<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 Hepatitis B and can you explain it in depth? [/INST] Hepatitis B is an infectious disease caused by the Hepatitis B virus (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection.Many people have no symptoms during an initial infection. For others, symptoms may appear 30 to 180 days after becoming infected and can include a rapid onset of sickness with nausea, vomiting, yellowish skin, fatigue, dark urine, and abdominal pain. Symptoms during acute infection typically last for a few weeks, though some people may feel sick for up to six months. Deaths resulting from acute stage HBV infections are rare. An HBV infection lasting longer than six months is usually considered chronic. The likelihood of developing chronic hepatitis B is higher for those who are infected with HBV at a younger age. About 90% of those infected during or shortly after birth develop chronic hepatitis B, while less than 10% of those infected after the age of five develop chronic cases. Most of those with chronic disease have no symptoms; however, cirrhosis and liver cancer eventually develop in about 25% of those with chronic HBV.The virus is transmitted by exposure to infectious blood or body fluids. In areas where the disease is common, infection around the time of birth or from contact with other peoples blood during childhood are the most frequent methods by which hepatitis B is acquired. In areas where the disease is rare, intravenous drug use and sexual intercourse are the most frequent routes of infection. Other risk factors include working in healthcare, blood transfusions, dialysis, living with an infected person, travel in countries with high infection rates, and living in an institution. Tattooing and acupuncture led to a significant number of cases in the 1980s; however, this has become less common with improved sterilization. The hepatitis B viruses cannot be spread by holding hands, sharing eating utensils, kissing, hugging, coughing, sneezing, or breastfeeding. The infection can be diagnosed 30 to 60 days after exposure. The diagnosis is usually confirmed by testing the blood for parts of the virus and for antibodies against the virus. It is one of five main hepatitis viruses: A, B, C, D, and E. During an initial infection, care is based on a persons symptoms. In those who develop chronic disease, antiviral medication such as tenofovir or interferon may be useful; however, these drugs are expensive. Liver transplantation is sometimes recommended for cases of cirrhosis or hepatocellular carcinoma.Hepatitis B infection has been preventable by vaccination since 1982. As of 2022, the hepatitis B vaccine is between 98% and 100% effective in preventing infection. The vaccine is administered in several doses; after an initial dose, two or three more vaccine doses are required at a later time for full effect. The World Health Organization (WHO) recommends infants receive the vaccine within 24 hours after birth when possible. National programs have made the hepatitis B vaccine available for infants in 190 countries as of the end of 2021. To further prevent infection, the WHO recommends testing all donated blood for hepatitis B before using it for transfusion. Using antiviral prophylaxis to prevent mother-to-child transmission is also recommended, as is following safe sex practices, including the use of condoms In 2016, the WHO set a goal of eliminating viral hepatitis as a threat to global public health by 2030. Achieving this goal would require the development of therapeutic treatments to cure chronic hepatitis B, as well as preventing its transmission and using vaccines to prevent new infections.An estimated 296 million people, or 3.8% of the global population, had chronic hepatitis B infections as of 2019. Another 1.5 million developed acute infections that year, and 820,000 deaths occurred as a result of HBV. Cirrhosis and liver cancer are responsible for most HBV-related deaths. The disease is most prevalent in Africa (affecting 7.5% of the continent’s population) and in the Western Pacific region (5.9%). Infection rates are 1.5% in Europe and 0.5% in the Americas. According to some estimates, about a third of the worlds population has been infected with hepatitis B at one point in their lives. Hepatitis B was originally known as "serum hepatitis".

Signs and symptoms
Acute infection with hepatitis B virus is associated with acute viral hepatitis, an illness that begins with general ill-health, loss of appetite, nausea, vomiting, body aches, mild fever, and dark urine, and then progresses to development of jaundice. The illness lasts for a few weeks and then gradually improves in most affected people. A few people may have a more severe form of liver disease known as fulminant hepatic failure and may die as a result. The infection may be entirely asymptomatic and may go unrecognized.Chronic infection with hepatitis B virus may be asymptomatic or may be associated with chronic inflammation of the liver (chronic hepatitis), leading to cirrhosis over a period of several years. This type of infection dramatically increases the incidence of hepatocellular carcinoma (HCC; liver cancer). Across Europe, hepatitis B and C cause approximately 50% of hepatocellular carcinomas. Chronic carriers are encouraged to avoid consuming alcohol as it increases their risk for cirrhosis and liver cancer. Hepatitis B virus has been linked to the development of membranous glomerulonephritis (MGN).Symptoms outside of the liver are present in 1–10% of HBV-infected people and include serum-sickness–like syndrome, acute necrotizing vasculitis (polyarteritis nodosa), membranous glomerulonephritis, and papular acrodermatitis of childhood (Gianotti–Crosti syndrome). The serum-sickness–like syndrome occurs in the setting of acute hepatitis B, often preceding the onset of jaundice. The clinical features are fever, skin rash, and polyarteritis. The symptoms often subside shortly after the onset of jaundice but can persist throughout the duration of acute hepatitis B. About 30–50% of people with acute necrotizing vasculitis (polyarteritis nodosa) are HBV carriers. HBV-associated nephropathy has been described in adults but is more common in children. Membranous glomerulonephritis is the most common form. Other immune-mediated hematological disorders, such as essential mixed cryoglobulinemia and aplastic anemia have been described as part of the extrahepatic manifestations of HBV infection, but their association is not as well-defined; therefore, they probably should not be considered etiologically linked to HBV.

Cause
Transmission
Transmission of hepatitis B virus results from exposure to infectious blood or body fluids containing blood. HBV is 50 to 100 times more infectious than human immunodeficiency virus (HIV). HBV can be transmitted through several routes of infection. In vertical transmission, HBV is passed from mother to child (MTCT) during childbirth. Without intervention, a mother who is positive for HBsAg has a 20% risk of passing the infection to her offspring at the time of birth. This risk is as high as 90% if the mother is also positive for HBeAg.Early life horizontal transmission can occur through bites, lesions, certain sanitary habits, or other contact with secretions or saliva containing HBV. Adult horizontal transmission is known to occur through sexual contact, blood transfusions and transfusion with other human blood products, re-use of contaminated needles and syringes. Breastfeeding after proper immunoprophylaxis does not appear to contribute to mother-to-child-transmission (MTCT) of HBV.

Virology
Structure
Hepatitis B virus (HBV) is a member of the hepadnavirus family. The virus particle (virion) consists of an outer lipid envelope and an icosahedral nucleocapsid core composed of core protein. These virions are 30–42 nm in diameter. The nucleocapsid encloses the viral DNA and a DNA polymerase that has reverse transcriptase activity. The outer envelope contains embedded proteins that are involved in viral binding of, and entry into, susceptible cells. The virus is one of the smallest enveloped animal viruses.  The 42 nm virions, which are capable of infecting liver cells known as hepatocytes, are referred to as "Dane particles". In addition to the Dane particles, filamentous and spherical bodies lacking a core can be found in the serum of infected individuals.   These particles are not infectious and are composed of the lipid and protein that forms part of the surface of the virion, which is called the surface antigens (HBsAg), and is produced in excess during the life cycle of the virus.

Genome
The genome of HBV is made of circular DNA, but it is unusual because the DNA is not fully double-stranded. One end of the full length strand is linked to the viral DNA polymerase. The genome is 3020–3320 nucleotides long (for the full-length strand) and 1700–2800 nucleotides long (for the short length-strand). The negative-sense (non-coding) is complementary to the viral mRNA. The viral DNA is found in the nucleus soon after infection of the cell. The partially double-stranded DNA is rendered fully double-stranded by completion of the (+) sense strand and removal of a protein molecule from the (−) sense strand and a short sequence of RNA from the (+) sense strand. Non-coding bases are removed from the ends of the (−) sense strand and the ends are rejoined. There are four known genes encoded by the genome, called C, X, P, and S. The core protein is coded for by gene C (HBcAg), and its start codon is preceded by an upstream in-frame AUG start codon from which the pre-core protein is produced. HBeAg is produced by proteolytic processing of the pre-core protein. In some rare strains of the virus known as Hepatitis B virus precore mutants, no HBeAg is present.
The DNA polymerase is encoded by gene P. Gene S is the gene that codes for the surface antigen (HBsAg). The HBsAg gene is one long open reading frame but contains three in frame "start" (ATG) codons that divide the gene into three sections, pre-S1, pre-S2, and S. Because of the multiple start codons, polypeptides of three different sizes called large (the order from surface to the inside: pre-S1, pre-S2, and S ), middle (pre-S2, S), and small (S) are produced. There is a myristyl group, which plays an important role in infection, on the amino-terminal end of the preS1 part of the large (L) protein. In addition to that, N terminus of the L protein have virus attachment and capsid binding sites. Because of that, the N termini of half of the L protein molecules are positioned outside the membrane and the other half positioned inside the membrane.The function of the protein coded for by gene X is not fully understood but it is associated with the development of liver cancer. It stimulates genes that promote cell growth and inactivates growth regulating molecules.

Pathogenesis
The life cycle of hepatitis B virus is complex. Hepatitis B is one of a few known pararetroviruses: non-retroviruses that still use reverse transcription in their replication process. The virus gains entry into the cell by binding to NTCP on the surface and being endocytosed. Because the virus multiplies via RNA made by a host enzyme, the viral genomic DNA has to be transferred to the cell nucleus by host proteins called chaperones. The partially double-stranded viral DNA is then made fully double stranded by a viral polymerase and transformed into covalently closed circular DNA (cccDNA). This cccDNA serves as a template for transcription of four viral mRNAs by host RNA polymerase. The largest mRNA, (which is longer than the viral genome), is used to make the new copies of the genome and to make the capsid core protein and the viral DNA polymerase. These four viral transcripts undergo additional processing and go on to form progeny virions that are released from the cell or returned to the nucleus and re-cycled to produce even more copies. The long mRNA is then transported back to the cytoplasm where the virion P protein (the DNA polymerase) synthesizes DNA via its reverse transcriptase activity.

