<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Tick-borne disease and explain in detail? [/INST] Tick-borne diseases, which afflict humans and other animals, are caused by infectious agents transmitted by tick bites. They are caused by infection with a variety of pathogens, including rickettsia and other types of bacteria, viruses, and protozoa.
The economic impact of tick-borne diseases is considered to be substantial in humans, and tick-borne diseases are estimated to affect ~80 % of cattle worldwide.As of 2020  18 tick-borne pathogens have been identified in the United States according to the Centers for Disease Control and at least 27 are known globally.
New tick-borne diseases have been discovered in the 21st century, due in part to the use of molecular assays and next-generation sequencing.The occurrence of ticks and tick-borne illnesses in humans is increasing. Tick populations are spreading into new areas, in part due to climate change. Tick populations are also affected by changes in the populations of their hosts (e.g. deer, cattle, mice, lizards) and those hosts predators (e.g. foxes).  Diversity and availability of hosts and predators can be affected by deforestation and habitat fragmentation.Because individual ticks can harbor more than one disease-causing agent, patients can be infected with more than one pathogen at the same time, compounding the difficulty in diagnosis and treatment.
As the incidence of tick-borne illnesses increases and the geographic areas in which they are found expand, health workers increasingly must be able to distinguish the diverse, and often overlapping, clinical presentations of these diseases.

Prevention
Exposure
Ticks tend to be more active during warmer months, though this varies by geographic region and climate. Areas with woods, bushes, high grass, or leaf litter are likely to have more ticks. Those bitten commonly experience symptoms such as body aches, fever, fatigue, joint pain, or rashes. People can limit their exposure to tick bites by wearing light-colored clothing (including pants and long sleeves), using insect repellent with 20%–30% N,N-Diethyl-3-methylbenzamide (DEET), tucking their pants legs into their socks, checking for ticks frequently, and washing and drying their clothing (in a hot dryer).According to the World Health Organization, tick-to-animal transmission is difficult to prevent because animals do not show visible symptoms; the only effective prevention relies on killing ticks on the livestock production facility.

Tick removal
Ticks should be removed as soon as safely possible once discovered. They can be removed either by grasping tweezers as close to the mouth as possible and pulling without rotation; some companies market grooved tools that rotate the hypostome to facilitate removal. Chemical methods to make the tick self-detach, or trying to pull the tick out with one’s fingers, are not efficient methods.

Diagnosis
In general, specific laboratory tests are not available for rapid diagnosis of tick-borne diseases. Due to their seriousness, antibiotic treatment is often justified based on clinical presentation alone.

Assessing risk
For a person or pet to acquire a tick-borne disease requires that the individual gets bitten by a tick and that the tick feeds for a sufficient period of time. The feeding time required to transmit pathogens differs for different ticks and different pathogens. Transmission of the bacterium that causes Lyme disease is well understood to require a substantial feeding period. In general, soft ticks (Argasidae) transmit pathogens within minutes of attachment because they feed more frequently, whereas hard ticks (Ixodidae) take hours or days, but the latter are more common and harder to remove.For an individual to acquire infection, the feeding tick must also be infected. Not all ticks are infected. In most places in the US, 30-50% of deer ticks will be infected with Borrelia burgdorferi (the agent of Lyme disease). Other pathogens are much more rare. Ticks can be tested for infection using a highly specific and sensitive qPCR procedure. Several commercial labs provide this service to individuals for a fee. The Laboratory of Medical Zoology (LMZ), a nonprofit lab at the University of Massachusetts, provides a comprehensive TickReport  for a variety of human pathogens and makes the data available to the public. Those wishing to know the incidence of tick-borne diseases in their town or state can search the LMZ surveillance database.

Examples
Major tick-borne diseases include:

