<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Anterior cruciate ligament injury and explain in detail? [/INST] An anterior cruciate ligament injury occurs when the anterior cruciate ligament (ACL) is either stretched, partially torn, or completely torn. The most common injury is a complete tear. Symptoms include pain, an audible cracking sound during injury, instability of the knee, and joint swelling. Swelling generally appears within a couple of hours. In approximately 50% of cases, other structures of the knee such as surrounding ligaments, cartilage, or meniscus are damaged.The underlying mechanism often involves a rapid change in direction, sudden stop, landing after a jump, or direct contact to the knee. It is more common in athletes, particularly those who participate in alpine skiing, football (soccer), netball, American football, or basketball. Diagnosis is typically made by physical examination and is sometimes supported by magnetic resonance imaging (MRI). Physical examination will often show tenderness around the knee joint, reduced range of motion of the knee, and increased looseness of the joint.Prevention is by neuromuscular training and core strengthening. Treatment recommendations depend on desired level of activity. In those with low levels of future activity, nonsurgical management including bracing and physiotherapy may be sufficient. In those with high activity levels, surgical repair via arthroscopic anterior cruciate ligament reconstruction is often recommended. This involves replacement with a tendon taken from another area of the body or from a cadaver. Following surgery rehabilitation involves slowly expanding the range of motion of the joint, and strengthening the muscles around the knee. Surgery, if recommended, is generally not performed until the initial inflammation from the injury has resolved.About 200,000 people are affected per year in the United States. In some sports, females have a higher risk of ACL injury, while in others, both sexes are equally affected. While adults with a complete tear have a higher rate of knee osteoarthritis, treatment strategy does not appear to change this risk. ACL tears can also occur in some animals, such as dogs. The most common knee injury in dogs is ACL or CCL rupture; in fact, till proven otherwise, unexpected hind limb lameness is usually due to a ruptured cruciate.

Signs and symptoms
When an individual has an ACL injury, they are likely to hear a "pop" in their knee followed by pain and swelling. They may also experience instability in the knee once they resume walking and other activities, as the ligament can no longer stabilize the knee joint and keep the tibia from sliding forward.Reduced range of motion of the knee and tenderness along the joint line are also common signs of an acute ACL injury. The pain and swelling may resolve on its own; however, the knee will remain unstable and returning to sport without treatment may result in further damage to the knee.

Causes
Causes may include:

Changing direction rapidly (also known as "cutting")
Landing from a jump awkwardly
Coming to a sudden stop when running
A direct contact or collision to the knee (e.g. during a football tackle or a motor vehicle collision)These movements cause the tibia to shift away from the femur rapidly, placing strain on the knee joint and potentially leading to rupture of the ACL. About 80% of ACL injuries occur without direct trauma. Risk factors include female anatomy, specific sports, poor conditioning, fatigue, and playing on a turf field.

Female predominance
Female athletes are two to eight times more likely to strain their ACL in sports that involve cutting and jumping as compared to men who play the same particular sports. NCAA data has found relative rates of injury per 1000 athlete exposures as follows:
Mens basketball 0.07, womens basketball 0.23
Mens lacrosse 0.12, womens lacrosse 0.17
Mens football 0.09, womens football 0.28The highest rate of ACL injury in women occurred in gymnastics, with a rate of injury per 1000 athlete exposures of 0.33.
Of the four sports with the highest ACL injury rates, three were womens – gymnastics, basketball and soccer.Differences between males and females identified as potential causes are the active muscular protection of the knee joint, differences in leg/pelvis alignment, and relative ligament laxity caused by differences in hormonal activity from estrogen and relaxin. Birth control pills also appear to decrease the risk of ACL injury.

Dominance theories
Some studies have suggested that there are four neuromuscular imbalances that predispose women to higher incidence of ACL injury. Female athletes are more likely to jump and land with their knees relatively straight and collapsing in towards each other, while most of their bodyweight falls on a single foot and their upper body tilts to one side. Several theories have been described to further explain these imbalances. These include the ligament dominance, quadriceps dominance, leg dominance, and trunk dominance theories.The ligament dominance theory suggests that when females athletes land after a jump, their muscles do not sufficiently absorb the impact of the ground. As a result, the ligaments of the knee must absorb the force, leading to a higher risk of injury. Quadriceps dominance refers to a tendency of female athletes to preferentially use the quadriceps muscles to stabilize the knee joint. Given that the quadriceps muscles work to pull the tibia forward, an overpowering contraction of the quadriceps can place strain on the ACL, increasing risk of injury.Leg dominance describes the observation that women tend to place more weight on one leg than another. Finally, trunk dominance suggests that males typically exhibit greater control of the trunk in performance situations as evidenced by greater activation of the internal oblique muscle. Female athletes are more likely to land with their upper body tilted to one side and more weight on one leg than the other, therefore placing greater rotational force on their knees.

Hormonal and anatomic differences
Before puberty, there is no observed difference in frequency of ACL tears between the sexes. Changes in sex hormone levels, specifically elevated levels of estrogen and relaxin in females during the menstrual cycle, have been hypothesized as causing predisposition of ACL ruptures. This is because they may increase joint laxity and extensibility of the soft tissues surrounding the knee joint. Ongoing research has observed a greater occurrence of ACL injuries in females during ovulation and fewer injuries during the follicular and luteal phases of the menstrual cycle.Study results have shown that female collegiate athletes with concentration levels of relaxin that are greater than 6.0 pg/mL are at four times higher risk of an ACL tear than those with lower concentrations.Additionally, female pelvises widen during puberty through the influence of sex hormones. This wider pelvis requires the femur to angle toward the knees. This angle towards the knee is referred to as the Q angle. The average Q angle for men is 14 degrees and the average for women is 17 degrees. Steps can be taken to reduce this Q angle, such as using orthotics. The relatively wider female hip and widened Q angle may lead to an increased likelihood of ACL tears in women.

ACL, muscular stiffness, and strength
During puberty, sex hormones also affect the remodeled shape of soft tissues throughout the body. The tissue remodeling results in female ACLs that are smaller and will fail (i.e. tear) at lower loading forces, and differences in ligament and muscular stiffness between men and women. Womens knees are less stiff than mens during muscle activation. Force applied to a less stiff knee is more likely to result in ACL tears.In addition, the quadriceps femoris muscle is an antagonist to the ACL. According to a study done on female athletes at the University of Michigan, 31% of female athletes recruited the quadriceps femoris muscle first as compared to 17% in males. Because of the elevated contraction of the quadriceps femoris muscle during physical activity, an increased strain is placed onto the ACL due to the "tibial translation anteriorly".

Pathophysiology
The knee joint is formed by three bones: the femur (thighbone), the tibia (shinbone), and the patella (kneecap). These bones are held together by ligaments, which are strong bands of tissue that keep the joint stable while an individual is walking, running, jumping, etc. There are two types of ligaments in the knee: the collateral ligaments and the cruciate ligaments.The collateral ligaments include the medial collateral ligament (along the inside of the knee) and the lateral or fibular collateral ligament (along the outside of the knee). These two ligaments function to limit sideways movement of the knee.The cruciate ligaments form an "X" inside the knee joint with the anterior cruciate ligament running from the front of the tibia to the back of the femur, and the posterior cruciate ligament running from the back of the tibia to the front of the femur. The anterior cruciate ligament prevents the tibia from sliding out in front of the femur and provides rotational stability.There are also two C-shaped structures made of cartilage called the medial meniscus and lateral meniscus that sit on top of the tibia in the knee joint and serve as cushion for the bones.

Diagnosis
Manual tests
Most ACL injuries can be diagnosed by examining the knee and comparing it to the other, non-injured knee. When a doctor suspects ACL injury in a person who reports a popping sound in the knee followed by swelling, pain, and instability of the knee joint, they can perform several tests to evaluate the damage to the knee. These tests include the pivot-shift test, anterior drawer test, and Lachman test. The pivot-shift test involves flexing the knee while holding onto the ankle and slightly rotating the tibia inwards. In the anterior drawer test, the examiner flexes the knees to 90 degrees, sits on the persons feet, and gently pulls the tibia towards themself. The Lachman test is performed by placing one hand on the persons thigh and the other on the tibia and pulling the tibia forward. These tests are meant to test whether the ACL is intact and therefore able to limit the forward motion of the tibia. The Lachman test is recognized by most authorities as the most reliable and sensitive of the three.

Medical imaging
Though clinical examination in experienced hands can be accurate, the diagnosis is usually confirmed by magnetic resonance imaging, which provides images of the soft tissues like ligaments and cartilage around the knee. It may also permit visualization of other structures which may have been coincidentally involved, such as the menisci or collateral ligaments. An x-ray may be performed in addition to evaluate whether one of the bones in the knee joint was broken during the injury.MRI is perhaps the most used technique for diagnosing the state of the ACL, but it is not always the most reliable technique as the ACL can be obscured by blood that fills the joint after an injury.