Serotypes and genotypes
The virus is divided into four major serotypes (adr, adw, ayr, ayw) based on antigenic epitopes presented on its envelope proteins, and into eight major genotypes (A–H). The genotypes have a distinct geographical distribution and are used in tracing the evolution and transmission of the virus. Differences between genotypes affect the disease severity, course and likelihood of complications, and response to treatment and possibly vaccination. There are two other genotypes I and J but they are not universally accepted as of 2015. The diversity of genotypes is not shown equally in the world. For example, A, D, and E genotypes have been seen in Africa prevalently while B and C genotypes are observed in Asia as widespread.Genotypes differ by at least 8% of their sequence and were first reported in 1988 when six were initially described (A–F). Two further types have since been described (G and H). Most genotypes are now divided into subgenotypes with distinct properties.

Mechanisms
Hepatitis B virus primarily interferes with the functions of the liver by replicating in hepatocytes. A functional receptor is NTCP. There is evidence that the receptor in the closely related duck hepatitis B virus is carboxypeptidase D. The virions bind to the host cell via the preS domain of the viral surface antigen and are subsequently internalized by endocytosis. HBV-preS-specific receptors are expressed primarily on hepatocytes; however, viral DNA and proteins have also been detected in extrahepatic sites, suggesting that cellular receptors for HBV may also exist on extrahepatic cells.During HBV infection, the host immune response causes both hepatocellular damage and viral clearance. Although the innate immune response does not play a significant role in these processes, the adaptive immune response, in particular virus-specific cytotoxic T lymphocytes(CTLs), contributes to most of the liver injury associated with HBV infection. CTLs eliminate HBV infection by killing infected cells and producing antiviral cytokines, which are then used to purge HBV from viable hepatocytes. Although liver damage is initiated and mediated by the CTLs, antigen-nonspecific inflammatory cells can worsen CTL-induced immunopathology, and platelets activated at the site of infection may facilitate the accumulation of CTLs in the liver.

Diagnosis
The tests, called assays, for detection of hepatitis B virus infection involve serum or blood tests that detect either viral antigens (proteins produced by the virus) or antibodies produced by the host. Interpretation of these assays is complex.The hepatitis B surface antigen (HBsAg) is most frequently used to screen for the presence of this infection. It is the first detectable viral antigen to appear during infection. However, early in an infection, this antigen may not be present and it may be undetectable later in the infection as it is being cleared by the host. The infectious virion contains an inner "core particle" enclosing viral genome. The icosahedral core particle is made of 180 or 240 copies of the core protein, alternatively known as hepatitis B core antigen, or HBcAg. During this window in which the host remains infected but is successfully clearing the virus, IgM antibodies specific to the hepatitis B core antigen (anti-HBc IgM) may be the only serological evidence of disease.  Therefore, most hepatitis B diagnostic panels contain HBsAg and total anti-HBc (both IgM and IgG).Shortly after the appearance of the HBsAg, another antigen called hepatitis B e antigen (HBeAg) will appear. Traditionally, the presence of HBeAg in a hosts serum is associated with much higher rates of viral replication and enhanced infectivity; however, variants of the hepatitis B virus do not produce the e antigen, so this rule does not always hold true. During the natural course of an infection, the HBeAg may be cleared, and antibodies to the e antigen (anti-HBe) will arise immediately afterwards. This conversion is usually associated with a dramatic decline in viral replication.

If the host is able to clear the infection, eventually the HBsAg will become undetectable and will be followed by IgG antibodies to the hepatitis B surface antigen and core antigen (anti-HBs and anti HBc IgG). The time between the removal of the HBsAg and the appearance of anti-HBs is called the window period. A person negative for HBsAg but positive for anti-HBs either has cleared an infection or has been vaccinated previously.
Individuals who remain HBsAg positive for at least six months are considered to be hepatitis B carriers. Carriers of the virus may have chronic hepatitis B, which would be reflected by elevated serum alanine aminotransferase (ALT) levels and inflammation of the liver, if they are in the immune clearance phase of chronic infection. Carriers who have seroconverted to HBeAg negative status, in particular those who acquired the infection as adults, have very little viral multiplication and hence may be at little risk of long-term complications or of transmitting infection to others. However, it is possible for individuals to enter an "immune escape" with HBeAg-negative hepatitis.

PCR tests have been developed to detect and measure the amount of HBV DNA, called the viral load, in clinical specimens. These tests are used to assess a persons infection status and to monitor treatment. Individuals with high viral loads, characteristically have ground glass hepatocytes on biopsy.

Prevention
Vaccine
Vaccines for the prevention of hepatitis B have been routinely recommended for babies since 1991 in the United States. The first dose is generally recommended within a day of birth. The hepatitis B vaccine was the first vaccine capable of preventing cancer, specifically liver cancer.Most vaccines are given in three doses over a course of days. A protective response to the vaccine is defined as an anti-HBs antibody concentration of at least 10 mIU/ml in the recipients serum. The vaccine is more effective in children and 95 percent of those vaccinated have protective levels of antibody. This drops to around 90% at 40 years of age and to around 75 percent in those over 60 years. The protection afforded by vaccination is long lasting even after antibody levels fall below 10 mIU/ml. For newborns of HBsAg-positive mothers: hepatitis B vaccine alone, hepatitis B immunoglobulin alone, or the combination of vaccine plus hepatitis B immunoglobulin, all prevent hepatitis B occurrence. Furthermore, the combination of vaccine plus hepatitis B immunoglobulin is superior to vaccine alone. This combination prevents HBV transmission around the time of birth in 86% to 99% of cases.Tenofovir given in the second or third trimester can reduce the risk of mother to child transmission by 77% when combined with hepatitis B immunoglobulin and the hepatitis B vaccine, especially for pregnant women with high hepatitis B virus DNA levels. However, there is no sufficient evidence that the administration of hepatitis B immunoglobulin alone during pregnancy, might reduce transmission rates to the newborn infant. No randomized control trial has been conducted to assess the effects of hepatitis B vaccine during pregnancy for preventing infant infection.All those with a risk of exposure to body fluids such as blood should be vaccinated, if not already. Testing to verify effective immunization is recommended and further doses of vaccine are given to those who are not sufficiently immunized.In 10- to 22-year follow-up studies there were no cases of hepatitis B among those with a normal immune system who were vaccinated. Only rare chronic infections have been documented. Vaccination is particularly recommended for high risk groups including: health workers, people with chronic kidney failure, and men who have sex with men.Both types of the hepatitis B vaccine, the plasma-derived vaccine (PDV) and recombinant vaccine (RV) are of similar effectiveness in preventing the infection in both healthcare workers and chronic kidney failure groups. With one difference noticed among health worker group, that the RV intramuscular route is significantly more effective compared with RV intradermal route of administration.

Other
In assisted reproductive technology, sperm washing is not necessary for males with hepatitis B to prevent transmission, unless the female partner has not been effectively vaccinated. In females with hepatitis B, the risk of transmission from mother to child with IVF is no different from the risk in spontaneous conception.Those at high risk of infection should be tested as there is effective treatment for those who have the disease. Groups that screening is recommended for include those who have not been vaccinated and one of the following: people from areas of the world where hepatitis B occurs in more than 2%, those with HIV, intravenous drug users, men who have sex with men, and those who live with someone with hepatitis B. Screening during pregnancy is recommended in the United States.

Treatment
Acute hepatitis B infection does not usually require treatment and most adults clear the infection spontaneously. Early antiviral treatment may be required in fewer than 1% of people, whose infection takes a very aggressive course (fulminant hepatitis) or who are immunocompromised. On the other hand, treatment of chronic infection may be necessary to reduce the risk of cirrhosis and liver cancer. Chronically infected individuals with persistently elevated serum alanine aminotransferase, a marker of liver damage, and HBV DNA levels are candidates for therapy. Treatment lasts from six months to a year, depending on medication and genotype. Treatment duration when medication is taken by mouth, however, is more variable and usually longer than one year.Although none of the available medications can clear the infection, they can stop the virus from replicating, thus minimizing liver damage. As of 2018, there are eight medications licensed for the treatment of hepatitis B infection in the United States. These include antiviral medications lamivudine, adefovir, tenofovir disoproxil, tenofovir alafenamide, telbivudine, and entecavir, and the two immune system modulators interferon alpha-2a and PEGylated interferon alpha-2a. In 2015 the World Health Organization recommended tenofovir or entecavir as first-line agents. Those with current cirrhosis are in most need of treatment.The use of interferon, which requires injections daily or thrice weekly, has been supplanted by long-acting PEGylated interferon, which is injected only once weekly. However, some individuals are much more likely to respond than others, and this might be because of the genotype of the infecting virus or the persons heredity. The treatment reduces viral replication in the liver, thereby reducing the viral load (the amount of virus particles as measured in the blood). Response to treatment differs between the genotypes. Interferon treatment may produce an e antigen seroconversion rate of 37% in genotype A but only a 6% seroconversion in type D. Genotype B has similar seroconversion rates to type A while type C seroconverts only in 15% of cases. Sustained e antigen loss after treatment is ~45% in types A and B but only 25–30% in types C and D.It seems unlikely that the disease will be eliminated by 2030, the goal set in 2016 by WHO. However, progress is being made in developing therapeutic treatments. In 2010, the Hepatitis B Foundation reported that 3 preclinical and 11 clinical-stage drugs were under development, based on largely similar mechanisms. In 2020, they reported that there were 17 preclinical- and 32 clinical-stage drugs under development, using diverse mechanisms.