Bacterial
Lyme disease or borreliosis
Organism: Borrelia burgdorferi sensu lato (bacterium)
Vector: at least 15 species of ticks in the genus Ixodes, including deer tick (Ixodes scapularis (=I. dammini), I. pacificus, I. ricinus (Europe), I. persulcatus (Asia))
Endemic to: The Americas and Eurasia
Symptoms: Fever, arthritis, neuroborreliosis, erythema migrans, cranial nerve palsy, carditis, fatigue, and influenza-like illness
Treatment: Antibiotics - amoxicillin in pregnant adults and children), (doxycycline in other adults
Relapsing fever (tick-borne relapsing fever, different from Lyme disease due to different Borrelia species and ticks)
Organisms: Borrelia species such as B. hermsii, B. parkeri, B. duttoni, B.  miyamotoi
Vector: Ornithodoros species
Regions : Primarily in Africa, Spain, Saudi Arabia, Asia in and certain areas of Canada and the western United States
Symptoms: Relapsing fever typically presents as recurring high fevers, flu-like symptoms, headaches, and muscular pain, with less common symptoms including rigors, joint pain, altered mentation, cough, sore throat, painful urination, and rash
Treatment: Antibiotics are the treatment for relapsing fever, with doxycycline, tetracycline, or erythromycin being the treatment of choice.
Typhus Several diseases caused by Rickettsia bacteria (below)
Rocky Mountain spotted fever
Organism: Rickettsia rickettsii
Vector:  Wood tick (Dermacentor variabilis), D. andersoni
Region (US): East, Southwest
Vector: Amblyomma cajennense
Region (Brazil): São Paulo, Rio de Janeiro, Minas Gerais.
Symptoms:Fever, headache, altered mental status, myalgia, and rash
Treatment: Antibiotic therapy, typically consisting of doxycycline or tetracycline
Helvetica spotted fever
Organism: Rickettsia helvetica
Region(R. helvetica): Confirmed common in ticks in Sweden, Switzerland, France, and Laos
Vector/region(s)#1: Ixodes ricinus is the main European vector.
Symptoms: Most often small red spots, other symptoms are fever, muscle pain, headache and respiratory problems
Treatment: Broad-spectrum antibiotic therapy is needed, phenoxymethylpenicillin likely is sufficient.
Human granulocytic anaplasmosis (formerly human granulocytic ehrlichiosis or HGE)
Organism: Anaplasma phagocytophilum (formerly Ehrlichia phagocytophilum or Ehrlichia equi)
Vector: Lone star tick (Amblyomma americanum), I. scapularis
Region (US): South Atlantic, South-central
Bartonella: Bartonella transmission rates to humans via tick bite are not well established  but Bartonella is common in ticks. For example: 4.76% of 2100 ticks tested in a study in Germany
Tularemia
Organism: Francisella tularensis, A. americanum
Vector: D. variabilis, D. andersoni
Region (US): Southeast, South-central, West, widespread

Viral
Tick-borne meningoencephalitis
Organism: TBEV (FSME) virus, a flavivirus from family Flaviviridae
Vector: deer tick (Ixodes scapularis), Ixodes ricinus (Europe), Ixodes persulcatus (Russia + Asia))
Endemic to: Europe and northern Asia
Powassan virus/deer tick virusOrganism: Powassan virus (POWV), a flavivirus from family Flaviviridae </s>


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Diabetic foot ulcer and explain in detail? [/INST] Diabetic foot ulcer is a major complication of diabetes mellitus, and probably the major component of the diabetic foot.
Wound healing is an innate mechanism of action that works reliably most of the time. A key feature of wound healing is stepwise repair of lost extracellular matrix (ECM) that forms the largest component of the dermal skin layer. But in some cases, certain disorders or physiological insult disturbs the wound healing process. Diabetes mellitus is one such metabolic disorder that impedes the normal steps of the wound healing process. Many studies show a prolonged inflammatory phase in diabetic wounds, which causes a delay in the formation of mature granulation tissue and a parallel reduction in wound tensile strength.Treatment of diabetic foot ulcers should include: blood sugar control, removal of dead tissue from the wound, wound dressings, and removing pressure from the wound through techniques such as total contact casting. Surgery in some cases may improve outcomes. Hyperbaric oxygen therapy may also help but is expensive.It occurs in 15% of people with diabetes, and precedes 84% of all diabetes-related lower-leg amputations.

Risk factors
Risk factors implicated in the development of diabetic foot ulcers are infection, older age, diabetic neuropathy, peripheral vascular disease, cigarette smoking, poor glycemic control, previous foot ulcerations or amputations, and ischemia of small and large blood vessels. Prior history of foot  disease, foot deformities that produce abnormally high forces of pressure, callus at pressure areas  renal  failure, oedema, impaired ability to look after personal care (e.g. visual impairment) are further risk factors for diabetic foot ulcer.People with diabetes often develop diabetic neuropathy due to several metabolic and neurovascular factors. Peripheral neuropathy causes loss of pain or feeling in the toes, feet, legs, and arms due to distal nerve damage and low blood flow. Autonomic neuropathy causes Sudomotor dysfunction and dryness of the skin. Blisters and sores may appear on numb areas of the feet and legs, such as metatarsophalangeal joints and the heel region, as a result of pressure or injury which may go unnoticed and eventually become a portal of entry for bacteria and infection.