Arthrometers/Laximeters
Another form of evaluation that may be used in case physical examination and MRI are inconclusive is laximetry testing (i.e. arthrometry and stress imaging), which involve applying a force to the leg and quantifying the resulting displacement of the knee. These medical devices basically replicate manual tests but offer objective assessments. The GNRB arthrometer, for example, is a knee arthrometer that is considered more effective than the Lachman test.

Classification
An injury to a ligament is called a sprain. The American Academy of Orthopedic Surgeons defines ACL injury in terms of severity and classifies them as Grade 1, 2, or 3 sprains. Grade 1 sprains occur when the ligament is stretched slightly but the stability of the knee joint is not affected. Grade 2 sprains occur when the ligament is stretched to the point that it becomes loose; this is also referred to as a partial tear. Grade 3 sprains occur when the ligament is completely torn into two pieces, and the knee joint is no longer stable. This is the most common type of ACL injury.Around half of ACL injuries occur in conjunction with injury to other structures in the knee, including the other ligaments, menisci, or cartilage on the surface of the bones. A specific pattern of injury called the "unhappy triad" (also known as the "terrible triad," or "ODonoghues triad") involves injury to the ACL, MCL, and medial meniscus, and occurs when a lateral force is applied to the knee while the foot is fixed on the ground.

Prevention
Interest in reducing non-contact ACL injury has been intense. The International Olympic Committee, after a comprehensive review of preventive strategies, has stated that injury prevention programs have a measurable effect on reducing injuries. These programs are especially important in female athletes who bear higher incidence of ACL injury than male athletes, and also in children and adolescents who are at high risk for a second ACL tear.Researchers have found that female athletes often land with the knees relatively straight and collapsing inwards towards each other, with most of their bodyweight on a single foot and their upper body tilting to one side; these four factors put excessive strain on the ligaments on the knee and thus increase the likelihood of ACL tear. There is evidence that engaging in neuromuscular training (NMT), which focus on hamstring strengthening, balance, and overall stability to reduce risk of injury by enhancing movement patterns during high risk movements. Such programs are beneficial for all athletes, particularly adolescent female athletes.Injury prevention programs (IPPs), are reliable in reducing the risk factors of ACL inquiries, referring to dominance theories. The ligament dominance theory reduced peak knee abduction moment but should be more focused on prioritizing individualized, task-specific exercises focusing on an athletes risk profile. It is more beneficial than a generic program. There is an increase in hip and knee flexion angles, such as plyometrics and jump-landing tasks, which reduces the risk of quadriceps dominance. However, there were no changes found for peak vGRF, which measures for "softer" landings. Unfortunately, there was no conclusive data on how IPPs reduces the risk associated with leg dominance theory.

Treatment
Treatment for ACL tears is important to:
Reduce abnormal knee movements and improve knee function
Build trust and confidence to use the knee normally again
Prevent further injury to the knee and reduce the risk of osteoarthritis
Optimise long-term quality of life following the injury

Nonsurgical
Nonsurgical treatment for ACL rupture involves progressive, structured rehabilitation that aims to restore muscle strength, dynamic knee control and psychological confidence. For some, the ACL may heal without surgery during the rehabilitation process (i.e. the torn pieces re-unite to form a functional ligament).The purpose of exercise treatment is to restore the normal functioning of the muscular and balance system around the knee. Research has demonstrated that by training the muscles around the knee appropriately through exercise treatment, the body can learn to control the knee again, and despite extra movement inside the knee, the knee can feel strong and able to withstand force.Typically, this approach involves visiting a physical therapist or sports medicine professional soon after injury to oversee an intensive, structured program of exercises. Other treatments may be used initially such as hands-on therapies in order to reduce pain. The physiotherapist will act as a coach through rehabilitation, usually by setting goals for recovery and giving feedback on progress.
Estimated non-surgical recovery timeframe is 3–6 months and depends on the extent of the original injury, pre-existing fitness and commitment to the rehabilitation and sporting goals. Some may not be satisfied with the outcome of non-surgical management and may opt for surgery later.

Surgery
ACL reconstruction surgery involves replacing the torn ACL with a "graft," which is a tendon taken from another source. Grafts can be taken from the patellar tendon, hamstring tendon, quadriceps tendon from either the person undergoing the procedure ("autograft") or a cadaver ("allograft"). The graft serves as scaffolding upon which new ligament tissue will grow.The surgery is done with an arthroscope or tiny camera inserted inside the knee, with additional small incisions made around the knee to insert surgical instruments. This method is less invasive and is proven to result in less pain from surgery, less time in the hospital, and quicker recovery times than "open" surgery (in which a long incision is made down the front of the knee and the joint is opened and exposed).The timing of ACL reconstruction has been controversial, with some studies showing worse outcomes when surgery is done immediately after injury, and others showing no difference in outcomes when surgery is done immediately compared to when surgery is delayed. The American Academy of Orthopedic Surgeons has stated that there is moderate evidence to support the guideline that ACL reconstruction should occur within five months of injury in order to improve a persons function and protect the knee from further injury; however, additional studies need to be done to determine the best time for surgery and to better understand the effect of timing on clinical outcomes.Young athletes who have early surgical reconstruction are more likely to return to their previous level of athletic ability when compared to those who underwent delayed surgery or nonoperative treatment. They are also less likely to experience instability in their knee if they undergo early surgery.
There are over 100,000 ACL reconstruction surgeries per year in the United States.  Over 95% of ACL reconstructions are performed in the outpatient setting. The most common procedures performed during ACL reconstruction are partial meniscectomy and chondroplasty. Asymmetry in the repaired knee is a possibility and has been found to have a large effect between limbs for peak vertical ground reaction force, peak knee-extension moment, and loading rate during double-limb landings, as well as mean knee-extension moment and knee energy absorption during both double- and single-limb landings. Analysis of joint symmetry along with movement patterns should be a part of return to sports criteria.

Rehabilitation
The goals of rehabilitation following an ACL injury are to regain knee strength and motion. If an individual with an ACL injury undergoes surgery, the rehabilitation process will first focus on slowly increasing the range of motion of the joint, then on strengthening the surrounding muscles to protect the new ligament and stabilize the knee. Finally, functional training specific to the activities required for certain sports is begun. It may take six or more months before an athlete can return to sport after surgery, as it is vital to regain a sense of balance and control over the knee in order to prevent a second injury.

Prognosis
The prognosis of ACL injury is generally good, with many people regaining function of the injured leg within months. ACL injury used to be a career-ending injury for competitive athletes; however, in recent years ACL reconstruction surgery followed by physical therapy has allowed many athletes to return to their pre-injury level of performance.Long term complications of ACL injury include early onset arthritis of the knee and/or re-tearing the ligament. Factors that increase risk of arthritis include severity of the initial injury, injury to other structures in the knee, and level of activity following treatment. Not repairing tears to the ACL can sometimes cause damage to the cartilage inside the knee because with the torn ACL, the tibia and femur bone are more likely to rub against each other.Unfortunately, young female athletes have a significant risk of re-tearing an ACL graft, or tearing the ACL on the other knee after their recovery. This risk has been recorded as being nearly 1 out of every 4 young athletes </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Rotor syndrome and explain in detail? [/INST] Rotor syndrome (also known as Rotor type hyperbilirubinemia) is a rare cause of mixed direct (conjugated) and indirect (unconjugated) hyperbilirubinemia, relatively benign, autosomal recessive bilirubin disorder characterized by non-hemolytic jaundice due to the chronic elevation of predominantly conjugated bilirubin.Rotor type hyperbilirubinemia is a distinct yet similar disorder to Dubin–Johnson syndrome – both diseases cause an increase in conjugated bilirubin. Whereas rotor syndrome differs in that it is a result of impaired hepatocellular storage of conjugated bilirubin that leaks into plasma causing hyperbilirubinemia.

Signs and symptoms
Rotor syndrome has many features in common with Dubin–Johnson syndrome, an exception being that the liver cells are not pigmented. The main symptom is a non-itching jaundice. There is a rise in bilirubin in the patients serum, mainly of the conjugated type.
It can be differentiated from Dubin–Johnson syndrome in the following ways:
Rotor syndrome may exacerbate toxic side effects of the medication irinotecan.

Pathophysiology
Rotor syndrome is caused by mutations in two proteins responsible for transporting bilirubin and other compounds from the blood to the liver to be metabolized and cleared from the body.Coproporphyrin I, a major coproporphyrin isomer in bile, is transported from the hepatocyte back into the circulation and is excreted in the urine. Thus, urine coproporphyrin is elevated in Rotor syndrome.Cholescintigraphy using sulfobromophthalein (BSP) have shown that the transport capacity of dye into bile is reduced by less than 50%, and the storage capacity in the hepatocytes is decreased more than 5-fold compared with normal values in this disease.

