<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 Kniest dysplasia and can you explain it in depth? [/INST] Kniest dysplasia is a rare form of dwarfism caused by a mutation in the COL2A1 gene on chromosome 12. The COL2A1 gene is responsible for producing type II collagen. The mutation of COL2A1 gene leads to abnormal skeletal growth and problems with hearing and vision. What characterizes Kniest dysplasia from other type II osteochondrodysplasia is the level of severity and the dumb-bell shape of shortened long tubular bones.This condition was first described by Dr. Wilhelm Kniest in 1952, publishing the case history of a 3 1⁄2 year-old girl. Dr. Kniest noticed that his patient had bone deformities and restricted joint mobility. The patient also had short stature and later developed blindness, resulting from retinal detachment and glaucoma. Upon analysis of the patients DNA in 1992, sequencing revealed deletion of a 28 base pair sequence encompassing a splice site in exon 12 and a G to A transition in exon 50 of the COL2A1 gene.This condition is very rare and occurs less than 1 in 1,000,000 people. Males and females have equal chances of having this condition. Currently, there is no cure for Kniest dysplasia. Alternative names for Kniest Dysplasia can include Kniest syndrome, swiss cheese cartilage syndrome, Kniest chondrodystrophy, or metatrophic dwarfism type II.

Signs and symptoms
Because collagen plays an important role in the development of the body, people with Kniest Dysplasia will typically have their first symptoms at birth. These symptoms can include:
Musculoskeletal Problems
Short limbs
Shortened body trunk
Flattened bones in the spine (platyspondyly)
kyphoscoliosis
Scoliosis (Lateral curvature of the spine)
Early development of arthritis
Respiratory problems
Respiratory tract infection
Difficulty breathing
Eye problems
Severe myopia (near-sightedness)
Cataract (cloudiness in the lens of the eye)
Cranial structure may elongate the eyeball, causing a thinning of the retina, thereby predisposing retinal detachment
Hearing problems
progressive hearing loss
ear infectionsMost symptoms are chronic and will continue to worsen as the individual ages. It is essential to have regular checkups with general doctors, orthopedist, ophthalmologists, and/or otorhinolaryngologists. This will help to detect whether there are any changes that could cause concern.

Genetics
Mechanism
Studies have shown that a mutated COL2A1 gene is responsible for all type II chondroldysplasias, including Kniest dysplasia. It is believed that point mutations or the alteration of splice sites in COL2A1 domains will result in Kniest Dysplasia. The COL2A1 domain typically spans between exon 12 and 24. Mutations that occur at a splice donor site results in the loss of function at that site. This leads to the skipping of the exon and deletion of amino acids. The loss of these amino acids result in an abnormal procollagen II structure. The structure is not stable like the normal procollagen II structure and is normally degraded at a faster rate.

Diagnosis
Family/medical history
Kniest dysplasia is an autosomal dominant condition. This means that the person only needs to have one copy of the mutated gene in order to have the condition. People with a family history are at a higher risk of having the disease than people with no family history. A random mutation in the gene can cause a person with no family history to also have the condition.

Diagnostic techniques
A combination of medical tests are used to diagnosis Kniest dysplasia. These tests can include:
Computer Tomography Scan (CT scan) - This test uses multiple images taken at different angles to produce a cross-sectional image of the body.
Magnetic Resonance Imaging (MRI) - This technique proves detailed images of the body by using magnetic fields and radio waves.
EOS Imaging - EOS imaging provides information on how musculoskeletal system interacts with the joints. The 3D image is scanned while the patient is standing and allows the physician to view the natural, weight-bearing posture.
X-rays - X-ray images will allow the physician to have a closer look on whether or not the bones are growing abnormally.The images taken will help to identify any bone anomalies. Two key features to look for in a patient with Kniest dysplasia is the presence of dumb-bell shaped femur bones and coronal clefts in the vertebrae </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Low-set ears 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 Pulpitis and can you explain it in depth? [/INST] Pulpitis is inflammation of dental pulp tissue. The pulp contains the blood vessels, the nerves, and connective tissue inside a tooth and provides the tooth’s blood and nutrients. Pulpitis is mainly caused by bacterial infection which itself is a secondary development of caries (tooth decay). It manifests itself in the form of a toothache.

Signs and symptoms
Increased sensitivity to stimuli, specifically hot and cold, is a common symptom of pulpitis. A prolonged throbbing pain may be associated with the disease.  However, pulpitis can also occur without any pain.Reversible pulpitis is characterised by intermittent, brief discomfort initiated by a hot, cold or sweet stimulus. The pain evoked is of short duration and there is no lingering or spontaneous pain. The pain ceases within a short period after removal of the stimulus. With a reversible pulpitis, sleep is usually not affected and no analgesics are necessary.  Usually, no atypical change is evident on the radiograph. Pulp vitality tests are positive and it is possible to preserve a healthy vital pulp.
Irreversible pulpitis, in contrast, is characterised by a constant severe pain that arises without provocation. Characteristics may include sharp pain upon thermal stimulus, lingering thermal pain, spontaneity, and referred pain. Sometimes, the pain may be accentuated by postural changes such as lying down or bending over. If a stimulus is applied, the pain persists for minutes or hours after removal of the stimulus. These indicate that the vital inflamed pulp is not capable of healing and it is often indicated for the pulp to be removed as it is too damaged. Sleep may be disturbed and over-the-counter painkillers are often taken in an attempt to provide relief, but are usually ineffective.

Causes
Pulpitis may be caused by bacteria from dental caries that penetrate through the enamel and dentin to reach the pulp, or it may be mechanical, a result of trauma, such as physical damage to the tooth.
Inflammation is commonly associated with a bacterial infection but can also be due to other insults such as repetitive trauma or in rare cases periodontitis. The inflammation of dental pulp is mainly caused by an opportunistic infection of the pulp by a commensal oral microorganism. To reach the pulp, the most common route of the microorganism is through dental caries as well as from trauma, dentinal cracks and exposed dentin. Exposed dentin gives the microorganisms access to the pulp of the tooth through the dentinal tubules. In the case of penetrating decay, the pulp chamber is no longer sealed off from the environment of the oral cavity.When the pulp becomes inflamed, pressure begins to build up in the pulp cavity, exerting pressure on the nerve of the tooth and the surrounding tissues. Pressure from inflammation can cause mild to extreme pain, depending upon the severity of the inflammation and the bodys response. Unlike other parts of the body where pressure can dissipate through the surrounding soft tissues, the pulp cavity is very different. It is surrounded by dentin, a hard tissue that does not allow for pressure dissipation, so increased blood flow, a hallmark of inflammation, will cause pain.The infection can also come from the apical foramen of the root. Cells in the dental pulp trigger an immune response from the invasion of foreign microorganisms. The inflammation of the pulp is a side effect of the immune response and causes pain.Pulpitis can often create so much pressure on the tooth nerve that the individual will have trouble locating the source of the pain, confusing it with neighboring teeth, called referred pain. The pulp cavity inherently provides the body with an immune system response challenge, which makes it very difficult for a bacterial infection to be eliminated.If the teeth are denervated, this can lead to irreversible pulpitis, depending on the area, rate of infection, and length of injury. This is why people who have lost their dental innervation have a reduced healing ability and increased rate of tooth injury. Thus, as people age, their gradual loss of innervation leads to pulpitis.

