<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 Dysexecutive syndrome and can you explain it in depth? [/INST] Dysexecutive syndrome (DES) consists of a group of symptoms, usually resulting from brain damage, that fall into cognitive, behavioural and emotional categories and tend to occur together. The term was introduced by Alan Baddeley to describe a common pattern of dysfunction in executive functions, such as planning, abstract thinking, flexibility and behavioural control. It is thought to be Baddeleys hypothesized working memory system and the central executive that are the hypothetical systems impaired in DES. The syndrome was once known as frontal lobe syndrome; however dysexecutive syndrome is preferred because it emphasizes the functional pattern of deficits (the symptoms) over the location of the syndrome in the frontal lobe, which is often not the only area affected.
Classification code in ICD-10 - F07

Symptoms and signs
Symptoms of DES fall into three broad categories: cognitive, emotional and behavioural. Many of the symptoms can be seen as a direct result of impairment to the central executive component of working memory, which is responsible for attentional control and inhibition. Although many of the symptoms regularly co-occur, it is common to encounter patients who have several, but not all symptoms. The accumulated effects of the symptoms have a large impact on daily life.

Cognitive symptoms
Cognitive symptoms refer to a persons ability to process thoughts. Cognition primarily refers to memory, the ability to learn new information, speech, and reading comprehension. Deficits within this area cause many problems with everyday life decisions.One of the main difficulties for an individual with DES is planning and reasoning. Impaired planning and reasoning affect the individuals ability to realistically assess and manage the problems of everyday living. New problems and situations may be especially poorly handled because of the inability to transfer previous knowledge to the new event. An individual that has DES may have a short attention span due to impairment in attentional control. This may alter the individuals ability to focus, and as such have difficulty with reading and following a storyline or conversation. For instance, they can easily lose track of conversations which can make it difficult to hold a meaningful conversation and may result in avoiding social interactions.Individuals with DES will have very poor working memory and short term memory due to executive dysfunction. The dysfunction can range from mild and subtle to severe and obvious. There is a tremendous variability in the manifestations of executive dysfunction with strong influences often apparent from the affected persons personality, life experiences and intellect. Individuals with DES may experience confabulation, which is the spontaneous reporting of events that never happened. This can affect their autobiographical memory. It is thought that patients may not be able to assess the accuracy of memory retrieval and therefore elaborate on implausible memories.Individuals with dementia, delirium or other severe psychiatric illnesses combined with DES often have disturbed sleep patterns. Some will not recognize that it is night-time and may become upset when someone tries to correct them.

Emotional symptoms
The emotional symptoms that individuals with DES experience may be quite extreme and can cause extensive problems. They may have difficulty inhibiting many types of emotions such as anger, excitement, sadness, or frustration. Due to multiple impairments of cognitive functioning, there can be much more frustration when expressing certain feelings and understanding how to interpret everyday situations. Individuals with DES may have higher levels of aggression or anger because they lack abilities that are related to behavioural control. They can also have difficulty understanding others points of view, which can lead to anger and frustration.

Behavioural symptoms
Behavioural symptoms are evident through an individuals actions. People with DES often lose their social skills because their judgments and insights into what others may be thinking are impaired. They may have trouble knowing how to behave in group situations and may not know how to follow social norms. The central executive helps control impulses; therefore when impaired, patients have poor impulse control. This can lead to higher levels of aggression and anger. DES can also cause patients to appear self-centered and stubbornUtilization behaviour is when a patient automatically uses an object in the appropriate manner, but at an inappropriate time. For example, if a pen and paper are placed in front of an individual with DES they will start to write or if there is a deck of cards they will deal them out. Patients showing this symptom will begin the behaviour in the middle of conversations or during auditory tests. Utilization behaviour is thought to occur because an action is initiated when an object is seen, but patients with DES lack the central executive control to inhibit acting it out at inappropriate times.Perseveration is also often seen in patients with DES. Perseveration is the repetition of thoughts, behaviours, or actions after they have already been completed. For instance, continually blowing out a match, after it is no longer lit is an example of perseveration behaviour. There are three types of perseveration: continuous perseveration, stuck-in-set perseveration, and recurrent perseveration. Stuck-in-set perseveration is most often seen in dysexecutive syndrome. This type of perseveration refers to when a patient cannot get out of a specific frame of mind, such as when asked to name animals they can only name one. If you ask them to then name colours, they may still give you animals. Perseveration may explain why some patients appear to have obsessive-compulsive disorder.

Comorbid disorders
DES often occurs with other disorders, which is known as comorbidity. Many studies have examined the presence of DES in patients with schizophrenia. Results of schizophrenic patients on the Behavioural Assessment of the Dysexecutive Syndrome (BADS) test (discussed below) are comparable to brain injured patients. Further, results of BADS have been shown to correlate with phases of schizophrenia. Patients in the chronic phase of the disorder have significantly lower scores than those who are acute. This is logical due to the similarities in executive disruptions that make everyday life difficult for those with  schizophrenia and symptoms that form DES.
Patients with Alzheimers disease and other forms of dementia have been shown to exhibit impairment in executive functioning as well. The effects of DES symptoms on the executive functions and working memory, such as attentiveness, planning and remembering recently learned things, are some of the earliest indicators of Alzheimers disease and dementia with Lewy bodies.
Studies have also indicated that chronic alcoholism (see Korsakoffs syndrome) can lead to a mild form of DES according to results of BADS.

Causes
The most frequent cause of the syndrome is brain damage to the frontal lobe. Brain damage leading to the dysexecutive pattern of symptoms can result from physical trauma such as a blow to the head or a stroke  or other internal trauma.
It is important to note that frontal lobe damage is not the only cause of the syndrome. It has been shown that damage, such as lesions, in other areas of the brain may indirectly affect executive functions and lead to similar symptoms (such as ventral tegmental area, basal ganglia and thalamus). There is not one specific pattern of damage that leads to DES, as multiple affected brain structures and locations have led to the symptoms. This is one reason why the term frontal lobe syndrome is not preferred.

Diagnosis
Assessment of patients with DES can be difficult because traditional tests generally focus on one specific problem for a short period of time. People with DES can do fairly well on these tests because their problems are related to integrating individual skills into everyday tasks. The lack of everyday application of traditional tests is known as low ecological validity.

Behavioural
The Behavioural Assessment of the Dysexecutive Syndrome (BADS) was designed to address the problems of traditional tests and evaluate the everyday problems arising from DES. BADS is designed around six subtests and ends with the Dysexecutive Questionnaire (DEX). These tests assess executive functioning in more complex, real-life situations, which improves their ability to predict day-to-day difficulties of DES.

The six tests are as follows:Rule Shift Cards - Assesses the subjects ability to ignore a prior rule after being given a new rule to follow.
Action Program - This test requires the use of problem solving to accomplish a new, practical task.
Key Search - This test reflects the real-life situation of needing to find something that has been lost. It assesses  the patients ability to plan how to accomplish the task and monitor their own progress.
Temporal Judgment - Patients are asked to make estimated guesses to a series of questions such as, "how fast do racehorses gallop?". It tests the ability to make sensible guesses.
Zoo Map - Tests the ability to plan while following a set of rules.
Modified Six Elements - This test assesses the subjects ability to plan, organize and monitor behaviour.The Dysexecutive Questionnaire (DEX) is a 20-item questionnaire designed to sample emotional, motivational, behavioural and cognitive changes in a subject with DES. One version is designed for the subject to complete and another version is designed for someone who is close to the individual, such as a relative or caregiver. Instructions are given to the participant to read 20 statements describing common problems of everyday life and to rate them according to their personal experience. Each item is scored on a 5-point scale according to its frequency from never (0 point) to very often (4 points).

