<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 Porencephaly and can you explain it in depth? [/INST] Porencephaly is an extremely rare cephalic disorder involving encephalomalacia. It is a neurological disorder of the central nervous system characterized by cysts or cavities within the cerebral hemisphere. Porencephaly was termed by Heschl in 1859 to describe a cavity in the human brain. Derived from Greek roots, the word porencephaly means holes in the brain.  The cysts and cavities (cystic brain lesions) are more likely to be the result of destructive (encephaloclastic) cause, but can also be from abnormal development (malformative), direct damage, inflammation, or hemorrhage. The cysts and cavities cause a wide range of physiological, physical, and neurological symptoms. Depending on the patient, this disorder may cause only minor neurological problems, without any disruption of intelligence, while others may be severely disabled or die before the second decade of their lives. However, this disorder is far more common within infants, and porencephaly can occur both before or after birth.

Signs and symptoms
Patients diagnosed with porencephaly display a variety of symptoms, from mild to severe effects on the patient. Patients with severe cases of porencephaly have epileptic seizures and developmental delays, whereas patients with a mild case of porencephaly display little to no seizures and typical neurodevelopment. Infants with extensive defects show symptoms of the disorder shortly after birth, and the diagnosis is usually made before the age of 1.The following text lists out common signs and symptoms of porencephaly in affected individuals along with a short description of certain terminologies.

Cause
Porencephaly is a rare disorder. The exact prevalence of porencephaly is not known; however, it has been reported that 6.8% of patients with cerebral palsy or 68% of patients with epilepsy and congenital vascular hemiparesis have porencephaly. Porencephaly has a number of different, often unknown, causes including absence of brain development and destruction of brain tissue. With limited research, the most commonly regarded cause of porencephaly is disturbances in blood circulation, ultimately leading to brain damage. However, a number of different and multiple factors such as abnormal brain development or damage to the brain tissue can also affect the development of porencephaly.The following text lists out potential risk factors of developing porencephaly and porencephalic cysts and cavities along with brief description of certain terminologies.

Cysts or cavities can occur anywhere within the brain and the locations of these cysts depend highly on the patient. Cysts can develop in the frontal lobe, parietal lobe, forebrain, hindbrain, temporal lobe, or virtually anywhere in the cerebral hemisphere.

Genetics
From recent studies, de novo and inherited mutations in the gene COL4A1, suggesting genetic predisposition within the family, that encodes type IV collagen α1 chain has shown to be associated with and present in patients with porencephaly. COL4A1 mutation causes a variety of phenotypes, including porencephaly, infantile hemiplegia, and cerebral small vessel diseases involving both stroke and infarction. Abnormal gene expression of COL4A1 can contribute to the development of porencephaly. COL4A1 gene expresses a type IV collagen (basement protein) that is present in all tissue and blood vessels and is extremely important for the structural stability of vascular basement membranes. The COL4A1 protein provides a strong layer around blood vessels. The mutation can weaken the blood vessels within the brain, elevating the probability of a hemorrhage, and eventually promoting internal bleeding then leading to porencephaly during neurodevelopment of infantile stage. Therefore, the formation of cavities can be a result of hemorrhages which promote cerebral degeneration. In a mouse model, mouse with COL4A1 mutations displayed cerebral hemorrhage, porencephaly, and abnormal development of vascular basement membranes, such as uneven edges, inconsistent shapes, and highly variable thickness. Purposely causing a mutation in the COL4A1 gene caused several mouse to develop cerebral hemorrhage and porencephaly-like diseases. Though, there is no direct correlation between mutations of the COL4A1 gene, it appears that it has an influential effect on the development of porencephaly.Another genetic mutation, factor V G1691A mutation, has been reported to show possible association to the development of porencephaly. A mutation in factor V G1691A increases the risk of thrombosis, blood clots, in neonates, infants, and children. Therefore, 76 porencephalic and 76 healthy infants were investigated for factor V G1691A mutation along with other different prothrombotic risk factors. The results indicated that there was  higher prevalence of the factor V G1691A mutation in the porencephalic patient group. The prediction that childhood porencephaly is caused by hypercoagulable state, a condition where one has a higher chance of developing blood clots, was supported by the significance of the factor V G1691A mutation. Also, pregnant women in hypercoagulable state can cause the fetus to have the same risks, therefore possibly causing fetal loss, brain damage, lesions, and infections that lead to porencephaly.  However, other different prothrombotic risk factors individually did not reach statistical significance to link it to the development of porencephaly, but a combination of multiple prothrombotic risk factors in the porencephaly group was significant. Overall, factor V G1691A mutation has been linked to the development of porencephaly. However, this one mutation is not the cause of porencephaly, and whether further prothrombiotic risk factors are associated with porencephaly still remains unknown.

Cocaine and other street drugs
In utero exposure to cocaine and other street drugs can lead to porencephaly.

Diagnostics
The presence of porencephalic cysts or cavities can be detected using trans-illumination of the skull of infant patients. Porencephaly is usually diagnosed clinically using the patients and families history, clinical observations, or based on the presence of certain characteristic neurological and physiological features of porencephaly. Advanced medical imaging with computed tomography (CT), magnetic resonance imaging (MRI), or with ultrasonography can be used as a method to exclude other possible neurological disorders. The diagnosis can be made antenatally with ultrasound. Other assessments include memory, speech, or intellect testing to help further determine the exact diagnose of the disorder.

Treatments
Currently, there is no cure for porencephaly because of the limited resources and knowledge about the neurological disorder </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Corneal ulcers in animals and can you explain it in depth? [/INST] A corneal ulcer, or ulcerative keratitis, is an inflammatory condition of the cornea involving loss of its outer layer. It is very common in dogs and is sometimes seen in cats. In veterinary medicine, the term corneal ulcer is a generic name for any condition involving the loss of the outer layer of the cornea, and as such is used to describe conditions with both inflammatory and traumatic causes.

Corneal anatomy of the dog and cat
The cornea is a transparent structure that is part of the outer layer of the eye. It refracts light and protects the contents of the eye. The cornea is about one-half to one millimeter thick in the dog and cat. The trigeminal nerve supplies the cornea via the long ciliary nerves. There are pain receptors in the outer layers and pressure receptors deeper.
Transparency is achieved through a lack of blood vessels, pigmentation, and keratin, and through the organization of the collagen fibers. The collagen fibers cross the full diameter of the cornea in a strictly parallel fashion and allow 99 percent of the light to pass through without scattering.
There are four important layers in the dog and cat cornea. The outer layer is the epithelium, which is 25 to 40 micrometers and five to seven cell layers thick. The epithelium holds the tear film in place and also prevents water from invading the cornea and disrupting the collagen fibers. This prevents corneal edema, which gives it a cloudy appearance. It is also a barrier to infectious agents. The epithelium sticks to the basement membrane, which also separates the epithelium from the stroma. The corneal stroma comprises 90 percent of the thickness of the cornea. It contains the collagen fibers organized into lamellae. The lamellae are in sheets which separate easily. Posterior to the stroma is Descemets membrane, which is a basement membrane for the corneal endothelium. The endothelium is a single cell layer that separates the cornea from the aqueous humor.

Corneal healing
A healing of a corneal ulcer involves two processes: migration of surrounding epithelial cells followed by mitosis (dividing) of the cells, and introduction of blood vessels from the conjunctiva. Superficial small ulcers heal rapidly by the first process. However, larger or deeper ulcers often require the presence of blood vessels to supply inflammatory cells. White blood cells and fibroblasts produce granulation tissue and then scar tissue, effectively healing the cornea.

Superficial and deep corneal ulcers
Corneal ulcers are one of the most common eye diseases in dogs. They are caused by trauma, detergent burns, and infections. Other eye conditions can cause corneal ulcers, such as entropion, distichiae, corneal dystrophy, and keratoconjunctivitis sicca (dry eye). There have been at least two cases where corneal ulceration was caused by canine herpesvirus.Superficial ulcers involve a loss of part of the epithelium. Deep ulcers extend into or through the stroma and can result in severe scarring and corneal perforation. Descemetoceles occur when the ulcer extends through the stroma, exposing Descemets membrane. This type of ulcer is especially dangerous and can result in perforation.
The location of the ulcer depends somewhat on the cause. Central ulcers are typically caused by trauma, dry eye, or exposure from facial nerve paralysis or exophthalmos. Ulcers in the inferior nasal cornea may be caused by foreign material trapped under the third eyelid. Entropion or distichiae may cause ulceration of the peripheral cornea. Immune-mediated eye disease can cause ulcers at the border of the cornea and sclera.

Symptoms
Corneal ulcers are painful due to nerve exposure, and can cause tearing, squinting, and pawing at the eye. There may also be signs of anterior uveitis, such as miosis (small pupil), aqueous flare (protein in the aqueous humour), and redness of the eye. An axon reflex may be responsible for uveitis formation — stimulation of pain receptors in the cornea results in release inflammatory mediators such as prostaglandins, histamine, and acetylcholine.

Diagnosis
Diagnosis is through direct observation of the ulcer with the use of fluorescein stain, which is taken up by exposed corneal stroma and appears green (see photos above and below). With descemetoceles, Descemets membrane will bulge forward and after staining will appear as a dark circle with a green boundary, because it does not absorb the stain. Other tests that may be necessary include a Schirmers test for keratoconjunctivitis sicca and an analysis of facial nerve function for facial nerve paralysis.

