<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 Pagets disease of bone and can you explain it in depth? [/INST] Pagets disease of bone (commonly known as Pagets disease or, historically, osteitis deformans) is a condition involving cellular remodeling and deformity of one or more bones. The affected bones show signs of dysregulated bone remodeling at the microscopic level, specifically excessive bone breakdown and subsequent disorganized new bone formation. These structural changes cause the bone to weaken, which may result in deformity, pain, fracture or arthritis of associated joints.The exact cause is unknown, although leading theories indicate both genetic and acquired factors (see Causes). Pagets disease may affect any one or several bones of the body (most commonly pelvis, tibia, femur, lumbar vertebrae, and skull), but never the entire skeleton, and does not spread from bone to bone. Rarely, a bone affected by Pagets disease can transform into a malignant bone cancer.
As the disease often affects people differently, treatments of Pagets disease can vary. Although there is no cure for Pagets disease, medications (bisphosphonates and calcitonin) can help control the disorder and lessen pain and other symptoms. Medications are often successful in controlling the disorder, especially when started before complications begin.
Pagets disease affects from 1.5 to 8.0 percent of the population, and is most common in those of British descent. It is primarily diagnosed in older people and is rare in people less than 55 years of age. Men are more commonly affected than women (3:2). The disease is named after English surgeon Sir James Paget, who described it in 1877.

Signs and symptoms
Mild or early cases of Pagets are asymptomatic, and so most people are diagnosed with Pagets disease incidentally during medical evaluation for another problem. Approximately 35% of patients with Pagets have symptoms related to the disease when they are first diagnosed. Overall, the most common symptom is bone pain. When symptoms do occur, they may be confused with those of arthritis or other disorders, and so diagnosis may be delayed. Pagets may first be noticed as an increasing deformity of a persons bones.Pagets disease affecting the skull may cause frontal bossing, increased hat size, and headaches. Often patients may develop loss of hearing in one or both ears due to auditory foramen narrowing and resultant compression of the nerves in the inner ear. Rarely, skull involvement may lead to compression of the nerves that supply the eye, leading to vision loss.

Associated conditions
Pagets disease is a frequent component of multisystem proteinopathy.
Advanced Pagets disease may lead to other medical conditions, including:

Osteoarthritis may result from changes in bone shape that alter normal skeletal mechanics. For example, bowing of a femur affected by Pagets may distort overall leg alignment, subjecting the knee to abnormal mechanical forces and accelerating degenerative wear.
Heart failure is a rare, reported consequence of severe Pagets disease (i.e. more than 40% skeletal involvement). The abnormal bone formation is associated with recruitment of abnormal blood vessels, forcing the cardiovascular system to work harder (pump more blood) to ensure adequate circulation.
Kidney stones are somewhat more common in patients with Pagets disease.
Nervous system problems may occur in Pagets disease, resulting from increased pressure on the brain, spinal cord, or nerves, and reduced blood flow to the brain and spinal cord.
When Pagets disease affects the facial bones, the teeth may become loose. Disturbance in chewing may occur. Chronic dental problems may lead to infection of the jaw bone.
Angioid streaks may develop, possibly as a result of calcification of collagen or other pathological deposition.Pagets disease is not associated with osteoporosis. Although Pagets disease and osteoporosis can occur in the same patient, they are different disorders. Despite their marked differences, several treatments for Pagets disease are also used to treat osteoporosis.

Causes
Viral
Pagets disease may be caused by a slow virus infection (i.e., paramyxoviridae) present for many years before symptoms appear. Associated viral infections include respiratory syncytial virus, canine distemper virus, and the measles virus. However, recent evidence has cast some doubt upon the measles association. Laboratory contamination may have played a role in past studies linking paramyxovirus (e.g. measles) to Pagets disease.

Genetic
There is a hereditary factor in the development of Pagets disease of bone. Two genes, SQSTM1 and RANK, and specific regions of chromosome 5 and 6 are associated with Pagets disease of bone. Genetic causes may or may not involve a family history of Pagets disease.About 40–50% of people with the inherited version of Pagets disease have a mutation in the gene SQSTM1, which encodes a protein, called p62, that is involved in regulating the function of osteoclasts (bone cells). However, about 10-15 percent of people that develop the disease without any family history also have a mutation in the SQSTM1 gene.Pagets disease of bone is associated with mutations in RANK. Receptor Activator of Nuclear Factor κ B (RANK), which is a type I membrane protein that is expressed on the surface of osteoclasts and is involved in their activation upon ligand binding. Additional genetic associations include:

Pathogenesis
The pathogenesis of Pagets disease is described in four stages:
Osteoclastic activity
Mixed osteoclastic – osteoblastic activity
Osteoblastic activity
Malignant degenerationInitially, there is a marked increase in the rate of bone resorption in localized areas, caused by large and numerous osteoclasts. These localized areas of pathological destruction of bone tissue (osteolysis) are seen radiologically as an advancing lytic wedge in long bones or the skull. When this occurs in the skull, it is called osteoporosis circumscripta. The osteolysis is followed by a compensatory increase in bone formation induced by the bone-forming cells, called osteoblasts, that are recruited to the area. This is associated with accelerated deposition of lamellar bone in a disorganized fashion. This intense cellular activity produces a chaotic picture of trabecular bone ("mosaic" pattern), rather than the normal linear lamellar pattern. The resorbed bone is replaced and the marrow spaces are filled by an excess of fibrous connective tissue with a marked increase in blood vessels, causing the bone to become hypervascular. The bone hypercellularity may then diminish, leaving a dense "pagetic bone," also known as burned-out Pagets disease. A later phase of the disease is characterized by the replacement of normal bone marrow with highly vascular fibrous tissue.Sir James Paget first suggested the disease was due to an inflammatory process. Some evidence suggests that a paramyxovirus infection is the underlying cause of Pagets disease, which may support the possible role of inflammation in the pathogenesis. However, no infectious virus has yet been isolated as a causative agent, and other evidence suggests an intrinsic hyperresponsive reaction to vitamin D and RANK ligand is the cause. Further research is therefore necessary.

Diagnosis
The first clinical manifestation of Pagets disease is usually an elevated alkaline phosphatase in the blood.
Pagets disease may be diagnosed using one or more of the following tests:

Pagetic bone has a characteristic appearance on X-rays. A skeletal survey is therefore indicated.
An elevated level of alkaline phosphatase in the blood in combination with normal calcium, phosphate, and aminotransferase levels in an elderly patient are suggestive of Pagets disease.
Markers of bone turnover in urine eg. Pyridinoline
Elevated levels of serum and urinary hydroxyproline are also found.
Bone scans are useful in determining the extent and activity of the condition. If a bone scan suggests Pagets disease, the affected bone(s) should be X-rayed to confirm the diagnosis.

Differential diagnosis
Treatment
Although initially diagnosed by a primary care physician, endocrinologists (internal medicine physicians who specialize in hormonal and metabolic disorders), rheumatologists (internal medicine physicians who specialize in joint and muscle disorders), orthopedic surgeons, neurosurgeons, neurologists, oral and maxillofacial surgeons, and otolaryngologists are generally knowledgeable about treating Pagets disease and may be called upon to evaluate specialized symptoms. It can sometimes be difficult to predict whether a person with Pagets disease, who otherwise has no signs or symptoms of the disorder, will develop symptoms or complications (such as a bone fracture) in the future.

Medication
The goal of treatment is to relieve bone pain and prevent the progression of the disease. These medications are usually recommended for people with Pagets disease who:
have bone pain, headache, back pain, or a nerve-related symptom (such as "shooting" pains in the leg) that is directly associated with the disease;
have elevated levels of serum alkaline phosphatase (ALP) in their blood;
display evidence that a bone fracture will occur;
require pretreatment therapy for affected bones that require surgery;
have active symptoms in the skull, long bones, or vertebrae (spine);
have the disease in bones located next to major joints, placing them at risk of developing osteoarthritis;
develop hypercalcemia that occurs when a person, with several bones affected by Pagets disease and a high serum alkaline phosphatase level, is immobilized.

Bisphosphonates
Five bisphosphonates are currently available. In general, the most commonly prescribed are risedronic acid, alendronic acid, and pamidronic acid. Etidronic acid and other bisphosphonates may be appropriate therapies for selected patients but are less commonly used. In one study it was reported that people experienced side effects when taking bisphosphonates for six months, however the quality of evidence was low. None of these drugs should be used by people with severe kidney disease.
Neridronate
Etidronate disodium The approved regimen is once daily for six months; a higher dose is more commonly used. No food, beverage, or medications should be consumed for two hours before and after taking. The course should not exceed six months, but repeat courses can be given after rest periods, preferably of three to six months duration.
Pamidronate disodium in intravenous form: the approved regimen uses an infusion over four hours on each of three consecutive days, but a more commonly used regimen is over two to four hours for two or more consecutive or nonconsecutive days.
Alendronate sodium is given as tablets once daily for six months; patients should wait at least 30 minutes after taking before eating any food, drinking anything other than tap water, taking any medication, or lying down (patient may sit).
Tiludronate disodium is taken once daily for three months; they may be taken any time of day, as long as there is a period of two hours before and after resuming food, beverages, and medications.
Risedronate sodium tablet taken once daily for 2 months is the prescribed regimen; patients should wait at least 30 minutes after taking before eating any food, drinking anything other than tap water, taking any medication, or lying down (patient may sit).
Zoledronic acid is given as an intravenous infusion; a single dose is effective for two years. This is recommended for most people at high risk with active disease.

