<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 Hydrocephalus and can you explain it in depth? [/INST] Hydrocephalus is a condition in which an accumulation of cerebrospinal fluid (CSF) occurs within the brain. This typically causes increased pressure inside the skull. Older people may have headaches, double vision, poor balance, urinary incontinence, personality changes, or mental impairment. In babies, it may be seen as a rapid increase in head size. Other symptoms may include vomiting, sleepiness, seizures, and downward pointing of the eyes.Hydrocephalus can occur due to birth defects or be acquired later in life. Associated birth defects include neural tube defects and those that result in aqueductal stenosis. Other causes include meningitis, brain tumors, traumatic brain injury, intraventricular hemorrhage, and subarachnoid hemorrhage. The four types of hydrocephalus are communicating, noncommunicating, ex vacuo, and normal pressure. Diagnosis is typically made by physical examination and medical imaging.Hydrocephalus is typically treated by the surgical placement of a shunt system. A procedure called a third ventriculostomy is an option in some people. Complications from shunts may include overdrainage, underdrainage, mechanical failure, infection, or obstruction. This may require replacement. Outcomes are variable, but many people with shunts live normal lives. Without treatment, death or permanent disability may occur.About one to two per 1,000 newborns have hydrocephalus. Rates in the developing world may be higher. Normal pressure hydrocephalus is estimated to affect about 5 per 100,000 people, with rates increasing with age. Description of hydrocephalus by Hippocrates dates back more than 2,000 years. The word hydrocephalus is from the Greek ὕδωρ, hydōr, meaning water and κεφαλή, kephalē, meaning head.

Signs and symptoms
The clinical presentation of hydrocephalus varies with chronicity. Acute dilatation of the ventricular system is more likely to manifest with the nonspecific signs and symptoms of increased intracranial pressure (ICP). By contrast, chronic dilatation (especially in the elderly population) may have a more insidious onset presenting, for instance, with Hakims triad (Adams triad).Symptoms of increased ICP may include headaches, vomiting, nausea, papilledema, sleepiness, or coma. With increased levels of CSF, there have been cases of hearing loss due to CSF creating pressure on the auditory pathways or disrupting the communication of inner ear fluid. Elevated ICP of different etiologies have been linked to sensorineural hearing loss (SNHL). Transient SNHL has been reported after the loss of CSF with shunt surgeries. Hearing loss is a rare but well-known sequela of procedures resulting in CSF loss. Elevated ICP may result in uncal or tonsillar herniation, with resulting life-threatening brain stem compression.Hakims triad of gait instability, urinary incontinence, and dementia is a relatively typical manifestation of the distinct entity normal-pressure hydrocephalus. Focal neurological deficits may also occur, such as abducens nerve palsy and vertical gaze palsy (Parinaud syndrome due to compression of the quadrigeminal plate, where the neural centers coordinating the conjugated vertical eye movement are located). The symptoms depend on the cause of the blockage, the persons age, and how much brain tissue has been damaged by the swelling.In infants with hydrocephalus, CSF builds up in the central nervous system (CNS), causing the fontanelle (soft spot) to bulge and the head to be larger than expected. Early symptoms may also include:
Eyes that appear to gaze downward
Irritability
Seizures
Separated sutures
Sleepiness
VomitingSymptoms that may occur in older children can include:
Brief, shrill, high-pitched cry
Changes in personality, memory, or the ability to reason or think
Changes in facial appearance and eye spacing (craniofacial disproportion)
Crossed eyes or uncontrolled eye movements
Difficulty feeding
Excessive sleepiness
Headaches
Irritability, poor temper control
Loss of bladder control (urinary incontinence)
Loss of coordination and trouble walking
Muscle spasticity (spasm)
Slow growth (child 0–5 years)
Delayed milestones
Failure to thrive
Slow or restricted movement
VomitingBecause hydrocephalus can injure the brain, thought and behavior may be adversely affected. Learning disabilities, including short-term memory loss, are common among those with hydrocephalus, who tend to score better on verbal IQ than on performance IQ, which is thought to reflect the distribution of nerve damage to the brain. Hydrocephalus that is present from birth can cause long-term complications with speech and language. Children can have issues such as nonverbal learning disorder, difficulty understanding complex and abstract concepts, difficulty retrieving stored information, and spatial/perceptual disorders. Children with hydrocephalus are often known in having the difficulty in understanding the concepts within conversation and tend to use words they know or have heard. However, the severity of hydrocephalus can differ considerably between individuals, and some are of average or above-average intelligence. Someone with hydrocephalus may have coordination and visual problems, or clumsiness. They may reach puberty earlier than the average child (this is called precocious puberty). About one in four develops epilepsy.

Cause
Congenital
Congenital hydrocephalus is present in the infant prior to birth, meaning the fetus developed hydrocephalus in utero during fetal development. The most common cause of congenital hydrocephalus is aqueductal stenosis, which occurs when the narrow passage between the third and fourth ventricles in the brain is blocked or too narrow to allow sufficient cerebral spinal fluid to drain. Fluid accumulates in the upper ventricles, causing hydrocephalus.Other causes of congenital hydrocephalus include neural-tube defects, arachnoid cysts, Dandy–Walker syndrome, and Arnold–Chiari malformation.
The cranial bones fuse by the end of the third year of life. For head enlargement to occur, hydrocephalus must occur before then. The causes are usually genetic, but can also be acquired and usually occur within the first few months of life, which include intraventricular matrix hemorrhages in premature infants, infections, type II Arnold-Chiari malformation, aqueduct atresia and stenosis, and Dandy-Walker malformation. Hydrocephalus has also been seen in cases of congenital syphilis.In newborns and toddlers with hydrocephalus, the head circumference is enlarged rapidly and soon surpasses the 97th percentile. Since the skull bones have not yet firmly joined, bulging, firm anterior and posterior fontanelles may be present even when the person is in an upright position.The infant exhibits fretfulness, poor feeding, and frequent vomiting. As the hydrocephalus progresses, torpor sets in, and infants show lack of interest in their surroundings. Later on, their upper eyelids become retracted and their eyes are turned downwards ("sunset eyes") (due to hydrocephalic pressure on the mesencephalic tegmentum and paralysis of upward gaze). Movements become weak and the arms may become tremulous. Papilledema is absent, but vision may be reduced. The head becomes so enlarged that they eventually may be bedridden.About 80–90% of fetuses or newborn infants with spina bifida—often associated with meningocele or myelomeningocele—develop hydrocephalus.

Acquired
This condition is acquired as a consequence of CNS infections, meningitis, brain tumors, head trauma, toxoplasmosis, or intracranial hemorrhage (subarachnoid or intraparenchymal), and is usually painful.

Type
The cause of hydrocephalus is not known with certainty and is probably multifactorial. It may be caused by impaired CSF flow, reabsorption, or excessive CSF production.
Obstruction to CSF flow hinders its free passage through the ventricular system and subarachnoid space (e.g., stenosis of the cerebral aqueduct or obstruction of the interventricular foramina secondary to tumors, hemorrhages, infections or congenital malformations) and can cause increases in ICP.
Hydrocephalus can also be caused by overproduction of CSF (relative obstruction) (e.g., choroid plexus papilloma, villous hypertrophy).
Bilateral ureteric obstruction is a rare, but reported, cause of hydrocephalus.Hydrocephalus can be classified into communicating and noncommunicating (obstructive). Both forms can be either congenital or acquired.

Communicating
Communicating hydrocephalus, also known as nonobstructive hydrocephalus, is caused by impaired CSF reabsorption in the absence of any obstruction of CSF flow between the ventricles and subarachnoid space. This may be due to functional impairment of the arachnoidal granulations (also called arachnoid granulations or Pacchionis granulations), which are located along the superior sagittal sinus, and is the site of CSF reabsorption back into the venous system. Various neurologic conditions may result in communicating hydrocephalus, including subarachnoid/intraventricular hemorrhage, meningitis, and congenital absence of arachnoid villi. Scarring and fibrosis of the subarachnoid space following infectious, inflammatory, or hemorrhagic events can also prevent reabsorption of CSF, causing diffuse ventricular dilatation.

Noncommunicating
Noncommunicating hydrocephalus, or obstructive hydrocephalus, is caused by an obstruction to the flow of CSF.
Foramen of Monro obstruction may lead to dilation of one, or if large enough (e.g., in colloid cyst), both lateral ventricles.
The aqueduct of Sylvius, normally narrow, may be obstructed by a number of genetic or acquired lesions (e.g., atresia, ependymitis, hemorrhage, or tumor) and lead to dilation of both lateral ventricles, as well as the third ventricle.
Fourth ventricle obstruction leads to dilatation of the aqueduct, as well as the lateral and third ventricles (e.g., Chiari malformation).
The foramina of Luschka and foramen of Magendie may be obstructed due to congenital malformation (e.g., Dandy–Walker malformation).

Other
Normal pressure hydrocephalus (NPH) is a particular form of chronic communicating hydrocephalus, characterized by enlarged cerebral ventricles, with only intermittently elevated cerebrospinal fluid pressure. Characteristic triad of symptoms are; dementia, apraxic gait and urinary incontinence. The diagnosis of NPH can be established only with the help of continuous intraventricular pressure recordings (over 24 hours or even longer), since more often than not instant measurements yield normal pressure values. Dynamic compliance studies may be also helpful. Altered compliance (elasticity) of the ventricular walls, as well as increased viscosity of the cerebrospinal fluid, may play a role in the pathogenesis.
Hydrocephalus ex vacuo also refers to an enlargement of cerebral ventricles and subarachnoid spaces, and is usually due to brain atrophy (as it occurs in dementias), post-traumatic brain injuries, and even in some psychiatric disorders, such as schizophrenia. As opposed to hydrocephalus, this is a compensatory enlargement of the CSF-spaces in response to brain parenchyma loss; it is not the result of increased CSF pressure.