Responses
Inflammatory response
In the pulp, just as in other areas of the body, inflammation can be present.  Inflammation of the pulp does not take place until the bacteria in the decay have reached the pulp.  Bacterial products may reach the pulp much earlier and begin the inflammatory response.  The inflammation may be acute or chronic because just like other tissues in the body, the pulp will react to irritants with innate and/or adaptive immune responses.Innate immunity in the pulp is not specific but uses receptors to recognize molecular patterns common to microbes to initiate bacterial killing (phagocytosis). The components of the innate response of the dentin/pulp complex to caries include at least the following six: (1) outward flow of dentinal fluid; (2) odontoblasts; (3) neuropeptides and neurogenic inflammation; (4) innate immune cells, including immature dendritic cells (DCs), natural killer (NK) cells, and T cells, as well as (5) their cytokines and (6) chemokines. Although the first two items are not classic components of innate immunity, they are uniquely involved in the initial inflammatory response to caries.Odontoblasts, (the cells that form dentin) have cellular processes that extend into dentinal tubules and are the first to encounter the caries bacterial antigens.  They express low levels of interleukin 8 (IL-8) and genes related to chemokines and chemokine receptors.  The odontoblasts have been shown to attract immature dendritic cells.Dendritic cells (DCs) are a heterogeneous leukocyte (white blood cell) population.  DCs in healthy peripheral tissues (steady state) are in an immature state.  The cells are capable of sensing microbes as well as antigen capture and processing capabilities.  A rapid accumulation of pulpal DCs has been observed beneath cavity preparations, and an increased number of DCs accumulated under caries.  Immature DCs are therefore considered to be part of the innate phase of pulpal immune response.Persistent infection leads to the activation of adaptive immunity.  A transition to an adaptive immune response will take place in the dental pulp as the caries and bacteria approach the pulp.  Antigens are recognized individually and lines of lymphocytes are developed to produce specific antibodies which attach to the recognized cells and initiate their destruction. Phagocytes remove the remains.  B cells and T cells are the major lymphocytes involved.A variety of cytokines have been observed in the pulp. Patients with symptomatic and asymptomatic irreversible pulpitis have been shown to have an almost 23-fold increase in the cytokine IL-8 in the pulp. Cytokines in the pulp interact with each other.  The ultimate effect on pulpal inflammation and healing is dependent upon the integrated actions of these inflammatory mediators.In addition to the lymphocytes, macrophages also provide defense against certain intracellular pathogens. Activated macrophages can function as class II antigen-presenting cells, similar to pulpal dendritic and B cells. In addition, activated macrophages secrete many inflammatory mediators.Macrophages in the pulp become activated after receiving two signals. The first is a priming stimulus and the second is an activating signal. The priming stimulus is secreted by activated T-helper cells. The activating stimulus may include bacterial lipopolysaccharides, muramyl dipeptide, and other chemical mediators.Macrophages are professional phagocytes in innate immune responses. Activated macrophages are effective killers that eliminate pathogens in both innate and adaptive immune responses, and are also important in tissue homeostasis, through the clearance of senescent cells, and in remodeling and repair of tissue after inflammation. The number of macrophages increases with the progression of caries and is always higher than that of DCs at all stages of the caries invasion.

Neurological responses
According to the Brännströms hydrodynamic theory, activated nociceptors from fluid movement and other irritants through the patent dentine tubules result in pulp pain. Unmyelinated, slow conducting C-fibers aid in feeling a slowset, burning pain. According to neuronal studies, 70-80% of pulpal axons are unmyelinated. Highly myelinated Aδ-fibers, which allow for fast conduction, are responsible for the sharp, shooting pain.Thus, the stimulus intensities are based on various fibers. Fast-conducting Aβ and Aδ-fibers provide the lowest stimulus intensities (typically referred to as prepain sensations), and those sensations eventually receive higher stimulation levels. The dull aches are associated with C-fibers and slow Aδ-fibers. As inflammation intensifies, the A-fibers are increasingly activated. C-fiber innervation and Aδ-fibers are polymodal receptors that are sensitive to capsaicin and inflammatory mediators.The pain mechanisms associated with pulpitis are similar to those of the rest of the body (i.e. receptors, intracellular signaling, transmitters, etc.). The inflammatory mediators act on specific receptors relating to nociceptive neurons, leading to the production of second messengers and activation of phospholipases and protein kinases. The second messengers regulate receptors ion channels that deal with sensitization. The ion channels open based on pain stimuli propagating action potentials in sensory neurons.In order for excitability and conduction to occur, voltage-gated sodium channels must be activated. Changes in sodium channel (NaCH)  expression occur after inflammatory lesions, which may generate different pain states seen when neuronal fibers are activated. Studies have been done on major NaCh isoforms to examine expression patterns. Nav1.6 nodal accumulations do not vary in size or immunofluorescence staining activity in typical or atypical nodal sites; however, the proportion of typical nodal sites decreases and increase in atypical nodes in painful tooth samples compared to normal tooth samples.  Nav1.7 has an increased expression in typical and atypical nodal sites in painful samples. As a result, an increased co-expression of multiple isoforms at demyelinating nodal sites in painful dental pulp. This isoforms of sodium channels may be a main factor in pain sensations due to their production of axonal excitability properties.Neuropeptides are increasingly being researched for having a role in molecular mechanisms involved with pain, including ion channels and inflammation. Substance P (SP) is a neuropeptide produced by capsaicin neuron cell bodies (localized in trigeminal ganglia and dorsal root) and plays a major role in dental pain and inflammation. Other peptides include cGRP, galanin, somatostatin, and neurokinin A-B. The biological effects of SP are expressed by the binding of specific G protein-coupled NK receptors. Interaction with SP receptors induces vasodilation and allows for plasma extravasation and mastocyte degranulation. SP is highly expressed in dental pulp and dentin. When pain, thermal, and/or chemical stimulation is present, SP production and release increases. Current studies focus on whether controlling Substance P expression may control tooth pain.In addition, dental caries is more likely to develop pulpitis due to less time for the dental pulp to react and protect itself by occluding the dentinal tubules. Based on the tooth injury, sensory nerve fibers react to pulpitis by growing terminal branches into the adjacent surviving pulp, which also changes the cytochemical phenotype. This neural growth typically lasts few a few days and function and form is retained. Thus, pain is poorly localized, and the level of pain stemming from pulpitis varies based on severity, quality, duration, onset, trigger.
As caries invades dentin, the number of permeable dentinal tubules correlates with the degree of pain. Intrapulp pressure have an effect on the sensory nerves of varying diameters: blocking larger diameter Aδ-fibres and activating smaller C-fibers. Under hypoxic environments and pulp degeneration (symptom of pulpitis), C-fibers may still function. Once reparative dentin forms, odontoblasts associated with the dentin change, and the pulpal fibroblasts lose p75 expression, which is a neurotrophin receptor.

