<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 Conjoined twins and can you explain it in depth? [/INST] Conjoined twins – sometimes popularly referred to as Siamese twins – are twins joined in utero. A very rare phenomenon, the occurrence is estimated to range from 1 in 49,000 births to 1 in 189,000 births, with a somewhat higher incidence in Southwest Asia and Africa. Approximately half are stillborn, and an additional one-third die within 24 hours. Most live births are female, with a ratio of 3:1.Two theories exist to explain the origins of conjoined twins. The more generally accepted theory is fission, in which the fertilized egg splits partially. The other theory, no longer believed to be the basis of conjoined twinning, is fusion, in which a fertilized egg completely separates, but stem cells (which search for similar cells) find similar stem cells on the other twin and fuse the twins together. Conjoined twins share a single common chorion, placenta, and amniotic sac, although these characteristics are not exclusive to conjoined twins, as there are some monozygotic but non-conjoined twins who also share these structures in utero.Chang and Eng Bunker (1811–1874) were brothers born in Siam (now Thailand) who traveled widely for many years and were labeled as The Siamese Twins. Chang and Eng were joined at the torso by a band of flesh, cartilage, and their fused livers. In modern times, they could have been easily separated. Due to the brothers fame and the rarity of the condition, the term "Siamese twins" came to be associated with conjoined twins.

Causes
There are two theories about the development of conjoined twins. The first is that a single fertilized egg does not fully split during the process of forming identical twins. If the zygote division occurs after two weeks of the development of the embryonic disc, it results in the formation of conjoined twins. The second theory is that a fusion of two fertilized eggs occurs earlier in development.
Partial splitting of the primitive node and streak may result in the formation of conjoined twins. These twins are classified according to the nature and degree of their union. Occasionally, monozygotic twins are connected only by a common skin bridge or by a common liver bridge. The type of twins formed depends on when and to what extent abnormalities of the node and streak occurred. Misexpression of genes, such as Goosecoid, may also result in conjoined twins. Goosecoid activates inhibitors of BMP4 and contributes to regulation of head development. Over- or underexpression of this gene in laboratory animals results in severe malformations of the head region, including duplications, similar to some types of conjoined twins.

Types
Conjoined twins are typically classified by the point at which their bodies are joined. The most common types of conjoined twins are:

Thoraco-omphalopagus (28% of cases): Two bodies fused from the upper chest to the lower chest. These twins usually share a heart and may also share the liver or part of the digestive system.
Thoracopagus (18.5%): Two bodies fused from the upper chest to lower belly. The heart is always involved in these cases. As of 2015, separation of a genuinely shared heart has not offered survival to two twins; a designated twin may survive if allotted the heart, sacrificing the other twin.
Omphalopagus (10%):  Two bodies fused at the lower abdomen. Unlike thoracopagus, the heart is never involved in these cases; however, the twins often share a liver, digestive system, diaphragm and other organs.
Parasitic twins (10%): Twins that are asymmetrically conjoined, resulting in one twin that is small, less formed, and dependent on the larger twin for survival.
Craniopagus (6%): Fused skulls, but separate bodies. These twins can be conjoined at the back of the head, the front of the head, or the side of the head, but not on the face or the base of the skull.Other, less common types of conjoined twins include:

Cephalopagus: Two faces on opposite sides of a single, conjoined head; the upper portion of the body is fused while the bottom portions are separate. These twins generally cannot survive due to severe malformations of the brain. Also known as janiceps (after the two-faced Roman deity Janus).
Syncephalus: One head with a single face but four ears, and two bodies.
Cephalothoracopagus: Bodies fused in the head and thorax. In this type of twins, there are two faces facing in opposite directions, or sometimes a single face and an enlarged skull.
Xiphopagus: Two bodies fused in the xiphoid cartilage, which is approximately from the navel to the lower breastbone. These twins almost never share any vital organs, with the exception of the liver. A famous example is Chang and Eng Bunker.
Ischiopagus: Fused lower half of the two bodies, with spines conjoined end-to-end at a 180° angle. These twins have four arms; one, two, three or four legs; and typically one external set of genitalia and anus.
Omphalo-Ischiopagus: Fused in a similar fashion to ischiopagus twins, but facing each other with a joined abdomen akin to omphalopagus. These twins have four arms, and two, three, or four legs.
Parapagus: Fused side by side with a shared pelvis. Twins that are dithoracic parapagus are fused at the abdomen and pelvis, but not the thorax. Twins that are diprosopic parapagus have one trunk and two faces. Twins that are dicephalic parapagus have one trunk and two heads, and have two (dibrachius), three (tribrachius), or four (tetrabrachius) arms.
Craniopagus parasiticus: Like craniopagus, but with a second bodiless head attached to the dominant head.
Pygopagus or Iliopagus: Two bodies joined at the pelvis.
Rachipagus: Twins joined along the back of their bodies, with fusion of the vertebral arches and the soft tissue from the head to the buttocks
Tricephalus (conjoined triplets): Extremely rare conjoining of 3 fetuses. Very few confirmed cases, both human and animal, are known.

Management
Separation
Surgery to separate conjoined twins may range from very easy to very difficult depending on the point of attachment and the internal parts that are shared. Most cases of separation are extremely risky and life-threatening. In many cases, the surgery results in the death of one or both of the twins, particularly if they are joined at the head or share a vital organ. This makes the ethics of surgical separation, where the twins can survive if not separated, contentious. Alice Dreger of Northwestern University found the quality of life of twins who remain conjoined to be higher than is commonly supposed. Lori and George Schappell and Abby and Brittany Hensel are notable examples.
The first record of separating conjoined twins took place in the Byzantine Empire in the 900s. One of the conjoined twins had already died, so the doctors of the town attempted to separate the dead twin from the surviving twin. The result was partly successful as the remaining twin lived for three days after separation. The next case of separating conjoined twins was recorded in 1689 in Germany several centuries later. The first recorded successful separation of conjoined twins was performed in 1689 by Johannes Fatio. In 1955, neurosurgeon Harold Voris (1902-1980) and his team at Mercy Hospital in Chicago performed the first successful operation to separate craniopagus twins (conjoined at the head), which resulted in long-term survival for both. The larger girl was reported in 1963 as developing normally, but the smaller girl was permanently impaired.In 1957, Bertram Katz and his surgical team made international medical history performing the worlds first successful separation of conjoined twins sharing a vital organ. Omphalopagus twins John Nelson and James Edward Freeman (Johnny and Jimmy) were born in Youngstown, Ohio, on April 27, 1956. The boys shared a liver but had separate hearts and were successfully separated at North Side Hospital in Youngstown, Ohio, by Bertram Katz. The operation was funded by the Ohio Crippled Childrens Service Society.Recent successful separations of conjoined twins include that of the separation of Ganga and Jamuna Shreshta in 2001, who were born in Kathmandu, Nepal, in 2000. The 97-hour surgery on the pair of craniopagus twins was a landmark one which took place in Singapore; the team was led by neurosurgeons Chumpon Chan and Keith Goh. The surgery left Ganga with brain damage and Jamuna unable to walk. Seven years later, Ganga Shrestha died at the Model Hospital in Kathmandu in July 2009, at the age of eight, three days after being admitted for treatment of a severe chest infection.Infants Rose and Grace Attard, conjoined twins from Malta, were separated in the United Kingdom by court order Re A over the religious objections of their parents, Michaelangelo and Rina Attard. The twins were attached at the lower abdomen and spine. The surgery took place in November 2000, at St Marys Hospital in Manchester. The operation was controversial because Rose, the weaker twin, would die as a result of the procedure as her heart and lungs were dependent upon Graces. However, if the operation had not taken place, it was certain that both twins would die. Grace survived to enjoy a normal childhood.In 2003, two 29-year-old women from Iran, Ladan and Laleh Bijani, who were joined at the head but had separate brains (craniopagus) were surgically separated in Singapore, despite surgeons warnings that the operation could be fatal to one or both. Their complex case was accepted only because technologically advanced graphical imagery and modeling would allow the medical team to plan the risky surgery. However, an undetected major vein hidden from the scans was discovered during the operation. The separation was completed but both women died while still in surgery.
In 2019 Safa and Marwa Ullah were separated at Great Ormond Street Hospital in London, England. The twins, born January 2017 were joined at the top of the head with separate brains and a cylindrical shared skull with the twins each facing in opposite directions to one another. The surgery was jointly led by neurosurgeon Owase Jeelani and plastic surgeon Professor David Dunaway. The surgery presented particular difficulties due to a number of shared veins and a distortion in the shape of the girls brains, causing them to overlap. The distortion would need to be corrected in order for the separation to go ahead. The surgery utilized a team of more than 100 including bio engineers, 3D modelers and a virtual reality designer. The separation was completed in February 2019 following a total of 52 hours of surgery over three separate operations. As of July 2019, both girls remain healthy and the family planned to return to their home in Pakistan in 2020.