Pathophysiology
Extracellular matrix
Extra cellular matrix (or "ECM") is the external structural framework that cells attach to in multicellular organisms. The dermis lies below the epidermis, and these two layers are collectively known as the skin. Dermal skin is primarily a combination of fibroblasts growing in this matrix. The specific species of ECM of connective tissues often differ chemically, but collagen generally forms the bulk of the structure.Through the interaction of a cell with its extracellular matrix (transmitted through the anchoring molecules classed as integrins) there forms a continuous association between the cell interior, cell membrane and its extracellular matrix components that helps drive various cellular events in a regulated fashion. Wound healing is a localized event involving the reaction of cells to the damage sustained.The cells break down damaged ECM and replace it, generally increasing in number to react to the harm. The process is activated, though perhaps not exclusively, by cells responding to fragments of damaged ECM, and the repairs are made by reassembling the matrix by cells growing on and through it. Because of this, extracellular matrix is often considered as a conductor of the wound healing symphony. In the Inflammatory phase, neutrophils and macrophages recruit and activate fibroblasts which in subsequent granulation phase migrate into the wound, laying down new collagen of the subtypes I and III.In the initial events of wound healing, collagen III predominates in the granulation tissue which later on in remodeling phase gets replaced by collagen I giving additional tensile strength to the healing tissue. It is evident from the known collagen assembly that the tensile strength is basically due to fibrillar arrangement of collagen molecules, which self-assemble into microfibrils in a longitudinal as well as lateral manner producing extra strength and stability to the collagen assembly. Metabolically altered collagen is known to be highly inflexible and prone to break down, particularly over pressure areas. Fibronectin is the major glycoprotein secreted by fibroblasts during initial synthesis of extracellular matrix proteins. It serves important functions, being a chemo-attractant for macrophages, fibroblasts and endothelial cells.The basement membrane that separates the epidermis from the dermal layer and the endothelial basement membrane mainly contains collagen IV that forms a sheet and binds to other extracellular matrix molecules like laminin and proteoglycans. In addition to collagen IV, the epidermal and endothelial basement membrane also contains laminin, perlecan and nidogen. Hyaluronic acid, a pure glycosaminoglycan component, is found in high amounts in damaged or growing tissues. It stimulates cytokine production by macrophages and thus promotes angiogenesis. In normal skin chondroitin sulfate proteoglycan is mainly found in the basement membrane, but in healing wounds they are up-regulated throughout the granulation tissue especially during the second week of wound repair where they provide a temporary matrix with highly hydrative capacity. Binding of growth factors is clearly an important role of perlecan in wound healing and angiogenesis. Poor wound healing in diabetes mellitus may be related to perlecan expression. High levels of glucose can decrease perlecan expression in some cells, probably through transcriptional and post-transcriptional modification. Wound healing phases especially, granulation, re-epithelization and remodelling exhibit controlled turnover of extracellular matrix components.