Diagnosis
Pulp sensibility tests are routinely used in the diagnosis of pulpitis. Pulp testing is combined with information taken from history, examination and other special investigations such as radiographs in order to reach a diagnosis. Pulp sensibility tests assess the pulp’s sensory response to a stimulus. There are 3 general types:

Thermal: Agents are applied to increase or decrease the temperature of a tooth and stimulate a pulp sensory response.Cold tests: Most commonly, ethyl chloride is sprayed onto a small ball of cotton wool and is applied to the tooth, which produces intense cold. Alternatively, CO2 snow and other refrigerants such as dichlorodifluoromethane (DDM) have been shown to be effective.
Heat tests: Gutta percha can be heated and directly applied to the tooth to produce heat.
Electrical pulp test: Electric pulp testing (EPT) has been available for over a century and is used by dentists worldwide. It is used to determine the health of the pulp and pulp-related pain.EPT is based on the stimulation of sensory nerves in the pulp. It does not provide information on vascular supply to the pulp. The probe tip of the test device is placed directly onto the tooth surface and an electrical stimulus is produced. This stimulus causes an ionic change across the neural membrane, inducing an action potential in the myelinated nerves. The threshold of pain is determined by increasing the voltage. A tingling sensation is felt once the voltage reaches the pain threshold. This threshold level varies between patients, and is affected by factors such as age, pain perception, tooth surface conduction and resistance.
The requirements of an EPT are appropriate application method, careful interpretation of the results, and an appropriate stimulus. EPT must be done with tooth isolation and conduction media. Key factors in pulp testing are the enamel and dentine thickness, and the number of nerve fibers in the underlying the pulp. EPT is not used in patients with orthodontic bands or crowned teeth, as the current may be conducted to adjacent teeth, resulting in false-positive responses. Pulp nerve fibers also respond to lower current intensities and only a small number of pulpal nerves are required to create responses when electrical stimulation is applied. This means that EPT may result in false-positive responses in teeth with pulpal necrosis. Furthermore, as pulpal and periodontal nerve thresholds overlap, the periodontal nerves may give a false indication of tooth sensibility.Possible explanations for false-positives include:

Response caused by conduction of the current because of periodontal or gingival issues
Breakdown products associated with pulp necrosis may be able to conduct electric current next to infected and hypersensitive pulp tissue
Inflamed pulp tissue may still be present
Metallic restorations or orthodontic gear are still presentStudies have indicated that there is little correlation between histopathological status of the pulp and clinical information. A negative EPT response showed localized necrosis in 25.7% of cases and 72% of cases. Thus, 97.7% of cases with a negative response to EPT indicated that a root canal treatment should be carried out.
Test cavity: The preparation of a test cavity involves cutting into the dentine of a tooth to determine whether the sensory element of the pulp is still functioning. Test cavity preparation is a last resort as this method is considered invasive and irreversible. It is also unlikely that this procedure would provide any more information than thermal and electric pulp sensibility tests. Therefore, test cavities are not generally used in practice as a means of testing pulp sensibility.

Treatment
Once the pulp has become inflamed, the tooth can be diagnostically divided into two categories: reversible pulpitis and irreversible pulpitis

Reversible
This is the condition where the pulp is inflamed and is actively responding to an irritant.  This may include a carious lesion that has not reached the pulp.
Symptoms include transient pain or sensitivity resulting from many stimuli, notably hot, cold, sweet, water and touch. The pulp is still considered to be vital.  This means that once the irritant is eliminated, usually by removal of decay and the placement of a restoration, that the pulp will return to its normal, healthy state. When it becomes painful and decayed the tooth may become known as a "hot tooth" and local anesthetic may not work as well.

Irreversible
This is the condition where the pulp is irreversibly damaged </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 Greater trochanteric pain syndrome and can you explain it in depth? [/INST] Greater trochanteric pain syndrome (GTPS), a form of bursitis, is inflammation of the trochanteric bursa, a part of the hip.
This bursa is at the top, outer side of the femur, between the insertion of the gluteus medius and gluteus minimus muscles into the greater trochanter of the femur and the femoral shaft. It has the function, in common with other bursae, of working as a shock absorber and as a lubricant for the movement of the muscles adjacent to it.Occasionally, this bursa can become inflamed and clinically painful and tender.  This condition can be a manifestation of an injury (often resulting from a twisting motion or from overuse), but sometimes arises for no obviously definable cause. The symptoms are pain in the hip region on walking, and tenderness over the upper part of the femur, which may result in the inability to lie in comfort on the affected side.More often the lateral hip pain is caused by disease of the gluteal tendons that secondarily inflames the bursa.  This is most common in middle-aged women and is associated with a chronic and debilitating pain which does not respond to conservative treatment. Other causes of trochanteric bursitis include uneven leg length, iliotibial band syndrome, and weakness of the hip abductor muscles.Greater trochanteric pain syndrome can remain incorrectly diagnosed for years, because it shares the same pattern of pain with many other musculoskeletal conditions. Thus people with this condition may be labeled malingerers, or may undergo many ineffective treatments due to misdiagnosis. It may also coexist with low back pain, arthritis, and obesity.

Signs and symptoms
The primary symptom is hip pain, especially hip pain on the outer (lateral) side of the joint.  This pain may appear when the affected person is walking or lying down on that side.

Diagnosis
A doctor may begin the diagnosis by asking the patient to stand on one leg and then the other, while observing the effect on the position of the hips. Palpating the hip and leg may reveal the location of the pain, and range-of-motion tests can help to identify its source.X-rays, ultrasound and magnetic resonance imaging may reveal tears or swelling. But often these imaging tests do not reveal any obvious abnormality in patients with documented GTPS.

Prevention
Because wear on the hip joint traces to the structures that support it (the posture of the legs, and ultimately, the feet), proper fitting shoes with adequate support are important to preventing GTPS. For someone who has flat feet, wearing proper orthotic inserts and replacing them as often as recommended are also important preventive measures.Strength in the core and legs is also important to posture, so physical training also helps to prevent GTPS. But it is equally important to avoid exercises that damage the hip.