History
The Moche culture of ancient Peru depicted conjoined twins in their ceramics dating back to 300 CE. Writing around 415 CE, St. Augustine of Hippo, in his book, City of God, refers to a man "double in his upper, but single in his lower half—having two heads, two chests, four hands, but one body and two feet like an ordinary man."According to Theophanes the Confessor, a Byzantine historian of the 9th century, around 385/386 CE, "in the village of Emmaus in Palestine, a child was born perfectly normal below the navel but divided above it, so that it had two chests and two heads, each possessing the senses. One would eat and drink but the other did not eat; one would sleep but the other stayed awake. There were times when they played with each other, when both cried and hit each other. They lived for a little over two years. One died while the other lived for another four days and it, too, died."In Arabia, the twin brothers Hashim ibn Abd Manaf and Abd Shams were born with Hashims leg attached to his twin brothers head. Legend says that their father, Abd Manaf ibn Qusai, separated his conjoined sons with a sword and that some priests believed that the blood that had flowed between them signified wars between their progeny (confrontations did occur between Banu alAbbas and Banu Ummaya ibn Abd Shams in the year 750 AH). The Muslim polymath Abū al-Rayhān al-Bīrūnī described conjoined twins in his book Kitab-al-Saidana.The English twin sisters Mary and Eliza Chulkhurst, who were conjoined at the back (pygopagus), lived from 1100 to 1134 (or 1500 to 1534) and were perhaps the best-known early historical example of conjoined twins. Other early conjoined twins to attain notice were the "Scottish brothers", allegedly of the dicephalus type, essentially two heads sharing the same body (1460–1488, although the dates vary); the pygopagus Helen and Judith of Szőny, Hungary (1701–1723), who enjoyed a brief career in music before being sent to live in a convent; and Rita and Cristina of Parodi of Sardinia, born in 1829. Rita and Cristina were dicephalus tetrabrachius (one body with four arms) twins and although they died at only eight months of age, they gained much attention as a curiosity when their parents exhibited them in Paris.

Several sets of conjoined twins lived during the nineteenth century and made careers for themselves in the performing arts, though none achieved quite the same level of fame and fortune as Chang and Eng. Most notably, Millie and Christine McCoy (or McKoy), pygopagus twins, were born into slavery in North Carolina in 1851. They were sold to a showman, J.P. Smith, at birth, but were soon kidnapped by a rival showman. The kidnapper fled to England but was thwarted because England had already banned slavery. Smith traveled to England to collect the girls and brought with him their mother, Monimia, from whom they had been separated. He and his wife provided the twins with an education and taught them to speak five languages, play music, and sing. For the rest of the century, the twins enjoyed a successful career as "The Two-Headed Nightingale" and appeared with the Barnum Circus. In 1912, they died of tuberculosis, 17 hours apart.
Giovanni and Giacomo Tocci, from Locana, Italy, were immortalized in Mark Twains short story "Those Extraordinary Twins" as fictitious twins Angelo and Luigi. The Toccis, born in 1877, were dicephalus tetrabrachius twins, having one body with two legs, two heads, and four arms. From birth they were forced by their parents to perform and never learned to walk, as each twin controlled one leg (in modern times, physical therapy allows twins like the Toccis to learn to walk on their own). They are said to have disliked show business. In 1886, after touring the United States, the twins returned to Europe with their family. They are believed to have died around this time, though some sources claim they survived until 1940, living in seclusion in Italy.

Notable people
Born 19th century and earlier
Mary and Eliza Chulkhurst, alleged names of the Biddenden Maids (per tradition, born in the 12th century) of Kent, England. They are the earliest set of conjoined twins whose names are (purportedly) known.
Lazarus and Joannes Baptista Colloredo (1617 — after 1646), autosite-and-parasite pair
Helen and Judith of Szony (Hungary, 1701 — 1723), pygopagus.
Chang and Eng Bunker (1811–1874). The Bunker twins were born of Chinese origin in Siam (now  Thailand), and the expression Siamese twins is derived from their case. They were joined by the areas around their xiphoid cartilages, but over time, the connective tissue stretched.
In 1834, a set of conjoined triplets were born in Cattania. Two of the heads shared a neck while the other head had its own. The infant, a male, was described by Galvagni.
Millie and Christine McCoy (July 11, 1851 – October 8, 1912), (oblique pygopagus). The McCoy twins were born into slavery in Columbus County, North Carolina, United States. They went by the stage names "The Two-Headed Nightingale" and "The Eighth Wonder of the World" and had an extensive career before retiring to the farm on which they were born.
Giacomo and Giovanni Battista Tocci (1875? — 1912?), (dicephalus tetrabrachius dipus)
Josefa and Rosa Blazek (January 20, 1878 — March 30, 1922), pygopagus. The Blazek twins were born in Skrejšov, Bohemia (now the Czech Republic). They began performing in public exhibitions at the age of 13, and their act later included Rosas son Franz. The sisters died in Chicago, Illinois.

Born 20th century
Daisy and Violet Hilton of Brighton, England (1908–1969), pygopagus. The Hilton twins were performers who played musical instruments, sang, and danced. At the height of their career, they had the highest paid act in vaudeville. They also appeared in the movies Freaks and Chained for Life.
Lucio and Simplicio Godina of Samar, Philippines (1908–1936)
Masha and Dasha Krivoshlyapova of Moscow, Russia (1950–2003), the rarest form of conjoined twins, one of few cases of dicephalus tetrabrachius tripus (two heads, four arms, three legs)
Ronnie and Donnie Galyon of Ohio (1951–2020), omphalopagus; longest-lived conjoined twins in the world at 68 years and 250 days.
Tjitske and Folkje de Vries of Mûnein, Netherlands (b. 1953)
Wariboko and Tamunotonye Davies, born July 25, 1953, in Kano, Nigeria. Separated in London by a team led by Ian Aird. Tamunotonye died postoperatively. Wariboko became a nurse.
Lori and George Schappell, born September 18, 1961, in Reading, Pennsylvania, American entertainers, craniopagus.  As of 2022, they are the worlds oldest living conjoined twins.
Ganga and Jamuna Mondal of India, born 1969 or 1970, known professionally as The Spider Girls and The Spider Sisters. Ischiopagus.
Anna and Barbara Rozycki (born 1970), the first conjoined twins successfully separated.
Ma Nan Soe and Ma Nan San (born 1971 in Myanmar), separated in July 1971 at Yangon Pediatric Hospital. They were joined from chest to belly button. Ma Nan San died after one month and seven days after operation.
Elisa and Lisa Hansen, Ogden, Utah (1977–2020). Born by Caesarean section on October 18, 1977, were conjoined at the top of their head (craniopagus). They were separated 1979 after 16-hour surgery, were first to both survive surgery.
Ladan and Laleh Bijani of Shiraz, Iran (1974–2003); died during separation surgery in Singapore. Craniopagus.
Baby Girl A and Baby Girl B (born 1977 in New Jersey) shared a single six-chambered heart. Separation surgery, led by C. Everett Koop, involved the instant death of Baby Girl A; the difficult ethical and religious concerns generated significant local newspaper coverage. Baby Girl B survived for 3 months.
Viet and Duc Nguyen, born on February 25, 1981, in Kon Tum Province, Vietnam, and separated in 1988 in Ho Chi Minh City. Viet died on October 6, 2007. Ischiopagus.
Maria and Consolata Mwakikuti of Tanzania (1986?–2018); conjoined by the abdomen; died of respiratory problems resulting from an abnormal, inoperable chest deformity.
Patrick and Benjamin Binder, separated in 1987 by team of doctors led by Ben Carson. Craniopagus.
Andrew and Alex Olson, born in 1987, separated in April 1988 at the University of Nebraska Medical Center. Omphalopagus. Alex died in 2018.
Katie and Eilish Holton, born August 1988 in Ireland; Katie died after separation due to cardiac arrest at the age of 3,5 years.
Abigail and Brittany Hensel are dicephalic parapagus twins born on March 7, 1990, in Carver County, Minnesota. Both graduated in 2012 from Bethel University, St. Paul, hired as teachers.
Tiesha and Iesha Turner (born 1991 in Texas), separated in 1992 at Texas Childrens Hospital in Houston, Texas. Omphalopagus.
Ashley and Ashil Fokeer, born on November 2, 1992, in Mauritius
Joseph and Luka Banda (born January 23, 1997, in Zambia), separated in 1997 in South Africa by Ben Carson (with a later intervention in 2001 to artificially close their skulls). Craniopagus.
José Armando and José Luis Cevallos Herrera were born in September 1999 in Milagro, Ecuador. They were accepted in 2021 to the State University of Milagro.
Maria del Carmen Andrade Solis and Maria Guadalupe Andrade Solis (better known as Carmen and Lupita) were born in June 2000 in Veracruz, Mexico. They later moved to the United States for healthcare with their parents.