Calcitonin
Salcatonin, also called calcitonin-salmon is a synthetic copy of a polypeptide hormone secreted by the ultimobranchial gland of salmon. Miacalcin is administered by injection, three times per week or daily, for 6–18 months. Repeat courses can be given after brief rest periods. Miacalcin may be appropriate for certain patients but is seldom used. Calcitonin was putatively linked to increased chance of cancer. The European Medicines Agency (EMA) recommended that calcitonin be used only on a short-term basis for 3 conditions for which it had previously been approved in the European Union: Pagets disease, acute bone loss resulting from sudden immobilization, and hypercalcemia caused by cancer. As a solution for injection or infusion, calcitonin should be administered for no more than 4 weeks to prevent acute bone loss resulting from sudden immobilization, and normally for no more than 3 months to treat Pagets disease, the EMA said. The agency did not specify a time frame for the short-term use of calcitonin for treating hypercalcemia caused by cancer. The EMA based its recommendations on a review of the benefits and risks of calcitonin-containing medicines. Conducted by the agencys Committee for Medicinal Products for Human Use (CHMP), the review encompassed available data from the companies that market these drugs, postmarketing safety data, randomized controlled studies, 2 studies of unlicensed oral calcitonin drugs, and experimental cancer studies, among other sources.In 2014, the FDA noted the risk imbalances in the prescribing information for Miacalcin but declined to label this product with a boxed warning as a causal association was not identified.A more recent meta-analysis determined that a causal link between calcitonin and cancer is both unlikely and antithetical to known biology, although a weak association was not definitively excluded. The available studies for analysis were inconsistent and nonspecific, with one study noting an increased risk of liver cancer and decreased risk of breast cancer. This was not replicated in any other study.Additionally, there is question of the overall efficacy of calcitonin-containing nasal sprays. A phase III trial found no difference between placebo and nasal calcitonin sprays on lumbar bone mineral density in osteoporosis. It did find a significant increase in bone mineral density with oral calcitonin. This result was replicated in another study, but this study found that the bone mineral density increase did not significantly impact fracture risk. However, these studies were only inclusive of osteoporosis.

Surgery
Medical therapy prior to surgery helps to decrease bleeding and other complications. Patients who are having surgery should discuss treatment with their physician. There are generally three major complications of Pagets disease for which surgery may be recommended.
Fractures — Surgery may allow fractures to heal in a better position.
Severe degenerative arthritis — If disability is severe and medication and physical therapy are no longer helpful, joint replacement of the hips and knees may be considered.
Bone deformity — Cutting and realignment of pagetic bone (osteotomy) may help painful weight bearing joints, especially the knees.Complications resulting from enlargement of the skull or spine may injure the nervous system. However, most neurologic symptoms, even those that are moderately severe, can be treated with medication and do not require neurosurgery.

Diet and exercise
In general, patients with Pagets disease should receive 1000–1500 mg of calcium, adequate sunshine, and at least 400 units of vitamin D daily. This is especially important in patients being treated with bisphosphonates; however, taking oral bisphosphonates should be separated from taking calcium by at least two hours, because the calcium can inhibit the absorption of the bisphosphonate. Patients with a history of kidney stones should discuss calcium and vitamin D intake with their physicians.Exercise is very important in maintaining skeletal health, avoiding weight gain, and maintaining joint mobility. Since undue stress on affected bones should be avoided, people with Pagets disease of bone should discuss any exercise program with their physicians or physical therapists before beginning.

Prognosis
The disease is progressive and slowly worsens with time, although people may remain minimally symptomatic. Treatment is aimed at controlling symptoms, but there is no cure. Any bone or bones can be affected, but Pagets disease occurs most frequently in the spine, skull, pelvis, femur, and lower legs. Osteogenic sarcoma, a form of bone cancer, is a rare complication of Pagets disease occurring in less than one percent of those affected. The development of osteosarcoma may be suggested by the sudden onset or worsening pain.

Epidemiology
Pagets disease of bone is the second most common metabolic bone disorder, after osteoporosis. The overall prevalence and severity of Pagets disease are decreasing; the cause for these changes is unclear. Pagets disease is rare in people less than 55 years of age, and the prevalence increases with age. Evidence from studies of autopsy results have demonstrated Pagets disease in about 3 percent of people older than 40 years of age. Pagets disease is more common in males than females. Rates of Pagets disease are about 50 percent higher in men than in women.
About 15 percent of people with Pagets disease also have a family member with the disease. In cases where the disease is familial, it is inherited in an autosomal dominant fashion, although not all people that inherit the affected version of the genes will express the disease (incomplete penetrance).The incidence of Pagets disease varies considerably with geographic location. Pagets predominantly affects people of European descent, whereas people of African, Asian, or Indian descent are less commonly affected </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 Focal seizure and can you explain it in depth? [/INST] Focal seizures (also called partial seizures and localized seizures) are seizures which affect initially only one hemisphere of the brain. The brain is divided into two hemispheres, each consisting of four lobes – the frontal, temporal, parietal and occipital lobes. A focal seizure is generated in and affects just one part of the brain – a whole hemisphere or part of a lobe. Symptoms will vary according to where the seizure occurs. When seizures occur in the frontal lobe the patient may experience a wave-like sensation in the head. When seizures occur in the temporal lobe, a feeling of déjà vu may be experienced. When seizures are localized to the parietal lobe, a numbness or tingling may occur. With seizures occurring in the occipital lobe, visual disturbances or hallucinations have been reported.

Types
As of 2017, focal seizures are split into two main categories, focal onset aware, and focal onset impaired awareness. What was previously termed a secondary generalised seizure is now termed a focal to bilateral seizure.In focal onset aware seizures, a small part of one of the lobes may be affected and the person remains conscious. This can often be a precursor to a larger focal onset impaired awareness seizure. When this is the case, the focal aware seizure is usually called an aura.
A focal impaired awareness seizure affects a larger part of the hemisphere and the person may lose consciousness.
If a focal seizure spreads from one hemisphere to the other side of the brain, this will give rise to a focal to bilateral seizure. The person will become unconscious and may experience a tonic clonic seizure. When people have multiple focal seizures they generally have a condition known as temporal lobe epilepsy. (A generalized seizure is one that involves both sides of the brain from the onset.)

Simple partial seizures
Simple partial seizures are seizures which affect only a small region of the brain, often the temporal lobes or structures found there, such as the hippocampi. People who have focal aware seizures remain conscious. Focal aware seizures often precede larger focal impaired awareness seizures, where the abnormal electrical activity spreads to a larger area of the brain. This can result in a tonic-clonic seizure.

Presentation
Simple partial seizures are a very subjective experience, and the symptoms vary greatly between people. Since symptoms can be subtle, diagnosis can be delayed by months or years. The symptoms of these seizures can also be misconstrued as auras, especially for epilepsy patients with multiple types of seizure diagnosis. This is due to the varying locations of the brain in which the seizures originate (e.g., Rolandic). A Simple partial seizure may go unnoticed by others or shrugged off by the patient as merely a "funny turn." Focal aware seizures usually start suddenly and are very brief, typically lasting 60 to 120 seconds.Some common symptoms of a simple partial seizure, when the person is awake, are:
preserved consciousness
sudden and inexplicable feelings of fear, anger, sadness, happiness or nausea
sensations of falling or movement
experiencing of unusual feelings or sensations
altered sense of hearing, smelling, tasting, seeing, and tactile perception (sensory illusions or hallucinations), or feeling as though the environment is not real (derealization) or dissociation from the environment or self (depersonalization)
a sense of spatial distortion—things close by may appear to be at a distance
déjà vu (familiarity) or jamais vu (unfamiliarity)
laboured speech or inability to speak at all
usually the event is remembered in detailWhen a seizure occurs during sleep, the person will often become semi-conscious and act out a dream they were having while engaging with the real environment as normal. Objects and people usually appear normal or only slightly distorted to them, and will be able to communicate with them on an otherwise normal level. However, since the person is still acting in a dream-like state, they will assimilate any hallucinations or delusions into their communication, often speaking to a hallucinatory person or speaking of events or thoughts pertaining to their dream or a hallucination.
While-asleep symptoms include:

onset usually in REM sleep
dream-like state
appearance of full consciousness
hallucinations or delusions
behavior or visions typical in dreams
ability to engage with the environment and other people as in full consciousness, though often behaving abnormally, erratically, or failing to be coherent
complete amnesia or assimilating the memory as though it was a normal dream on regaining full consciousness
dreams of daily life that appear as if they happened in reality, and can cause disorientation upon awakeningAlthough hallucinations may occur during focal aware seizures they are differentiated from psychotic symptoms by the fact that the person is usually aware that the hallucinations are not real.

Jacksonian march
Jacksonian march or Jacksonian seizure is a phenomenon where a simple partial seizure spreads from the distal part of the limb toward the ipsilateral face (on same side of body). They involve a progression of the location of the seizure in the brain, which leads to a "march" of the motor presentation of symptoms.Jacksonian seizures are initiated with abnormal electrical activity within the primary motor cortex. They are unique in that they travel through the primary motor cortex in succession, affecting the corresponding muscles, often beginning with the fingers. This is felt as a tingling sensation, or a feeling of waves through the fingers when touched together. It then affects the hand and moves on to more proximal areas on the same side of body. Symptoms often associated with a Jacksonian seizure are sudden head and eye movements, tingling, numbness, smacking of the lips, and sudden muscle contractions. Most of the time any one of these actions can be seen as normal movements, without being associated with the seizure occurring. They occur at no particular moment and last only briefly. They may result in secondary generalized seizure involving both hemispheres. They can also start at the feet, manifesting as tingling or pins and needles, and there are painful cramps in the foot muscles, due to the signals from the brain. Because it is a partial seizure, the postictal state is of normal consciousness.
Jacksonian seizures are named after their discoverer, John Hughlings Jackson, an English neurologist, whose studies led to the discovery of the seizures initiation point (in the primary motor cortex) in 1863.

Complex partial seizures
A complex partial seizure is a seizure that is associated with unilateral cerebral hemisphere involvement and causes impairment of awareness or responsiveness, i.e. alteration of consciousness.