Treatment
There is no cure for individuals with DES, but there are therapies to help them cope with their symptoms. DES can affect a number of functions in the brain and vary from person to person. Because of this variance, it is suggested that the most successful therapy would include multiple methods. Researchers suggest that a number of factors in the executive functioning need to be improved, including self-awareness, goal setting, planning, self-initiation, self-monitoring, self-inhibition, flexibility, and strategic behaviour.
One method for individuals to improve in these areas is to help them plan and carry out actions and intentions through a series of goals and sub-goals. To accomplish this, therapists teach patients a three-step model called the General Planning Approach. The first step is Information and Awareness, in which the patients are taught about their own problems and shown how this affects their lives. The patients are then taught to monitor their executive functions and begin to evaluate them.  The second stage, Goal Setting and Planning, consists of patients making specific goals, as well as devising a plan to accomplish them. For example, patients may decide they will have lunch with a friend (their goal). They are taught to write down which friend it may be, where they are going for lunch, what time they are going, how they will get there, etc. (sub-goals). They are also taught to make sure the steps go in the correct order. The final stage, named Initiation, Execution, and Regulation, requires patients to implement their goals in their everyday lives. Initiation can be taught through normal routines. The first step can cue the patient to go to the next step in their plan. Execution and regulation are put into action with reminders of how to proceed if something goes wrong in the behavioural script. This treatment method has resulted in improved daily executive functioning, however no improvements were seen on formal executive functioning tests.
Since planning is needed in many activities, different techniques have been used to improve this deficit in patients with DES. Autobiographical memories can be used to help direct future behaviour. You can draw on past experiences to know what to do in the future. For example, when you want to take a bus, you know from past experience that you have to walk to the bus stop, have the exact amount of change, put the change in the slot, and then you can go find a seat. Patients with DES seem to not be able to use this autobiographical memory as well as a normal person. Training for DES patients asks them to think of a specific time when they did an activity previously. They are then instructed to think about how they accomplished this activity. An example includes "how would you plan a holiday". Patients are taught to think of specific times they went on a holiday and then to think how they may have planned these holidays. By drawing on past experiences patients were better able to make good decisions and plans.
Cognitive Analytic Therapy (CAT) has also been used to help those with DES. Because individuals with this syndrome have trouble integrating information into their actions it is often suggested that they have programmed reminders delivered to a cell phone or pager. This helps them remember how they should behave and discontinue inappropriate actions. Another method of reminding is to have patients write a letter to themselves. They can then read the letter whenever they need to. To help patients remember how to behave, they may also create a diagram </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 Nasolacrimal duct obstruction and can you explain it in depth? [/INST] Nasolacrimal duct obstruction is the obstruction of the nasolacrimal duct and may be either congenital or acquired. Obstruction of the nasolacrimal duct leads to the excess overflow of tears called epiphora.

Sign and symptoms
Excessive tearing is the most common complaint of patients with nasolacrimal duct obstruction, followed by acute or chronic infections.  Pain at the side of the nose suggests dacryocystitis.
Nasolacrimal duct obstruction is more common with increasing age and more common in females than males.

Cause
Involutional stenosis
Involutional stenosis is probably the most common cause of nasolacrimal duct obstruction in older people. It affects women twice as frequently as men. Although the inciting event in this process is unknown, clinicopathologic study suggests that compression of the lumen of the nasolacrimal duct is caused by inflammatory infiltrates and edema. This may be the result of an unidentified infection or possibly an autoimmune disease.

Dacryolith
Dacryoliths or cast formation, within the lacrimal sac can also produce obstruction of the nasolacrimal duct.

Sinus disease
Sinus disease often occurs in conjunction with, and in other instances may contribute to the development of nasolacrimal duct obstruction. Patients should be asked about previous sinus surgery, as the nasolacrimal duct is sometimes damaged when the maxillary sinus ostium is being enlarged anteriorly.

Trauma
Naso-orbital fractures may involve the nasolacrimal duct. Early treatment by fracture reduction with stenting of the entire lacrimal drainage system should be considered. However, such injuries are often not recognized or are initially neglected as more serious injuries are managed. In such cases, late treatment of persistent epiphora usually requires dacryocystorhinostomy.

Inflammatory disease
Granulomatous disease, including sarcoidosis, granulomatosis with polyangiitis, and  midline granuloma, may also lead to nasolacrimal duct obstruction.

Lacrimal plugs
As with similar cases of canalicular obstruction, dislodged punctual and canalicular plugs can migrate to and occlude the nasolacrimal duct.

Neoplasm
Neoplasm should be considered in any patient presenting with nasolacrimal duct obstruction. In patients with atypical presentations, including younger age and male gender, further workup is appropriate. Bloody punctual discharge or lacrimal sac distension above the medial canthal tendon is also highly suggestive of neoplasm.

Congenital
Congenital nasolacrimal duct obstruction, or dacryostenosis, occurs when the lacrimal duct has failed to open at the time of birth, most often due to an imperforate membrane at the valve of Hasner. Around 6% of infants have congenital nasolacrimal duct obstruction, or dacryostenosis, usually experiencing a persistent watery eye even when not crying. If a secondary infection occurs (Dacryocystitis), purulent (yellow / green) discharge may be present.
Most cases resolve spontaneously, with antibiotics reserved only if conjunctivitis occurs. Lacrimal sac massage has been proposed as helping to open the duct, though this is not always successful. The aim of massage is to generate enough hydrostatic pressure (downward, toward the nose) to "pop" open any obstruction.  Additional massage may then be performed up toward the lacrimal punctum, in order to express any infectious material out of the nasolacrimal sac.  When discharge or crusting is present, the lids should be gently cleaned using cooled pre-boiled water or saline.
Referral to an ophthalmologist is indicated if symptoms are still present at 12 months, or sooner if significant symptoms or recurrent infections occur.  Nasolacrimal duct probing may be performed in the office setting (usually from 4 to 8 months of age) or under general anesthesia in an operating room for older patients.  The success rate of probing is higher for younger children.  A silastic tube or stent may be employed along with probing to maintain tear duct patency. A systematic review comparing immediate probing with deferred probing found that in children with unilateral nasolacrimal duct obstruction, immediate probing resulted in a higher success rate of treatment compared to deferred probing.

Diagnosis
Evaluation is in the form of a dye disappearance test followed by irrigation test. By using this sequence (with modifications) as a guide, the physician can frequently streamline diagnostic testing.

Dye disappearance test
The dye disappearance test is useful for assessing the presence or absence of adequate lacrimal outflow, especially in unilateral cases. It is more heavily relied upon in children, in whom lacrimal irrigation is impossible without deep sedation. Using a drop of sterile 2% fluorescein solution or a moistened fluorescein strip, the examiner instills fluorescein into the conjunctival fornices of each eye and then observes the tear film, preferably with the cobalt blue filter of the slit lamp </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 Bronchocele and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Hypertrophic osteoarthropathy and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Epidermal nevus syndrome and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Sacroiliac joint dysfunction and can you explain it in depth? [/INST] Sacroiliac joint dysfunction generally refers to pain in the sacroiliac joint region that is caused by abnormal motion in the sacroiliac joint, either too much motion or too little motion.

Signs and symptoms
Common symptoms include lower back pain, buttocks pain, sciatic leg pain, groin pain, hip pain (for explanation of leg, groin, and hip pain, see referred pain), urinary frequency, and "transient numbness, prickling, or tingling."  Pain can range from dull aching to sharp and stabbing and increases with physical activity.  Symptoms also worsen with prolonged or sustained positions (i.e., sitting, standing, lying).  Bending forward, stair climbing, hill climbing, and rising from a seated position can also provoke pain. Pain can increase during menstruation in women.  People with severe and disabling sacroiliac joint dysfunction can develop insomnia and depression. Sacral torsion that is untreated over a long period of time can cause severe Achilles tendinosis.

Causes
Hypermobility
Sacroiliac joint dysfunction is an outcome of either extra-articular dysfunction or from intraarticular dysfunction.
SI joint dysfunction is sometimes referred to as "sacroiliac joint instability" or "sacroiliac joint insufficiency"  due to the support the once strong and taut ligaments can no longer sustain. When the joint is hypermobile or loose, it is classified as an extra-articular dysfunction because abnormal joint movement and alignment is a consequence of weakened, injured, or sprained ligaments, while the joint itself is structurally normal and healthy. The sacroiliac joint itself often will not show degenerative changes, such as arthritis, until many years of the dysfunction being allowed to continue. Injury to the ligaments that hold the sacroiliac joints in proper support is thought to be caused by a torsion or high impact injury (such as an automobile accident) or a hard fall, resulting in the hypermobility.  As many as 58% of people diagnosed with sacroiliac joint pain had some inciting traumatic injury based on clinical examination findings.  The joint that was once stabilized by strong ligaments, now overly stretched, sprained, or torn, will move beyond its normal range. This is thought to result in the ilium and sacral surfaces "locking" in an incongruent or asymmetrical fashion (one innominate bone is tilted anteriorly; the other innominate bone is tilted posteriorly) causing pain that can be debilitating.Hormone imbalances, particularly those associated with pregnancy and the hormone relaxin, can also cause a ligamentous laxity resulting in the weakening of the sacroiliac structure.
  During pregnancy, relaxin serves as natures way of allowing the female pelvis to achieve distention of the birthing canal. Pelvic joint pain in post pregnancy women is thought to be derived from the inability of the stretched out ligaments to return to normal tautness. Women who have delivered large babies or who have had extended labors also are prone to developing chronic sacroiliac joint pain and instability.In some people, the sacroiliac joints reverse the normal concave-convex locking relationship, which can lead to rotational misalignment.  The variation in joint configuration results in some sacroiliac joints being inherently weaker or more prone to misalignment.Certain biomechanical or muscle length imbalances may ultimately predispose a person to sacroiliac dysfunction and pain. Likely, this is a result of altered gait patterns and repetitive stress to the SI joint and related structures. These conditions exist in persons with leg-length inequality, scoliosis, a history of polio, poor-quality footwear, and hip osteoarthritis.There is also a notable incidence of lumbar spinal fusion patients that present with sacroiliac pain and hypermobility, potentially due to the adjacent lumbar joints being fixed and unable to move. Clinical studies have found up to 75% of post-lumbar fusion patients develop SI joint degeneration within five years of surgery.

