions increase in size and distribution throughout the body, behaving physiologically like a severe burn.
Before the advent of modern treatments, mortality for the disease was close to 90%.  Today, the mortality rate with treatment is between 5-15% due to the introduction of corticosteroids as primary treatment. Nevertheless, in 1998, pemphigus vulgaris was the fourth most common cause of death due to a skin disorder.
The disease mainly affects middle-aged and older adults between 50–60 years old. There has historically been a higher incidence in women.

Signs and symptoms
Pemphigus vulgaris most commonly presents with oral blisters (buccal and palatine mucosa, especially), but also includes cutaneous blisters. Other mucosal surfaces, the conjunctiva, nose, esophagus, penis, vulva, vagina, cervix, and anus, may also be affected. Flaccid blisters over the skin are frequently seen with sparing of the skin covering the palms and soles.Blisters commonly erode and leave ulcerated lesions and erosions. A positive Nikolsky sign (induction of blistering in normal skin or at the edge of a blister) is indicative of the disease.Severe pain with chewing can lead to weight loss and malnutrition.

Pathophysiology
Pemphigus is an autoimmune disease caused by antibodies directed against both desmoglein 1 and desmoglein 3 present in desmosomes.  Loss of desmosomes results in loss of cohesion between keratinocytes in the epidermis, and a disruption of the barrier function served by intact skin.  The process is classified as a type II hypersensitivity reaction (in which antibodies bind to antigens on the bodys own tissues). On histology, the basal keratinocytes are usually still attached to the basement membrane leading to a characteristic appearance called "tombstoning".  Transudative fluid accumulates in between the keratinocytes and the basal layer (suprabasal split), forming a blister and resulting in what is known as a positive Nikolskys sign.  This is a contrasting feature from bullous pemphigoid, which is thought to be due to anti-hemidesmosome antibodies, and where the detachment occurs between the epidermis and dermis (subepidermal bullae). Clinically, pemphigus vulgaris is characterized by extensive flaccid blisters and mucocutaneous erosions. The severity of the disease, as well as the mucosal lesions, is believed to be directly proportional to the levels of desmoglein 3. Milder forms of pemphigus (like foliacious and erythematoses) are more anti-desmoglein 1 heavy.
The disease arises most often in middle-aged or older people, usually starting with a blister that ruptures easily. It can also start with blisters in the mouth. The lesions can become quite extensive.

Diagnosis
Because it is a rare disease, diagnosis is often complicated and takes a long time.  Early in the disease patients may have erosions in the mouth or blisters on the skin.  These blisters can be itchy or painful.  Theoretically, the blisters should demonstrate a positive Nikolskys sign, in which the skin sloughs off from slight rubbing, but this is not always reliable. The gold standard for diagnosis is a punch biopsy from the area around the lesion that is examined by direct immunofluorescent staining, in which cells are acantholytic, that is, lacking the normal intercellular connections that hold them together. These can also be seen on a Tzanck smear. These cells are basically rounded, nucleated keratinocytes formed due to antibody mediated damage to cell adhesion protein desmoglein.
Pemphigus vulgaris is easily confused with impetigo and candidiasis.  IgG4 is considered pathogenic.  The diagnosis can be confirmed by testing for the infections that cause these other conditions, and by a lack of response to antibiotic treatment.

Treatment
Corticosteroids and other immunosuppressive medications have historically been employed to reduce pemphigus symptoms, yet steroids are associated with serious and long-lasting side effects and their use should be limited as much as possible. Intravenous immunoglobulin, mycophenolate mofetil, methotrexate, azathioprine, and cyclophosphamide have also been used with varying degrees of success.
An established alternative to steroids are monoclonal antibodies such as rituximab, which are increasingly being used as first-line treatment.  In summer 2018, the FDA granted full approval to rituximab for this application, following successful fast track evaluation. In numerous case series, many patients achieve remission after one cycle of rituximab. Treatment is more successful if initiated early on in the course of disease, perhaps even at diagnosis. Rituximab treatment combined with monthly IV immunoglobulin infusions has resulted in long-term remission with no recurrence of disease in 10 years after treatment was halted. This was a small trial study of 11 patients with 10 patients followed to completion.
Rituximab demonstrated superior efficacy compared to mycophenolate mofetil in a Phase III clinical trial, results of which were published in 2021.