Genetics
Rotor syndrome is inherited in an autosomal recessive manner. The SLCO1B1 and SLCO1B3 genes are involved in Rotor syndrome. Mutations in both genes are required for the condition to occur. The SLCO1B1 and SLCO1B3 genes provide instructions for making similar proteins, called organic anion transporting polypeptide 1B1 (OATP1B1) and organic anion transporting polypeptide 1B3 (OATP1B3), respectively. Both proteins are found in liver cells; they transport bilirubin and other compounds from the blood into the liver so that they can be cleared from the body. In the liver, bilirubin is dissolved in a digestive fluid called bile and then excreted from the body. The SLCO1B1 and SLCO1B3 gene mutations that cause Rotor syndrome lead to abnormally short, nonfunctional OATP1B1 and OATP1B3 proteins or an absence of these proteins. Without the function of either transport protein, bilirubin is less efficiently taken up by the liver and removed from the body. The buildup of this substance leads to jaundice in people with Rotor syndrome.

Diagnosis
Increased conjugated hyperbilirubinemia is the hallmark for diagnosing Rotor syndrome. There is no distinct black pigmentation of the liver as seen in a similar, Dubin-Johnson Syndrome. Genes, SLCO1B1 and SLCO1B3 that result in complete functional deficiencies of both protein products (OATP1B1 and OATP1B3, respectively), are also present.Rotor syndrome is largely a diagnosis of exclusion </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Erbs palsy and explain in detail? [/INST] Erbs palsy  is a paralysis of the arm caused by injury to the upper group of the arms main nerves, specifically the severing of the upper trunk C5–C6 nerves. These form part of the brachial plexus, comprising the ventral rami of spinal nerves C5–C8 and thoracic nerve T1. These injuries arise most commonly, but not exclusively, from shoulder dystocia during a difficult birth.  Depending on the nature of the damage, the paralysis can either resolve on its own over a period of months, necessitate rehabilitative therapy, or require surgery.

Presentation
The paralysis can be partial or complete; the damage to each nerve can range from bruising to tearing. The most commonly involved root is C5 (aka Erbs point: the union of C5 & C6 roots) as this is mechanically the furthest point from the force of traction, therefore, the first/most affected. Erb–Duchenne palsy presents as a lower motor neuron syndrome associated with sensibility disturbance and vegetative phenomena.The most commonly involved nerves are the suprascapular nerve, musculocutaneous nerve, and the axillary nerve.The signs of Erbs palsy include loss of sensation in the arm and paralysis and atrophy of the deltoid, biceps, and brachialis muscles. "The position of the limb, under such conditions, is characteristic: the arm hangs by the side and is rotated medially; the forearm is extended and pronated. The arm cannot be raised from the side; all power of flexion of the elbow is lost, as is also supination of the forearm". The resulting biceps damage is the main cause of this classic physical position commonly called "waiters tip".If the injury occurs at age early enough to affect development (e.g. as a neonate or infant), it often leaves the patient with stunted growth in the affected arm with everything from the shoulder through to the fingertips smaller than the unaffected arm. This also leaves the patient with impaired muscular, nervous and circulatory development. The lack of muscular development leads to the arm being much weaker than the unaffected one, and less articulate, with many patients unable to lift the arm above shoulder height unaided, as well as leaving many with an elbow contracture.The lack of development to the circulatory system can leave the arm with almost no ability to regulate its temperature, which often proves problematic during winter months when it would need to be closely monitored to ensure that the temperature of the arm was not dropping too far below that of the rest of the body. However the damage to the circulatory system also leaves the arm with another problem. It reduces the healing ability of the skin, so that skin damage takes far longer than usual to heal, and infections in the arm can be quite common if cuts are not sterilized as soon as possible.The neurological damage is often the most problematic aspect of Erbs palsy, but it is also the most varying. There have been cases of patients who have lost complete sensory perception within the arm after procedures whereas they had full sensory perception before. The most common area for a loss of sensory perception (except where the arm faces a total loss) is between the shoulder and the elbow, since the nerves which provide information from that area to the brain are also those first damaged in the initial causative trauma.

Cause
The most common cause of Erbs palsy is dystocia,  an abnormal or difficult childbirth or labor. For example, it can occur if the infants head and neck are pulled toward the side at the same time as the shoulders pass through the birth canal. The condition can also be caused by excessive pulling on the shoulders during a cephalic presentation (head first delivery), or by pressure on the raised arms during a breech (feet first) delivery. Erbs palsy can also affect neonates affected by a clavicle fracture unrelated to dystocia.A similar injury may be observed at any age following trauma to the head and shoulder, which cause the nerves of the plexus to violently stretch, with the upper trunk of the plexus sustaining the greatest injury. Injury may also occur as the result of direct violence, including gunshot wounds and traction on the arm, or attempting to diminish shoulder joint dislocation. The level of damage to the constituent nerves is related to the amount of paralysis.

Diagnosis
The appearance of the affected arm (or arms) depends on the individual case. In some cases the arm may lack the ability to straighten or rotate but otherwise function normally giving the overall appearance of the arm to be stiff and crooked. Whereas in other circumstances the arm has little to no control and has a "loose" appearance. Treatment such as physiotherapy, massage and electrical stimulation can help to prevent this early on (or throughout) the patients life by strengthening the arm.In some cases, again, individuals may experience a great deal of discomfort. For example, they may experience a severe cramping pain that lasts for some time and is particularly painful after they have slept, running from the shoulder all the way down to the wrist. Although pain does not affect everyone with Erbs palsy, it can be extremely uncomfortable to those that it does and can even cause patients to be physically sick or faint. This extreme nerve pain is mostly common during the final stages of growth and almost always eases off in time. Other pains that people with Erbs palsy might endure include strained muscle, stiffness, circulatory problems and cramp. Different factors are dependent on the severity of the condition and can vary, so whilst some patient experience a lot of pain, some patients may experience no pain at all and for their affected arm to simply be visually crooked.Discomfort with the shoulder blade is also extremely common in Erbs palsy as the shoulder is often at risk of dislocation. This can result, again, in sickness or lack of sleep.

Treatment
Some babies recover on their own; however, some may require specialist intervention.Neonatal/pediatric neurosurgery is often required for avulsion fracture repair. Lesions may heal over time and function return. Physiotherapeutic care is often required to regain muscle usage.
Although range of motion is recovered in many children under one year in age, individuals who have not yet healed after this point will rarely gain full function in their arm and may develop arthritis.The three most common treatments for Erbs palsy are nerve transfers (usually from the opposite arm or limb), subscapularis releases and latissimus dorsi tendon transfers.Nerve transfers are usually performed on babies under the age of 9 months since the fast development of younger babies increases the effectiveness of the procedure. They are not usually carried out on patients older than this because when the procedure is done on older infants, more harm than good is done, and it can result in nerve damage in the area from which the nerves were taken. Scarring can vary from faint scars along the lines of the neck to full "T" shapes across the whole shoulder depending on the training of the surgeon and the nature of the transplant.Subscapularis releases, however, are not time limited. Since it is merely cutting a "Z" shape into the subscapularis muscle to provide stretch within the arm, it can be carried out at almost any age and can be carried out repeatedly on the same arm; however, this will compromise the integrity of the muscle.Latissimus dorsi tendon transfers involve cutting the latissimus dorsi in half horizontally in order to pull part of the muscle around and attach it to the outside of the biceps. This procedure provides external rotation with varying degrees of success. A side effect may be increased sensitivity of the part of the biceps where the muscle will now lie, since the latissimus dorsi has roughly twice the number of nerve endings per square inch of other muscles.

History
The renowned British obstetrician William Smellie is credited with the first medical description of an obstetric brachial plexus palsy.  In his 1768 treatise on midwifery, he reported a case of transient bilateral arm paralysis in a newborn after difficult labour.

In 1861, Guillaume Benjamin Amand Duchenne coined the term "obstetric palsy of the brachial plexus" after analyzing four infants with paralysis of identical muscles in the arm and shoulder, after publishing his initial findings in 1855.  In 1874, Wilhelm Heinrich Erb concluded in his thesis on adult brachial plexus injuries that associated palsies of the deltoid, biceps and subscapularis are derived from a radicular lesion at the level of C5 and C6 rather than isolated peripheral nerve lesions.

Notable people with Erbs palsy
Notable individuals with Erbs palsy include Emperor Wilhelm II of Germany, King of Prussia, the Palestinian psychiatrist Samah Jabr, and the Canadian journalist Barbara Frum. Martin Sheen was injured during birth and developed the condition in his left arm.  His difference in arm length and range of motion can be seen in his work, especially Apocalypse Now and the jacket flip during The West Wing.
Professional wrestler Traci Brooks has Erbs palsy and has achieved a successful career. Another is former Iowa Hawkeyes standout defensive lineman Adrian Clayborn. Gangster rapper and Academy Award winner DJ Paul of Three Six Mafia also has the condition in his arm, which he often hides by wearing a cast during public appearances </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Cutaneous larva migrans and explain in detail? [/INST] Cutaneous larva migrans (abbreviated CLM) is a skin disease in humans, caused by the larvae of various nematode parasites of the hookworm family (Ancylostomatidae). These parasites live in the intestines of dogs, cats, and wild animals and should not be confused with other members of the hookworm family for which humans are definitive hosts, namely Ancylostoma duodenale and Necator americanus.
Colloquially called creeping eruption due to its presentation, the disease is also somewhat ambiguously known as "ground itch" or (in some parts of the southern United States) "sandworms", as the larvae like to live in sandy soil. Another vernacular name is plumbers itch. The medical term CLM literally means "wandering larvae in the skin".