Altered metabolism
Diabetes mellitus is a metabolic disorder and hence the defects observed in diabetic wound healing are thought to be the result of altered protein and lipid metabolism and thereby abnormal granulation tissue formation. Increased glucose levels in the body end up in uncontrolled covalent bonding of aldose sugars to a protein or lipid without any normal glycosylation enzymes. These stable products then accumulate over the surface of cell membranes, structural proteins and circulating proteins. These products are called advanced glycation endproducts (AGEs) or Amadori products. Formation of AGEs occurs on extracellular matrix proteins with slow turnover rate. AGEs alter the properties of matrix proteins such as collagen, vitronectin, and laminin through AGE-AGE intermolecular covalent bonds or cross-linking. AGE cross-linking on type I collagen and elastin results in increased stiffness. AGEs are also known to increase synthesis of type III collagen that forms the granulation tissue. AGEs on laminin result in reduced binding to type IV collagen in the basement membrane, reduced polymer elongation and reduced binding of heparan sulfate proteoglycan.
Impaired NO synthesis
Nitric oxide is known as an important stimulator of cell proliferation, maturation and differentiation. Thus, nitric oxide increases fibroblast proliferation and thereby collagen production in wound healing. Also, L-arginine and nitric oxide are required for proper cross linking of collagen fibers, via proline, to minimize scarring and maximize the tensile strength of healed tissue. Endothelial cell specific nitric oxide synthase (EcNOS) is activated by the pulsatile flow of blood through vessels. Nitric oxide produced by EcNOS, maintains the diameter of blood vessels and proper blood flow to tissues. In addition to this, nitric oxide also regulates angiogenesis, which plays a major role in wound healing. Thus, diabetic patients exhibit reduced ability to generate nitric oxide from L-arginine. Reasons that have been postulated in the literature include accumulation of nitric oxide synthase inhibitor due to high glucose associated kidney dysfunction and reduced production of nitric oxide synthase due to ketoacidosis observed in diabetic patients and pH dependent nature of nitric oxide synthase.Structural and functional changes in fibroblasts
Diabetic ulcer fibroblasts show various morphological differences compared to fibroblasts from age matched controls. Diabetic ulcer fibroblasts are usually large and widely spread in the culture flask compared to the spindle shaped morphology of the fibroblasts in age-matched controls. They often show dilated endoplasmic reticulum, numerous vesicular bodies and lack of microtubular structure in transmission electron microscopy study. Therefore, interpretation of these observations would be that in spite of high protein production and protein turnover in diabetic ulcer fibroblasts, vesicles containing secretory proteins could not travel along the microtubules to release the products outside. Fibroblasts from diabetic ulcer exhibit proliferative impairment that probably contributes to a decreased production of extracellular matrix proteins and delayed wound contraction and impaired wound healing.Increased matrix metalloproteinases (MMP) activity
In order for a wound to heal, extracellular matrix not only needs to be laid down but also must be able to undergo degradation and remodeling to form a mature tissue with appropriate tensile strength. Proteases, namely matrix metalloproteinases are known to degrade almost all the extracellular matrix components. They are known to be involved in fibroblast and keratinocyte migration, tissue re-organization, inflammation and remodeling of the wounded tissue. Due to persistently high concentrations of pro-inflammatory cytokines in diabetic ulcers, MMP activity is known to increase by 30 fold when compared to acute wound healing. MMP-2 and MMP-9 show sustained overexpression in chronic non-healing diabetic ulcers. Balance in the MMP activity is usually achieved by tissue inhibitor of metalloproteinases (TIMP). Rather than absolute concentrations of either two, it is the ratio of MMP and TIMP that maintains the proteolytic balance and this ratio is found to be disturbed in diabetic ulcer. In spite of these findings, the exact mechanism responsible for increased MMP activity in diabetes is not known yet. One possible line of thought considers Transforming growth factor beta (TGF-β) as an active player. Most MMP genes have TGF-β inhibitory element in their promoter regions and thus TGF–β regulates the expression of both MMP and their inhibitor TIMP. In addition to the importance of cell-cell and cell-matrix interactions, all phases of wound healing are controlled by a wide variety of different growth factors and cytokines. To mention precisely, growth factors promote switching of early inflammatory phase to the granulation tissue formation. Decrease in growth factors responsible for tissue repair such as TGF-β is documented in diabetic wounds. Thus, reduced levels of TGFβ in diabetes cases lower down the effect of inhibitory regulatory effect on MMP genes and thus cause MMPs to over express.

Biomechanics
Complications in the diabetic foot and foot-ankle complex are wider and more destructive than expected and may compromise the structure and function of several systems: vascular, nervous, somatosensory, musculoskeletal. Thus, deeper comprehension of the alteration of gait and foot biomechanics in the diabetic foot is of great interest and may play a role in the design and onset of preventive as well as therapeutic actions.Briefly, the effect of diabetes on the main structures of the foot-ankle complex can be summarised as:

effects on the skin: skin – and the soft tissues immediately underneath the skin – undergo greater compression and shear loading than usual, thus explaining the onset of tissue damage so deeply correlated to traumatic ulceration processes. Besides this, skin of the diabetic foot loses autonomic nervous control and consequently reduced hydration, making it less elastic and thus more vulnerable to the action of increased mechanical stress;
effects on tendons and ligaments: protein glycosylation and the resulting collagen abnormalities lead to greater transversal section – i.e. thickening – of tendons and ligaments and a greater coefficient of elasticity. Particularly impacted by this process are Plantar Fascia and Achilles Tendon. Both causes lead to increased stiffness of those structures;
effects on cartilage: similar to what happens to tendons and ligaments, cartilage changes its composition mainly due to the modification of collagen fibers. This increases its stiffness and decreases the range of motion of all joints in the foot and ankle.
effects on muscles: Diabetes mellitus causes severe damage to nerve conduction, thus causing a worsening in the management of the related muscle fibers. As a consequence, both intrinsic and extrinsic muscles of the foot-ankle complex are damaged in structure (reduction of muscle volume) and function (reduction of muscle strength);
effects on the peripheral sensory system: impaired nerve conduction has a dramatic effect on the peripheral sensory system since it leads to loss of protective sensation under the sole of the foot. This exposes the diabetic foot to thermal or mechanical trauma, and to the late detection of infection processes or tissue breakdown;
effects on foot morphology (deformities): due to most of the above alterations, a significant imbalance of peripheral musculature and soft tissue occur in the foot which seriously alters its morphology and determines the onset of foot deformities. Most common deformities of the diabetic foot are represented by a high longitudinal arch (rigid cavus foot), hammer toes and hallux valgus. A completely different morphologic degeneration is represented by neuropathic arthropathy, whose analysis is not part of this discussion.