Mechanism
Hydrocephalus is usually due to blockage of CSF outflow in the ventricles or in the subarachnoid space over the brain. In a person without hydrocephalus, CSF continuously circulates through the brain, its ventricles and the spinal cord and is continuously drained away into the circulatory system. Alternatively, the condition may result from an overproduction of the CSF, from a congenital malformation blocking normal drainage of the fluid, or from complications of head injuries or infections.Compression of the brain by the accumulating fluid eventually may cause neurological symptoms such as convulsions, intellectual disability, and epileptic seizures. These signs occur sooner in adults, whose skulls are no longer able to expand to accommodate the increasing fluid volume within. Fetuses, infants, and young children with hydrocephalus typically have an abnormally large head, excluding the face, because the pressure of the fluid causes the individual skull bones—which have yet to fuse—to bulge outward at their juncture points. Another medical sign, in infants, is a characteristic fixed downward gaze with whites of the eyes showing above the iris, as though the infant were trying to examine its own lower eyelids.The elevated ICP may cause compression of the brain, leading to brain damage and other complications. A complication often overlooked is the possibility of hearing loss due to ICP. The mechanism of ICP on hearing loss is presumed that the transmission of CSF pressure to and from the Perilymphatic space through a patent cochlear aqueduct. The cochlear aqueduct connects the Perilymphatic space of the inner ear with the subarachnoid space of the posterior cranial fossa. A loss of CSF pressure can induce Perilymphatic loss or endolymphatic hydrops resembling the clinical presentation of Ménières disease associated hearing loss in the low frequencies.CSF can accumulate within the ventricles, this condition is called internal hydrocephalus and may result in increased CSF pressure. The production of CSF continues, even when the passages that normally allow it to exit the brain are blocked. Consequently, fluid builds inside the brain, causing pressure that dilates the ventricles and compresses the nervous tissue. Compression of the nervous tissue usually results in irreversible brain damage. If the skull bones are not completely ossified when the hydrocephalus occurs, the pressure may also severely enlarge the head. The cerebral aqueduct may be blocked at the time of birth or may become blocked later in life because of a tumor growing in the brainstem.

Treatments
Procedures
Hydrocephalus treatment is surgical, creating a way for the excess fluid to drain away. In the short term, an external ventricular drain (EVD), also known as an extraventricular drain or ventriculostomy, provides relief. In the long term, some people will need any of various types of cerebral shunt. It involves the placement of a ventricular catheter (a tube made of silastic) into the cerebral ventricles to bypass the flow obstruction/malfunctioning arachnoidal granulations and drain the excess fluid into other body cavities, from where it can be resorbed. Most shunts drain the fluid into the peritoneal cavity (ventriculoperitoneal shunt), but alternative sites include the right atrium (ventriculoatrial shunt), pleural cavity (ventriculopleural shunt), and gallbladder. A shunt system can also be placed in the lumbar space of the spine and have the CSF redirected to the peritoneal cavity (lumbar-peritoneal shunt). An alternative treatment for obstructive hydrocephalus in selected people is the endoscopic third ventriculostomy (ETV), whereby a surgically created opening in the floor of the third ventricle allows the CSF to flow directly to the basal cisterns, thereby shortcutting any obstruction, as in aqueductal stenosis. This may or may not be appropriate based on individual anatomy. For infants, ETV is sometimes combined with choroid plexus cauterization, which reduces the amount of cerebrospinal fluid produced by the brain. The technique, known as ETV/CPC, was pioneered in Uganda by neurosurgeon Benjamin Warf and is now in use in several U.S. hospitals. Hydrocephalus can be successfully treated by placing a drainage tube (shunt) between the brain ventricles and abdominal cavity. Some risk exists of infection being introduced into the brain through these shunts, however, and the shunts must be replaced as the person grows.

External hydrocephalus
External hydrocephalus is a condition generally seen in infants which involves enlarged fluid spaces or subarachnoid spaces around the outside of the brain. This condition is generally benign, and resolves spontaneously by two years of age and therefore usually does not require insertion of a shunt. Imaging studies and a good medical history can help to differentiate external hydrocephalus from subdural hemorrhages or symptomatic chronic extra-axial fluid collections which are accompanied by vomiting, headaches, and seizures.

Shunt complications
Examples of possible complications include shunt malfunction, shunt failure, and shunt infection, along with infection of the shunt tract following surgery (the most common reason for shunt failure is infection of the shunt tract). Although a shunt generally works well, it may stop working if it disconnects, becomes blocked (clogged) or infected, or it is outgrown. If this happens, the CSF begins to accumulate again and a number of physical symptoms develop (headaches, nausea, vomiting, photophobia/light sensitivity), some extremely serious, such as seizures. The shunt failure rate is also relatively high (of the 40,000 surgeries performed annually to treat hydrocephalus, only 30% are a persons first surgery) and people not uncommonly have multiple shunt revisions within their lifetimes.Another complication can occur when CSF drains more rapidly than it is produced by the choroid plexus, causing symptoms of listlessness, severe headaches, irritability, light sensitivity, auditory hyperesthesia (sound sensitivity), hearing loss, nausea, vomiting, dizziness, vertigo, migraines, seizures, a change in personality, weakness in the arms or legs, strabismus, and double vision to appear when the person is vertical. If the person lies down, the symptoms usually vanish quickly. A CT scan may or may not show any change in ventricle size, particularly if the person has a history of slit-like ventricles. Difficulty in diagnosing over-drainage can make treatment of this complication particularly frustrating for people and their families. Resistance to traditional analgesic pharmacological therapy may also be a sign of shunt overdrainage or failure.Following placement of a ventriculoperitoneal shunt there have been cases of a decrease in post-surgery hearing. It is presumed that the cochlea aqueduct is responsible for the decrease in hearing thresholds. The cochlea aqueduct has been considered as a probable channel where CSF pressure can be transmitted. Therefore, the reduced CSF pressure could cause a decrease in Perilymphatic pressure and cause secondary endolymphatic hydrops. In addition to the increased hearing loss, there have also been findings of resolved hearing loss after ventriculoperitoneal shunt placement, where there is a release of CSF pressure on the auditory pathways.The diagnosis of CSF buildup is complex and requires specialist expertise. Diagnosis of the particular complication usually depends on when the symptoms appear, that is, whether symptoms occur when the person is upright or in a prone position, with the head at roughly the same level as the feet.Standardized protocols for inserting cerebral shunts have been shown to reduce shunt infections. There is tentative evidence that preventative antibiotics may decrease the risk of shunt infections.

Epidemiology
The hydrocephalus disease burden are concentrated in the developing world while North America and Canada has the least number of cases. A systematic review in 2019 estimated that there are 180,000 childhood hydrocephalus cases from African continent alone per year, followed by 90,000 cases from Southeast Asia and Western Pacific. Latin America also has high prevalence of hydrocephalus. However, data on hydrocephalus disease burden in adults are lacking.

History
In the pre-historic area, there were various paintings or artifacts depicting children or adults with macrocephaly (large head) or clinical findings of hydrocephalus. However, due to lack of writing, it was unknown how the people thought of the disorder at that time and the ways to treat the disease.References to hydrocephalic skulls can be found in ancient Egyptian medical literature from 2,500 BC to 500 AD. Hydrocephalus was described more clearly by the ancient Greek physician Hippocrates in the fourth century BC, while a more accurate description was later given by the Roman physician Galen in the second century AD.The first clinical description of an operative procedure for hydrocephalus appears in the Al-Tasrif (1,000 AD) by the Arab surgeon Abulcasis, who clearly described the evacuation of superficial intracranial fluid in hydrocephalic children. He described it in his chapter on neurosurgical disease, describing infantile hydrocephalus as being caused by mechanical compression. He wrote:
The skull of a newborn baby is often full of liquid, either because the matron has compressed it excessively or for other, unknown reasons. The volume of the skull then increases daily, so that the bones of the skull fail to close. In this case, we must open the middle of the skull in three places, make the liquid flow out, then close the wound and tighten the skull with a bandage.

In 1881, a few years after the landmark study of Retzius and Key, Carl Wernicke pioneered sterile ventricular puncture and external drainage of CSF for the treatment of hydrocephalus. It remained an intractable condition until the 20th century, when cerebral shunt and other neurosurgical treatment modalities were developed.It is a lesser-known medical condition; relatively little research is conducted to improve treatment, and still no cure has been found. In developing countries, the condition often goes untreated at birth. Before birth, the condition is difficult to diagnose, and access to medical treatment is limited. However, when head swelling is prominent, children are taken at great expense for treatment. By then, brain tissue is undeveloped and neurosurgery is rare and difficult. Children more commonly live with undeveloped brain tissue and consequential intellectual disabilities and restrictions.

Society and culture
Name
The word hydrocephalus is from the Greek ὕδωρ, hydōr meaning water and κεφαλή, kephalē meaning head. Other names for hydrocephalus include "water on the brain", a historical name, and "water baby syndrome".

Awareness campaign
September was designated National Hydrocephalus Awareness Month in July 2009 by the U.S. Congress in H.Res. 373. The resolution campaign is due in part to the advocacy work of the Pediatric Hydrocephalus Foundation. Prior to July 2009, no awareness month for this condition had been designated </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 Xanthinuria 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 Hospital-acquired pneumonia and can you explain it in depth? [/INST] Hospital-acquired pneumonia (HAP) or nosocomial pneumonia refers to any pneumonia contracted by a patient in a hospital at least 48–72 hours after being admitted. It is thus distinguished from community-acquired pneumonia. It is usually caused by a bacterial infection, rather than a virus.HAP is the second most common nosocomial infection (after urinary tract infections) and accounts for 15–20% of the total. It is the most common cause of death among nosocomial infections and is the primary cause of death in intensive care units.HAP typically lengthens a hospital stay by 1–2 weeks.

Signs and symptoms
New or progressive infiltrate on the chest X-ray with one of the following:
Fever > 37.8 °C (100 °F)
Purulent sputum
Leukocytosis > 10,000 cells/μlIn an elderly person, the first sign of hospital-acquired pneumonia may be mental changes or confusion.
Other symptoms may include:

A cough with greenish or pus-like phlegm (sputum)
Fever and chills
General discomfort, uneasiness, or ill feeling (malaise)
Loss of appetite
Nausea and vomiting
Sharp chest pain that gets worse with deep breathing or coughing
Shortness of breath
Decreased blood pressure and fast heart rate

Types
Bacterial pneumonia: The majority of cases related to various rod shaped gram-negative organisms (52%) and Staphylococcus aureus (19%), usually of the MRSA type. Others are Haemophilus spp. (5%). In the ICU results were S. aureus (17.4%), Pseudomonas aeruginosa (17.4%), Klebsiella pneumoniae and Enterobacter spp. (18.1%), and Haemophilus influenzae (4.9%).
Viral pneumonia: influenza and respiratory syncytial virus and, in the immunocompromised host, cytomegalovirus – cause 10–20% of infections.