Treatment
Treatment of corneal ulcers includes topical antibiotic therapy to prevent infection, and pain medications, including topical atropine to stop spasms of the ciliary muscle. Atropine may decrease tear production and interfere with corneal healing. Superficial ulcers usually heal in less than a week. Deep ulcers and descemetoceles may require corneal suturing, conjunctival grafts or conjunctival flaps, soft contact lenses, or corneal transplant. Topical corticosteroids and anesthetics should not be used on any type of corneal ulcer because they prevent healing and will often make them worse.

Bioscaffold
A new bioscaffold developed by TR BioSurgical is being evaluated for refractory corneal ulcers in dogs. The study is being conducted by board certified veterinary ophthalmologists and has shown promise in healing refractory ulcers that have failed conventional treatment .

Refractory corneal ulcers
Refractory corneal ulcers are superficial ulcers that heal poorly and tend to recur. They are also known as indolent ulcers or Boxer ulcers. They are believed to be caused by a defect in the basement membrane and a lack of hemidesmosomal attachments. They are recognized by undermined epithelium that surrounds the ulcer and easily peels back. Refractory corneal ulcers are most commonly seen in middle aged or older dogs and often occur in the other eye later. They are similar to Cogans cystic dystrophy in humans.

Commonly affected breeds
Alaskan Malamute
American Cocker Spaniel
Boston Terrier
Boxer
Brussels Griffon
Cairn Terrier
Chesapeake Bay Retriever
Chihuahua
Chinese Shar Pei
Dachshund
Bulldog
English Springer Spaniel
German Shepherd Dog
Golden Retriever
Irish Setter
Japanese Chin
Lhasa Apso
Maltese
Pekingese
Poodle
Pug
Rottweiler
Samoyed
Shih Tzu
Silky Terrier
Weimaraner
Welsh Corgi
Welsh Springer Spaniel
West Highland White Terrier
Wirehaired Fox Terrier

Treatment
Refractory corneal ulcers can take a long time to heal, sometimes months. Topical antibiotics are used continually to prevent infection. Pain medications are given as needed. Loose epithelium is removed with a dry cotton swab under topical anesthesia. This is in order to allow production of normal basement membrane and division of normal epithelium. Often further treatment is necessary, such as a keratotomy, which is superficial cutting or piercing of the cornea. There are two main types used in dogs: multiple punctate keratotomy (MPK) and grid keratotomy (GK). MPK involves making small superficial punctures into the cornea with a needle. GK is more commonly used and involves making parallel and perpendicular scratches in the corneal surface. Usually only topical anesthesia is necessary. By scoring the corneal surface, anchoring points are provided for attachment of new epithelium. Of course, these procedures should only be performed by a veterinarian, particularly one with some experience in this treatment. Complete healing takes about three to four weeks. Keratotomies may lead to corneal sequestration in cats. Other medications have been shown to be useful in topical treatment of refractory ulcers, including glycosaminoglycans such as sodium hyaluronate and chondroitin sulfate, aminocaproic acid, and acetylcysteine.

Melting ulcers
Melting ulcers are a type of corneal ulcer involving progressive loss of stroma in a dissolving fashion. This is most commonly seen in Pseudomonas infection, but it can be caused by other types of bacteria or fungi. These infectious agents produce proteases and collagenases which break down the corneal stroma. Complete loss of the stroma can occur within 24 hours. Treatment includes antibiotics and collagenase inhibitors such as acetylcysteine and homologous blood serum. Surgery may be necessary.

Corneal ulcers in cats
Corneal ulcers in cats can be caused by trauma, detergent burns, infections, and other eye diseases. One common cause not seen in dogs is infection with feline herpesvirus 1 (FHV-1). FHV-1 causes ulceration by direct infection of the epithelial cells. Lesions appear as round or dendritic (branching) ulcers. FHV-1 also suppresses healing of the cornea. Symptoms include conjunctivitis, squinting, eye discharge, and blood vessels on the cornea. It can cause severe scarring. Treatment is with topical antiviral drugs and antibiotics, and oral L-lysine, which competes with arginine and inhibits viral replication.

Corneal ulcers in horses
Corneal ulceration is a very common disease of the equine eye and can have sight-threatening consequences. Aggressive treatment is always indicated, as even apparently mild ulcers can progress quickly, causing serious complications.

Causes
A distinct cause for initial ulceration is not commonly found, although in many cases it can be assumed to be traumatic in origin. The horses eye is especially vulnerable to trauma due to its prominent position, compared with other species. Exposure keratitis (inflamed cornea) can occur in the horse, most commonly secondary to facial nerve paralysis. Hospitalised animals have been shown to have a decreased corneal reflex, and this corresponds to an increased incidence of ulcers in the hospitalised population. Foreign bodies embedded in the palpebral conjunctiva or the nictitating membrane can cause persistent irritation and ulceration. Often the shape and distribution of the lesion is suggestive of this aetiology, but even in the absence of a characteristic lesion their presence should be considered and sought out.
Bacterial and fungal infection occurs readily after the initial ulceration, as disruption of the corneal epithelium allows attachment and colonisation of the underlying tissues by normal corneal commensals. Commonly isolated bacteria include Staphylococcus, Streptococcus and Pseudomonas, and empirical anti-microbial therapy should be effective against these bacteria.

Symptoms
Ocular Pain
Blepharospasm
Increased lacrimation
Photophobia
Corneal Oedema (1⁰/2⁰)
Scleral injection
Conjunctivitis

Diagnosis
Differential diagnoses for the painful equine eye:

Ulceration
Uveitis
Blepharitis
Conjunctivitis
Glaucoma
DachrocystitisA full ocular exam should be performed for every case of eye pain. Fluoroscein staining is usually diagnostic for corneal ulcers, although staining with Rose Bengal is also recommended as it can pick up early viral/fungal lesions, which will appear as multifocal disturbances to the tear film.
Culture and sensitivity is recommended for rapidly progressive or deep corneal ulcers. Cotton swabbing is often inadequate, and corneal scraping, for example, with the blunt side of a scalpel blade is usually required. This can be greatly facilitated by the use of local nerve blocks and topical anaesthesia.
There is almost invariably a secondary uveitis present with corneal ulceration, and signs of this may also be seen: miosis, corneal oedema, aqueous flare, hypopyon, IOP changes.

Treatment
Medical therapy should be based upon the severity of disease initially, and then by the response to therapy.  The aims of the initial therapy are:

Antibiosis
Analgesia
Anti-inflammatory
MydriaticThe initial choice of antibiotic depends upon personal choice, experience and availability, but could include chloramphenicol, chlortetracycline, bacitracin-neomycin-polymyxin (BNP), ciprofloxacin, ofloxacin and tobramycin.  Topical gentamicin formulations are also available, but in the opinion of some, should be reserved for cases with stromal melting.  Frequency of application can vary from q1h to q8h, depending on both the severity of the lesion, and the formulation used (ointment vs. drops).
Much of the pain associated with corneal ulceration is due to the secondary uveitis and miosis, and effective relief can often be gained with topical atropine(1%), leading to mydriasis.  Dosing is generally q4h initially, and then as required to maintain dilation.  Mydriasis is also important to avoid some of the complications associated with uveitis, such as synechiae formation and glaucoma.  Pain is also associated with inflammatory response occurring in the adjacent sclera and conjunctiva, and systemic analgesia in the form of NSAIDs is usually indicated, for example, flunixin meglumin 1.1 mg/kg, BID.  Topical NSAIDs are available (diclofenac, flurbiprofen) and effective, but have been shown to increase corneal healing time.
In horses that are difficult to treat, or in cases that require very frequent treatment, then placement of a sub-palpebral lavage system can be very useful.  As an adjunct to therapy, physical protection of the eye may be required, in the form of a mask.  Some horses will rub their eyes in response to pain, and this can cause further corneal damage.  Box rest is also vital, as over-exertion has been linked to intra-ocular haemorrhage and increased severity of uveitis.
Success in your therapeutic regime can be judged by a reduction in pain, and a decrease in size of the ulcer.  Healing generally occurs rapidly at first, followed by a slowing after 5–7 days </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 Malignant multiple sclerosis and can you explain it in depth? [/INST] Malignant multiple sclerosis is used to describe MS patients who reach significant level of disability in a short period of time. Malignant MS cases are not common, less than 5% of patients with MS experience this type of progression.The National MS Society Advisory Committee on Clinical Trials of New Agents consensus defined it as: disease with a rapid progressive course, leading to significant disability in multiple neurologic systems or death in a relatively short time after disease onset. Reaching Expanded Disability Status Scale of 6.0 or higher, which is equivalent of needing unilateral support to ambulate  (or worse) is generally considered this significant disability level.Patients with severe forms of more common relapsing remitting or progressive MS subtypes, as well as rare Marburg variant and Balo concentric sclerosis, could be considered to have malignant MS. Patients should be carefully worked up to rule out Neuromyelitis optica (Devics disease) due to the distinctive pathophysiology and management strategies of this disease.