Diagnosis
Assessment of diabetic foot ulcer includes identifying risk factors such as diabetic peripheral neuropathy, noting that 50 percent of people are asymptomatic, and ruling out other causes of peripheral neuropathy such as alcohol use disorder and spinal injury.The location of the ulcer, its size, shape, depth and whether the tissue is granulating or sloughy needs to be considered. Further considerations include whether there is malodour, condition of the border of the wound and palpable bone and sinus formation should be investigated. Signs of infection require to be considered such as development of grey or yellow tissue, purulent discharge, unpleasant smell, sinus, undermined edges and exposure of bone or tendon.Identification of diabetic foot in medical databases, such as commercial claims and prescription data, is complicated by the lack of a specific ICD-9 code for diabetic foot and variation in coding practices. The following codes indicate ulcer of the lower limb or foot:
707.1 Ulcer of lower limbs, except pressure ulcer
707.14 Ulcer of heel and midfoot
707.15 Ulcer of other part of foot
707.19 Ulcer of other part of lower limbOne or more codes, in combination with a current or prior diagnosis of diabetes may be sufficient to conclude diabetic foot:

250.0 Diabetes Mellitus
250.8 Diabetes with other specified manifestations

Classification
Diabetic foot ulcer is a complication of diabetes. Diabetic foot ulcers are classified as either neuropathic, neuroischaemic or ischaemic.Doctors also use the Wagner Grades to describe the severity of an ulcer. The purpose of the Wagner Grades is to allow specialists to better monitor and treat diabetic foot ulcers. This grading system classifies Diabetic foot ulcers using numbers, from 0 to 5.
Wagner Grades 0 through 5 are as follows:
0. No diabetic foot ulcer is present, but there is a high risk of developing one.
1. A surface ulcer involves full skin thickness, but does not yet involve the underlying tissues.
2. A deep ulcer penetrates past the surface, down to the ligaments and muscle. There is no abscess or bone involved yet.
3. A deep ulcer occurs with inflammation of subcutaneous connective tissue or an abscess. This can include infections in the muscle, tendon, joint, and/or bone.
4. The tissue around the area of the ulcer (limited to the toes and forefoot) has begun to decay. This condition is called gangrene.
5. Gangrene has spread from the localized area of the ulcer to become extensive. This involves the whole foot.

Prevention
Steps to prevent diabetic foot ulcers include frequent review by a foot specialist and multidisciplinary team, good foot hygiene, diabetic socks and shoes, as well as avoiding injury. Foot-care education combined with increased surveillance can reduce the incidence of serious foot lesions.There is no high quality researches that evaluate complex intervention of combining two or more preventive strategies in preventing diabetic foot ulcer.

Monitoring and prediction
People with loss of feeling in their feet should inspect their feet on a daily basis, to ensure that there are no wounds starting to develop. Monitoring a persons feet can help in predicting the likelihood of developing ulcers.A common method for this is using a special thermometer to look for spots on the foot that have higher temperature which indicate the possibility of an ulcer developing. At the same time there is no strong scientific evidence supporting the effectiveness of at-home foot temperature monitoring.The current guideline in the United Kingdom recommends collecting 8-10 pieces of information for predicting the development of foot ulcers. A simpler method proposed by researchers provides a more detailed risk score based on three pieces of information (insensitivity, foot pulse, previous history of ulcers or amputation). This method is not meant to replace people regularly checking their own feet but complement it.

