<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 Retrograde amnesia and can you explain it in depth? [/INST] In neurology, retrograde amnesia (RA) is a loss of memory-access to events that occurred or information that was learned in the past. It is caused by an injury or the onset of a disease. It tends to negatively affect episodic, autobiographical, and declarative memory, while keeping procedural memory intact without increasing difficulty for learning new information. RA can be temporally graded, or more permanent based on the severity of its cause. It is usually consistent with Ribots law. The law states that subjects are more likely to lose memories closer to the traumatic incident than more memories that happened further from the incident. The type of information that is forgotten can range from a specific memory, such as a single event, or a more general memory. This would resemble generic amnesia. Anterograde amnesia is a similar condition that deals with the inability to form new memories following the onset of an injury or disease.

Cause
RA commonly results from damage to regions of the brain that are associated with episodic and declarative memory, including autobiographical information. In extreme cases, individuals may completely forget who they are. Generally, this is a more severe type of amnesia known as global, or generalized amnesia. However, memory loss can also be selective or categorical, manifested by a persons inability to remember events related to a specific incident or topic. Patients also differ in durations of RA (how long they cant recall information) and durations of what is forgotten (past time frame for which information is unavailable).

Temporally graded retrograde amnesia
In temporally graded retrograde amnesia, patients eventually recover most memories following the onset of RA. This suggests that the hippocampal formation/ consolidation, the process of coding new information, is only used in systematic consolidation for temporary storage, and short periods of time. Systemic consolidation then moves the information and long-term consolidation takes place in other brain structures. The fact that damage to the hippocampal formation can eventually overcome RA suggests that other brain structures are able to take over the jobs of the malfunctioning regions. RA can also progress and further deteriorate memory recollection, as in the case of Korsakoff syndrome and Alzheimers disease, due to the ongoing nature of the damage caused by the illnesses. The degree to which different patients recover from RA differs in time (some take a few days while others a few decades) and content (some will only remember certain specific instances while others more).

Focal, isolated, and pure retrograde amnesia
Focal isolated, and pure retrograde amnesia are terms used to describe a pure form of RA, with an absence of anterograde amnesia (AA). In addition, Focal RA in particular, has also been used to describe a RA situation in which there is a lack of observable physical deficit as well. This could be described as a psychogenic form of amnesia with mild anterograde and retrograde loss. A case study of DH revealed that the patient was unable to provide personal or public information, however there was no parahippocampal or entorhinal damage found. Individuals with focal brain damage have minimal RA.Isolated RA is associated with a visible thalamic lesion. Consistent with other forms of RA, the isolated form is marked by the inability to recall past information.Pure retrograde amnesia (PRA) refers to the behavioral syndrome that is characterized by the inability to retrieve remote information in the face of a normal ability to learn new information, with no other ecological or psychometric evidence of cognitive impairment. It should not be confused with brief periods of peritraumatic amnesia that are common in mild concussive head traumas. The findings of pure retrograde amnesia have helped form the dissociation between mechanisms for RA and AA. Several studies have found numerous causes for PRA like vascular diseases, head traumas ranging from mild to severe, encephalitis, as well as purely psychological conditions and totally unidentifiable etiologies. Most people who have PRA can function normally and learn new informationA pure form of RA is rare as most cases of RA co-occur with AA. A famous example is that of patient ML. The patients MRI revealed damage to the right ventral frontal cortex and underlying white matter, including the uncinate fasciculus, a band of fibers previously thought to mediate retrieval of specific events from ones personal past.During consolidation, the hippocampus acts as an intermediate tool that quickly stores new information until it is transferred to the neocortex for the long-term. The temporal lobe, which holds the hippocampus, entorhinal, perirhinal and parahippocampal cortices, has a reciprocal connection with the neocortex. The temporal lobe is temporarily needed when consolidating new information; as the learning becomes stronger, the neocortex becomes more independent of the temporal lobe.Studies on specific cases demonstrate how particular impaired areas of the hippocampus are associated with the severity of RA. Damage can be limited to the CA1 field of the hippocampus, causing very limited RA for about one to two years. More extensive damage limited to the hippocampus causes temporally graded amnesia for 15 to 25 years. Another study suggests that large medial temporal lobe lesions, that extend laterally to include other regions, produce more extensive RA, covering 40 to 50 years. These findings suggest that density of RA becomes more severe and long-term as the damage extends beyond the hippocampus to surrounding structures.
The common studied causes of RA do not always lead to the onset of RA. It may even be that in some cases both conscious feigning and unconscious processes are at play.

Traumatic brain injury (TBI) or post-traumatic amnesia
Traumatic brain injury (TBI), also known as post-traumatic amnesia, occurs from an external force that causes structural damage to the brain, such as a sharp blow to the head, a diffuse axonal injury, or childhood brain damage (e.g., shaken baby syndrome). In cases of sudden rapid acceleration, the brain continues moving around in the skull, harming brain tissue as it hits internal protrusions.TBI varies according to impact of external forces, location of structural damage, and severity of damage ranging from mild to severe. Retrograde amnesia can be one of the many consequences of brain injury but it is important to note that it is not always the outcome of TBI. An example of a subgroup of people who are often exposed to TBI are individuals who are involved in high-contact sports. Research on football players takes a closer look at some of the implications to their high-contact activities. Enduring consistent head injuries can have an effect on the neural consolidation of memory.Specific cases, such as that of patient ML, support the evidence that severe blows to the head can cause the onset of RA. In this specific case there was an onset of isolated RA following a severe head injury. The brain damage did not affect the persons ability to form new memories. Therefore, the idea that specific sections of retrograde memory are independent of anterograde is supported. Normally, there is a very gradual recovery, however, a dense period of amnesia immediately preceding the trauma usually persists.

Traumatic events
RA can occur without any anatomical damage to the brain, lacking an observable neurobiological basis. Primarily referred to as psychogenic amnesia or psychogenic fugue, it often occurs due to a traumatic situation that individuals wish to consciously or unconsciously avoid through intrapsychic conflicts or unconscious repressions. The onset of psychogenic amnesia can be either global (i.e., individual forgets all history) or situation specific (i.e., individual is unable to retrieve memories of specific situations).Patients experiencing psychogenic amnesia have impaired episodic memory, instances of wandering and traveling, and acceptance of a new identity as a result of inaccessible memories pertaining to their previous identity.Recent research has begun to investigate the effects of stress and fear-inducing situations with the onset of RA. Long-term potentiation (LTP) is the process by which there is a signal transmission between neurons after the activation of a neuron, which has been known to play a strong role in the hippocampus in learning and memory. Common changes in the hippocampus have been found to be related to stress and induced LTP. The commonalities support the idea that variations of stress can play a role in producing new memories as well as the onset of RA for other memories. The amygdala plays a crucial role in memory and can be affected by emotional stimuli, evoking RA.Studies of specific cases, such as AMN, support evidence  of traumatic experiences as a plausible cause of RA. AMN escaped a small fire in his house, did not inhale any smoke, and had no brain damage. Nevertheless, he was unable to recall autobiographical knowledge the next day. This case shows that RA can occur in the absence of structural brain damage.After a traumatic head injury, emotional disturbances can occur at three different levels: neurological, reactionary, and long-term disturbances. Neurological disturbances can change emotional and motivational responses. Reactionary disturbances effect emotional and motivational responses as well, but reflect the failure to cope with environmental demands. Someone with this might withdraw from the environment that they are placed in because they no longer know how to handle the cognitive resources.

Nutritional deficiency
RA has been found among alcohol-dependent patients who have Korsakoffs syndrome. Korsakoffs syndrome patients develop retrograde amnesia due to a thiamine deficiency (lack of vitamin B1). Also, chronic alcohol use disorders are associated with a decrease in the volume of the left and right hippocampus.These patients regular diet consists mostly of hard alcohol intake, which lacks the necessary nutrients for typical development and maintenance. Therefore, after a prolonged time consuming primarily alcohol, these people undergo memory difficulties and ultimately develop RA. However, some of the drawbacks of using Korsakoff patients to study RA is the progressive nature of the illness and the unknown time of onset.

Infections
Infections that pass the blood–brain barrier can cause brain damage (encephalitis), sometimes resulting in the onset of RA. In the case of patient SS, the infection led to focal or isolated retrograde amnesia where there was an absence of or limited AA. Brain scans show abnormalities in the bilateral medial temporal lobes, including two thirds of the hippocampal formation and the posterior part of the amygdala.

Surgery
Henry Molaison had epilepsy that progressed and worsened by his late twenties. The severity of his condition caused him to undergo surgery in an effort to prevent his seizures. Unfortunately, due to a lack of overall known neurological knowledge, Molaisons surgeons removed his bilateral medial temporal lobe, causing profound AA and RA. The removed brain structures included the hippocampus, the amygdala, and the parahippocampal gyrus, now called the medial temporal lobe memory system. HM was one of the most studied memory cases to date and started the examination of neurological structures in relation to memory.
Patients who have RA due to surgery are "P.B." and "F.C." who had unilateral removal of the medial areas in the left temporal lobe.

Controlled induction
Clinically induced RA has been achieved using different forms of electrical induction.

Electroconvulsive therapy (ECT), used as a depression therapy, can cause impairments in memory. Tests show that information from days and weeks before the ECT can be permanently lost. The results of this study also show that severity of RA is more extreme in cases of bilateral ECT rather than unilateral ECT. Impairments can also be more intense if ECT is administered repetitively (sine wave simulation) as opposed to a single pulse (brief-pulse stimulation).
Electroconvulsive shock (ECS): The research in this field has been advanced by using animals as subjects. Researchers induce RA in rats, for example, by giving daily ECS treatments. This is done to further understand RA.