Ventilator-associated pneumonia
Ventilator-associated pneumonia (VAP) is a sub-type of hospital-acquired pneumonia (HAP) which occurs in people who are receiving mechanical ventilation. VAP is not characterized by the causative agents; rather, as its name implies, definition of VAP is restricted to patients undergoing mechanical ventilation while in a hospital. A positive culture after intubation is indicative of ventilator-associated pneumonia and is diagnosed as such. In order to appropriately categorize the causative agent or mechanism it is usually recommended to obtain a culture prior to initiating mechanical ventilation as a reference.

Healthcare-associated pneumonia (HCAP)
HCAP is a condition in patients who can come from the community, but have frequent contact with the healthcare environment. Historically, the etiology and prognosis of nursing home pneumonia appeared to differ from other types of community acquired pneumonia, with studies reporting a worse prognosis and higher incidence of multi drug resistant organisms as etiology agents. The definition criteria which has been used is the same as the one which has been previously used to identify bloodstream healthcare associated infections.
HCAP is no longer recognized as a clinically independent entity. This is due to increasing evidence from a growing number of studies that many patients defined as having HCAP are not at high risk for MDR pathogens. As a result, 2016 IDSA guidelines removed consideration of HCAP as a separate clinical entity.

Definition
Healthcare-associated pneumonia can be defined as pneumonia in a patient with at least one of the following risk factors:

hospitalization in an acute care hospital for two or more days in the last 90 days;
residence in a nursing home or long-term care facility in the last 30 days
receiving outpatient intravenous therapy (like antibiotics or chemotherapy) within the past 30 days
receiving home wound care within the past 30 days
attending a hospital clinic or dialysis center in the last 30 days
having a family member with known multi-drug resistant pathogens

Causes
In some studies, the bacteria found in patients with HCAP were more similar to HAP than to CAP; compared to CAP, they could have higher rates of Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa, and less Streptococcus pneumoniae and Haemophilus influenzae. In European and Asian studies, the etiology of HCAP was similar to that of CAP, and rates of multi drug resistant pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa were not as high as seen in North American studies. It is well known that nursing home residents have high rates of colonization with MRSA. However, not all studies have found high rates of S. aureus and gram-negative bacteria. One factor responsible for these differences is the reliance on sputum samples and the strictness of the criteria to discriminate
between colonising or disease-causing bacteria. Moreover, sputum samples might be less frequently obtained in the elderly. Aspiration (both of microscopic drops and macroscopic amounts of nose and throat secretions) is thought to be the most important cause of HCAP. Dental plaque might also be a reservoir for bacteria in HCAP.
Bacteria have been the most commonly isolated pathogens, although viral and fungal pathogens are potentially found in immunocompromised hosts (patients on chronic immunosuppressed medications, solid organ and bone marrow transplant recipients). In general, the distribution of microbial pathogens varies among institutions, partly because of differences in patient population and local patterns of anti microbial resistance in hospitals and critical care units Common bacterial pathogens include aerobic GNB, such as Pseudomonas aeruginosa, Acinetobacter baumanii, Klebsiella pneumoniae, Escherichia coli as well as gram-positive organisms such as Staphylococcus aureus. In patients with an early onset pneumonia (within 5 days of hospitalization), they are usually due to anti microbial-sensitive bacteria such as Enterobacter spp, E. coli, Klebsiella spp, Proteus spp, Serratia mare scans, community pathogens such as Streptococcus pneumoniae, Haemophilus influenzae, and methicillin-sensitive S. aureus should also be considered.
Pneumonia that starts in the hospital tends to be more serious than other lung infections because: people in the hospital are often very sick and cannot fight off germs. The types of germs present in a hospital are often more dangerous and more resistant to treatment than those outside in the community. Pneumonia occurs more often in people who are using a respirator. This machine helps them breathe. Hospital-acquired pneumonia can also be spread by health care workers, who can pass germs from their hands or clothes from one person to another. This is why hand-washing, wearing gloves, and using other safety measures is so important in the hospital.

Treatment
Patients with HCAP are more likely than those with community-acquired pneumonia to receive inappropriate antibiotics that do not target the bacteria causing their disease.In 2002, an expert panel made recommendations about the evaluation and treatment of probable nursing home-acquired pneumonia. They defined probably pneumonia, emphasized expedite antibiotic treatment (which is known to improve survival) and drafted criteria for the hospitalization of willing patients.
For initial treatment in the nursing home, a fluoroquinolone antibiotic suitable for respiratory infections (moxifloxacin, for example), or amoxicillin with clavulanic acid plus a macrolide has been suggested. In a hospital setting, injected (parenteral) fluoroquinolones or a second- or third-generation cephalosporin plus a macrolide could be used. Other factors that need to be taken into account are recent antibiotic therapy (because of possible resistance caused by recent exposure), known carrier state or risk factors for resistant organisms (for example, known carrier of MRSA or presence of bronchiectasis predisposing to Pseudomonas aeruginosa), or suspicion of possible Legionella pneumophila infection (legionnaires disease).In 2005, the American Thoracic Society and Infectious Diseases Society of America have published guidelines suggesting antibiotics specifically for HCAP. The guidelines recommend combination therapy with an agent from each of the following groups to cover for both Pseudomonas aeruginosa and MRSA. This is based on studies using sputum samples and intensive care patients, in whom these bacteria were commonly found.

cefepime, ceftazidime, imipenem, meropenem or piperacillin–tazobactam; plus
ciprofloxacin, levofloxacin, amikacin, gentamicin, or tobramycin; plus
linezolid or vancomycinIn one observational study, empirical antibiotic treatment that was not according to international treatment guidelines was an independent predictor of worse outcome among HCAP patients.Guidelines from Canada suggest that HCAP can be treated like community-acquired pneumonia with antibiotics targeting Streptococcus pneumoniae, based on studies using blood cultures in different settings which have not found high rates of MRSA or Pseudomonas.Besides prompt antibiotic treatment, supportive measure for organ failure (such as cardiac decompensation) are also important. Another consideration goes to hospital referral; although more severe pneumonia requires admission to an acute care facility, this also predisposes to hazards of hospitalization such as delirium, urinary incontinence, depression, falls, restraint use, functional decline, adverse drug effects and hospital infections. Therefore, mild pneumonia might be better dealt with inside the long-term care facility. In patients with a limited life expectancy (for example, those with advanced dementia), end-of-life pneumonia also requires recognition and appropriate, palliative care.

Prognosis
Healthcare-associated pneumonia seems to have fatality rates similar to hospital-acquired pneumonia, worse than community-acquired pneumonia but less severe than pneumonia in ventilated patients. Besides clinical markers like tachypnea (fast breathing) or a high white cell count (leukocytosis), the prognosis seems to be influenced by the underlying associated diseases (comorbidities) and functional capacities (for example, the ADL score). Many patients have a decreased health condition after the episode.

Epidemiology
Several studies found that healthcare-associated pneumonia is the second most common type of pneumonia, occurring less commonly than community-acquired pneumonia but more frequently than hospital-acquired pneumonia and ventilator-associated pneumonia. In a recent observational study, the rates for CAP, HCAP and HAP were 60%, 25% and 15% respectively. Patients with HCAP are older and more commonly have simultaneous health problems (such as previous stroke, heart failure and diabetes).The number of residents in long-term care facilities is expected to rise dramatically over the next 30 years. These older adults are known to develop pneumonia 10 times more than their community-dwelling peers, and hospital admittance rates are 30 times higher.

Nursing home-acquired pneumonia
Nursing home-acquired pneumonia is an important subgroup of HCAP. Residents of long-term care facilities may become infected through their contacts with the healthcare system; as such, the microbes responsible for their pneumonias may be different from those traditionally seen in community-dwelling patients, requiring therapy with different antibiotics. Other groups include patients who are admitted as a day case for regular hemodialysis or intravenous infusion (for example, chemotherapy). Especially in the very old and in demented patients, HCAP is likely to present with atypical symptoms.

Risk factors
Among the factors contributing to contracting HAP are mechanical ventilation (ventilator-associated pneumonia), old age, decreased filtration of inspired air, intrinsic respiratory, neurologic, or other disease states that result in respiratory tract obstruction, trauma, (abdominal) surgery, medications, diminished lung volumes, or decreased clearance of secretions may diminish the defenses of the lung.  Also, poor hand-washing and inadequate disinfection of respiratory devices cause cross-infection and are important factors.

Pathogenesis
Most nosocomial respiratory infections are caused by so-called microaspiration of upper airway secretions, through inapparent aspiration, into the lower respiratory tract. Also, "macroaspirations" of esophageal or gastric material is known to result in HAP.  Since it results from aspiration either type is called aspiration pneumonia.Although gram-negative bacilli are a common cause they are rarely found in the respiratory tract of people without pneumonia, which has led to speculation of the mouth and throat as origin of the infection.

Diagnosis
In hospitalised patients who develop respiratory symptoms and fever, one should consider the diagnosis.  The likelihood increases when upon investigation symptoms are found of respiratory insufficiency, purulent secretions, newly developed infiltrate on the chest X-Ray, and increasing leucocyte count.  If pneumonia is suspected material from sputum or tracheal aspirates are sent to the microbiology department for cultures.  In case of pleural effusion, thoracentesis is performed for examination of pleural fluid.  In suspected ventilator-associated pneumonia it has been suggested that bronchoscopy or bronchoalveolar lavage is necessary because of the risks of incorrect clinical diagnoses.