Symptoms and signs
The infection causes a red, intensely pruritic (itchy) eruption, and may look like twirling lesions. The itching can become very painful and if scratched may allow a secondary bacterial infection to develop. Cutaneous larva migrans usually heals spontaneously over weeks to months and has been known to last as long as one year. However, the severity of the symptoms usually causes those infected to seek medical treatment before spontaneous resolution occurs </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Hypertensive emergency and explain in detail? [/INST] A hypertensive emergency is very high blood pressure with potentially life-threatening symptoms and signs of acute damage to one or more organ systems (especially brain, eyes, heart, aorta, or kidneys). It is different from a hypertensive urgency by this additional evidence for impending irreversible hypertension-mediated organ damage (HMOD). Blood pressure is often above 200/120 mmHg, however there are no universally accepted cutoff values. Signs of organ damage will be discussed below.

Signs and symptoms
Symptoms may include headache, nausea, or vomiting. Chest pain may occur due to increased workload on the heart resulting in inadequate delivery of oxygen to meet the heart muscles metabolic needs. The kidneys may be affected, resulting in blood or protein in the urine, and acute kidney failure. People can have decreased urine production, fluid retention, and confusion.Other signs and symptoms can include:
Chest pain
Abnormal heart rhythms
Headache
Nosebleeds that are difficult to stop
Dyspnea
Fainting or the sensation of the world spinning around them (vertigo)
Severe anxiety
Agitation
Altered mental status
Abnormal sensationsThe most common presentations of hypertensive emergencies are cerebral infarction (24.5%), pulmonary edema (22.5%), hypertensive encephalopathy (16.3%), and congestive heart failure (12%). Less common presentations include intracranial bleeding, aortic dissection, and  pre-eclampsia or eclampsia.Massive, rapid elevations in blood pressure can trigger any of these symptoms, and warrant further work-up by physicians. Physical exam would include measurement of blood pressure in both arms. Laboratory tests to be conducted include urine toxicology, blood glucose, a basic metabolic panel evaluating kidney function, or a complete metabolic panel evaluating liver function, EKG, chest x-rays, and pregnancy screening.The eyes may show bleeding in the retina, an exudate, cotton-wool spots, scattered splinter hemorrhages, or swelling of the optic disc called papilledema.

Causes
Many factors and causes are contributory in hypertensive crises. The most common cause is patients with diagnosed, chronic hypertension who have discontinued anti hypertensive medications.Other common causes of hypertensive crises are autonomic hyperactivity such as pheochromocytoma, collagen-vascular diseases, drug use particularly stimulants, cocaine and amphetamines and their substituted analogues, monoamine oxidase inhibitors or food-drug interactions, spinal cord disorders, glomerulonephritis, head trauma, neoplasias, preeclampsia and eclampsia, hyperthyroidism and renovascular hypertension. People withdrawing from medications such as clonidine or beta-blockers have been frequently found to develop hypertensive crises. It is important to note that these conditions exist outside of hypertensive emergency, in that patients diagnosed with these conditions are at increased risk of hypertensive emergencies or end organ failure.

Pathophysiology
The pathophysiology of hypertensive emergency is not well understood. Failure of normal autoregulation and an abrupt rise in systemic vascular resistance are typical initial components of the disease process.Hypertensive emergency pathophysiology includes:
Abrupt increase in systemic vascular resistance, likely related to humoral vasoconstrictors
Endothelial injury and dysfunction
Fibrinoid necrosis of the arterioles
Deposition of platelets and fibrin
Breakdown of normal autoregulatory functionThe resulting ischemia prompts further release of vasoactive substances including prostaglandins, free radicals, and thrombotic/mitotic growth factors, completing a vicious cycle of inflammatory changes. If the process is not stopped, homeostatic failure begins, leading to loss of cerebral and local autoregulation, organ system ischemia and dysfunction, and myocardial infarction. Single-organ involvement is found in approximately 83% of hypertensive emergency patients, two-organ involvement in about 14% of patients, and multi-organ failure (failure of at least 3 organ systems) in about 3% of patients.In the brain, hypertensive encephalopathy - characterized by hypertension, altered mental status, and swelling of the optic disc - is a manifestation of the dysfunction of cerebral autoregulation. Cerebral autoregulation is the ability of the blood vessels in the brain to maintain a constant blood flow. People with chronic hypertension can tolerate higher arterial pressure before their autoregulation system is disrupted. Hypertensives also have an increased cerebrovascular resistance which puts them at greater risk of developing cerebral ischemia if the blood flow decreases into a normotensive range. On the other hand, sudden or rapid rises in blood pressure may cause hyperperfusion and increased cerebral blood flow, causing increased intracranial pressure and cerebral edema, with increased risk of intracranial bleeding.In the heart, increased arterial stiffness, increased systolic blood pressure, and widened pulse pressures, all resulting from chronic hypertension, can cause significant damage. Coronary perfusion pressures are decreased by these factors, which also increase myocardial oxygen consumption, possibly leading to left ventricular hypertrophy. As the left ventricle becomes unable to compensate for an acute rise in systemic vascular resistance, left ventricular failure and pulmonary edema or myocardial ischemia may occur.In the kidneys, chronic hypertension has a great impact on the kidney vasculature, leading to pathologic changes in the small arteries of the kidney. Affected arteries develop endothelial dysfunction and impairment of normal vasodilation, which alter kidney autoregulation. When the kidneys autoregulatory system is disrupted, the intraglomerular pressure starts to vary directly with the systemic arterial pressure, thus offering no protection to the kidney during blood pressure fluctuations.  The renin-aldosterone-angiotensin system can be activated, leading to further vasoconstriction and damage. During a hypertensive crisis, this can lead to acute kidney ischemia, with hypoperfusion, involvement of other organs, and subsequent dysfunction. After an acute event, this endothelial dysfunction has persisted for years.

Diagnosis
The term hypertensive emergency is primarily used as a specific term for a hypertensive crisis with a diastolic blood pressure greater than or equal to 120 mmHg or systolic blood pressure greater than or equal to 180 mmHg. Hypertensive emergency differs from hypertensive urgency in that, in the former, there is evidence of acute organ damage. Both of these definitions had collectively been known as malignant hypertension, although this medical term is replaced.In the pregnant patient, the definition of hypertensive emergency (likely secondary to pre-eclampsia or eclampsia) is only a blood pressure exceeding 160 mmHg systolic blood pressure or 110 mmHg diastolic blood pressure.

Treatment
In a hypertensive emergency, treatment should first be to stabilize the patients airway, breathing, and circulation per ACLS guidelines. Patients should have their blood pressure slowly lowered over a period of minutes to hours with an antihypertensive agent. Documented goals for blood pressure include a reduction in the mean arterial pressure by less than or equal to 25% within the first 8 hours of emergency. If blood pressure is lowered aggressively, patients are at increased risk of complications including stroke, blindness, or kidney failure. Several classes of anti hypertensive agents are recommended, with the choice depending on the cause of the hypertensive crisis, the severity of the elevation in blood pressure, and the patients baseline blood pressure prior to a hypertensive emergency. Physicians will attempt to identify a cause of the patients hypertension, including chest radiograph, serum laboratory studies evaluating kidney function, urinalysis, as that will alter the treatment approach for a more patient-directed regimen.Hypertensive emergencies differ from hypertensive urgency in that they are treated parenterally, whereas in urgency it is recommended to use oral anti hypertensives to reduce the risk of hypotensive complications or ischemia. Parenteral agents are classified into beta-blockers, calcium channel blockers, systemic vasodilators, or other (fenoldopam, phentolamine, clonidine). Medications include labetalol, nicardipine, hydralazine, sodium nitroprusside, esmolol, nifedipine, minoxidil, isradipine, clonidine, and chlorpromazine. These medications work through a variety of mechanisms. Labetalol is a beta-blocker with mild alpha antagonism, decreasing the ability of catecholamine activity to increase systemic vascular resistance, while also decreasing heart rate and myocardial oxygen demand. Nicardipine, Nifedipine, and Isradipine are calcium channel blockers that work to decrease systemic vascular resistance and subsequently lower blood pressure. Hydralazine and Sodium nitroprusside are systemic vasodilators, thereby reducing afterload, however can be found to have reflex tachycardia, making them likely second or third line choices. Sodium nitroprusside was previously the first-line choice due to its rapid onset, although now it is less commonly used due to side effects, drastic drops in blood pressure, and cyanide toxicity. Sodium nitroprusside is also contraindicated in patients with myocardial infarction, due to coronary steal. It is again important that the blood pressure is lowered slowly. The initial goal in hypertensive emergencies is to reduce the pressure by no more than 25% the mean arterial pressure. Excessive reduction in blood pressure can precipitate coronary, cerebral, or kidney ischemia and, possibly, infarction.A hypertensive emergency is not based solely on an absolute level of blood pressure, but also on a patients baseline blood pressure before the hypertensive crisis occurs. Individuals with a history of chronic hypertension may not tolerate a "normal" blood pressure, and can therefore present symptomatically with hypotension, including fatigue, light-headedness, nausea, vomiting, or syncope.