Hypomobility
Pathological hypomobility (too little movement) of the sacroiliac joint is an intra-articular disorder in which the joint locks due to wearing down with age or degenerative joint disease.Hypomobility of this kind can also occur with an inflammatory disease such as ankylosing spondylitis, rheumatoid arthritis, or an infection.

Pathophysiology
The sacroiliac joint is a true diarthrodial joint that joins the sacrum to the pelvis.  The sacrum connects on the right and left sides to the ilia (pelvic bones) to form the sacroiliac joints. The pelvic girdle is made up of two innominate bones (the iliac bones) and the sacrum. The innominate bones join in the front of the pelvis to form the pubic symphysis, and at back of the sacrum to form the sacroiliac (SI) joints. Each innominate bone (ilium) joins the femur (thigh bone) to form the hip joint; thus the sacroiliac joint moves with walking and movement of the torso.In this joint, hyaline cartilage on the sacral side moves against fibrocartilage on the iliac side. The sacroiliac joint contains numerous ridges and depressions that function in stability. Studies have documented that motion does occur at the joint; therefore, slightly subluxed and even locked positions can occur.Muscles and ligaments surround and attach to the SI joint in the front and back, primarily on the ilial or sacral surfaces. These can all be a source of pain and inflammation if the SI joint is dysfunctional.  The sacroiliac joint is highly dependent on its strong ligamentous structure for support and stability. The most commonly disrupted and/or torn ligaments are the iliolumbar ligament and the posterior sacroiliac ligament. The ligamentous structures offer resistance to shear and loading. The deep anterior, posterior, and interosseous ligaments resist the load of the sacrum relative to the ilium.  More superficial ligaments (e.g., the sacrotuberous ligament) react to dynamic motions (such as straight-leg raising during physical motion). The long dorsal sacroiliac ligament can become stretched in periods of increased lumbar lordosis (e.g., during pregnancy).

Affected muscle groups
Many large and small muscles have relationships with the ligaments of the sacroiliac joint including the piriformis (see "piriformis syndrome", a condition often related with sacroiliac joint dysfunction), rectus femoris, gluteus maximus and minimus, erector spinae, latissimus dorsi, thoracolumbar fascia, and iliacus.  Any of these muscles can be involved or spasm with a painful and dysfunctional sacroiliac joint.  The SI joint is a pain-sensitive structure richly innervated by a combination of unmyelinated free nerve endings and the posterior primary rami of spinal segments L2-S3. The wide possibility of innervation may explain why pain originating from the joint can manifest in so many various ways, with different and unique referral patterns (see "referred pain") for individual patients. Patients with sacroiliac joint dysfunction can also develop tightness and dysfunction in the hamstring, quadriceps, iliotibial tract (see "iliotibial band syndrome") and hip flexors, including the psoas muscle. Individuals with severe and long-standing sacroiliac joint dysfunction can develop muscle deconditioning and atrophy throughout the body due to limitation of activities and exercise that bring about pain in the low back.

Diagnosis
Perhaps the biggest reason for misdiagnosis or lack of diagnosis of sacroiliac joint dysfunction is based on the inability of common radiological imaging to discern the disorder. Diagnostic testing, such as X-ray, CT scan, or MRI, do not usually reveal abnormalities; therefore, they cannot reliably be used for diagnosis of sacroiliac joint dysfunction. There is a new imaging test SPECT/CT which can sometimes detect sacroiliac joint dysfunction. There is also a lack of evidence that sacroiliac joint mobility maneuvers (Gillet, Standing flexion test, and Seated Flexion test) detect motion abnormalities. Given the inherent technical limitations of the visible and palpable signs from these sacroiliac joint mobility maneuvers another broad category of clinical signs have been described called provocative maneuvers. These maneuvers are designed to reproduce or increase pain emanating within the sacroiliac joint.A clinician (i.e., a spine surgeon, orthopedic surgeon, sports medicine doctor, athletic trainer, medical massage therapist, physical therapist, physiatrist, osteopath or chiropractor) can develop a probable diagnosis of sacroiliac joint dysfunction by using a hands on approach through palpating the painful areas and performing the  following provocative maneuvers below:
Gaenslen test  - This pain provocation test applies torsion to the joint. With one hip flexed onto the abdomen, the other leg is allowed to dangle off the edge of the table. Pressure should then be directed downward on the leg in order to achieve hip extension and stress the sacroiliac joint.
Iliac Gapping Test - Distraction can be performed to the anterior sacroiliac ligaments by applying pressure to the anterior superior iliac spine.
Iliac Compression Test - Apply compression to the joint with the patient lying on his or her side. Pressure is applied downward to the uppermost iliac crest.
FABER or Patrick test - To identify if pain may come from the sacroiliac joint during flexion, abduction, and external rotation, the clinician externally rotates the hip while the patient lies supine. Then, downward pressure is applied to the medial knee stressing both the hip and sacroiliac joint.
Thigh Thrust - This test applies anteroposterior shear stress on the SI joint. The patient lies supine with one hip flexed to 90 degrees. The examiner stands on the same side as the flexed leg. The examiner provides either a quick thrust or steadily increasing pressure through the line of the femur. The pelvis is stabilized at the sacrum or at the opposite ASIS with the hand of the examinerCautious interpretation is warranted because there are no biomechanical studies showing that the Thigh Thrust test isolates forces in the SIJ when performed at 90 degrees and due to intra-individual variation in body type, hip flexibility, general flexibility of the trunk and pelvis.
In all the tests, pain along the typical area raises suspicion for sacroiliac joint dysfunction. However no single test is very reliable in the diagnosis of sacroiliac joint dysfunction.  It is important to remember true neurogenic weakness, numbness, or loss of reflex should alert the clinician to consider nerve root pathology.The current "gold standard" for diagnosis of sacroiliac joint dysfunction emanating within the joint is sacroiliac joint injection confirmed under fluoroscopy or CT-guidance using a local anesthetic solution.  The diagnosis is confirmed when the patient reports a significant change in relief from pain and the diagnostic injection is performed on 2 separate visits.  Published studies have used at least a 75 percent change in relief of pain before a response is considered positive and the sacroiliac joint deemed the source of pain.
However, several other injection studies have compared intra-articular with extra-articular injection, and indicate that the ligament injection behind the joint is oftentimes superior to injection in the joint and seems to be a very underutilized diagnostic tool.

Misdiagnosis
In the early 1900s, dysfunction of the sacroiliac joint was a common diagnosis associated with low back and sciatic nerve pain.  However, research by Danforth and Wilson in 1925 concluded that the sacroiliac joint could not cause sciatic nerve pain because the joint does not have a canal in which the nerves can be entrapped against the joint. The biomechanical relationship between the sacroiliac joint, the piriformis muscle (see "piriformis syndrome"), and the sciatic nerve had not yet been discovered.In 1934, the work of Mixter and Barr shifted all emphasis in research and treatment from the sacroiliac to the herniated intervertebral disc, namely lumbar discs. Medical focus on herniated discs was further forwarded by the invention of the MRI in 1977. Over-diagnosis and attention on herniated discs has led to the SI joint becoming an underappreciated pain generator in an estimated 15% to 25% of patients with axial low back pain.The ligaments in the sacroiliac are among the strongest in the body and are not suspected by many clinicians to be susceptible to spraining or tearing. Skepticism of the existence of sacroiliac joint dysfunction within the medical community is furthered by the debate on how little or much the sacroiliac joint moves. A discrepancy as large as 2-17 degrees has been reported in clinical findings.