Footwear
Diabetic shoes, insoles and socks are personalised products that relieve pressure on the foot in order to prevent ulcers. The evidence for special footwear to treat foot ulcers is poor but their effectiveness for prevention is well-established. Design features of footwear that are effective in reducing pressure are arch supports, cushioned cut-outs around points at risk of damage, and cushioning at the ball of the foot. Technology for measuring the pressure within the shoes is recommended during designing diabetic footwear.People with loss of feeling in their feet should not walk around barefoot, but use proper footwear at all times.

Treatment
Foot ulcers in diabetes require multidisciplinary assessment, usually by diabetes nurse specialist, a tissue viability nurse, podiatrists, diabetes specialists and surgeons. An aim to improve glycaemic  control, if poor, forms part of the management, to slow disease progression. Individuals who have sausage shaped toes, a positive probe to bone test, evidence suggesting osteomyelitis, suspected charcot neuroarthropathy, or those whose ulcers do not improve within 4 weeks of standard care and where there is evidence that exudate is of synovial membrane in origin. When osteomyelitis is suspected to be involved in the foot ulcer, but not evidenced on an x-ray, an MRI scan should be obtained.With regards to infected foot ulcers, the presence of microorganisms is not in itself enough to determine whether an infection is present. Signs such as inflammation and purulence are the best indicators of an active infection. The most common organism causing infection is staphylococcus. The treatment consists of debridement, appropriate bandages, managing peripheral arterial disease and appropriate use of antibiotics (against pseudomonas aeruginosa, staphylococcus, streptococcus and anaerobe strains), and arterial revascularisation.

Fespixon Cream(ON101)
There was a novel topical medication developed by a Taiwanese company, Oneness Biotech Co. Ltd (4743:Taipei), called ON101(officially named Fespixon cream(速必一) later), which showed promising efficacy on diabetic foot ulcer healing. During a 3rd phase clinical trial of 236 patients, it showed superior complete healing rate with 60.7% in 16 weeks in average, comparing to aquacel with 35.1%. Its active components were PA-F4(from Plectranthus amboinicus) and S1(from Centella asiatica).Fespixon Cream(ON101) is a first-in-class macrophage-regulating new drug for the chronic wounds. It can effectively regulate the immune environment in the DFU (hyperglycemia causes dermatological immunopathy on DM patients) by suppressing M1 φ overexpression and increase M2 φ to transit the inflammation stage to proliferation stage and to resolve DFU chronicity. On 2021 February, it was approved by Taiwan Food and Drug Administration to be launched in Taiwan market.

Antibiotics
The length of antibiotic courses depend on the severity of the infection and whether bone infection is involved but can range from 1 week to 6 weeks or more. Current recommendations are that antibiotics are only used when there is evidence of infection and continued until there is evidence that the infection has cleared, instead of evidence of ulcer healing. Choice of antibiotic depends on common local bacterial strains known to infect ulcers. Microbiological swabs are believed to be of limited value in identifying causative strain. Microbiological investigation is of value in cases of osteomyelitis. Most ulcer infections involve multiple microorganisms.There is limited safety and efficacy data of topical antibiotics in treating diabetic foot ulcers.

Wound dressings
There are many types of dressings used to treat diabetic foot ulcers such as absorptive fillers, hydrogel dressings, and hydrocolloids. There is no good evidence that one type of dressing is better than another for diabetic foot ulcers. In selecting dressings for chronic non healing wounds it is recommended that the cost of the product be taken into account.Hydrogel dressings may have shown a slight advantage over standard dressings, but the quality of the research is of concern. Dressings and creams containing silver have not been properly studied nor have alginate dressings. Biologically active bandages that combine hydrogel and hydrocolloid traits are available, however more research needs to be conducted as to the efficacy of this option over others.

Total contact casting
Total contact casting (TCC) is a specially designed cast designed to take weight of the foot (off-loading) in patients with DFUs. Reducing pressure on the wound by taking weight of the foot has proven to be very effective in DFU treatment. DFUs are a major factor leading to lower leg amputations among the diabetic population in the US with 85% of amputations in diabetics being preceded by a DFU. Furthermore, the 5 year post-amputation mortality rate among diabetics is estimated at 45% for those with neuropathic DFUs.TCC has been used for off-loading DFUs in the US since the mid-1960s and is regarded by many practitioners as the "reference standard" for off-loading the bottom surface (sole) of the foot.TCC helps patients to maintain their quality of life. By encasing the patients complete foot — including the toes and lower leg — in a specialist cast to redistribute weight and pressure from the foot to the lower leg during everyday movements, patients can remain mobile. The manner in which TCC redistributes pressure protects the wound, letting damaged tissue regenerate and heal. TCC also keeps the ankle from rotating during walking, which helps prevent shearing and twisting forces that can further damage the wound.Effective off loading is a key treatment modality for DFUs, particularly those where there is damage to the nerves in the feet (peripheral neuropathy). Along with infection management and vascular assessment, TCC is vital aspect to effectively managing DFUs. TCC is the most effective and reliable method for off-loading DFUs.A 2013 meta-analysis by the Cochrane Collaboration compared the effectiveness of non-removable pressure relieving interventions, such as casts, with therapeutic shoes, dressings, removable pressure relieving orthotic devices, and surgical interventions. Non-removable pressure relieving interventions, including non-removable casts with an Achilles tendon lengthening component, were found to be more effective at healing foot ulcers related to diabetes that therapeutic shoes and other pressure relieving approaches.TCC systems include TCC-EZ (Integra LifeSciences) and Cutimed Off-loader (BSN Medical).