Born 21st century
Carl and Clarence Aguirre, born with vertical craniopagus in Silay City, Negros Occidental, on April 21, 2002. They were successfully separated on August 4, 2004.
Tabea and Lea Block, from Lemgo, Germany, were born as craniopagus twins joined on the tops of their heads on August 9, 2003. The girls shared some major veins, but their brains were separate. They were separated on September 16, 2004, although Tabea died about 90 minutes later.
Sohna and Mohna from Amritsar, India. Born in New Delhi on June 14, 2003. They have two hearts, arms, kidneys and spinal cords while share liver, gall bladder and legs.
Anastasia and Tatiana Dogaru, born outside Rome in Lazio, Italy, on January 13, 2004. As craniopagus twins, the top of Tatianas head is attached to the back of Anastasias head.
Lakshmi Tatma (born 2005) was an ischiopagus conjoined twin born in Araria district in the state of Bihar, India. She had four arms and four legs, resulting from a joining at the pelvis with a headless undeveloped parasitic twin.
In 2005 a set of conjoined triplets was detected, characterized as tricephalus, tetrabrachius, and tetrapus parapagothoracopagus, and the pregnancy interrupted at 22 weeks.
Kendra and Maliyah Herrin, ischiopagus twins separated in 2006 at age 4
Krista and Tatiana Hogan, Canadian twins conjoined at the head. Born October 25, 2006. Share part of their brain and can pass sensory information and thoughts between each other.
Trishna and Krishna from Bangladesh were born in December 2006. They are craniopagus twins, joined on the tops of their skulls and sharing a small amount of brain tissue. In 2009, they were separated in Melbourne, Australia.
Maria and Teresa Tapia, born in the Dominican Republic on April 8, 2010. Conjoined by the liver, pancreas, and a small portion of their small intestine. Separation occurred on November 7, 2011, at Childrens Hospital of Richmond at VCU.
Aung Myat Kyaw and Aung Khant Kyaw (born in May 2011, Mandalay, Myanmar), connected at pelvis.
Jesus and Emanuel de Nazaré are dicephalic parapagus twins born in Pará, Brazil on December 19, 2011.
Zheng Han Wei and Zheng Han Jing, born in China on August 11, 2013. Conjoined by their sternum, pericardium, and liver. In 2014, they were separated in Shanghai, China, at the Shanghai Childrens Medical Center.
Asa and Eli Hamby were born in 2014 in Georgia but died less than two days after birth due to heart failure. The twins were dicephalic parapagus  having two heads but being conjoined at the torso, arms and legs. They had separate spinal columns but one heart making postnatal operations impossible.
Jadon and Anias McDonald, born in September 2015. Conjoined by the head. Successfully separated at Childrens Hospital of Montefiore Medical Center by James T. Goodrich in October 2016.
Erin and Abby Delaney, born in Philadelphia, Pennsylvania on July 24, 2016. Conjoined by the head. They were successfully separated at Childrens Hospital of Philadelphia on June 16, 2017.
Marieme and Ndeye Ndiaye, twin girls born in Senegal in 2017, living in Cardiff, UK in 2019.
Safa and Marwa Bibi, twin girls born in Hayatabad, Pakistan on January 17, 2017, conjoined by the head. Successfully separated at Great Ormond Street Hospital in February 2019.
Callie and Carter Torres, born January 30, 2017, in Houston Texas, from Blackfoot Idaho. They are Omphalo-Ischiopagus conjoined twins, attached by their pelvic area and sharing all organs from the belly button down with just one leg each.
Yiğit and Derman Evrensel, twin boys born on June 21, 2018, Antalya, Turkey. They are craniopagus twins and were separated at Great Ormond Street Hospital in 2019 by the same surgeons that separated Safa and Marwa Bibi.
Ervina and Prefina, born June 29, 2018, in the Central African Republic. They were separated on June 5, 2020, at the Bambino Gesù Pediatric Hospital in Rome, Italy.
Mercy and Goodness Ede, born August 13, 2019, conjoined by the chest and abdomen.  Successfully separated at the National Hospital in Abuja, Nigeria in November 2019.
Marie-Cléa and Marie-Cléanne Papillon, born in Mauritius in 2019. Conjoined from neck to abdomen, but also from heart which had seven rooms, instead of four. Marie-Cléa did not survive the surgery to separate the two.
Susannah and Elizabeth Castle, born April 22, 2021, and separated December 10, 2021 in Philadelphia, Pennsylvania.

In fiction
Conjoined twins have been the focus of several noteworthy works of entertainment, including:

Stuck on You (2003 film), a 2003 American comedy film screen written and directed by the Farrelly brothers and starring Matt Damon and Greg Kinnear as conjoined twin brothers, whose conflicting aspirations provide both conflict and humorous situations, in particular when one of them wishes to move to Hollywood to pursue a career as an actor.
Alone, a Thai horror film following Pim after the death of her sister Ploy and their subsequent separation.
Blood Sisters focuses on a French Canadian model who has a separated conjoined twin.
Irish author Sarah Crossan won the Carnegie Medal for her verse novel, One. The story follows the life and survival of conjoined twin sisters. The book also won The Booksellers 2016 prize for young adult fiction and the Irish Childrens Book of the Year.
Tarot: Witch of the Black Rose graphic novel debut the ghost twin, She/they are constant companion(s) of Skeleton Man, her protector.
The Broadway musical Side Show depicts the lives of real-life conjoined twins Daisy and Violet Hilton, portrayed in the original Broadway production by Alice Ripley and Emily Skinner.
Reiko the Zombie Shop, 1990s womens horror manga, bonus chapters focus on unexpectedly life of Noriko and her "sister". Summoners Dr. Zero can resurrect and control fuse zombies called medicinal death.
MA GI & CA L., a conjoined magical alternative android, from psychology horror manga Magical Girl Apocalypse.
In the TV series The Addams Family, there are extended family members of the Addams Family who are mentioned to have two heads. In "Mother Lurch Visits the Addams Family," Morticia Addams mentions that she has a Cousin Slimy who has two good heads on his shoulder. In "Progress and the Addams Family," Morticia was making a knitted hat for Cousin Plato where Gomez Addams has stated that his left head is size 6 and his right head is size 8 3/4. In "Lurchs Little Helper," Morticia made a portrait of Cousin Crimp who has a male head and a female head.
Tamil actor Suriya portrays Vimalan and Akilan, conjoined twins in the 2012 film, Maattrraan.
The book The Girls, by Canadian novelist Lori Lansens, published in 2005, is the fictional autobiography of Canadian craniopagus twins Rose and Ruby Darlen with Slovakian background.
Irish author Sarah Crossan won the Carnegie Medal for her verse novel, One. The story follows the life and survival of conjoined twin sisters. The book also won The Booksellers 2016 prize for young adult fiction and the Irish Childrens Book of the Year.
In Lilo & Stitch: The Series, Swapper are Ischiopagus twin green stubby limbed lizard-like experiment with black eyes, purple markings on his back and three purple-tipped tendrils on each head that can emit a green ray from each heads eyes. The ray will swap the minds and voices of the targets,  and the only means of returning to normal is through Swapper choosing to do so. Because Swapper is two heads on the same body, Swapper is two beings cooperating as one, though their personalities mirror each other: they can be indecisive at times but usually work well together.
In Big-Top Pee-wee, the Cabrini Circus has some conjoined twins named Ruth and Dot (portrayed by Helen Infield Siff and Carol Infield Sender).
In The Addams Family and Addams Family Values, there are conjoined twins named Flora and Fauna Amor (portrayed by Darlene and Maureen Sue Levin) who were once dates to Gomez Addams and Uncle Fester. Both films also featured a two-headed relative named Dexter and Donald Addams (portrayed by Douglas Brian Martin and Steven M. Martin).
In The Addams Family cartoon in 1992, the episode "N.J. Addams" featured Aunt Noggin who was a two-headed person who wears a Victorian dress. One head is black and speaks in a Jamaican accent and the other head is Caucasian and speaks in a Brooklyn accent.
The Farrelly brothers film Stuck on You depicts Bob and Walt Tenor, conjoined twins portrayed by Matt Damon and Greg Kinnear. 2003.
In Midnighter issue #13, Shock & Awe is a superheroine working for Los Angeles Strike Force.
Delilah and Jezebel in video games Bully.
CatDog depicts Cat and Dog, a hybrid of a dog and cat who are brothers.
On a LeapFrog Enterprises commercial advertising the Leapster from 2007, a boy is constantly playing video games from the console itself. The more he praises the Leapster, the more he grows extra heads.
Zaphod Beeblebrox is a character from Douglas Adams Hitchhikers Guide to the Galaxy, who has a second head along with a third arm.
Vaka-Waka and Nurp-Naut in Cartoon Network and The Lego Groups Mixels.
Fender and Bender (also known individually as HeadBanger) are characters in the 90s television series Toxic Crusaders, based on The Toxic Avenger films by Troma Entertainment. Fender is supposed to be a Mad Scientist while Bender is a Surfer.
Dragon Tales, a childrens show, depicts Zak and Wheezie (voiced by Jason Michas and Kathleen Barr) as a two-headed dragon that are brother and sister making them dicephalic parapagus twins.
In the Canadian mobile game My Singing Monsters, a bird-like species known as the Quibble is made up of elements Air and Water. The two-headed species plays a piano and has different colored feathers on both heads.
The Simpsons features Hugo in "Treehouse of Horror VII", who is Bart Simpsons conjoined twin. They were separated at birth by Dr. Hibbert and Hugo was imprisoned in the Simpsons attic.
The Oblongs, depicts  Biff Oblong (Randy Sklar) and Chip Oblong (Jason Sklar)—17-year-old conjoined twins who are attached at the waist and share a middle leg due to their valleys pollution and radiation.
In the DC Comics series Hitman, villain Moe and Joe Dubelz is a conjoined twin gangster. Moe was alive at the time of introduction, but Joe had already died and is, in fact, undergoing putrefaction.
In the episode "Humbug" of The X-Files, Vincent Schiavelli portrayed a circus performer named Lanny, with an underdeveloped conjoined twin named Leonard. The episode also includes a reference to Chang and Eng.
The Prophet of Yonwood has a reference to Chang and Eng when the main character, Nickie, finds a picture of them in her great-grandfathers old house in Siam.
In the anime Naruto, Sakon (左近) and his conjoined twin brother Ukon (右近) are the strongest of the Sound Four and count as one member due to their abilities to merge bodies and kill an opponent at a cellular level. They both serve as antagonists.
The Broadway musical Side Show depicts the lives of real-life conjoined twins Daisy and Violet Hilton, portrayed in the original Broadway production by Alice Ripley and Emily Skinner.
The American medical drama Greys Anatomy featured several cases of conjoined twins.
The 2001 movie Not Another Teen Movie depicts Kara and Sara Fratelli, conjoined twins portrayed by Samaire Armstrong and Nectar Rose.
The musical group Evelyn, Evelyn depicts a pair of conjoined twin sisters—often referred to as "The Evelyn Sisters"—in many of their songs and music videos. The fictional sisters are shown to be child prostitutes in the music video for "Sandy Fishnets", and the song "Evelyn, Evelyn" describes their longing for privacy and to be separated from one another.
The Bride with White Hair, a 1993 Hong Kong movie, features conjoined twin villains.
The animated series Duckman featured Eric T. Duckmans sons Charles (voiced by Dana Hill in 1994–1996, Pat Musick in 1997) and Mambo (voiced by E. G. Daily) who are dicephalic parapagus twins where their heads share a body.
Fran Bow, a 2015 indie psychological horror game, includes Clara and Mia Buhalmet, a set of mentally ill conjoined twins, as characters. They were surgically sewn together, much like an experiment performed by Josef Mengele, also known as the Angel of Death, in which a pair of twins were sewn together back to back by blood vessels and organs, in an attempt to create conjoined twins.
The Peach Tree, a Korean novel and film, portrays conjoined twin brothers falling in love with the same woman.
The 1999 movie Twin Falls Idaho portrays conjoined twin brothers who are played by two non-conjoined identical twin brothers, one of whom directed the film, and both of whom co-wrote the screenplay.
In the fourth season of the American television series American Horror Story titled American Horror Story: Freak Show, the main character Bette and Dot Tattler (Sarah Paulson in a dual role) are a dicephalic parapagus twin where their two heads are side by side on one torso. This performance is done with the help of CGI.
In season two, episode eight of Rick and Morty, Michael and Pichael Thompson (voiced by Justin Roiland) are depicted as conjoined twins hosting separate TV shows at the same time.
In the Cirque Du Soleil show Kurios: Cabinetes des Curiosities, a pair of conjoined twins are among the Seekers collection. They later split during an aerial straps duo and reunite for the rest of the show.
The bilingual film Chaarulatha stars Priyamani as a conjoined twin.
In the Disney-distributed movie Jagga Jasoos, starring Ranbir Kapoor and Katrina Kaif, Basheer Alexander is shown with two heads.
On the television series Ruby Gloom, the characters Frank and Len are conjoined twins who comprise a rock group called RIP.
In the film Monsters University, two of the members of the fictitious fraternity Oozma Kappa are named Terri and Terry Perry (voiced by Sean Hayes and Dave Foley). They are dicephalic parapagus twins where they have four arms and share the same tentacles that are in place of their legs.
In the childrens cartoon Steven Universe, the Rutile twins are conjoined.
Fire and Water are conjoined twins in Chris Abanis 2014 novel The Secret History of Las Vegas.
The Knick portrays conjoined twins Zoya and Nika, who share a liver. They are successfully separated by the doctors.
Brian Aldisss 1977 novel Brothers of the Head depicts conjoined twins who become rock stars </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 Reticular erythematous mucinosis 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 Aneurysmal bone cyst and can you explain it in depth? [/INST] Aneurysmal bone cyst (ABC) is a non-cancerous bone tumor composed of multiple varying sizes of spaces in a bone which are filled with blood. The term is a misnomer, as the lesion is neither an aneurysm nor a cyst. It generally presents with pain and swelling in the affected bone. Pressure on neighbouring tissues may cause compression effects such as neurological symptoms.The cause is unknown. Diagnosis involves medical imaging. CT scan and X-ray show lytic expansion lesions with clear borders. MRI reveals fluid levels.Treatment is usually by curettage, bone grafting or surgically removing the part of bone. 20–30% may recur, usually in the first couple of years after treatment, particularly in children.It is rare. The incidence is around 0.15 cases per one million per year. Aneurysmal bone cyst was first described by Jaffe and Lichtenstein in 1942.