Brain structures
The most commonly affected areas are associated with episodic and declarative memory such as the hippocampus, the diencephalon, and the temporal lobes.
The hippocampus deals largely with memory consolidation, where information from the working memory and short-term memory is encoded into long-term storage for future retrieval. Amnesic patients with damage to the hippocampus are able to demonstrate some degree of unimpaired semantic memory, despite a loss of episodic memory, due to spared parahippocampal cortex. In other words, retrograde amnesics "know" about information or skill, but cannot "remember" how they do.
The diencephalon and the surrounding areas role in memory is not well understood. However, this structure appears to be involved in episodic memory recall.
The temporal lobes are essential for semantic and factual memory processing. Aside from helping to consolidate memory with the hippocampus, the temporal lobes are extremely important for semantic memory. Damage to this region of the brain can result in the impaired organization and categorization of verbal material, disturbance of language comprehension, and impaired long-term memory. The right frontal lobe is critical for the retrieval of episodic information, while the left frontal region is more active for the retrieval of semantic information. [56] Lesions in the right hemisphere and right frontal lobes result in the impaired recall of non-verbal material, such as music and drawings. Difficulties in studying this region of the brain extends to its duties in comprehension, naming objects, verbal memory, and other language functions.Brain plasticity has helped explain the recovery process of brain damage induced retrograde amnesia, where neuro-structures use different neural pathways to avoid the damaged areas while still performing their tasks. Thus, the brain can learn to be independent of the impaired hippocampus, but only to a certain extent.
For example, older memories are consolidated over time and in various structures of the brain, including Wernickes area and the neocortex, making retrieval through alternate pathways possible.

Diagnosis
Testing for retrograde amnesia
As previously mentioned, RA can affect peoples memories in different degrees, but testing is required to help determine if someone is experiencing RA. Several tests exist, for example, testing for factual knowledge such as known public events. A problem with this form of testing is that people generally differ in their knowledge of such subjects. The tests also have to be changed regularly to adapt to the period of time patients have been alive, and include questions about autobiographical events that range in amount of detail. Due to the nature of the information being tested, it is often difficult to verify the accuracy of the memories being recalled, especially if they are from a distant past. One way to confirm information is by consulting close family members or caregivers. Another problem that arises is that this type of testing can result in a significant amount of data that needs to be processed and confirmed. Other ways to test someone is via autobiographical knowledge using the Autobiographical Memory Interview (AMI). A test that comprises names of relatives, personal information, and job history. The AMI was created by Kopelman, Wilson, and Baddeley (1990).  This information could help  determine if someone is experiencing RA and the degree of memory affected. Some researchers have found that the time interval after the head injury occurred did not seem to matter. The effect of the memory loss was the same no matter how long it had been after from the injury.Brain abnormalities can be measured using magnetic resonance imaging (MRI),  computed tomography scan (CT) and electroencephalography (EEG), which can provide detailed information about specific brain structures. In many cases, an autopsy helps identify the exact brain region affected and the extent of the damage that caused RA once the patient has died.
There are some aspects essential to the patient that remain unaffected by RA. In many patients, their personality remains the same. Also, semantic memory, that is general knowledge about the world, is usually unaffected. However, episodic memory, which refers to ones life experiences, is impaired.Another real life problem with RA is malingering, which is conceived as the rational output of a neurologically normal brain aiming at the surreptitious achievement of a well identified gain. Since it is common for people who have committed a crime to report having RA for that specific event in order to avoid their punishment, the legal system has pushed for the creation of a standardized test of amnesia. However, since most cases differ in onset, duration, and content forgotten, this task has shown to be a rather complex one.

Spontaneous recovery
When someone has RA, their memory cannot be recovered by simply being informed about their personal experiences and their identity. This is called reminder effect or reminder treatment. The reminder effect consists of re-exposing the patient to past personal information, which cannot reverse RA. Thus, reminding the patient about details of their life has no scientific bearings on recovering memory. Fortunately, memory can be and usually is recovered due to spontaneous recovery and plasticity.

Case studies
Since researchers are interested in examining the effects of disrupted brain areas and conducting experiments for further understanding of an unaffected, normal brain, many individuals with brain damage have volunteered to undergo countless tests to advance our scientific knowledge of the human brain. For example, Henry Molaison (HM) was someone with significant brain damage and participated in a lot of neurological research. Furthermore, he was also the most tested person in neuropsychology. All living people who participate are referred to in literature using only their initials to protect privacy.
Each case of RA has led to different symptoms and durations, where some patients have exhibited an inability to describe future plans, whether in the near future (e.g., this afternoon) or in the distant future (e.g., next summer) because of their inability to consolidate memories. Furthermore, researchers have also found that some patients can identify themselves and loved ones in photographs, but cannot determine the time or place the photo was taken. It has also been found that patients with RA greatly differ from the general population in remembering past events.A few case examples are:

After a head injury, AB had to relearn personal information. Many of ABs habits had also changed.
Patient CD reported disorientation of place and time following his injuries as well as relearning previously learned information and activities (e.g., using a razor).
EF was examined and found to be very confused about social norms (e.g., appropriate attire outside his home). EF exhibited memory loss of his personal experiences (e.g., childhood), and the impaired ability to recognize his wife and parents.
JG is the first recorded patient with isolated RA.
GH, a mother and a wife, had surgery in August 2002. When GH woke up after the surgery, she believed it was May 1989. Due to her amnesia, GH experienced great difficulty in her social environment, being overwhelmed by relationships to others.
DH, a learning disabilities instructor and husband, sustained a closed head injury. He did not show any normal signs of memory loss but he could not recall anything prior to the accident.
CDA is a 20-year-old man who fell and experienced head trauma after being unconscious for a little less than an hour. He had a self-identity loss and a retrograde deficit limited to the autobiographical events 5 years before the trauma. He often showed signs of spontaneous speech that was iterative and sometimes incoherent. When he saw his family and friends, he was shocked at how old they looked because he remembered them from 5 years earlier. This case also included amnesia for procedural skills like the fear of shaving or driving, which ultimately was overcome. There were no psychological, neuropsychological, or brain damage problems. His recovery of memory was progressive and spontaneous, where after several months the amnesia was limited to the two years preceding the trauma. This was a classic case of PRA. [57]
GC was a 38 year old accountant that was found in a town square unable to remember anything about himself and unaware of where he was and how he got there. He was eventually able to recall basic information about himself and his family, but could not recall emotionally charged autobiographical events pertaining to the last 7 years of his life. Within 3–4 days, it was determined that his autobiographical amnesia was clearly and strictly selective for professional events, as he could remember everything that was not related to his job. It was ultimately learned that the job had created severe emotional stress and anxiety due to the extreme hours that triggered a sudden fugue state. He was eventually able to recover most of his memories minus a single work event where he had stolen money from the company. This was a classic case of psychogenic amnesia. [57]
AF is a 15-year-old boy who hit his head and lost consciousness. He could not remember anything but was able to play songs on the piano, showing that his procedural memory was still intact. He gradually recovered some memories within the first 2–3 days but had autobiographical amnesia as well as significant memory loss for famous public facts and events for the 2 years prior to the injury. [57]Although it may seem that people living with brain damage have great difficulty continuing the usual day-to-day aspects, they still can accomplish many feats. People with RA are able to lead a normal life </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 Leg and can you explain it in depth? [/INST] A leg is a weight-bearing and locomotive anatomical structure, usually having a columnar shape. During locomotion, legs function as "extensible struts".  The combination of movements at all joints can be modeled as a single, linear element capable of changing length and rotating about an omnidirectional "hip" joint.
As an anatomical animal structure it is used for locomotion. The distal end is often modified to distribute force (such as a foot). Most animals have an even number of legs.
As a component of furniture, it is used for the economy of materials needed to provide the support for the useful surface such as the table top or chair seat.

Terminology
Uniped: 1 leg, such as clams
Biped: 2 legs, such as humans and birds
Triped: 3 legs, which typically does not occur naturally in healthy animals
Quadruped: 4 legs, such as dogs and horsesMany taxa are characterized by the number of legs:

Tetrapods have four legs. Squamates of genus Bipes have only two </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 Burkitt lymphoma and can you explain it in depth? [/INST] Burkitt lymphoma is a cancer of the lymphatic system, particularly B lymphocytes found in the germinal center.  It is named after Denis Parsons Burkitt, the Irish surgeon who first described the disease in 1958 while working in equatorial Africa. The overall cure rate for Burkitt lymphoma in developed countries is about 90%, and it is worse in low-income countries. Burkitt lymphoma is uncommon in adults, in whom it has a worse prognosis.

Classification
Burkitt lymphoma can be divided into three main clinical variants: the endemic, the sporadic, and the immunodeficiency-associated variants. By morphology (i.e., microscopic appearance), immunophenotype, and genetics, the variants of Burkitt lymphoma are alike.
The endemic variant (also called "African variant") most commonly occurs in children living in malaria-endemic regions of the world (e.g., equatorial Africa, Brazil, and Papua New Guinea). Epstein–Barr virus (EBV) infection is found in nearly all patients. Chronic malaria is believed to reduce resistance to EBV, allowing it to take hold. The disease characteristically involves the jaw or other facial bone, distal ileum, cecum, ovaries, kidney, or breast.
The sporadic type of Burkitt lymphoma (also known as "non-African") is the most common variant found in places where malaria is not prevalent such as North America and parts of Europe. The tumor cells have a similar appearance to the cancer cells of classical endemic Burkitt lymphoma. Sporadic lymphomas are rarely associated with the EBV. The jaw is less commonly involved in this variant. The abdominal region is the common site of involvement.
Immunodeficiency-associated Burkitt lymphoma is usually associated with HIV infection, but can also occur in the setting of post-transplant patients.Burkitt lymphoma is commonly associated with the infection of B cell lymphocytes with the EBV and in these cases is considered to be one form of the Epstein–Barr virus-associated lymphoproliferative diseases. The endemic variant of Burkitt lymphoma is in almost all cases associated with EBV infection. The fact that some Burkitt lymphoma cases do not involve EBV allows that many cases of the disease are not caused and/or promoted by EBV, i.e. the virus may be an innocent passenger virus in these cases. However, the almost ubiquitous presence of the virus in the endemic variant of Burkitt lymphoma suggests that it contributes to the development and/or progression of this variant. The mutational landscape in Burkitt lymphoma has recently been found to differ between tumors with and without EBV infection, further strengthening the role of the virus in disease origin.