Treatment
Treatment is often dependent on the duration and severity of the pain and dysfunction. In the acute phase (first 1–2 weeks) for a mild sprain of the sacroiliac, it is typical for the patient to be prescribed rest, ice/heat, spinal manipulation, and physical therapy; anti-inflammatory medicine can also be helpful.If the pain does not resolve in the first 1–2 weeks, then the patient may benefit from a steroid and anesthetic mixture fluoroscopically injected into the joint (this also serves in confirming diagnosis), as well as manipulative or manual therapy. For the most severe and chronic forms of sacroiliac dysfunction, treatment should proceed with the support of a sacroiliac belt, injection therapy, and finally, surgery.  The anti-inflammatory effect of injection therapy is not permanent, and the injections do not offer an opportunity to stabilize an incompetent joint. Surgery is often considered a last resort, but for some patients, it is the only method of effectively stabilizing the loose joint </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Warty dyskeratoma and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Urethral hypermobility and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Acrodysostosis and can you explain it in depth? [/INST] Acrodysostosis  is a rare congenital malformation syndrome which involves shortening of the interphalangeal joints of the hands and feet, intellectual disability in approximately 90% of affected children, and peculiar facies. Other common abnormalities include short head (as measured front to back), small broad upturned nose with flat nasal bridge, protruding jaw, increased bone age, intrauterine growth retardation, juvenile arthritis and short stature. Further abnormalities of the skin, genitals, teeth, and skeleton may occur.Other common abnormalities include short head (as measured front to back), small broad upturned nose with flat nasal bridge, protruding jaw, increased bone age, intrauterine growth retardation, juvenile arthritis and short stature </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Pemphigus herpetiformis and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Papular mucinosis and can you explain it in depth? [/INST] Papular mucinosis (also known as scleromyxedema, "generalized lichen myxedematosus" and "sclerodermoid lichen myxedematosus") is a rare skin disease. Localized and disseminated cases are called papular mucinosis or lichen myxedematosus while generalized, confluent papular forms with sclerosis are called scleromyxedema. Frequently, all three forms are regarded as papular mucinosis. However, some authors restrict it to only mild cases. Another form, acral persistent papular mucinosis is regarded as a separate entity.

Presentation
Papular mucinosis is chronic and may be progressive. The dermal layer of the skin breaks out into small and solid bumps, usually conical in shape and measured from 2 to 4 mm or sometimes flat-topped papules. Unlike pustules, these bumps do not contain pus. Instead they contain mucin, a waxy substance of mucus, the bodys natural and protective lubricant found in saliva and epithelial cells in lungs and the sensitive part of the nose. They usually come in clusters such as linear arrays. Less frequently, urticarial, nodular, or sometimes annular lesions may be appreciated. The dorsal aspect of the hands, face, elbows, and extensor portions of the extremities are most frequently affected. Mucosal lesions are absent. The coalescence of papules on the face, particularly on the glabella, results in longitudinal folding and gives the appearance of a leonine facies.
In scleromyxedema, symptoms can occur on larger part of the body. Redness and scleroderma-like induration occurs on the skin. In addition, the mobility of the lips, hands, arms, and legs is reduced. Proximal myopathy, inflammatory polyarthritis, central nervous system symptoms, esophageal aperistalsis, and hoarseness are among the notable systemic symptoms. If viscera is involved, the disease will be fatal. The dermatoneuro syndrome is a rare neurological complication of the disease presenting with fever, seizures and altered mental status.

Diagnosis
Classification
Papular mucinosis may be divided into several types or variants:
Acral persistent papular mucinosis
Self-healing papular mucinosis
Papular mucinosis of infancy
Cutaneous mucinosis of infancy
Nodular lichen myxedematosus
Localized lichen myxedematosus
Discrete papular lichen myxedematosus

Treatment
There is no effective treatment for this condition </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 Epstein syndrome and can you explain it in depth? [/INST] Epstein syndrome is a rare genetic disease characterized by a mutation in the MYH9 gene in nonmuscle myosin. This disease affects the patients renal system and can result in kidney failure. Epstein Syndrome was first discovered in 1972 when two families had similar symptoms to Alport syndrome. Epstein syndrome and other Alport-like disorders were seen to be caused by mutations in the MYH9 (myosin heavy chain 9)  gene, however, Epstein syndrome differs as it was more specifically linked to a mutation on the R702 codon on the MYH9 gene. Diseases with mutations on the MYH9 gene also include May–Hegglin anomaly, Sebastian syndrome and Fechtner syndrome.

Signs and symptoms
Initial symptoms are often described as bleeding tendency and thrombocytopenia. Bleeding tendency may be observed in epistaxis and purpura. Other symptoms may include macrothrombocytopenia, proteinuria, nephropathy, sensorineural hearing loss, low platelet count, oral lesions and cataracts. The most common symptoms include macrothrombocytopenia, mild sensorineural hearing loss and nephritis. The symptoms and the severity of these symptoms vary between patients where most patients experience nephritis in childhood and then progress to kidney failure in adolescence.  In macrothrombocytopenia platelet sizes can reach to approximately 6.6 um compared to a normal platelet size of 2.5 um where 30% platelets can reach the size of an erythrocytes. This large platelet size can be compared with MYH9 disorders where platelet size can vary between 4.5 um and the 6.6 um that is found in Epstein Syndrome with mutations on the R207 codon.

Causes
Epstein Syndrome is caused by a mutation in MYH9 gene. This mutation is autosomal dominant and is thereby inherited if one or both parents carry the mutated gene. However, there have been cases where Epstein Syndrome has been sporadic or non-congenital. Mutations are found in the nonmuscle myosin heavy chain IIA and is associated with chromosome 22. The MYH9 gene encodes for tissues including platelets, cochlea, renal cells, neutrophils and eyes.

Pathophysiology
The main symptom in Epstein Syndrome is thrombocytopaenia. Thrombocytopaenia is generally inherited as an autosomal dominant gene and platelets are found to aggregate with either epinephrine or collagen. Platelets assist in blood clotting and coagulate when there are damages blood vessels. This coagulation attempts to cease bleeding. Thrombocytopaenia means there is low platelet volume in the blood. This means there are less platelets to coagulate in presence of a damaged blood vessel, which can result in bleeding problems. The platelets are large (macrothrombocytopenia) and often consist of neutrophil inclusions. The large size of platelets may be due to excess microtubule coils and tublin. This large size of the platelets also affects their ability to bind to each other to seal damaged blood vessels and stop bleeding.Nephritis involves the inflammation of the kidney and this inflammation results in a reduced ability to filter blood and remove nitrogenous wastes. This excessive accumulation of wastes will result in a continued build-up of wastes including urea which interferes with metabolism.One of the kidneys functions include osmoregulation which involves the regulation of osmotic pressure in the blood by regulating the water content in blood pressure. Through osmosis (water movement from a low solute concentration to an area of high solute concentration) water is reabsorbed back into the blood from nephron tubules in the kidney. This maintenance of water concentration in the blood is essential for maintaining blood pressure and is affected in nephritis.

Diagnosis
The cardinal symptom in Epstein syndrome is thrombocytopaenia with giant platelets (macrothrombocytopenia). A peripheral blood smear is taken from the patient and a light microscope is used to these identify giant platelets. Leukocyte inclusions are also examined for, because approximately 41.1% of R207 mutations have leukocyte inclusions. These are often abnormal neutrophils with a small size of approximately less than 0.7 um and have an abnormallocation on the non-muscle myosin heavy chain IIA (NMMHC-II). These inclusion bodies have RNA and no DNA. RNA in these inclusion bodies can be located in immunofluorescence analysis with the anti nonmuscle heavy chain IIA antibody.Hematology analysers or a hemocytometer can be used to determine the amount of platelets. A sample of blood is drawn from a patients arm. A small amount of platelets in blood smears compared to the normal range of 150,000 to 450,000 platelets in microliter of blood suggest thrombocytopaenia, which is a common symptom in Epstein syndrome.A urine sample is often collected where a urinalysis can be used to determine the volume of proteins excreted in urine. Abnormal amounts of protein detected means the patient has proteinuria. Patients with Epstein syndrome often have large proteinuria where they excrete above 3.5g of protein in their urine in a day. This is one of the initial signs of renal disease.Easy bruising and abnormal bleeding tendencies are also described in initial diagnosis. This supports the common misdiagnosis for chronic idiopathic thrombocytopaenia purpura in patients with Epstein syndrome. These symptoms are often noticed in early childhood due to the congenital cause of the disease.

Treatment
Epstein syndrome is regarded as a refractory disease. Treatments include renal transplantation, however, this may become problematic as patients low platelet count (thrombocytopaenia) increase the risks of complications in surgery. Successful Renal transplants can arise from cadavers or from live donors. To minimize the risk of patients losing too much blood during the perioperative period, HLA-matched platelet infusions can be used to maintain satisfactory platelet levels. Nephritis involves the inflammation of the kidney and this inflammation results in a reduced ability to filter blood. In order to ensure the transplanted kidney is recognised as ‘self’ by Major Histocompatibility cells, immunosuppression drugs are used post operation. Immunosuppression medication may include calcineurin inhibitor, antimetabolite and methylprednisolone and assist in suppressing the immune systems response to the transplanted kidney

Maintenance
As a result of nephritis, a healthy blood pressure becomes difficult to maintain and hence medication including vasopressin may be prescribed to maintain blood pressure. Severe nephritis may mean kidney dialysis is required to ensure the blood is being filtered. This may include either peritoneal dialysis or haemodialysis, however, haemodialysis is most common as Epstein syndrome patients will often eventually have renal transplants. Peritoneal dialysis involves blood being filtered through a membrane in the abdomen (peritoneum). Whereas haemodialysis involves blood being filtered through a dialyser, which consists of a semi-permeable membrane where toxins including urea are removed from the blood. Haemodialysis also filters blood quicker than peritoneal dialysis.Intravenous immunoglobin treatments can be used to support the patients immune system as well as medication with Prednisolone to reduce inflammation.Sensorineural hearing loss is a common symptom in Epstein syndrome and can be treated with cochlea implants. Cochlea implants have four main parts including the electrode array, the transmitter, the receiver/stimulator and the microphone. The microphone is positioned behind the ear and receives sound waves, the processor then converts the sound into electrical signals. These electrical signals are further converted into electrical impulses in the cochlea where the transmitter is located, which in turn sends the signal to the auditory nerve. This results in a nervous impulse sent to the brain where the ‘sound’ is deciphered.