Prognosis
Hepatitis B virus infection may be either acute (self-limiting) or chronic (long-standing). Persons with self-limiting infection clear the infection spontaneously within weeks to months.
Children are less likely than adults to clear the infection. More than 95% of people who become infected as adults or older children will stage a full recovery and develop protective immunity to the virus. However, this drops to 30% for younger children, and only 5% of newborns that acquire the infection from their mother at birth will clear the infection. This population has a 40% lifetime risk of death from cirrhosis or hepatocellular carcinoma. Of those infected between the age of one to six, 70% will clear the infection.Hepatitis D (HDV) can occur only with a concomitant hepatitis B infection, because HDV uses the HBV surface antigen to form a capsid. Co-infection with hepatitis D increases the risk of liver cirrhosis and liver cancer. Polyarteritis nodosa is more common in people with hepatitis B infection.

Cirrhosis
A number of different tests are available to determine the degree of cirrhosis present. Transient elastography (FibroScan) is the test of choice, but it is expensive. Aspartate aminotransferase to platelet ratio index may be used when cost is an issue.

Reactivation
Hepatitis B virus DNA remains in the body after infection, and in some people, including those that do not have detectable HBsAg, the disease recurs. Although rare, reactivation is seen most often following alcohol or drug use, or in people with impaired immunity. HBV goes through cycles of replication and non-replication. Approximately 50% of overt carriers experience acute reactivation. Males with baseline ALT of 200 UL/L are three times more likely to develop a reactivation than people with lower levels. Although reactivation can occur spontaneously, people who undergo chemotherapy have a higher risk. Immunosuppressive drugs favor increased HBV replication while inhibiting cytotoxic T cell function in the liver. The risk of reactivation varies depending on the serological profile; those with detectable HBsAg in their blood are at the greatest risk, but those with only antibodies to the core antigen are also at risk. The presence of antibodies to the surface antigen, which are considered to be a marker of immunity, does not preclude reactivation. Treatment with prophylactic antiviral drugs can prevent the serious morbidity associated with HBV disease reactivation.

Epidemiology
At least 296 million people, or 3.8% of the worlds population, had chronic HBV infection as of 2019. Another 1.5 million cases of acute HBV infection also occurred that year. Regional prevalences across the globe range from around 7.5% in Africa to 0.5% in the Americas.The primary method of HBV transmission and the prevalence of chronic HBV infection in specific regions often correspond with one another. In populations where HBV infection rates are 8% or higher, which are classified as high prevalence, vertical transmission (usually occurring during birth) is most common, though rates of early childhood transmission can also be significant among these populations. In 2021, 19 African countries had infection rates ranging between 8-19%, placing them in the high prevalence category.In moderate prevalence areas where 2–7% of the population is chronically infected, the disease is predominantly spread horizontally, often among children, or vertically. China’s HBV infection rate is at the higher end of the moderate prevalence classification with an infection rate of 6.89% as of 2019. HBV prevalence in India is also moderate, with studies placing India’s infection rate between 2-4%.Countries with low HBV prevalence include Australia (0.9%), those in the WHO European Region (which average 1.5%), and most countries in North and South America (which average 0.28%).
In the United States, an estimated 0.26% of the population was living with HBV infection as of 2018.

History
Findings of HBV DNA in ancient human remains have shown that HBV has infected humans since at least ten millennia, both in Eurasia and in the Americas. This disproved the belief that hepatitis B originated in the New World and spread to Europe around 16th century. Hepatitis B virus subgenotype C4 is exclusively present in Australian aborigines, suggesting an ancient origin as much as 50,000 years old. However, analyses of ancient HBV genomes suggested that the most recent common ancestor of all known human HBV strains was dated to between 20,000 and 12,000 years ago, pointing to a more recent origin for all HBV genotypes. The evolution of HBV in humans was shown to reflect known events of human history such as the first peopling of the Americas during the late Pleistocene and the Neolithic transition in Europe. Ancient DNA studies have also showed that some ancient hepatitis viral strains still infect humans, while other became extinct.The earliest record of an epidemic caused by hepatitis B virus was made by Lurman in 1885 </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 Omphalomesenteric duct cyst and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Abdomen and can you explain it in depth? [/INST] The abdomen (colloquially called the belly, tummy, midriff, tucky or stomach) is the part of the body between the thorax (chest) and pelvis, in humans and in other vertebrates. The abdomen is the front part of the abdominal segment of the torso. The area occupied by the abdomen is called the abdominal cavity. In arthropods it is the posterior tagma of the body; it follows the thorax or cephalothorax.In humans, the abdomen stretches from the thorax at the thoracic diaphragm to the pelvis at the pelvic brim. The pelvic brim stretches from the lumbosacral joint (the intervertebral disc between L5 and S1) to the pubic symphysis and is the edge of the pelvic inlet. The space above this inlet and under the thoracic diaphragm is termed the abdominal cavity. The boundary of the abdominal cavity is the abdominal wall in the front and the peritoneal surface at the rear.
In vertebrates, the abdomen is a large body cavity enclosed by the abdominal muscles, at front and to the sides, and by part of the vertebral column at the back. Lower ribs can also enclose ventral and lateral walls. The abdominal cavity is continuous with, and above, the pelvic cavity. It is attached to the thoracic cavity by the diaphragm. Structures such as the aorta, inferior vena cava and esophagus pass through the diaphragm. Both the abdominal and pelvic cavities are lined by a serous membrane known as the parietal peritoneum. This membrane is continuous with the visceral peritoneum lining the organs. The abdomen in vertebrates contains a number of organs belonging to, for instance, the digestive system, urinary system, and muscular system.

Contents
The abdominal cavity contains most organs of the digestive system, including the stomach, the small intestine, and the colon with its attached appendix. Other digestive organs are known as the accessory digestive organs and include the liver, its attached gallbladder, and the pancreas, and these communicate with the rest of the system via various ducts. The spleen, and organs of the urinary system including the kidneys, and adrenal glands also lie within the abdomen, along with many blood vessels including the aorta and inferior vena cava. The urinary bladder, uterus, fallopian tubes, and ovaries may be seen as either abdominal organs or as pelvic organs. Finally, the abdomen contains an extensive membrane called the peritoneum. A fold of peritoneum may completely cover certain organs, whereas it may cover only one side of organs that usually lie closer to the abdominal wall. This is called the retroperitoneum, and the kidneys and ureters are known as retroperitoneal organs.
Abdominal organs can be highly specialized in some animals. For example, the stomach of ruminants, (a suborder of mammals that includes cattle and sheep), is divided into four chambers – rumen, reticulum, omasum and abomasum.

Muscles
There are three layers of muscles in the abdominal wall. They are, from the outside to the inside: external oblique, internal oblique, and transverse abdominal. The first three layers extend between the vertebral column, the lower ribs, the iliac crest and pubis of the hip. All of their fibers merge towards the midline and surround the rectus abdominis in a sheath before joining up on the opposite side at the linea alba. Strength is gained by the criss-crossing of fibers, such that the external oblique runs downward and forward, the internal oblique upward and forward, and the transverse abdominal horizontally forward.The transverse abdominal muscle is flat and triangular, with its fibers running horizontally. It lies between the internal oblique and the underlying transverse fascia. It originates from the inguinal ligament, costal cartilages 7-12, the iliac crest and thoracolumbar fascia. Inserts into the conjoint tendon, xiphoid process, linea alba and the pubic crest.
The rectus abdominis muscles are long and flat. The muscle is crossed by three fibrous bands called the tendinous intersections. The rectus abdominis is enclosed in a thick sheath, formed as described above, by fibers from each of the three muscles of the lateral abdominal wall. They originate at the pubis bone, run up the abdomen on either side of the linea alba, and insert into the cartilages of the fifth, sixth, and seventh ribs. In the region of the groin, the inguinal canal, is a passage through the layers. This gap is where the testes can drop through the wall and where the fibrous cord from the uterus in the female runs. This is also where weakness can form, and cause inguinal hernias.The pyramidalis muscle is small and triangular. It is located in the lower abdomen in front of the rectus abdominis. It originates at the pubic bone and is inserted into the linea alba halfway up to the navel.

Function
Functionally, the human abdomen is where most of the digestive tract is placed and so most of the absorption and digestion of food occurs here. The alimentary tract in the abdomen consists of the lower esophagus, the stomach, the duodenum, the jejunum, ileum, the cecum and the appendix, the ascending, transverse and descending colons, the sigmoid colon and the rectum. Other vital organs inside the abdomen include the liver, the kidneys, the pancreas and the spleen.
The abdominal wall is split into the posterior (back), lateral (sides), and anterior (front) walls.

Movement, breathing and other functions
The abdominal muscles have different important functions. They assist as muscles of exhalation in the breathing process during forceful exhalation. Moreover, these muscles serve as protection for the inner organs. Furthermore, together with the back muscles they provide postural support and are important in defining the form. When the glottis is closed and the thorax and pelvis are fixed, they are integral in the cough, urination, defecation, childbirth, vomit, and singing functions. When the pelvis is fixed, they can initiate the movement of the trunk in a forward motion. They also prevent hyperextension. When the thorax is fixed, they can pull up the pelvis and finally, they can bend the vertebral column sideways and assist in the trunks rotation.

Posture
The transverse abdominis muscle is the deepest muscle, therefore, it cannot be touched from the outside. It can greatly affect the bodys posture. The internal obliques are also deep and also affect body posture. Both of them are involved in rotation and lateral flexion of the spine and are used to bend and support the spine from the front. The external obliques are more superficial and they are also involved in rotation and lateral flexion of the spine. Also they stabilize the spine when upright. The rectus abdominis muscle is not the most superficial abdominal muscle. The tendonous sheath extending from the external obliques cover the rectus abdominis. The rectus abdominis is the muscle that very fit people develop into the 6-pack ab look. Although it should really be a 10 pack as there are 5 vertical sections on each side. The 2 bottom sections are just above the pubic bone and usually not visible, hence, the 6 pack abs. The rectus abdominals function is to bend ones back forward (flexion). The main work of the abdominal muscles is to bend the spine forward when contracting concentrically.