Pathophysiology
Genetics
All types of Burkitt lymphoma are characterized by dysregulation of the c-myc gene by one of three chromosomal translocations. This gene is found at 8q24.

The most common variant is t(8;14)(q24;q32), which accounts for about 85% of cases. This involves c-myc and IGH@. A variant of this, a three-way translocation, t(8;14;18), has also been identified.
A rare variant is at t(2;8)(p12;q24). This involves IGK@ and c-myc.
Another rare variant is t(8;22)(q24;q11). This involves IGL@ and c-myc.Combined, the two less-common translocations, t(2;8)(p12;q24) and t(8;22)(q24;q11), account for the remaining 15% of cases not due to the t(8;14)(q24;q32) translocation.The c-myc gene found on chromosome 8 is part of the Myc family of genes that serve as regulators of cellular transcription and is associated with Burkitt lymphoma. Expression of the c-myc gene results in the synthesis of transcriptional factors that increase the expression of other genes involved in aerobic glycolysis. Ultimately, an increase in aerobic glycolysis plays a role in providing the necessary energy for cellular growth to occur. The translocation of the c-myc gene to the IGH, IGK, or IGL region moves the gene to a location in the genome near immunoglobulin enhancers which increases the expression of the c-myc gene. Overall, this translocation leads to increased cellular proliferation that is found in Burkitt lymphoma. Point mutations can also be present in the translocated c-myc gene resulting in the expressed c-myc protein being overactive. Other mutations found include the TCF transcription factor mutation, which increases cellular proliferation via the increased expression of other genes. Along with mutations that support cell proliferation, Burkitt lymphoma has been found to also harbor mutations in the TP53 gene that is a tumor suppressor and would normally function to limit cellular growth.

Virology
The complete role of EBV in the pathogenesis of endemic Burkitt lymphoma is not completely elucidated, but it has been shown to cause DNA damage, dysfunction of telomeres, and genome instability. B cell infection with EBV is latent, and the virus does not undergo replication. These latently infected B cells can then go on to produce proteins that function to promote cellular growth through modification of normal signaling pathways. EBV promotes the development of malignant B cells via proteins that limit apoptosis in cells that had the c-myc translocation. Apoptosis is limited by EBV through various means such as the EBNA-1 protein, BHF1 protein, EBER transcripts, vIL-10 gene, BZLF1, and LMP1. Malaria has been found to cause genomic instability in endemic Burkitt lymphoma. Malaria can lead to the reactivation of latent EBV and also MYC translocations via activation of the toll-like receptor 9. Malaria also promotes B-cell proliferation by altering the regular immune response. The immune system targets antigens (e.g., EBNA2 and LMP-1) and eliminates most B cells infected with EBV. Downregulation of antigens targeted by the immune system leads to the development of persistent B cells. These B cells can then undergo further mutations (e.g., c-myc translocation) that promote cancer development.

Immunology
Burkitt Lymphoma cells express HLA class I molecules normally, as well as some HLA class II complexes; however, CD4+ T cells are not properly activated. Burkitt lymphoma cells only express EBNA 1, a poorly antigenic EBV-associated antigen, that is able to escape HLA class I presentation, thus evades an immune response. EBNA 1 can be presented via HLA class II molecules, however HLA Class II pathway is unable to activate the CD4+ T cells.

Diagnosis
Malignant B cell characteristics
Normal B cells of a germinal center possess rearranged immunoglobulin heavy and light chain genes, and each isolated B cell possesses a unique IgH gene rearrangement. Since Burkitt lymphoma and other B-cell lymphomas are a clonal proliferative process, all tumor cells from one patient are supposed to possess identical IgH genes. When the DNA of tumor cells is analyzed using electrophoresis, a clonal band can be demonstrated, since identical IgH genes will move to the same position.  On the contrary, when a normal or reactive lymph node is analyzed using the same technique, a smear rather than a distinct band will be seen. This technique is useful since sometimes benign reactive processes (e.g. infectious mononucleosis) and malignant lymphoma can be difficult to distinguish.

Microscopy
The tumor consists of sheets of a monotonous (i.e., similar in size and morphology) population of medium-sized lymphoid cells with high proliferative and apoptotic activity.  The "starry sky" appearance seen under low power is due to scattered tingible body-laden macrophages (macrophages containing dead apoptotic tumor cells). The old descriptive term of "small non-cleaved cell" is misleading. The tumor cells are mostly medium in size (i.e., tumor nuclei size similar to that of histiocytes or endothelial cells). "Small non-cleaved cells" are compared to "large non-cleaved cells" of normal germinal center lymphocytes. Tumor cells possess small amounts of basophilic cytoplasm with three to four small nucleoli. The cellular outline usually appears squared off.

Immunohistochemistry
The tumor cells in Burkitt lymphoma generally strongly express markers of B cell differentiation (CD20, CD22, CD19), as well as CD10 and BCL6.  The tumor cells are generally negative for BCL2 and TdT.  The high mitotic activity of Burkitt lymphoma is confirmed by nearly 100% of the cells staining positive for Ki67.

Treatment
In general, the first line of treatment for Burkitt lymphoma is chemotherapy. A few of these regimens are: the GMALL-B-ALL/NHL2002 protocol, the modified Magrath regimen (R-CODOX-M/IVAC). COPADM, hyper-CVAD, and the Cancer and Leukemia Group B (CALGB) 8811 regimen; these can be associated with rituximab. In older patients, treatment may be dose-adjusted EPOCH with rituximab.The effects of the chemotherapy, as with all cancers, depend on the time of diagnosis. With faster-growing cancers, such as Burkitt, the cancer actually responds faster than with slower-growing cancers. This rapid response to chemotherapy can be hazardous to the patient, as a phenomenon called "tumor lysis syndrome" could occur. Close monitoring of the patient and adequate hydration is essential during the process. Since Burkitt lymphoma has high propensity to spread to the central nervous system (lymphomatous meningitis), intrathecal chemotherapy with methotrexate and/or ARA-C and/or prednisolone is given along with systemic chemotherapy.Chemotherapy

cyclophosphamide
doxorubicin
vincristine
methotrexate
cytarabine
ifosfamide
etoposide
rituximabOther treatments for Burkitt lymphoma include immunotherapy, bone marrow transplants, stem cell transplant, surgery to remove the tumor, and radiotherapy.

Prognosis
The prognosis for Burkitt lymphoma is superior in children and increased age is a negative prognostic indicator.
The overall cure rate for sporadic Burkitt lymphoma in developed countries is about 90%. In adults, Burkitt lymphoma is uncommon and has poor outcomes. Unsatisfactory initial response to the treatment of Burkitt lymphoma with cyclophosphamide, vincristine, and prednisolone indicates a negative prognosis. Furthermore, failed initial treatment and return of Burkitt lymphoma after a six-month stint of time serve as a poor prognostic indicator. The adequate utilization of therapeutic drugs during initial treatment limits additional treatment options following the return of the disease. Notably, in areas of the world where the initial treatment of Burkitt lymphoma is inadequate further treatment options may remain for cases when the disease returns. Laboratory studies such as lactate dehydrogenase (LDH), CD4 count, and other cytogenetic studies are also prognostic indicators. Unsatisfactory outcomes have been associated with an LDH that is found to be two times above the upper limit of normal. Specifically, there is a poor prognosis associated with a CD4 count that is decreased in the immunodeficiency-associated variant of Burkitt lymphoma. Genetic mutations extending beyond the previously described MYC translocation may also serve as negative prognostic indicators. Some notable genetic findings that may be associated with poor outcomes include: 13q deletion, 7q gain, ID3 and CCND3 double-hit mutations, and 18q21 CN-LOH mutations. The prognosis for Burkitt lymphoma can be better determined following staging utilizing imaging modalities such as positron emission tomography and computed tomography scans where tumor burden and invasion of the central nervous system have been found to indicate a poor prognosis.

Epidemiology
As a non-Hodgkin lymphoma (NHL), Burkitt lymphoma makes up 1-5% of cases, and it is more common in males than females with a 3–4 to 1 ratio. The endemic variant mainly impacts areas with an increased prevalence of malaria and EBV in Africa and Papua New Guinea. For children less than 18 years of age from equatorial Africa, the annual incidence of Burkitt lymphoma is 4–5/100,000. Additionally, in equatorial Africa, 50% of tumors that are diagnosed during childhood as well as 90% of lymphoma cases can be attributed to Burkitt lymphoma. The peak incidence for endemic Burkitt lymphoma is from ages 4 to 7 with an average age of 6 years </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 Interstitial nephritis and can you explain it in depth? [/INST] Interstitial nephritis, also known as tubulointerstitial nephritis, is inflammation of the area of the kidney known as the renal interstitium, which consists of a collection of cells, extracellular matrix, and fluid surrounding the renal tubules. In addition to providing a scaffolding support for the tubular architecture, the interstitium has been shown to participate in the fluid and electrolyte exchange as well as endocrine functions of the kidney.There are a variety of known factors that can provoke the inflammatory process within the renal interstitium, including pharmacologic, environmental, infectious and systemic disease contributors. The spectrum of disease presentation can range from an acute process to a chronic condition with progressive tubular cell damage and renal dysfunction.

Signs and symptoms
Interstitial nephritis may present with a variety of signs and symptoms, many of these nonspecific. Fever is the most common, occurring in 30-50% of patients, particularly those with drug-induced interstitial nephritis. Other general symptoms that occur with variable frequency include nausea, vomiting, fatigue, lack of appetite, and weight loss. More specific symptoms, such as flank pain, pain with urination, and visible blood in the urine, as well as signs like hypertension can be helpful in increasing suspicion for the diagnosis. The "classic" triad of symptoms reported in early documented cases consisted of rash, joint pain, and increased eosinophils in the blood; however, more recent epidemiology suggests that this grouping of symptoms only occurs in a small minority (5-10%) of patients.  With modern drugs causing between 70 and 90% of current cases, the possibility of a change in presentation exists.