Signs and symptoms
Some common physical symptoms may include: "weakness in extremities, difficulties with coordination and balance, spasticity, paresthesia, speech impediments, tremors, dizziness, hearing loss, vision impairments, bowel and bladder difficulties"

Diagnosis
Earlier signs include an increase in mobility over a short period of time. Malignant MS happens in patients that already have or have been diagnosed with MS </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 Transient neonatal diabetes 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 Dysglycemia and can you explain it in depth? [/INST] Dysglycemia is a general definition for any abnormalities in blood glucose levels. They include hyperglycemia, hypoglycemia, impaired glucose tolerance test, impaired fasting glucose, among others.

Hyperglycemia
If blood sugar levels remain too high the body suppresses appetite over the short term. Long-term hyperglycemia causes many health problems including heart disease, cancer, eye, kidney, and nerve damage.Blood sugar levels above 300 mg/dL can cause fatal reactions. Ketones will be very high (a magnitude higher than when eating a very low carbohydrate diet) initiating ketoacidosis </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 Genital trauma and can you explain it in depth? [/INST] Genital trauma is trauma to the genitalia.

History of studying genital trauma
Doctors and nurses have been conducting sexual assault examinations and have been collecting evidence for victims of assault for 20 years. But the amount of scientific data collected on genital injuries post-sexual assault are still minimal. Therefore, there is no available evidence to show specific patterns of injury resulting from sexual assault. The motivation for investigating and collecting data on genital injuries has primarily been within the context of the legal system, such as proving or disproving sexual assault, rather than for medical purposes. The studies that have been done in the past 25 years in relation to sexual assault cases in the judicial system has laid the groundwork for interpreting sexual assault injuries. It is important for there to research on genital injuries more broadly relating to sexual activity (and not just sexual assault) to improve medical knowledge on the subject. Methods of studying and documenting genital injury has greatly improved through the use of tissue staining dyes and colposcopy. The first studies that used newer methods were retrospective chart reviews done in a hospital by a doctor or nurse. These studies used several different methods to identify and document injuries, such as direct visualization, colposcopy, and/or tissue staining dyes. Earlier studies only used direct visualization for their data.

Vaginal trauma from consensual and non-consensual intercourse
Vaginal trauma is possible during and after consensual and non-consensual intercourse so it is difficult to determine the circumstances in which the trauma occurs only based on a physical examination. It can be difficult to differentiate between injuries from consensual sex and injuries from sexual assault in adolescents. Women are three times more likely to have vaginal injuries and intercourse-related injuries from a forced assault than from a consensual sexual experience. Vaginal lacerations that happen during consensual or non consensual intercourse might need surgery, but victims of a forced assault will need additional services such as police intervention and trauma counseling. There is little research on minor injuries in adult, pre-menopausal women, adolescent girls, and post-menopausal women that do not require surgery or treatment.

Why does vaginal trauma occur?
There are factors that can predispose women to vaginal injury during consensual sex. These things include: first sexual experience, pregnancy, vigorous penetration, vaginal atrophy and spasm, previous operation or radiation therapy, disproportionate genitalia, penile ornamentation, and congenital anomalies. During vaginal intercourse in the missionary position with legs tilted all the way back, the penis reaches its deepest penetration and the extreme rotation of the uterus leads to hyper distention of the vaginal wall, which in some cases can cause it to rupture. This position is the most likely position for vaginal laceration. The vaginal wall on the right side is the most commonly torn sight in this position. Vaginal lengthening and lubrication usually occurs naturally in a consensual sexual situation. Vaginal tearing can occur in rape victims because those two things will not occur. This is consistent with the fact that more injuries result from sexual assault than from consensual intercourse. An inability to produce adequate vaginal lubrication and dilatation is thought to be an underlying cause of severe tears in the upper area of the vagina.

Types of vaginal trauma
Intercourse-related lacerations can range from superficial tears to more severe lacerations, tears rarely extend into the rectal lumen and the peritoneal cavity. Recto-vaginal injuries are usually a result of assault with a foreign object, rape, or accidental gynecologic injury. Injuries of this severity that resulted from consensual sex are very rare. Posterior and right vaginal fornix lacerations have been known to occur during consensual vaginal intercourse. The location of these lacerations is usually based on a womans reproductive anatomy. It is common for women to have a uterus that lies slightly to the right, this exposes the right fornix and makes it easier for some type of tearing or trauma to occur. Lacerations to the posterior peri-cervical vagina tend to occur in the missionary position, hips and legs hyperflexed. Other positions can also expose the posterior vaginal wall that usually protected by the cervix, this allows for posterior fornix tears. Tears in the upper area of the vagina are more often reported in consensual intercourse than forced intercourse. Complications from severe vaginal lacerations, such as from an assault, can include hemoperitoneum, pneumoperitoneum, and retroperitoneal hematoma with or without vaginal perforation. Tears along the long axis of the vagina or the posterior fourchette lacerations are more likely to occur from rape. Lacerations or tears of the hymen are common but are not indicative of consensual or non-consensual intercourse.

Treatment of vaginal trauma
Diagnosing and treating vaginal trauma can often be difficult and delayed due to the sensitive and personal nature of these types of injuries; this also may be enhanced if the patient is young in age. The repair of most genital injuries require suture and the bleeding from the area is usually minimal. The bleeding that results from extreme vaginal tears can be copious, leading to hemorrhagic shock, and the patient may need a blood transfusion. Treatment of these lacerations could warrant surgical repair.

Vulvar trauma
Vulvar trauma is more common in prepubertal children due to small labial fat pads and more physical activity. Adults are more protected. Though some injuries are serious, most are accidental minor blunt traumas. The most common type of injury is a straddle injury, which can be incurred through normal activities like bicycle riding. Due to the vascularity of the vulva, it may form a large hematoma when injured. The vulva can also be injured through sexual assault. Vulvar trauma can occur concurrently with vaginal trauma, especially if a sharp object is involved.

Vaginal trauma
Vaginal trauma can occur when something is inserted into the vagina, for example, a sharp object, causing penetrating trauma. Vaginal trauma can occur as a result as an initial painful sexual experience or sexual abuse. Vaginal trauma can occur in children as a result of a straddle injury. Most of these, though distressing, are not serious injuries. In some instances a severe injury occurs and requires immediate medical attention especially if the bleeding wont stop. Vaginal trauma occurs during an episiotomy.

Penile trauma
Penile trauma can take several forms. Abrasions can be caused by a zipper injury, and fractures can be caused by sexual activity. One type of penile trauma is penile amputation </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 Generalized vaccinia 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 Sitosterolemia and can you explain it in depth? [/INST] Sitosterolemia  is a rare autosomal recessively inherited lipid metabolic disorder. It is characterized by hyperabsorption and decreased biliary excretion of dietary sterols (including the plant phytosterol beta-sitosterol). Healthy persons absorb only about 5% of dietary plant sterols, but sitosterolemia patients absorb 15% to 60% of ingested sitosterol without excreting much into the bile. The phytosterol campesterol is more readily absorbed than sitosterol.Sitosterolemia patients develop hypercholesterolemia, tendon and tuberous xanthomas, premature development of atherosclerosis, and abnormal hematologic and liver function test results.

Signs and symptoms
Sitosterolemia may share several clinical characteristics with the well-characterized  familial hypercholesterolemia (FH), such as the development of tendon xanthomas in the first 10 years of life and the development of premature atherosclerosis. However, in contrast to FH patients, sitosterolemia patients usually have normal to moderately elevated total sterol levels and very high levels of plant sterols (sitosterol, campesterol, stigmasterol, avenosterol) and 5α-saturated stanols in their plasma. Plasma sitosterol levels in sitosterolemia patients are 10–25 times higher than in normal individuals (8–60 mg/dl). Not all patients with sitosterolemia have tendon xanthomas, thus absence of this should not be used to exclude this diagnosis.
Xanthomas may appear at any age, even in childhood. These may be present as subcutaneous xanthomas on the buttocks in children or in usual locations (e.g., Achilles tendon, extensor tendons of the hand) in children and adults. Xanthelasma and corneal arcus are less common. Decreased range of motion with possible redness, swelling, and warmth of joints due to arthritis may be present. In addition, sitosterolemia patients may develop hemolytic episodes and splenomegaly.
Untreated, the condition causes a significant increase in morbidity and mortality. Coronary heart disease and its inherent health consequences are the primary causes of illness and premature death in untreated patients.

Pathogenesis
Mammalian cells cannot use plant sterols. Normally, plant sterols are poorly absorbed from the gastrointestinal tract; fewer than 5% of plant sterols are absorbed compared to approximately 40% of cholesterol absorbed. The liver preferentially excretes plant sterols over cholesterol. Dietary sterols have recently been shown to passively enter intestinal cells, and subsequently the vast majority are pumped back into the gut lumen by ATP-binding cassette transporter (ABC transporter) proteins.
Sitosterolemia is inherited as a rare autosomal recessive condition. It has been shown to result from mutations in either of  two adjacent and oppositely oriented genes (ABCG5 and ABCG8) located in chromosome 2 in band 2p21 and encode for  ABC transporter proteins named sterolin-1 and sterolin-2, respectively. Thus, the active pumping back into the intestine of passively absorbed plant sterols is disrupted, and hepatic secretion of the resultant accumulation of these sterols is decreased.
The ability of the liver to preferentially excrete plant sterols into the bile is apparently impaired. While bile acid synthesis remains the same as in healthy people, the total excretion of sterols in the bile is reportedly less than 50% in subjects with sitosterolemia compared to control subjects. The mechanism for decreased hepatic secretion is unknown.
Patients have markedly reduced whole-body cholesterol biosynthesis associated with suppressed hepatic, ileal, and mononuclear leukocyte hydroxymethylglutaryl-coenzyme A reductase (HMG-CoA reductase), the rate-controlling enzyme in the cholesterol biosynthetic pathway. Whether or not the down-regulation is due to accumulated sitosterol is still debatable, but most recent data indicate that secondary effects of unknown regulators other than sitosterol can lead to reduced HMG-CoA reductase activity in the disease. This is coupled with significantly increased low-density lipoprotein (LDL) receptor expression.