Differential diagnosis
Atelectasis
Congestive heart failure
Pulmonary embolism

Treatment
Usually initial therapy is empirical. If sufficient reason to suspect influenza, one might consider oseltamivir. In case of legionellosis, erythromycin or fluoroquinolone.A third generation cephalosporin (ceftazidime) + carbapenems (imipenem) + beta lactam & beta lactamase inhibitors (piperacillin/tazobactam)

References
Further reading
Carratalà J, Garcia-Vidal C (2008) </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 Central sleep apnea and can you explain it in depth? [/INST] Central sleep apnea (CSA) or central sleep apnea syndrome (CSAS) is a  sleep-related disorder in which the effort to breathe is diminished or absent, typically for 10 to 30 seconds either intermittently or in cycles, and is usually associated with a reduction in blood oxygen saturation.  CSA is usually due to an instability in the bodys feedback mechanisms that  control respiration. Central sleep apnea can also be an indicator of Arnold–Chiari malformation.

Signs and symptoms
In a healthy person during sleep, breathing is regular so oxygen levels and carbon dioxide levels in the bloodstream stay fairly constant:  After exhalation, the blood level of oxygen decreases and that of carbon dioxide increases. Exchange of gases with a lungful of fresh air is necessary to replenish oxygen and rid the bloodstream of built-up carbon dioxide. Oxygen and carbon dioxide receptors in the body (called chemoreceptors) send nerve impulses to the brain, which then signals for reflexive opening of the larynx (enlarging the opening between the vocal cords) and movements of the rib cage muscles and diaphragm. These muscles expand the thorax (chest cavity) so that a partial vacuum is made within the lungs and air rushes in to fill it. In the absence of central apnea, any sudden drop in oxygen or excess of carbon dioxide, even if small, strongly stimulates the brains respiratory centers to breathe; the respiratory drive is so strong that even conscious efforts to hold ones breath do not overcome it.In pure central sleep apnea, the brains respiratory control centers, located in the region of the human brain known as the pre-Botzinger complex, are imbalanced during sleep and fail to give the signal to inhale, causing the individual to miss one or more cycles of breathing. The neurological feedback mechanism that monitors blood levels of carbon dioxide and in turn stimulates respiration fails to react quickly enough to maintain an even respiratory rate, allowing the entire respiratory system to cycle between apnea and hyperpnea, even for a brief time following an awakening during a breathing pause. The sleeper stops breathing for up to two minutes and then starts again. There is no effort made to breathe during the pause in breathing: there are no chest movements and no muscular struggling, although when awakening occurs in the middle of a pause, the inability to immediately operate the breathing muscles often results in cognitive struggle accompanied by a feeling of panic exacerbated by the feeling associated with excessive blood CO2 levels. Even in severe cases of central sleep apnea, however, the effects almost always result in pauses that make breathing irregular rather than cause the total cessation of breathing over the medium term. After the episode of apnea, breathing may be faster and/or more intense (hyperpnea) for a period of time, a compensatory mechanism to blow off retained waste gases, absorb more oxygen, and, when voluntary, enable a return to normal instinctive breathing patterns by restoring oxygen to the breathing muscles themselves.

Secondary effects
The conditions of hypoxia and hypercapnia, whether caused by apnea or not, trigger additional effects on the body. The immediate effects of central sleep apnea on the body depend on how long the failure to breathe endures, how short is the interval between failures to breathe, and the presence or absence of independent conditions whose effects amplify those of an apneic episode.
Brain cells need constant oxygen to live, and if the level of blood oxygen remains low enough for long enough, brain damage and even death will occur. These effects, however, are rarely a result of central sleep apnea, which is a chronic condition whose effects are usually much milder.
Drops in blood oxygen levels that are severe but not severe enough to trigger brain-cell or overall death may trigger seizures even in the absence of epilepsy.
In severe cases of sleep apnea, the more translucent areas of the body will show a bluish or dusky cast from cyanosis, the change in hue ("turning blue") produced by the deoxygenation of blood in vessels near the skin.
Compounding effects of independent conditions:In persons with epilepsy, the hypoxia caused by apnea may be powerful enough to trigger seizures even in the presence of medication that otherwise controls those seizures well.
In adults with coronary artery disease, a severe drop in blood oxygen level can cause angina, arrhythmias, or heart attacks (myocardial infarction).
Longstanding and recurrent episodes of apnea may, over months and years, have the cumulative effect of increasing blood carbon-dioxide levels to the point that enough carbon dioxide dissolves in the blood to form carbonic acid in overall proportions sufficient to cause respiratory acidosis.
In persons who have either or both forms of sleep apnea, breathing irregularities during sleep can be dangerously aggravated by taking respiration-depressing drugs, especially sedative drugs that operate by depressing the central nervous system generally; respiratory depressants include opiates, barbiturates, benzodiazepines, and, in large quantities, alcohol, the last three of which are broad-spectrum CNS depressants. Quantities that are normally considered safe may cause the person with chronic sleep apnea to stop breathing altogether. Should these individuals have general anaesthesia, for example, they require prolonged monitoring after initial recovery, as compared against a person with no history of sleep apnea, because apnea is likely to occur with even low levels of the drugs in their system.
Sudden infant death syndrome is sometimes theorized to be attributable to sleep apnea; the recommendation, prevalent since the mid-1980s, of placing infants on their backs rather than their stomachs for sleep represents an attempt to prevent those instances of breathing cessation that are attributable to compressive obstruction.
Premature infants with immature brains and reflex systems are at high risk for central sleep apnea syndrome, even if these babies are otherwise healthy. Premature babies who have the syndrome will generally outgrow it as they mature, provided that they receive careful enough monitoring and supportive care during infancy to survive. Because of premature infants propensity toward central apnea, medications that can cause respiratory drive depression are either not given to them or administered to them only under careful monitoring, with equipment for resuscitation immediately available. Such precautions are routinely taken for premature infants after general anesthesia; administration of caffeine has been found not only to aid in maintenance of respiratory function after general anaesthesia but to reduce apnea for preterm infants regardless of context.

Diagnosis
A diagnosis of sleep apnea requires determination by a physician. The examination may require a study of an individual in a sleep lab, although the AAST has said a two belt IHT (In Home Test) will replace a PSG for diagnosing obstructive apnea. There, the patient will be monitored while at rest, and the periods when breathing ceases will be measured with respect to length and frequency. During  a PSG (polysomnography) (a sleep study), a person with sleep apnea shows breathing interruptions followed by drops/reductions in blood oxygen and increases in blood carbon dioxide level.

In adults, a pause must last 10 seconds to be scored as an apnea. However, in young children, who normally breathe at a much faster rate than adults, shorter pauses may still be considered apneas.
Hypopneas in adults are defined as a 30% reduction in air flow for more than ten seconds, followed by oxygen-saturation declines of at least 3% or 4% per the AASM standards. and/or EEG arousal. The Apnea-Hypopnea Index (AHI) is expressed as the number of apneas or hypopneas per hour of sleep.As noted above, in central sleep apnea, the cessation of airflow is associated with the absence of physical attempts to breathe; specifically, polysomnograms reveal correlation between absence of rib cage and abdominal movements and cessation of airflow at the nose and lips. By contrast, in obstructive sleep apnea, pauses are not correlated with the absence of attempts to breathe and may even be correlated with more effortful breathing in an instinctive attempt to overcome the pressure on the affected persons airway. If the majority of a sleep-apnea patients apneas/hypopneas are central, their condition is classified as central; likewise, if the majority are obstructive, their condition is classified as obstructive.

Criteria
CSA is divided in 6 categories, Primary CSA, Cheyne–Stokes respiration, High-altitude periodic breathing, CSA due to a medical condition without CSB, Central sleep apnea due to a medication or substance and Treatment Emergent Central Apnea (also called Complex Sleep Apnea). The following symptoms are present in the Primary CSA: excessive daytime sleepiness, frequent arousals and awakenings during sleep or insomnia complaints, awakening short of breath, snoring, witness apneas. His polysomnography shows ≥5 central apneas and/or central hypopneas per hour of sleep, representing at least 50% of total respiratory events in the apnea-hypopnea index. CSA with Cheyne-Stokes breathing is characterized by at least one of the criteria of Primary CSA or the presence of atrial fibrillation/flutter, CHF, or a neurologic disorder. His polysomnography looks like the Primary CSA polysomnography with the addition of a ventilatory pattern compatible with CSB. High-Altitude Periodic Breathing requires that the patient has recently been at least 2500 meters. In the CSA due to a medication or substance, opioid or respiratory depressants must had been taken. For the CSA due to a medical condition without CSB, the criteria are the same as Primary CSA, but the symptoms are caused by a disease. In the Treatment Emergent Central Apnea, there was firstly some obstructive respiratory events but after their disappearance, the CSA has appeared.

Differential diagnosis
Although central and obstructive sleep apnea have some signs and symptoms in common, others are present in one but absent in another, enabling differential diagnosis as between the two types:Signs and symptoms of sleep apnea generally

Signs:Observed breathing pauses during sleep
High carbon-dioxide saturation of blood, especially just before awakenings during which a patient experiences urgent need to breathe (see "Symptoms" below)
Low oxygen saturation of blood
Heart rate increase (response to both hypercapnia and hypoxemia/hypoxia), unless there also exist problems with the heart muscle itself or the autonomic nervous system severe enough to make this compensatory increase impossibleSymptoms:High frequency of urgent need to breathe upon awakening (symptom created by hypercapnia), especially among subset of awakenings occurring at times other than normal for an individuals sleep schedule and circadian rhythmsSigns and symptoms of central sleep apnea