Epidemiology
Pemphigus vulgaris is a relatively rare disease that only affects about 1 to 5 people in 1 million in the United Kingdom, with an incidence of 1-10 cases per 1 million people across the world. There is an estimated prevalence of 30,000-40,000 cases in the United States. Cases of P. vulgaris usually dont develop until after the age of 50 or so. The disease is not contagious which means it cannot be spread from person to person. There is currently no way of knowing who will be affected with P. vulgaris in their life as it is usually not a genetic disorder and is usually triggered later in life by environmental factors. Men and women are both equally affected and the disease has been found to affect people of many different cultures and racial backgrounds, especially Ashkenazi Jews, people of Mediterranean, North Indian and Persian descent. There has been no found difference in the rate of disease when looking at socioeconomic factors as well.If left untreated, 8 of 10 people with the disease die within a year with a cause of death being infection or loss of fluids, which is very common for raw, open sores that are characteristic of P </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 Periodic paralysis and can you explain it in depth? [/INST] Periodic paralysis is a group of rare genetic diseases that lead to weakness or paralysis from common triggers such as cold, heat, high carbohydrate meals, not eating, stress or excitement and physical activity of any kind. The underlying mechanism of these diseases are malfunctions in the ion channels in skeletal muscle cell membranes that allow electrically charged ions to leak in or out of the muscle cell, causing the cell to depolarize and become unable to move.The symptoms of periodic paralysis can also be caused by hyperthyroidism, and are then labeled thyrotoxic periodic paralysis; however, if this is the underlying condition there are likely to be other characteristic manifestations, enabling a correct diagnosis.

Types
Periodic paralysis is an autosomal dominant myopathy with considerable variation in penetrance, leading to a spectrum of familial phenotypes (only one parent needs to carry the gene mutation to affect the children, but not all family members who share the gene are affected to the same degree). Specific diseases include:
Hypokalemic periodic paralysis (Online Mendelian Inheritance in Man (OMIM): 170400), where potassium leaks into the muscle cells from the bloodstream.
Hyperkalemic periodic paralysis (Online Mendelian Inheritance in Man (OMIM): 170500), where potassium leaks out of the cells into the bloodstream.
Paramyotonia congenita (Online Mendelian Inheritance in Man (OMIM): 168300), a form which often accompanies hyperkalemic periodic paralysis, but may present alone. The primary symptom of paramyotonia congenita is muscle contracture which develops during exercise or activity. Paramyotonia congenita attacks may also be triggered by a low level of potassium in the bloodstream. This means people with both hyperkalemic periodic paralysis and paramyotonia congenita can have attacks with fluctuations of potassium up or down.
Andersen-Tawil syndrome (Online Mendelian Inheritance in Man (OMIM): 170390), a form of periodic paralysis that includes significant heart rhythm problems, fainting and risk of sudden death. Potassium levels may be low, high, or normal during attacks of ATS. Patients with ATS may also have skeletal abnormalities like scoliosis (curvature of the spine), webbing between the second and third toes or fingers (syndactyly), crooked fingers (clinodactyly), a small jaw (micrognathia) and low-set ears.  Patients need to have another form of periodic paralysis to have the Andersen-Tawil.  If a patient has hypo or hyper periodic paralysis they have a 50% chance of getting Andersen-Tawil.  They just have to have the gene that causes it.  This is a rare occurrence of having this.  Only around 100 people in the world are recorded to have it.

Cause
One of the most common descriptions of periodic paralysis are episodic attacks of muscle weakness, which are commonly associated with serum potassium levels. Physical activity and diet content (carbohydrates) have been identified as PP triggers. Unlike non-dystrophic myotonias, the periodic paralysis phenotype is triggered after resting following exercise. Voltage-gated sodium channel (Nav1.4) mutations are among the key causes behind periodic paralysis.Hyper-kalemic PP (hyperPP) is identified with high extracellular potassium levels which are typically greater than 5 mM during attacks; however, HyperPP attacks can also take place without rise in potassium concentrations. HyperPP has a prevalence rate of 1/100,000. Patients become symptomatic around the age of 10. The weakness attacks in hyperPP are relatively short lasting, and range from minutes to hours. The attacks can happen upwards of ten times per month.Hypo-kalemic PP (hypoPP) is associated with low potassium levels. The onset of hypoPP occurs between the ages of 15 and 35. The prevalence of hypoPP is estimated to 1/100,000. HypoPP can be triggered by many external factors such as stress, high-sugar diet, and rest after exercise. During hypoPP attacks, the serum potassium concentrations can drop to less than 3 mM. Furthermore, hypoPP attacks are considerably longer lasting than hyperPP. As exercise is a trigger for periodic paralysis attacks, recently there is more research going into the physiological changes that accompany exercise including changes in blood pH.

Diagnosis
This disease is unusually difficult to diagnose. Patients often report years of wrong diagnosis and treatments that made them worse instead of better. Part of this may be that migraines are present in up to 50% of patients and can cause a confusing array of symptoms including headaches, speech difficulties and visual, auditory or sensory auras. DNA testing is available for only a half dozen common gene mutations, while dozens of known mutations are possible but are not routinely tested. Electromyography (EMG) findings are not specific but the McManis Protocol, also called the Compound Muscle Amplitude Potential test (CMAP) can be used by a skilled neurologist capable of utilizing the EMG, which can give assistance in diagnosing several of these PP disorders. The old glucose/insulin provocative testing can cause life-threatening symptoms and should not be used.Also of note is that potassium levels do not have to range outside of normal limits to cause serious, even life-threatening paralysis </s>