Presentation
Complex partial seizures are often preceded by an aura.  The seizure aura is a focal aware seizure.  The aura may manifest itself as a feeling of déjà vu, jamais vu, fear, euphoria or depersonalization.  The aura might also occur as a visual disturbance, such as tunnel vision or a change in the perceived size of objects. Once consciousness is impaired, the person may display automatisms, such as lip smacking, chewing or swallowing </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 Bipolar disorder in children and can you explain it in depth? [/INST] Bipolar disorder in children, or pediatric bipolar disorder (PBD), is a controversial mental disorder in children and adolescents that is mainly diagnosed in the United States, and is hypothesized to be like bipolar disorder (BD) in adults, thus is proposed as an explanation for extreme changes in mood and behavior accompanying periods of depressed or irritable moods and periods of elevated moods so called manic or hypomanic episodes. These shifts are sometimes quick, but usually are gradual. The average age of onset of pediatric bipolar disorder is unclear, but the risk increases with the onset of puberty. Bipolar disorder is rare in childhood. Pediatric bipolar disorder is typically more severe and has a poorer prognosis than bipolar disorder with onset in late-adolescence or adulthood.The DSM has specified that the criteria for bipolar disorder can be applied to children since 1980. However, the exact criteria for diagnosing pediatric bipolar disorder remains controversial and heavily debated. There are big differences in how commonly it is diagnosed across clinics and in different countries. There has been a rapid increase in research on the topic, but training and clinical practice lag behind.
Identifying bipolar disorder in youth is challenging. Children often exhibit chronic rather than episodic mania periods. Almost always, these chronic problems have causes other than bipolar disorder. The criteria for pediatric bipolar disorder can also often be masked by developmental differences. Comorbid disorders make determining what symptoms are signs of bipolar disorder and which are due to other disorders (e.g., OCD, ADHD, disruptive behavior problems) difficult, leading to complications in treatment. For example, a common treatment for OCD are serotonin re-uptake inhibitors (SRIs), however, SRIs can lead to mood instability and worsening bipolar disorder. The most common misdiagnosis for ADHD in the USA is pediatric bipolar disorder due to hyperactivity being described as prolonged periods of mania. Empirical research conducted in 2004 found that "bipolar disorder (in preadolescence) was initially misdiagnosed in 12 out of 24 youths" (Mahoney, 2004). This is a dangerous misdiagnosis due to the vastly different treatment forms. Firstly, ADHD does not require mood stabilizers like pediatric bipolar disorder. Secondly, the stimulants given to treat ADHD have been shown to cause psychosis and exacerbate mania in pediatric bipolar disorder (Wendling, 2009). This misuse of medication can lead to mood episodes, suicidality, and hospitalization.

Diagnosis
Diagnosis is made based on a clinical interview by a psychiatrist or other licensed mental health practitioner. There are no blood tests or brain scans to diagnose bipolar disorder. Obtaining information on family history and the use of questionnaires and checklists are helpful in making an accurate diagnosis. Commonly used assessment tools include the K-SADS (Kiddie Schedule for Affective Disorders and Schizophrenia), the Diagnostic Interview Schedule for Children (DISC), and the Child Mania Rating Scale (CMRS).

Signs and symptoms
In both the American Psychiatric Associations DSM-5 and the World Health Organizations ICD-10, the same criteria used to diagnose bipolar disorder in adults are used to make the diagnosis in children with some adjustments to account for differences in age and developmental stage. For example, the DSM-5 specifies that in children, depressive episodes can manifest as persistently irritable moods.In diagnosing manic episodes, it is important to compare the changes in mood and behavior to the childs normal mood and behaviors at baseline instead of to other children or adults. For example, grandiosity (i.e., unrealistic overestimation of ones intelligence, talent, or abilities) is normal at varying degrees during childhood and adolescence. Therefore, grandiosity is only considered symptomatic of mania in children when the beliefs are held despite being presented with concrete evidence otherwise or when they lead to a child attempting activities that are clearly dangerous, and most importantly, when the grandiose beliefs are an obvious change from that particular childs normal self-view in between episodes.

Controversy
The diagnosis of childhood bipolar disorder is controversial, although it is recognized that bipolar disorder typical symptoms are dysfunctional and have negative consequences for minors with the condition. Main discussion is centered on whether what is called bipolar disorder in children refers to the same disorder than when diagnosing adults, and the related question on whether adults criteria for diagnosis are useful and accurate when applied to children. More specifically, main discussion over diagnosis in children circles around mania symptomatology and its differences between children and adults.Diagnostic criteria may not correctly separate children with bipolar disorder from other problems such as ADHD, and emphasize fast mood cycles.

Treatment
Medications can produce important side effects, so interventions have been recommended to be closely monitored and families of patients to be informed of the different possible problems that can arise. Atypical antipsychotics are more effective than mood stabilizers, but have more side effects Typical antipsychotics may produce weight gains as well as other metabolic problems, including diabetes mellitus type 2 and hyperlipidemia. Extrapyramidal secondary effects may appear with these medications. These include tardive dyskinesia, a difficult-to-treat movement disorder (dyskinesia) that can appear after long-term use of anti-psychotics. Liver and kidney damage are a possibility with mood stabilizers.Psychological treatment usually includes some combination of education on the disease, group therapy and cognitive behavioral therapy. Children with bipolar disorder and their families are informed, in ways accordingly to their age and family role, about the different aspects of bipolar disorder and its management including causes, signs and symptoms and treatments. Group therapy aims to improve social skills and manage group conflicts, with role-playing as a critical tool. Finally, cognitive-behavioral training is directed towards the participants having a better understanding and control over their emotions and behaviors.BPD I, manic or mixed, without psychosis
Stage 1: Monotherapy with a mood stabilizer (lithium, Divalproex, or carbamazepine), or atypical antipsychotic (olanzapine, quetiapine, or risperidone). Lithium or Divalproex is recommended for first-line treatment. Partial (minimal to moderate) improvement with monotherapy, augment with another of the first-line recommendations.
Stage 2: Monotherapy with an alternative drug, then augmentation.
Stage 3: Possible medication combinations—lithium plus Divalproex, lithium plus atypical, or Divalproex plus atypical.
Stage 4: Combination of 2-3 mood stabilizers
Stage 5: Alternate monotherapy with oxcarbazepine, ziprasidone, or aripiprazole (all Level D).
Stage 6: For nonresponse or intolerable side effects—clozapine for children or adolescents, or electroconvulsive therapy (ECT) for adolescents only.
BPD II, manic or mixed, with psychosis
Stage 1: Same as BPD I without psychosis except for first-line treatment warrants a combination of mood stabilizer and an atypical antipsychotic.
Stages 2–4: Varying combinations and augmentations.
Stage 5: Alternate monotherapy (oxcarbazepine) plus an atypical antipsychotic. (Bipolar Disorder in Children and Adolescents, 2005).

Prognosis
Chronic medication is often needed, with relapses of individuals reaching rates over 90% in those not following medication indications and almost to 40% in those complying with medication regimens in some studies. Compared to adults, a juvenile onset has in general a similar or worse course, although age of onset predicts the duration of the episodes more than the prognosis. A risk factor for a worse outcome is the existence of additional (comorbid) pathologies.Children with bipolar disorder are more likely to commit suicide than other children.

Epidemiology
The prevalence of bipolar in youth is estimated at 2%.

History
Descriptions of children with symptoms similar to contemporary concepts of mania date back to the 18th century. In 1898, a detailed psychiatric case history was published about a 13-year-old that met Jean-Pierre Falret and Jules Baillargers criteria for folie circulaire, which is congruent to the modern conception of bipolar I disorder.In Emil Kraepelins descriptions of bipolar disorder in the 1920s, which he called "manic depressive insanity", he noted the rare possibility that it could occur in children. In addition to Kraepelin, Adolf Meyer, Karl Abraham, and Melanie Klein were some of the first to document bipolar disorder symptoms in children in the first half of the 20th century. It was not mentioned much in English literature until the 1970s when interest in researching the subject increased. It became more accepted as a diagnosis in children in the 1980s after the DSM-III (1980) specified that the same criteria for diagnosing bipolar disorder in adults could also be applied to children.Recognition came twenty years after, with epidemiological studies showing that approximately 20% of adults with bipolar disorder already had symptoms in childhood or adolescence. Nevertheless, onset before age 10 was thought to be rare, below 0.5% of the cases. During the second half of the century misdiagnosis with schizophrenia was not rare in the non-adult population due to common co-occurrence of psychosis and mania, this issue diminishing with an increased following of the DSM criteria in the last part of the 20th century.

References
Bipolar disorder in children and adolescents: treatment and diagnosis: new treatment guidelines available. (2005) </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 Mycoplasma and can you explain it in depth? [/INST] Mycoplasma is a genus of bacteria that, like the other members of the class Mollicutes, lack a cell wall around their cell membranes. Peptidoglycan (murein) is absent. This characteristic makes them naturally resistant to antibiotics that target cell wall synthesis (like the beta-lactam antibiotics). They can be parasitic or saprotrophic. Several species are pathogenic in humans, including M. pneumoniae, which is an important cause of "walking" pneumonia and other respiratory disorders, and M. genitalium, which is believed to be involved in pelvic inflammatory diseases. Mycoplasma species (like the other species of the class Mollicutes) are among the smallest organisms yet discovered, can survive without oxygen, and come in various shapes. For example, M. genitalium is flask-shaped (about 300 x 600 nm), while M. pneumoniae is more elongated (about 100 x 1000 nm), many Mycoplasma species are coccoid. Hundreds of Mycoplasma species infect animals.The trivial name “mycoplasma” (plural mycoplasmas or mycoplasms) is commonly used for all members of the class Mollicutes. In scientific classification, the designation Mycoplasma refers exclusively to the genus, a member of the Mycoplasmataceae, the only family of the order Mycoplasmatales (see “scientific classification”).

Etymology
The term "mycoplasma", from the Greek μύκης, mykes (fungus) and πλάσμα, plasma (formed), was first used by Albert Bernhard Frank in 1889 to describe an altered state of plant cell cytoplasm resulting from infiltration by fungus-like microorganisms. Julian Nowak later proposed the name mycoplasma for certain filamentous microorganisms imagined to have both cellular and acellular stages in their lifecycles, which could explain how they were visible with a microscope, but passed through filters impermeable to other bacteria. Later, the name for these mycoplasmas was pleuropneumonia-like organisms (PPLO), broadly referring to organisms similar in colonial morphology and filterability to the causative agent (a Mycoplasma species) of contagious bovine pleuropneumonia. At present, all these organisms are classified as Mollicutes and the term Mycoplasma refers solely to the genus.