Society and culture
Social and cultural perceptions of the outward appearance of the abdomen has varying significance around the world. Depending on the type of society, excess weight can be perceived as an indicator of wealth and prestige due to excess food, or as a sign of poor health due to lack of exercise. In many cultures, bare abdomens are distinctly sexualized and perceived similarly to breast cleavage.

Exercise
Being key elements of spinal support, and contributors to good posture, it is important to properly exercise the abdominal muscles together with the back muscles because when these are weak or overly tight they can suffer painful spasms and injuries. When properly exercised, abdominal muscles contribute to improved posture and balance, reduce the likelihood of back pain episodes, reduce the severity of back pain, protect against injury by responding efficiently to stresses, help avoid some back surgeries, and help with the healing of back problems, or after spine surgery. When strengthened, the abdominal muscles provide flexibility as well. The abdominal muscles can be worked by practicing disciplines of general body strength such as Pilates, yoga, Tai chi, and jogging. There are also specific routines which target each of these muscles.

Clinical significance
Abdominal obesity is a condition where abdominal fat or visceral fat, has built up excessively between the abdominal organs. This is associated with a higher risk of heart disease, asthma and type 2 diabetes.
Abdominal trauma is an injury to the abdomen and can involve damage to the abdominal organs. There is an associated risk of severe blood loss and infection. Injury to the lower chest can cause injuries to the spleen and liver.A scaphoid abdomen is when the abdomen is sucked inwards. In a newborn, it may represent a diaphragmatic hernia. In general, it is indicative of malnutrition.

Disease
Many gastrointestinal diseases affect the abdominal organs. These include stomach disease, liver disease, pancreatic disease, gallbladder and bile duct disease; intestinal diseases include enteritis, coeliac disease, diverticulitis, and IBS.

Examination
Different medical procedures can be used to examine the organs of the gastrointestinal tract. These include endoscopy, colonoscopy, sigmoidoscopy, enteroscopy, oesophagogastroduodenoscopy and virtual colonoscopy. There are also a number of medical imaging techniques that can be used. Surface landmarks are important in the examination of the abdomen.

Surface landmarks
In the mid-line a slight furrow extends from the xiphoid process above to the pubic symphysis below, representing the linea alba in the abdominal wall. At about its midpoint sits the umbilicus or navel. The rectus abdominis on each side of the linea alba stands out in muscular people. The outline of these muscles is interrupted by three or more transverse depressions indicating the tendinous intersections. There is usually one about the xiphoid process, one at the navel, and one in between. It is the combination of the linea alba and the tendinous intersections which form the abdominal "six-pack" sought after by many people.
The upper lateral limit of the abdomen is the subcostal margin (at or near the subcostal plane) formed by the cartilages of the false ribs (8, 9, 10) joining one another. The lower lateral limit is the anterior crest of the ilium and Pouparts ligament, which runs from the anterior superior spine of the ilium to the spine of the pubis. These lower limits are marked by visible grooves. Just above the pubic spines on either side are the external abdominal rings, which are openings in the muscular wall of the abdomen through which the spermatic cord emerges in the male, and through which an inguinal hernia may rupture.
One method by which the location of the abdominal contents can be appreciated is to draw three horizontal and two vertical lines.

Horizontal lines
The highest of the former is the transpyloric line of C. Addison, which is situated halfway between the suprasternal notch and the top of the pubic symphysis, and often cuts the pyloric opening of the stomach an inch to the right of the mid-line. The hilum of each kidney is a little below it, while its left end approximately touches the lower limit of the spleen. It corresponds to the first lumbar vertebra behind.
The second line is the subcostal line, drawn from the lowest point of the subcostal arch (tenth rib). It corresponds to the upper part of the third lumbar vertebra, and it is an inch or so above the umbilicus. It indicates roughly the transverse colon, the lower ends of the kidneys, and the upper limit of the transverse (3rd) part of the duodenum.
The third line is called the intertubercular line, and runs across between the two rough tubercles, which can be felt on the outer lip of the crest of the ilium about two and a half inches (64 mm) from the anterior superior spine. This line corresponds to the body of the fifth lumbar vertebra, and passes through or just above the ileo-caecal valve, where the small intestine joins the large intestine.

Vertical lines
The two vertical or mid-Poupart lines are drawn from the point midway between the anterior superior spine and the pubic symphysis on each side, vertically upward to the costal margin.

The right one is the most valuable, as the ileo-caecal valve is situated where it cuts the intertubercular line. The orifice of the appendix lies an inch lower, at McBurneys point. In its upper part, the vertical line meets the transpyloric line at the lower margin of the ribs, usually the ninth, and here the gallbladder is situated.
The left mid-Poupart line corresponds in its upper three-quarters to the inner edge of the descending colon.The right subcostal margin corresponds to the lower limit of the liver, while the right nipple is about half an inch above its upper limit.

Quadrants and regions
The abdomen can be divided into quadrants or regions to describe the location of an organ or structure. Classically, quadrants are described as the left upper, left lower, right upper, and right lower. Quadrants are also often used in describing the site of an abdominal pain.The abdomen can also be divided into nine regions.

These terms stem from "hypo" meaning "below" and "epi" means "above", while "chondron" means "cartilage" (in this case, the cartilage of the rib) and "gaster" means stomach. The reversal of "left" and "right" is intentional, because the anatomical designations reflect the patients own right and left.)
The "right iliac fossa" (RIF) is a common site of pain and tenderness in patients who have appendicitis. The fossa is named for the underlying iliac fossa of the hip bone, and thus is somewhat imprecise. Most of the anatomical structures that will produce pain and tenderness in this region are not in fact in the concavity of the ileum </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 Solitary fibrous tumor and can you explain it in depth? [/INST] Solitary fibrous tumor (SFT), also known as fibrous tumor of the pleura, is a rare mesenchymal tumor originating in the pleura or at virtually any site in the soft tissue including seminal vesicle. Approximately 78% to 88% of SFTs are benign and 12% to 22% are malignant. The World Health Organization (2020) classified SET as specific type of tumor in the category of malignant fibroblastic and myofibroblastic tumors.

Signs and symptoms
About 80% of pleural SFTs originate in the visceral pleura, while 20% arise from parietal pleura. Although they are often very large tumors (up to 40 cm </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 Spastic hemiplegia and can you explain it in depth? [/INST] Spastic hemiplegia is a neuromuscular condition of spasticity that results in the muscles on one side of the body being in a constant state of contraction. It is the "one-sided version" of spastic diplegia. It falls under the mobility impairment umbrella of cerebral palsy. About 20–30% of people with cerebral palsy have spastic hemiplegia. Due to brain or nerve damage, the brain is constantly sending action potentials to the neuromuscular junctions on the affected side of the body. Similar to strokes, damage on the left side of the brain affects the right side of the body and damage on the right side of the brain affects the left side of the body. Other side can be effected for lesser extent.
The affected side of the body is rigid, weak and has low functional abilities. In most cases, the upper extremity is much more affected than the lower extremity. This could be due to preference of hand usage during early development. If both arms are affected, the condition is referred to as double hemiplegia. Some patients with spastic hemiplegia only experience minor impairments, where in severe cases one side of the body could be completely paralyzed. The severity of spastic hemiplegia is dependent upon the degree of the brain or nerve damage.

Presentation
Complications
The muscle spasticity can cause gait patterns to be awkward and jerky. The constant spastic state of the muscle can lead to bone and tendon deformation, further complicating the patients mobility. Many patients with spastic hemiplegia are subjected to canes, walkers and even wheelchairs. Due to the decrease in weight bearing, patients are at a higher risk of developing osteoporosis. An unhealthy weight can further complicate mobility. Patients with spastic hemiplegia are a high risk for experiencing seizures. Oromotor dysfunction puts patients at risk for aspiration pneumonia. Visual field deficits can cause impaired two-point discrimination. Many patients experience the loss of sensation in the arms and legs on the affected side of the body.  Nutrition is essential for the proper growth and development for a child with spastic hemiplegia.

Causes
There are many different brain dysfunctions that can account for the cause for spastic hemiplegia. Spastic hemiplegia occurs either at birth or in the womb. The cause can be all types of strokes, cerebral palsy head injuries, hereditary diseases, brain injuries and infections. Malformations of the veins or arteries in any part of the body can lead to spastic hemiplegia. The artery most commonly affected is the middle cerebral artery. Unborn and newborn babies are susceptible to strokes. Leukodystrophies are a group of hereditary diseases that are known to cause spastic hemiplegia. Brain infections that cause spastic hemiplegia are meningitis, multiple sclerosis, and encephalitis. The spasticity occurs when the afferent pathways in the brain are compromised and the communication between the brain to the motor fibers is lost. When the inhibitory signals to deactivate the stretch reflex is lost the muscle remains in a constantly contracted state. With spastic hemiplegia, one upper extremity and one lower extremity is affected, so cervical, lumbar and sacral segments of the spinal column can be affected.

Diagnosis
Infants with spastic hemiplegia may develop a hand preference earlier than is typical.