Causes
Common causes include infection, or reaction to medication such as an analgesic, anti-inflammatory, or antibiotics such as methicillin (meticillin). Reaction to medications causes 71% to 92% of cases.

Drugs
This disease is also caused by other diseases and toxins that damage the kidney. Both acute and chronic tubulointerstitial nephritis can be caused by a bacterial infection in the kidneys known as pyelonephritis, but the most common cause is by an adverse reaction to a medication. The medications that are known to cause this sort of reaction are β-lactam antibiotics such as penicillin
and cephalexin, and nonsteroidal anti-inflammatory drugs (aspirin less frequently than others), as well as proton-pump inhibitors, rifampicin, sulfa medications, fluoroquinolones, diuretics, allopurinol, mesalamine, and phenytoin.  The time between exposure to the drug and the development of acute tubulointerstitial nephritis can be anywhere from 5 days to 5 months (fenoprofen-induced).

Diagnosis
The condition can appear without symptoms. When present they may appear widely varied and can occur rapidly or gradually.When caused by an allergic reaction, the symptoms of acute tubulointerstitial nephritis are fever (27% of patients), rash (15% of patients), and enlarged kidneys.  Some people experience dysuria, and lower back pain.
In chronic tubulointerstitial nephritis the patient can experience symptoms such as nausea, vomiting, fatigue, and weight loss.  Other conditions that may develop include a high concentration of potassium in the blood, metabolic acidosis, and kidney failure.

Blood tests
About 23% of patients have a high level of eosinophils in the blood.

Urinary findings
Urinary findings include:

Eosinophiluria: Original studies with Methicillin-induced AIN showed sensitivity of 67% and specificity of 83%. The sensitivity is higher in patients with interstitial nephritis induced by methicillin or when the Hansels stain is used. However, a 2013 study showed that the sensitivity and specificity of urine eosinophil testing are 35.6% and 68% respectively.
Isosthenuria
Blood in the urine and occasional RBC casts
Sterile pyuria: white blood cells and no bacteria. About 50% of patients with AIN have pyuria.
Nephrotic-range amount of protein in the urine may be seen with NSAID-associated AIN. Low grade proteinuria may be seen in a majority of other causes of AIN.
White blood cell (WBC) casts: Fewer than one in five patients with AIN have WBC casts in urine.

Pathology
While non-invasive patient evaluation (physical examination, blood and urine testing, imaging studies) can be suggestive, the only way to definitively diagnosis interstitial nephritis is with a tissue diagnosis obtained by kidney biopsy. Pathologic examination will reveal the presence of interstitial edema and inflammatory infiltration with various white blood cells, including neutrophils, eosinophils, and lymphocytes. Generally, blood vessels and glomeruli are not affected. Electron microscopy shows mitochondrial damage in the tubular epithelial cells, vacuoles in the cytoplasm, and enlarged endoplasmic reticulum.

Gallium scan
The sensitivity of an abnormal gallium scan has been reported to range from 60% to 100%. A study of Gallium scan in 76 patients [23 with AIN, 8 with biopsy-proven AIN] showed an AUC of 0.75.

Novel biomarkers
Given the challenges with clinical diagnosis of AIN due to lack of clinical features and lack of accuracy of existing tests, there has been significant interest in identifying non-invasive biomarkers for this disease. One study showed that monocyte chemotactic protein-1 (chemokine CCL-2) and neutrophil gelatinase associated lipocalin (NGAL) were higher in patients with AIN than in controls (in this case healthy participants). A more recent study, showed that urine cytokines interleukin-9 and tumor necrosis factor-α were higher in patients with AIN than in controls without AIN who underwent a biopsy for evaluation of acute kidney injury and showed an AUC of 0.79 </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 Abnormal posturing and can you explain it in depth? [/INST] Abnormal posturing is an involuntary flexion or extension of the arms and legs, indicating severe brain injury. It occurs when one set of muscles becomes incapacitated while the opposing set is not, and an external stimulus such as pain causes the working set of muscles to contract. The posturing may also occur without a stimulus. Since posturing is an important indicator of the amount of damage that has occurred to the brain, it is used by medical professionals to measure the severity of a coma with the Glasgow Coma Scale (for adults) and the Pediatric Glasgow Coma Scale (for infants).
The presence of abnormal posturing indicates a severe medical emergency requiring immediate medical attention. Decerebrate and decorticate posturing are strongly associated with poor outcome in a variety of conditions. For example, near-drowning patients that display decerebrate or decorticate posturing have worse outcomes than those that do not. Changes in the condition of the patient may cause alternation between different types of posturing.

Types
Three types of abnormal posturing are decorticate posturing, with the arms flexed over the chest; decerebrate posturing, with the arms extended at the sides; and opisthotonus, in which the head and back are arched backward.

Decorticate
Decorticate posturing is also called decorticate response, decorticate rigidity, flexor posturing, or, colloquially, "mummy baby". Patients with decorticate posturing present with the arms flexed, or bent inward on the chest, the hands are clenched into fists, and the legs extended and feet turned inward. A person displaying decorticate posturing in response to pain gets a score of three in the motor section of the Glasgow Coma Scale, caused by the flexion of muscles due to the neuro-muscular response to the trauma.There are two parts to decorticate posturing.

The first is the disinhibition of the red nucleus with facilitation of the rubrospinal tract. The rubrospinal tract facilitates motor neurons in the cervical spinal cord supplying the flexor muscles of the upper extremities. The rubrospinal tract and medullary reticulospinal tract biased flexion outweighs the medial and lateral vestibulospinal and pontine reticulospinal tract biased extension in the upper extremities.
The second component of decorticate posturing is the disruption of the lateral corticospinal tract which facilitates motor neurons in the lower spinal cord supplying flexor muscles of the lower extremities. Since the corticospinal tract is interrupted, the pontine reticulospinal and the medial and lateral vestibulospinal biased extension tracts greatly overwhelm the medullary reticulospinal biased flexion tract.The effects on these two tracts (corticospinal and rubrospinal) by lesions above the red nucleus is what leads to the characteristic flexion posturing of the upper extremities and extensor posturing of the lower extremities.Decorticate posturing indicates that there may be damage to areas including the cerebral hemispheres, the internal capsule, and the thalamus. It may also indicate damage to the midbrain. While decorticate posturing is still an ominous sign of severe brain damage, decerebrate posturing is usually indicative of more severe damage at the rubrospinal tract, and hence, the red nucleus is also involved, indicating a lesion lower in the brainstem.

Decerebrate
Decerebrate posturing is also called decerebrate response, decerebrate rigidity, or extensor posturing. It describes the involuntary extension of the upper extremities in response to external stimuli. In decerebrate posturing, the head is arched back, the arms are extended by the sides, and the legs are extended. A hallmark of decerebrate posturing is extended elbows. The arms and legs are extended and rotated internally. The patient is rigid, with the teeth clenched. The signs can be present on only one side of the body or on both sides, and they may be present just in the arms, and they may be intermittent.A person displaying decerebrate posturing in response to pain receives a score of two in the motor section of the Glasgow Coma Scale (for adults) and the Pediatric Glasgow Coma Scale (for infants), due to the muscles extending because of the neuro-muscular response to the trauma.Decerebrate posturing indicates brain stem damage, specifically damage below the level of the red nucleus (e.g. mid-collicular lesion). It is exhibited by people with lesions or compression in the midbrain and lesions in the cerebellum. Decerebrate posturing is commonly seen in pontine strokes. A patient with decorticate posturing may begin to show decerebrate posturing, or may go from one form of posturing to the other </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 Bleeding and can you explain it in depth? [/INST] Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, vagina or anus, or through a puncture in the skin.
Hypovolemia is a massive decrease in blood volume, and death by excessive loss of blood is referred to as exsanguination. Typically, a healthy person can endure a loss of 10–15% of the total blood volume without serious medical difficulties (by comparison, blood donation typically takes 8–10% of the donors blood volume). The stopping or controlling of bleeding is called hemostasis and is an important part of both first aid and surgery.

Types
Upper head
Intracranial hemorrhage – bleeding in the skull.
Cerebral hemorrhage – a type of intracranial hemorrhage, bleeding within the brain tissue itself.
Intracerebral hemorrhage – bleeding in the brain caused by the rupture of a blood vessel within the head. See also hemorrhagic stroke.
Subarachnoid hemorrhage (SAH) implies the presence of blood within the subarachnoid space from some pathologic process. The common medical use of the term SAH refers to the nontraumatic types of hemorrhages, usually from rupture of a berry aneurysm or arteriovenous malformation (AVM). The scope of this article is limited to these nontraumatic hemorrhages.
Eyes
Subconjunctival hemorrhage – bloody eye arising from a broken blood vessel in the sclera (whites of the eyes). Often the result of strain, including sneezing, coughing, vomiting or other kind of strain
Nose

Epistaxis – nosebleed
Mouth
Tooth eruption – losing a tooth
Hematemesis – vomiting fresh blood
Hemoptysis – coughing up blood from the lungs
Lungs
Pulmonary hemorrhage
Gastrointestinal
Upper gastrointestinal bleed
Lower gastrointestinal bleed
Occult gastrointestinal bleed
Urinary tract
Hematuria – blood in the urine from urinary bleeding
Gynecologic
Vaginal bleeding
Postpartum hemorrhage
Breakthrough bleeding
Ovarian bleeding – This is a potentially catastrophic and not so rare complication among lean patients with polycystic ovary syndrome undergoing transvaginal oocyte retrieval.
Anus
Melena – upper gastrointestinal bleeding
Hematochezia – lower gastrointestinal bleeding, or brisk upper gastrointestinal bleeding
Vascular
Ruptured aneurysm
Aortic transection
Iatrogenic injury

Causes
Bleeding arises due to either traumatic injury, underlying medical condition, or a combination.