Species that infect humans
Species of Mycoplasma, other than those listed below, have been recovered from humans, but are assumed to have been contracted from a non-human host. The following species use humans as the primary host:

Pathophysiology
Mycoplasma species have been isolated from women with bacterial vaginosis. M. genitalium is found in women with pelvic inflammatory disease. In addition, infection is associated with increased risk of cervicitis, infertility, preterm birth and spontaneous abortion. Mycoplasma genitalium has developed resistance to some antibiotics. Mycoplasma species are associated with infant respiratory distress syndrome, bronchopulmonary dysplasia, and intraventricular hemorrhage in preterm infants.

Characteristics
Over 100 species have been included in the genus Mycoplasma, a member of the class Mollicutes. They are parasites or commensals of humans, animals, and plants. The genus Mycoplasma uses vertebrate and arthropod hosts.
Dietary nitrogen availability has been shown to alter codon bias and genome evolution in Mycoplasma and Phytoplasma.Mycoplasma species are among the smallest free-living organisms (about 0.2 - 0.3 µm in diameter). They have been found in the pleural cavities of cattle suffering from pleuropneumonia. These organisms are often called MLO (mycoplasma-like organisms) or, formerly, PPLO (pleuropneumonia-like organisms).

Important characteristics of Mycoplasma species
Cell wall is absent and plasma membrane forms the outer boundary of the cell.
Due to the absence of cell walls these organisms can change their shape and are pleomorphic.
Lack of nucleus and other membrane-bound organelles.
Genetic material is a single DNA duplex and is naked.
Ribosomes are 70S type.
Possess a replicating disc at one end which assists replication process and also the separation of the genetic materials.
Heterotrophic nutrition. Some live as saprophytes but the majority are parasites of plants and animals. The parasitic nature is due to the inability of mycoplasmal bacteria to synthesise the required growth factor.

Cell and colony morphology
Due to the lack of a rigid cell wall, Mycoplasma species (like all Mollicutes)  can contort into a broad range of shapes, from round to oblong. They are pleomorphic and therefore cannot be identified as rods, cocci or spirochetes.Colonies show the typical „fried egg” appearance (about 0.5 mm in diameter).

Reproduction
In 1954, using phase-contrast microscopy, continual observations of live cells have shown that Mycoplasma species ("mycoplasmas", formerly called pleuropneumonia-like organisms, PPLO, now classified as Mollicutes) and L-form bacteria (previously also called L-phase bacteria) do not proliferate by binary fission, but by a uni- or multi-polar budding mechanism. Microphotograph series of growing microcultures of different strains of PPLOs, L-form bacteria and, as a control, a Micrococcus species (dividing by binary fission) have been presented.  Additionally, electron microscopic studies have been performed.

Phylogeny
Previously, Mycoplasma species (often commonly called "mycoplasmas", now classified as Mollicutes) were sometimes considered stable L-form bacteria or even viruses, but phylogenetic analysis has identified them as bacteria that have lost their cell walls in the course of evolution.The genus Mycoplasma as originally described is highly paraphyletic, as such it was redescibed by Gupta et al. 2018 and its emendation was accompanied by the removal of 78 species. The currently accepted taxonomy is based on the List of Prokaryotic names with Standing in Nomenclature (LPSN) and National Center for Biotechnology Information (NCBI)
Unassigned species:

Laboratory contaminant
Mycoplasma species are often found in research laboratories as contaminants in cell culture. Mycoplasmal cell culture contamination occurs due to contamination from individuals or contaminated cell culture medium ingredients. Mycoplasma cells are physically small – less than 1  µm, so are difficult to detect with a conventional microscope.Mycoplasmae may induce cellular changes, including chromosome aberrations, changes in metabolism and cell growth. Severe Mycoplasma infections may destroy a cell line. Detection techniques include DNA probe, enzyme immunoassays, PCR, plating on sensitive agar and staining with a DNA stain including DAPI or Hoechst.An estimated 11 to 15% of U.S. laboratory cell cultures are contaminated with mycoplasma.
A Corning study showed that half of U.S. scientists did not test for Mycoplasma contamination in their cell cultures. The study also stated that, in former Czechoslovakia, 100% of cell cultures that were not routinely tested were contaminated while only 2% of those routinely tested were contaminated (study p. 6). Since the U.S. contamination rate was based on a study of companies that routinely checked for Mycoplasma, the actual contamination rate may be higher. European contamination rates are higher and that of other countries are higher still (up to 80% of Japanese cell cultures).
About 1% of published Gene Expression Omnibus data may have been compromised. Several antibiotic-containing formulations of antimycoplasmal reagents have been developed over the years.

Synthetic mycoplasma genome
A chemically synthesized genome of a mycoplasmal cell based entirely on synthetic DNA which can self-replicate has been referred to as Mycoplasma laboratorium.

Pathogenicity
The P1 antigen is the primary virulence factor of mycoplasma. P1 is a membrane associated protein that allows adhesion to epithelial cells. The P1 receptor is also expressed on erythrocytes which can lead to autoantibody agglutination from mycobacteria infection. Several Mycoplasma species can cause disease, including M. pneumoniae, which is an important cause of atypical pneumonia (formerly known as "walking pneumonia"), and M. genitalium, which has been associated with pelvic inflammatory diseases. Mycoplasma infections in humans are associated with skin eruptions in 17% of cases.: 293

Sexually transmitted infections
Mycoplasma and Ureaplasma species are not part of the normal vaginal flora. Some Mycoplasma species are spread through sexual contact.

Infertility
Some Mycoplasma species have a negative effect on fertility. M. hominis causes male sterility/Genitals inflammation in humans.

Infant mortality
Low birth-weight, preterm infants are susceptible to Mycoplasma infections.

Links to cancer
Several species of Mycoplasma are frequently detected in different types of cancer cells. These species are:

M. fermentans
M. genitalium
M. hyorhinis
M. penetrans
U. urealyticumThe majority of these Mycoplasma species have shown a strong correlation to malignant transformation in mammalian cells in vitro.

Mycoplasma infection and host cell transformation
The presence of Mycoplasma was first reported in samples of cancer tissue in the 1960s. Since then, several studies tried to find and prove the connection between Mycoplasma and cancer, as well as how the bacterium might be involved in the formation of cancer. Several studies have shown that cells that are chronically infected with the bacteria go through a multistep transformation. The changes caused by chronic mycoplasmal infections occur gradually and are both morphological and genetic. The first visual sign of infection is when the cells gradually shift from their normal form to sickle-shaped. They also become hyperchromatic due to an increase of DNA in the nucleus of the cells. In later stages, the cells lose the need for solid support to grow and proliferate, as well as the normal contact-dependent inhibition cells.

Possible intracellular mechanisms of mycoplasmal malignant transformation
Karyotypic changes related to mycoplasma infections
Cells infected with Mycoplasma for an extended period of time show significant chromosomal abnormalities. These include the addition of chromosomes, the loss of entire chromosomes, partial loss of chromosomes, and chromosomal translocation. All of these genetic abnormalities may contribute to the process of malignant transformation. Chromosomal translocation and extra chromosomes help create abnormally high activity of certain proto-oncogenes, which caused by these genetic abnormalities and include those encoding c-myc, HRAS, and vav. The activity of proto-oncogenes is not the only cellular function that is affected; tumour suppressor genes are affected by the chromosomal changes induced by mycoplasma, as well. Partial or complete loss of chromosomes causes the loss of important genes involved in the regulation of cell proliferation. Two genes whose activities are markedly decreased during chronic infections with mycoplasma are the Rb and the p53 tumour suppressor genes. Another possible mechanism of carcinogenesis is RAC1 activation by a small GTPase-like protein fragment of Mycoplasma. A major feature that differentiates mycoplasmas from other carcinogenic pathogens is that the mycoplasmas do not cause the cellular changes by insertion of their own genetic material into the host cell. The exact mechanism by which the bacterium causes the changes is not yet known.

Partial reversibility of malignant transformationsThe malignant transformation induced by Mycoplasma species is also different from that caused by other pathogens in that the process is reversible. The state of reversal is, however, only possible up to a certain point during the infection. The window of time when reversibility is possible varies greatly; it depends primarily on the Mycoplasma involved. In the case of M. fermentans, the transformation is reversible until around week 11 of infection and starts to become irreversible between weeks 11 and 18. If the bacteria are killed using antibiotics (i.e </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 Pulmonary insufficiency and can you explain it in depth? [/INST] Pulmonary (or pulmonic) insufficiency (or incompetence, or regurgitation) is a condition in which the pulmonary valve is incompetent and allows backflow from the pulmonary artery to the right ventricle of the heart during diastole. While a small amount of backflow may occur ordinarily, it is usually only shown on an echocardiogram and is harmless. More pronounced regurgitation that is noticed through a routine physical examination is a medical sign of disease and warrants further investigation. If it is secondary to pulmonary hypertension it is referred to as a Graham Steell murmur.

Signs and symptoms
Because pulmonic regurgitation is the result of other factors in the body, any noticeable symptoms are ultimately caused by an underlying medical condition rather than the regurgitation itself. However, more severe regurgitation may contribute to right ventricular enlargement by dilation, and in later stages, right heart failure. A diastolic decrescendo murmur can sometimes be identified,( heard best) over the left lower sternal border.

Causes
Among the causes of pulmonary insufficiency are:

Pathophysiology
The pathophysiology is due to diastolic pressure variations between the pulmonary artery and right ventricle, differences are often very small, but increase regurgitation. An elevation in pulmonary insufficiency due to elevated intrathoracic pressure is relevant in ventilated patients (having acute restrictive right ventricular physiology). The reasons for changes in stiffness of the right ventricles walls are  not well understood, but such stiffness is thought to increase with hypertrophy of the ventricle.

Diagnosis
In the diagnosis of pulmonary insufficiency both echocardiograms and ECG is used to ascertain if the individual has this condition, as well as, the use of a chest x-ray to expose enlargement of the right atrium or ventricle.