Treatment
Conservative treatments have a 90% success rate and can include any or a combination of the following: pain relief medication, NSAIDs, physiotherapy, shockwave therapy (SWT) and corticosteroid injection. Surgery is usually for cases that are non-respondent to conservative treatments and is often a combination of bursectomy, iliotibial band (ITB) release, trochanteric reduction osteotomy or gluteal tendon repair. A 2011 review found that traditional nonoperative treatment helped most patients, low-energy SWT was a good alternative, and surgery was effective in refractory cases and superior to corticosteroid therapy and physical therapy. There are numerous case reports in which surgery has relieved GTPS, but its effectiveness is not documented in clinical trials as of 2009.The primary treatment is rest. This does not mean bed rest or immobilizing the area but avoiding actions which result in aggravation of the pain </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 Mallory–Weiss syndrome and can you explain it in depth? [/INST] Mallory–Weiss syndrome or gastro-esophageal laceration syndrome refers to bleeding from a laceration in the mucosa at the junction of the stomach and esophagus. This is usually caused by severe vomiting because of alcoholism or bulimia, but can be caused by any condition which causes violent vomiting and retching such as food poisoning. The syndrome presents with hematemesis. The laceration is sometimes referred to as a Mallory–Weiss tear.

Signs and symptoms
Mallory–Weiss Syndrome often presents as an episode of vomiting up blood (hematemesis) after violent retching or vomiting, but may also be noticed as old blood in the stool (melena), and a history of retching may be absent.
In most cases, the bleeding stops spontaneously after 24–48 hours, but endoscopic or surgical treatment is sometimes required. The condition is rarely fatal.

Causes
It is often associated with alcoholism and eating disorders and there is some evidence that presence of a hiatal hernia is a predisposing condition </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Malignant histiocytosis and can you explain it in depth? [/INST] Malignant histiocytosis  is a rare hereditary disease found in the Bernese Mountain Dog and humans, characterized by histiocytic infiltration of the lungs and lymph nodes.  The liver, spleen, and central nervous system can also be affected.  Histiocytes are a component of the immune system that proliferate abnormally in this disease.  In addition to its importance in veterinary medicine, the condition is also important in human pathology.

Histiocytic disorders
A histiocyte is a differentiated tissue cell that has its origin in the bone marrow.  The source for histiocytes is the monocyte/macrophage line.  Monocytes (found in the blood) and macrophages (found in tissue) are responsible for phagocytosis (ingestion) of foreign material in the body.  Langerhans cells are dendritic cells found in the skin and function by internalizing antigens (foreign particles) and presenting them to T cells </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 Chorionic hematoma 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 Rumination syndrome and can you explain it in depth? [/INST] Rumination syndrome, or merycism, is a chronic motility disorder characterized by effortless regurgitation of most meals following consumption, due to the involuntary contraction of the muscles around the abdomen. There is no retching, nausea, heartburn, odour, or abdominal pain associated with the regurgitation, as there is with typical vomiting, and the regurgitated food is undigested. The disorder has been historically documented as affecting only infants, young children, and people with cognitive disabilities (the prevalence is as high as 10% in institutionalized patients with various mental disabilities).
It is increasingly being diagnosed in a greater number of otherwise healthy adolescents and adults, though there is a lack of awareness of the condition by doctors, patients and the general public.
Rumination syndrome presents itself in a variety of ways, with especially high contrast existing between the presentation of the typical adult patient without a mental disability and the presentation of an adult with a mental disability. Like related gastrointestinal disorders, rumination can adversely affect normal functioning and the social lives of individuals. It has been linked with depression.
Little comprehensive data regarding rumination syndrome in otherwise healthy individuals exists because most people are private about their illness and are often misdiagnosed due to the number of symptoms and the clinical similarities between rumination syndrome and other disorders of the stomach and esophagus, such as gastroparesis and bulimia nervosa. These symptoms include the acid-induced erosion of the esophagus and enamel, halitosis, malnutrition, severe weight loss and an unquenchable appetite. Individuals may begin regurgitating within a minute following ingestion, and the full cycle of ingestion and regurgitation can mimic the binging and purging of bulimia.
Diagnosis of rumination syndrome is non-invasive and based on a history of the individual. Treatment is promising, with upwards of 85% of individuals responding positively to treatment, including infants and mentally disabled people.

Signs and symptoms
While the number and severity of symptoms vary among individuals, repetitive regurgitation of undigested food (known as rumination) after the start of a meal is always present. In some individuals, the regurgitation is small, occurring over a long period of time following ingestion, and can be rechewed and swallowed. In others, the amount can be bilious and short-lasting, and must be expelled.
While some only experience symptoms following some meals, most experience episodes following any ingestion, from a single bite to a large meal. However, some long-term patients will find a select couple of food or drink items that do not trigger a response.
Unlike typical vomiting, regurgitation is typically described as effortless and unforced. There is seldom nausea preceding the expulsion, and the undigested food lacks the bitter taste and odour of stomach acid and bile.Symptoms can begin to manifest at any point from the ingestion of the meal to 120 minutes thereafter. However, the more common range is between 30 seconds to 1 hour after the completion of a meal. Symptoms tend to cease when the ruminated contents become acidic.Abdominal pain (38.1%), lack of fecal production or constipation (21.1%), nausea (17.0%), diarrhea (8.2%), bloating (4.1%), and dental decay (3.4%) are also described as common symptoms in day-to-day life. These symptoms are not necessarily prevalent during regurgitation episodes, and can happen at any time. Weight loss is often observed (42.2%) at an average loss of 9.6 kilograms, and is more common in cases where the disorder has gone undiagnosed for a longer period of time, though this may be expected of the nutrition deficiencies that often accompany the disorder as a consequence of its symptoms. Depression has also been linked with rumination syndrome, though its effects on rumination syndrome are unknown.Acid erosion of the teeth can be a feature of rumination, as can halitosis (bad breath).

Causes
The cause of rumination syndrome is unknown. However, studies have drawn a correlation between hypothesized causes and the history of patients with the disorder. In infants and the cognitively impaired, the disease has normally been attributed to overstimulation and under-stimulation from parents and caregivers, causing the individual to seek self-gratification and self-stimulus due to the lack or abundance of external stimuli. The disorder has also commonly been attributed to a bout of illness, a period of stress in the individuals recent past, and to changes in medication.In adults and adolescents, hypothesized causes generally fall into one of either category: habit-induced, and trauma-induced. Habit-induced individuals generally have a history of bulimia nervosa or of intentional regurgitation (magicians and professional regurgitators, for example), which though initially self-induced, forms a subconscious habit that can continue to manifest itself outside the control of the affected individual. Trauma-induced individuals describe an emotional or physical injury (such as recent surgery, psychological distress, concussions, deaths in the family, etc.), which preceded the onset of rumination, often by several months.