Treatment
There is no known cure for cerebral palsy, however, there is a large array of treatments proven effective at improving quality of life and relieving some of the symptoms associated with CP, especially SHCP.  Some treatments are aimed at improving mobility, strengthening muscle and improving coordination. Although CP is due to permanent damage and is not progressive in nature, without treatment the symptoms can become worse, intensifying in pain and severity, and create complications that were not initially present. Some treatments are preventative measures to help prevent further complications, such as complete paralysis of the arm due to non-use and subsequent worsening hypertonia and joint contracture. Others forms of treatment are corrective in nature. Many treatments target symptoms that are indirectly related to or caused by the SHCP. Many of these treatments are common for other forms of CP as well. Treatment is individualized based on each case and the specific needs of the patient. Treatments are often combined with other forms of treatment and a long-term treatment plan is created and continuously evaluated. Treatment can include the following:

Physical therapy – Physical therapy is the most common form of treatment (source needed). It may include sensory stimulation, stretching, strengthening and positioning. Constraint-induced movement therapy is a newer form of physical therapy for SHCP that involves casting or splinting the unaffected arm to promote the use of the affected arm (Taub). The theory behind constraint-induced movement therapy is that new neural pathways are created. Alternative forms of physical therapy include yoga and dance. Physical therapy may also include the use of braces while not actively involved with the therapist.
Occupational therapy – Occupational therapy evaluates and treats patients through selected activities in order to enable people to function as effectively and independently as possible in daily life. Occupational therapy is geared toward the individual to achieve optimal results and performance while learning to cope with their disability.
Speech therapy – Due to difficulties in speech, speech therapy is often necessary. Aside from helping with understanding language and increasing communication skills, speech therapists can also assist children that have difficulty eating and drinking.
Behavioral therapy —  Psychotherapy and counseling are heavily used in the treatment of individuals with SHPD to help them cope emotionally with their needs and frustrations. Counseling through social work can be very beneficial for social issues and adjustments to society. Psychotherapy becomes a more important aspect of therapy when more serious issues such as depression become problematic. Play therapy is a common treatment for all young children with or without disabilities but can be very useful in helping children with SHCP. This therapy again is individualized geared to improve emotional and social development; reduce aggression; improve cooperation with others; assist a child in processing a traumatic event or prepare for an upcoming event such as surgery.
Surgery – Although surgery may become necessary in some cases, physical therapy and the consistent use of braces can help mitigate the need for surgery. Surgical procedures are painful with long and difficult recoveries and do not cure the condition. Most common is a surgery that effectively lengthens the muscle. This type of surgery is usually performed on the legs, but can be performed on the arms as well. Surgeries also may be necessary to realign joints. Other, less popular surgical techniques try to reduce spasticity by severing selected overactive nerves that control muscles. This procedure, known as selective dorsal root rhizotomy, is still somewhat controversial and is generally used only on the lower extremities of severe cases. Other experimental surgical techniques are also being investigated. The benefits of surgery can also be negated or reversed if the patient does not participate in physical therapy and braces (or casts) are not worn regularly.
Medicinal – Medication targeting symptoms associated with spasticity is also a relatively new treatment that is utilized but is still in the early stages of development. Drugs such as baclofen, benzodiazepines (e.g., diazepam), tizanidine, and sometimes dantrolene have shown promise in the effort to diminish spasticity. Botulinum toxin ("Botox") type A may reduce spasticity a few months at a time and has frequently been considered a beneficial treatment for children with SHCP and other forms of CP. Botox has been shown to be especially beneficial to reducing spasticity in the gastrocnemius (calf) muscle. This therapy can improve range of motion, reduce deformity, improve response to occupational and physical therapy, and delay the need for surgery </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 Gynecomastia and can you explain it in depth? [/INST] Gynecomastia (also spelled gynaecomastia) is the abnormal non-cancerous enlargement of one or both breasts in males due to the growth of breast tissue as a result of a hormone imbalance between estrogens and androgens. Gynecomastia can cause significant psychological distress or unease.Gynecomastia can be normal in newborn babies due to exposure to estrogen from the mother, in adolescents going through puberty, in older men over age 50, and/or in obese men. Most occurrences of gynecomastia do not require diagnostic tests. Gynecomastia may be caused by abnormal hormone changes, any condition that leads to an increase in the ratio of estrogens/androgens such as liver disease, kidney failure, thyroid disease and some non-breast tumors. Alcohol and some drugs can also cause breast enlargement. Other causes may include Klinefelter syndrome, metabolic dysfunction, or a natural decline in testosterone production. This may occur even if the levels of estrogens and androgens are both appropriate, but the ratio is altered.Gynecomastia is the most common benign disorder of the male breast tissue and affects 35% of men, being most prevalent between the ages of 50 and 69. It is normal for up to 70% of adolescent boys to develop gynecomastia. Of these, 75% resolve within two years of onset without treatment. If the condition does not resolve within 2 years, or if it causes embarrassment, pain or tenderness, treatment is warranted. Medical treatment of gynecomastia that has persisted beyond two years is often ineffective. Gynecomastia is different from "pseudogynecomastia", which is commonly present in men with obesity.Medications such as aromatase inhibitors have been found to be effective and even in rare cases of gynecomastia from disorders such as aromatase excess syndrome or Peutz–Jeghers syndrome, but surgical removal of the excess tissue can be needed to correct the condition. In 2019, 24,123 male patients underwent the procedure in the United States, accounting for a 19% increase since 2000.

Definition
Gynecomastia is the abnormal non-cancerous enlargement of one or both breasts in men due to the growth of breast tissue as a result of a hormone imbalance between estrogen and androgen. Gynecomastia is different from "pseudogynecomastia", which is defined as an excess of skin and/or adipose tissue in the male breasts without the growth of true glandular breast tissue; this is commonly associated with obesity and can be ruled out by physical exam.

Signs and symptoms
In gynecomastia there is typically enlargement of one or both breasts, symmetrically or asymmetrically, in a man. A soft, compressible, and mobile mass of breast tissue is felt under the nipple and its surrounding skin in contrast to softer fatty tissue which is not associated with a mass. It may also be accompanied by breast tenderness or nipple sensitivity, which is commonly associated with gynecomastia observed in adolescents, typically early in development. Gynecomastia that is painful, bothersome, rapidly-growing, associated with masses in other areas of the body, or persistent should be evaluated by a clinician for potential causes. Dimpling of the skin, nipple discharge, and nipple retraction are not typical features of gynecomastia and may be associated with other disorders. Milky discharge from the nipple is not a typical finding, but may be seen in a gynecomastic individual with a prolactin secreting tumor. An increase in the diameter of the areola and asymmetry of the chest are other possible signs of gynecomastia.Gynecomastia has psychosocial implications that may be particularly challenging for adolescents who are experiencing physical maturation and self-identity formation, which includes body image disturbances, negative attitudes towards eating, self-esteem problems, social withdrawal, anxiety, and shame. Men with gynecomastia may appear anxious or stressed due to concerns about its appearance and the possibility of having breast cancer.

Causes
Gynecomastia is thought to be caused by an altered ratio of estrogens to androgens mediated by an increase in estrogen action, a decrease in androgen action, or a combination of these two factors. Estrogen and androgens have opposing actions on breast tissue: estrogens stimulate proliferation while androgens inhibit proliferation. The cause of gynecomastia is unknown in around 25% of cases. Known causes can be physiologic (occurring normally) or non-physiologic due to underlying pathologies such as drug use, chronic disease, tumors, or malnutrition.

Physiologic
Physiologic or normal gynecomastia can occur at three timepoints in life: shortly after birth in both female and male infants, during puberty in adolescent males, and in older adults over the age of 60.

Newborns
60-90% of male and female newborns may show breast development at birth or in the first weeks of life. During pregnancy, the placenta converts the androgenic hormones dehydroepiandrosterone (DHEA) and DHEA sulfate to the estrogenic hormones estrone and estradiol, respectively; after these estrogens are produced by the placenta, they are transferred into the babys circulation, thereby leading to temporary gynecomastia in the baby. In some infants, neonatal milk (also known as "witchs milk") can leak from the nipples. The temporary gynecomastia seen in newborn babies usually resolves after two or three weeks.

Adolescents
Hormonal imbalance (elevated ratio of estrogen to androgen) during early puberty, either due to decreased androgen production from the adrenals and/or increased conversion of androgens to estrogens, leads to transient gynecomastia in adolescent males. It can occur in up to 65% of adolescents as early as age 10 and peaks at ages 13 and 14. It is self-limited in 75-90% of adolescents and usually resolves spontaneously within 1 to 3 years as pubertal progression increases testosterone levels and cause regression of breast tissue. By age 17, only 10% of adolescent males have persistent gynecomastia.

Older adults
Declining testosterone levels and an increase in the level of subcutaneous fatty tissue seen as part of the normal aging process can lead to gynecomastia in older males. Increased fatty tissue, a major site of aromatase activity, leads to increased conversion of androgenic hormones such as testosterone to estrogens. Additionally, levels of sex hormone binding globulin (SHBG) increase with age and bind with less affinity to estrogen than androgens. Put together, the elevated ratio of estrogen to androgen leads to gynecomastia, also known as senile gynecomastia in this group. There is a 24-65% prevalence of senile gynecomastia in older males.

Non-physiologic
Drugs
About 10–25% of gynecomastia cases are estimated to result from the use of medications or exogenous chemicals. Drugs can increase estrogen activity or increase the estrogen to androgen ratio through various mechanisms, such as binding to estrogen receptors, promoting estrogen synthesis, providing precursors that can be aromatized into estrogen, causing damage to the testes, inhibiting testosterone synthesis, inhibiting the action of androgens, or displacing estrogen from SHBG. Drugs with good evidence for association with gynecomastia include cimetidine, ketoconazole, gonadotropin-releasing hormone analogues, human growth hormone, human chorionic gonadotropin, 5α-reductase inhibitors such as finasteride and dutasteride, certain estrogens used for prostate cancer, and antiandrogens such as bicalutamide, flutamide, and spironolactone.Drugs with fair evidence for association with gynecomastia include calcium channel blockers such as verapamil, amlodipine, and nifedipine; risperidone, olanzapine, anabolic steroids, alcohol, opioids, efavirenz, alkylating agents, and omeprazole. Certain components of personal skin care products such as lavender or tea tree oil have been reported to cause prepubertal gynecomastia due to its estrogenic and anti-androgenic effects. Certain dietary supplements such as dong quai and Tribulus terrestris have also been associated with gynecomastia.