Hyperbaric oxygen
In 2015, a Cochrane review concluded that for people with diabetic foot ulcers, hyperbaric oxygen therapy reduced the risk of amputation and may improve the healing at 6 weeks. However, there was no benefit at one year and the quality of the reviewed trials was inadequate to draw strong conclusions.

Negative pressure wound therapy
This treatment uses vacuum to remove excess fluid and cellular waste that usually prolong the inflammatory phase of wound healing. Despite a straightforward mechanism of action, results of negative pressure wound therapy studies have been inconsistent. Research needs to be carried out to optimize the parameters of pressure intensity, treatment intervals and exact timing to start negative pressure therapy in the course of chronic wound healing.There is low-certainty evidence that negative pressure wound therapy would improve wound healing in diabetic foot ulcers.

Other treatments
Ozone therapy – there is only limited and poor-quality information available regarding the effectiveness of ozone therapy for treating foot ulcers in people with diabetes.Growth factors - there is some low-quality evidence that growth factors may increase the likelihood that diabetic foot ulcers will heal completely.Continuous diffusion of oxygen (CDO) - CDO delivers continuous oxygen to an occluded, moist wound site at much lower flow rates of 3–12 mL/h for 24 h 7 days a week for up to several weeks or months, depending on the wound status.Phototherapy - there is very weak evidence to suggest that people with foot ulcers due to diabetes may have improved healing </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Tethered spinal cord syndrome and explain in detail? [/INST] Tethered cord syndrome (TCS) refers to a group of neurological disorders that relate to malformations of the spinal cord. Various forms include tight filum terminale, lipomeningomyelocele, split cord malformations (diastematomyelia), occult, dermal sinus tracts, and dermoids.
All forms involve the pulling of the spinal cord at the base of the spinal canal, literally a tethered cord. The spinal cord normally hangs loose in the canal, free to move up and down with growth, and with bending and stretching. A tethered cord, however, is held taut at the end or at some point in the spinal canal. In children, a tethered cord can force the spinal cord to stretch as they grow. In adults the spinal cord stretches in the course of normal activity, usually leading to progressive spinal cord damage if untreated. TCS is often associated with the closure of a spina bifida. It can be congenital, such as in tight filum terminale, or the result of injury later in life.

Signs and symptoms
In children, symptoms may include:

Lesions, hairy patches, dimples, hemangiomas, or fatty tumours on the lower back
Foot and spinal deformities
Weakness in the legs (loss of muscle strength and tone)
Change in or abnormal gait including awkwardness while running or wearing the tips or side of one shoe
Low back pain
Scoliosis (abnormal curvature of the spine to the left or right)
Urinary irregularities (incontinence or retention)Tethered spinal cord syndrome may go undiagnosed until adulthood, when sensory, motor, bowel, and bladder control issues emerge. This delayed presentation of symptoms relates to the degree of strain on the spinal cord over time.
Tethering may also develop after spinal cord injury. Scar tissue can block the flow of fluids around the spinal cord. Fluid pressure may cause cysts to form in the spinal cord, a condition called syringomyelia. This can lead to additional loss of movement or feeling, or the onset of pain or autonomic nervous system symptoms.
In adults, onset of symptoms typically include:

Severe pain (in the lower back and radiating into the legs, groin, and perineum)
Bilateral muscle weakness and numbness
Loss of feeling and movement in lower extremities
Urinary irregularities (incontinence or retention)
Bowel control issuesNeurological symptoms can include a mixed picture of upper and lower motor neuron findings, such as amyotrophy, hyperreflexia or hyporeflexia, a positive stretch sign, and pathologic plantar response, occurring in the same limb. Profound sensory changes, such as loss of pain, temperature, and proprioceptive sensations, are common. Last, progressive symptoms of a neuropathic bladder are noted on over 70% of adult patients, versus only 20% to 30% of children. These symptoms include urinary frequency and urgency, feeling of incomplete voiding, poor voluntary control, nocturia, and urge and stress incontinence. Chronic recurrent infections are common and occasionally lead to nephrolithiasis (kidney stones), kidney failure, or kidney transplantation. Female patients also give a history of ineffective labor and postpartum rectal prolapse, presumably due to an atonic pelvic floor.