Pathophysiology
Rumination syndrome is a poorly understood disorder, and a number of theories have speculated the mechanisms that cause the regurgitation, which is a unique symptom to this disorder. While no theory has gained a consensus, some are more notable and widely published than others.The most widely documented mechanism is that the ingestion of food causes gastric distention, which is followed by abdominal compression and the simultaneous relaxation of the lower esophageal sphincter (LES). This creates a common cavity between the stomach and the oropharynx that allows the partially digested material to return to the mouth. There are several offered explanations for the sudden relaxation of the LES. Among these explanations is that it is a learned voluntary relaxation, which is common in those with or having had bulimia. While this relaxation may be voluntary, the overall process of rumination is still generally involuntary. Relaxation due to intra-abdominal pressure is another proposed explanation, which would make abdominal compression the primary mechanism. The third is an adaptation of the belch reflex, which is the most commonly described mechanism. The swallowing of air immediately prior to regurgitation causes the activation of the belching reflex that triggers the relaxation of the LES. Patients often describe a feeling similar to the onset of a belch preceding rumination.

Diagnosis
Rumination syndrome is diagnosed based on a complete history of the individual. Costly and invasive studies such as gastroduodenal manometry and esophageal pH testing are unnecessary and will often aid in misdiagnosis. Based on typical observed features, several criteria have been suggested for diagnosing rumination syndrome. The primary symptom, the regurgitation of recently ingested food, must be consistent, occurring for at least six weeks of the past twelve months. The regurgitation must begin within 30 minutes of the completion of a meal. Patients may either chew the regurgitated matter or expel it. The symptoms must stop within 90 minutes, or when the regurgitated matter becomes acidic. The symptoms must not be the result of a mechanical obstruction, and should not respond to the standard treatment for gastroesophageal reflux disease.In adults, the diagnosis is supported by the absence of classical or structural diseases of the gastrointestinal system. Supportive criteria include a regurgitant that does not taste sour or acidic, is generally odourless, is effortless, or at most preceded by a belching sensation, that there is no retching preceding the regurgitation, and that the act is not associated with nausea or heartburn.Patients visit an average of five physicians over 2.75 years before being correctly diagnosed with rumination syndrome.

Differential diagnosis
Rumination syndrome in adults is a complicated disorder whose symptoms can mimic those of several other gastroesophageal disorders and diseases. Bulimia nervosa and gastroparesis are especially prevalent among the misdiagnoses of rumination.Bulimia nervosa, among adults and especially adolescents, is by far the most common misdiagnosis patients will hear during their experiences with rumination syndrome. This is due to the similarities in symptoms to an outside observer—"vomiting" following food intake—which, in long-term patients, may include ingesting copious amounts to offset malnutrition, and a lack of willingness to expose their condition and its symptoms. While it has been suggested that there is a connection between rumination and bulimia, unlike bulimia, rumination is not self-inflicted. Adults and adolescents with rumination syndrome are generally well aware of their gradually increasing malnutrition, but are unable to control the reflex. In contrast, those with bulimia intentionally induce vomiting, and seldom re-swallow food.Gastroparesis is another common misdiagnosis. Like rumination syndrome, patients with gastroparesis often bring up food following the ingestion of a meal. Unlike rumination, gastroparesis causes vomiting (in contrast to regurgitation) of food, which is not being digested further, from the stomach. This vomiting occurs several hours after a meal is ingested, preceded by nausea and retching, and has the bitter or sour taste typical of vomit.

Classification
Rumination syndrome is a condition which affects the functioning of the stomach and esophagus, also known as a functional gastroduodenal disorder. In patients that have a history of eating disorders, Rumination syndrome is grouped alongside eating disorders such as bulimia and pica, which are themselves grouped under non-psychotic mental disorder. In most healthy adolescents and adults who have no mental disability, Rumination syndrome is considered a motility disorder instead of an eating disorder, because the patients tend to have had no control over its occurrence and have had no history of eating disorders.

Treatment and prognosis
There is presently no known cure for rumination. Proton pump inhibitors and other medications have been used to little or no effect.
Treatment is different for infants and mentally disabled adults than for adults and adolescents of typical intelligence. Among infants and mentally disabled adults, behavioral and mild aversion training has been shown to cause improvement in most cases. Aversion training involves associating the ruminating behavior with negative results, and rewarding good behavior and eating. Placing a sour or bitter taste on the tongue when the individual begins the movements or breathing patterns typical of his or her ruminating behavior is the generally accepted method for aversion training,
although some older studies advocate the use of pinching.
In patients of normal intelligence, rumination is not an intentional behavior and is habitually reversed using diaphragmatic breathing to counter the urge to regurgitate. Alongside reassurance, explanation and habit reversal, patients are shown how to breathe using their diaphragms prior to and during the normal rumination period. A similar breathing pattern can be used to prevent normal vomiting. Breathing in this method works by physically preventing the abdominal contractions required to expel stomach contents.
Supportive therapy and diaphragmatic breathing has shown to cause improvement in 56% of cases, and total cessation of symptoms in an additional 30% in one study of 54 adolescent patients who were followed up 10 months after initial treatments. Patients who successfully use the technique often notice an immediate change in health for the better. Individuals who have had bulimia or who intentionally induced vomiting in the past have a reduced chance for improvement due to the reinforced behavior. The technique is not used with infants or young children due to the complex timing and concentration required for it to be successful. Most infants grow out of the disorder within a year or with aversive training.

Epidemiology
Rumination disorder was initially documented
as affecting newborns,
infants, children
and individuals with mental and functional disabilities (cognitively disabled).
It has since been recognized to occur in both males and females of all ages and cognitive abilities.Among cognitively disabled people, it is described with almost equal prevalence among infants (6–10% of the population) and institutionalized adults (8–10%).
In infants, it typically occurs within the first 3–12 months of age.The occurrence of rumination syndrome within the general population has not been defined. Rumination is sometimes described as rare, but has also been described as not rare, but rather rarely recognized.
The disorder has a female predominance. The typical age of adolescent onset is 12.9, give or take 0.4 years (±), with males affected sooner than females (11.0 ± 0.8 for males versus 13.8 ± 0.5 for females).There is little evidence concerning the impact of hereditary influence in rumination syndrome. However, case reports involving entire families with rumination exist.

History
The term rumination is derived from the Latin word ruminare, which means to chew the cud. First described in ancient times, and mentioned in the writings of Aristotle, rumination syndrome was clinically documented in 1618 by Italian anatomist Fabricus ab Aquapendente, who wrote of the symptoms in a patient of his.Among the earliest cases of rumination was that of a physician in the nineteenth century, Charles-Édouard Brown-Séquard, who acquired the condition as the result of experiments upon himself. As a way of evaluating and testing the acid response of the stomach to various foods, the doctor would swallow sponges tied to a string, then intentionally regurgitate them to analyze the contents. As a result of these experiments, the doctor eventually regurgitated his meals habitually by reflex.Numerous case reports exist from before the twentieth century, but were influenced greatly by the methods and thinking used in that time. By the early twentieth century, it was becoming increasingly evident that rumination presented itself in a variety of ways in response to a variety of conditions </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 Glioma and can you explain it in depth? [/INST] A glioma is a type of tumor that starts in the glial cells of the brain or the spine. Gliomas comprise about 30 percent of all brain tumors and central nervous system tumours, and 80 percent of all malignant brain tumours.