Treatment
In treating pulmonary insufficiency, it should be determined if pulmonary hypertension is causing the problem to therefore begin the most appropriate therapy as soon as possible (primary pulmonary hypertension or secondary pulmonary hypertension due to thromboembolism). Furthermore, pulmonary insufficiency is generally treated by addressing the underlying condition, in certain cases, the pulmonary valve may be surgically replaced.

See also
Pulmonary valve stenosis

References
Further reading
Lake, Carol L.; Booker, Peter D. (2005-01-01). Pediatric Cardiac Anesthesia. Lippincott Williams & Wilkins. ISBN 9780781751759.
Bruce, Charles J.; Connolly, Heidi M. (2009-05-26). "Right-Sided Valve Disease Deserves a Little More Respect" </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 Stomach cancer and can you explain it in depth? [/INST] Stomach cancer, also known as gastric cancer, is a cancer that develops from the lining of the stomach. Most cases of stomach cancers are gastric carcinomas, which can be divided into a number of subtypes, including gastric adenocarcinomas. Lymphomas and mesenchymal tumors may also develop in the stomach. Early symptoms may include heartburn, upper abdominal pain, nausea, and loss of appetite. Later signs and symptoms may include weight loss, yellowing of the skin and whites of the eyes, vomiting, difficulty swallowing, and blood in the stool, among others. The cancer may spread from the stomach to other parts of the body, particularly the liver, lungs, bones, lining of the abdomen, and lymph nodes.The most common cause is infection by the bacterium Helicobacter pylori, which accounts for more than 60% of cases. Certain types of H. pylori have greater risks than others. Smoking, dietary factors such as pickled vegetables and obesity are other risk factors. About 10% of cases run in families, and between 1% and 3% of cases are due to genetic syndromes inherited from a persons parents such as hereditary diffuse gastric cancer. Most of the time, stomach cancer develops in stages over years. Diagnosis is usually by biopsy done during endoscopy. This is followed by medical imaging to determine if the disease has spread to other parts of the body. Japan and South Korea, two countries that have high rates of the disease, screen for stomach cancer.A Mediterranean diet lowers the risk of stomach cancer, as does the stopping of smoking. Tentative evidence indicates that treating H. pylori decreases the future risk. If stomach cancer is treated early, it can be cured. Treatments may include some combination of surgery, chemotherapy, radiation therapy, and targeted therapy. For certain subtypes of gastric cancer, cancer immunotherapy is an option as well. If treated late, palliative care may be advised. Some types of lymphoma can be cured by eliminating H. pylori. Outcomes are often poor, with a less than 10% five-year survival rate in the Western world for advanced cases. This is largely because most people with the condition present with advanced disease. In the United States, five-year survival is 31.5%, while in South Korea it is over 65% and Japan over 70%, partly due to screening efforts.Globally, stomach cancer is the fifth-leading type of cancer and the third-leading cause of death from cancer, making up 7% of cases and 9% of deaths. In 2018, it newly occurred in 1.03 million people and caused 783,000 deaths. Before the 1930s, in much of the world, including most Western developed countries, it was the most common cause of death from cancer. Rates of death have been decreasing in many areas of the world since then. This is believed to be due to the eating of less salted and pickled foods as a result of the development of refrigeration as a method of storing food. Stomach cancer occurs most commonly in East Asia and Eastern Europe. It occurs twice as often in males as in females.

Signs and symptoms
Stomach cancer is often either asymptomatic (producing no noticeable symptoms) or it may cause only nonspecific symptoms (which may also be present in other related or unrelated disorders) in its early stages. By the time symptoms are recognized, the cancer has often reached an advanced stage (see below) and may have metastasized (spread to other, perhaps distant, parts of the body), which is one of the main reasons for its relatively poor prognosis. Stomach cancer can cause the following signs and symptoms: Unexplained nausea, vomiting, diarrhoea and constipation. Patients also can experience unexplained weight loss.Early cancers may be associated with indigestion or a burning sensation (heartburn). However, fewer than one in every 50 people referred for endoscopy due to indigestion has cancer. Abdominal discomfort and loss of appetite, especially for meat, can occur.Gastric cancers that have enlarged and invaded normal tissue can cause weakness, fatigue, bloating of the stomach after meals, abdominal pain in the upper abdomen, nausea and occasional vomiting. Further enlargement may cause weight loss or bleeding with vomiting blood or having blood in the stool, the latter apparent as black discolouration (melena) and sometimes leading to anemia. Dysphagia suggests a tumour in the cardia or extension of the gastric tumour into the esophagus.These can be symptoms of other problems such as a stomach virus, gastric ulcer, or tropical sprue.

Risk factors
Gastric cancer can occur as a result of many factors. It occurs twice as commonly in males as females. Estrogen may protect women against the development of this form of cancer.

Infections
Helicobacter pylori infection is an essential risk factor in 65–80% of gastric cancers, but only 2% of people with H. pylori infections develop stomach cancer. The mechanism by which H. pylori induces stomach cancer potentially involves chronic inflammation, or the action of H. pylori virulence factors such as CagA. It was estimated that Epstein–Barr virus is responsible for 84,000 cases per year. AIDS is also associated with elevated risk.

Smoking
Smoking increases the risk of developing gastric cancer significantly, from 40% increased risk for current smokers to 82% increase for heavy smokers. Gastric cancers due to smoking mostly occur in the upper part of the stomach near the esophagus. Some studies show increased risk with alcohol consumption as well.

Diet
Dietary factors are not proven causes, and the association between stomach cancer and various foods and beverages is weak. Some foods including smoked foods, salt and salt-rich foods, red meat, processed meat, pickled vegetables, and brackens are associated with a higher risk of stomach cancer. Nitrates and nitrites in cured meats can be converted by certain bacteria, including H. pylori, into compounds that have been found to cause stomach cancer in animals.Fresh fruit and vegetable intake, citrus fruit intake, and antioxidant intake are associated with a lower risk of stomach cancer. A Mediterranean diet is associated with lower rates of stomach cancer, as is regular aspirin use.Obesity is a physical risk factor that has been found to increase the risk of gastric adenocarcinoma by contributing to the development of gastroesophageal reflux disease (GERD). The exact mechanism by which obesity causes GERD is not completely known. Studies hypothesize that increased dietary fat leading to increased pressure on the stomach and the lower esophageal sphincter, due to excess adipose tissue, could play a role, yet no statistically significant data have been collected. However, the risk of gastric cardia adenocarcinoma, with GERD present, has been found to increase more than 2 times for an obese person. There is a correlation between iodine deficiency and gastric cancer.

Genetics
About 10% of cases run in families, and between 1 and 3% of cases are due to genetic syndromes inherited from a persons parents such as hereditary diffuse gastric cancer.A genetic risk factor for gastric cancer is a genetic defect of the CDH1 gene known as hereditary diffuse gastric cancer (HDGC). The CDH1 gene, which codes for E-cadherin, lies on the 16th chromosome. When the gene experiences a particular mutation, gastric cancer develops through a mechanism that is not fully understood. This mutation is considered autosomal dominant, meaning that half of a carriers children will likely experience the same mutation. Diagnosis of hereditary diffuse gastric cancer usually takes place when at least two cases involving a family member, such as a parent or grandparent, are diagnosed, with at least one diagnosed before the age of 50. The diagnosis can also be made if at least three cases occur in the family, in which case age is not considered.The International Cancer Genome Consortium is leading efforts to identify genomic changes involved in stomach cancer. A very small percentage of diffuse-type gastric cancers (see Histopathology below) arise from an inherited abnormal CDH1 gene. Genetic testing and treatment options are available for families at risk.

Other
Other risk factors include diabetes, pernicious anemia, chronic atrophic gastritis, Menetriers disease (hyperplastic, hypersecretory gastropathy), and intestinal metaplasia.In addition, Foxp3 polymorphism (rs3761548) might contribute to gastric cancer development through influencing Treg cell activity.

Diagnosis
To find the cause of symptoms, the doctor asks about the patients medical history, does a physical examination, and may order laboratory studies.
The patient may also have one or all of these exams:

Gastroscopic exam is the diagnostic method of choice. This involves insertion of a fibre optic camera into the stomach to visualise it.
Upper GI series (may be called barium roentgenogram)
Computed tomography or CT scanning of the abdomen may reveal gastric cancer. It is more useful to determine invasion into adjacent tissues or the presence of spread to local lymph nodes. Wall thickening of more than 1 cm that is focal, eccentric, and enhancing favours malignancy.In 2013, Chinese and Israeli scientists reported a successful pilot study of a breathalyzer-style breath test intended to diagnose stomach cancer by analyzing exhaled chemicals without the need for an intrusive endoscopy. A larger-scale clinical trial of this technology was completed in 2014.Abnormal tissue seen in a gastroscope examination is biopsied by the surgeon or gastroenterologist. This tissue is then sent to a pathologist for histological examination under a microscope to check for the presence of cancerous cells. A biopsy, with subsequent histological analysis, is the only sure way to confirm the presence of cancer cells.Various gastroscopic modalities have been developed to increase yield of detected mucosa with a dye that accentuates the cell structure and can identify areas of dysplasia. Endocytoscopy involves ultra-high magnification to visualise cellular structure to better determine areas of dysplasia. Other gastroscopic modalities such as optical coherence tomography are being tested investigationally for similar applications.A number of cutaneous conditions are associated with gastric cancer. A condition of darkened hyperplasia of the skin, frequently of the axilla and groin, known as acanthosis nigricans, is associated with intra-abdominal cancers such as gastric cancer. Other cutaneous manifestations of gastric cancer include "tripe palms" (a similar darkening hyperplasia of the skin of the palms) and the Leser-Trelat sign, which is the rapid development of skin lesions known as seborrheic keratoses.Various blood tests may be done, including a complete blood count  to check for anaemia, and a fecal occult blood test to check for blood in the stool.