Signs:Lack of abdominal and thoracic movement for 10 seconds or longer during sleep and coincident with breathing pausesSymptoms:Inability, either complete or without excessive effort, to voluntarily operate diaphragm and other thoracic muscles upon awakeningThe combination of this symptom with a high frequency of urgent need to breathe upon awakening is especially specific in that the co-presence of the latter symptom differentiates central sleep apneas presentation from that of sleep paralysis generally.Signs and symptoms of and conditions associated with obstructive sleep apnea
Signs:Observably ineffective respiratory movements (observable lack of air flow despite observable muscle movements indicating efforts to breathe)
Snoring (high-sensitivity but low-specificity)
Observably dry mouth or throat (high-sensitivity but low-specificity)Symptoms:Sleepiness, fatigue, or tiredness, often rising to the level of excessive daytime sleepiness
Frequent feelings of choking (airway and/or lung compression), as distinguished from mere feeling of suffocation nonspecific with respect to presence/absence of pressure, upon awakeningAssociated conditions:Opioid medication use
Large neck circumference (>16" for females, > 17" for males) (frequent causal factor and possible indirect symptom; see "Obesity" below)
Obesity (frequent causal factor and possible, albeit low-specificity, sign both direct and indirect): Obesity frequently involves accumulation of fat below the chin and around the neck, depressing the trachea when one is in the supine position, and central obesity can, depending on an individuals fat distribution, lead to increased direct pressure on the thoracic cavity and/or compressive anterior (headward) displacement of the abdominal organs, in the second case reducing space for and increasing difficulty of the motion of the diaphragm. Poor breathing during sleep a] reduces oxygen available for metabolism and may therefore depress basal metabolic rate during sleep, increasing the difference between supply of food energy and demand for it during that time and thereby promoting weight gain, and b] reduces sleep quality and recovery per time unit of sleep, resulting in sleepiness or fatigue that may prompt affected people to eat more in an attempt to increase short-term energy levels.
Correlation with cardiac disorders:Atrial fibrillation (AF): A study in the medical journal Sleep found that the prevalence of atrial fibrillation among patients with idiopathic central sleep apnea was significantly higher than the prevalence among patients with obstructive sleep apnea or no sleep apnea (27%, 1.7%, and 3.3%, respectively). The study was based on 180 subjects with 60 people in each of the 3 groups. Possible explanations for the association between CSA and AF include a causal relationship in one direction or the other between the two conditions or a common cause involving an abnormality of central cardiorespiratory regulation.
Adults with congestive heart failure are at risk for a form of central apnea called Cheyne-Stokes respiration, which manifests itself both during sleep and during waking hours. Cheyne-Stokes respiration is characterized by periodic breathing featuring recurrent episodes of apnea alternating with episodes of rapid breathing. There is good evidence that replacement of the failing heart (heart transplant) cures central apnea in these patients. Temporary measures (e.g., those taken pending the availability of an organ donor) include the administration of drugs whose effects include respiratory stimulation, although these drugs are not universally effective in reducing the severity of Cheyne-Stokes apneas.

Congenital central hypoventilation syndrome
Congenital central hypoventilation syndrome (CCHS), often referred to by its older name "Ondines curse," is a rare and very severe inborn form of abnormal interruption and reduction in breathing during sleep. This condition involves a specific homeobox gene, PHOX2B, which guides maturation of the autonomic nervous system; certain loss-of-function mutations interfere with the brains development of the ability to effectively control breathing. There may be a recognizable pattern of facial features among individuals affected by this syndrome.Once almost uniformly fatal, CCHS is now treatable. Children who have it must have tracheotomies and access to mechanical ventilation on respirators while sleeping, but most do not need to use a respirator while awake. The use of a diaphragmatic pacemaker may offer an alternative for some patients. When pacemakers have enabled some children to sleep without the use of a mechanical respirator, reported cases still required the tracheotomy to remain in place because the vocal cords did not move apart with inhalation.Persons with the syndrome who survive to adulthood are strongly instructed to avoid certain condition-aggravating factors, such as alcohol use, which can easily prove lethal.

Treatment
After a patient receives a diagnosis, the diagnosing physician can provide different options for treatment. If central sleep apnea is medication-induced (e.g., opioids), reducing the dose or eventual withdrawal of the offending medication often improves CSA.
The FDA has recently approved a pacemaker-like implantable device called the remedē System for adult patients with moderate to severe central sleep apnea. After a commonly performed procedure, the device stimulates a nerve in the chest (phrenic nerve) to send signals to the large muscle that controls breathing (the diaphragm). It monitors respiratory signals during sleep and helps restore normal breathing patterns. The device is silent, activates automatically during the night, and does not require the patient to wear a mask.
Mechanical regulation of airflow and/or airway pressure:Treatment for central sleep apnea differs in that the device is set not at one constant optimal pressure but rather at two different settings, one for inhalation (IPAP) and for exhalation (EPAP), maintaining normal breathing rhythm by inflating the patients lungs at regular intervals whose specifics, such as the breathing rate and the duration of a single breath, can be programmed. Devices tailored to this purpose are known as BiPAP ("bilevel positive airway pressure") devices.
Both CPAP and BiPAP devices can be connected to a humidifier to humidify and heat the inhaled air, thus reducing unpleasant symptoms such as a sore throat or blocked nose that can result from inhaling cold, dry air.
CPAP and BiPAP devices can trigger central Apneas in those with obstructive sleep apnea requiring the use of an ASV (adaptive servo ventilation) device, which is also the proper machine for those who have central sleep apnea or mixed/complex apnea.

Epidemiology
Central sleep apnea is less prevalent than obstructive sleep apnea. In one study, CSA is stated to have a prevalence of 0.9% in comparison to OSA.There are many factors that increase the risk of developing CSA. Chronic opioid use produces a mean prevalence in central sleep apnea development of 24%. An estimate of 10% of chronic kidney disease (CKD) patients have a CSA diagnosis </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 Birthmark and can you explain it in depth? [/INST] A birthmark is a congenital, benign irregularity on the skin which is present at birth or appears shortly after birth—usually in the first month. They can occur anywhere on the skin. Birthmarks are caused by overgrowth of blood vessels, melanocytes, smooth muscle, fat, fibroblasts, or keratinocytes.
Dermatologists divide birthmarks into two types: pigmented birthmarks and vascular birthmarks. Pigmented birthmarks caused by excess skin pigment cells include: moles, café au lait spots, and Mongolian spots. Vascular birthmarks, also called red birthmarks, are caused by increased blood vessels and include macular stains (salmon patches), hemangiomas, and port-wine stains. A little over 1 in 10 babies have a vascular birthmark present by age 1. Several birthmark types are part of the group of skin lesions known as nevi or naevi, which is Latin for "birthmarks".
Birthmarks occur as a result of a localized imbalance in factors controlling the development and migration of skin cells. In addition, it is known that vascular birthmarks are not hereditary.

Pigmented types
Mole
Congenital melanocytic nevus is a type of  melanocytic nevus, the medical term for what is colloquially called a "mole", found in infants at birth. Occurring in about 1% of infants in the United States, it is located in the area of the head and neck 15% of the time, but may occur anywhere on the body. It may appear as light brown in fair-skinned people, to almost black in people with darker skin. Coming in a variety of sizes and appearances, they may be irregular in shape and flat, or raised and lumpy in appearance and feel. Such naevi can also manifest themselves as beauty marks, which most commonly appear on the face, neck or arms.

Café au lait spot
Café au lait spot macules may occur anywhere on the body. They are most commonly oval in shape and light brown, or milk coffee, in color. These birthmarks may be present at birth, or appear in early childhood, and do not fade much with age. One or two on an individual is common; however, four or more may be an indicator of neurofibromatosis. In the event of weight gain, the birthmark can stretch with the skin and become larger.

Mongolian spot
A Mongolian blue spot (dermal melanocytosis) is a benign flat congenital birthmark with wavy borders and irregular shape, most common among East Asians and Turkic people (excluding Turks of Asia Minor), and named after Mongolians. It is also extremely prevalent among East Africans and Native Americans. It normally disappears three to five years after birth and almost always by puberty. The most common color is blue, although they can be blue-gray, blue-black or even deep brown.
The Mongolian spot is a congenital developmental condition exclusively involving the skin. The blue colour is caused by melanocytes, melanin-containing cells, that are deep under the skin. Usually, as multiple spots or one large patch, it covers one or more of the lumbosacral area (lower back), the buttocks, sides, and shoulders. It results from the entrapment of melanocytes in the dermis during their migration from the neural crest to the epidermis during embryonic development.Among those who are not aware of the background of the Mongolian spots, it may sometimes be mistaken for a bruise indicative of child abuse.

Vascular types
Stork bite
Colloquially called a "stork bite", "angels kiss" or "salmon patch", telangiectatic nevus appears as a pink or tanned, flat, irregularly shaped mark on the knee, back of the neck, and/or the forehead, eyelids and, sometimes, the top lip. The skin is not thickened and feels no different from anywhere else on the body; the only difference is in appearance. Nearly half of all babies have such a birthmark.

Strawberry mark
An infantile hemangioma, colloquially called a strawberry mark, is a benign self-involuting tumor (swelling or growth) of endothelial cells, the cells that line blood vessels. It usually appears during the first weeks of life and resolves by age 10. It is the most common tumor of infancy.PHACES Syndrome, a rare condition that often involves brain, heart, and arterial abnormalities, is generally accompanied by the presence of large facial hemangiomas.  In such cases, what appears to be a small bruise or birthmark may grow rapidly and take on a puffy appearance in the first days or weeks of life.

Port-wine stain
Port-wine stains, also known as nevus flammeus and sometimes mistaken for strawberry marks, are present at birth and range from a pale pink in color, to a deep wine-red. Irregular in appearance, they are usually quite large, and caused by a deficiency or absence in the nerve supply to blood vessels. This causes vasodilation, the dilation of blood vessels, causing blood to pool or collect in the affected area. Over time, port-wine stains may become thick or develop small ridges or bumps, and do not fade with age. Such birthmarks may have emotional or social repercussions </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 Toxic anterior segment 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 Dermatosis papulosa nigra and can you explain it in depth? [/INST] Dermatosis papulosa nigra (DPN) is a condition of many small, benign skin lesions on the face, a condition generally presenting on dark-skinned individuals.: 638–9  DPN is extremely common, affecting up to 30% of Black people in the US. From a histological perspective, DPN resembles seborrheic keratoses. The condition may be cosmetically undesirable to some.
They should not be confused for Leser-Trélat sign, a sudden explosion of lesions due to a growing tumor.

Pathophysiology
The pathophysiology of DPN is unknown. Evidence of family history may suggest a genetic propensity.