Diagnosis
Diagnosis is made by measuring serum plant sterol concentrations.

Treatment
The disorder is treated by strictly reducing the intake of foods rich in plant sterols (e.g., vegetable oils, olives and avocados). However, dietary therapy is often never fully sufficient to control this disease since plant sterols are constituents of all plant-based foods. Statins have been used, and while these lower cholesterol levels and may ameliorate atherosclerotic disease, plant sterol levels are insufficiently lowered by their use alone.
If dietary treatment alone is insufficient, bile acid-binding resins (e.g., cholestyramine, colestipol) could be considered. In October 2002, a new cholesterol absorption inhibitor, ezetimibe, received US Food and Drug Administration (FDA) approval for use in sitosterolemia. This drug is now the standard of care, as it blocks sterol entry and can be used in combination with bile-acid resins.
Finally, ileal bypass has been performed in select cases to decrease the levels of plant sterols in the body, though this therapy was undertaken prior to the advent of ezetimibe.

Epidemiology
Around 80 cases have been reported in the literature worldwide, hence this condition appears to be relatively rare. More than likely, sitosterolemia is significantly underdiagnosed and many patients are probably misdiagnosed with hyperlipidemia.

See also
ABCG5 and ABCG8 Genes
Cerebrotendinous xanthomatosis

Notes
References
Lee M, Lu K, Patel SB (2001). "Genetic basis of sitosterolemia". Current Opinion in Lipidology. 12 (2): 141–149 </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Interstitial keratitis and can you explain it in depth? [/INST] Interstitial keratitis (IK) is corneal scarring due to chronic inflammation of the corneal stroma </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 Nonverbal learning disorder and can you explain it in depth? [/INST] Nonverbal learning disability (NVLD) is a neurodevelopmental disorder characterized by core deficits in visual-spatial processing in the presence of intact verbal ability. Additional diagnostic criteria include Average to Superior verbal intelligence and deficits in visuoconstruction abilities, fine-motor coordination, mathematical reasoning, visuospatial memory and social skills.   In clinical settings, some diagnoses of attention deficit hyperactivity disorder would be more appropriately classified as NVLD.

Signs and symptoms
Considered to be neurologically based, nonverbal learning disorder is characterized by:

impairments in visuospatial processing
discrepancy between Average to Superior verbal abilities and impaired nonverbal abilities such as:
visuoconstruction
fine motor coordination
mathematical reasoning
visuospatial memory
socioemotional skillsPeople with NVLD may have trouble understanding charts, reading maps, assembling jigsaw puzzles, and using an analog clock to tell time. "Clumsiness" is not unusual in people with NVLD, especially children, and it may take a child with NVLD longer than usual to learn how to tie shoelaces or to ride a bicycle.At the beginning of their school careers, children with symptoms of NVLD struggle with tasks that require eye–hand coordination, such as coloring and using scissors, but often excel at memorizing verbal content, spelling, and reading once the shapes of the letters are learned. A child with NVLDs Average or Superior verbal skills can be misattributed to attention deficit hyperactivity disorder, defiant behavior, inattention, or lack of effort.  Early researchers in the syndrome of NVLD Johnson and Myklebust characterize how the children appear in a classroom: "An example is the child who fails to learn the meaning of the actions of others....We categorize this child as having a deficiency in social perception, meaning that he has an inability which precludes acquiring the significance of basic nonverbal aspects of daily living, though his verbal level of intelligence falls within or above the average."In the adolescent years, when schoolwork becomes more abstract and the executive demands for time management, organization, and social interactions increase, students with NVLD begin to struggle. They focus on separate details and struggle to summarize information or to integrate ideas into a coherent whole, and they struggle to apply knowledge to other situations, to infer implicit information, to make predictions, and to organize information logically.As adults, tasks such as driving a car or navigating to an unfamiliar location may be difficult.  Difficulty with keeping track of responsibilities or managing social interactions may affect job performance.People with NVLD may also fit the diagnostic criteria of dyscalculia, dysgraphia, or dyspraxia.

Cause
Research suggests that there is an association with an imbalance of neural activity in the right hemisphere of the brain connected to the white matter.

Diagnosis
Nonverbal learning disability (NVLD) is characterized by core deficits in visualspatial processing in the presence of intact verbal ability.  Additional diagnostic criteria include Average to Superior verbal intelligence and deficits in visuoconstruction abilities, fine-motor coordination, mathematical reasoning, visuospatial memory and social skills."While NVLD is not classified into any distinct diagnosis in DSM-5 (American Psychiatric Association, 2013) or ICD-10 (World Health Organization, 1992), it does have a robust research base."  "The majority of researchers and clinicians agree that the profile of NLD clearly exists...but they disagree on the need for a specific clinical category and on the criteria for its identification." (One researcher notes, "just because we cannot reasonably place such children into our present classification scheme does not mean they do not exist.")
Assorted diagnoses have been discussed as sharing symptoms with NVLD.  In some cases, especially the form of autism previously called Asperger syndrome, the overlap can be so significant as to render NVLD a pointless duplication in the mind of its detractors, with the only difference being that NVLD criteria do not mention the presence or absence of either repetitive behaviors or narrow subject-matter interests.  (These are not required for a diagnosis of autism.) These overlapping conditions include, among others:

attention deficit hyperactivity disorder (ADHD)
autism spectrum disorders, especially high-functioning autism
developmental coordination disorder
social communication disorder
right hemisphere brain damage and developmental right hemisphere syndrome
social-emotional processing disorder
Gerstmann syndromeThere is diagnostic overlap between nonverbal learning disorder and autism spectrum disorder, and some clinicians and researchers consider them to be the same condition.  In clinical settings, some diagnoses of attention deficit hyperactivity disorder would be more appropriately classified as NVLD.

History
While various nonverbal learning difficulties were recognized since early studies in child neurology, there is ongoing debate as to whether/or the extent to which existing conceptions of NVLD provide a valid diagnostic framework.As presented in 1967, "nonverbal disabilities" (p. 44) or "disorders of nonverbal learning" was a category encompassing non-linguistic learning problems. "Nonverbal learning disabilities" were further discussed by Myklebust in 1975 as representing a subtype of learning "disability" with a range of presentations involving "mainly visual cognitive processing," social imperception, a gap between higher verbal ability and lower nonverbal processing, as well as difficulty with handwriting. Later neuropsychologist Byron Rourke sought to develop consistent criteria with a theory and model of brain functioning that would establish NVLD as a distinct syndrome (1989).Questions remain about how best to frame the perceptual, cognitive and motor issues associated with NVLD.

See also
Alexithymia – difficulty with understanding emotions
Childrens Nonverbal Learning Disabilities Scale
Deficits in attention, motor control and perception

References
Further reading
Books
Thompson, Sue (1997). The Source for Nonverbal Learning Disorders. East Moline, IL: LinguiSystems. ISBN 978-0760601631.
Palombo, Joseph (2006). Nonverbal Learning Disabilities: A Clinical Perspective. New York: W.W. Norton. ISBN 9780393704785.
Broitman, Jessica; Davis, John M. (2013). Treating NVLD in Children Professional Collaborations for Positive Outcomes. New York: Springer. ISBN 978-1461461791.

By Authors with NVLD
Murphy, Michael Brian (2016) </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 Hand-foot-genital syndrome and can you explain it in depth? [/INST] Hand-foot-genital syndrome (HFGS) is characterized by limb malformations and urogenital defects. Mild bilateral shortening of the thumbs and great toes, caused primarily by shortening of the distal phalanx and/or the first metacarpal or metatarsal, is the most common limb malformation and results in impaired dexterity or apposition of the thumbs </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 Cerebral amyloid angiopathy and can you explain it in depth? [/INST] Cerebral amyloid angiopathy (CAA) is a form of angiopathy in which amyloid beta peptide deposits in the walls of small to medium blood vessels of the central nervous system and meninges. The term congophilic is sometimes used because the presence of the abnormal aggregations of amyloid can be demonstrated by microscopic examination of brain tissue after staining with Congo red. The amyloid material is only found in the brain and as such the disease is not related to other forms of amyloidosis.

Signs and symptoms
CAA is associated with brain hemorrhages, particularly microhemorrhages. Since CAA can be caused by the same amyloid protein that is associated with Alzheimers dementia, brain bleeds are more common in people who have a diagnosis of Alzheimers disease. However, they can also occur in those who have no history of dementia.  The bleeding within the brain is usually confined to a particular lobe and this is slightly different compared to brain bleeds which occur as a consequence of high blood pressure (hypertension) – a more common cause of a hemorrhagic stroke (or bleeding in the brain).