Traumatic injury
Traumatic bleeding is caused by some type of injury. There are different types of wounds which may cause traumatic bleeding. These include:
Abrasion – Also called a graze, this is caused by transverse action of a foreign object against the skin, and usually does not penetrate below the epidermis.
Excoriation – In common with Abrasion, this is caused by mechanical destruction of the skin, although it usually has an underlying medical cause.
Hematoma – Caused by damage to a blood vessel that in turn causes blood to collect in an enclosed area.
Laceration – Irregular wound caused by blunt impact to soft tissue overlying hard tissue or tearing such as in childbirth. In some instances, this can also be used to describe an incision.
Incision – A cut into a body tissue or organ, such as by a scalpel, made during surgery.
Puncture Wound – Caused by an object that penetrated the skin and underlying layers, such as a nail, needle or knife.
Contusion – Also known as a bruise, this is a blunt trauma damaging tissue under the surface of the skin.
Crushing Injuries – Caused by a great or extreme amount of force applied over a period of time. The extent of a crushing injury may not immediately present itself.
Ballistic Trauma – Caused by a projectile weapon such as a firearm. This may include two external wounds (entry and exit) and a contiguous wound between the two.The pattern of injury, evaluation and treatment will vary with the mechanism of the injury. Blunt trauma causes injury via a shock effect; delivering energy over an area. Wounds are often not straight and unbroken skin may hide significant injury. Penetrating trauma follows the course of the injurious device. As the energy is applied in a more focused fashion, it requires less energy to cause significant injury. Any body organ, including bone and brain, can be injured and bleed. Bleeding may not be readily apparent; internal organs such as the liver, kidney and spleen may bleed into the abdominal cavity. The only apparent signs may come with blood loss. Bleeding from a bodily orifice, such as the rectum, nose, or ears may signal internal bleeding, but cannot be relied upon. Bleeding from a medical procedure also falls into this category.

Medical condition
"Medical bleeding" denotes hemorrhage as a result of an underlying medical condition (i.e. causes of bleeding that are not directly due to trauma). Blood can escape from blood vessels as a result of 3 basic patterns of injury:
Intravascular changes – changes of the blood within vessels (e.g. ↑ blood pressure, ↓ clotting factors)
Intramural changes – changes arising within the walls of blood vessels (e.g. aneurysms, dissections, AVMs, vasculitides)
Extravascular changes – changes arising outside blood vessels (e.g. H pylori infection, brain abscess, brain tumor)The underlying scientific basis for blood clotting and hemostasis is discussed in detail in the articles, coagulation, hemostasis and related articles. The discussion here is limited to the common practical aspects of blood clot formation which manifest as bleeding.
Some medical conditions can also make patients susceptible to bleeding. These are conditions that affect the normal hemostatic (bleeding-control) functions of the body. Such conditions either are, or cause, bleeding diatheses. Hemostasis involves several components. The main components of the hemostatic system include platelets and the coagulation system.
Platelets are small blood components that form a plug in the blood vessel wall that stops bleeding. Platelets also produce a variety of substances that stimulate the production of a blood clot. One of the most common causes of increased bleeding risk is exposure to nonsteroidal anti-inflammatory drugs (NSAIDs). The prototype for these drugs is aspirin, which inhibits the production of thromboxane. NSAIDs inhibit the activation of platelets, and thereby increase the risk of bleeding. The effect of aspirin is irreversible; therefore, the inhibitory effect of aspirin is present until the platelets have been replaced (about ten days). Other NSAIDs, such as "ibuprofen" (Motrin) and related drugs, are reversible and therefore, the effect on platelets is not as long-lived.There are several named coagulation factors that interact in a complex way to form blood clots, as discussed in the article on coagulation. Deficiencies of coagulation factors are associated with clinical bleeding. For instance, deficiency of Factor VIII causes classic hemophilia A while deficiencies of Factor IX cause "Christmas disease"(hemophilia B). Antibodies to Factor VIII can also inactivate the Factor VII and precipitate bleeding that is very difficult to control. This is a rare condition that is most likely to occur in older patients and in those with autoimmune diseases. Another common bleeding disorder is Von Willebrand disease. It is caused by a deficiency or abnormal function of the "Von Willebrand" factor, which is involved in platelet activation. Deficiencies in other factors, such as factor XIII or factor VII are occasionally seen, but may not be associated with severe bleeding and are not as commonly diagnosed.
In addition to NSAID-related bleeding, another common cause of bleeding is that related to the medication, warfarin ("Coumadin" and others). This medication needs to be closely monitored as the bleeding risk can be markedly increased by interactions with other medications. Warfarin acts by inhibiting the production of Vitamin K in the gut. Vitamin K is required for the production of the clotting factors, II, VII, IX, and X in the liver. One of the most common causes of warfarin-related bleeding is taking antibiotics. The gut bacteria make vitamin K and are killed by antibiotics. This decreases vitamin K levels and therefore the production of these clotting factors.
Deficiencies of platelet function may require platelet transfusion while deficiencies of clotting factors may require transfusion of either fresh frozen plasma or specific clotting factors, such as Factor VIII for patients with hemophilia.

Infection
Infectious diseases such as Ebola, Marburg virus disease and yellow fever can cause bleeding.

Diagnosis/Imaging
Dioxaborolane chemistry enables radioactive fluoride (18F) labeling of red blood cells, which allows for positron emission tomography (PET) imaging of intracerebral hemorrhages.

Classification
Blood loss
Hemorrhaging is broken down into four classes by the American College of Surgeons advanced trauma life support (ATLS).
Class I Hemorrhage involves up to 15% of blood volume. There is typically no change in vital signs and fluid resuscitation is not usually necessary.
Class II Hemorrhage involves 15-30% of total blood volume. A patient is often tachycardic (rapid heart beat) with a reduction in the difference between the systolic and diastolic blood pressures. The body attempts to compensate with peripheral vasoconstriction. Skin may start to look pale and be cool to the touch. The patient may exhibit slight changes in behavior. Volume resuscitation with crystalloids (Saline solution or Lactated Ringers solution) is all that is typically required. Blood transfusion is not usually required.
Class III Hemorrhage involves loss of 30-40% of circulating blood volume </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 Object 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 Malingering and can you explain it in depth? [/INST] Malingering is the fabrication, feigning, or exaggeration of physical or psychological symptoms designed to achieve a desired outcome, such as relief from duty or work.Malingering is not a medical diagnosis, but may be recorded as a "focus of clinical attention" or a "reason for contact with health services". Malingering is categorized as distinct from other forms of excessive illness behavior such as somatization disorder and factitious disorder, although not all mental health professionals agree with this formulation.Failure to detect actual cases of malingering imposes an economic burden on health care systems, workers compensation programs, and disability programs, such as Social Security Disability Insurance and veterans disability benefits. False accusations of malingering often harm genuine patients or claimants.

History
Antiquity
According to 1 Samuel in the Old Testament, King David feigned madness to Achish, the king of the Philistines </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 Dysphagia and can you explain it in depth? [/INST] Dysphagia is difficulty in swallowing. Although classified under "symptoms and signs" in ICD-10, in some contexts it is classified as a condition in its own right.It may be a sensation that suggests difficulty in the passage of solids or liquids from the mouth to the stomach, a lack of pharyngeal sensation or various other inadequacies of the swallowing mechanism. Dysphagia is distinguished from other symptoms including odynophagia, which is defined as painful swallowing, and globus, which is the sensation of a lump in the throat. A person can have dysphagia without odynophagia (dysfunction without pain), odynophagia without dysphagia (pain without dysfunction) or both together. A psychogenic dysphagia is known as phagophobia.

Classification
Dysphagia is classified into the following major types:
Oropharyngeal dysphagia
Esophageal and obstructive dysphagia
Neuromuscular symptom complexes
Functional dysphagia is defined in some patients as having no organic cause for dysphagia that can be found.

Signs and symptoms
Some patients have limited awareness of their dysphagia, so lack of the symptom does not exclude an underlying disease. When dysphagia goes undiagnosed or untreated, patients are at a high risk of pulmonary aspiration and subsequent aspiration pneumonia secondary to food or liquids going the wrong way into the lungs. Some people present with "silent aspiration" and do not cough or show outward signs of aspiration. Undiagnosed dysphagia can also result in dehydration, malnutrition, and kidney failure.Some signs and symptoms of oropharyngeal dysphagia include difficulty controlling food in the mouth, inability to control food or saliva in the mouth, difficulty initiating a swallow, coughing, choking, frequent pneumonia, unexplained weight loss, gurgly or wet voice after swallowing, nasal regurgitation, and patient complaint of swallowing difficulty. When asked where the food is getting stuck, patients will often point to the cervical (neck) region as the site of the obstruction. The actual site of obstruction is always at or below the level at which the level of obstruction is perceived.The most common symptom of esophageal dysphagia is the inability to swallow solid food, which the patient will describe as becoming stuck or held up before it either passes into the stomach or is regurgitated. Pain on swallowing or odynophagia is a distinctive symptom that can be highly indicative of carcinoma, although it also has numerous other causes that are not related to cancer. Achalasia is a major exception to usual pattern of dysphagia in that swallowing of fluid tends to cause more difficulty than swallowing solids. In achalasia, there is idiopathic destruction of parasympathetic ganglia of the Auerbachs (Myenteric) plexus of the entire esophagus, which results in functional narrowing of the lower esophagus, and peristaltic failure throughout its length.

Complications
Complications of dysphagia may include aspiration, pneumonia, dehydration, and weight loss.

Cause
Following table enumerates possible causes of dysphagia:

Difficulty with or inability to swallow may be caused or exacerbated by usage of opiate and/or opioid drugs.