Histopathology
Gastric adenocarcinoma is a malignant epithelial tumour, originating from glandular epithelium of the gastric mucosa. Stomach cancers are about 90% adenocarcinomas. Histologically, there are two major types of gastric adenocarcinoma (Lauren classification): intestinal type or diffuse type. Adenocarcinomas tend to aggressively invade the gastric wall, infiltrating the muscularis mucosae, the submucosa and then the muscularis propria. Intestinal type adenocarcinoma tumour cells describe irregular tubular structures, harbouring pluristratification, multiple lumens, reduced stroma ("back to back" aspect). Often, it associates intestinal metaplasia in neighbouring mucosa. Depending on glandular architecture, cellular pleomorphism and mucosecretion, adenocarcinoma may present 3 degrees of differentiation: well, moderate and poorly differentiated. Diffuse type adenocarcinoma (mucinous, colloid, linitis plastica or leather-bottle stomach) tumour cells are discohesive and secrete mucus, which is delivered in the interstitium, producing large pools of mucus/colloid (optically "empty" spaces). It is poorly differentiated. In signet-ring cell carcinomas, the mucus remains inside the tumour cell and pushes the nucleus to the periphery, giving rise to signet-ring cells.
Around 5% of gastric cancers are lymphomas. These may include extranodal marginal zone B-cell lymphomas (MALT type) and to a lesser extent diffuse large B-cell lymphomas. MALT type make up about half of stomach lymphomas.
Carcinoid and stromal tumors may occur.

Staging
If cancer cells are found in the tissue sample, the next step is to stage, or find out the extent of the disease. Various tests determine whether the cancer has spread, and if so, what parts of the body are affected. Because stomach cancer can spread to the liver, pancreas, and other organs near the stomach, as well as to the lungs, the doctor may order a CT scan, a PET scan, an endoscopic ultrasound exam, or other tests to check these areas. Blood tests for tumor markers, such as carcinoembryonic antigen and carbohydrate antigen may be ordered, as their levels correlate to extent of metastasis, especially to the liver, and the cure rate.Staging may not be complete until after surgery. The surgeon removes nearby lymph nodes and possibly samples of tissue from other areas in the abdomen for examination by a pathologist.The clinical stages of stomach cancer are:
Stage 0 – Limited to the inner lining of the stomach, it is treatable by endoscopic mucosal resection when found very early (in routine screenings), or otherwise by gastrectomy and lymphadenectomy without need for chemotherapy or radiation.
Stage I –   Penetration to the second or third layers of the stomach (stage 1A) or to the second layer and nearby lymph nodes (stage 1B): Stage 1A is treated by surgery, including removal of the omentum. Stage 1B may be treated with chemotherapy (5-fluorouracil) and radiation therapy.
Stage II – Penetration to the second layer and more distant lymph nodes, or the third layer and only nearby lymph nodes, or all four layers but not the lymph nodes, it is treated as for stage I, sometimes with additional neoadjuvant chemotherapy.
Stage III – Penetration to the third layer and more distant lymph nodes, or penetration to the fourth layer and either nearby tissues or nearby or more distant lymph nodes, it is treated as for stage II; a cure is still possible in some cases.
Stage IV – Cancer has spread to nearby tissues and more distant lymph nodes, or has metastasized to other organs. A cure is very rarely possible at this stage. Some other techniques to prolong life or improve symptoms are used, including laser treatment, surgery, and/or stents to keep the digestive tract open, and chemotherapy by drugs such as 5-fluorouracil, cisplatin, epirubicin, etoposide, docetaxel, oxaliplatin, capecitabine, or irinotecan.
The TNM staging system is also used.In a study of open-access endoscopy in Scotland, patients were diagnosed 7% in stage I, 17% in stage II, and 28% in stage III. A Minnesota population was diagnosed 10% in stage I, 13% in stage II, and 18% in stage III. However, in a high-risk population in the Valdivia Province of southern Chile, only 5% of patients were diagnosed in the first two stages and 10% in stage III.

Prevention
Getting rid of H. pylori in those who are infected decreases the risk of stomach cancer, at least in those who are Asian. A 2014 meta-analysis of observational studies found that a diet high in fruits, mushrooms, garlic, soybeans, and green onions was associated with a lower risk of stomach cancer in the Korean population. Low doses of vitamins, especially from a healthy diet, decrease the risk of stomach cancer. A previous review of antioxidant supplementation did not find supporting evidence and possibly worse outcomes.

Management
Cancer of the stomach is difficult to cure unless it is found at an early stage (before it has begun to spread). Unfortunately, because early stomach cancer causes few symptoms, the disease is usually advanced when the diagnosis is made.Treatment for stomach cancer may include surgery, chemotherapy, or radiation therapy. New treatment approaches such as immunotherapy or gene therapy and improved ways of using current methods are being studied in clinical trials.

Surgery
Surgery remains the only curative therapy for stomach cancer. Of the different surgical techniques, endoscopic mucosal resection (EMR) is a treatment for early gastric cancer (tumor only involves the mucosa) that was pioneered in Japan and is available in the United States at some centers. In EMR, the tumor, together with the inner lining of stomach (mucosa), is removed from the wall of the stomach using an electrical wire loop through the endoscope. The advantage is that it is a much smaller operation than removing the stomach. Endoscopic submucosal dissection is a similar technique pioneered in Japan, used to resect a large area of mucosa in one piece. If the pathologic examination of the resected specimen shows incomplete resection or deep invasion by tumor, the patient would need a formal stomach resection. A 2016 Cochrane review found low-quality evidence of no difference in short-term mortality between laparoscopic and open gastrectomy (removal of stomach), and that benefits or harms of laparoscopic gastrectomy cannot be ruled out. Post-operatively, up to 70% of people undergoing total gastrectomy develop complications such as dumping syndrome and reflux esophagitis. Construction of a "pouch", which serves as a "stomach substitute", reduced the incidence of dumping syndrome and reflux esophagitis by 73% and 63% respectively, and led to improvements in quality-of-life, nutritional outcomes, and body mass index.Those with metastatic disease at the time of presentation may receive palliative surgery, and while it remains controversial, due to the possibility of complications from the surgery itself and because it may delay chemotherapy, the data so far are mostly positive, with improved survival rates being seen in those treated with this approach.

Chemotherapy
The use of chemotherapy to treat stomach cancer has no firmly established standard of care. Unfortunately, stomach cancer has not been particularly sensitive to these drugs, and chemotherapy, if used, has usually served to palliatively reduce the size of the tumor, relieve symptoms of the disease, and increase survival time. Some drugs used in stomach cancer treatment have included: fluorouracil or its analog capecitabine, BCNU (carmustine), methyl-CCNU (semustine) and doxorubicin (Adriamycin), as well as mitomycin C, and more recently cisplatin and taxotere, often using drugs in various combinations. The relative benefits of these different drugs, alone and in combination, are unclear. Clinical researchers are exploring the benefits of giving chemotherapy before surgery to shrink the tumor, or as adjuvant therapy after surgery to destroy remaining cancer cells.

Targeted therapy
Recently, treatment with human epidermal growth factor receptor 2 (HER2) inhibitor, trastuzumab, has been demonstrated to increase overall survival in inoperable locally advanced or metastatic gastric carcinoma over-expressing the HER2/neu gene. In particular, HER2 is overexpressed in 13–22% of patients with gastric cancer. Of note, HER2 overexpression in gastric neoplasia is heterogeneous and comprises a minority of tumor cells (less than 10% of gastric cancers overexpress HER2 in more than 5% of tumor cells). Hence, this heterogeneous expression should be taken into account for HER2 testing, particularly in small samples such as biopsies, requiring the evaluation of more than one bioptic sample.

Radiation
Radiation therapy (also called radiotherapy) may be used to treat stomach cancer, often as an adjuvant to chemotherapy and/or surgery.

Lymphoma
MALT lymphomas can often be fully treated by treating an underlying H. pylori infection. This results in remission in about 80% of cases.

Prognosis
The prognosis of stomach cancer is generally poor, because the tumor has often metastasized by the time of discovery, and most people with the condition are elderly (median age is between 70 and 75 years) at presentation. The average life expectancy after being diagnosed is around 24 months, and the five-year survival rate for stomach cancer is less than 10%.Almost 300 genes are related to outcomes in stomach cancer, with both unfavorable genes where high expression is related to poor survival and favorable genes where high expression is associated with longer survival times. Examples of poor prognosis genes include ITGAV, DUSP1 and P2RX7.

Epidemiology
Worldwide, stomach cancer is the fifth most-common cancer with 952,000 cases diagnosed in 2012. It is more common both in men and in developing countries. In 2012, it represented 8.5% of cancer cases in men, making it the fourth-most common cancer in men. Also in 2012, the number of deaths was 700,000, having decreased slightly from 774,000 in 1990, making it the third-leading cause of cancer-related death (after lung cancer and liver cancer).Less than 5% of stomach cancers occur in people under 40 years of age, with 81.1% of that 5% in the age-group of 30 to 39 and 18.9% in the age-group of 20 to 29.In 2014, stomach cancer resulted in 0.61% of deaths (13,303 cases) in the U.S. In China, stomach cancer accounted for 3.56% of all deaths (324,439 cases). The highest rate of stomach cancer was in Mongolia, at 28 cases per 100,000 people.In the United Kingdom, stomach cancer is the 15th-most common cancer (around 7,100 people were diagnosed with stomach cancer in 2011), and it is the 10th-most common cause of cancer-related deaths (around 4,800 people died in 2012).Incidence and mortality rates of gastric cancer vary greatly in Africa. The GLOBOCAN system is currently the most widely used method to compare these rates between countries, but African incidence and mortality rates are seen to differ among countries, possibly due to the lack of universal access to a registry system for all countries. Variation as drastic as estimated rates from 0.3/100000 in Botswana to 20.3/100000 in Mali have been observed. In Uganda, the incidence of gastric cancer has increased from the 1960s measurement of 0.8/100000 to 5.6/100000. Gastric cancer, though present, is relatively low when compared to countries with high incidence like Japan and China. One suspected cause of the variation within Africa and between other countries is due to different strains of the H. pylori bacteria. The trend commonly seen is that H. pylori infection increases the risk for gastric cancer, but this is not the case in Africa, giving this phenomenon the name the "African enigma" </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 Snoring and can you explain it in depth? [/INST] Snoring is the vibration of respiratory structures and the resulting sound due to obstructed air movement during breathing while sleeping. The sound may be soft or loud and unpleasant. Snoring during sleep may be a sign, or first alarm, of obstructive sleep apnea (OSA). Research suggests that snoring is one of the factors of sleep deprivation.