Refeeding gynecomastia
Malnutrition and significant loss of body fat suppress gonadotropin secretion, leading to hypogonadism. This is reversible when adequate nutrition resumes, where the return of gonadotropin secretion and gonadal function cause a transient imbalance of estrogen and androgen that mimics puberty, resulting in transient gynecomastia. This phenomenon, also known as refeeding gynecomastia, was first observed when men returning home from prison camps during World War II developed gynecomastia after resuming a normal diet. Similar to pubertal gynecomastia, refeeding gynecomastia resolves on its own in 1–2 years.

Chronic disease
Many kidney failure patients experience a hormonal imbalance due to the suppression of testosterone production and testicular damage from high levels of urea also known as uremia-associated hypogonadism. Additionally, gynecomastia has been observed in 50% of patients with chronic kidney disease undergoing dialysis. Similar to the mechanism behind refeeding gynecomastia, dialysis allows patients with renal failure who were previously malnourished to expand their diets and regain weight. Dialysis-associated gynecomastia resolves spontaneously within 1–2 years.In individuals with liver failure or cirrhosis, the livers ability to properly metabolize hormones such as estrogen may be impaired. Additionally, those with alcoholic liver disease are further put at risk for development of gynecomastia; ethanol may directly disrupt the synthesis of testosterone and the presence of phytoestrogens in alcoholic drinks may also contribute to a higher estrogen to testosterone ratio. Conditions that can cause malabsorption such as cystic fibrosis or ulcerative colitis may also produce gynecomastia.A small proportion of male gynecomastia cases may be seen with rare inherited disorders such as spinal and bulbar muscular atrophy and the very rare aromatase excess syndrome.

Hypogonadism
Gynecomastia can be caused by absolute deficiency in androgen production due to primary or secondary hypogonadism. Primary hypogonadism results when there is damage to the testes (due to radiation, chemotherapy, infections, trauma, etc), leading to impaired androgen production. It can also be caused by chromosomal abnormality seen in Klinefelter syndrome, which is associated with gynecomastia in about 80% of cases. Secondary hypogonadism results when there is damage to the hypothalamus or pituitary (due to radiation, chemotherapy, infection, trauma, etc), and similarly lead to impaired androgen production. The net effect is reduced androgen production while serum estrogen levels (from peripheral aromatization of androgens) remain unaffected. The lack of androgen-mediated inhibition of breast tissue proliferation combined with relative estrogen excess result in gynecomastia.

Tumors
Testicular tumors such as Leydig cell tumors, Sertoli cell tumors (such as in Peutz–Jeghers syndrome) and hCG-secreting choriocarcinoma may result in rapid-onset gynecomastia by causing excess production of estrogen. Other tumors such as adrenal tumors, pituitary gland tumors (such as a prolactinoma), or lung cancer, can produce hormones that alter the male–female hormone balance and cause gynecomastia.Individuals with prostate cancer who are treated with androgen deprivation therapy may experience gynecomastia.

Pathophysiology
The causes of common gynecomastia remain uncertain, but are thought to result from an imbalance between the actions of estrogen, which stimulates breast tissue growth, and androgens, which inhibit breast tissue growth. Breast prominence can result from enlargement of glandular breast tissue, chest adipose tissue (fat) and skin, and is typically a combination. As in females, estrogen stimulates the growth of breast tissue in males. In addition to directly stimulating breast tissue growth, estrogens indirectly decrease secretion of testosterone by suppressing luteinizing hormone secretion, resulting in decreased testicular secretion of testosterone.

Estrogen excess
One of the main mechanisms for imbalance between estrogens and androgens is the overproduction of estrogens. A possible cause may be a neoplasm that originates from estrogen-secreting cells. Tumors that produce hCG stimulate production of estradiol while reducing other testicular hormone production. Obesity is another common cause of excess serum estrogens due to the presence of aromatase in peripheral tissue, which is a protein that converts androgens into estrogens. Peutz-Jeghers syndrome is a rare cause of testicular tumors that affect aromatase expression, which results in elevated serum estrogen levels. Aromatase excess syndrome is a rare genetic disorder that leads to increased conversion of androgens to estrogens in the body.

Androgen deficiency
Primary hypogonadism (indicating an intrinsic problem with the testes in males) leads to decreased testosterone synthesis and increased conversion of testosterone to estradiol potentially leading to a gynecomastic appearance. Klinefelter syndrome is a notable example of a disorder that causes hypogonadism and gynecomastia, and has a higher risk of breast cancer in males (20–50 times higher than males without the disorder). Secondary hypogonadism (indicating a problem with the brain) leads to decreased production and release of luteinizing hormone (LH, a stimulatory signal for endogenous steroid hormone synthesis) which leads to decreased production of testosterone and estradiol in the testes.

Increased levels of sex hormone-binding globulin
Estrogens can increase blood levels of the protein sex hormone-binding globulin (SHBG), which binds free testosterone (the active form) more strongly than estrogen, leading to decreased action of testosterone in male breast tissue. Conditions such as hyperthyroidism and chronic liver disease affect levels of SHBG, leading to symptomatic gynecomastia.

Androgen resistance
Dysfunction in the androgen receptor prevents the effects of testosterone from acting on its target tissues. Androgen insensitivity syndromes result from the different degrees of resistance to the effects of androgens, and can cause external genitalia that may not be aligned with the genotype of the individuals sex chromosomes. Complete androgen insensitivity syndrome results in the failure to develop external genitalia such as the penis and scrotum along with development of breasts in an individual with testes. Partial androgen insensitivity syndrome may result in a variety of presentations. Minimal androgen insensitivity syndrome may present as gynecomastia in adolescence and may additionally be associated with infertility.

Medications
Medications are known to cause gynecomastia through several different mechanisms. These mechanisms include increasing estrogen levels, mimicking estrogen, decreasing levels of testosterone or other androgens, blocking androgen receptors, increasing prolactin levels, or through unidentified means. Potential sources of estrogen include oral contraceptive pills, spironolactone, and anabolic steroids.High levels of prolactin in the blood (which may occur as a result of certain tumors or as a side effect of certain medications) has been associated with gynecomastia. A high level of prolactin in the blood can inhibit the release of gonadotropin-releasing hormone and therefore cause secondary hypogonadism. Receptors for prolactin and other hormones including insulin-like growth factor 1, insulin-like growth factor 2, luteinizing hormone, progesterone, and human chorionic gonadotropin have been found in male breast tissue, but the impact of these various hormones on gynecomastia development is not well understood.

Chronic disease
Individuals who have cirrhosis or chronic liver disease may develop gynecomastia for several reasons. Those diagnosed with cirrhosis tend to have increased secretion of the androgenic hormone androstenedione from the adrenal glands, increased conversion of this hormone into various types of estrogen, and increased levels of SHBG, which leads to decreased blood levels of free testosterone. Around 10–40% of males with Graves disease (a common form of hyperthyroidism) experience gynecomastia. Increased conversion of testosterone to estrogen by increased aromatase activity, increased levels of SHBG and increased production of testosterone and estradiol by the testes due to elevated levels of LH cause the gynecomastia. Proper treatment of the hyperthyroidism can lead to the resolution of the gynecomastia.

Diagnosis
To diagnose gynecomastia, a thorough history and physical examination are obtained by a physician. Important aspects of the physical examination include evaluation of the male breast tissue with palpation to evaluate for breast cancer and pseudogynecomastia (male breast tissue enlargement solely due to excess fatty tissue), evaluation of penile size and development, evaluation of testicular development and an assessment for masses that raise suspicion for testicular cancer, and proper development of secondary sex characteristics such as the amount and distribution of pubic and underarm hair. Gynecomastia usually presents with bilateral involvement of the breast tissue but may occur unilaterally as well.Diagnosis of men with breast enlargement can be evaluated using an algorithm. A review of the medications or substances an individual takes may reveal the cause of gynecomastia. Recommended laboratory investigations to find the underlying cause of gynecomastia include tests for aspartate transaminase and alanine transaminase to rule out liver disease, serum creatinine to determine if kidney damage is present, and thyroid-stimulating hormone levels to evaluate for hyperthyroidism. If these initial laboratory tests fail to uncover the cause of gynecomastia, then additional tests to evaluate for an underlying hormonal balance due to hypogonadism or a testicular tumor should be checked including total and free levels of testosterone, luteinizing hormone, follicle stimulating hormone, estradiol, serum beta human chorionic gonadotropin (β-hCG), and prolactin.High levels of prolactin are uncommon in people with gynecomastia. If β-hCG levels are abnormally high, then ultrasound of the testicles should be performed to check for signs of a hormone-secreting testicular tumor. Markers of testicular, adrenal, or other tumors such as urinary 17-ketosteroid or serum dehydroepiandrosterone may also be checked if there is evidence of hormonal imbalance on physical examination. If this evaluation does not reveal the cause of gynecomastia, then it is considered to be idiopathic gynecomastia (of unclear cause).

Differential diagnosis
While there can be many potential causes of male patients that present with increased breast tissue, differential diagnoses are most concerning for gynecomastia, pseudogynecomastia, and breast cancer (which is rare in men). Other potential causes of male breast enlargement such as mastitis, lipoma, sebaceous cyst, dermoid cyst, hematoma, metastasis, ductal ectasia, fat necrosis, or a hamartoma are typically excluded before making the diagnosis.

Imaging
Mammography is the method of choice for radiologic examination of male breast tissue in the diagnosis of gynecomastia when breast cancer is suspected on physical examination. If a mass/lump is felt during a physical exam some features of the lump that would point to malignancy would be painless, non moveable (fixed), irregularly shaped, and skin changes. Mammography is rarely indicated for men since breast cancer is an unlikely diagnosis. If mammography is performed and does not reveal findings suggestive of breast cancer, further imaging is not typically necessary. If a tumor of the adrenal glands or the testes is thought to be responsible for the gynecomastia, ultrasound examination of these structures may be performed.