Signs and symptoms
The afflicted may have relatively small amounts of pain that will quickly increase in severity over a time period of 6–12 weeks.  The skin temperature around the bone may increase, a bony swelling may be evident, and movement may be restricted in adjacent joints.Spinal lesions may cause quadriplegia and patients with skull lesions may have headaches.

Sites
Commonly affected sites are metaphyses of vertebra, flat bones, femur and tibia.   Approximate percentages by sites are as shown:
Skull and mandible (4%)
Spine (16%)
Clavicle and ribs (5%)
Upper extremity (21%)
Pelvis and sacrum (12%)
Femur (13%)
Lower leg (24%)
Foot (3%)

Causes
Aneurysmal bone cyst has been widely regarded a reactive process of uncertain cause since its initial description by Jaffe and Lichtenstein in 1942. Many hypotheses have been proposed to explain the cause and pathogenesis of aneurysmal bone cyst, and until very recently the most commonly accepted idea was that aneurysmal bone cyst was the consequence of an increased venous pressure and resultant dilation and rupture of the local vascular network. However, studies by Panoutsakopoulus et al. and Oliveira et al. uncovered the clonal neoplastic nature of aneurysmal bone cyst. Primary cause has been regarded arteriovenous fistula within bone.The lesion may arise de novo or may arise secondarily within a pre-existing bone tumor, because the abnormal bone causes changes in hemodynamics.  An aneurysmal bone cyst can arise from a pre-existing chondroblastoma, a chondromyxoid fibroma, an osteoblastoma, a giant cell tumor, or fibrous dysplasia.  A giant cell tumor is the most common cause, occurring in 19–39% of cases. Less frequently, it results from some malignant tumors, such as osteosarcoma, chondrosarcoma, and hemangioendothelioma.

Pathology
Histologically, they are classified in two variants.
The classic (or standard) form (95%) has blood filled clefts among bony trabeculae. Osteoid tissue is found in stromal matrix.
The solid form (5%) shows fibroblastic proliferation, osteoid production and degenerated calcifying fibromyxoid elements.According to Buraczewski and Dabska, the development of the aneurysmal bone cyst follows three stages.
They can also be associated with a TRE17/USP6 translocation.Aneurysmal bone cysts may be intraosseous, staying inside of the bone marrow.  Or they may be extraosseous, developing on the surface of the bone, and extending into the marrow. A radiograph will reveal a soap bubble appearance.

Diagnosis
X-ray and CT scan show lytic expansion lesions with clear borders </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 Junctional ectopic tachycardia and can you explain it in depth? [/INST] Junctional ectopic tachycardia (JET) is a rare syndrome of the heart that manifests in patients recovering from heart surgery. It is characterized by cardiac arrhythmia, or irregular beating of the heart, caused by abnormal conduction from or through the atrioventricular node (AV node). In newborns and infants up to 6 weeks old, the disease may also be referred to as His bundle tachycardia or congenital JET.

Pathophysiology
In normal individuals, electrical activity in the heart is initiated in the sinoatrial (SA) node (located in the right atrium), propagates to the atrioventricular (AV) node, and then through the bundle of His to the ventricles of the heart.
The AV node acts as a gatekeeper, limiting the electrical activity that reaches the ventricles of the heart.  This function of the AV node is important, because if the signals generated in the atria of the heart were to increase in rate (as they do during atrial fibrillation or atrial flutter), the AV node will limit the electrical activity that conducts to the ventricles.  For instance, if the atria are electrically activated at 300 beats per minute, half those electrical impulses are blocked by the AV node, so that the ventricles are activated at 150 beats per minute (giving a pulse of 150 beats per minute).  Another important property of the AV node is that it slows down individual electrical impulses.  This is manifest on the ECG as the PR interval, which is about less than 200 milliseconds, the time from activation of the atria (manifest as the P wave) and activation of the ventricles (manifest as the QRS complex).Individuals with JET have a "short-circuit" in their heart, where the electricity bypasses the AV node, causing the heart to beat faster than normal. The cause of the arrhythmia, the ectopic focus, is usually near the AV node in the triangle of Koch (a rough triangle with points at the coronary sinus, the tendon of Todaro, and the tricuspid valve).Patients of heart surgery may experience an accelerated narrow complex tachycardia, usually within the first 24–48 hours (but occasionally longer) after surgery. There may be atrio-ventricular disassociation with more ventricular signals than atrial signals.  The cause of JET is felt to be due to manipulation of the tissue surrounding the AV node during surgery, however debate exists regarding the exact cause, as it is seen after procedures even without significant manipulation of this area.JET-like symptoms can also manifest congenitally and in the first six months of life. This syndrome, which may also referred to as His bundle tachycardia, is resistant to therapy and can be difficult to treat.

Diagnosis
JET is most commonly diagnosed using a 12-lead ECG.  The appearance is usually of a tachycardia with rapid, regular ventricular rates of 170-260 beats per minute.  The QRS complexes are usually narrow, but may be broad if a bundle branch block is present.  There may a 1:1 relationship between atria and ventricular activity with a short RP interval, or atrioventricular dissociation with slower atrial than ventricular rates if the AV node is unable to conduct from the ventricles to the atria.The differential diagnosis of JET includes other forms of supraventricular tachycardia, most commonly atrioventricular nodal reentrant tachycardia (AVNRT). These can be distinguished using adenosine. The response to adenosine in JET is a temporary loss of conduction to the atria leading to continuation of the tachycardia but with atrioventricular dissociation.  In contrast, administration of adenosine in AVNRT will usually terminate the arrhythmia.  The diagnosis can be conclusively proven by performing an invasive electrophysiological study.