Diagnosis
Esophagoscopy and laryngoscopy can give direct view of lumens.
Esophageal motility study is useful in cases of esophageal achalasia and diffuse esophageal spasms.
Exfoliative cytology can be performed on esophageal lavage obtained by esophagoscopy. It can detect malignant cells in early stage.
Ultrasonography and CT scan are not very useful in finding causes of dysphagia, but can detect masses in mediastinum and aortic aneurysms.
FEES (Fibreoptic endoscopic evaluation of swallowing), sometimes with sensory evaluation, is done usually by a Medical Speech Pathologist or Deglutologist. This procedure involves the patient eating different consistencies as above.
Swallowing sounds and vibrations could be potentially used for dysphagia screening, but these approaches are in the early research stages.

Differential diagnosis
All causes of dysphagia are considered as differential diagnoses. Some common ones are:
Esophageal atresia
Paterson-Kelly syndrome
Zenkers diverticulum
Esophageal varices
Benign strictures
Achalasia
Esophageal diverticula
Scleroderma
Diffuse esophageal spasm
Polymyositis
Webs and rings
Esophageal cancer
Eosinophilic esophagitis
Hiatus hernia, especially paraesophageal type
Dysphagia lusoria
Stroke
Fahrs disease
Wernicke encephalopathy
Charcot–Marie–Tooth disease
Parkinsons disease
Multiple sclerosis
Amyotrophic lateral sclerosis
Rabies
Cervical SpondylosisEsophageal dysphagia is almost always caused by disease in or adjacent to the esophagus but occasionally the lesion is in the pharynx or stomach. In many of the pathological conditions causing dysphagia, the lumen becomes progressively narrowed and indistensible. Initially, only fibrous solids cause difficulty but later the problem can extend to all solids and later even to liquids. Patients with difficulty swallowing may benefit from thickened fluids if the person is more comfortable with those liquids, although, so far, there is no scientific study that proves that those thickened liquids are beneficial.
Dysphagia may manifest as the result of autonomic nervous system pathologies including stroke and ALS, or due to rapid iatrogenic correction of an electrolyte imbalance.In older adults, presbyphagia - the normal healthy changes in swallowing associated with age - should be considered as an alternative explanation for symptoms.

Treatments
There are many ways to treat dysphagia, such as swallowing therapy, dietary changes, feeding tubes, certain medications, and surgery. Treatment for dysphagia is managed by a group of specialists known as a multidisciplinary team. Members of the multidisciplinary team include: a speech language pathologist specializing in swallowing disorders (swallowing therapist), primary physician, gastroenterologist, nursing staff, respiratory therapist, dietitian, occupational therapist, physical therapist, pharmacist, and radiologist. The role of the members of the multidisciplinary team will differ depending on the type of swallowing disorder present. For example, the swallowing therapist will be directly involved in the treatment of a patient with oropharyngeal dysphagia, while a gastroenterologist will be directly involved in the treatment of an esophageal disorder.

Treatment strategies
The implementation of a treatment strategy should be based on a thorough evaluation by the multidisciplinary team. Treatment strategies will differ on a patient to patient basis and should be structured to meet the specific needs of each individual patient. Treatment strategies are chosen based on a number of different factors including diagnosis, prognosis, reaction to compensatory strategies, severity of dysphagia, cognitive status, respiratory function, caregiver support, and patient motivation and interest.

Oral vs. nonoral feeding
Adequate nutrition and hydration must be preserved at all times during dysphagia treatment. The overall goal of dysphagia therapy is to maintain or return the patient to, oral feeding. However, this must be done while ensuring adequate nutrition and hydration and a safe swallow (no aspiration of food into the lungs) </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 Kidney disease and can you explain it in depth? [/INST] Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an inflammatory kidney disease and has several types according to the location of the inflammation. Inflammation can be diagnosed by blood tests. Nephrosis is non-inflammatory kidney disease. Nephritis and nephrosis can give rise to nephritic syndrome and nephrotic syndrome respectively. Kidney disease usually causes a loss of kidney function to some degree and can result in kidney failure, the complete loss of kidney function. Kidney failure is known as the end-stage of kidney disease, where dialysis or a kidney transplant is the only treatment option.
Chronic kidney disease is defined as prolonged kidney abnormalities (functional and/or structural in nature) that last for more than three months. Acute kidney disease is now termed acute kidney injury and is marked by the sudden reduction in kidney function over seven days. In 2007, about one in eight Americans had chronic kidney disease. This rate is increasing over time to where about 1 in 7 Americans are estimated to have CKD as of 2021.With the increasing prevalence of chronic kidney disease, there are many treatment plans available. Individuals can get blood or urine tests to access the health and function of the kidneys. For severe kidney disease, dialysis and kidney transplants are the most popular options. Dialysis is a treatment where it acts as an artificial kidney and removes waste products and fluid from an individuals blood. This is accomplished via a machine. Kidney transplants are the surgical procedure of transporting a healthy kidney from a donor into an individual with kidney disease. Both of these options have their pros and con, the success varies by individual.

Causes
Causes of kidney disease include deposition of the Immunoglobulin A antibodies in the glomerulus, administration of analgesics, xanthine oxidase deficiency, toxicity of chemotherapy agents, and long-term exposure to lead or its salts. Chronic conditions that can produce nephropathy include systemic lupus erythematosus, diabetes mellitus and high blood pressure (hypertension), which lead to diabetic nephropathy and hypertensive nephropathy, respectively.

Analgesics
One cause of nephropathy is the long term usage of pain medications known as analgesics. The pain medicines which can cause kidney problems include aspirin, acetaminophen, and nonsteroidal anti-inflammatory drugs (NSAIDs).  This form of nephropathy is "chronic analgesic nephritis," a chronic inflammatory change characterized by loss and atrophy of tubules and interstitial fibrosis and inflammation (BRS Pathology, 2nd edition).
Specifically, long-term use of the analgesic phenacetin has been linked to renal papillary necrosis (necrotizing papillitis).

Diabetes
Diabetic nephropathy is a progressive kidney disease caused by angiopathy of the capillaries in the glomeruli. It is characterized by nephrotic syndrome and diffuse scarring of the glomeruli. It is particularly associated with poorly managed diabetes mellitus and is a primary reason for dialysis in many developed countries. It is classified as a small blood vessel complication of diabetes.

Autosomal dominant polycystic kidney disease
Gabow 1990 talks about Autosomal Dominant Polycystic Kidney disease and how this disease is genetic. They go on to say "Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disease, affecting a half million Americans. The clinical phenotype can result from at least two different gene defects. One gene that can cause ADPKD has been located on the short arm of chromosome 16." The same article also goes on to say that millions of Americans are effected by this disease and is very common.

Long COVID and Kidney Disease
Yende & Parikh 2021 talk about the effects that COVID can have on a person that has a pre-existing health issue regarding kidney diseases. "frailty, chronic diseases, disability and immunodeficiency are at increased risk of kidney disease and progression to kidney failure, and infection with SARS-CoV-2 can further increase this risk” (Long COVID and Kidney Disease, 2021).

Diet
Higher dietary intake of animal protein, animal fat, and cholesterol may increase risk for microalbuminuria, a sign of kidney function decline, and generally, diets higher in fruits, vegetables, and whole grains but lower in meat and sweets may be protective against kidney function decline. This may be because sources of animal protein, animal fat, and cholesterol, and sweets are more acid-producing, while fruits, vegetables, legumes, and whole grains are more base-producing.

IgA nephropathy
IgA nephropathy is the most common glomerulonephritis throughout the world  Primary IgA nephropathy is characterized by deposition of the IgA antibody in the glomerulus. The classic presentation (in 40-50% of the cases) is episodic frank hematuria which usually starts within a day or two of a non-specific upper respiratory tract infection (hence synpharyngitic) as opposed to post-streptococcal glomerulonephritis which occurs some time (weeks) after initial infection. Less commonly gastrointestinal or urinary infection can be the inciting agent. All of these infections have in common the activation of mucosal defenses and hence IgA antibody production.

Iodinated contrast media
Kidney disease induced by iodinated contrast media (ICM) is called CIN (= contrast induced nephropathy) or contrast-induced AKI (= acute kidney injury). Currently, the underlying mechanisms are unclear. But there is a body of evidence that several factors including apoptosis-induction seem to play a role.

Lithium
Lithium, a medication commonly used to treat bipolar disorder and schizoaffective disorders, can cause nephrogenic diabetes insipidus; its long-term use can lead to nephropathy.

Lupus
Despite expensive treatments, lupus nephritis remains a major cause of morbidity and mortality in people with relapsing or refractory lupus nephritis.

Xanthine oxidase deficiency
Another possible cause of Kidney disease is due to decreased function of xanthine oxidase in the purine degradation pathway. Xanthine oxidase will degrade hypoxanthine to xanthine and then to uric acid. Xanthine is not very soluble in water; therefore, an increase in xanthine forms crystals (which can lead to kidney stones) and result in damage to the kidney. Xanthine oxidase inhibitors, like allopurinol, can cause nephropathy.

Polycystic disease of the kidneys
Additional possible cause of nephropathy is due to the formation of cysts or pockets containing fluid within the kidneys. These cysts become enlarged with the progression of aging causing renal failure. Cysts may also form in other organs including the liver, brain, and ovaries. Polycystic Kidney Disease is a genetic disease caused by mutations in the PKD1, PKD2, and PKHD1 genes. This disease affects about half a million people in the US. Polycystic kidneys are susceptible to infections and cancer.

Toxicity of chemotherapy agents
Nephropathy can be associated with some therapies used to treat cancer.  The most common form of kidney disease in cancer patients is Acute Kidney Injury (AKI) which can usually be due to volume depletion from vomiting and diarrhea that occur following chemotherapy or occasionally due to kidney toxicities of chemotherapeutic agents.  Kidney failure from break down of cancer cells, usually after chemotherapy, is unique to onconephrology. Several chemotherapeutic agents, for example Cisplatin, are associated with acute and chronic kidney injuries. Newer agents such as anti Vascular Endothelial Growth Factor (anti VEGF) are also associated with similar injuries, as well as proteinuria, hypertension and thrombotic microangiopathy.