Signs and symptoms
Symptoms of gliomas depend on which part of the central nervous system is affected.  A brain glioma can cause headaches, vomiting, seizures, and cranial nerve disorders as a result of increased intracranial pressure. A glioma of the optic nerve can cause visual loss.  Spinal cord gliomas can cause pain, weakness, or numbness in the extremities.  Gliomas do not usually metastasize by the bloodstream, but they can spread via the cerebrospinal fluid and cause "drop metastases" to the spinal cord. Complex visual hallucinations have been described as a symptom of low-grade glioma.A child who has a subacute disorder of the central nervous system that produces cranial nerve abnormalities (especially of cranial nerve VII and the lower bulbar nerves), long-tract signs, unsteady gait secondary to spasticity, and some behavioral changes is most likely to have a pontine glioma.

Causes
Hereditary disorders
The exact causes of gliomas are not known. Hereditary disorders such as neurofibromatoses (type 1 and type 2) and tuberous sclerosis complex are known to predispose to their development. Different oncogenes can cooperate in the development of gliomas.

Diet
Some studies of diet and vitamin supplementation appear to point out that dietary N-nitroso compounds may affect the risk of both childhood and adult brain tumors. Researchers have observed in some studies that brain tumor patients (or their mothers) have generally consumed more cured foods (also known as Curing) than control groups.  Recently, Drs. Lee, Wrensch and others found that adults with glioma were more likely to consume diets high in cured foods and low in vitamin C-rich fruits and vegetables, and to consume diets high in nitrites and low in vitamin C. The effect was more pronounced in men than women. However, the pattern of increased risk with increased consumption of cured foods, and decreased risk with greater consumption of fruits, vegetables, and antioxidant vitamins is compatible with other cancer studies that show increased consumption of vegetables and possibly of fruits is associated with decreased cancer risk.

Radiation
A link between gliomas and electromagnetic radiation from cell phones has not been conclusively proven. It was considered possible, though several large studies have found no conclusive evidence, as summarized by the NIHs National Cancer Institute review of the topic and its numerous citations, and the FCC. However, further research is still being pursued to obtain more robust evidence and verify that there is no relationship (the NIHs National Institute of Environmental Health Sciences most recent press release discussed an ongoing study showing mildly positive results, although it appears there may have been issues with the control group dying prematurely).

Infection with cytomegalovirus
Some studies have reported that glioblastomas are infected with cytomegalovirus, with suggestions that this may speed the development of tumors. However, this is a controversial opinion, with recent in-depth studies failing to find an association between viral infection and glioma growth. There is also evidence that previous studies may have been impacted by false-positive antibody staining artifacts.

Other causes
Though some studies have shown that farmers have higher rates of gliomas compared to the general population, exposure to farm animals or manure is not associated with glioma. Later studies have not found an association between farming and gliomas; similar conflicting data concerns teachers and glioma. More consistent data show that architects, surveyors, retail workers, butchers, and engineers have higher rates of gliomas. Most studies have found that pesticide exposure is probably not a cause of glioma, though a minority of studies have found an association.

Inherited polymorphisms of the DNA repair genes
Germ-line (inherited) polymorphisms of the DNA repair genes ERCC1, ERCC2 (XPD) and XRCC1 increase the risk of glioma. This indicates that altered or deficient repair of DNA damage contributes to the formation of gliomas.  DNA damages are a likely major primary cause of progression to cancer in general.  Excess DNA damages can give rise to mutations through translesion synthesis. Furthermore, incomplete DNA repair can give rise to epigenetic alterations or epimutations.  Such mutations and epimutations may provide a cell with a proliferative advantage which can then, by a process of natural selection, lead to progression to cancer.Epigenetic repression of DNA repair genes is often found in progression to sporadic glioblastoma.  For instance, methylation of the DNA repair gene MGMT promoter was observed in 51% to 66% of glioblastoma specimens.  In addition, in some glioblastomas, the MGMT protein is deficient due to another type of epigenetic alteration.  MGMT protein expression may also be reduced due to increased levels of a microRNA that inhibits the ability of the MGMT messenger RNA to produce the MGMT protein.  Zhang et al. found, in the glioblastomas without methylated MGMT promoters, that the level of microRNA miR-181d is inversely correlated with protein expression of MGMT and that the direct target of miR-181d is the MGMT mRNA 3UTR (the three prime untranslated region of MGMT messenger RNA).Epigenetic reductions in expression of another DNA repair protein, ERCC1, were found in an assortment of 32 gliomas.  For 17 of the 32 (53%) of the gliomas tested, ERCC1 protein expression was reduced or absent.  In the case of 12 gliomas (37.5%) this reduction was due to methylation of the ERCC1 promoter.  For the other 5 gliomas with reduced ERCC1 protein expression, the reduction could have been due to epigenetic alterations in microRNAs that affect ERCC1 expression.When expression of DNA repair genes is reduced, DNA damages accumulate in cells at a higher than normal level, and such excess damages cause increased frequencies of mutation.  Mutations in gliomas frequently occur in either isocitrate dehydrogenase (IDH) 1 or 2 genes.  One of these mutations (mostly in IDH1) occurs in about 80% of low grade gliomas and secondary high-grade gliomas.  Wang et al. pointed out that IDH1 and IDH2 mutant cells produce an excess metabolic intermediate, 2-hydroxyglutarate, which binds to catalytic sites in key enzymes that are important in altering histone and DNA promoter methylation. Thus, mutations in IDH1 and IDH2 generate a "DNA CpG island methylator phenotype or CIMP" that causes promoter hypermethylation and concomitant silencing of tumor suppressor genes such as DNA repair genes MGMT and ERCC1.  On the other hand, Cohen et al. and Molenaar et al. pointed out that mutations in IDH1 or IDH2 can cause increased oxidative stress.  Increased oxidative damage to DNA could be mutagenic. This is supported by an increased number of DNA double-strand breaks in IDH1-mutated glioma cells. Thus, IDH1 or IDH2 mutations act as driver mutations in glioma carcinogenesis, though it is not clear by which role they are primarily acting.  A study, involving 51 patients with brain gliomas who had two or more biopsies over time, showed that mutation in the IDH1 gene occurred prior to the occurrence of a p53 mutation or a 1p/19q loss of heterozygosity, indicating that an IDH1 mutation is an early driver mutation.