Treatment
DPN lesions are benign and no treatment generally is indicated unless lesions are cosmetically undesirable. Surgical options including curettage, cryotherapy and laser therapy are options </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 Fanconi anemia and can you explain it in depth? [/INST] Fanconi anaemia (FA) is a rare genetic disease resulting in impaired response to DNA damage. Although it is a very rare disorder, study of this and other bone marrow failure syndromes has improved scientific understanding of the mechanisms of normal bone marrow function and development of cancer. Among those affected, the majority develop cancer, most often acute myelogenous leukemia (AML), and 90% develop aplastic anemia (the inability to produce blood cells) by age 40. About 60–75% have congenital defects, commonly short stature, abnormalities of the skin, arms, head, eyes, kidneys, and ears, and developmental disabilities. Around 75% have some form of endocrine problem, with varying degrees of severity.
FA is the result of a genetic defect in a cluster of proteins responsible for DNA repair via homologous recombination.Treatment with androgens and hematopoietic (blood cell) growth factors can help bone marrow failure temporarily, but the long-term treatment is bone marrow transplant if a donor is available. Because of the genetic defect in DNA repair, cells from people with FA are sensitive to drugs that treat cancer by DNA crosslinking, such as mitomycin C. The typical age of death was 30 years in 2000.FA occurs in about one per 130,000 births, with a higher frequency in Ashkenazi Jews and Afrikaners in South Africa. The disease is named after the Swiss pediatrician who originally described this disorder, Guido Fanconi. It should not be confused with Fanconi syndrome, a kidney disorder also named after Fanconi.

Signs and symptoms
FA is characterized by bone marrow failure, AML, solid tumors, and developmental abnormalities. Classic features include abnormal thumbs, absent radii, short stature, skin hyperpigmentation, including café au lait spots, abnormal facial features (triangular face, microcephaly), abnormal kidneys, and decreased fertility. Many FA patients (about 30%) do not have any of the classic physical findings, but diepoxybutane chromosome fragility assay showing increased chromosomal breaks can make the diagnosis. About 80% of FA will develop bone marrow failure by age 20.The first sign of a hematologic problem is usually petechiae and bruises, with later onset of pale appearance, feeling tired, and infections. Because macrocytosis usually precedes a low platelet count, patients with typical congenital anomalies associated with FA should be evaluated for an elevated red blood cell mean corpuscular volume.

Genetics
FA is primarily an autosomal recessive genetic disorder. This means that two mutated alleles (one from each parent) are required to cause the disease. The risk is 25% that each subsequent child will have FA. About 2% of FA cases are X-linked recessive, which means that if the mother carries one mutated Fanconi anemia allele on one X chromosome, a 50% chance exists that male offspring will present with Fanconi anemia.Scientists have identified 21 FA or FA-like genes: FANCA, FANCB, FANCC, FANCD1 (BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (BRIP1), FANCL, FANCM, FANCN (PALB2), FANCO (RAD51C), FANCP (SLX4), FANCQ (XPF), FANCS (BRCA1), FANCT (UBE2T), FANCU (XRCC2), FANCV (REV7), and FANCW (RFWD3). FANCB is the one exception to FA being autosomal recessive, as this gene is on the X chromosome. These genes are involved in DNA repair.The carrier frequency in the Ashkenazi Jewish population is about one in 90. Genetic counseling and genetic testing are recommended for families who may be carriers of Fanconi anemia.Because of the failure of hematologic components—white blood cells, red blood cells, and platelets—to develop, the bodys capabilities to fight infection, deliver oxygen, and form clots are all diminished.

Pathogenesis
Clinically, hematological abnormalities are the most serious symptoms in FA. By the age of 40, 98% of FA patients will have developed some type of hematological abnormality. However,  a few cases have occurred  in which older patients have died without ever developing them. Symptoms appear progressively, and often lead to complete bone marrow failure. While at birth, blood count is usually normal, macrocytosis/megaloblastic anemia, defined as unusually large red blood cells, is the first detected abnormality, often within the first decade of life (median age of onset is 7 years). Within the next 10 years, over 50% of patients presenting haematological abnormalities will have developed pancytopenia, defined as abnormalities in two or more blood cell lineages. This is in contrast to Diamond–Blackfan anemia, which affects only erythrocytes, and Shwachman–Diamond syndrome, which primarily causes neutropenia. Most commonly, a low platelet count (thrombocytopenia) precedes a low neutrophil count (neutropenia), with both appearing with relative equal frequencies. The deficiencies cause increased risk of hemorrhage and recurrent infections, respectively.As FA is now known to affect DNA repair, specifically homologous recombination, and given the current knowledge about dynamic cell division in the bone marrow, patients are consequently more likely to develop bone marrow failure, myelodysplastic syndromes, and acute myeloid leukemia (AML).

Myelodysplastic syndromes
MDSs, formerly known as preleukemia, are a group of bone marrow neoplastic diseases that share many of the morphologic features of AML, with some important differences. First, the percentage of undifferentiated progenitor cells, blast cells, is always less than 20%, with considerably more dysplasia, defined as cytoplasmic and nuclear morphologic changes in erythroid, granulocytic, and megakaryocytic precursors, than what is usually seen in cases of AML. These changes reflect delayed apoptosis or a failure of programmed cell death. When left untreated, MDS can lead to AML in about 30% of cases. Due to the nature of the FA pathology, MDS diagnosis cannot be made solely through cytogenetic analysis of the marrow. Indeed, it is only when morphologic analysis of marrow cells is performed, that a diagnosis of MDS can be ascertained. Upon examination, MDS-affected FA patients will show many clonal variations, appearing either prior or subsequent to the MDS. Furthermore, cells will show chromosomal aberrations, the most frequent being monosomy 7 and partial trisomies of chromosome 3q 15. Observation of monosomy 7 within the marrow is well correlated with an increased risk of developing AML and with a very poor prognosis, death generally ensuing within 2 years (unless prompt allogeneic hematopoietic progenitor cell transplant is an option).

Acute myeloid leukemia
FA patients are at elevated risk for the development of AML defined as presence of 20% or more of myeloid blasts in the marrow or 5 to 20% myeloid blasts in the blood. All of the subtypes of AML can occur in FA with the exception of promyelocytic. However, myelomonocytic and acute monocytic are the most common subtypes observed. Many MDS patients diseases evolve into AML if they survive long enough. Furthermore, the risk of developing AML increases with the onset of bone-marrow failure.Although risk of developing either MDS or AML before the age of 20 is only 27%, this risk increases to 43% by the age of 30 and 52% by the age of 40. Historically, even with a marrow transplant, about a quarter of FA patients diagnosed with MDS/ALS have died from MDS/ALS-related causes within two years, although more recent published evidence suggests that earlier allogeneic hematopoietic progenitor cell transplantation in children with FA is leading to better outcomes over time.

Bone marrow failure
The last major haematological complication associated with FA is bone marrow failure, defined as inadequate blood cell production. Several types of  failure are observed in FA patients, and generally precede MDS and AML. Detection of decreasing blood count is generally the first sign used to assess necessity of treatment and possible transplant. While most FA patients are initially responsive to androgen therapy and haemopoietic growth factors, these have been shown to promote leukemia, especially in patients with clonal cytogenetic abnormalities, and have severe side effects, including hepatic adenomas and adenocarcinomas. The only treatment left would be bone marrow transplant; however, such an operation has a relatively low success rate in FA patients when the donor is unrelated (30% 5-year survival). It is, therefore, imperative to transplant from an HLA-identical sibling. Furthermore, due to the increased susceptibility of FA patients to chromosomal damage, pretransplant conditioning cannot include high doses of radiation or immunosuppressants, thus increased chances of patients developing graft-versus-host disease. If all precautions are taken, and the marrow transplant is performed within the first decade of life, two-year probability of survival can be as high as 89%. However, if the transplant is performed at ages older than 10, two-year survival rates drop to 54%.A recent report by Zhang et al. investigates the mechanism of bone marrow failure in FANCC-/- cells. They hypothesize and successfully demonstrate that continuous cycles of hypoxia-reoxygenation, such as those seen by haemopoietic and progenitor cells as they migrate between hyperoxic blood and hypoxic marrow tissues, leads to premature cellular senescence and therefore inhibition of haemopoietic function. Senescence, together with apoptosis, may constitute a major mechanism of haemopoietic cell depletion occurred in bone marrow failure.

Molecular basis
There are 19 genes responsible for FA, one of them being the breast-cancer susceptibility gene BRCA2. They are involved in the recognition and repair of damaged DNA; genetic defects leave them unable to repair DNA. The FA core complex of 8 proteins is normally activated when DNA stops replicating because of damage. The core complex adds ubiquitin, a small protein that combines with BRCA2 in another cluster to repair DNA (see Figure Recombinational repair of DNA double-strand damage). At the end of the process, ubiquitin is removed.Recent studies have shown that eight of these proteins, FANCA, -B, -C, -E, -F, -G, -L and -M, assemble to form a core protein complex in the nucleus. According to current models, the complex moves from the cytoplasm into the nucleus following nuclear localization signals on FANCA and FANCE. Assembly is activated by replicative stress, particularly DNA damage caused by cross-linking agents (such as mitomycin C or cisplatin) or reactive oxygen species (ROS) that is detected by the FANCM protein.Following assembly, the protein core complex activates FANCL protein which acts as an E3 ubiquitin-ligase and monoubiquitinates FANCD2.Monoubiquitinated FANCD2, also known as FANCD2-L, then goes on to interact with a BRCA1/BRCA2 complex (see Figure Recombinational repair of DNA double-strand damage). Details are not known, but similar complexes are involved in genome surveillance and associated with a variety of proteins implicated in DNA repair and chromosomal stability. With a crippling mutation in any FA protein in the complex, DNA repair is much less effective, as shown by its response to damage caused by cross-linking agents such as cisplatin, diepoxybutane and Mitomycin C. Bone marrow is particularly sensitive to this defect.
In another pathway responding to ionizing radiation, FANCD2 is thought to be phosphorylated by protein complex ATM/ATR activated by double-strand DNA breaks, and takes part in S-phase checkpoint control. This pathway was proven by the presence of radioresistant DNA synthesis, the hallmark of a defect in the S phase checkpoint, in patients with FA-D1 or FA-D2. Such a defect readily leads to uncontrollable replication of cells and might also explain the increase frequency of AML in these patients.