Treatment
Treatment is aimed at slowing the rate by correcting acidosis, correcting electrolytes (especially magnesium and calcium), cooling the patient, and antiarrhythmic medications.  Occasionally pacing of the atrium at a rate higher than the JET may allow improved cardiac function by allowing atrial and ventricular synchrony.Medications used to treat JET include beta-adrenoceptor blockers such as propranolol,  calcium channel antagonists such as verapamil, and antiarrhythmics such as flecainide, amiodarone, and propafenone. Amiodarone is frequently used in the short term in children experiencing JET following heart surgery, although propanolol, flecainide and propafenone are more commonly recommended for long term use due to the frequency of side effects associated with amiodarone.In those who experience recurrent episodes of JET, an alternative to long term medical therapy is catheter ablation </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 Primary cutaneous amyloidosis 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 Erythema induratum and can you explain it in depth? [/INST] Erythema induratum is a panniculitis on the calves. It occurs mainly in women, but it is very rare now. Historically, when it has occurred, it has often been concomitant with cutaneous tuberculosis, and it was formerly thought to be always a reaction to the TB bacteria. It is now considered a panniculitis that is not associated with just a single defined pathogen </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 Peeling skin syndrome and can you explain it in depth? [/INST] Peeling skin syndrome (also known as "acral peeling skin syndrome", "continual peeling skin syndrome", "familial continual skin peeling", "idiopathic deciduous skin", and "keratolysis exfoliativa congenita") is an autosomal recessive disorder characterized by lifelong peeling of the stratum corneum, and may be associated with pruritus, short stature, and easily removed anagen hair.: 502 "Acral" refers to the fact that the peeling of the skin is most noticeable on the hands and feet of this state. Peeling happens sometimes on the arms and legs, too. The peeling is typically apparent from birth, although it may start in childhood or later on in life as well. Skin peeling is caused by sun, humidity, moisture, and friction.The acral form can be associated with TGM5.

Syndromes
Peeling skin syndrome is also associated with 6 syndromes that are each caused by a different genetic defect. The various syndromes include peeling skin syndrome 1, 2, 3, 4, 5, and 6.

Peeling skin syndrome 1
Peeling skin syndrome 1 is caused by a genetic defect in the corneodesmosin (CDSN) gene. This gene localizes to the human epidermis and other epithelia. The protein experiences a chain of cleavages during corneocyte maturation.  Its symptoms include short stature, abnormality of metabolism/homeostasis, scaling skin, pruritus, erythema, asthma, brittle hair, and abnormality of hair texture.

Peeling skin syndrome 2
Peeling Skin Syndrome 2 is caused by a genetic defect in the TGM5 gene. Transglutaminase 5 is best for catalyzing the cross-linking of proteins and the conjugation of polyamines to proteins. It also adds to the development of the cornified cell envelope of keratinocytes. Its symptoms include excessive wrinkling of palmar skin, skin erosion, hyperpigmentation of the skin, ichthyosis, and allergy.

Peeling skin syndrome 3
Peeling skin syndrome 3 is caused by a genetic defect in the carbohydrate sulfotransferase (CHST8) gene. This gene is characterized by a way of asymptomatic lifelong and non-stop dropping of the stratum corneum of the dermis. Its symptoms begin for the duration of the second half of the primary decade of existence and encompass generalized white scaling taking place over the upper and lower extremities.

Peeling skin syndrome 4
Peeling skin syndrome 4 is caused by a genetic defect in the cystatin A (CSTA) gene. This gene is an intracellular thiol proteinase inhibitor. It has an essential role in desmosome-mediated cell-cellular adhesion inside the lower levels of the dermis. Its symptoms include well-circumcised peeling of skin on the extremities and neck, generalized dry skin with fine scaling and sparing of face, hyperkeratosis, and palmoplantar keratoderma

Peeling skin syndrome 5
Peeling skin syndrome 5 is caused by a genetic defect in the serpin (serpin family member 8) gene. This gene is produced by platelets and can bind to and inhibit the function of furin, which is a serine protease involved in platelet functions </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 Rubinstein–Taybi syndrome and can you explain it in depth? [/INST] Rubinstein–Taybi syndrome (RTS) is a rare genetic condition characterized by short stature, moderate to severe learning difficulties, distinctive facial features, and broad thumbs and first toes. Other features of the disorder vary among affected individuals. These characteristics are caused by a mutation or deletion in the CREBBP and/or EP300 gene located on chromosome 16.
People with this condition have an increased risk of developing noncancerous and cancerous tumors, leukemia, and lymphoma. This condition is sometimes inherited as an autosomal dominant pattern and is uncommon. Many times it occurs as a de novo (not inherited) occurrence. It occurs in an estimated 1 in 125,000-300,000 births.

Presentation
Rubinstein–Taybi syndrome presents itself from birth, and is usually hallmarked by delayed physical and cognitive growth.Typical features of the disorder include:

Broad thumbs and broad first toes and clinodactyly of the 5th finger
Mental disability
Small height, low bone growth, small head
Cryptorchidism in males
Unusual facies involving the eyes, nose, and palate
Anesthesia may be dangerous in these patients: "According to the medical literature, in some cases, individuals with Rubinstein–Taybi syndrome may have complications (e.g., respiratory distress and/or irregular heart beats [cardiac arrythmias]) associated with a certain muscle relaxant (succinylcholine) and certain anesthesia. Any situations requiring the administration of anesthesia or succinylcholine (e.g., surgical procedures) should be closely monitored by skilled professionals (Anesthesiologists)." Primary literature suggests the children may have a higher rate of cardiac physical and conduction abnormalities which may cause unexpected results with cardioactive medications. A further editorial reply in the British Journal of Anaesthesia discusses changes in the face and airway structure making it more difficult to secure the airway under anaesthesia, however, complications appeared in a minority of cases, and routine methods of airway control in the operating room appears to be successful. They recommended close individual evaluation of Rubinstein–Taybi patients for anaesthetic plans.A 2009 study found that children with RTS were more likely to be overweight and to have a short attention span, motor stereotypies, and poor coordination. The study hypothesized that the identified CREBBP gene impaired motor skills learning. Other research has shown a link with long-term memory (LTM) deficit.It is diagnosed when a heterozygous pathogenic variant of the CREBBP gene is identified in the individual. It exhibits an autosomal dominant inheritance pattern, but some documented cases show heterozygous individuals exhibiting germline mosaicism. This condition affects men and women equally, and is often misdiagnosed with other diseases or disabilities that result in delayed mental development.

Genetics
Rubinstein–Taybi syndrome is a microdeletion syndrome involving chromosomal segment 16p13.3 and is characterized by mutations in the CREBBP gene. Varying amounts of material are deleted from this section of the chromosome and accounts for the spectrum of physiological symptoms.The CREBBP gene makes a protein that helps control the activity of many other genes. The protein, called CREB-binding protein, plays an important role in regulating cell growth and division and is essential for normal fetal development. If one copy of the CREBBP gene is deleted or mutated, cells make only half of the normal amount of CREB binding protein. A reduction in the amount of this protein disrupts normal development before and after birth, leading to the signs and symptoms of Rubinstein–Taybi syndrome.Mutations in the EP300 gene are responsible for a small percentage of cases of Rubinstein–Taybi syndrome. These mutations result in the loss of one copy of the gene in each cell, which reduces the amount of p300 protein by half. Some mutations lead to the production of a very short, nonfunctional version of the p300 protein, while others prevent one copy of the gene from making any protein at all. Although researchers do not know how a reduction in the amount of p300 protein leads to the specific features of Rubinstein–Taybi syndrome, it is clear that the loss of one copy of the EP300 gene disrupts normal development.A mouse model has been identified in order to perform experimental research procedures. The model has exhibited the same clinical symptoms seen in humans and has become a foundation for future research.Unfortunately, in nearly 40% of cases, neither gene, CREBBP or EP300, can be implicated in the cause of the disease. In these cases, there is no mutation on the 16th chromosome leaving many more questions yet to be answered. However, new research shows that around 55% of cases involve a mutation in the CBP gene, further suggesting that this disease has its origins in mutation of the regulatory mechanisms of transcription (Izumi, 2016).

Treatment
There is no existing treatment that reverses or cures RTS. There are, however, ways to manage and reduce symptoms for patients. Patients with RTS suffer from a diverse breadth of symptoms. These include cognitive-developmental impairment, heart abnormalities, delayed bone growth and skeletal abnormalities, auditory impairment, urinary tract abnormalities, including kidney problems, and dental and speech problems. Not every patient will suffer from all or multiple symptoms, and not every patient will experience the same symptoms, meaning they differ from patient to patient. Due to there being a wide range of symptoms, RTS patients are referred to specialists that focus on each specific symptom. There is not a specialist for RTS. For example, patients will go to an orthopedic surgeon and physical therapy for skeletal and growth abnormalities, like scoliosis but will go to a cardiologist if they suffer from heart abnormalities or a dentist if they suffer from dental abnormalities. Individuals suffering from cognitive developments usually are part of special education programs and speech therapy. The specialists the individuals go to match the symptoms the individuals have. Regular check-ups and monitoring are needed for cardiac, dental, auditory, and renal abnormalities. Genetic counseling is also recommended for affected individuals and their families.

History
Rubinstein–Taybi syndrome was first unofficially mentioned in a French orthopedic medical journal in 1957 by Greek physicians doctors: Michail, Matsoukas, and Theodorou. The medical journal reported a case concerning a seven-year-old boy with radically deviated/arched thumbs, long nose, muscular hypotonia, along with physical and mental underdevelopment. At this point in time the case study mentioned by the Greek physicians was considered to be an anomaly due to the fact that there hadnt been any other reported cases of children with these specific physical and mental characteristics. The doctors accredited with discovering the syndrome and therefore bear its name-sake were unaware of this journal at the time of their discovery. However, it is acknowledged that the 1957 case reported in the French journal of orthopedic medicine is most likely the first reported case of RTS.Dr. Jack Herbert Rubinstein, an American pediatrician reported assessing a three-year-old girl with unusual facial and digital findings in 1958. Similarly, that same year Rubinstein had evaluated another child with similar characteristics, this time a seven-year-old boy. Having sensed a striking similarity between these two unrelated cases Rubinstein tried distributing photos and information concerning these two cases to other clinics in the U.S. from 1959 to 1960. Rubinstein graduated from Harvard Medical School and worked as the director of the Hamilton County Diagnostic Clinic for the Mentally Retarded. He has worked in behavioral and developmental pediatrics for many years prior to the discovery of this new syndrome.In 1961, Dr. Hooshang Taybi, an Iranian-American pediatric radiologist, reported having assessed a three-year-old boy that appeared to have the same syndrome as described by Rubinstein </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 Amok 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 Ophiasis 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 Sulfite oxidase and can you explain it in depth? [/INST] Sulfite oxidase (EC 1.8.3.1) is an enzyme in the mitochondria of all eukaryotes, with exception of the yeasts. It oxidizes sulfite to sulfate and, via cytochrome c, transfers the electrons produced to the electron transport chain, allowing generation of ATP in oxidative phosphorylation.  This is the last step in the metabolism of sulfur-containing compounds and the sulfate is excreted.
Sulfite oxidase is a metallo-enzyme that utilizes a molybdopterin cofactor and a heme group (in a case of animals).  It is one of the cytochromes b5 and belongs to the enzyme super-family of molybdenum oxotransferases that also includes DMSO reductase, xanthine oxidase, and nitrite reductase.
In mammals, the expression levels of sulfite oxidase is high in the liver, kidney, and heart, and very low in spleen, brain, skeletal muscle, and blood.