Causes
CAA has been identified as occurring either sporadically (generally in elderly populations) or in familial forms such as Flemish, Iowa, and Dutch types. In all cases, it is defined by the deposition of amyloid beta (Aβ) in the leptomeningal and cerebral vessel walls. CAA occurring in the Flemish type has been observed to be linked to large dense-core plaques observed in this pedigree.The reason for increased deposition of Aβ in sporadic CAA is still unclear with both increased production of the peptide and abnormal clearance having been proposed as potential causes. Under normal physiology Aβ is cleared from the brain by four pathways: (1) endocytosis by astrocytes and microglial cells, (2) enzymatic degradation by neprilysin or insulysin (3) cleared by way of the blood brain barrier or (4) drained along periarterial spaces. Abnormalities in each of these identified clearance pathways have been linked to CAA.In familial forms of CAA, the cause of Aβ build up is likely due to increased production rather than poor clearance. Mutations in the amyloid precursor protein (APP), Presenilin (PS) 1 and PS2 genes can result in increased rates of cleavage of the APP into Aβ. An immune mechanism has also been proposed. apolipoprotein E (APOE) ε2 and ε4 are associated with increased risk of getting cerebral amyloid antipathy. The use of antiplatelet and anticoagulant therapy increases the risk of getting intracerebral haemorrhage in CAA.

Types
Several familial variants exist. The condition is usually associated with amyloid beta. However, there are types involving other amyloid peptides:

the "Icelandic type" is associated with Cystatin C amyloid (ACys).
the "British type" and "Danish type" are associated with British amyloid (ABri) and Danish amyloid (ADan) respectively. Both peptides are linked to mutations in ITM2B.
Familial amyloidosis-Finnish type is associated with gelsolin amyloid (AGel).

Pathophysiology
The vascular amyloid pathology characteristic of CAA can be classified as either Type 1 or Type 2, the latter type being the more common. Type 1 CAA pathology entails detectable amyloid deposits within cortical capillaries as well as within the leptomeningeal and cortical arteries and arterioles. In type 2 CAA pathology, amyloid deposits are present in leptomeningeal and cortical arteries and arterioles, but not in capillaries. Deposits in veins or venules are possible in either type but are far less prevalent.

Diagnosis
CAA can only be definitively diagnosed by a post-mortem autopsy. Biopsies can play a role in diagnosing probable cases. When no tissue is available for biopsy, the Boston Criteria are used to determine probable CAA cases from MRI or CT scan data. The Boston Criteria require evidence of multiple lobar or cortical hemorrhages to label a patient as probably having CAA. Susceptibility weighted imaging has been proposed as a tool for identifying CAA-related microhemorrhages.

Imaging
Cerebral amyloid angiopathy can be presented with lobar intracerebral hemorrhage or microbleeds in the brain. The bleeding usually occurs on the surfaces of the brain in contrast with intracranial haemorrhage due to high blood pressure which occurs in deep locations of the brain such as basal ganglia and pons. In lobar intracerebral bleed, computed tomography (CT) scan would show hyperdense haemorrhage area and hypodense odema around the haemorrhagic site.MRI sequence of gradient echo and susceptibility weighted imaging (SWI) are useful in detecting microbleeds and deposition of iron on the brain cortex (cortical superficial siderosis). Other MRI indicators of CAA include white matter hyperintensities and cortical thinning.

Management
The aim in cerebral amyloid angiopathy is to treat the symptoms, as there is no current cure. Physical, occupational and/or speech therapy may be helpful in the management of this condition.

History
Gustav Oppenheim was the first to report vascular amyloid β deposits on the vasculature of the central nervous system in 1909. The first paper focusing solely on what would come to be known as CAA was published in 1938 by WZ Scholz </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 Hepatic encephalopathy and can you explain it in depth? [/INST] Hepatic encephalopathy (HE) is an altered level of consciousness as a result of liver failure. Its onset may be gradual or sudden. Other symptoms may include movement problems, changes in mood, or changes in personality. In the advanced stages it can result in a coma.Hepatic encephalopathy can occur in those with acute or chronic liver disease. Episodes can be triggered by infections, GI bleeding, constipation, electrolyte problems, or certain medications. The underlying mechanism is believed to involve the buildup of ammonia in the blood, a substance that is normally removed by the liver. The diagnosis is typically based on symptoms after ruling out other potential causes. It may be supported by blood ammonia levels, an electroencephalogram, or a CT scan of the brain.Hepatic encephalopathy is possibly reversible with treatment. This typically involves supportive care and addressing the triggers of the event. Lactulose is frequently used to decrease ammonia levels. Certain antibiotics (such as rifaximin) and probiotics are other potential options. A liver transplant may improve outcomes in those with severe disease.More than 40% of people with cirrhosis develop hepatic encephalopathy. More than half of those with cirrhosis and significant HE live less than a year. In those who are able to get a liver transplant, the risk of death is less than 30% over the subsequent five years. The condition has been described since at least 1860.

Signs and symptoms
The mildest form of hepatic encephalopathy is difficult to detect clinically, but may be demonstrated on neuropsychological testing. It is experienced as forgetfulness, mild confusion, and irritability. The first stage of hepatic encephalopathy is characterised by an inverted sleep-wake pattern (sleeping by day, being awake at night). The second stage is marked by lethargy and personality changes. The third stage is marked by worsened confusion. The fourth stage is marked by a progression to coma.More severe forms of hepatic encephalopathy lead to a worsening level of consciousness, from lethargy to somnolence and eventually coma. In the intermediate stages, a characteristic jerking movement of the limbs is observed (asterixis, "liver flap" due to its flapping character); this disappears as the somnolence worsens. There is disorientation and amnesia, and uninhibited behaviour may occur. In the third stage, neurological examination may reveal clonus and positive Babinski sign. Coma and seizures represent the most advanced stage; cerebral edema (swelling of the brain tissue) leads to death.Encephalopathy often occurs together with other symptoms and signs of liver failure. These may include jaundice (yellow discolouration of the skin and the whites of the eyes), ascites (fluid accumulation in the abdominal cavity), and peripheral oedema (swelling of the legs due to fluid build-up in the skin). The tendon reflexes may be exaggerated, and the plantar reflex may be abnormal, namely extending rather than flexing (Babinskis sign) in severe encephalopathy. A particular smell on an affected persons breath (foetor hepaticus) may be detected.

Causes
In a small proportion of cases, the encephalopathy is caused directly by liver failure; this is more likely in acute liver failure. More commonly, especially in chronic liver disease, hepatic encephalopathy is triggered by an additional cause, and identifying these triggers can be important to treat the episode effectively.
Hepatic encephalopathy may also occur after the creation of a transjugular intrahepatic portosystemic shunt (TIPS). This is used in the treatment of refractory ascites, bleeding from oesophageal varices and hepatorenal syndrome. TIPS-related encephalopathy occurs in about 30% of cases, with the risk being higher in those with previous episodes of encephalopathy, higher age, female sex, and liver disease due to causes other than alcohol.

Pathogenesis
There are various explanations why liver dysfunction or portosystemic shunting might lead to encephalopathy. In healthy subjects, nitrogen-containing compounds from the intestine, generated by gut bacteria from food, are transported by the portal vein to the liver, where 80–90% are metabolised through the urea cycle and/or excreted immediately. This process is impaired in all subtypes of hepatic encephalopathy, either because the hepatocytes (liver cells) are incapable of metabolising the waste products or because portal venous blood bypasses the liver through collateral circulation or a medically constructed shunt. Nitrogenous waste products accumulate in the systemic circulation (hence the older term "portosystemic encephalopathy"). The most important waste product is ammonia (NH3). This small molecule crosses the blood–brain barrier and is absorbed and metabolised by the astrocytes, a population of cells in the brain that constitutes 30% of the cerebral cortex. Astrocytes use ammonia when synthesising glutamine from glutamate. The increased levels of glutamine lead to an increase in osmotic pressure in the astrocytes, which become swollen. There is increased activity of the inhibitory γ-aminobutyric acid (GABA) system and the energy supply to other brain cells is decreased. This can be thought of as an example of brain edema of the "cytotoxic" type.Despite numerous studies demonstrating the central role of ammonia, ammonia levels do not always correlate with the severity of the encephalopathy; it is suspected that this means that more ammonia has already been absorbed into the brain in those with severe symptoms whose serum levels are relatively low. Other waste products implicated in hepatic encephalopathy include mercaptans (substances containing a thiol group), short-chain fatty acids, and phenol.Numerous other abnormalities have been described in hepatic encephalopathy, although their relative contribution to the disease state is uncertain. Loss of glutamate transporter gene expression (especially EAAT 2) has been attributed to acute liver failure. Benzodiazepine-like compounds have been detected at increased levels as well as abnormalities in the GABA neurotransmission system. An imbalance between aromatic amino acids (phenylalanine, tryptophan and tyrosine) and branched-chain amino acids (leucine, isoleucine and valine) has been described; this would lead to the generation of false neurotransmitters (such octopamine and 2-hydroxyphenethylamine). Dysregulation of the serotonin system, too, has been reported. Depletion of zinc and accumulation of manganese may play a role. Inflammation elsewhere in the body may precipitate encephalopathy through the action of cytokines and bacterial lipopolysaccharide on astrocytes.