Spermatogenesis
In humans, infertility is one of the characteristics of individuals with mutational defects in the FANC genes.  In mice, spermatogonia, preleptotene spermatocytes, and spermatocytes in the meiotic stages of leptotene, zygotene and early pachytene are enriched for FANC proteins.  This finding suggests that recombinational repair processes mediated by the FANC proteins are active during germ cell development, particularly during meiosis, and that defects in this activity can lead to infertility.

Neural stem cell homeostasis
Microphthalmia and microcephaly are frequent congenital defects in FA patients </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 Syndesmophyte 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 Transient acantholytic dermatosis and can you explain it in depth? [/INST] Grovers disease (GD) is a polymorphic, pruritic, papulovesicular dermatosis characterized histologically by acantholysis: 529  with or without dyskeratosis.  Once confirmed, most cases of Grovers disease last six to twelve months, which is why it was originally called "transient". However it may last much longer. Nevertheless, it is not to be confused with relapsing linear acantholytic dermatosis.

Signs and symptoms
Grovers disease often starts quite suddenly. There are intensely itchy spots on the central back, mid chest and occasionally elsewhere. Frequently, it follows sweating or some unexpected heat stress.
The itchy eruption lasts an average of 10–12 months. It is characterized by papules and papulovesicles with excoriations occurring on the chest, back, lower sternum, arms, and thighs.  The papules are most commonly found on the mid chest.
Sometimes the features of Grovers are found in people who do not itch or have a conspicuous rash.  Most of the people with Grovers who visit a dermatologist, however, itch a lot.

Cause
The cause of Grovers disease is unknown </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 Trichoblastoma 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 Pacman dysplasia and can you explain it in depth? [/INST] Pacman dysplasia  is a lethal autosomal recessive skeletal dysplasia.  The dysplasia is present during fetal development.

References
Wilcox WR, Wenger DA, Lachman RS, Rimoin DL (2005). "Distinguishing Pacman dysplasia from mucolipidosis II: comment on Saul et al. [2005]". Am J Med Genet A. 135 (3): 333. doi:10.1002/ajmg.a.30717. PMID 15887286. S2CID 38848656.
Saul RA, Proud V, Taylor HA, Leroy JG, Spranger J (2005). "Prenatal mucolipidosis type II (I-cell disease) can present as Pacman dysplasia". Am J Med Genet A. 135 (3): 328–32. doi:10.1002/ajmg.a.30716. PMID 15887289. S2CID 2151584.
Wilcox WR, Lucas BC, Loebel B, Bachman RP, Lachman RS, Rimoin DL (1998). "Pacman dysplasia: report of two affected sibs". Am J Med Genet. 77 (4): 272–6. doi:10.1002/(SICI)1096-8628(19980526)77:4<272::AID-AJMG4>3.0.CO;2-P. PMID 9600734.
Shohat M, Rimoin DL, Gruber HE, Lachman R (1993). "New epiphyseal stippling syndrome with osteoclastic hyperplasia" </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 Axillary lymphadenopathy 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 Radial neuropathy and can you explain it in depth? [/INST] Radial neuropathy  is a type of mononeuropathy which results from acute trauma to the radial nerve that extends the length of the arm. It is known as transient paresthesia when sensation is temporarily abnormal.

Signs and symptoms
Symptoms of radial neuropathy vary depending on the severity of the trauma; however, common symptoms may include wrist drop, numbness on the back of the hand and wrist, and inability to voluntarily straighten the fingers. Loss of wrist extension is due to loss of the ability to move of the posterior compartment of forearm muscles. In the event of lacerations to the wrist area the symptom would therefore be sensory. Additionally, depending on the type of trauma, other nerves may be affected such as the median nerve and axillary nerves.

Causes
There are many ways to acquire radial nerve neuropathy, including:
Upper arm - a fracture of the bone
Elbow - entrapment of the nerve
Wrist - elbow deformity and soft-tissue masses
Axilla - here the most common cause is compression. However, a dislocation of the humerus is a possible factor as well. It could also be due to brachial plexus compression.

Mechanism
The mechanism of radial neuropathy is such that it can cause focal demyelination and axonal degeneration. These would be caused via laceration or compression of the nerve in question.

Diagnosis
Radial neuropathy may be diagnosed using MRI, ultrasound, nerve conduction study or electromyography (EMG).

Treatment
The treatment and management of radial neuropathy can be achieved via the following methods:
Physical therapy or occupational therapy
Surgery (depending on the specific area and extent of damage)Tendon transfer (the origin remains the same but insertion is moved)Splinting

Prognosis
Radial neuropathy is not necessarily permanent, though there could be partial loss of movement or sensation. Complications include deformity of the hand in some individuals. If the injury is axonal (the underlying nerve fiber itself is damaged), recovery may take months or years and full recovery may never occur. EMG and nerve conduction studies are typically performed to diagnose the extent and distribution of the damage, and to help with prognosis for recovery.

Culture and society
There are a number of terms used to describe radial nerve injuries, which are dependent on the causation factor such as:

Honeymoon palsy from another individual sleeping on and compressing ones arm overnight.
Saturday night palsy from falling asleep with ones arm hanging over the arm rest of a chair, compressing the radial nerve.
Squash palsy, from traction forces associated with the sport squash, happens to squash players during periods between matches.

See also
Crutch paralysis
Peripheral neuropathy

References
Further reading
Cartwright, Michael S.; Yoon, Joon Shik; Lee, Kyu Ho; Deal, Nicole; Walker, Francis O. (1 April 2011). "Diagnostic Ultrasound for Traumatic Radial Neuropathy". American Journal of Physical Medicine & Rehabilitation. 90 (4): 342–343. doi:10.1097/PHM.0b013e3181e29daa </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 Uncombable hair syndrome and can you explain it in depth? [/INST] Uncombable hair syndrome (UHS) is a rare structural anomaly of the hair with a variable degree of effect. It is characterized by hair that is silvery, dry, frizzy, wiry, and impossible to comb. It was first reported in the early 20th century. It typically becomes apparent between the ages of 3 months and 12 years. UHS has several names, including "pili trianguli et canaliculi," "cheveux incoiffables," and "spun-glass hair." This disorder is believed to be autosomal recessive in most instances, but there are a few documented cases where multiple family members display the trait in an autosomal dominant fashion. Based on the current scientific studies related to the disorder, the three genes that have been causally linked to UHS are PADI3, TGM3, and TCHH. These genes encode proteins important for hair shaft formation. Clinical symptoms of the disorder arise between 3 months and 12 years of age. The quantity of hair on the head does not change, but hair starts to grow more slowly and becomes increasingly "uncombable." To be clinically apparent, 50% of all scalp hair shafts must be affected by UHS. This syndrome only affects the hair shaft of the scalp and does not influence hair growth in terms of quantity, textural feel, or appearance on the rest of the body.

Presentation
The hair is normal in quantity and is usually silvery-blond or straw-colored. It is disorderly, stands out from the scalp, and cannot be combed flat, but it can be controlled by braiding methods. This is caused by mutations in one of three possible genes; PADI3, TGM, or TCHH. These genes code for proteins involved in hair shaft formation and improvement often occurs in later childhood. Uncombable hair syndrome is mainly autosomal recessive, but it can also be autosomal dominant because there are other involved genes that have yet to be identified.By early adulthood, phenotypic symptoms of UHS spontaneously improve or disappear. The hair of people with UHS may eventually lie flat and appear near normal in texture by adolescence or early adulthood for unknown reasons. Basmanav et al. have suggested that either different, non-mutated isoforms of the hair-forming enzymes are produced as we age, or that aging-related mechanistic changes in hair such as greater diameter and length help resolve UHS.

Symptoms
Coarse hair
Trichodysplasia
White hair
Woolly hair
Patchy baldness

Cause
As one would expect from the name, individuals affected by this disorder have difficulty managing and grooming their hair. Affected individuals usually possess blonde or silver hair that may be present at birth or develop over time. The hair is wiry, frizzy, and stands straight out from the scalp. It is often dry but not fragile or brittle. This is due to several structural abnormalities in the hair shaft. A cross-section of the hair shaft from affected individuals reveals a kidney bean, triangular, or oval diameter, unlike the circular shaft shape displayed in straight hair. This irregularity in the diameter of the hair shaft prevents the hair from lying neatly against adjacent hair fibers. Trichohyalin (TCHH) is a structural protein responsible for the proper cylindrical fiber topology of the hair shaft. TCHH binds other TCHH and keratin-intermediate filaments creating the proper cross-links and cylindrical shape of the hair shaft. PADI3 and TGM3 are two enzymes responsible for post-translational modification of TCHH important for cross-linking of TCHH within the hair. In Uncombable Hair Syndrome mutations in TCHH, PADI3, or TGM3 result in improper cross-linking and the resulting irregular shape of the hair shaft.The particular defect in TCHH as a structural component of hair may be a defect of deimination. Deimination converts the amino acid arginine to the amino acid citrulline. This conversion is done by calcium-dependent enzymes known as peptidylarginine deiminases (PADs). PADI3 is a member of this enzyme class. One study reported PAD involvement in skin and skin-related diseases, particularly at the hair follicle. Alterations to PAD activity resulted in the development of Uncombable Hair Syndrome. Another study examined the transglutaminase (TG) family of enzymes and their involvement in UHS. This family of enzymes includes TGM3, which is expressed in epidermal cells. Mutations in TGM3 may therefore reduce or alter the intermolecular cross-linking important for hair shaft formation, leading to Uncombable Hair Syndrome.Another molecular mechanism of UHS was proposed by Ralph Trueb in 2003. He suggested that premature keratinization of the inner hair root forms a rigid sheath that alters the shape of a hair strand as it grows out of the root.