Structure
As a homodimer, sulfite oxidase contains two identical subunits with an N-terminal domain and a C-terminal domain. These two domains are connected by ten amino acids forming a loop. The N-terminal domain has a heme cofactor with three adjacent antiparallel beta sheets and five alpha helices. The C-terminal domain hosts a molybdopterin cofactor that is surrounded by thirteen beta sheets and three alpha helices. The molybdopterin cofactor has a Mo(VI) center, which is bonded to a sulfur from cysteine, an ene-dithiolate from pyranopterin, and two terminal oxygens.  It is at this molybdenum center that the catalytic oxidation of sulfite takes place.
The pyranopterin ligand which coordinates the molybdenum centre via the enedithiolate. The molybdenum centre has a square pyramidal geometry and is distinguished from the xanthine oxidase family by the orientation of the oxo group facing downwards rather than up.

Active site and mechanism
The active site of sulfite oxidase contains the molybdopterin cofactor and supports molybdenum in its highest oxidation state, +6 (MoVI).  In the enzymes oxidized state, molybdenum is coordinated by a cysteine thiolate, the dithiolene group of molybdopterin, and two terminal oxygen atoms (oxos). Upon reacting with sulfite, one oxygen atom is transferred to sulfite to produce sulfate, and the molybdenum center is reduced by two electrons to MoIV </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 Rhizomelic chondrodysplasia punctata 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 Impaired fasting glucose and can you explain it in depth? [/INST] Impaired fasting glucose is a type of prediabetes, in which a persons blood sugar levels during fasting are consistently above the normal range, but below the diagnostic cut-off for a formal diagnosis of diabetes mellitus. Together with impaired glucose tolerance, it is a sign of insulin resistance </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 Alcoholic polyneuropathy and can you explain it in depth? [/INST] Alcoholic polyneuropathy is a neurological disorder in which peripheral nerves throughout the body malfunction simultaneously. It is defined by axonal degeneration in neurons of both the sensory and motor systems and initially occurs at the distal ends of the longest axons in the body. This nerve damage causes an individual to experience pain and motor weakness, first in the feet and hands and then progressing centrally. Alcoholic polyneuropathy is caused primarily by chronic alcoholism; however, vitamin deficiencies are also known to contribute to its development. This disease typically occurs in chronic alcoholics who have some sort of nutritional deficiency. Treatment may involve nutritional supplementation, pain management, and abstaining from alcohol.

Signs and symptoms
An early warning sign (prodrome) of the possibility of developing alcoholic polyneuropathy, especially in a chronic alcoholic, would be weight loss because this usually signifies a nutritional deficiency that can lead to the development of the disease.Alcoholic polyneuropathy usually has a gradual onset over months or even years, although axonal degeneration often begins before an individual experiences any symptoms.The disease typically involves sensory issues and motor loss, as well as painful physical perceptions, though all sensory modalities may be involved.
Symptoms that affect the sensory and motor systems seem to develop symmetrically. For example, if the right foot is affected, the left foot is affected simultaneously or soon becomes affected.
In most cases, the legs are affected first, followed by the arms. The hands usually become involved when the symptoms reach above the ankle. This is called a stocking-and-glove pattern of sensory disturbances.

Sensory
Common manifestations of sensory issues include numbness or painful sensations in the arms and legs, abnormal sensations like "pins and needles," and heat intolerance. Pain experienced by individuals depends on the severity of the polyneuropathy. It may be dull and constant in some individuals while being sharp and lancinating in others. In many subjects, tenderness is seen upon the palpitation of muscles in the feet and legs. Certain people may also feel cramping sensations in the muscles affected and others say there is a burning sensation in their feet and calves.

Motor
Sensory symptoms are gradually followed by motor symptoms. Motor symptoms may include muscle cramps and weakness, erectile dysfunction in men, problems urinating, constipation, and diarrhea. Individuals also may experience muscle wasting and decreased or absent deep tendon reflexes. Some people may experience frequent falls and gait unsteadiness due to ataxia. This ataxia may be caused by cerebellar degeneration, sensory ataxia, or distal muscle weakness. Over time, alcoholic polyneuropathy may also cause difficulty swallowing (dysphagia), speech impairment (disarthria), muscle spasms, and muscle atrophy.In addition to alcoholic polyneuropathy, the individual may also show other related disorders such as Wernicke–Korsakoff syndrome and cerebellar degeneration that result from alcoholism-related nutritional disorders.

Severity
Polyneuropathy spans a large range of severity. Some cases are seemingly asymptomatic and may only be recognized on careful examination. The most severe cases may cause profound physical disability.

Causes
The general cause of this disease appears to be prolonged and heavy consumption of alcohol accompanied by a nutritional deficiency. However, there is ongoing debate over the active mechanisms, including whether the main cause is the direct toxic effect of alcohol itself or whether the disease is a result of alcoholism-related malnutrition. A 2019 metastudy found that the relationship between ethanol toxicity and neuropathy remained unproven.

Effects due to nutritional deficiency
Frequently alcoholics have disrupted social links in their lives and have an irregular lifestyle. This may cause an alcoholic to change their eating habits including more missed meals and a poor dietary balance. Alcoholism may also result in loss of appetite, alcoholic gastritis, and vomiting, which decrease food intake. Alcohol abuse damages the lining of the gastrointestinal system and reduces absorption of nutrients that are taken in. The combination of all of them may result in a nutritional deficiency that is linked to the development of alcoholic polyneuropathy.There is evidence that providing individuals with adequate vitamins improves symptoms despite continued alcohol intake, indicating that vitamin deficiency may be a major factor in the development and progression of alcoholic polyneuropathy. In experimental models of alcoholic polyneuropathy utilizing rats and monkeys no convincing evidence was found that proper nutritional intake along with alcohol results in polyneuropathy.

In most cases, individuals with alcoholic polyneuropathy have some degree of nutritional deficiency. Alcohol, a carbohydrate, increases the metabolic demand for thiamine (vitamin B1) because of its role in the metabolism of glucose. Thiamine levels are usually low in alcoholics due to their decreased nutritional intake. In addition, alcohol interferes with intestinal absorption of thiamine, thereby further decreasing thiamine levels in the body. Thiamine is important in three reactions in the metabolism of glucose: the decarboxylation of pyruvic acid, d-ketoglutaric acid, and transketolase. A lack of thiamine in the cells may therefore prevent neurons from maintaining necessary adenosine triphosphate (ATP) levels as a result of impaired glycolysis. Thiamine deficiency alone could explain the impaired nerve conduction in those with alcoholic polyneuropathy, but other factors likely play a part.The malnutrition many alcoholics experience deprives them of important cofactors for the oxidative metabolism of glucose. Neural tissues depend on this process for energy, and disruption of the cycle would impair cell growth and function. Schwann cells produce myelin that wraps around the sensory and motor nerve axons to enhance action potential conduction in the periphery. An energy deficiency in Schwann cells would account for the disappearance of myelin on peripheral nerves, which may result in damage to axons or loss of nerve function altogether. In peripheral nerves, oxidative enzyme activity is most concentrated around the nodes of Ranvier, making these locations most vulnerable to cofactor deprivation. Lacking essential cofactors reduces myelin impedance, increases current leakage, and slows signal transmission. Disruptions in conductance first affect the peripheral ends of the longest and largest peripheral nerve fibers because they suffer most from decreased action potential propagation. Thus, neural deterioration occurs in an accelerating cycle: myelin damage reduces conductance, and reduced conductance contributes to myelin degradation. The slowed conduction of action potentials in axons causes segmental demyelination extending proximally; this is also known as retrograde degeneration.Many of the studies conducted that observe alcoholic polyneuropathy in patients are often criticized for their criteria used to assess nutritional deficiency in the subjects because they may not have completely ruled out the possibility of a nutritional deficiency in the genesis of the polyneuropathy. Many researchers favor the nutritional origin of this disease, but the possibility of alcohol having a toxic effect on the peripheral nerves has not been completely ruled out.

Effects due to alcohol ingestion
The consumption of alcohol may lead to the buildup of certain toxins in the body. For example, in the process of breaking down alcohol, the body produces acetaldehyde, which can accumulate to toxic levels in alcoholics. This suggests that there is a possibility ethanol (or its metabolites) may cause alcoholic polyneuropathy. There is evidence that polyneuropathy is also prevalent in well nourished alcoholics, supporting the idea that there is a direct toxic effect of alcohol.The metabolic effects of liver damage associated with alcoholism may also contribute to the development of alcoholic polyneuropathy. Normal products of the liver, such as lipoic acid, may be deficient in alcoholics. This deficiency would also disrupt glycolysis and alter metabolism, transport, storage, and activation of essential nutrients.Acetaldehyde is toxic to peripheral nerves. There are increased levels of acetaldehyde produced during ethanol metabolism. If the acetaldehyde is not metabolized quickly the nerves may be affected by the accumulation of acetaldehyde to toxic levels.