Prognosis
Severe hypertension is a serious and potentially life-threatening medical condition. It is estimated that people who do not receive appropriate treatment only live an average of about three years after the event.The morbidity and mortality of hypertensive emergencies depend on the extent of end-organ dysfunction at the time of presentation and the degree to which blood pressure is controlled afterward. With good blood pressure control and medication compliance, the 5-year survival rate of patients with hypertensive crises approaches 55%.The risks of developing a life-threatening disease affecting the heart or brain increase as the blood flow increases. Commonly, ischemic heart attack and stroke are the causes that lead to death in patients with severe hypertension. It is estimated that for every 20 mm Hg systolic or 10 mm Hg diastolic increase in blood pressures above 115/75 mm Hg, the mortality rate for both ischemic heart disease and stroke doubles.Consequences of hypertensive emergency result after prolonged elevations in blood pressure and associated end-organ dysfunction </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Overlap syndrome and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Fifth disease and explain in detail? [/INST] Erythema infectiosum, fifth disease, or slapped cheek syndrome is one of several possible manifestations of infection by parvovirus B19. Fifth disease typically presents as a rash and is more common in children. While parvovirus B19 can affect humans of all ages, only two out of ten individuals will present with physical symptoms.The name "fifth disease" comes from its place on the standard list of rash-causing childhood diseases, which also includes measles (first), scarlet fever (second), rubella (third), Dukes disease (fourth, but is no longer widely accepted as distinct from scarlet fever), and roseola (sixth). Treatment is mostly supportive.

Signs and symptoms
Fifth disease starts with a low-grade fever, headache, rash, and cold-like symptoms, such as a runny or stuffy nose.  These symptoms pass, then a few days later, the rash appears. The bright red rash most commonly appears in the face, particularly the cheeks. This is a defining symptom of the infection in children (hence the name "slapped cheek disease"). Occasionally, the rash will extend over the bridge of the nose or around the mouth. In addition to red cheeks, children often develop a red, lacy rash on the rest of the body, with the upper arms, torso, and legs being the most common locations. The rash typically lasts a few days and may itch; some cases have been known to last for several weeks. Patients are usually no longer infectious once the rash has appeared.Teenagers and adults may present with a self-limited arthritis. It manifests in painful swelling of the joints that feels similar to arthritis. Older children and adults with fifth disease may have difficulty in walking and in bending joints such as wrists, knees, ankles, fingers, and shoulders.The disease is usually mild, but in certain risk groups and rare circumstances, it can have serious consequences:

In pregnant women, infection in the first trimester has been linked to hydrops fetalis, causing spontaneous miscarriage.
In people with sickle-cell disease or other forms of chronic hemolytic anemia such as hereditary spherocytosis, infection can precipitate an aplastic crisis.
Those who are immunocompromised (HIV/AIDS, chemotherapy) may be at risk for complications if exposed.
In less than 5% of women with parvovirus B19 infection, a baby may develop severe anemia leading to miscarriage. This occurs most often during the first half of pregnancy.

Causes
Fifth disease, also known as erythema infectiosum, is caused by parvovirus B19, which only infects humans. Infection by parvovirus B19 can lead to multiple clinical manifestations, but the most common is fifth disease.Parvovirus B19 (B19V) is a small, single-stranded, non-enveloped DNA virus. Binding of B19V capsid to the cellular receptor globoside (Gb4Cer) results in a cascade of structural changes and subsequent signal transduction processes facilitating the entry of parvovirus B19 into the host cell. After gaining access to the host cell, BV19 binds to glycosphingolipid globoside (blood group P antigen) targeting erythroid lineage in the bone marrow. Replication of viral genome and release of virus from infected cells lead to various complex effects on hosts cellular environment such as induction of DNA damage, hijack of cell cycle and apoptosis (killing of infected cells).B19V DNA has been found in a wide range of tissues in healthy and diseased individuals indicates the persistence of B19V infection. According to a clinical microbiology review published by Jianming Qiu "Persistence of viral DNA has been detected in up to 50% of biopsy specimens of the spleen, lymph nodes, tonsils, liver, heart, synovial tissues, skin, brain, and testes, for decades after infection."Recovery from parvovirus B19 infection is achieved by production of IgM antibodies which are specific for virus and are generated 10–12 days after infection. After day 16, when signs of fifth disease (red rashes) and arthralgia (pain in joints) becomes apparent, specific anti B19 IgG is produced by immune cells. Production of serum anti B19 IgG keeps infection under control and facilitates the recovery of erythroid cell production in erythroid lineage cells that were targeted by parvovirus B19.

Diagnosis
The "slapped cheek" appearance of the rash can be suggestive of fifth disease, however, the rash can be mistaken with other skin related disease or infections. Blood samples testing can be definitive in confirming diagnosis. Anti-parvovirus B19 IgM antibody serum assay is the preferred method to detect previous infection. An antibody assay uses antibodies designed to detect parvovirus antigen or protein in blood circulation. The assay can result positive one week after initial infection. Negative results may prompt retesting in the future to rule out early sampling of blood serum.  A positive result can also be indicative of an infection within the past two to six months. People acquire lifetime immunity if IgG antibodies are produced in response to parvovirus B19 exposure. Infection by parvovirus B19 can also be confirmed by isolation of viral DNA detected by PCR or direct hybridization. PCR Is considered significantly more sensitive to detecting viral antigen compared direct DNA hybridization. DNA hybridization assay can better detect variants of the parvovirus B19. There exists 3 biological similar genotypes of parvovirus B19, numbered one through three. The most common genotype circulating is genotype one. Laboratory tests can indicate complications of infection, including anemia, liver damage, and low platelet count.

Transmission
Fifth disease is transmitted primarily by respiratory secretions (saliva, mucus, etc.), but can also be spread by contact with infected blood. The incubation period (the time between the initial infection and the onset of symptoms) is usually between 4 and 21 days. Individuals with fifth disease are most infectious before the onset of symptoms. Typically, school children, day-care workers, teachers, and parents are most likely to be exposed to the virus. When symptoms are evident, the risk of transmission is small; therefore, symptomatic individuals do not need to be isolated. Vertical transmission from maternal infection may also occur, which can lead to hydrops fetalis due to the infections detrimental effects on red blood cell production.

Treatment
Treatment is supportive, as the infection is frequently self-limiting. No specific therapy is recommended. Antipyretics are commonly used to reduce fevers. In cases of arthropathy, such as those with arthritis or arthralgia, non-steroidal anti-inflammatories (NSAIDs) or other ant-inflammatories can be used. The rash usually does not itch, but can be mildly painful. The rash itself is not considered contagious. The infection generally lasts about 5 to 10 days. Stress, hot temperatures, exercise, and exposure to sunlight can contribute to reoccurrence within months of the initial infection. Upon resolution, immunity is considered life-long. Populations at greater risk of complications (see below) may need referral to a specialist. Anemia is a more severe complication that could result from parvovirus B19 infection and requires a blood transfusion as part of therapy.

Epidemiology
Fifth Disease is a viral illness caused by Parvovirus B19. The illness is very common and self-limiting. The modes of transmission include respiratory droplets, blood, or mother to fetus. Fifth Disease is most prevalent in children aged 5 to 15 years old. Fifth disease occurs at lower rates in adults. The virus spreads easily and once contracted, the body will begin developing lasting immunity to reinfection. The prevalence of antibodies is 50% in children and 70% to 85% in adults. The virus affects both men and women equally. During the spring and winter, epidemic outbreaks are most likely to occur. In the summer and fall, sporadic cases and outbreaks occur. The outbreaks most commonly occur in daycares and schools. The periodicity of the outbreak cycle is three-to-seven years. The risk of acquiring the viral illness increases when exposed to an infected person or contaminated blood. Individuals who have an occupation that requires close contact with infected people such as healthcare workers and teachers are at an increased risk of acquiring the viral illness. Another risk factor of fifth disease are immunocompromised individuals, those with anemia are at a higher risk of developing complications. Pregnant women are at risk for acquiring viral illness, especially during the first half of pregnancy. Though, complications are very rare and less than 5% of these cases will experience serious complications. The most common complication among pregnant women is anemia. In rare cases, severe anemia can occur, and a buildup of fluid can develop. A buildup of fluid can cause congestive heart failure or death. A blood infusion or induction may be necessary. No vaccine is available for human parvovirus B19, though attempts have been made to develop one.