Histology
Early histological features expected to be seen on examination of gynecomastic tissue attained by fine-needle aspiration biopsy include the following: proliferation and lengthening of the ducts, an increase in connective tissue, an increase in inflammation, and swelling surrounding the ducts, and an increase in fibroblasts in the connective tissue. Chronic gynecomastia may show different histological features such as increased connective tissue fibrosis, an increase in the number of ducts, less inflammation than in the acute stage of gynecomastia, increased subareolar fat, and hyalinization of the stroma. When surgery is performed, the gland is routinely sent to the lab to confirm the presence of gynecomastia and to check for tumors under a microscope. The utility of pathologic examination of breast tissue removed from male adolescent gynecomastia patients has recently been questioned due to the rarity of breast cancer in this population.

Classification
The spectrum of gynecomastia severity has been categorized into a grading system:
Grade I: Minor enlargement, no skin excess
Grade II: Moderate enlargement, no skin excess
Grade III: Moderate enlargement, skin excess
Grade IV: Marked enlargement, skin excess

Treatment
Mild cases of gynecomastia in adolescence may be treated with advice on lifestyle habits such as proper diet and exercise with reassurance. In more severe cases, medical treatment may be offered including medication or surgical intervention.

Medication
Gynecomastia can respond well to medical treatment although it is usually only effective when done within the first two years after the start of male breast enlargement. Selective estrogen receptor modulators (SERMs) such as tamoxifen, raloxifene, and clomifene may be beneficial in the treatment of gynecomastia but are not approved by the Food and Drug Administration for use in gynecomastia. Clomifene seems to be less effective than tamoxifen or raloxifene. Tamoxifen may be used to treat gynecomastia in adults and of the medical treatments used, tamoxifen is the most effective. Recent studies have shown that treatment with tamoxifen may represent a safe and effective mode of treatment in cases of cosmetically disturbing or painful gynecomastia. Aromatase inhibitors (AIs) such as anastrozole have been used off-label for cases of gynecomastia occurring during puberty but are less effective than SERMs.A few cases of gynecomastia caused by the rare disorders aromatase excess syndrome and Peutz–Jeghers syndrome have responded to treatment with AIs such as anastrozole. Androgens/anabolic steroids may be effective for gynecomastia. Testosterone itself may not be suitable to treat gynecomastia as it can be aromatized into estradiol, but nonaromatizable androgens like topical androstanolone (dihydrotestosterone) can be useful.

Surgery
If chronic gynecomastia does not respond to medical treatment, surgical removal of glandular breast tissue is usually required. The American Board of Cosmetic Surgery reports surgery is the "most effective known treatment for gynecomastia." Surgical treatment should be considered if the gynecomastia persists for more than 12 months, causes distress (ie physical discomfort or psychological distress), and is in the fibrotic stage. In adolescent males, it is recommended that surgery is postponed until puberty is completed (penile and testicular development should reach Tanner scale Stage V).Surgical approaches to the treatment of gynecomastia include subcutaneous mastectomy, liposuction-assisted mastectomy, laser-assisted liposuction, and laser-lipolysis without liposuction. Complications of mastectomy may include hematoma, surgical wound infection, breast asymmetry, changes in sensation in the breast, necrosis of the areola or nipple, seroma, noticeable or painful scars, and contour deformities. In 2019, 24,123 male patients underwent surgical treatment for gynecomastia in the United States, accounting for a 19% increase since 2000. Thirty-five percent of those patients were between the ages of 20 and 29, and 60% were younger than age 29 at the time of the operation. At an average surgeons fee of $4,123, gynecomastia surgery was also the 11th most costly male cosmetic surgery of 2019.

Others
Radiation therapy and tamoxifen have been shown to help prevent gynecomastia and breast pain from developing in prostate cancer patients who will be receiving androgen deprivation therapy. The efficacy of these treatments is limited once gynecomastia has occurred and are therefore most effective when used prophylactically.In the United States, many insurance companies deny coverage for surgery for gynecomastia treatment or male breast reduction on the basis that it is a cosmetic procedure.

Prognosis
Gynecomastia itself is a benign finding. It does not confer a poor prognosis, for some patients with underlying pathologies such as testicular cancer the prognosis may be worse. The glandular tissue typically grows under the influence of hormonal stimulation and is often tender or painful. Furthermore, gynecomastia frequently presents social and psychological difficulties such as low self-esteem, depression or shame.

Epidemiology
Gynecomastia is the most common benign disorder of the male breast tissue and affects 35 percent of men, being most prevalent between the ages of 50 and 69.New cases of gynecomastia are common in three age populations: newborns, adolescents, and men older than 50 years. Newborn gynecomastia occurs in about 60–90 percent of male babies and most cases resolve on their own in about 2–3 weeks after delivery. During adolescence, on average 33 percent of males are estimated to exhibit signs of gynecomastia. Gynecomastia in older men is estimated to be present in 24–65 percent of men between the ages of 50 and 80. Estimates on asymptomatic gynecomastia is about up to 70% in men aged 50 to 69 years.The prevalence of gynecomastia in men may have increased in recent years, but the epidemiology of the disorder is not fully understood. The use of anabolic steroids and exposure to chemicals that mimic estrogen in cosmetic products, organochlorine pesticides, and industrial chemicals have been suggested as possible factors driving this increase </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 Duct ectasia of breast and can you explain it in depth? [/INST] Duct ectasia of the breast, mammary duct ectasia or plasma cell mastitis is a condition that occurs when a milk duct beneath the nipple widens, the duct walls thicken, and the duct fills with fluid. This is the most common cause of greenish discharge.
Mammary duct ectasia can mimic breast cancer. It is a disorder of peri- or post-menopausal age.Duct ectasia syndrome is a synonym for nonpuerperal mastitis, but the term has also been occasionally used to describe special cases of fibrocystic diseases or mastalgia or as a wastebasket definition of benign breast disease.
Correlation of duct widening with the "classical" symptoms of duct ectasia syndrome is unclear. However, duct widening was recently very strongly correlated with noncyclic breast pain.Duct diameter is naturally variable, subject to hormonal interactions. Duct ectasia syndrome in the classical meaning is associated with additional histological changes.

Symptoms
Signs of duct ectasia can include nipple retraction, inversion, pain, and classic green-brown discharge.

Causes
Breasts are made up of fibrous connective tissues, which are made up of cells, fibers and a gel-like substance.

Pathogenesis
The duct widening is commonly believed to be a result of secretory stasis, including stagnant colostrum, which also causes periductal inflammation and fibrosis. However, because nonspecific duct widening is common it might be also coincidental finding in many processes.
Smokers seem more often affected by duct ectasia syndrome although the reported results are not entirely consistent </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 Ocular albinism and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Simple-type schizophrenia and can you explain it in depth? [/INST] Simple-type schizophrenia is a sub-type of schizophrenia included in the International Classification of Diseases (ICD-10), in which it is classified as a mental and behaviour disorder. It is not included in the current Diagnostic and Statistical Manual of Mental Disorders (DSM-5) or the upcoming ICD-11, effective on the 1st of January 2022. Simple-type schizophrenia is characterized by negative ("deficit") symptoms, such as avolition, apathy, anhedonia, reduced affect display, lack of initiative, lack of motivation, low activity; with absence of hallucinations or delusions of any kind.
Simple schizophrenia was included as a proposed diagnosis for further study in the appendix of the former DSM-IV.

Signs and symptoms
It has possibly the earliest onset compared to all other schizophrenias, considered to begin in some within childhood. Symptoms of schizophrenia simplex include an absence of will, impoverished thinking and flattening of affect. There is a gradual deterioration of functioning with increased amotivation and reduced socialization. It is considered to be rarely diagnosed and is a schizophrenia without psychotic symptoms.In a study of patients in a Massachusetts hospital, persons with simple schizophrenia were found to make attempts at reality fulfillment with respect to the more primitive needs; tending toward the achievement of fulfillment of these needs rather than engaging in fantasy as is typically found as a reaction to environmental stimuli by the psychotic person.

Causes
A progressive state of simple schizophrenia results often in cases of adolescent onset juvenile general paresis. Paresis is caused by placental-foetal transfer of infection and results in intellectual (mental) subnormality. Occurrence of this type of paresis is altogether uncommon (Lishman 1998).

Diagnosis
Classification
ICD
The WHO first listed the condition in the 6th revision of the International Classification of Diseases ICD-6 (1949) and it stayed in the manual until the present version ICD-10.

ICD-9
The ICD-9 simple-type schizophrenia description:

A psychosis in which there is insidious development of oddities of conduct, inability to meet the demands of society, and decline in total performance. Delusions and hallucinations are not in evidence and the condition is less obviously psychotic than are the hebephrenic, catatonic and paranoid types of schizophrenia. With increasing social impoverishment vagrancy may ensue and the patient becomes self-absorbed, idle and aimless. Because the schizophrenic symptoms are not clear-cut, diagnosis of this form should be made sparingly, if at all.

ICD-10
These are the current criteria:

Slowly progressive development over a period of at least one year, of all three of the following:
(a) A significant and consistent change in the overall quality of some aspects of personal behaviour, manifest as loss of drive and interests, aimlessness, idleness, a self-absorbed attitude and social withdrawal.
(b) Gradual appearance and deepening of negative symptoms such as marked apathy, paucity of speech, underactivity, blunting of affect, passivity and lack of initiative, and poor non-verbal communication.
(c) Marked decline in social, scholastic or occupational performance.
2. Absence, at any time, of any symptoms referred to in G1 in F20.0 - F20.3 and of hallucinations or well formed delusions of any kind, i.e. the subject must never have met the criteria for any other type of schizophrenia, or any other psychotic disorder.

3. Absence of evidence of dementia or any other organic mental disorder.
The ICD is currently in revision 10, and the ICD-11 was accepted in May 2019 will come into effect in 2022. In the ICD-11, there is no longer a diagnostic category of simple schizophrenia, and all subtypes of schizophrenia have been eliminated.