Diagnosis
The standard diagnostic workup of suspected kidney disease includes a medical history, physical examination, a urine test, and an ultrasound of the kidneys (renal ultrasonography). An ultrasound is essential in the diagnosis and management of kidney disease.

Treatment
Treatment approaches for kidney disease focus on managing the symptoms, controlling the progression, and also treating co-morbidities that a person may have.

Dialysis
Transplantation
Millions of people across the world have kidney disease. Of those millions, several thousand will need dialysis or a kidney transplant at its end-stage. In the United States, as of 2008, 16,500 people needed a kidney transplant. Of those, 5,000 died while waiting for a transplant. Currently, there is a shortage of donors, and in 2007 there were only 64,606 kidney transplants in the world. This shortage of donors is causing countries to place monetary value on kidneys </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 Pseudallescheria boydii and can you explain it in depth? [/INST] Pseudallescheria boydii is a species of fungus classified in the Ascomycota. It is associated with some forms of eumycetoma/maduromycosis and is the causative agent of pseudallescheriasis. Typically found in stagnant and polluted water, it has been implicated in the infection of immunocompromised and near-drowned pneumonia patients. Treatment of infections with P. boydii is complicated by  resistance to many of the standard antifungal agents normally used to treat infections by filamentous fungi.Pseudallescheria boydii fungal infection was the cause of death in three athletes submerged in the Yarkon River after a bridge collapsed during the 1997 Maccabiah Games.

Taxonomy
The fungus was originally described by American mycologist Cornelius Lott Shear in 1922 as a species of Allescheria. Shear obtained cultures from a patient of the Medical Department of the University of Texas. The microbe was apparently associated with a penetrating thorn the patient had incurred in his ankle while running barefoot 12 years before. The diseased area was found to contain hyphae-containing granules that, when cultured, led to the growth of the organism. Shear considered the fungus most closely related to Eurotiopsis gayoni (now called Allescheria gayoni). The specific epithet boydii refers to Dr. Mark F. Boyd, who sent Lott the specimen. David Malloch moved the species to the newly created genus Petriellidium in 1970. The genus name of Petriellidium was in honour of Lionello Petri (1875-1946), who was an Italian botanist (Mycology) and Phytopathologist from Florence. The species was then transferred to the genus Pseudallescheria in 1982 when examination of the type specimens of Petriellidium and Pseudallescheria revealed that they were the same genus.

Ecology
An ability to tolerate minimal aeration and high osmotic pressure enables P. boydii to grow on soil, polluted and stagnant water and manure. Although this fungus is commonly found in temperate climates, it is thermotolerant and can survive in tropical climates and in environments with low oxygen pressure. Growth of P. boydii  can be seen in environments where nitrogen-containing compounds are common, usually due to human pollution. Its ability to use natural gas and other volatile organic compounds suggests a capacity for bioremediation.

Growth and morphology
Pseudallescheria boydii is a saprotrophic fungus with broad hyphae growing up to 2–5 μm in width. Colonies change in colour from white to pale brown and develop a cottony texture with maturity. After a 2–3 week incubation period, cleistothecia may form containing asci filled with eight fusiform, one-celled ascospores measuring 12–18 × 9–13 μm in diameter. This fungus grows on most standard media, maturing in 7 days. Its primary nutrients are the sugars xylose, arabinose, glucose, sucrose, ribitol, xylitol and L-arabinitol. It cannot assimilate maltose or lactose; however, it is able to assimilate urea, asparagine, potassium nitrate and ammonium nitrate. The optimal temperature for growth is 25 °C (77 °F) and the fungus is generally considered to be mesophilic, although it can grow at higher temperatures (up to 37 °C (99 °F)) as well. Asexual reproduction manifests in one of two forms: the Scedosporium type (the most common type) and the Graphium type. Scedosporium apiospermum forms greyish-white colonies with a grey-black reverse. The conidia are single-celled, pale brown and oval in form. Their size ranges from 4–9 x 6–10 μm and their development is annellidic.

Pathogenicity
Pseudallescheria boydii is an emerging opportunistic pathogen. Immune response is characterized by TLR2 recognition of P. boydii derived α-glucans, while TLR4 mediates the recognition of P. boydii derived rhamnomannans. Human infection takes one of two forms: mycetoma (99% of infections), a chronic, subcutaneous disease, and pseudallescheriasis, which includes all other forms of the disease commonly presented in the central nervous system, lungs, joints and bone. The former can also be distinguished by the presence of sclerotia, or granules, which are typically absent in pseudallescheriasis-type infections. Infection is initiated via inhalation or traumatic implantation in the skin.  Infection can lead to arthritis, otitis, endocarditis, sinusitis, and other manifestations. Masses of hyphae can form "fungus balls" in the lungs. While "fungus balls" can also form in other organs, they are commonly derived from host necrotic tissue resulting from nodular infarction and thrombosis of lung vessels following infection.This species is second in prevalence after Aspergillus fumigatus as a fungal pathogen in cystic fibrosis patients. It causes allergic bronchopulmonary disease and chronic lung lesions that resemble aspergillosis. Infections can also occur in immunocompetent individuals, usually in the lungs and upper respiratory tract. Infections in the CNS, which are rare, present as neutrophilic meningitis or multiple brain abscesses and have a mortality rate of up to 75%. Infections have also been observed in animals, notably corneal infection, abdominal mycetoma and disseminated infections in dogs and horses. Transient colonization is more likely than disease. However, invasive pseudoallescheriasis can be found in patients with prolonged neutropenia, high-dose corticosteroid therapy and allotransplantation of bone marrow. Pseudallescheria boydii has also been implicated in pneumonia subsequent to near-drowning events with infection developing anywhere between a few weeks to several months after exposure yielding high mortality. Dissemination of the organism to the central nervous system has been observed in some cases. This species is also known as a non-invasive colonist of the external ear and airways of patients with poor lung or sinus clearance, and the first documented case of human pseudallescheriasis involved the ear canal. It has also been implicated in infection of joints following traumatic injury, and these infections can progress to osteomyelitis. Infections of the skin and cornea have also been reported. Typical host-related risk factors for infection include lymphopenia, steroid treatment, serum albumin levels of < 3 mg/dL and neutropenia.

Diagnosis
Detection and diagnosis of S. apiospermum is possible through isolation of the fungus in culture or through cytology and histopathology in the tissues of diseased individuals. In mycetoma-type infections, a confluence of symptoms is necessary for diagnosis, including tumefaction, draining sinuses and extrusion of grains. Furthermore, P. boydii grains and hyphae should be cultured and observed microscopically after staining with H&E, periodic acid–Schiff stain, Tissue Gram or Grocotts methenamine silver stain. A radiological diagnosis may be helpful in elucidating the extent of the disease in terms of bone and soft tissue involvement. Scedosporium-caused eumycetomas have been found to have thick-walled cavities and grains appearing as hyperreflective echoes on scans, while actinomycetomas show fine echoes at the bottom of cavities.Direct detection is possible in samples histochemically stained in 20% KOH followed by fluorescence microscopy with antibody. The characteristic shape, texture and colour of tissues can help identify S. apiospermum grains, which are often surrounded by an eosinophilic zone. Histopathologically, hyalohyphomycotic fungi like Scedosporium spp., Aspergillus spp., Fusarium spp. and Petriella spp. are similar in that they show septation of hyphae at regular intervals, have dichotomous branching and invade blood vessels. However, Scedosporium presents more irregular branching, sometimes with terminal or intercalary chlamydospores. In serum, Scedosporium infections can be detected by counterimmunoelectrophoresis. Molecular diagnostics appear to be promising in complementing current conventional diagnostic methods.Culture detection is accomplished by rinsing "grains" in 70% ethanol and sterile saline solution to avoid bacterial contamination prior to inoculation on growth medium. Selection of Scedosporium growth can be achieved on Leonians agar supplemented with 10 g/mL benomyl, or on media containing cycloheximide or amphotericin B. Optimal incubation is at a temperature of 25–35 °C (77–95 °F).

Treatment
Pseudallescheria boydii is resistant to amphotericin B and nearly all other antifungal drugs. Consequently, there is currently no consistently effective antifungal therapy for this agent </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 Polydipsia and can you explain it in depth? [/INST] Polydipsia is excessive thirst or excess drinking. The word derives from the Greek πολυδίψιος (poludípsios) "very thirsty", which is derived from πολύς (polús, "much, many") + δίψα (dípsa, "thirst").  Polydipsia is a nonspecific symptom in various medical disorders. It also occurs as an abnormal behaviour in some non-human animals, such as in birds.

Causes
Diabetes
Polydipsia can be characteristic of diabetes mellitus, often as an initial symptom. It is observed in cases of poorly controlled diabetes, which is sometimes the result of low patient adherence to anti-diabetic medication.Diabetes insipidus ("tasteless" diabetes, as opposed to diabetes mellitus) can also cause polydipsia.

Other physiological causes
It can also be caused by a change in the osmolality of the extracellular fluids of the body, hypokalemia, decreased blood volume (as occurs during major hemorrhage), and other conditions that create a water deficit. This is usually a result of osmotic diuresis.
Polydipsia is also a symptom of anticholinergic poisoning. Zinc is also known to reduce symptoms of polydipsia by causing the body to absorb fluids more efficiently (reduction of diarrhea, induces constipation) and it causes the body to retain more sodium; thus a zinc deficiency can be a possible cause. The combination of polydipsia and (nocturnal) polyuria is also seen in (primary) hyperaldosteronism (which often goes with hypokalemia).
Antipsychotics can have side effects such as dry mouth that may make the patient feel thirsty.