Prognosis
In most case Epstein syndrome patients will endure early-onset end-stage renal disease (ESRD) at the end of adolescence. Expected kidney failure means patients will need renal transplants in the near future.

Notable cases
In a study which investigated suitable management for severe Epstein syndrome, four patients were observed. Patient 1 demonstrated a common background and symptoms for Epstein syndrome </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 Bufotoxin and can you explain it in depth? [/INST] Bufotoxins are a family of toxic steroid lactones or substituted Tryptamines of which some may or may not be toxic. They occur in the parotoid glands, skin and poison of many toads (genus Bufo) and other amphibians, and in some plants and mushrooms </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 Palpation thyroiditis and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Syringobulbia and can you explain it in depth? [/INST] Syringobulbia is a medical condition in which syrinxes, or fluid-filled cavities, affect the brainstem (usually the lower brainstem). The exact cause is often unknown, but may be linked to a widening of the central canal of the spinal cord. This may affect one or more cranial nerves, resulting in various kinds of facial palsies. Sensory and motor nerve pathways may be affected by interruption or compression of nerves. This disorder is associated with syringomyelia, a syrinx limited to the spinal cord. It can be diagnosed using magnetic resonance imaging </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 Hypochondriasis and can you explain it in depth? [/INST] Hypochondriasis or hypochondria is a condition in which a person is excessively and unduly worried about having a serious illness. An old concept, the meaning of hypochondria has repeatedly changed. It has been claimed that this debilitating condition results from an inaccurate perception of the condition of body or mind despite the absence of an actual medical diagnosis. An individual with hypochondriasis is known as a hypochondriac. Hypochondriacs become unduly alarmed about any physical or psychological symptoms they detect, no matter how minor the symptom may be, and are convinced that they have, or are about to be diagnosed with, a serious illness.Often, hypochondria persists even after a physician has evaluated a person and reassured them that their concerns about symptoms do not have an underlying medical basis or, if there is a medical illness, their concerns are far in excess of what is appropriate for the level of disease. It is also referred to hypochondriaism which is the act of being in a hypochondriatic state, acute hypochondriaism. Many hypochondriacs focus on a particular symptom as the catalyst of their worrying, such as gastro-intestinal problems, palpitations, or muscle fatigue. To qualify for the diagnosis of hypochondria the symptoms must have been experienced for at least 6 months.International Classification of Diseases (ICD-10) classifies hypochondriasis as a mental and behavioral disorder. In the Diagnostic and Statistical Manual of Mental Disorders, DSM-IV-TR defined the disorder, "Hypochondriasis", as a somatoform disorder and one study has shown it to affect about 3% of the visitors to primary care settings. The 2013 DSM-5 replaced the diagnosis of hypochondriasis with the diagnoses of somatic symptom disorder (75%)  and illness anxiety disorder (25%).Hypochondria is often characterized by fears that minor bodily or mental symptoms may indicate a serious illness, constant self-examination and self-diagnosis, and a preoccupation with ones body. Many individuals with hypochondriasis express doubt and disbelief in the doctors diagnosis, and report that doctors’ reassurance about an absence of a serious medical condition is unconvincing, or short-lasting. Additionally, many hypochondriacs experience elevated blood pressure, stress, and anxiety in the presence of doctors or while occupying a medical facility, a condition known as "white coat syndrome". Many hypochondriacs require constant reassurance, either from doctors, family, or friends, and the disorder can become a debilitating challenge for the individual with hypochondriasis, as well as their family and friends. Some individuals with hypochondria completely avoid any reminder of illness, whereas others frequently visit medical facilities, sometimes obsessively. Some may never speak about it.

Signs and symptoms
Hypochondriasis is categorized as a somatic amplification disorder—a disorder of "perception and cognition"—that involves a hyper-vigilance of situation of the body or mind and a tendency to react to the initial perceptions in a negative manner that is further debilitating. Hypochondriasis manifests in many ways. Some people have numerous intrusive thoughts and physical sensations that push them to check with family, friends, and physicians. For example, a person who has a minor cough may think that they have tuberculosis. Or sounds produced by organs in the body, such as those made by the intestines, might be seen as a sign of a very serious illness to patients dealing with hypochondriasis.Other people are so afraid of any reminder of illness that they will avoid medical professionals for a seemingly minor problem, sometimes to the point of becoming neglectful of their health when a serious condition may exist and go undiagnosed. Yet others live in despair and depression, certain that they have a life-threatening disease and no physician can help them. Some consider the disease as a punishment for past misdeeds.Hypochondriasis is often accompanied by other psychological disorders. Bipolar disorder, clinical depression, obsessive-compulsive disorder (OCD), phobias, and somatization disorder,
panic disorder are the most common accompanying conditions in people with hypochondriasis, as well as a generalized anxiety disorder diagnosis at some point in their life.Many people with hypochondriasis experience a cycle of intrusive thoughts followed by compulsive checking, which is very similar to the symptoms of obsessive-compulsive disorder. However, while people with hypochondriasis are afraid of having an illness, patients with OCD worry about getting an illness or of transmitting an illness to others. Although some people might have both, these are distinct conditions.Patients with hypochondriasis often are not aware that depression and anxiety produce their own physical symptoms, and mistake these symptoms for manifestations of another mental or physical disorder or disease. For example, people with depression often experience changes in appetite and weight fluctuation, fatigue, decreased interest in sex, and motivation in life overall. Intense anxiety is associated with rapid heartbeat, palpitations, sweating, muscle tension, stomach discomfort, dizziness, shortness of breath, and numbness or tingling in certain parts of the body (hands, forehead, etc.).If a person is ill with a medical disease such as diabetes or arthritis, there will often be psychological consequences, such as depression. Some even report being suicidal. In the same way, someone with psychological issues such as depression or anxiety will sometimes experience physical manifestations of these affective fluctuations, often in the form of medically unexplained symptoms. Common symptoms include headaches; abdominal, back, joint, rectal, or urinary pain; nausea; fever and/or night sweats; itching; diarrhea; dizziness; or balance problems. Many people with hypochondriasis accompanied by medically unexplained symptoms feel they are not understood by their physicians, and are frustrated by their doctors’ repeated failure to provide symptom relief.

Cause
The genetic contribution to hypochondriasis is probably moderate, with heritability estimates around 10-37%. Non-shared environmental factors (i.e., experiences that differ between twins in the same family) explain most of the variance in key components of the condition such as the fear of illness and disease conviction. In contrast, the contribution of shared environmental factors (i.e., experiences shared by twins in the same family) to hypochondriasis is approximately zero.Although little is known about exactly which non-shared environmental factors typically contribute to causing hypochondriasis, certain factors such as exposure to illness-related information are widely believed to lead to short-term increases in health anxiety and to have contributed to hypochondriasis in individual cases. Overly protective caregivers and an excessive focus on minor health concerns have also been implicated as potential causes of hypochondriasis.In the media and on the Internet, articles, TV shows, and advertisements regarding serious illnesses such as cancer and multiple sclerosis often portray these diseases as being random, obscure, and somewhat inevitable. In the short term, inaccurate portrayal of risk and the identification of non-specific symptoms as signs of serious illness may contribute to exacerbating fear of illness. Major disease outbreaks or predicted pandemics can have similar effects.
Anecdotal evidence suggests that some individuals become hypochondriac after experiencing major medical diagnosis or death of a family member or friend. Similarly, when approaching the age of a parents premature death from disease, many otherwise healthy, happy individuals fall prey to hypochondria. These individuals believe they have the same disease that caused their parents death, sometimes causing panic attacks with corresponding symptoms.