History
Parvovirus, the virus causing the fifth disease, was first discovered in 1975 by Yvonne Cossart. It,  or a disease presenting similarly, was first described by Robert Willan in his book called On Cutaneous Diseases in 1808 as "rubeola, sine catarrho". It was better defined by Anton Tschamer in 1889 as a rubella variant (Ortliche Rotheln) and described it as abortive rubella, identified as a distinct condition in 1896 by Theodor Escherich, and given the name "erythema infectiosum" in 1899. The term "Fifth disease" was coined in 1905 by the Russian-French physician Léon Cheinisse (1871-1924), who proposed a numbered classification of the six most common childhood exanthems. The virus was first described in 1957 at the University of Pennsylvania  by Werner, Brachman et al.

Vulnerable populations
A 2019 systematic review examined the rates of parvovirus B19 infection among daycare workers. Since transmission typically occurs through respiratory secretions, it was thought that daycare workers would be at an increased risk of infection because young children can spread saliva through drool. The systematic review indicates that daycare workers are at an increased risk for infection. Another review also supports the finding that daycare workers have an increased risk of contracting parvovirus B19 infection. A 2019 meta-analysis examined rates of parvovirus B19 infection among those with Sickle Cell Disease (SCD) using IgG and IgM antibody detection. Pooled data from Africa, Asia, and the Americas revealed a 48.8% parvovirus B19 infection prevalence among persons with SCD. Prevalence of infection was also determined by geographic location, where areas with reduced access to adequate housing had higher prevalence (Africa was 55.5%). A 2020 literature review also supports the finding that persons with SCD, as well as those with the blood disorder beta-thalassemia, are at a higher risk of parvovirus B19 infection.

Complications
There are some known complications associated with Fifth Disease relating to pregnancy. While parvovirus B19 is typically transmitted via respiratory secretions or hand to mouth contact, it has also been known to be passed from pregnant mothers to fetuses. Roughly 50-75% of all pregnant women are immune to parvovirus B19 while the remainder of women are susceptible to mild illness. A majority of fetuses who do contract parvovirus B19 show either no significant symptoms or complete resolution of the virus. However, the following serious complications are rare but possible: miscarriage, stillbirth, fetal anemia, hepatic failure, and abnormal neurodevelopment outcome. In some cases, fetuses would develop hydrops fetalis due to congenital parvovirus B19. This condition was studied as a determinant of later fetal outcomes, such as miscarriage or perinatal death, in 2016 systematic review </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Marfan syndrome and explain in detail? [/INST] Marfan syndrome (MFS) is a multi-systemic genetic disorder that affects the connective tissue. Those with the condition tend to be tall and thin, with long arms, legs, fingers, and toes. They also typically have overly-flexible joints and scoliosis. The most serious complications involve the heart and aorta, with an increased risk of mitral valve prolapse and aortic aneurysm. The lungs, eyes, bones, and the covering of the spinal cord are also commonly affected. The severity of the symptoms is variable.MFS is caused by a mutation in FBN1, one of the genes that makes fibrillin, which results in abnormal connective tissue. It is an autosomal dominant disorder. In about 75% of cases, it is inherited from a parent with the condition, while in about 25% it is a new mutation. Diagnosis is often based on the Ghent criteria.There is no known cure for MFS. Many of those with the disorder have a normal life expectancy with proper treatment. Management often includes the use of beta blockers such as propranolol or atenolol or, if they are not tolerated, calcium channel blockers or ACE inhibitors. Surgery may be required to repair the aorta or replace a heart valve. Avoiding strenuous exercise is recommended for those with the condition.About 1 in 5,000 to 1 in 10,000 people have MFS. Rates of the condition are similar  in different regions of the world. It is named after French pediatrician Antoine Marfan, who first described it in 1896.

Signs and symptoms
More than 30 signs and symptoms are variably associated with Marfan syndrome. The most prominent of these affect the skeletal, cardiovascular, and ocular systems, but all fibrous connective tissue throughout the body can be affected.

Skeletal system
Most of the readily visible signs are associated with the skeletal system. Many individuals with Marfan syndrome grow to above-average height, and some have disproportionately long, slender limbs with thin, weak wrists and long fingers and toes.
The Steinberg sign, also known as the thumb sign, is one of the clinical examination tests for Marfan disease in the hands. It is a clinical test in which the tip of the thumb extends beyond the palm when the thumb is clasped in the clenched hand.Besides affecting height and limb proportions, people with Marfan syndrome may have abnormal lateral curvature of the spine scoliosis, thoracic lordosis, abnormal indentation (pectus excavatum) or protrusion (pectus carinatum) of the sternum, abnormal joint flexibility, a high-arched palate with crowded teeth and an overbite, flat feet, hammer toes, stooped shoulders, and unexplained stretch marks on the skin. It can also cause pain in the joints, bones, and muscles. Some people with Marfan have speech disorders resulting from symptomatic high palates and small jaws. Early osteoarthritis may occur. Other signs include limited range of motion in the hips due to the femoral head protruding into abnormally deep hip sockets.

Eyes
In Marfan syndrome, the health of the eye can be affected in many ways, but the principal change is partial lens dislocation, where the lens is shifted out of its normal position. This occurs because of weakness in the ciliary zonules, the connective tissue strands which suspend the lens within the eye. The mutations responsible for Marfan syndrome weaken the zonules and cause them to stretch. The inferior zonules are most frequently stretched resulting in the lens shifting upwards and outwards, but it can shift in other directions as well. Nearsightedness (myopia), and blurred vision are common due to connective tissue defects in the eye. Farsightedness can also result particularly if the lens is highly subluxated. Subluxation (partial dislocation) of the lens can be detected clinically in about 60% of people with Marfan syndrome by the use of a slit-lamp biomicroscope. If the lens subluxation is subtle, then imaging with high-resolution ultrasound biomicroscopy might be used.Other signs and symptoms affecting the eye include increased length along an axis of the globe, myopia, corneal flatness, strabismus, exotropia, and esotropia. Those with MFS are also at a high risk for early glaucoma and early cataracts.

Cardiovascular system
The most serious signs and symptoms associated with Marfan syndrome involve the cardiovascular system: undue fatigue, shortness of breath, heart palpitations, racing heartbeats, or chest pain radiating to the back, shoulder, or arm. Cold arms, hands, and feet can also be linked to MFS because of inadequate circulation. A heart murmur, abnormal reading on an ECG, or symptoms of angina can indicate further investigation. The signs of regurgitation from prolapse of the mitral or aortic valves (which control the flow of blood through the heart) result from cystic medial degeneration of the valves, which is commonly associated with MFS (see mitral valve prolapse, aortic regurgitation). However, the major sign that would lead a doctor to consider an underlying condition is a dilated aorta or an aortic aneurysm. Sometimes, no heart problems are apparent until the weakening of the connective tissue (cystic medial degeneration) in the ascending aorta causes an aortic aneurysm or aortic dissection, a surgical emergency. An aortic dissection is most often fatal and presents with pain radiating down the back, giving a tearing sensation.Because underlying connective tissue abnormalities cause MFS, the incidence of dehiscence of prosthetic mitral valve is increased. Care should be taken to attempt repair of damaged heart valves rather than replacement.

Lungs
Individuals with Marfan Syndrome may be affected by various lung-related problems. One study found that only 37% of the patient sample studied (mean age 32±14 years; M 45%) had normal lung function. Spontaneous pneumothorax is common. In spontaneous unilateral pneumothorax, air escapes from a lung and occupies the pleural space between the chest wall and a lung. The lung becomes partially compressed or collapsed. This can cause pain, shortness of breath, cyanosis, and, if not treated, death. Other possible pulmonary manifestations of MFS include sleep apnea and idiopathic obstructive lung disease. Pathologic changes in the lungs have been described such as cystic changes, emphysema, pneumonia, bronchiectasis, bullae, apical fibrosis and congenital malformations such as middle lobe hypoplasia.

Nervous system
Dural ectasia, the weakening of the connective tissue of the dural sac encasing the spinal cord, can result in a loss of quality of life. It can be present for a long time without producing any noticeable symptoms. Symptoms that can occur are lower back pain, leg pain, abdominal pain, other neurological symptoms in the lower extremities, or headaches – symptoms which usually diminish when lying flat. On X-ray, however, dural ectasia is not often visible in the early stages. A worsening of symptoms might warrant an MRI of the lower spine. Dural ectasia that has progressed to this stage would appear in an MRI as a dilated pouch wearing away at the lumbar vertebrae. Other spinal issues associated with MFS include degenerative disc disease, spinal cysts, and dysfunction of the autonomic nervous system.

Genetics
Each parent with the condition has a 50% risk of passing the genetic defect on to any child due to its autosomal dominant nature. Most individuals with MFS have another affected family member.  About 75% of cases are inherited. On the other hand, about 15–30% of all cases are due to de novo genetic mutations; such spontaneous mutations occur in about one in 20,000 births. Marfan syndrome is also an example of dominant negative mutation and haploinsufficiency. It is associated with variable expressivity; incomplete penetrance has not been definitively documented.