Pathophysiology
High-grade gliomas are highly vascular tumors and have a tendency to infiltrate diffusely.  They have extensive areas of necrosis and hypoxia.  Often, tumor growth causes a breakdown of the blood–brain barrier in the vicinity of the tumor.  As a rule, high-grade gliomas almost always grow back even after complete surgical excision, so are commonly called recurrent cancer of the brain.Conversely, low-grade gliomas grow slowly, often over many years, and can be followed without treatment unless they grow and cause symptoms.Several acquired (not inherited) genetic mutations have been found in gliomas. Tumor suppressor protein 53 (p53) is mutated early in the disease. p53 is the "guardian of the genome", which, during DNA and cell duplication, makes sure the DNA is copied correctly and destroys the cell (apoptosis) if the DNA is mutated and cannot be fixed. When p53 itself is mutated, other mutations can survive. Phosphatase and tensin homolog (PTEN), another tumor suppressor gene, is itself lost or mutated. Epidermal growth factor receptor, a growth factor that normally stimulates cells to divide, is amplified and stimulates cells to divide too much. Together, these mutations lead to cells dividing uncontrollably, a hallmark of cancer. In 2009, mutations in IDH1 and IDH2 were found to be part of the mechanism and associated with a less favorable prognosis.

Diagnosis
Classification
Gliomas are classified by cell type, by grade, and by location.

By type of cell
Gliomas are named according to the specific type of cell with which they share histological features, but not necessarily from which they originate. The main types of glioma are:
Ependymomas: ependymal cells
Astrocytomas: astrocytes (glioblastoma multiforme is a malignant astrocytoma and the most common primary brain tumor among adults).
Oligodendrogliomas: oligodendrocytes
Brainstem glioma: develop in the brain stem
Optic nerve glioma: develop in or around the optic nerve
Mixed gliomas, such as oligoastrocytomas, contain cells from different types of glia

By grade
Gliomas are further categorized according to their grade, which is determined by pathologic evaluation of the tumor. The neuropathological evaluation and diagnostics of brain tumor specimens is performed according to WHO Classification of Tumours of the Central Nervous System.

Biologically benign gliomas [WHO grade I] are comparatively low risk and can be removed surgically depending on their location
Low-grade gliomas [WHO grade II] are well-differentiated (not anaplastic);  these tend to exhibit  benign tendencies and portend a better prognosis for the patient. However, they have a uniform rate of recurrence and increase in grade over time so should be classified as malignant.
High-grade [WHO grades III–IV] gliomas are undifferentiated or anaplastic; these are malignant and carry a worse prognosis.Of numerous grading systems in use, the most common is the World Health Organization (WHO) grading system for astrocytoma, under which tumors are graded from I (least advanced disease—best prognosis) to IV (most advanced disease—worst prognosis).

By location
Gliomas can be classified according to whether they are above or below a membrane in the brain called the tentorium. The tentorium separates the cerebrum (above) from the cerebellum (below).

The supratentorial is above the tentorium, in the cerebrum, and mostly found in adults (70%).
The infratentorial is below the tentorium, in the cerebellum, and mostly found in children (70%).
The pontine tumors are located in the pons of the brainstem. The brainstem has three parts (pons, midbrain, and medulla); the pons controls critical functions such as breathing, making surgery on these extremely dangerous.

Treatment
Treatment for brain gliomas depends on the location, the cell type, and the grade of malignancy. Often, treatment is a combined approach, using surgery, radiation therapy, and chemotherapy. A prolonged survival was observed when treating with radiotherapy and concomitant temozolomide. Radiotherapy was given for 5 days a week for 6 week, with a total of 60 Gy. Temozolomide was given daily during the treatment of radiotherapy, at a dose of 75 mg per square meter of body surface area per day. When radiotherapy ended additionally six cycles of temozolomide were given, for five days during each cycle of 28 days. The radiation therapy is in the form of external beam radiation or the stereotactic approach using radiosurgery. Spinal cord tumors can be treated by surgery and radiation. Temozolomide is a chemotherapy drug which can be administered easily in an outpatient setting and is able to cross the blood–brain barrier effectively. Treatment via immunotherapy may help some gliomas. Experimental therapies like oncolytic viruses have shown potential therapeutic benefits in clinical trials but has not been approved for use in clinic.

Refractory disease
For recurrent high-grade glioblastoma, recent studies have taken advantage of angiogenic blockers such as bevacizumab in combination with conventional chemotherapy, with encouraging results.

Relative effectiveness
A 2017 meta-analysis compared surgical resection versus biopsy as the initial surgical management option for a person with a low-grade glioma.  Results show the evidence is insufficient to make a reliable decision. The relative effectiveness of surgical resection compared to biopsy for people with malignant glioma (high-grade) is unknown.For high-grade gliomas, a 2003 meta-analysis compared radiotherapy with radiotherapy and chemotherapy.  It showed a small but clear improvement from using chemotherapy with radiotherapy. A 2019 meta-analysis suggested that for people with less aggressive gliomas, radiotherapy may increase the risk of long term neurocognitive side effects. Whilst, evidence is uncertain on whether there are long term neurocognitive side effects associated with chemoradiotherapy.Temozolomide is effective for treating Glioblastoma Multiforme (GBM) compared to radiotherapy alone. A 2013 meta-analysis showed that Temozolomide prolongs survival and delays progression, but is associated with an increase in side effects such as blood complications, fatigue, and  infection.  For people with recurrent GBM, when comparing temozolomide with chemotherapy, there may be an improvement in the time-to-progression and the persons quality of life, but no improvement in overall survival, with temozolomide treatment. Evidence suggests that for people with recurrent high-grade gliomas who have not had chemotherapy before, there are similar survival and time-to-progression outcomes between treatment with temozolomide or the chemotherapy multidrug known as PCV (procarvazine, lomustine and vincristine).A mutational analysis of 23 initial low-grade gliomas and recurrent tumors from the same patients has challenged the benefits and usage of Temozolomide. The study showed that when lower-grade brain tumors of patients are removed and patients are further treated with Temozolomide, 6 out of 10 times the recurrent tumors were more aggressive and acquired alternative and more mutations. As one of the last authors, Costello, stated "They had a 20- to 50-fold increase in the number of mutations. A patient who received surgery alone who might have had 50 mutations in the initial tumor and 60 in the recurrence. But patients who received TMZ might have 2,000 mutations in the recurrence." Further, new mutations were verified to carry known signatures of Temozolomide induced mutations. The research suggests that Temozolomide for the treatment of certain brain tumors should be thoroughly thought. Unjudicious usage of Temozolomide might lower the prognosis of the patients further, or increase their burden. Further understanding of the mechanisms of Temozolomide induced mutations and novel combination approaches could be promising.

Prognosis
Prognosis of gliomas is given in relation to what grade (as scored by the World Health Organization system) of tumour the patient presents with. Typically, any tumour presenting as above WHO grade I (i.e. a malignant tumour as opposed to a benign tumour) will have a prognosis resulting in eventual death, varying from years (WHO grade II/III) to months (WHO grade IV). Prognosis can also be given based on cellular subtype, which may also impact prognosis.