Diagnosis
The ICD-10 defines hypochondriasis as follows:

A. Either one of the following:
A persistent belief, of at least six months duration, of the presence of a minimum of two serious physical diseases (of which at least one must be specifically named by the patient).
A persistent preoccupation with a presumed deformity or disfigurement (body dysmorphic disorder).B. Preoccupation with the belief and the symptoms causes persistent distress or interference with personal functioning in daily living and leads the patient to seek medical treatment or investigations (or equivalent help from local healers).C. Persistent refusal to accept medical advice that there is no adequate physical cause for the symptoms or physical abnormality, except for short periods of up to a few weeks at a time immediately after or during medical investigations.D. Most commonly used exclusion criteria: not occurring only during any of the schizophrenia and related disorders (F20–F29, particularly F22) or any of the mood disorders (F30–F39).The DSM-IV defines hypochondriasis according to the following criteria:

A. Preoccupation with fears of having, or the idea that one has, a serious disease based on the persons misinterpretation of bodily symptoms.
B. The preoccupation persists despite appropriate medical evaluation and reassurance.
C. The belief in Criterion A is not of delusional intensity (as in Delusional Disorder, Somatic Type) and is not restricted to a circumscribed concern about appearance (as in Body Dysmorphic Disorder).
D. The preoccupation causes clinically significant distress or impairment in
social, occupational, or other important areas of functioning.
E. The duration of the disturbance is at least 6 months.
F. The preoccupation is not better accounted for by Generalized Anxiety Disorder, Obsessive-Compulsive Disorder, Panic Disorder, a Major Depressive Episode, Separation Anxiety, or another Somatoform Disorder.

In the fifth version of the DSM (DSM-5), most who met criteria for DSM-IV hypochondriasis instead meet criteria for a diagnosis of somatic symptom disorder (SSD) or illness anxiety disorder (IAD).

Classification
The classification of hypochondriasis in relation to other psychiatric disorders has long been a topic of scholarly debate and has differed widely between different diagnostic systems and influential publications.
In the case of the DSM, the first and second versions listed hypochondriasis as a neurosis, whereas the third and fourth versions listed hypochondriasis as a somatoform disorder. The current version of the DSM (DSM-5) lists somatic symptom disorder (SSD) under the heading of "somatic symptom and related disorders", and illness anxiety disorder (IAD) under both this heading and as an anxiety disorder.
The ICD-10, like the third and fourth versions of the DSM, lists hypochondriasis as a somatoform disorder. The ICD-11, however, lists hypochondriasis under the heading of "obsessive-compulsive or related disorders".
There are also numerous influential scientific publications that have argued for other classifications of hypochondriasis. Notably, since the early 1990s, it has become increasingly common to regard hypochondriasis as an anxiety disorder, and to refer to the condition as "health anxiety" or "severe health anxiety".

Treatment
Approximately 20 randomized controlled trials and numerous observational studies indicate that cognitive behavioral therapy (CBT) is an effective treatment for hypochondriasis </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 Femoral nerve and can you explain it in depth? [/INST] The femoral nerve is a nerve in the thigh that supplies skin on the upper thigh and inner leg, and the muscles that extend the knee.

Structure
The femoral nerve is the major nerve supplying the anterior compartment of the thigh </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 Tay–Sachs disease and can you explain it in depth? [/INST] Tay–Sachs disease is a genetic disorder that results in the destruction of nerve cells in the brain and spinal cord. The most common form is infantile Tay–Sachs disease, which becomes apparent around three to six months of age, with the baby losing the ability to turn over, sit, or crawl. This is then followed by seizures, hearing loss, and inability to move, with death usually occurring by the age of three to five. Less commonly, the disease may occur in later childhood or adulthood (juvenile or late-onset). These forms tend to be less severe, but the juvenile form typically results in death by age 15.Tay–Sachs disease is caused by a genetic mutation in the HEXA gene on chromosome 15, which codes form a subunit of the hexosaminidase enzyme known as hexosaminidase A. It is inherited from a persons parents in an autosomal recessive manner. The mutation disrupts the activity of the enzyme, which results in the build-up of the molecule GM2 ganglioside within cells, leading to toxicity. Diagnosis may be supported by measuring the blood hexosaminidase A level or genetic testing. Tay–Sachs disease is a type of GM2 gangliosidosis and sphingolipidosis.The treatment of Tay–Sachs disease is supportive in nature. This may involve multiple specialities as well as psychosocial support for the family. The disease is rare in the general population. In Ashkenazi Jews, French Canadians of southeastern Quebec, the Old Order Amish of Pennsylvania, and the Cajuns of southern Louisiana, the condition is more common. Approximately 1 in 3,600 Ashkenazi Jews at birth are affected.The disease is named after British ophthalmologist Waren Tay, who in 1881 first described a symptomatic red spot on the retina of the eye; and American neurologist Bernard Sachs, who described in 1887 the cellular changes and noted an increased rate of disease in Ashkenazi Jews. Carriers of a single Tay–Sachs allele are typically normal. It has been hypothesized that being a carrier may confer protection from tuberculosis, explaining the persistence of the allele in certain populations. Researchers are looking at gene therapy or enzyme replacement therapy as possible treatments.

Signs and symptoms
Tay–Sachs disease is typically first noticed in infants around 6 months old displaying an abnormally strong response to sudden noises or other stimuli, known as the "startle response". There may also be listlessness or muscle stiffness (hypertonia). The disease is classified into several forms, which are differentiated based on the onset age of neurological symptoms.

Infantile
Infants with Tay–Sachs disease appear to develop normally for the first six months after birth. Then, as neurons become distended with GM2 gangliosides, a relentless deterioration of mental and physical abilities begins. The child may become blind, deaf, unable to swallow, atrophied, and paralytic. Death usually occurs before the age of four.

Juvenile
Juvenile Tay–Sachs disease is rarer than other forms of Tay–Sachs, and usually is initially seen in children between two and ten years old. People with Tay–Sachs disease experience cognitive and motor skill deterioration, dysarthria, dysphagia, ataxia, and spasticity. Death usually occurs between the ages of five and fifteen years.

Late-onset
A rare form of this disease, known as Adult-Onset or Late-Onset Tay–Sachs disease, usually has its first symptoms during the 30s or 40s. In contrast to the other forms, late-onset Tay–Sachs disease is usually not fatal as the effects can stop progressing. It is frequently misdiagnosed. It is characterized by unsteadiness of gait and progressive neurological deterioration. Symptoms of late-onset Tay–Sachs – which typically begin to be seen in adolescence or early adulthood – include speech and swallowing difficulties, unsteadiness of gait, spasticity, cognitive decline, and psychiatric illness, particularly a schizophrenia-like psychosis. People with late-onset Tay–Sachs may become full-time wheelchair users in adulthood.Until the 1970s and 1980s, when the diseases molecular genetics became known, the juvenile and adult forms of the disease were not always recognized as variants of Tay–Sachs disease. Post-infantile Tay–Sachs was often misdiagnosed as another neurological disorder, such as Friedreichs ataxia.

Genetics
Tay–Sachs disease is an autosomal recessive genetic disorder, meaning that when both parents are carriers, there is a 25% risk of giving birth to an affected child with each pregnancy. The affected child would have received a mutated copy of the gene from each parent. If one parent has this Genetic disorder and is passed down to the child, then the child becomes a carrier.Tay–Sachs results from mutations in the HEXA gene on chromosome 15, which encodes the alpha-subunit of beta-N-acetylhexosaminidase A, a lysosomal enzyme. By 2000, more than 100 different mutations had been identified in the human HEXA gene. These mutations have included single base insertions and deletions, splice phase mutations, missense mutations, and other more complex patterns. Each of these mutations alters the genes protein product (i.e., the enzyme), sometimes severely inhibiting its function. In recent years, population studies and pedigree analysis have shown how such mutations arise and spread within small founder populations. Initial research focused on several such founder populations:

Ashkenazi Jews. A four base pair insertion in exon 11 (1278insTATC) results in an altered reading frame for the HEXA gene. This mutation is the most prevalent mutation in the Ashkenazi Jewish population, and leads to the infantile form of Tay–Sachs disease.
Cajuns. The same 1278insTATC mutation found among Ashkenazi Jews occurs in the Cajun population of southern Louisiana. Researchers have traced the ancestry of carriers from Louisiana families back to a single founder couple – not known to be Jewish – who lived in France in the 18th century.
French Canadians. Two mutations, unrelated to the Ashkenazi/Cajun mutation, are absent in France but common among certain French-Canadian communities living in southeastern Quebec and Acadians from the Province of New Brunswick. Pedigree analysis suggests the mutations were uncommon before the late 17th century.In the 1960s and early 1970s, when the biochemical basis of Tay–Sachs disease was first becoming known, no mutations had been sequenced directly for genetic diseases. Researchers of that era did not yet know how common polymorphisms would prove to be. The "Jewish Fur Trader Hypothesis," with its implication that a single mutation must have spread from one population into another, reflected the knowledge at the time. Subsequent research, however, has proven that a large variety of different HEXA mutations can cause the disease. Because Tay–Sachs was one of the first genetic disorders for which widespread genetic screening was possible, it is one of the first genetic disorders in which the prevalence of compound heterozygosity has been demonstrated.Compound heterozygosity ultimately explains the diseases variability, including the late-onset forms. The disease can potentially result from the inheritance of two unrelated mutations in the HEXA gene, one from each parent. Classic infantile Tay–Sachs disease results when a child has inherited mutations from both parents that completely stop the biodegradation of gangliosides. Late onset forms occur due to the diverse mutation base – people with Tay–Sachs disease may technically be heterozygotes, with two differing HEXA mutations that both inactivate, alter, or inhibit enzyme activity. When a patient has at least one HEXA copy that still enables some level of hexosaminidase A activity, a later onset disease form occurs. When disease occurs because of two unrelated mutations, the patient is said to be a compound heterozygote.Heterozygous carriers (individuals who inherit one mutant allele) show abnormal enzyme activity but manifest no disease symptoms. This phenomenon is called dominance; the biochemical reason for wild-type alleles dominance over nonfunctional mutant alleles in inborn errors of metabolism comes from how enzymes function. Enzymes are protein catalysts for chemical reactions; as catalysts, they speed up reactions without being used up in the process, so only small enzyme quantities are required to carry out a reaction. Someone homozygous for a nonfunctional mutation in the enzyme-encoding gene has little or no enzyme activity, so will manifest the abnormal phenotype. A heterozygote (heterozygous individual) has at least half of the normal enzyme activity level, due to the expression of the wild-type allele. This level is normally enough to enable normal function and thus prevent phenotypic expression.