Pathophysiology
The pathophysiology of alcoholic polyneuropathy is unclear.

Diagnosis
Alcoholic polyneuropathy is very similar to other axonal degenerative polyneuropathies and therefore can be difficult to diagnose. When alcoholics have sensorimotor polyneuropathy as well as a nutritional deficiency, a diagnosis of alcoholic polyneuropathy is often reached.To confirm the diagnosis, a physician must rule out other causes of similar clinical syndromes. Other neuropathies can be differentiated on the basis of typical clinical or laboratory features. Differential diagnoses to alcoholic polyneuropathy include amyotrophic lateral sclerosis, beriberi, Charcot-Marie-Tooth disease, diabetic lumbosacral plexopathy, Guillain Barre Syndrome, diabetic neuropathy, mononeuritis multiplex and post-polio syndrome.To clarify the diagnosis, medical workup most commonly involves laboratory tests, though, in some cases, imaging, nerve conduction studies, electromyography, and vibrometer testing may also be used.A number of tests may be used to rule out other causes of peripheral neuropathy.  One of the first presenting symptoms of diabetes mellitus may be peripheral neuropathy, and hemoglobin A1C can be used to estimate average blood glucose levels.  Elevated blood creatinine levels may indicate chronic kidney disease and may also be a cause of peripheral neuropathy.  A heavy metal toxicity screen should also be used to exclude lead toxicity as a cause of neuropathy.Alcoholism is normally associated with nutritional deficiencies, which may contribute to the development of alcoholic polyneuropathy. Thiamine, vitamin B-12, and folic acid are vitamins that play an essential role in the peripheral and central nervous system and should be among the first analyzed in laboratory tests. It has been difficult to assess thiamine status in individuals due to difficulties in developing a method to directly assay thiamine in the blood and urine. A liver function test may also be ordered, as alcoholic consumption may cause an increase in liver enzyme levels.

Management
Although there is no known cure for alcoholic polyneuropathy, there are a number of treatments that can control symptoms and promote independence.  Physical therapy is beneficial for strength training of weakened muscles, as well as for gait and balance training.

Nutrition
To best manage symptoms, refraining from consuming alcohol is essential. Abstinence from alcohol encourages proper diet and helps prevent progression or recurrence of the neuropathy. Once an individual stops consuming alcohol it is important to make sure they understand that substantial recovery usually isnt seen for a few months. Some subjective improvement may appear right away, but this is usually due to the overall benefits of alcohol detoxification.  If alcohol consumption continues, vitamin supplementation alone is not enough to improve the symptoms of most individuals.Nutritional therapy with parenteral multivitamins is beneficial to implement until the person can maintain adequate nutritional intake. Treatments also include vitamin supplementation (especially thiamine). In more severe cases of nutritional deficiency 320 mg/day of benfotiamine for 4 weeks followed by 120 mg/day for 4 more weeks may be prescribed in an effort to return thiamine levels to normal.

Pain
Painful dysesthesias caused by alcoholic polyneuropathy can be treated by using gabapentin or amitriptyline in combination with over-the-counter pain medications, such as aspirin, ibuprofen, or acetaminophen. Tricyclic antidepressants such as amitriptyline, or carbamazepine may help stabbing pains and have central and peripheral anticholinergic and sedative effects. These agents have central effects on pain transmission and block the active reuptake of norepinephrine and serotonin.Anticonvulsant drugs like gabapentin or pregabalin block the active reuptake of norepinephrine and serotonin and have properties that relieve neuropathic pain.  However, these medications take a few weeks to become effective and are rarely used in the treatment of acute pain.Topical analgesics like capsaicin may also relieve minor aches and pains of muscles and joints.

Prognosis
Alcoholic polyneuropathy is not life-threatening but may significantly affect ones quality of life. Effects of the disease range from mild discomfort to severe disability.It is difficult to assess the prognosis of a patient because it is hard to convince chronic alcoholics to abstain from drinking alcohol completely. It has been shown that a good prognosis may be given for mild neuropathy if the alcoholic has abstained from drinking for 3–5 years.

Early stage
During the early stages of the disease the damage appears reversible when people take adequate amounts of vitamins, such as thiamine. If the polyneuropathy is mild, the individual normally experiences a significant improvement and symptoms may be eliminated within weeks to months after proper nutrition is established. When those people diagnosed with alcohol polyneuropathy experience a recovery, it is presumed to result from regeneration and collateral sprouting of the damaged axons.

Progressed disease
As the disease progresses, the damage may become permanent. In severe cases of thiamine deficiency, a few of the positive symptoms (including neuropathic pain) may persist indefinitely. Even after the restoration of a balanced nutritional intake, those patients with severe or chronic polyneuropathy may experience lifelong residual symptoms.

Epidemiology
In 2020 the NIH quoted an estimate that in the United States 25% to 66% of chronic alcohol users experience some form of neuropathy. The rate of incidence of alcoholic polyneuropathy involving sensory and motor polyneuropathy has been stated as from 10% to 50% of alcoholics depending on the subject selection and diagnostic criteria. If electrodiagnostic criteria are used, alcoholic polyneuropathy may be found in up to 90% of individuals being assessed.The distribution and severity of the disease depends on regional dietary habits, individual drinking habits, as well as an individuals genetics. Large studies have been conducted and show that alcoholic polyneuropathy severity and incidence correlates best with the total lifetime consumption of alcohol. Factors such as nutritional intake, age, or other medical conditions are correlate in lesser degrees. For unknown reasons, alcoholic polyneuropathy has a high incidence in women.Certain alcoholic beverages can also contain congeners that may also be bioactive; therefore, the consumption of varying alcohol beverages may result in different health consequences. An individuals nutritional intake also plays a role in the development of this disease. Depending on the specific dietary habits, they may have a deficiency of one or more of the following: thiamine (vitamin B1), pyridoxine (vitamin B6), pantothenic acid and biotin, vitamin B12, folic acid, niacin (vitamin B3), and vitamin A.

Acetaldehyde
It is also thought there is perhaps a genetic predisposition for some alcoholics that results in increased frequency of alcoholic polyneuropathy in certain ethnic groups. During the bodys processing of alcohol, ethanol is oxidized to acetaldehyde mainly by alcohol dehydrogenase; acetaldehyde is then oxidized to acetate mainly by aldehyde dehydrogenase (ALDH). ALDH2 is an isozyme of ALDH and ALDH2 has a polymorphism (ALDH2*2, Glu487Lys) that makes ADLH2 inactive; this allele is more prevalent among Southeast and East Asians and results in a failure to quickly metabolize acetaldehyde. The neurotoxicity resulting from the accumulation of acetaldehyde may play a role in the pathogenesis of alcoholic polyneuropathy.

History
The first description of symptoms associated with alcoholic polyneuropathy were recorded by John C </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 Rectovaginal fistula and can you explain it in depth? [/INST] A rectovaginal fistula is a medical condition where there is a fistula or abnormal connection between the rectum and the vagina.Rectovaginal fistulae may be extremely debilitating. If the opening between the rectum and vagina is wide it will allow both flatulence and feces to escape through the vagina, leading to fecal incontinence. There is an association with recurrent urinary and vaginal infections.  The fistula may also connect the rectum and urethra, which is called recto-urethral fistula.  Either conditions can lead to labial fusion. This type of fistula can cause pediatricians to misdiagnose imperforate anus. The severity of the symptoms will depend on the size of fistula. Most often, it appears after about one week or so after delivery.

Causes
Rectovaginal fistulas are often the result of trauma during childbirth (in which case it is known as obstetric fistula), with increased risk associated with significant lacerations or interventions are used such as episiotomy or operative (forceps/vacuum extraction) deliveries or in situations where there is inadequate health care, such as in some developing countries. Rectovaginal fistula is said to be known as the leading cause in maternal death in developing countries. Risk factors include prolonged labour, difficult instrumental delivery and paramedian episiotomy </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 Familial eosinophilia and can you explain it in depth? [/INST] Familial eosinophilia is a rare congenital disorder characterized by the presence of sustained elevations in blood eosinophil levels that reach ranges diagnostic of eosinophilia (i.e. 500-1500/microliter) or, far more commonly, hypereosinophilia (i.e. >1,500/microliter). Although high eosinophil levels are associated with certain diseases and thought to contribute to the tissue destruction found in many other eosinophilia-related diseases (see clonal eosinophilia), clinical manifestations and tissue destruction related to the eosinophilia in familial eosinophilia is uncommon: this genetic disease typically has a benign phenotype and course compared to other congenital and acquired eosinophilic diseases.

Presentation
Individuals with familial eosinophilia exhibit hypereosinophilia presumably from birth (earliest documentation at 4 months of age). Elevated blood levels of eosinophils are remarkably stable over time in affected family members. These individuals are generally detected on routine blood cell counts and at the time of diagnosis present without symptoms or at least no symptoms related to their eosinophilia. Their blood cell counts are typically normal except for  eosinophil numbers which range between ~2000 and 5000 cells/microliter (normal <450 cells/microliter). Peripheral blood smears revealed that eosinophils showed normal morphology, a finding distinctly different from many other types of hypereosinophilia in which blood smears commonly shown immature blood cells and eosinophils showing distinctly abnormal areas of cytoplasmic clearing. Ultrastructural changes characteristic of eosinophil activation (e.g. piecemeal degranulation of eosinophils and increases in the number of their lipid bodies), other eosinophil activation markers (e.g. elevated serum levels of eosinophil-derived neurotoxin and major basic protein), and increased expression of a marker for T cell activation, interleukin-2 receptor alpha chain, are absent in individuals with familial eosinophilia but common in other types of hypereosinophilia.