Diagnosis
Investigations
The diagnosis of hepatic encephalopathy can only be made in the presence of confirmed liver disease (types A and C) or a portosystemic shunt (type B), as its symptoms are similar to those encountered in other encephalopathies. To make the distinction, abnormal liver function tests and/or ultrasound suggesting liver disease are required, and ideally a liver biopsy. The symptoms of hepatic encephalopathy may also arise from other conditions, such as bleeding in the brain and seizures (both of which are more common in chronic liver disease). A CT scan of the brain may be required to exclude bleeding in the brain, and if seizure activity is suspected an electroencephalograph (EEG) study may be performed. Rarer mimics of encephalopathy are meningitis, encephalitis, Wernickes encephalopathy and Wilsons disease; these may be suspected on clinical grounds and confirmed with investigations.The diagnosis of hepatic encephalopathy is a clinical one, once other causes for confusion or coma have been excluded; no test fully diagnoses or excludes it. Serum ammonia levels are elevated in 90% of people, but not all hyperammonaemia (high ammonia levels in the blood) is associated with encephalopathy. A CT scan of the brain usually shows no abnormality except in stage IV encephalopathy, when brain swelling (cerebral oedema) may be visible. Other neuroimaging modalities, such as magnetic resonance imaging (MRI), are not currently regarded as useful, although they may show abnormalities. Electroencephalography shows no clear abnormalities in stage 0, even if minimal HE is present; in stages I, II and III there are triphasic waves over the frontal lobes that oscillate at 5 Hz, and in stage IV there is slow delta wave activity. However, the changes in EEG are not typical enough to be useful in distinguishing hepatic encephalopathy from other conditions.Once the diagnosis of encephalopathy has been made, efforts are made to exclude underlying causes (such as listed above in "causes"). This requires blood tests (urea and electrolytes, full blood count, liver function tests), usually a chest X-ray, and urinalysis. If there is ascites, a diagnostic paracentesis (removal of a fluid sample with a needle) may be required to identify spontaneous bacterial peritonitis (SBP).

Classification
West Haven criteria
The severity of hepatic encephalopathy is graded with the West Haven Criteria; this is based on the level of impairment of autonomy, changes in consciousness, intellectual function, behavior, and dependence on therapy.
Grade 0 - No obvious changes other than a potentially mild decrease in intellectual ability and coordination
Grade 1 - Trivial lack of awareness; euphoria or anxiety; shortened attention span; impaired performance of addition or subtraction
Grade 2 - Lethargy or apathy; minimal disorientation for time or place; subtle personality change; inappropriate behaviour
Grade 3 - Somnolence to semistupor, but responsive to verbal stimuli; confusion; gross disorientation
Grade 4 - Coma

Types
A classification of hepatic encephalopathy was introduced at the World Congress of Gastroenterology 1998 in Vienna. According to this classification, hepatic encephalopathy is subdivided in type A, B and C depending on the underlying cause.
Type A (=acute) describes hepatic encephalopathy associated with acute liver failure, typically associated with cerebral oedema
Type B (=bypass) is caused by portal-systemic shunting without associated intrinsic liver disease
Type C (=cirrhosis) occurs in people with cirrhosis - this type is subdivided in episodic, persistent and minimal encephalopathyThe term minimal encephalopathy (MHE) is defined as encephalopathy that does not lead to clinically overt cognitive dysfunction, but can be demonstrated with neuropsychological studies. This is still an important finding, as minimal encephalopathy has been demonstrated to impair quality of life and increase the risk of involvement in road traffic accidents.

Minimal HE
The diagnosis of minimal hepatic encephalopathy requires neuropsychological testing by definition. Older tests include the "numbers connecting test" A and B (measuring the speed at which one could connect randomly dispersed numbers 1–20), the "block design test" and the "digit-symbol test". In 2009 an expert panel concluded that neuropsychological test batteries aimed at measuring multiple domains of cognitive function are generally more reliable than single tests, and tend to be more strongly correlated with functional status. Both the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and PSE-Syndrom-Test may be used for this purpose. The PSE-Syndrom-Test, developed in Germany and validated in several other European countries, incorporates older assessment tools such as the number connection test.

Treatment
Those with severe encephalopathy (stages 3 and 4) are at risk of obstructing their airway due to decreased protective reflexes such as the gag reflex. This can lead to respiratory arrest. Transferring the person to a higher level of nursing care, such as an intensive care unit, is required, and intubation of the airway is often necessary to prevent life-threatening complications (e.g., aspiration or respiratory failure). Placement of a nasogastric tube permits the safe administration of nutrients and medication.The treatment of hepatic encephalopathy depends on the suspected underlying cause (types A, B, or C) and the presence or absence of underlying causes. If encephalopathy develops in acute liver failure (type A), even in a mild form (grade 1–2), it indicates that a liver transplant may be required, and transfer to a specialist centre is advised. Hepatic encephalopathy type B may arise in those who have undergone a TIPS procedure; in most cases this resolves spontaneously or with the medical treatments discussed below, but in a small proportion of about 5%, occlusion of the shunt is required to address the symptoms.In hepatic encephalopathy type C, the identification and treatment of alternative or underlying causes is central to the initial management. Given the frequency of infection as the underlying cause, antibiotics are often administered empirically (without knowledge of the exact source and nature of the infection). Once an episode of encephalopathy has been effectively treated, a decision may need to be made on whether to prepare for a liver transplant.

Diet
In the past, it was thought that consumption of protein even at normal levels increased the risk of hepatic encephalopathy. This has been shown to be incorrect. Furthermore, many people with chronic liver disease are malnourished and require adequate protein to maintain a stable body weight. A diet with adequate protein and energy is therefore recommended.Dietary supplementation with branched-chain amino acids has shown improvement of encephalopathy and other complications of cirrhosis.Some studies have shown benefit of administration of probiotics ("healthy bacteria").

Lactulose/lactitol
Lactulose and lactitol are disaccharides that are not absorbed from the digestive tract. They are thought to decrease the generation of ammonia by bacteria, render the ammonia inabsorbable by converting it to ammonium (NH4+) ions, and increase transit of bowel content through the gut. Doses of 15-30 mL are typically administered three times a day; the result is aimed to be 3–5 soft stools a day, or (in some settings) a stool pH of <6.0. Lactulose may also be given by enema, especially if encephalopathy is severe. More commonly, phosphate enemas are used. This may relieve constipation, one of the causes of encephalopathy, and increase bowel transit.Lactulose and lactitol are beneficial for treating hepatic encephalopathy, and are the recommended first-line treatment. Lactulose does not appear to be more effective than lactitol for treating people with hepatic encephalopathy. Side effects of lactulose and lactitol include the possibility of diarrhea, abdominal bloating, gassiness, and nausea. In acute liver failure, it is unclear whether lactulose is beneficial. The possible side effect of bloating may interfere with a liver transplant procedure if required.

Antibiotics
The antibiotic rifaximin may be recommended in addition to lactulose for those with recurrent disease. It is a nonabsorbable antibiotic from the rifamycin class. This is thought to work in a similar way to other antibiotics but without the complications attached to neomycin or metronidazole. Due to the long history and lower cost of lactulose use, rifaximin is generally only used as a second-line treatment if lactulose is poorly tolerated or not effective. When rifaximin is added to lactulose, the combination of the two may be more effective than each component separately. Rifaximin is more expensive than lactulose, but the cost may be offset by fewer hospital admissions for encephalopathy.The antibiotics neomycin and metronidazole are other antibiotics used to treat hepatic encephalopathy. The rationale of their use was the fact that ammonia and other waste products are generated and converted by intestinal bacteria, and killing these bacteria would reduce the generation of these waste products. Neomycin was chosen because of its low intestinal absorption, as neomycin and similar aminoglycoside antibiotics may cause hearing loss and kidney failure if used by injection. Later studies showed that neomycin was indeed absorbed when taken by mouth, with resultant complications. Metronidazole, similarly, is less commonly used because prolonged use can cause nerve damage, in addition to gastrointestinal side effects.

L-ornithine and L-aspartate
The combination of L-ornithine and L-aspartate (LOLA) lowers the level of ammonia in a persons blood. Very weak evidence from clinical trials indicates that LOLA treatment may benefit people with hepatic encephalopathy. LOLA lowers ammonia levels by increasing the generation of urea through the urea cycle, a metabolic pathway that removes ammonia by turning it into the neutral substance urea </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 Arcuate uterus and can you explain it in depth? [/INST] The arcuate uterus is a form of a uterine anomaly or variation where the uterine cavity displays a concave contour towards the fundus. Normally the uterine cavity is straight or convex towards the fundus on anterior-posterior imaging, but in the arcuate uterus the myometrium of the fundus dips into the cavity and may form a small septation. The distinction between an arcuate uterus and a septate uterus is not standardized.

Signs and symptoms
The condition may not be known to the affected individual and not result in any reproductive problems; thus normal pregnancies occur. Indeed, there is no consensus on the relationship of the arcuate uterus and recurrent pregnancy loss. Accordingly, the condition may be a variation or a pathology.One view maintains that the condition is associated with a higher risk for miscarriage, premature birth, and malpresentation. Thus a study that evaluated women with uterine bleeding by hysteroscopy found that 6.5% of subjects displayed the arcuate uterus and had evidence of reproductive impairments. A study based on hysterosalpingraphic detected arcuate lesions documented increased fetal loss and obstetrical complications as a risk for affected women </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 Feingold 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 Aromatic L-amino acid decarboxylase deficiency 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 Cardiospondylocarpofacial 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 Tropical ataxic neuropathy and can you explain it in depth? [/INST] Tropical ataxic neuropathy (TAN, also known as Strachan-Scott Syndrome and prisoners of war neuropathy) is a disease or category of diseases that commonly causes disability and increases mortality. The causes of TAN are not understood; there is no generally accepted treatment, and the reported outcomes are inconsistent. The disease affects poor tropical populations; there are no good statistics on how many people are affected worldwide, but in some populations, more than a quarter of people are affected.  Malnutrition may play a role.