Pathophysiology
Tay–Sachs disease is caused by insufficient activity of the enzyme hexosaminidase A. Hexosaminidase A is a vital hydrolytic enzyme, found in the lysosomes, that breaks down sphingolipids. When hexosaminidase A is no longer functioning properly, the lipids accumulate in the brain and interfere with normal biological processes. Hexosaminidase A specifically breaks down fatty acid derivatives called gangliosides; these are made and biodegraded rapidly in early life as the brain develops. Patients with and carriers of Tay–Sachs can be identified by a simple blood test that measures hexosaminidase A activity.The hydrolysis of GM2-ganglioside requires three proteins. Two of them are subunits of hexosaminidase A; the third is a small glycolipid transport protein, the GM2 activator protein (GM2A), which acts as a substrate-specific cofactor for the enzyme. Deficiency in any one of these proteins leads to ganglioside storage, primarily in the lysosomes of neurons. Tay–Sachs disease (along with AB-variant GM2-gangliosidosis and Sandhoff disease) occurs because a mutation inherited from both parents deactivates or inhibits this process. Most Tay–Sachs mutations probably do not directly affect protein functional elements (e.g., the active site). Instead, they cause incorrect folding (disrupting function) or disable intracellular transport.

Diagnosis
In patients with a clinical suspicion for Tay–Sachs disease, with any age of onset, the initial testing involves an enzyme assay to measure the activity of hexosaminidase in serum, fibroblasts, or leukocytes. Total hexosaminidase enzyme activity is decreased in individuals with Tay–Sachs as is the percentage of hexosaminidase A. After confirmation of decreased enzyme activity in an individual, confirmation by molecular analysis can be pursued. All patients with infantile onset Tay–Sachs disease have a "cherry red" macula in the retina, easily observable by a physician using an ophthalmoscope. This red spot is a retinal area that appears red because of gangliosides in the surrounding retinal ganglion cells. The choroidal circulation is showing through "red" in this foveal region where all retinal ganglion cells are pushed aside to increase visual acuity. Thus, this cherry-red spot is the only normal part of the retina; it shows up in contrast to the rest of the retina. Microscopic analysis of the retinal neurons shows they are distended from excess ganglioside storage. Unlike other lysosomal storage diseases (e.g., Gaucher disease, Niemann–Pick disease, and Sandhoff disease), hepatosplenomegaly (liver and spleen enlargement) is not seen in Tay–Sachs.

Prevention
Three main approaches have been used to prevent or reduce the incidence of Tay–Sachs:

Prenatal diagnosis. If both parents are identified as carriers, prenatal genetic testing can determine whether the fetus has inherited a defective gene copy from both parents. Chorionic villus sampling (CVS), the most common form of prenatal diagnosis, can be performed between 10 and 14 weeks of gestation. Amniocentesis is usually performed at 15–18 weeks. These procedures have risks of miscarriage of 1% or less.
Preimplantation genetic diagnosis. By retrieving the mothers eggs for in vitro fertilization, it is possible to test the embryo for the disorder prior to implantation. Healthy embryos are then selected and transferred into the mothers womb, while unhealthy embryos are discarded. In addition to Tay–Sachs disease, preimplantation genetic diagnosis has been used to prevent cystic fibrosis and sickle cell anemia among other genetic disorders.
Mate selection. In Orthodox Jewish circles, the organization Dor Yeshorim carries out an anonymous screening program so that carriers for Tay–Sachs and other genetic disorders can avoid marrying each other.

Management
As of 2010 there was no treatment that addressed the cause of Tay–Sachs disease or could slow its progression; people receive supportive care to ease the symptoms and extend life by reducing the chance of contracting infections. Infants are given feeding tubes when they can no longer swallow. In late-onset Tay–Sachs, medication (e.g., lithium for depression) can sometimes control psychiatric symptoms and seizures, although some medications (e.g., tricyclic antidepressants, phenothiazines, haloperidol, and risperidone) are associated with significant adverse effects.

Outcomes
As of 2010, even with the best care, children with infantile Tay–Sachs disease usually die by the age of 4. Children with the juvenile form are likely to die between the ages 5–15, while the lifespans of those with the adult form will probably not be affected.

Epidemiology
Ashkenazi Jews have a high incidence of Tay–Sachs and other lipid storage diseases. In the United States, about 1 in 27 to 1 in 30 Ashkenazi Jews is a recessive carrier. The disease incidence is about 1 in every 3,500 newborn among Ashkenazi Jews. French Canadians and the Cajun community of Louisiana have an occurrence similar to the Ashkenazi Jews. Irish Americans have a 1 in 50 chance of being a carrier. In the general population, the incidence of carriers as heterozygotes is about 1 in 300. The incidence is approximately 1 in 320,000 newborns in the general population in the United States.Three general classes of theories have been proposed to explain the high frequency of Tay–Sachs carriers in the Ashkenazi Jewish population:

Heterozygote advantage. When applied to a particular allele, this theory posits that mutation carriers have a selective advantage, perhaps in a particular environment.
Reproductive compensation. Parents who lose a child because of disease tend to "compensate" by having additional children following the loss. This phenomenon may maintain and possibly even increase the incidence of autosomal recessive disease.
Founder effect. This hypothesis states that the high incidence of the 1278insTATC chromosomes is the result of an elevated allele frequency that existed by chance in an early founder population.Tay–Sachs disease was one of the first genetic disorders for which epidemiology was studied using molecular data. Studies of Tay–Sachs mutations using new molecular techniques such as linkage disequilibrium and coalescence analysis have brought an emerging consensus among researchers supporting the founder effect theory.

History
Waren Tay and Bernard Sachs were two physicians. They described the diseases progression and provided differential diagnostic criteria to distinguish it from other neurological disorders with similar symptoms.Both Tay and Sachs reported their first cases among Ashkenazi Jewish families. Tay reported his observations in 1881 in the first volume of the proceedings of the British Ophthalmological Society, of which he was a founding member. By 1884, he had seen three cases in a single family. Years later, Bernard Sachs, an American neurologist, reported similar findings when he reported a case of "arrested cerebral development" to other New York Neurological Society members.Sachs, who recognized that the disease had a familial basis, proposed that the disease should be called amaurotic familial idiocy. However, its genetic basis was still poorly understood. Although Gregor Mendel had published his article on the genetics of peas in 1865, Mendels paper was largely forgotten for more than a generation – not rediscovered by other scientists until 1899. Thus, the Mendelian model for explaining Tay–Sachs was unavailable to scientists and doctors of the time. The first edition of the Jewish Encyclopedia, published in 12 volumes between 1901 and 1906, described what was then known about the disease:
It is a curious fact that amaurotic family idiocy, a rare and fatal disease of children, occurs mostly among Jews. The largest number of cases has been observed in the United States—over thirty in number. It was at first thought that this was an exclusively Jewish disease because most of the cases at first reported were between Russian and Polish Jews; but recently there have been reported cases occurring in non-Jewish children. The chief characteristics of the disease are progressive mental and physical enfeeblement; weakness and paralysis of all the extremities; and marasmus, associated with symmetrical changes in the macula lutea. On investigation of the reported cases, they found that neither consanguinity nor syphilitic, alcoholic, or nervous antecedents in the family history are factors in the etiology of the disease. No preventive measures have as yet been discovered, and no treatment has been of benefit, all the cases having terminated fatally.
Jewish immigration to the United States peaked in the period 1880–1924, with the immigrants arriving from Russia and countries in Eastern Europe; this was also a period of nativism (hostility to immigrants) in the United States. Opponents of immigration often questioned whether immigrants from southern and eastern Europe could be assimilated into American society. Reports of Tay–Sachs disease contributed to a perception among nativists that Jews were an inferior race.In 1969, Shintaro Okada and John S. OBrien showed that Tay–Sachs disease was caused by an enzyme defect; they also proved that Tay–Sachs patients could be diagnosed by an assay of hexosaminidase A activity. The further development of enzyme assays demonstrated that levels of hexosaminidases A and B could be measured in patients and carriers, allowing the reliable detection of heterozygotes. During the early 1970s, researchers developed protocols for newborn testing, carrier screening, and pre-natal diagnosis. By the end of 1979, researchers had identified three variant forms of GM2 gangliosidosis, including Sandhoff disease and the AB variant of GM2-gangliosidosis, accounting for false negatives in carrier testing.