Accompanying diseases
In spite of being generally considered a benign expression of eosinophilia, isolated cases of family members with familial eosinophilia have been afflicted with tissue dysfunctions that are often associated with more pathological forms of eosinophilia. These dysfunctions include fatal endomyocardial fibrosis, valvular heart disease, and diminished motor and/or sensory function in skin areas served by peripheral nerves. Three patients with heart tissue for pathology examination had eosinophilic infiltration or fibrosis in their hearts endomyocardium. One patient who died suddenly had autopsy findings of eosinophilic infiltration not only in the heart but also in lungs, gastrointestinal tract, and meninges. It is unclear whether these tissue damages were due to primary eosinophil infiltrations or eosinophil infiltrations secondary to other causes.

Genetics
Familial eosinophilia is an autosomal dominant disorder. Genetic linkage gene mapping family studies localize the gene responsible for this disease to chromosome 5 at position q31-q33, between markers D5S642 and D5S816. Studies on other disorders associated with high levels of blood eosinophils (e.g. childhood asthma, schistosomiasis) have likewise linked eosinophilia to the q31-q33 area of chromosome 5. The 5q31-q33 region contains a cytokine gene cluster that includes genes for Interleukin 3, interleukin 5, and granulocyte-macrophage colony-stimulating factor. Each of these genes functions to promote the proliferation and differentiation of eosinophil precursor cells. Nonetheless, no gene polymorphisms were found within the promoters, exons, or introns of these 3 genes or in the regions IL-3/GM-CSF enhancer. In addition to these studies, 8 affected members of a family with familial eosinophilia had peripheral blood or bone marrow cells that carried the same chromosome abnormality, a pericentric inversion of chromosome 10, inv (10) (p11.2q21.2). The meaning and relationship, if any, of this inversion to familial eosinophilia is unclear.

Pathophysiology
Earlier studies found no evidence of abnormal blood levels of interleukin 5, interleukin 3, or granulocyte-macrophage colony stimulating factor. A more recent study used a more sensitive assay for interleukin 5 to compare members of a single extended family with some members lacking the disorder </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 Mallet finger and can you explain it in depth? [/INST] A mallet finger, also known as hammer finger or PLF finger or Hannan finger, is an extensor tendon injury at the farthest away finger joint. This results in the inability to extend the finger tip without pushing it. There is generally pain and bruising at the back side of the farthest away finger joint.A mallet finger usually results from overbending of the finger tip. Typically this occurs when a ball hits an outstretched finger and jams it. This results in either a tear of the tendon or the tendon pulling off a bit of bone. The diagnosis is generally based on symptoms and supported by X-rays.During injury, this tendon is torn from its attachment site on the bone (called a tendinous mallet finger). But, there are also cases whereby the force of impact causes a small fracture at the base of bone where the tendon is attached to (called a bony mallet finger). In both cases, the tendon is no longer attached to the last bone of the digit and is thus unable to pull the end joint into a straightened position, resulting in a fingertip that droops.Treatment is generally with a splint that holds the fingertip straight continuously for 8 weeks. The middle joint is allowed to move. This should be begun within a week of the injury. If the finger is bent during these weeks, healing may take longer. If a large piece of bone has been torn off surgery may be recommended. Without proper treatment a permanent deformity of the finger may occur.

Diagnosis
The diagnosis is generally based on symptoms and supported by X-rays.  The injury can be accompanied by swelling and ecchymosis.

Treatment
The management goal is to restore extension of the joint </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 Congenital heart block and can you explain it in depth? [/INST] The congenital heart block (CHB) is the heart block that is diagnosed in fetus (in utero) or within the first 28 days after birth (neonatal period), some studies also include the diagnosis during early childhood to the definition of CHB. It refers to the disorder in the electrical conduction system within the heart muscle, which leads to the failure in pumping the blood efficiently into the aorta and the pulmonary trunk. The result of CHB can be first, second, or third-degree (complete) atrioventricular block (a block in the atrioventricular node) in which no electric signals move from the atrium to the ventriclesThe congenital heart block is a rare disease that affects around 1 child in every 15,000–20,000 births. However, its high mortality (which can be as high as 85% in some severe cases) makes the early diagnosis and intervention very important. CHB can be isolated, where the fetus does not suffer from any other problems, or it can be a result of other diseases either in the child or in the mother.In most cases, the congenital heart block is associated with other diseases, and therefore, the symptoms vary a lot between patients. However, low heart rate is usually the main clinical presentation that leads to the diagnosis. Also, the treatment varies as well due to the associated diseases and it can be non-invasive (medications given to the pregnant woman or to the child), or a surgery in some cases when the CHB is resulted from anatomical disorders in the heart.

Presentation
The symptoms of the congenital heart block can vary due to the underlying problems that associate / lead to the CHB, and the features of CHB reflects the other manifestations of these diseases.Bradycardia is usually the first symptom of CHB to be detected in utero. Due to the block in the atrioventricular node, less electric signals move from the sinoatrial node to the bundle of his and its right and left branches, leading to a lower heart rate. The atrioventricular block can be first degree or much more severe like a complete atrioventricular block (third degree). In addition, several changes in the ECG can be detected.Other manifestations of the congenital heart block can be related to the impact of the maternal autoantibodies in the autoimmune-mediated CHB. Fibrosis of the myocardium (Endocardial fibroelastosis) (EFE) is the obvious one and it occurs due to the damage caused by the maternal autoantibodies to the cardiac tissue of the fetus, and can lead to death in some cases. However, it is not a common feature of CHB.Another rare symptom that might accompany the autoimmune CHB is the disorder in the valvular function, and this happens due to the damage in the papillary muscles as a result of the maternal autoantibodies.

Causes
In some cases the reason behind CHB remains unknown but in the great majority of affected kids, this disease is associated with the transference of autoantibodies from the mother during gestation or with major cardiac structural abnormalities that lead to a disturbance in the conducting signals in the atrioventricular node. Also, in some rare cases, the congenital heart block was linked with viral infections or treatment with specific medications.

Maternal autoimmune disease
In the autoimmune-mediated congenital heart block, autoantibodies are passively transferred through the placenta during gestation. The mother might be asymptomatic during or after pregnancy but she is usually positive to anti-Ro\SSA or anti-La\SSB antibodies. In this case, the fetuss heart is normally developed and shows no structural malformations. Just like other autoimmune diseases, the autoimmune CHB shows signs of damage resulted from the autoantibodies attacking the normal tissue of the body, inflammation and fibrosis in the fetal heart tissue are the most common ones, mainly in the atrioventricular node. These antibodies lead to irreversible injuries in the atrioventricular node which heavily compromise the efficiency of the electrical conduction system, and this results in around 18% mortality rate and 70% of the live-born kids will need early pacemaker implantation.

Anti-Ro\SSA autoantibody
This autoantibody is found in the serum of the majority of kids with autoimmune CHB, and therefore it is the one mostly linked with this disease. It attacks the proteins Ro52 and Ro60 in the antigen Ro\SSA in the fetal heart tissue.

Anti-La\SSB autoantibody
This antibody attacks the ribonucleoprotein La48 on the surface of the fetal cardiomyocytes, the links between this autoantibody and autoimmune CHB are less strong than the anti-Ro autoantibody and it usually accompanies it in the majority of cases.Although the autoimmune CHB has a relatively high mortality and morbidity rates, the chance of kids from -mothers positive to anti-Ro\SSA and/or anti-La\SSB antibodies- to suffer from CHB is only around 1-5%, which suggests the existence of other factors to influence the disease such as genetic and environmental factors.

Other autoantibodies
Several autoantibodies were suggested to have links with the autoimmune CHB, mainly the ones associated with the different autoimmune diseases that are common among women (such as the antibodies associated with Systemic lupus erythematosus (SLE), Rheumatoid arthritis, Progressive systemic sclerosis (PSS), and Mixed connective tissue disease). However, the role of these autoantibodies was not studied comprehensively.Also, some antigens of the fetal heart tissue (apart from the "Ro" and the "La") were studied, but no clear link with the autoimmune CHB was proven.

Congenital cardiac structural abnormalities
The presence of a cardiac structural abnormality is a major determination of the outcome of CHB. Its existence affects the conduction system of the heart and increases the mortality rate and the need for pace-maker implantation.The cardiac structural diseases that are usually associated with the congenital heart block include the left atrial isomerism with or without atrioventricular septal defect. In addition, levo transpositions of the great arteries can accompany CHB but this is less common than the first one.These developmental abnormalities can impair the conduction system of the heart by disrupting its anatomical structure.

Diagnosis
There is  a difference in diagnosis between low risk pregnancies where mothers do not have (or are not aware of) any autoimmune disease, and the high risk ones where mothers are known to have a specific autoimmune disease and / or are positive to anti Ro/La autoanitbodies and / or had a CHB-affected pregnancy previously.In low risk pregnancies, testing the mothers serum is not part of the routine prenatal tests. Therefore, the congenital heart block is usually diagnosed during a routine obstetrical ultra sound. The first symptom in most cases is a slow heart rate which can be detected using fetal echocardiogram and Doppler ultra sound techniques between the weeks 18 - 30. The Doppler is very important to assess the level of AV block as well as to check for other cardiac structural abnormalities that might be associated with CHB such as left atrial isomerism, valvular damages and big arteries inversion, while the echocardiogram is useful to detect other complications such as the hydrops fetalis </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 Large plaque parapsoriasis and can you explain it in depth? [/INST]  </s>