Causes
Snoring is the result of the relaxation of the uvula and soft palate. These tissues can relax enough to partially block the airway, resulting in irregular airflow and vibrations. Snoring can be attributed to one or more of the following:

Genetic predisposition, a proportion of which may be mediated through other heritable lifestyle factors such as body mass index, smoking and alcohol consumption.
Throat weakness, causing the throat to close during sleep.
Mispositioned jaw, often caused by tension in the muscles.
Obesity that has caused fat to gather in and around the throat.
Obstruction in the nasal passageway.
Obstructive sleep apnea.
Sleep deprivation.
Relaxants such as alcohol or other drugs relaxing throat muscles.
Sleeping on ones back, which may result in the tongue dropping to the back of the mouth.
Mouth breathing

Possible consequences
Snoring is known to cause sleep deprivation to snorers and those around them, as well as daytime drowsiness, irritability, lack of focus and decreased libido. It has also been suggested that it can cause significant psychological and social damage to those affected. Multiple studies reveal a positive correlation between loud snoring and risk of heart attack (about +34% chance) and stroke (about +67% chance).Though snoring is often considered a minor condition, snorers can sometimes experience severe impairment of lifestyle. The between-subjects trial by Armstrong et al. discovered a statistically significant improvement in marital relations after snoring was surgically corrected. This was confirmed by evidence from Gall et al., Cartwright and Knight and Fitzpatrick et al.Studies have associated loud snoring with the development of carotid artery atherosclerosis. Amatoury et al. demonstrated that snoring vibrations are transmitted to the carotid artery, identifying a possible mechanism for snoring-associated carotid artery damage and atherosclerotic plaque development. These researchers also found amplification of the snoring energy within the carotid lumen at certain frequencies, adding to this scenario. Vibration of the carotid artery with snoring also lends itself as a potential mechanism for atherosclerotic plaque rupture and consequently ischemic stroke. Researchers also hypothesize that loud snoring could create turbulence in carotid artery blood flow. Generally speaking, increased turbulence irritates blood cells and has previously been implicated as a cause of atherosclerosis. While there is plausibility and initial evidence to support snoring as an independent source of carotid artery/cardiovascular disease, additional research is required to further clarify this hypothesis.

Treatment
So far, there is no certain treatment that can completely stop snoring. Almost all treatments for snoring revolve around lessening the breathing discomfort by clearing the blockage in the air passage. Medications are usually not helpful in treating snoring symptoms, though they can help control some of the underlying causes such as nasal congestion and allergic reactions. Doctors, therefore, often recommend lifestyle changes as a first line treatment to stop snoring. This is the reason snorers are advised to lose weight (to stop fat from pressing on the throat), stop smoking (smoking weakens and clogs the throat), avoid alcohol and sedative medications before bedtime (they relax the throat and tongue muscles, which in turn narrow the airways) and sleep on their side (to prevent the tongue from blocking the throat).
A number of other treatment options are also used to stop snoring. These range from over-the-counter aids such as nasal sprays, nasal strips or nose clips, lubricating sprays, oral appliances and "anti-snore" clothing and pillows, to unusual activities such as playing the didgeridoo. However, one needs to be wary of over-the-counter snore treatments that have no scientific evidence to support their claims, such as stop-snore rings or wrist worn electrical stimulation bands.

Tongue exercises
Myofunctional therapy, which incorporates oropharyngeal and tongue exercises, reduces snoring in adults based on both subjective questionnaires and objective sleep studies. Snoring intensity was reduced by 51%.

Orthopedic pillows
Orthopedic pillows are the least intrusive option for reducing snoring. These pillows are designed to support the head and neck in a way that ensures the jaw stays open and slightly forward. This helps keep the airways unrestricted as possible and in turn leads to a small reduction in snoring.

Dental appliances
Specially made dental appliances called mandibular advancement splints, which advance the lower jaw slightly and thereby pull the tongue forward, are a common mode of treatment for snoring. Such appliances have been proven to be effective in reducing snoring and sleep apnea in cases where the apnea is mild to moderate. Mandibular advancement splints are often tolerated much better than CPAP machines.

Positive airway pressure
A continuous positive airway pressure (CPAP) machine is often used to control sleep apnea and the snoring associated with it. It is a relatively safe medical treatment. To keep the airway open, a device pumps a controlled stream of air through a flexible hose to a mask worn over the nose, mouth, or both. A CPAP is usually applied through a CPAP mask which is placed over the nose and/or mouth. The air pressure required to keep the airway open is delivered through this and it is attached to a CPAP machine which is like an air compressor.
The air that CPAP delivers is generally "normal air" – not concentrated oxygen. The machine utilizes the air pressure as an "air splint" to keep the airway open. In obstructive sleep apnea, the airway at the rear of the throat is prone to closure.

Surgery
Surgery is also available as a method of correcting social snoring. Some procedures, such as uvulopalatopharyngoplasty, attempt to widen the airway by removing tissues in the back of the throat, including the uvula and pharynx. These surgeries are quite invasive, however, and there are risks of adverse side effects. The most dangerous risk is that enough scar tissue could form within the throat as a result of the incisions to make the airway more narrow than it was prior to surgery, diminishing the airspace in the velopharynx. Scarring is an individual trait, so it is difficult for a surgeon to predict how much a person might be predisposed to scarring. Currently, the American Medical Association does not approve of the use of lasers to perform operations on the pharynx or uvula.
Radiofrequency ablation (RFA) is a relatively new surgical treatment for snoring. This treatment applies radiofrequency energy and heat (between 77 °C and 85 °C) to the soft tissue at the back of the throat, such as the soft palate and uvula, causing scarring of the tissue beneath the skin. After healing, this results in stiffening of the treated area. The procedure takes less than one hour, is usually performed on an outpatient basis, and usually requires several treatment sessions. Radiofrequency ablation is frequently effective in reducing the severity of snoring, but often does not eliminate it.Bipolar radiofrequency ablation, a technique used for coblation tonsillectomy, is also used for the treatment of snoring.

Pillar procedure
The pillar procedure is a minimally invasive treatment for snoring and obstructive sleep apnea </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 Breech birth and can you explain it in depth? [/INST] A breech birth is when a baby is born bottom first instead of head first, as is normal. Around 3–5% of pregnant women at term (37–40 weeks pregnant) have a breech baby. Due to their higher than average rate of possible complications for the baby, breech births are generally considered higher risk. Breech births also occur in many other mammals such as dogs and horses, see veterinary obstetrics.
Most babies in the breech position are delivered via caesarean section because it is seen as safer than being born vaginally. Doctors and midwives in the developing world often lack many of the skills required to safely assist women giving birth to a breech baby vaginally. Also, delivering all breech babies by caesarean section in developing countries is difficult to implement as there are not always resources available to provide this service. OB-GYNs do not recommend home births if a breech birth is expected, even when attended by a medical professional.

Cause
With regard to the fetal presentation during pregnancy, three periods have been distinguished.During the first period, which lasts until the 24th gestational week, the incidence of a longitudinal lie increases, with equal proportions of breech or cephalic presentations from this lie. This period is characterized by frequent changes of presentations. The fetuses in breech presentation during this period have the same probability for breech and cephalic presentation at delivery.
During the second period, lasting from the 25th to the 35th gestational week, the incidence of cephalic presentation increases, with a proportional decrease of breech presentation. The second period is characterized by a higher than random probability that the fetal presentation during this period will also be present at the time of delivery. The increase of this probability is gradual and identical for breech and cephalic presentations during this period.
In the third period, from the 36th gestational week onward, the incidence of cephalic and breech presentations remain stable, i.e. breech presentation around 3–4% and cephalic presentation approximately 95%. In the general population, incidence of breech presentation at preterm corresponds to the incidence of breech presentation when birth occurs.A breech presentation at delivery occurs when the fetus does not turn to a cephalic presentation. This failure to change presentation can result from endogenous and exogenous factors. Endogenous factors involve fetal inability to adequately move, whereas exogenous factors refer to insufficient intrauterine space available for fetal movements.The incidence of breech presentation is affected by both maternal and fetal diseases and medical conditions. When these factors are present, the probability of breech presentation is between 4% and 50%.

Rates in various medical conditions
Fetal entities:
First twin 17–30%
Second twin 28–39%
Stillborn 26%
Prader–Willi syndrome 50%, Werdnig–Hoffman syndrome 10%
Smith–Lemli–Opitz syndrome 40%
Fetal alcohol syndrome 40%
Potter anomaly 36%
Zellweger syndrome 27%
Myotonic dystrophy 21%, 13 trisomy syndrome 12%
18 trisomy syndrome 43%
21 trisomy syndrome 5%
de Lange syndrome 10%
Anencephalus 6–18%, Spina bifida 20–30%
Congenital hydrocephalus 24–37%
Osteogenesis imperfecta 33.3%
Amyoplasia 33.3%
Achondrogenesis 33.3%
Amelia 50%
Craniosynostosis 8%
Sacral agenesis 30.4%
Arthrogriposis multiplex congenita 33.3
Congenital dislocation of the hip 33.3%
Hereditary sensory neuropathy type III 25%
Centronuclear myopathy 16.7%
Multiple pituitary hormone deficiency 50%
Isolated pituitary hormone deficiency 20%
Ectopic posterior pituitary gland 33.3%
Congenital bilateral perisilvian syndrome 33.3
Symmetric fetal growth restriction 40%
Asymmetric fetal growth restriction 40%
Nonimmune hydrops fetalis 15%
Atresia ani 18.2%
Microcephalus 15.4%
Omphalocele 12.5%
Prematurity 40%
Placental and amniotic fluid entities:
Amniotic sheet perpendicular to the placenta 50%
Cornual–fundal implantation of the placenta 30%
Placenta previa 12.5%
Oligohydramnios 17%
Polyhydramnios 15.8%
Maternal entities:
Uterus arcuatus 22.6%
Uterus unicornuatus 33.3%
Uterus bicornuatus 34.8%
Uterus didelphys 30–41%
Uterus septus 45.8%
Leiomyoma uteri 9–20%
Spinal cord injury 10%
Carriers of Duchenne muscular dystrophy 17%
Combination of two medical entities:
First twin in uterus with two bodies 14.29%
Second twin in uterus with two bodies 18.52%.Also, women with previous Caesarean deliveries have a risk of breech presentation at term twice that of women with previous vaginal deliveries.The highest possible probability of breech presentation of 50% indicates that breech presentation is a consequence of random filling of the intrauterine space, with the same probability of breech and cephalic presentation in a longitudinally elongated uterus.