Pathogenesis
Marfan syndrome is caused by mutations in the FBN1 gene on chromosome 15, which encodes fibrillin 1, a glycoprotein component of the extracellular matrix. Fibrillin-1 is essential for the proper formation of the extracellular matrix, including the biogenesis and maintenance of elastic fibers. The extracellular matrix is critical for both the structural integrity of connective tissue, but also serves as a reservoir for growth factors. Elastic fibers are found throughout the body, but are particularly abundant in the aorta, ligaments and the ciliary zonules of the eye; consequently, these areas are among the worst affected. It can also be caused by a range of intravenous crystal treatments in those susceptible to the disorder.A transgenic mouse has been created carrying a single copy of a mutant fibrillin-1, a mutation similar to that found in the human gene known to cause MFS. This mouse strain recapitulates many of the features of the human disease and promises to provide insights into the pathogenesis of the disease. Reducing the level of normal fibrillin 1 causes a Marfan-related disease in mice.Transforming growth factor beta (TGF-β) plays an important role in MFS. Fibrillin-1 directly binds a latent form of TGF-β, keeping it sequestered and unable to exert its biological activity. The simplest model suggests reduced levels of fibrillin-1 allow TGF-β levels to rise due to inadequate sequestration. Although how elevated TGF-β levels are responsible for the specific pathology seen with the disease is not proven, an inflammatory reaction releasing proteases that slowly degrade the elastic fibers and other components of the extracellular matrix is known to occur. The importance of the TGF-β pathway was confirmed with the discovery of the similar Loeys–Dietz syndrome involving the TGFβR2 gene on chromosome 3, a receptor protein of TGF-β. Marfan syndrome has often been confused with Loeys–Dietz syndrome, because of the considerable clinical overlap between the two pathologies.

Marfanoid–progeroid–lipodystrophy syndrome
Marfanoid–progeroid–lipodystrophy syndrome (MPL), also referred to as Marfan lipodystrophy syndrome (MFLS), is a variant of MFS in which Marfan symptoms are accompanied by features usually associated with neonatal progeroid syndrome (also referred to as Wiedemann–Rautenstrauch syndrome) in which the levels of white adipose tissue are reduced. Since 2010, evidence has been accumulating that MPL is caused by mutations near the 3-terminus of the FBN1 gene. It has been shown that these people are also deficient in asprosin, a gluco-regulatory protein hormone which is the C-terminal cleavage product of profibrillin. The levels of asprosin seen in these people were lower than expected for a heterozygous genotype, consistent with a dominant negative effect.

Diagnosis
Diagnostic criteria of MFS were agreed upon internationally in 1996. However, Marfan syndrome is often difficult to diagnose in children, as they typically do not show symptoms until reaching pubescence. A diagnosis is based on family history and a combination of major and minor indicators of the disorder, rare in the general population, that occur in one individual – for example: four skeletal signs with one or more signs in another body system such as ocular and cardiovascular in one individual. The following conditions may result from MFS, but may also occur in people without any known underlying disorder.

Revised Ghent nosology
In 2010, the Ghent nosology was revised, and new diagnostic criteria superseded the previous agreement made in 1996. The seven new criteria can lead to a diagnosis:In the absence of a family history of MFS:

Aortic root Z-score ≥ 2 AND ectopia lentis
Aortic root Z-score ≥ 2 AND an FBN1 mutation
Aortic root Z-score ≥ 2 AND a systemic score* > 7 points
Ectopia lentis AND an FBN1 mutation with known aortic pathologyIn the presence of a family history of MFS (as defined above):

Ectopia lentis
Systemic score* ≥ 7
Aortic root Z-score ≥ 2Points for systemic score:
Wrist AND thumb sign = 3 (wrist OR thumb sign = 1)
Pectus carinatum deformity = 2 (pectus excavatum or chest asymmetry = 1)
Hindfoot deformity = 2 (plain pes planus = 1)
Dural ectasia = 2
Protrusio acetabuli = 2
pneumothorax = 2
Reduced upper segment/lower segment ratio AND increased arm/height AND no severe scoliosis = 1
Scoliosis or thoracolumbar kyphosis = 1
Reduced elbow extension = 1
Facial features (3/5) = 1 (dolichocephaly, enophthalmos, downslanting palpebral fissures, malar hypoplasia, retrognathia)
Skin striae (stretch marks) = 1
Myopia > 3 diopters = 1
Mitral valve prolapse = 1The thumb sign (Steinbergs sign) is elicited by asking the person to flex the thumb as far as possible and then close the fingers over it. A positive thumb sign is where the entire distal phalanx is visible beyond the ulnar border of the hand, caused by a combination of hypermobility of the thumb as well as a thumb which is longer than usual.The wrist sign (Walker-Murdoch sign) is elicited by asking the person to curl the thumb and fingers of one hand around the other wrist. A positive wrist sign is where the little finger and the thumb overlap, caused by a combination of thin wrists and long fingers.

Differential diagnosis
Many other disorders can produce the same type of body characteristics as Marfan syndrome. Genetic testing and evaluating other signs and symptoms can help to differentiate these. The following are some of the disorders that can manifest as "marfanoid":
Congenital contractural arachnodactyly, also known as Beals-Hecht syndrome
Ehlers–Danlos syndrome
Homocystinuria
Loeys–Dietz syndrome
MASS phenotype
Multiple endocrine neoplasia, type 2B
Shprintzen–Goldberg syndrome
Stickler syndrome

Management
There is no cure for Marfan syndrome, but life expectancy has increased significantly over the last few decades and is now similar to that of the average person.Regular checkups are recommended to monitor the health of the heart valves and the aorta. Marfan syndrome is treated by addressing each issue as it arises and, in particular, preventive medication even for young children to slow progression of aortic dilation. The goal of this treatment strategy is to slow the progression of aortic dilation and prevent any damage to heart valves by eliminating heart arrythmias, minimizing the heart rate, and lowering the persons blood pressure.

Physical activity
The American Heart Association made the following recommendations for people with Marfan syndrome with no or mild aortic dilation:
Probably permissible activities: bowling, golf, skating (but not ice hockey), snorkeling, brisk walking, treadmill, stationary biking, modest hiking, and tennis (doubles and singles).
Intermediate risk: basketball (both full- and half-court), racquetball, squash, running (sprinting and jogging), skiing (downhill and cross-country), soccer, touch (flag) football, baseball, softball, biking, lap swimming, motorcycling, and horseback riding.
High risk: bodybuilding, weightlifting (non-free and free weights), ice hockey, rock climbing, windsurfing, surfing, and scuba diving.

Medication
Management often includes the use of beta blockers such as propranolol or if not tolerated calcium channel blockers or ACE inhibitors. Beta blockers are used to reduce the stress exerted on the aorta and to decrease aortic dilation.

Surgery
If the dilation of the aorta progresses to a significant-diameter aneurysm, causes a dissection or a rupture, or leads to failure of the aortic or other valve, then surgery (possibly a composite aortic valve graft or valve-sparing aortic root replacement) becomes necessary. Although aortic graft surgery (or any vascular surgery) is a serious undertaking it is generally successful if undertaken on an elective basis. Surgery in the setting of acute aortic dissection or rupture is considerably more problematic. Elective aortic valve/graft surgery is usually considered when aortic root diameter reaches 50 millimeters (2.0 inches), but each case needs to be specifically evaluated by a qualified cardiologist. New valve-sparing surgical techniques are becoming more common. As people with Marfan syndrome live longer, other vascular repairs are becoming more common, e.g., repairs of descending thoracic aortic aneurysms and aneurysms of vessels other than the aorta.The skeletal and ocular manifestations of Marfan syndrome can also be serious, although not life-threatening. These symptoms are usually treated in an appropriate manner for the condition, such as with pain medications or muscle relaxants. Because Marfan syndrome may cause asymptomatic spinal abnormalities, any spinal surgery contemplated on a person Marfan should only follow detailed imaging and careful surgical planning, regardless of the indication for surgery. The ocular complications of MFS can often be treated with surgery. Ectopia lentis can be treated, as artificial lenses can be surgically implanted. In addition, surgery can address glaucoma and cataracts.Treatment of a spontaneous pneumothorax is dependent on the volume of air in the pleural space and the natural progression of the individuals condition. A small pneumothorax might resolve without active treatment in one to two weeks. Recurrent pneumothoraces might require chest surgery. Moderately sized pneumothoraces might need chest drain management for several days in a hospital. Large pneumothoraces are likely to be medical emergencies requiring emergency decompression.As an alternative approach, custom-built supports for the aortic root are also being used. As of 2020 this procedure has been used in over 300 people with the first case occurring in 2004.

Pregnancy
During pregnancy, even in the absence of preconception cardiovascular abnormality, women with Marfan syndrome are at significant risk of aortic dissection, which is often fatal even when rapidly treated. Women with Marfan syndrome, then, should receive a thorough assessment prior to conception, and echocardiography should be performed every six to 10 weeks during pregnancy, to assess the aortic root diameter. For most women, safe vaginal delivery is possible.Prenatal testing can be performed in females with Marfan syndrome to determine if the condition has been inherited in their child. At 10 to 12 weeks of pregnancy, examining a piece of placental tissue through a test called chorionic villus sampling can be performed to make a diagnosis. Another prenatal test can be performed called amniocentesis at 16 to 18 weeks of pregnancy.Marfan syndrome is expressed dominantly. This means a child with one parent a bearer of the gene has a 50% probability of getting the syndrome. In 1996, the first preimplantation genetic testing (PGT) therapy for Marfan was conducted; in essence PGT means conducting a genetic test on early-stage IVF embryo cells and discarding those embryos affected by the Marfan mutation.