Low grade
For low-grade tumors, the prognosis is somewhat more optimistic. Patients diagnosed with a low-grade glioma are 17 times as likely to die as matched patients in the general population.
The age-standardized 10-year relative survival rate was 47%. One study reported that low-grade oligodendroglioma patients have a median survival of 11.6 years; another reported a median survival of 16.7 years. Unfortunately, approximately 70% of low-grade (WHO grade-II) will progress to high-grade tumours within 5–10 years

High grade
This group comprises anaplastic astrocytomas and glioblastoma multiforme. Whereas the median overall survival of anaplastic (WHO grade III) gliomas is approximately 3 years, glioblastoma multiforme has a poor median overall survival of c. 15 months.Postoperative conventional daily radiotherapy improves survival for adults with good functional well‐being and high grade glioma compared to no postoperative radiotherapy. Hypofractionated radiation therapy has similar efficacy for survival as compared to conventional radiotherapy, particularly for individuals aged 60 and older with glioblastoma.

Diffuse intrinsic pontine glioma
Diffuse intrinsic pontine glioma primarily affects children, usually between the ages of 5 and 7 </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 Calcinosis 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 Subdural effusion 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 Cracked nipple and can you explain it in depth? [/INST] Cracked nipple (nipple trauma or nipple fissure) is a condition that can occur in breastfeeding women as a result of a number of possible causes. Developing a cracked nipple can result in soreness, dryness or irritation to, or bleeding of, one or both nipples during breastfeeding. The mother with a cracked nipple can have severe nipple pain when the baby is nursing. This severe pain is a disincentive for continued breastfeeding. The crack can appear as a cut across the tip of the nipple and may extend to its base. Cracked nipple develop after the birth of the infant and is managed with pharmacological and nonpharmacological treatment.

Signs and symptoms
Cracked nipples are classified as a breast disorder. The nipple is not only the structure to deliver milk to the infant, it also contains small, sebaceous glands or Montgomery glands to lubricate the skin of the areola. Cracked nipples are most often associated with breastfeeding and appear as cracks or small lacerations or breaks in the skin of the nipple. In some instances an ulcer will form. The nipple in a nursing mother is in regular contact with a nursing infant. Cracked nipples are trauma to the nipple and can be quite painful. Cracked nipples typically appear three to seven days after the birth.If the nipples appears to be wedge-shaped, white and flattened, this may indicate that the latch is not good and there is a potential of developing cracked nipples.

Complications
Bacteria can enter the breast through cracked nipples, which increase the risk of mastitis. Candida infection (thrush) of the nipple can also occur, resulting in deep-pink, cracked, and sore nipples.

Contraindications for breastfeeding
Because cracked nipples can result in the infant being exposed to blood, women with certain blood-borne diseases may be advised to stop breastfeeding if they have a cracked nipple. It has been found safe for breastfeeding mothers with hepatitis B and cracked nipples to breastfeed. In the event that a nursing woman experiences cracked and bleeding nipples or breast inflammation within one to two weeks immediately following an acute Toxoplasmosis infection (when the organism is still circulating in her bloodstream), it is theoretically possible that she could transmit Toxoplasma gondii to the infant through her breast milk. Immune suppressed women could have circulating Toxoplasma for even longer periods of time. However, the likelihood of human milk transmission is very small. Transmission risk of HIV increases if the mother has cracked and bleeding nipples An uncommon infection in the mother, Chagas disease, can be transmitted to the nursing infant via cracked nipples. Women with hepatitis C are advised to abstain from breastfeeding if their nipples are cracked or bleeding.

Cause
Some studies indicate that cracked nipples are caused by poor latch. Yet other causes could be poor positioning, use of a feeding bottle, breast engorgement, inexperience, semi-protruding nipples, use of breast pumps and light pigmentation of the nipples. Breast engorgement is also a main factor in altering the ability of the infant to latch-on. Engorgement changes the shape and curvature of the nipple region by making the breast inflexible, flat, hard, and swollen. The nipples on an engorged breast are flat.When the baby is latched on correctly, the nipple is located against the soft palate in the back of the babys mouth. When the nipple is near the front of the mouth and being pinched against the hard palate, this will cause pain and development of cracked nipples. One cause of painful, cracked nipples is the incorrect positioning and incorrect latching on to the breast by the infant. The baby can create cracked nipples due to the strong sucking pressure, stretching and pulling the nipple, the friction and rubbing of skin to skin. The cause of sore, cracked nipples can also be from a yeast or Candida infection in the baby or the mother or both. Thrush can develop after the use of antibiotics. For first-time breastfeeding mothers, it normally takes a few tries before the latch is right, which can make the nipples tender and sore the first few days. If the nipples become cracked or bleed, the latch may need to be corrected. Women are advised to keep on breastfeeding, as it will actually help the nipples heal. A little breast milk or purified lanolin cream or ointment helps the healing process.If a feeding bottle is used in addition to breastfeeding, cracked nipples may result because the different sucking techniques required for the bottle and the breast vary. Bottle-feeding babies uses his or her tongue to regulate the flow of milk. This same technique will cause friction on the nipple while breastfeeding. This, in turn, encourages the continued use of the bottle with less time breastfeeding.Pain caused by cracked nipples can sometimes lead to the cessation of breast-feeding. In addition to cracks, blisters or ulcers can form.

Prevention
The nipples of nursing mothers naturally make a lubricant to prevent drying, cracking, or infections. Cracked nipples may be able to be prevented by:

Avoid soaps and harsh washing or drying of the breasts and nipples. This can cause dryness and cracking.
Rubbing a little breast milk on the nipple after feeding to protect it.
Keeping the nipples dry to prevent cracking and infection.
Using seashells to keep nipples healthy through continuous contact with breast milkRoman chamomile is sometimes used as a remedy in alternative medicine to treat cracked nipples by a topical application. However, there is no scientific evidence for its efficacy, and is in fact considered unsafe for use during pregnancy.

Treatment
Cracked nipples can be treated with 100% lanolin. Glycerin nipple pads can be chilled and placed over the nipples to help soothe and heal cracked or painful nipples. If the cause of cracked nipples is from thrush, treatment is usually begun with nystatin. If the mother is symptomatic then the mother and the baby can be treated. Continuing to breastfeed will actually help the nipples heal. A little breast milk or purified lanolin cream or ointment helps the healing process. Breastfeeding professionals that include nurses, midwives and lactation consultants are able to assist in the treatment of cracked nipples.Advice from others is abundant but there have been some treatments that have been identified as not being effective in healing or preventing cracked nipples. These ineffective treatments are keeping the breastfeeding short and using a nipple guard. Keeping the feedings short so that the nipples can rest is not effective in relieving the pain of cracked nipples and it could have a negative effect on the milk supply. Nipple shields do not improve latching on.

Epidemiology
In a survey in New York City, 35% of nursing mothers stopped breastfeeding after one week due to the pain of cracked nipples. Thirty percent stopped breastfeeding between weeks one and three </s>