Types
Types of breech depend on how the babys legs are lying.
A frank breech (otherwise known as an extended breech) is where the babys legs are up next to its abdomen, with its knees straight and its feet next to its ears. This is the most common type of breech.
A complete breech (or flexed breech) is when the baby appears as though it is sitting crossed-legged with its legs bent at the hips and knees.
A footling breech is when one or both of the babys feet are born first instead of the pelvis. This is more common in babies born prematurely or before their due date.
A kneeling breech is when the baby is born knees first.In addition to the above, breech births in which the sacrum is the fetal denominator can be classified by the position of a fetus. Thus sacro-anterior, sacro-transverse and sacro-posterior positions all exist, but left sacro-anterior is the most common presentation. Sacro-anterior indicates an easier delivery compared to other forms.

Complications
Umbilical cord prolapse may occur, particularly in the complete, footling, or kneeling breech. This is caused by the lowermost parts of the baby not completely filling the space of the dilated cervix. When the waters break the amniotic sac, it is possible for the umbilical cord to drop down and become compressed. This complication severely diminishes oxygen flow to the baby, so the baby must be delivered immediately (usually by Caesarean section) so that he or she can breathe. If there is a delay in delivery, the brain can be damaged. Among full-term, head-down babies, cord prolapse is quite rare, occurring in 0.4 percent. Among frank breech babies the incidence is 0.5 percent, among complete breeches 5 percent, and among footling breeches 15 percent.Head entrapment is caused by the failure of the fetal head to negotiate the maternal midpelvis.  At full term, the fetal bitrochanteric diameter (the distance between the outer points of the hips) is about the same as the biparietal diameter (the transverse diameter of the skull)—simply put the size of the hips are the same as the size of the head. The relatively larger buttocks dilate the cervix as effectively as the head does in the typical head-down presentation. In contrast, the relative head size of a preterm baby is greater than the fetal buttocks. If the baby is preterm, it may be possible for the babys body to emerge while the cervix has not dilated enough for the head to emerge.
Because the umbilical cord—the babys oxygen supply—is significantly compressed while the head is in the pelvis during a breech birth, it is important that the delivery of the aftercoming fetal head not be delayed.  If the arm is extended alongside the head, delivery will not occur. If this occurs, the Løvset manoeuvre may be employed, or the arm may be manually brought to a position in front of the chest. The Løvset manoeuvre involves rotating the fetal body by holding the fetal pelvis.  Twisting the body such that an arm trails behind the shoulder, it will tend to cross down over the face to a position where it can be reached by the obstetricians finger, and brought to a position below the head. A similar rotation in the opposite direction is made to deliver the other arm. In order to present the smallest diameter (9.5 cm) to the pelvis, the babys head must be flexed (chin to chest). If the head is in a deflexed position, the risk of entrapment is increased.  Uterine contractions and maternal muscle tone encourage the head to flex.
Oxygen deprivation may occur from either cord prolapse or prolonged compression of the cord during birth, as in head entrapment. If oxygen deprivation is prolonged, it may cause permanent neurological damage (for instance, cerebral palsy) or death. It has been suggested that a fast vaginal delivery would mean the risk of stopping babys oxygen supply is reduced.  However, there is not enough research to show this and a quick delivery might cause more harm to the baby than a conservative approach to the birth.Injury to the brain and skull may occur due to the rapid passage of the babys head through the mothers pelvis. This causes rapid decompression of the babys head. In contrast, a baby going through labor in the head-down position usually experiences gradual molding (temporary reshaping of the skull) over the course of a few hours. This sudden compression and decompression in breech birth may cause no problems at all, but it can injure the brain. This injury is more likely in preterm babies. The fetal head may be controlled by a special two-handed grip call the Mauriceau–Smellie–Veit maneuver or the elective application of forceps. This will be of value in controlling the rate of delivery of the head and reduce decompression. Related to potential head trauma, researchers have identified a relationship between breech birth and autism.Squeezing the babys abdomen can damage internal organs. Positioning the baby incorrectly while using forceps to deliver the after coming head can damage the spine or spinal cord.  It is important for the birth attendant to be knowledgeable, skilled, and experienced with all variations of breech birth.

Factors influencing safety
Birth attendants skill (and experience with breech birth) – The skill of the doctor or midwife and the number of breech births previously assisted is of crucial importance. Many of the dangers in vaginal birth for breech babies come from mistakes made by birth attendants. With the majority of breech babies being delivered by cesarean section there is more risk that birth attendants will lose their skills in delivering breech babies and therefore increase the risk of harm to the baby during a vaginal delivery.
Type of breech presentation – the frank breech has the most favorable outcomes in vaginal birth, with many studies suggesting no difference in outcome compared to head down babies. (Some studies, however, find that planned caesarean sections for all breech babies improve outcome. The difference may rest in part on the skill of the doctors who delivered babies in different studies.)  Complete breech presentation is the next most favorable position, but these babies sometimes shift and become footling breeches during labour.  Footling and kneeling breeches have a higher risk of cord prolapse and head entrapment.
Parity – Parity refers to the number of times a woman has given birth before.  If a woman has given birth vaginally, her pelvis has "proven" it is big enough to allow a baby of that babys size to pass through it. However, a head-down babys head often molds (shifts its shape to fit the maternal pelvis) and so may present a smaller diameter than the same-size baby born breech.
Fetal size in relation to maternal pelvic size – If the mothers pelvis is roomy and the baby is not large, this is favorable for vaginal breech delivery.  However, prenatal estimates of the size of the baby and the size of the pelvis are unreliable.
Hyperextension of the fetal head – this can be evaluated with ultrasound. Less than 5% of breech babies have their heads in the "star-gazing" position, face looking straight upwards and the back of the head resting against the back of the neck.  Caesarean delivery is absolutely necessary, because vaginal birth with the babys head in this position confers a high risk of spinal cord trauma and death.
Maturity of the baby – Premature babies appear to be at higher risk of complications if delivered vaginally than if delivered by caesarean section.
Progress of labor – A spontaneous, normally progressing, straightforward labor requiring no intervention is a favorable sign.
Second twins – If a first twin is born head down and the second twin is breech, the chances are good that the second twin can have a safe breech birth.

Management
As in labour with a baby in a normal head-down position, uterine contractions typically occur at regular intervals and gradually the cervix begins to thin and open. In the more common breech presentations, the babys bottom (rather than feet or knees) is what is first to descend through the maternal pelvis and emerge from the vagina.At the beginning of labour, the baby is generally in an oblique position, facing either the right or left side. The babys bottom is the same size in the term baby as the babys head.  Descent is thus as for the presenting fetal head and delay in descent is a cardinal sign of possible problems with the delivery of the head.
In order to begin the birth, descent of podalic pole along with compaction and internal rotation needs to occur.  This happens when the mothers pelvic floor muscles cause the baby to turn so that it can be born with one hip directly in front of the other.  At this point the baby is facing one of the mothers inner thighs.  Then, the shoulders follow the same path as the hips did.   At this time the baby usually turns to face the mothers back.   Next occurs external rotation, which is when the shoulders emerge as the babys head enters the maternal pelvis.  The combination of maternal muscle tone and uterine contractions cause the babys head to flex, chin to chest.   Then the  back of the babys head emerges and finally the face.
Due to the increased pressure during labour and birth, it is normal for the babys leading hip to be bruised and genitalia to be swollen. Babies who assumed the frank breech position in utero may continue to hold their legs in this position for some days after birth.

Cesarean or vaginal delivery
When a baby is born bottom first there is more risk that the birth will not be straight forward and that the baby could be harmed. For example, when the babys head passes through the mothers pelvis the umbilical cord can be compressed which prevents delivery of oxygenated blood to the baby. Due to this and other risks, babies in breech position are often born by a planned caesarean section in developed countries.Caesarean section reduces the risk of harm or death for the baby but does increase risk of harm to the mother compared with a vaginal delivery. It is best if the baby is in a head down position so that they can be born vaginally with less risk of harm to both mother and baby. The next section is looking at External cephalic version or ECV which is a method that can help the baby turn from a breech position to a head down position.
Vaginal birth of a breech baby has its risks but caesarean sections are not always available or possible, a mother might arrive in hospital at a late stage of her labour or may choose not to have a caesarean section. In these cases, it is important that the clinical skills needed to deliver breech babies are not lost so that mothers and babies are as safe as possible. Compared with developed countries, planned caesarean sections have not produced as good results in developing countries – it is suggested that this is due to more breech vaginal deliveries being performed by experienced, skilled practitioners in these settings.

Twin breech
In twin pregnancies, it is very common for one or both babies to be in the breech position. Most often twin babies do not have the chance to turn around because they are born prematurely. If both  babies are in the breech position and the mother has gone into labour early, a cesarean section may be the best option. About 30–40% of twin pregnancies result in only one baby being in the breech position. If this is the case, the babies can be born vaginally. After the first baby who is not in the breech position is delivered, the baby who is presented in the breech position may turn itself around, if this does not happen another procedure may performed called the breech extraction. The breech extraction is the procedure that involves the obstetrician grabbing the second twins feet and pulling him/her into the birth canal. This will help with delivering the second twin vaginally. However, if the second twin is larger than the first, complications with delivering the second twin vaginally may arise and a cesarean section should be performed. At times, the first twin (the twin closest to the birth canal) can be in the breech position with the second twin being in the cephalic position (vertical). When this occurs, risks of complications are higher than normal. In particular, a serious complication known as Locked twins </s>