Prognosis
Prior to modern cardiovascular surgical techniques and medications such as losartan, and metoprolol, the prognosis of those with Marfan syndrome was not good: a range of untreatable cardiovascular issues was common. Lifespan was reduced by at least a third, and many died in their teens and twenties due to cardiovascular problems. Today, cardiovascular symptoms of Marfan syndrome are still the most significant issues in diagnosis and management of the disease, but adequate prophylactic monitoring and prophylactic therapy offers something approaching a normal lifespan, and more manifestations of the disease are being discovered as more patients live longer. Women with Marfan syndrome live longer than men.

Epidemiology
Marfan syndrome affects males and females equally, and the mutation shows no ethnic or geographical bias. Estimates indicate about 1 in 5,000 to 10,000 individuals have Marfan syndrome.

History
Marfan syndrome is named after Antoine Marfan, the French pediatrician who first described the condition in 1896 after noticing striking features in a five-year-old girl. The gene linked to the disease was first identified by Francesco Ramirez at the Mount Sinai Medical Center in New York City in 1991.

Famous patients
Famous people who have had Marfan syndrome include:

Isaiah Austin
Javier Botet
Austin Carlile
Bradford Cox
Euell Gibbons
Flo Hyman
Jonathan Jeanne
Vincent Schiavelli
Troye Sivan
John TavenerIn addition the following historical figures and celebrities often appear on lists of people with Marfan syndrome, but from case to case the evidence is speculative, questionable, or even refuted.

See also
Ehlers–Danlos syndrome
Kashin–Beck disease
Loeys–Dietz syndrome
Nail-Patella syndrome
Mitral valve prolapse

Bibliography
Lorenz, Megaera. "Lorenz, Maegara "The Mystery of Akhenaton: Genetics or Aesthetics"" </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Coccydynia and explain in detail? [/INST] Coccydynia is a medical term meaning pain in the coccyx or tailbone area, often brought on by a fall onto the coccyx or by persistent irritation usually from sitting.

Synonyms
Coccydynia is also known as coccygodynia, coccygeal pain, coccyx pain, or coccalgia.

Anatomy
Structure
Coccydynia occurs in the lowest part of the spine, the coccyx, which is believed to be a vestigial tail, or in other words the “tail bone”. The name coccyx is derived from the Greek word for cuckoo due to its beak like appearance. The coccyx itself is made up of 3 to 5 vertebrae, some of which may be fused together. The ventral side of the coccyx is slightly concave whereas the dorsal aspect is slightly convex. Both of these sides have transverse grooves that show where the vestigial coccygeal units had previously fused. The coccyx attaches to the sacrum from the dorsal grooves, with the attachment being either a symphysis or as a true synovial joint, and also to the gluteus maximus muscle, the coccygeal muscle, and the anococcygeal ligament.

Orientations of the coccyx
There are four different orientations for the coccyx, as described by Postacchini and Massobrio. In type I the coccyx is curved anteriorly with its apex facing downward and caudally. In type II this forward curvature is more dramatic and the apex extends forward. Type III is where the coccyx angles forward sharply. Lastly, type IV is characterized by the coccyx being subluxated at the sacrococcygeal joint.

Pathophysiology
There are common pathophysiological ways that a person may develop coccydynia. The two main causes for this condition are sudden impact due to fall, and coccydynia caused by childbirth pressure in women. Other ways that coccydynia develops are partial dislocation of the sacrococcygeal synchondrosis that can possibly result in abnormal movement of the coccyx from excessive sitting, and repetitive trauma of the surrounding ligaments and muscles, resulting in inflammation of tissues and pain.

Diagnosis
A number of different conditions can cause pain in the general area of the coccyx, but not all involve the coccyx and the muscles attached to it. The first task of diagnosis is to determine whether the pain is related to the coccyx. Physical rectal examination, high resolution x-rays and MRI scans can rule out various causes unrelated to the coccyx, such as Tarlov cysts and pain referred from higher up the spine. Note that, contrary to most anatomical textbooks, most coccyxes consist of several segments: fractured coccyx is often diagnosed when the coccyx is in fact normal or just dislocated at an intercoccygeal joint.A simple test to determine whether the coccyx is involved is injection of local anesthetic into the area. If the pain relates to the coccyx, this should produce immediate relief.If the anesthetic test proves positive, then a dynamic (sit/stand) x-ray or MRI scan may show whether the coccyx dislocates when the patient sits.Use of dynamic x-rays on 208 patients who gave positive results with the anesthetic test showed:

31% Not possible to identify the cause of pain
27% Hypermobility (excessive flexing of the coccyx forwards and upwards when sitting)
22% Posterior luxation (partial dislocation of the coccyx backwards when sitting)
14% Spicule (bony spur) on the coccyx
5%  Anterior luxation (partial dislocation of the coccyx forwards when sitting)This study found that the pattern of lesions was different depending on the obesity of the patients: obese patients were most likely to have posterior luxation of the coccyx, while thin patients were most likely to have coccygeal spicules.

Angle of incidence
Sagittal coccygeal movement is measured using the angle of incidence—or the angle at which the coccyx strikes the seat when an individual sits down.  A smaller angle indicates the coccyx being more parallel to the seat, resulting in flexion (or “normal” movement) of the coccyx. A larger angle indicates the coccyx being more perpendicular to the seat, causing posterior subluxation (or “backward” movement) of the coccyx.

Causes
One way of classifying coccydynia is whether the onset was traumatic versus non-traumatic. In many cases the exact cause is unknown and is referred to as idiopathic coccydynia.
Coccydynia is a fairly common injury which can often result from falls, particularly in leisure activities such as cycling and skateboarding.
Coccydynia is often reported following a fall or after childbirth. In some cases, persistent pressure from activities like bicycling may cause the onset of coccyx pain.  Coccydynia due to these causes usually is not permanent, but it may become very persistent and chronic if not controlled. Coccydynia may also be caused by sitting improperly thereby straining the coccyx.
Rarely, coccydynia is due to the undiagnosed presence of a sacrococcygeal teratoma or other tumor in the vicinity of the coccyx.

Prevalence
A study of 2000 cases of back pain referred to hospital found that 2.7% were diagnosed as coccydynia. This type of pain occurs five times more frequently in women than in men. It can occur at any age, the mean age of onset being around 40.  There are no ethnicity or race associations with coccydynia.

Clinical features
Activities that put pressure on the affected area are bicycling, horseback riding, and other activities such as increased sitting that put direct stress on the coccyx. The medical condition is often characterized by pain that worsens with constipation and may be relieved with bowel movement. Rarely, even sexual intercourse can aggravate symptoms.

Non-surgical treatment
Since sitting on the affected area may aggravate the condition, a cushion with a cutout at the back under the coccyx is recommended. If there is tailbone pain with bowel movements, then stool softeners and increased fiber in the diet may help. Anti-inflammatory medications such as NSAIDS may be prescribed.If the pain persists, other treatments may be applied. Manual treatment is carried out by repeated massage of the muscles attached to the coccyx, via the anus. Such treatment is usually given by an intimate partner, chiropractor, osteopath or physical therapist. Thiele applied this treatment to a series of 169 coccydynia patients, and reported 63% cured.Orthopaedic surgeons commonly inject corticosteroids into the painful joint. Maigne and Tamalet applied this treatment to 86 patients under fluoroscopic guidance. Two months after the injection, 50% of the patients with luxation or hypermobility were improved or healed, but only 27% of the patients with no visible abnormality improved. Where an abnormality had been found, and injection relieved the pain, the abnormality remained but ceased to be painful.
Temporary or permanent nerve blocks are sometimes applied in cases of coccydynia. Foye et al reported that repeated temporary nerve blocks by injection at the ganglion impar could give relief in a number of cases, and occasionally a single injection was sufficient.

Surgical treatment
If non-surgical treatments fail to relieve the pain, or in cases of cancer, surgery to remove the coccyx (coccygectomy) may be required. In cases where pain persists after surgery, standard drugs for chronic pain, such as tri-cyclic anti-depressants, may help alleviate the pain.

Prevention or to ease coccyx pain
Body positioning and alignment is significant for producing less stress in the coccyx region. Bad posture can influence coccyx pain. People may not realize that they are over stressing their coccyx while doing daily activities. Pain in the coccyx can be caused from many incidents like falling, horseback riding, or even sitting on hard surfaces for a long period of time. The main focus is to prevent coccyx pain from occurring, by correcting everyday activities that contribute to tailbone pain. You can take hot or cold water baths. Have a stream of hot or cold water run down your back continuously if pain becomes unbearable. Use cold water if pain persists </s>