DSM
Simple-type schizophrenia also appeared in the first two editions of the DSM as an official diagnosis:
This psychosis is characterized chiefly by a slow and insidious reduction of external attachments and interests and by apathy and indifference leading to impoverishment of interpersonal relations, mental deterioration, and adjustment on a lower level of functioning. In general, the condition is less dramatically psychotic than are the hebephrenic, catatonic, and paranoid types of schizophrenia. Also, it contrasts with schizoid personality, in which there is little or no progression of the disorder.
But after that, it was omitted in later versions and has since then never returned as a formal diagnosis in any DSM. However, DSM-IV (1994) and DSM-IV-TR (2000) included Simple Schizophrenia in the appendix under the proposed category of simple deteriorative disorder. The provisional research criteria for it were:

Progressive development over a period of at least a year of all of the following:
(1) marked decline in occupational or academic functioning
(2) gradual appearance and deepening of negative
symptoms such as affective flattening, alogia, and avolition
(3) poor interpersonal rapport, social isolation or social withdrawal
B. Criterion A for Schizophrenia has never been met.

C. The symptoms are not better accounted for by Schizotypal or Schizoid Personality Disorder, a Psychotic Disorder, a Mood Disorder, an Anxiety Disorder, a dementia, or Mental Retardation and are not due to the direct physiological effects of a substance or a general medical condition.

Treatment
The use of antipsychotic medication is commonly the first line of treatment; however, the effectiveness after treatment is in question.
L-DOPA is effective against reduced affect display and emotional withdrawal, aloofness from society, apathy.

History
The early idea that a person with schizophrenia might present solely with symptoms and indications of deterioration (i.e. presenting with no accessory symptoms) was identified as dementia simplex.ICD-10 specifies the continuation of symptoms for a period of two years in the diagnosis of simple schizophrenia. This is because of disagreement on the classification validity of the sub-type, that having been retained by the ICD classification, has been omitted from DSM classifications </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 Sarcosinemia and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Drug tolerance and can you explain it in depth? [/INST] Drug tolerance or drug insensitivity is a pharmacological concept describing subjects reduced reaction to a drug following its repeated use. Increasing its dosage may re-amplify the drugs effects; however, this may accelerate tolerance, further reducing the drugs effects. Drug tolerance is indicative of drug use but is not necessarily associated with drug dependence or addiction. The process of tolerance development is reversible (e.g., through a drug holiday) and can involve both physiological factors and psychological factors.One may also develop drug tolerance to side effects, in which case tolerance is a desirable characteristic. A medical intervention that has an objective to increase tolerance (e.g., allergen immunotherapy, in which one is exposed to larger and larger amounts of allergen to decrease ones allergic reactions) is called drug desensitization.The opposite concept to drug tolerance is drug reverse tolerance (or drug sensitization), in which case the subjects reaction or effect will increase following its repeated use. The two notions are not incompatible and tolerance may sometimes lead to reverse tolerance. For example, heavy drinkers initially develop tolerance to alcohol (requiring them to drink larger amounts to achieve a similar effect) but excessive drinking can cause liver damage, which then puts them at risk of intoxication when drinking even very small amounts of alcohol.Drug tolerance should not be confused with drug tolerability, which refers to the degree to which overt adverse effects of a drug can be tolerated by a patient.

Tachyphylaxis
Tachyphylaxis is a subcategory of drug tolerance referring to cases of sudden, short-term onset of tolerance following the administration of a drug.

Pharmacodynamic tolerance
Pharmacodynamic tolerance begins when the cellular response to a substance is reduced with repeated use. A common cause of pharmacodynamic tolerance is high concentrations of a substance constantly binding with the receptor, desensitizing it through constant interaction. Other possibilities include a reduction in receptor density (usually associated with receptor agonists), or other mechanisms leading to changes in action potential firing rate. Pharmacodynamic tolerance to a receptor antagonist involves the reverse, i.e., increased receptor firing rate, an increase in receptor density, or other mechanisms.
While most occurrences of pharmacodynamic tolerance occur after sustained exposure to a drug, instances of acute or instant tolerance (tachyphylaxis) can occur.

Pharmacokinetic (metabolic) tolerance
Pharmacokinetics refers to the absorption, distribution, metabolism, and excretion of drugs (ADME) </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 Loin pain hematuria syndrome and can you explain it in depth? [/INST] Loin pain hematuria syndrome (LPHS) is the combination of debilitating unilateral or bilateral flank pain and microscopic or macroscopic amounts of blood in the urine that is otherwise unexplained.Loin pain-hematuria syndrome (LPHS) is a poorly defined disorder characterized by recurrent or persistent loin (flank) pain and hematuria that appears to represent glomerular bleeding. Most patients present with both manifestations, but some present with loin pain or hematuria alone. Pain episodes are rarely associated with low-grade fever and dysuria, but urinary tract infection is not present. The major causes of flank pain and hematuria, such as nephrolithiasis and blood clot, are typically not present. Renal arteriography may suggest focally impaired cortical perfusion, while renal biopsy may show interstitial fibrosis and arterial sclerosis.The pain is typically severe, and narcotic therapy is often prescribed as a way to manage chronic pain. Sleep can be difficult because the supine position increases pressure on the flank. The onset of pain is often associated with nausea and vomiting, making pain management by oral opiates complicated.

Cause
The cause of LPHS is not known.  One theory proposes that it is caused by a thin glomerular basement membrane and red blood cell (RBC) renal tubular congestion that leads to swelling of the kidney and distension of the renal fascia resulting in pain.Researchers have hypothesized that the syndrome may be due to blood vessel diseases of the kidney, spasms of the kidney vessels, or other bleeding disorders (coagulopathy).
The hematuria in LPHS may be due to an abnormal (thick or thin) glomerular basement membrane. The glomerular basement membrane is a tissue in the kidney that filters the blood. An abnormal glomerular basement membrane may allow red blood cells into the urinary space. Because kidney stones are so common in people with LPHS, crystals in the kidney tubules may also play a part in bleeding and pain.Other speculations on cause include
IgA nephropathy. This is a condition in which small amount of a type of normal antibody (called IgA) get stuck in the kidney as it passes through in the bloodstream. This is a chronic condition, which sometimes goes away on its own but occasionally can cause damage to the kidneys. A related condition called IgM nephropathy can sometimes cause pain.
Thin membrane disease. In this condition the membrane that filters the blood to make urine is too thin, and blood can pass across it in very small amounts. In a few cases of this condition, there is pain in the kidneys, usually occurring in attacks every so often. Although this condition can be painful, kidney failure does not seem to occur in the long term, so that the only real problem is the symptoms.
Infection. In some cases, loin pain-haematuria syndrome occurs after a bladder infection with involvement of the kidney. Even when the infection has been treated and bugs can no longer be found in the urine, pain may persist for 6 months, or even longer in some cases.
"Classic loin pain-haematuria syndrome". Some patients have none of the above diagnoses. In these cases there may be minor abnormalities on a kidney biopsy. Angiogram tests to look at the blood vessels in the kidney may show abnormal blood flow, perhaps causing a cramp like pain. The cause is not fully understood. It certainly is [more common] in women than in men, and there may be hormonal influences. Some women find the pain is worse at different times of their menstrual cycle, or comes on during pregnancy, or if they are taking [oral contraceptives].It has also been reported to be caused by microscopic granules of calcium oxylate into the glomerulus itself, causing blood vessels to rupture and increase the distention of the renal capsule.This condition may persist for some years, and can be lifelong. Damage to the kidneys leading to kidney failure does not occur. However, because LPHS is unusual in patients older than 60 years, some clinicians believe that LPHS eventually resolves.At this time no cure has been found for this disease. LPHS is a debilitating disease due to chronic pain and the inability to know how to control the glomerular aspect. The pain of LPHS can be worsened by acts as simple as riding in the car and undertaking daily activities. Many people with this disease are unable to maintain employment due to the debilitating pain.
Unpublished research by Dr. Ahmed Ghanem (who has cared for well over 100 women with LPHS found that untreated  Symptomatic Nephroptosis - SN (Hypermobile kidney) can lead to LPHS. Nephropexy can help to relieve symptoms. Severe renal colic caused by kinking ureter. Pain classically relieved a little by going on all fours with hips higher than head.

Diagnosis
LPHS is considered a diagnosis of exclusion. The syndrome presents with hematuria (blood in the urine) and flank (a region of the lower back beneath the ribs and above the ilium) pain which can result from a number of causes. Nonglomerular causes of bleeding (e.g., urinary infection, tumor, or nephrolithiasis) must be excluded. Obstruction of the urinary tract should not be present, confirmed by at least two imaging procedures while pain is present.
Diagnosis of loin pain-hematuria syndrome (LPHS) occurs when hematuria is present, recurrent or persistent pain is severe, and other causes of bleeding are excluded. Urine testing can be performed to detect microscopic levels of hematuria. Protein is also commonly found in the urine of patients with LPHS. Kidney biopsies are sometimes performed to look for evidence of glomerular hematuria, excess red blood cells in the kidney tubules, and to assess the width of the glomerular basement membrane.
Hematuria (more than 5 red blood cells per high power field) should be present in virtually every urinalysis and is typically characterized by dysmorphic red cells.
Recurrent or persistent severe pain for  six months or more, occurring in the costovertebral angles.

Relation to chronic pelvic pain
LPHS has considerable overlap with chronic pelvic pain syndrome.

Relation to thin basement membrane disease
A thin glomerular basement membrane, as in thin basement membrane disease, is proposed to be the characteristic finding on renal biopsy, but not part of the syndrome definition.

Differential diagnosis
Kidney stones
Nutcracker syndrome
IgA nephropathy
Cancer of the genitourinary tract
Chronic pelvic pain
Endometriosis
Pyelonephritis

Treatment
The treatment of LPHS varies considerably from centre to centre. As the condition is rare and poorly understood, a widely adopted standard of care is not existent.Treatment of loin pain-hematuria syndrome (LPHS) typically consists of pain management. Narcotics or oral opioids may be prescribed to help control pain </s>