Primary polydipsia
Primary polydipsia describes excessive thirst and water intake caused in the absence of physiological stimuli to drink </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 Nephroptosis and can you explain it in depth? [/INST] Nephroptosis,  is rare and abnormal condition in which the kidney drops down into the pelvis when the patient stands up. It is more common in women than in men. It has been one of the most controversial conditions in terms of both its diagnosis and its treatments.

Symptoms and signs
Nephroptosis is asymptomatic in most persons. However, nephroptosis can be characterized by violent attacks of colicky flank pain, nausea, chills, hypertension, hematuria and proteinuria. Persons with symptomatic nephroptosis often complain of sharp pains that radiate into the groin. Many persons also suggest a weighing feeling on the abdomen. Pain is typically relieved by lying down. It is believed that flank pain on standing that is relieved by lying down is due to movement of the kidney causing intermittent renal tract obstruction </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 Mosaic (genetics) and can you explain it in depth? [/INST] Mosaicism or genetic mosaicism is a condition in multicellular organisms in which a single organism possesses more than one genetic line as the result of genetic mutation. This means that various genetic lines resulted from a single fertilized egg. Genetic mosaics may often be confused with chimerism, in which two or more genotypes arise in one individual similarly to mosaicism. In chimerism, though, the two genotypes arise from the fusion of more than one fertilized zygote in the early stages of embryonic development, rather than from a mutation or chromosome loss.
Genetic mosaicism can result from many different mechanisms including chromosome nondisjunction, anaphase lag, and endoreplication. Anaphase lagging is the most common way by which mosaicism arises in the preimplantation embryo. Mosaicism can also result from a mutation in one cell during development, in which case the mutation will be passed on only to its daughter cells (and will be present only in certain adult cells). Somatic mosaicism is not generally inheritable as it does not generally affect germ cells.

History
In 1929, Alfred Sturtevant studied mosaicism in Drosophila, a genus of fly. Muller in 1930 demonstrated that mosaicism in Drosophila is always associated with chromosomal rearrangements and Schultz in 1936 showed that in all cases studied these rearrangements were associated with heterochromatic inert regions, several hypotheses on the nature of such mosaicism were proposed. One hypothesis assumed that mosaicism appears as the result of a break and loss of chromosome segments. Curt Stern in 1935 assumed that the structural changes in the chromosomes took place as a result of somatic crossing, as a result of which mutations or small chromosomal rearrangements in somatic cells. Thus the inert region causes an increase in mutation frequency or small chromosomal rearrangements in active segments adjacent to inert regions.In the 1930s, Stern demonstrated that genetic recombination, normal in meiosis, can also take place in mitosis. When it does, it results in somatic (body) mosaics. These organisms contain two or more genetically distinct types of tissue. The term somatic mosaicism was used by CW Cotterman in 1956 in his seminal paper on antigenic variation.In 1944, Belgovskii proposed that mosaicism could not account for certain mosaic expressions caused by chromosomal rearrangements involving heterochromatic inert regions. The associated weakening of biochemical activity led to what he called a genetic chimera.

Types
Germline mosaicism
Germline or gonadal mosaicism is a particular form of mosaicism wherein some gametes—i.e., sperm or oocytes—carry a mutation, but the rest are normal. The cause is usually a mutation that occurred in an early stem cell that gave rise to all or part of the gametes.

Somatic mosaicism
Somatic mosaicism occurs when the somatic cells of the body are of more than one genotype. In the more common mosaics, different genotypes arise from a single fertilized egg cell, due to mitotic errors at first or later cleavages.
Somatic mutation leading to mosaicism is prevalent in the beginning and end stages of human life.  Somatic mosaics are common in embryogenesis due to retrotransposition of long interspersed nuclear element-1 (LINE-1 or L1) and Alu transposable elements. In early development, DNA from undifferentiated cell types may be more susceptible to mobile element invasion due to long, unmethylated regions in the genome. Further, the accumulation of DNA copy errors and damage over a lifetime lead to greater occurrences of mosaic tissues in aging humans.  As  longevity has increased dramatically over the last century, human genome may not have had time to adapt to cumulative effects of mutagenesis. Thus, cancer research has shown that somatic mutations are increasingly present throughout a lifetime and are responsible for most leukemia, lymphomas, and solid tumors.

Trisomies, monosomies and related conditions
The most common form of mosaicism found through prenatal diagnosis involves trisomies. Although most forms of trisomy are due to problems in meiosis and affect all cells of the organism, some cases occur where the trisomy occurs in only a selection of the cells. This may be caused by a nondisjunction event in an early mitosis, resulting in a loss of a chromosome from some trisomic cells. Generally, this leads to a milder phenotype than in nonmosaic patients with the same disorder.
In rare cases, intersex conditions can be caused by mosaicism where some cells in the body have XX and others XY chromosomes (46, XX/XY).  In the fruit fly Drosophila melanogaster, where a fly possessing two X chromosomes is a female and a fly possessing a single X chromosome is a sterile male, a loss of an X chromosome early in embryonic development can result in sexual mosaics, or gynandromorphs.  Likewise, a loss of the Y chromosome can result in XY/X mosaic males.An example of this is one of the milder forms of Klinefelter syndrome, called 46,XY/47,XXY mosaic wherein some of the patients cells contain XY chromosomes, and some contain XXY chromosomes. The 46/47 annotation indicates that the XY cells have the normal number of 46 total chromosomes, and the XXY cells have a total of 47 chromosomes.
Also monosomies can present with some form of mosaicism. The only non-lethal full monosomy occurring in humans is the one causing Turners syndrome. Around 30% of Turners syndrome cases demonstrate mosaicism, while complete monosomy (45, X) occurs in about 50–60% of cases.
Mosaicism need not necessarily be deleterious, though. Revertant somatic mosaicism is a rare recombination event with a spontaneous correction of a mutant, pathogenic allele. In revertant mosaicism, the healthy tissue formed by mitotic recombination can outcompete the original, surrounding mutant cells in tissues such as blood and epithelia that regenerate often. In the skin disorder ichthyosis with confetti, normal skin spots appear early in life and increase in number and size over time.Other endogenous factors can also lead to mosaicism, including mobile elements, DNA polymerase slippage, and unbalanced chromosomal segregation.  Exogenous factors include nicotine and UV radiation. Somatic mosaics have been created in Drosophila using X‑ray treatment and the use of irradiation to induce somatic mutation has been a useful technique in the study of genetics.True mosaicism should not be mistaken for the phenomenon of X-inactivation, where all cells in an organism have the same genotype, but a different copy of the X chromosome is expressed in different cells. The latter is the case in normal (XX) female mammals, although it is not always visible from the phenotype (as it is in calico cats). However, all multicellular organisms are likely to be somatic mosaics to some extent.

Gonosomal mosaicism
Gonosomal mosaicism is a type of somatic mosaicism that occurs very early in the organisms development and thus is present within both germline and somatic cells. Somatic mosaicism is not generally inheritable as it does not usually affect germ cells.  In the instance of gonosomal mosaicism, organisms have the potential to pass the genetic alteration, including to potential offspring because the altered allele is present in both somatic and germline cells.

Brain cell mosaicism
A frequent type of neuronal genomic mosaicism is copy number variation.  Possible sources of such variation were suggested to be incorrect repair of DNA damages and somatic recombination.

Mitotic recombination
One basic mechanism that can produce mosaic tissue is mitotic recombination or somatic crossover. It was first discovered by Curt Stern in Drosophila in 1936. The amount of tissue that is mosaic depends on where in the tree of cell division the exchange takes place. A phenotypic character called "twin spot" seen in Drosophila is a result of mitotic recombination. However, it also depends on the allelic status of the genes undergoing recombination. Twin spot occurs only if the heterozygous genes are linked in repulsion, i.e. the trans phase. The recombination needs to occur between the centromeres of the adjacent gene. This gives an appearance of yellow patches on the wild-type background in Drosophila. another example of mitotic recombination is the Blooms syndrome, which happens due to the mutation in the blm gene. The resulting BLM protein is defective. The defect in RecQ, a helicase, facilitates the defective unwinding of DNA during replication, thus is associated with the occurrence of this disease.

Use in experimental biology
Genetic mosaics are a particularly powerful tool when used in the commonly studied fruit fly, where specially selected strains frequently lose an X or a Y chromosome in one of the first embryonic cell divisions.  These mosaics can then be used to analyze such things as courtship behavior, and female sexual attraction.More recently, the use of a transgene incorporated into the Drosophila genome has made the system far more flexible.  The flip recombinase (or FLP) is a gene from the commonly studied yeast Saccharomyces cerevisiae that recognizes "flip recombinase target" (FRT) sites, which are short sequences of DNA, and induces recombination between them.  FRT sites have been inserted transgenically near the centromere of each chromosome arm of D. melanogaster.  The FLP gene can then be induced selectively, commonly using either the heat shock promoter or the GAL4/UAS system. The resulting clones can be identified either negatively or positively.
In negatively marked clones, the fly is transheterozygous for a gene encoding a visible marker (commonly the green fluorescent protein) and an allele of a gene to be studied (both on chromosomes bearing FRT sites).  After induction of FLP expression, cells that undergo recombination will have progeny  homozygous for either the marker or the allele being studied.  Therefore, the cells that do not carry the marker (which are dark) can be identified as carrying a mutation.
Using negatively marked clones is sometimes inconvenient, especially when generating very small patches of cells, where seeing a dark spot on a bright background is more difficult than a bright spot on a dark background.  Creating positively marked clones is possible using the so-called MARCM ("mosaic analysis with a repressible cell marker" system, developed by Liqun Luo, a professor at Stanford University, and his postdoctoral student Tzumin Lee, who now leads a group at Janelia Farm Research Campus.  This system builds on the GAL4/UAS system, which is used to express GFP in specific cells.  However, a globally expressed GAL80 gene is used to repress the action of GAL4, preventing the expression of GFP.  Instead of using GFP to mark the wild-type chromosome as above, GAL80 serves this purpose, so that when it is removed by mitotic recombination, GAL4 is allowed to function, and GFP turns on </s>