Uncombable Hair Syndrome 1
Uncombable Hair Syndrome 1 is caused by a defect in the Trichohyalin gene (TCHH) found in hair follicles and some parts of hair strands. It serves as a scaffold protein, with involucrin, in cell envelope organization. The trichohyalin gene is produced and changed by other proteins and to molecules such as keratin intermediate filaments to form organized cross-links. These networks provide the hair shaft with its cylindrical form. This, in turn, leads to frizzy hair, resulting in uncombable hair. The chromosomal location for this TCHH gene is located on chromosome 1. The condition usually improves over time, and will have better hair structure once it reaches adolescence.It is still being decided whether TCHH is autosomal dominant, or autosomal recessive. In an experiment, they identified the causative mutations of UHS in 3 genes; PADI3, TGM3, and TCHH in 11 children. These children carried homozygous/heterozygous mutations in those 3 genes, which resulted in autosomal recessive inheritance. Because it was identified as autosomal recessive inheritance, scanning electron microscopy was performed in order to rule out autosomal dominance since this type of gene can also be autosomal dominant to a certain extent.

Uncombable Hair Syndrome 2
Uncombable Hair Syndrome 2 is caused by a defect in Transglutaminase 3 (TGM3) gene. This gene helps provide instructions for creating an enzyme known as Transglutaminase 3. This gene is found in skin cells known as keratinocytes and corneocytes. This helps frame the scalp, root, and strands of hair. It helps the molecules bind
proteins. The cross-links help provide strength and structure to the cells skin and hair cells. Chromosomal location of Transglutaminase 3 is located on chromosome 20.An experiment was done where Transglutaminase 3 reduced in esophageal cancer. They used western blot analysis and polymerase chain reaction. With the 58 pairs of tissues that were sampled, it was confirmed that Transglutaminase 3 is closely related to growth proliferation and migration. However, the over-expression of this gene induces cell proliferation, migration, and invasion, and promotes programmed cell death. This came to show that Transglutaminse 3 will be a candidate growth and could function as a helpful biomarker and a therapeutic target to esophageal cancer treatment.

Uncombable Hair Syndrome 3
Uncombable Hair Syndrome 3 is caused by a defect in the PADI3 gene (peptidylarginine-deiminase 3) and is located on chromosome 1.  This defect apparently is the most common cause of UHS. The PADI3 gene provides instructions for creating an enzyme called peptidylargine deiminase 3. PADI3 is found within the skins extreme external surface, inside cells called karinocytes. The protein also contributes to hair follicles that are specialized structures within the skin where development happens. In these hair follicles, the PADI3 gene adjusts proteins that are giving structure to the hair strand. The PADI3 gene also involves a process called deimination. This process modifies the proteins intuitive with other proteins.An experiment was performed in where the PADI3 is found in central centrifugal cicatricial alopecia which is mostly found in African women that suggests an autosomal dominant trait to occur. With this experiment, they performed a process called immunoblotting and immunofluorescence. With immunoblotting, it appeared that the transfected cells had a marginally lower expression of the mutant compared to the wild-type. With immunofluorescence it resulted in an irregular intracellular location of the protein. Therefore, it helped conclude that there was a reduction in enzymatic action that encodes a protein to hair shaft arrangement, which relates to central centrifugal cicatricial alopecia(CCCA).

Diagnosis
Differential diagnosis
Other syndromes with hair abnormalities may also show features of uncombable hair syndrome such as Rapp–Hodgkin ectodermal dysplasia syndrome, loose anagen syndrome, EEC syndrome (ectodermal dysplasia, ectrodactyly and cleft lip/palate) and familial tricho-odonto-onychial ectodermal dysplasia with syndactyly. However, unlike these conditions, uncombable hair syndrome alone is not associated with physical, neurologic, or mental abnormalities.According to the U.S. National Institute of Health, the condition tends to develop in childhood (age 3-12) and resolve by adolescence.Another observation that can be made when detecting uncombable hair syndrome in individuals is by observing the hair shaft under a special microscope. When individual hair strands are being viewed, the hair is triangular or kidney-shaped and has a longitudinal groove on one or two faces.Clinical diagnosis of UHS can be confirmed molecularly by performing high-resolution microscopy on hair shafts using scanning electron microscopy (SEM). SEM allows for the visualization of hair shaft cross-sections, which can appear triangular, heart-shaped, kidney-shaped, flat, or longitudinally grooved. Interestingly, multiple different cross sections can appear on a single shaft of hair. An alternative method for confirming a UHS diagnosis molecularly is by embedding UHS hairs into paraffin. Due to the atypical shape of the hair shafts in UHS, UHS hair will refract light differently than typical hair, causing a glistening effect.

Treatment
Although it tends to regress naturally later in childhood, there is no definitive treatment for Uncombable Hair Syndrome. The only recommended treatment is using soft brushes and gentle conditioners. It is also recommended to avoid hair treatments that can be harsh on hair (excessive brushing, blow drying, perms, or coloring hair). Biotin supplements have also been used as a treatment, due to their historical utility in controlling nail fragility and improving hair growth after 4 months of supplementation.

Epidemiology
While UHS is thought to be extremely rare, its precise frequency and prevalence is unknown. As of 2016, there were ~100 case studies of UHS in the scientific literature, and as of 2020, there are a few more documented case studies.UHS has been found in patients who also have diseases such as ectodermal dysplasia and loose anagen hair syndrome. While sometimes observed with other disorders, it is believed that Uncombable Hair Syndrome is an isolated disease.

History
The syndromes name comes directly from its abnormal, frizzy appearance that “totally resists any effort to control it with brush or comb.” A possible case of uncombable hair syndrome was reported in 1912 by A.F. Le Double and F. Houssay. The syndrome was described in 1973 by A. Dupré, P. Rochiccioli, and J.L. Bonafé, who named it "cheveux incoiffables". Later that year it was independently described as "spun-glass hair" by J.D. Stroud and A.H. Mehregan. The currently used term was coined in the early 1980s </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 Subacute cutaneous lupus erythematosus 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 3C syndrome and can you explain it in depth? [/INST] 3C syndrome is a rare condition whose symptoms include heart defects, cerebellar hypoplasia, and cranial dysmorphism. It was first described in the medical literature in 1987 by Ritscher and Schinzel, for whom the disorder is sometimes named.

Signs and symptoms
The classical triad of symptoms that defines 3C syndrome includes certain heart defects, hypoplasia (underdevelopment) of the cerebellum, and cranial dysmorphisms, which can take various forms. The heart defects and cranial dysmorphisms are heterogeneous in individuals who are all classed as having Ritscher-Schinzel syndrome.Heart defects commonly seen with Ritscher-Schinzel syndrome are associated with the endocardial cushion and are the most important factor in determining a diagnosis. The mitral valve and tricuspid valve of the heart can be malformed, the atrioventricular canal can be complete instead of developing into the interatrial septum and interventricular septum, and conotruncal heart defects, which include tetralogy of Fallot, double outlet right ventricle, transposition of the great vessels, and hypoplastic left heart syndrome. Aortic stenosis and pulmonary stenosis have also been associated with 3C syndrome.The cranial dysmorphisms associated with 3C syndrome are heterogeneous and include a degree of macrocephaly, a large anterior fontanel, a particularly prominent occiput and forehead, ocular hypertelorism (wide-set eyes), slanted palpebral fissures, cleft palate, a depressed nasal bridge, cleft palate with associated bifid uvula, low-set ears, micrognathia (an abnormally small jaw), brachycephaly (flattened head), and ocular coloboma. Low-set ears are the most common cranial dysmorphism seen in 3C syndrome, and ocular coloboma is the least common of the non-concurrent symptoms (cleft lip co-occurring with cleft palate is the least common).Cranial dysplasias associated with 3C syndrome are also reflected in the brain. Besides the cerebellar hypoplasia, cysts are commonly found in the posterior cranial fossa, the ventricles and the cisterna magna are dilated/enlarged, and Dandy–Walker malformation is present. These are reflected in the developmental delays typical of the disease. 75% of children with 3C syndrome have Dandy-Walker malformation and hydrocephalus.Signs and symptoms in other body systems are also associated with 3C syndrome. In the skeletal system, ribs may be absent, and hemivertebrae, syndactyly (fusion of fingers together), and clinodactyly (curvature of the fifth finger) may be present. In the GI and genitourinary systems, anal atresia, hypospadia (misplaced urethra), and hydronephrosis may exist. Adrenal hypoplasia and growth hormone deficiency are associated endocrine consequences of Ritscher-Schinzel syndrome. Some immunodeficiency has also been reported in connection with 3C syndrome. Many children with the disorder die as infants due to severe congenital heart disease. The proband of Ritscher and Schinzels original study was still alive at the age of 21. A fetus with 3C syndrome may have an umbilical cord with one umbilical artery instead of two.

Genetics
3C syndrome is an autosomal recessive disease, caused by a mutation on the long arm of chromosome 8 at 8q24.13, the locus for KIAA0196, the gene for the protein strumpellin. Strumpellin is highly expressed in skeletal muscle cells and mutations in it are also associated with spastic paraplegia. Strumpellin is involved in endosomal transport and cell death processes. The mutation occurs at a splice site  and causes a substantial decrease in the amount of strumpellin produced by the cell. The phenotype is similar to 6pter-p24 deletion syndrome and 6p25 deletion syndrome but has a different etiology.
Screening for the condition prenatally may be done with ultrasound.
First-trimester ultrasounds can detected nuchal abnormalities
Second-trimester ultrasounds can pick up characteristic major structural abnormalities.Prenatal diagnosis is possible through genetic testing.
Chorionic villus sampling or chorionic villus biopsy (CVS) in the first-trimester.
Amniocentesis in the second-trimester.Because 3C syndrome is an autosomal recessive disorder, parents with one child with the disorder have a 25% chance of having another child with the disorder.

Diagnosis
Differential diagnosis
There is an overlap in symptoms between 3C syndrome and Joubert syndrome. Joubert syndrome often manifests with similar cerebellar hypoplasia and its sequelae, including hyperpnea, ataxia, changes in eye movement, and cleft lip and palate. Occasionally, Joubert syndrome will include heart malformations. Brachmann–de Lange syndrome must also be differentiated from 3C syndrome. It presents with similar craniofacial and heart abnormalities and can include Dandy–Walker phenotype, making it difficult to distinguish. Dandy-Walker malformation is also occasionally seen in Ellis–Van Creveld syndrome, which is characterized by heart defects and malformed alveolar ridge. Many disorders include the Dandy–Walker phenotype and thus it is not pathognomonic for 3C syndrome.CHARGE syndrome can also be misdiagnosed </s>