Classification and signs and symptoms
TAN is one of many tropical myeloneuropathies. It was first described in Jamaica in 1897, by postmortems of 510 cases; in 1959, it was dubbed "tropical ataxic neuropathy". The diagnostic criteria were defined in 1968. TAN is defined by "bilateral optic atrophy, bilateral sensory neural deafness, predominant posterior column involvement, and pyramidal tract myelopathy, with ataxic polyneuropathy". The classification of TAN is still not settled, and researchers disagree about it.There are thought to be two neurological syndromes lumped together as TAN. One affects adolescents, appears with retrobulbar optic neuropathy and evidence of malnutrition, and improves with better nutrition. Half of these adolescents are seen to have spinal ataxia.The other affects middle-aged and elderly people. They suffer sensory polyneuropathy, including weakness and paresthesic sensations. Paresthesias include sensations of numbness, heat, cold, tightness, crawling motion, tingling, pins and needles, and a feeling of walking on cotton or pebbles. Weaknesses show as gait ataxia (lack of co-ordination). Affected people also suffer optic atrophy and sensory neural deafness, on both sides of the body. There is neurological damage to the pyramidal tract of the spinal cord. For these older patients, evidence of malnutrition is rarer, and improving nutrition does not improve symptoms.Most of those with the older-onset form have symptoms in their legs, but a third to a half also have arm symptoms </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 Crouzonodermoskeletal syndrome and can you explain it in depth? [/INST] Crouzonodermoskeletal syndrome is a disorder characterized by the premature joining of certain bones of the skull (craniosynostosis) during development and a skin condition called acanthosis nigricans.Some of the signs and symptoms of Crouzonodermoskeletal syndrome are similar to those seen with Crouzon syndrome. They include prematurely fused skull bones, which affect the shape of the head and face; wide-set, bulging eyes due to shallow eye sockets; eyes that do not point in the same direction (strabismus); a small, beaked nose; and an underdeveloped upper jaw. People with these conditions are generally of normal intelligence.Several features distinguish Crouzonodermoskeletal syndrome from Crouzon syndrome. People with Crouzonodermoskeletal syndrome have acanthosis nigricans, a skin condition characterized by thick, dark, velvety skin in body folds and creases, including the neck and underarms. In addition, subtle changes may be seen in the bones of the spine (vertebrae) </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 Autosomal dominant hypophosphatemic rickets and can you explain it in depth? [/INST] Autosomal dominant hypophosphatemic rickets (ADHR) is a rare hereditary disease in which excessive loss of phosphate in the urine leads to poorly formed bones (rickets), bone pain, and tooth abscesses. ADHR is caused by a mutation in the fibroblast growth factor 23 (FGF23). ADHR affects men and women equally; symptoms may become apparent at any point from childhood through early adulthood. Blood tests reveal low levels of phosphate (hypophosphatemia) and inappropriately normal levels of vitamin D. Occasionally, hypophosphatemia may improve over time as urine losses of phosphate partially correct.ADHR may be lumped in with X-linked hypophosphatemia under general terms such as hypophosphatemic rickets. Hypophosphatemic rickets are associated with at least nine other genetic mutations </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 Richters transformation and can you explain it in depth? [/INST] Richters syndrome (RS), also known as Richters transformation, is a transformation of B cell chronic lymphocytic leukemia (CLL) or hairy cell leukemia into a fast-growing diffuse large B cell lymphoma, a variety of non-Hodgkin lymphoma which is refractory to treatment and carries a bad prognosis.  There is also a less common variant in which the CLL changes into a Hodgkins lymphoma. Rarely, transformations to a form of myeloid leukemia have been observed. These extraordinarily rare transformations carry a very poor prognosis.
Richters transformation affects about 5% of CLL patients at some point during their lives.

Signs and symptoms
Symptoms of Richter’s transformation in a CLL patient include fever (without infection), elevated serum levels of lactate dehydrogenase, and rapidly enlarging lymph nodes.  While about 8% of all CLL patients will have elevated levels of serum lactate dehydrogenase (LDH), more than 50% of CLL patients with Richters transformation will have elevated LDH levels.Richters can appear suddenly, even in patients who were in remission.

Cause
A case of RS may have arisen by one of two different routes:  a transformation of the CLL cells into lymphoma, or the appearance of an unrelated lymphoma.It is thought that genetic defects may introduce the additional abnormalities necessary to transform CLL cells into Richters syndrome cells.

Treatment
Treatment with conventional immunochemotherapy is usually indicated; in younger patients, allogeneic bone marrow transplantation may be curative.

Prognosis
The prognosis is generally poor.  The RS score (Richter syndrome score), which is an estimate of the patients prognosis, is based on the patients performance status, LDH, platelet count, the size of the lymphoma tumors, and the number of prior therapies already received.  Overall, the median survival is between five and eight months.  Untreated, RS is invariably fatal.
The Hodgkins lymphoma variant of Richters carries a better prognosis than the predominant diffuse large B-cell lymphoma type, but a worse prognosis than a de novo case of Hodgkins.

Epidemiology
A SEER-based analysis estimated the risk of Richters transformation in Chronic Lymphocytic Leukemia (CLL) patients in the United States to be about 0.72%. The majority of transformations (85%) were Diffuse Large B-Cell Lymphoma (DLBCL), while transformation to Hodgkin occurred in 15% of cases </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 Talon cusp and can you explain it in depth? [/INST] Talon cusp is a rare dental anomaly resulting in an extra cusp or cusp-like projection on an anterior tooth, located on the inside surface of the affected tooth. Sometimes it can also be found on the facial surface of the anterior tooth.The term talon cusp refers to the same condition as dens evaginatus; however, talon cusp is more specifically the manifestation of dens evaginatus on the anterior teeth. Talon cusp can be simply defined as hyperplasia of the cingulum of an anterior tooth.
Although talon cusp may not appear serious, and in some people may be completely benign, it can cause clinical, diagnostic and functional problems, and alters the appearance of a persons teeth. The condition was first described by W.H. Mitchell in 1982 and named by J. Kimball Mellor B.S., D.D.S. and Louis W. Ripa, D.D.S., M.S. due to its similar appearance to an eagles talon. Some sources define a talon cusp as an extra cusp which extends at least half the distance between the cementoenamel junction and the incisal edge of the tooth. Other sources classify all enlarged cingula as talon cusps, and classify them according to the degree of enlargement.The incidence of talon cusp has been found to range from 1% to 6% of the population. Talon cusp tends to occur on permanent teeth only, being very rare in deciduous teeth. In most cases, the involved teeth are the permanent maxillary lateral incisors (55%), followed by maxillary central incisors (33%), mandibular incisors (6%), and maxillary canines (4%).

Signs and symptoms
Talon cusp will show physical signs of the irregular dental formation of the teeth and cause other symptoms of the disease that could possibly lead to dental problems in the future, depending on severity of the deformity.
Most commonly, the extra cusp is located on the lingual surface, giving a three-pronged appearance. Rarely, however, the extra cusp may be situated on the facial surface, or there may be extra cusps on both lingual and facial surfaces. There may be a deep groove between the talon cusp and the rest of the tooth. The extra cusp typically contains pulp tissue. When viewing talon cusp from the occlusal, the projection will appear "x-shaped", as well as appears conical, and mimic the shape of an eagles talon.Symptoms of talon cusp include:

Interference with occlusion or bite
Irritation of soft tissues and tongue
Accidental cusp fracture
Susceptible to dental caries

Cause
The cause of talon cusp is unknown. The anomaly can occur due to genetic and environmental factors but the onset can be spontaneous. Prevention is difficult because the occurrence happens during the development of teeth.
Talon cusp affects men and women equally, however the majority of reported cases are of the male gender. Individuals of Asian, Arabic, Native American and Inuit descent are affected more commonly. Talon cusp is also highly observed in patients with orofacial digital II syndrome and Rubinstein Taybi syndrome. Other anomalies that occur with talon cusp can include peg laterals, supernumerary teeth, dens envaginatus, agenesis and impaction. A person belonging to one of these particular demographics or one who has any of these deformities or syndromes may have a higher risk of having a talon cusp.

Mechanism
The exact mechanism of the formation of dens evaginatus and talon cusp is unknown. It has been suggested that the anomaly is caused by an evagination. The formation of the "cusp" is due to excess layering of the internal enamel epithelium and dental papilla into the stellate reticulum. This occurs during the morphological differentiation stage of tooth development. During the developmental stages of tooth formation, certain dental follicle cells were differentiated incorrectly which formed the excess enamel and incorrect morphology of the affected tooth.
Talon cusp can progress into severe dental problems if the severity of the cusp affects the persons hygiene and oral functions.
Talon cusp may occur on its own or associated with other dental anomalies such as mesiodens, odontome, unerupted or impacted teeth, peg-shaped maxillary incisor, dens invaginatus, cleft lip, bilateral gemination, fusion, and supernumerary teeth.