Society and culture
Since carrier testing for Tay–Sachs began in 1971, millions of Ashkenazi Jews have been screened as carriers. Jewish communities embraced the cause of genetic screening from the 1970s on. The success with Tay–Sachs disease has led Israel to become the first country that offers free genetic screening and counseling for all couples and opened discussions about the proper scope of genetic testing for other disorders in Israel.Because Tay–Sachs disease was one of the first autosomal recessive genetic disorders for which there was an enzyme assay test (prior to polymerase chain reaction testing methods), it was intensely studied as a model for all such diseases, and researchers sought evidence of a selective process. A continuing controversy is whether heterozygotes (carriers) have or had a selective advantage. The presence of four different lysosomal storage disorders in the Ashkenazi Jewish population suggests a past selective advantage for heterozygous carriers of these conditions."This controversy among researchers has reflected three debates among geneticists at large:
Dominance versus overdominance. In applied genetics (selective and agricultural breeding), this controversy has reflected the century-long debate over whether dominance or overdominance provides the best explanation for heterosis (hybrid vigor).
The classical/balance controversy. The classical hypothesis of genetic variability, often associated with Hermann Muller, maintains that most genes are of a normal wild type, and that most individuals are homozygous for that wild type, while most selection is purifying selection that operates to eliminate deleterious alleles. The balancing hypothesis, often associated with Theodosius Dobzhansky, states that heterozygosity will be common at loci, and that it frequently reflects either directional selection or balancing selection.
Selectionists versus neutralists. In theoretical population genetics, selectionists emphasize the primacy of natural selection as a determinant of evolution and of variation within a population, while neutralists favor a form of Motoo Kimuras neutral theory of molecular evolution, which emphasizes the role of genetic drift.

Research directions
Enzyme replacement therapy
Enzyme replacement therapy techniques have been investigated for lysosomal storage disorders, and could potentially be used to treat Tay–Sachs as well. The goal would be to replace the nonfunctional enzyme, a process similar to insulin injections for diabetes. However, in previous studies, the HEXA enzyme itself has been thought to be too large to pass through the specialized cell layer in the blood vessels that forms the blood–brain barrier in humans.Researchers have also tried directly instilling the deficient enzyme hexosaminidase A into the cerebrospinal fluid (CSF) which bathes the brain. However, intracerebral neurons seem unable to take up this physically large molecule efficiently even when it is directly by them. Therefore, this approach to treatment of Tay–Sachs disease has also been ineffective so far.

Jacob sheep model
Tay–Sachs disease exists in Jacob sheep. The biochemical mechanism for this disease in the Jacob sheep is virtually identical to that in humans, wherein diminished activity of hexosaminidase A results in increased concentrations of GM2 ganglioside in the affected animal. Sequencing of the HEXA gene cDNA of affected Jacobs sheep reveal an identical number of nucleotides and exons as in the human HEXA gene, and 86% nucleotide sequence identity. A missense mutation (G444R) was found in the HEXA cDNA of the affected sheep. This mutation is a single nucleotide change at the end of exon 11, resulting in that exons deletion (before translation) via splicing </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Congenital rubella syndrome and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Balanitis and can you explain it in depth? [/INST] Balanitis is inflammation of the glans penis. When the foreskin is also affected, the proper term is balanoposthitis. Balanitis on boys still in diapers must be distinguished from redness caused by ammoniacal dermatitis. The word balanitis is from the Greek βάλανος balanos, literally meaning acorn, used because of the similarity in shape to the glans penis.

Signs and symptoms
Small red erosions on the glans (first sign)
Redness of the foreskin
Redness of the penis
Other rashes on the head of the penis
Foul smelling discharge
Painful foreskin and penis

Complications
Recurrent bouts of balanitis may cause scarring of the preputial orifice; the reduced elasticity may lead to pathologic phimosis. Further complications may include:

Stricture of urethral meatus
Phimosis
Paraphimosis

Cause
Inflammation has many possible causes, including irritation by environmental substances, physical trauma, and infection such as bacterial, viral, or fungal. Some of these infections are sexually transmitted diseases.
It is less common among people who are circumcised, as in many cases, a dysfunction of the foreskin is a causal or contributing factor </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 Scleredema and can you explain it in depth? [/INST] Scleredema is a rare, self-limiting skin condition defined by progressive thickening and hardening of the skin, usually on the areas of the upper back, neck, shoulders and face. The skin may also change color to red or orange </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 Zygomycosis and can you explain it in depth? [/INST] Zygomycosis is the broadest term to refer to infections caused by bread mold fungi of the zygomycota phylum. However, because zygomycota has been identified as polyphyletic, and is not included in modern fungal classification systems, the diseases that zygomycosis can refer to are better called by their specific names: mucormycosis (after Mucorales), phycomycosis (after Phycomycetes) and basidiobolomycosis (after Basidiobolus). These rare yet serious and potentially life-threatening fungal infections usually affect the face or oropharyngeal (nose and mouth) cavity. Zygomycosis type infections are most often caused by common fungi found in soil and decaying vegetation. While most individuals are exposed to the fungi on a regular basis, those with immune disorders (immunocompromised) are more prone to fungal infection. These types of infections are also common after natural disasters, such as tornadoes or earthquakes, where people have open wounds that have become filled with soil or vegetative matter.The condition may affect the gastrointestinal tract or the skin, often beginning in the nose and paranasal sinuses. It is one of the most rapidly spreading fungal infections in humans. Treatment consists of prompt and intensive antifungal drug therapy and surgery to remove the infected tissue.

Causes
Pathogenic zygomycosis is caused by species in two orders: Mucorales or Entomophthorales, with the former causing far more disease than the latter. These diseases are known as "mucormycosis" and "entomophthoramycosis", respectively.
Order Mucorales (mucormycosis)
Family Mucoraceae
Absidia (Absidia corymbifera)
Apophysomyces (Apophysomyces elegans and Apophysomyces trapeziformis)
Mucor (Mucor indicus)
Rhizomucor (Rhizomucor pusillus)
Rhizopus (Rhizopus oryzae)
Family Cunninghamellaceae
Cunninghamella (Cunninghamella bertholletiae)
Family Thamnidiaceae
Cokeromyces (Cokeromyces recurvatus)
Family Saksenaeaceae
Saksenaea (Saksenaea vasiformis)
Family Syncephalastraceae
Syncephalastrum (Syncephalastrum racemosum)
Order Entomophthorales (entomophthoramycosis)
Family Basidiobolaceae
Basidiobolus (Basidiobolus ranarum)
Family Ancylistaceae
Conidiobolus (Conidiobolus coronatus/Conidiobolus incongruus)

Epidemiology
Zygomycosis has been found in survivors of the 2004 Indian Ocean earthquake and tsunami and in survivors of the 2011 Joplin, Missouri tornado.

Symptoms
In the primary cutaneous form, the lesions are usually painful and necrotic, with black eschar, accompanied by a fever. Patients will usually present with a history of poorly controlled diabetes or malignancy. Myocutaneous infections may lead to amputation. Pulmonary tract infections seen with lung transplant patients, who are at high risk for fatal invasive mycoses. Rhinocerebral infection is characterized by paranasal swelling with necrotic tissues. Patient may have hemorrhagic exudates (tissue fluid from lesions tinged with blood) from the nose and eyes as the fungi penetrate through blood vessels and other anatomical structures.

Diagnosis
Diagnosis is done with potassium hydroxide (KOH) preparation in tissue. On light microscopy, there will be broad, ribbon-like septate hyphae with 90 degree angles on branches. KOH wet mount of the black eschar will show aseptate fungal hyphae with right angle branching. Periodic Acid Schiff (PAS) staining will reveal similar broad hyphae in the dermis and cutis. Fungal culture can also confirm the organism. Diagnosis remains difficult due to the lack of laboratory tests as mortality remains high. In 2005, a multiplex PCR test was able to identify five species of Rhizopus and may prove useful as a screening method for visceral mucormycosis in the future.The clinical approach to diagnosis includes radiologic, where more than ten nodules and pleural effusion are associated to pulmonary forms of the disease. In CT, a reverse halo sign is noted. Direct microscopy and histopathology, and cultures remain the gold standards for diagnoses. Zygomycophyta share close clinical and radiological features to Aspergillosis </s>