Diagnosis
This anomaly is large enough to be seen with the naked eye. One can see the projection on the incisal edge of a tooth looking into the mouth of the affected person. The structure is described to be "Tshaped" or "X-shaped" however will differ depending on its shape, size, structure, location and site of origin. X-rays and radiographs can also show evidence of the abnormality. The digital images would show a tooth with talon cusp as if it were "double teeth".When looking at a radiograph some features to look for would be location, edge, shape and number. The location would be on an anterior tooth, the edge would be clear and well defined and can be seen even by the naked eye, and the shape would appear "talon-like" over the top portion or crown of the affected tooth. There could potentially be one, two or multiple protrusions depending on the type of cusp.
Talon cusp can fall under three categories: Type I, Type II and Type III. They are created based on the cusp formation shape and length of extension.

Type I - Talon: The additional cusp or talon projects from the palatal surface of a primary or permanent anterior (front) tooth that extends at least half of the distance from the cemento enamel junction to the incisal edge.
Type II - Semi Talon:  The semi talon cusp measures about 1mm or more in length but extends less than half of the distance seen in Type I Talon.
Type III - Trace Talon:  The projection originates from the cingulum (also known as the "cervical third") of the root and is enlarged or prominent in any form (conical, bifid or tubercle-like)Since many cases of Talon cusp go unreported, it is hard to draw linkage maps but it is safe to assume that dental formation is influenced by genetic factors. Talon cusp is also seen in association with conditions such as Rubinstein-Taybi syndrome, Mohr syndrome, Ellis–van Creveld syndrome, Incontinentia pigmenti achromians, Berardinelli-Seip syndrome, and Sturge–Weber syndrome.

Treatment
Treatment is only required if the occlusion or bite of the person is compromised and causing other dental problems. Multiple long-term clinical problems can arise such as occlusal interferences, aesthetic disturbances, loss of pulp vitality, irritation of tongue during mastication and speech, caries and displacement of the affected tooth </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 Organic brain syndrome and can you explain it in depth? [/INST] Organic brain syndrome, also known as organic brain disease, organic brain disorder, organic mental syndrome, or organic mental disorder, refers to any syndrome or disorder of mental function whose cause is alleged to be known as organic (physiologic) rather than purely of the mind. These names are older and nearly obsolete general terms from psychiatry, referring to many physical disorders that cause impaired mental function. They are meant to exclude psychiatric disorders (mental disorders). Originally, the term was created to distinguish physical (termed "organic") causes of mental impairment from psychiatric (termed "functional") disorders, but during the era when this distinction was drawn, not enough was known about brain science (including neuroscience, cognitive science, neuropsychology, and mind-brain correlation) for this cause-based classification to be more than educated guesswork labeled with misplaced certainty, which is why it has been deemphasized in current medicine. While mental or behavioural abnormalities related to the dysfunction can be permanent, treating the disease early may prevent permanent damage in addition to fully restoring mental functions. An organic cause to brain dysfunction is suspected when there is no indication of a clearly defined psychiatric or "inorganic" cause, such as a mood disorder.

Types
Organic brain syndrome can be divided into 2 major subgroups: acute (delirium or acute confusional state) and chronic (dementia). A third entity, encephalopathy (amnestic), denotes a gray zone between delirium and dementia. The Diagnostic and Statistical Manual of Mental Disorders has broken up the diagnoses that once fell under the diagnostic category organic mental disorder into three categories: delirium, dementia, and amnestic.

Delirium
Delirium or Acute organic brain syndrome is a recently appearing state of mental impairment, as a result of intoxication, drug overdose, infection, pain, and many other physical problems affecting mental status. In medical contexts, "acute" means "of recent onset". As is the case with most acute disease problems, acute organic brain syndrome is often temporary, although this does not guarantee that it will not recur or progress to become chronic, that is, long-term. A more specific medical term for the acute subset of organic brain syndromes is delirium. Thinking, remembering, sleeping, and paying attention can become difficult during alcohol withdrawal, after surgery, or with dementia.

Dementia
Dementia or chronic organic brain syndrome is long-term. For example, some forms of chronic drug or alcohol dependence can cause organic brain syndrome due to their long-lasting or permanent toxic effects on brain function. Other common causes of chronic organic brain syndrome sometimes listed are the various types of dementia, which result from permanent brain damage due to strokes, Alzheimers disease, or other damaging causes which are irreversible. Amnestic pertains to amnesia and is the impairment in ability to learn or recall new information, or recall previously learned information. Although similar, it is not coupled with dementia or delirium.

Amnestic
Amnestic conditions denotes a gray zone between delirium and dementia; its early course may fluctuate, but it is often persistent and progressive. Damage to brain functioning could be due not only to organic (physical) injury (a severe blow to the head, stroke, chemical and toxic exposures, organic brain disease, substance use, etc.) and also to non-organic means such as severe deprivation, abuse, neglect, and severe psychological trauma.

Symptoms
Many of the symptoms of Organic Mental Disorder depend on the cause of the disorder, but are similar and include physical or behavioral elements. Dementia and delirium are the cause of the confusion, orientation, cognition or alertness impairment. Therefore, these symptoms require more attention because hallucinations, delusions, amnesia, and personality changes are the result. These effects of the dementia and delirium are not joined with the changes of sensory or perception abilities. Memory impairment, judgment, logical function and agitation are also some extremely common symptoms. The more common symptoms of OBS are confusion; impairment of memory, judgment, and intellectual function;  and agitation. Often these symptoms are attributed to psychiatric illness, which causes a difficulty in diagnosis.

Associated conditions
Disorders that are related to injury or damage to the brain and contribute to OBS include, but are not limited to:

Alcoholism
Alzheimers disease
Attention deficit/hyperactivity disorder
Autism
Concussion
Encephalitis
Epilepsy
Fetal alcohol syndrome
Hypoxia
Parkinsons disease
Intoxication/overdose caused by substance use disorders including alcohol use disorder
Non-medical use of sedative hypnotics
Intracranial hemorrhage/trauma
Korsakoff syndrome
Mastocytosis
Meningitis
Psychoorganic syndrome
Stroke/transient ischemic attack (TIA)
Withdrawal from drugs, especially sedative hypnotics, e.g </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 Progressive osseous heteroplasia 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 Cervical weakness and can you explain it in depth? [/INST] Cervical weakness, also called cervical incompetence or cervical insufficiency, is a medical condition of pregnancy in which the cervix begins to dilate (widen) and efface (thin) before the pregnancy has reached term. Definitions of cervical weakness vary, but one that is frequently used is the inability of the uterine cervix to retain a pregnancy in the absence of the signs and symptoms of clinical contractions, or labor, or both in the second trimester. Cervical weakness may cause miscarriage or preterm birth during the second and third trimesters. It has been estimated that cervical insufficiency complicates about 1% of pregnancies, and that it is a cause in about 8% of women with second trimester recurrent miscarriages.A sign of cervical weakness is funneling at the internal orifice of the uterus, which is a dilation of the cervical canal at this location.In cases of cervical weakness, dilation and effacement of the cervix may occur without pain or uterine contractions. In a normal pregnancy, dilation and effacement occurs in response to uterine contractions. Cervical weakness becomes a problem when the cervix is pushed to open by the growing pressure in the uterus as pregnancy progresses. If the responses are not halted, rupture of the membranes and birth of a premature baby can result.
The older terminology is perceived as blaming the woman for the miscarriage, as if she were an incompetent or insufficient person.  Consequently, cervical weakness is the recommended term.

Risk factors
Risk factors for premature birth or stillbirth due to cervical weakness include:
diagnosis of cervical weakness in a previous pregnancy
previous preterm premature rupture of membranes
history of conization (cervical biopsy)
diethylstilbestrol exposure, which can cause anatomical defects, and
uterine anomaliesRepeated procedures (such as mechanical dilation, especially during late pregnancy) appear to create a risk.  Additionally, any significant trauma to the cervix can weaken the tissues involved.

Diagnosis
Diagnosis of cervical weakness can be challenging and is based on a history of painless cervical dilation usually after the first trimester without contractions or labor and in the absence of other clear pathology. In addition to history, some providers use assessment of cervical length in second trimester to identify cervical shortening using ultrasound. However, short cervical length has actually been shown to be a marker of preterm birth rather than cervical weakness. Other diagnostic tests that have been suggested which have not been validated include hysterosalpingography and radiographic imaging of balloon traction on the cervix, assessment of the patulous cervix with Hegar or Pratt dilators, the use of a balloon elastance test, and use of graduated cervical dilators to calculate a cervical resistance index.Normally, the cervix should be at least 30 mm in length. Cervical weakness is variably defined. However, a common definition is a cervical length of less than 25 mm at or before 24 weeks of gestational age. The risk of preterm birth is inversely proportional to cervical length:
Less than 25 mm; 18% risk of preterm birth
Less than 20 mm; 25% risk of preterm birth
Less than 15 mm; 50% risk of preterm birth

Treatment
Cervical weakness is not generally treated except when it appears to threaten a pregnancy.  Cervical weakness can be treated using cervical cerclage, a surgical technique that reinforces the cervical muscle by placing sutures above the opening of the cervix to narrow the cervical canal.Cerclage procedures usually entail closing the cervix through the vagina with the aid of a speculum </s>