Related disorders
Kyphosis
Scoliosis
Brain herniation
Spina Bifida
Ehlers-Danlos syndrome
Klippel-Feil syndrome
Syringomyelia

Cause
Tethered spinal cord can be caused by various conditions but the main cause is when tissue attachments limit the movement of the spinal cord in the spinal column which causes abnormal stretching of the cord.  The tethered spinal cord syndrome is correlated with having the causes:
Spina bifida
Occulta
Mylomeningocele
Meningocele
History of spinal trauma
History of spinal surgery
Tumor(s) in the spinal column
Thickened and/or tight filum terminale
Lipoma(s) in the spinal column
Dermal Sinus Tract (congenital deformity)
Diastematomyelia (split spinal cord)Tethered spinal cord is a disorder and not a mechanism so it does not spread to other people and there are no measures that can be done to prevent it beforehand.  The only preventative measure that is successful is to surgically untether the spinal cord though there might already be irreversible damage.

Spina bifida
In tethered spinal cord cases spina bifida can be accompanied by tethering of the spinal cord but in rare cases with Spina bifida occulta.  Tethering of the spinal cord tends to occur in the cases of Spina bifida with mylomeningocele.  In most people the spine grows faster than the spinal cord during development which causes the end of the spinal cord to appear to rise relative to the bony spine next to it.  By the time of birth the spinal cord is located between L1 and L2.  In a baby with Spina bifida the spinal cord is still attached to the skin around it preventing it from rising properly.  This occurs because the spinal cord in a child with Spina bifida is low lying and tethered at the bottom.  At the time of birth the mylomeningocele is separated from the skin but the spinal cord is still stuck in the same place.  As the child begins to grow the spinal cord remains in the same place becoming stretched out causing the tight cord and the tethering at the end.  With this type of tethering there is an interference with the blood supply to the nerves and body which can then cause the deterioration of the body causing orthopedic, neurological, and urological problems.  With milder forms of Spina bifida such as Occulta, may be related to the degree of strain on the cord which can become worse with physical activity, injury, pregnancy, bone spurs, or spinal stenosis.  The tethered cord in this case might not be diagnosed until adulthood when it worsens and can still cause neurological, orthopedic, and urological dysfunctions.

Mechanism
Tethered spinal cord syndrome is a clinical entity which is manifested by progressive motor and sensory changes in:

legs
incontinence
back of leg pain
scoliosisIn order to understand the pathophysiology that is involved in a tethered spinal cord, the reduction/oxidation ratio has to be used in vivo of cytochrome alpha and alpha 3 to signal the oxidative metabolic functioning in humans.  Studies have found that marked metabolic and electrophysiological susceptibility to hypoxic stress to the lumbar and sacral portion of the spinal cord under traction with various weights.  Similar effects were found in redox behavior of tethered spinal cord during the surgical procedures to repair it.  This can be due to impairment of mitochondrial oxidative metabolism under constant or intermittent stretching.  The act of prolonged stretching can lead to structural damage to the neural perikarya and eventually the axons in neurons. The untethering process can improve the oxidative metabolism and can help to repair injured neurons.

Diagnosis
For children younger than eight weeks of age (and possibly in utero), a tethered cord may be observed using ultrasonography. Ultrasonography may still be useful through age 5 in limited circumstances.
MRI imaging appears to be the gold standard for diagnosing a tethered cord.A tethered cord is often diagnosed as a "low conus." The conus medullaris (or lower termination of the spinal cord) normally terminates at or above the L1-2 disk space (where L1 is the first, or topmost lumbar vertebra). After about 3 months of age, a conus below the L1-2 disk space may indicate a tethered cord and termination below L3-4 is unmistakably tethered. "Cord tethering is often assumed when the conus is below the normal L2-3 level.
TCS, however, is a clinical diagnosis that should be based on "neurological and musculoskeletal signs and symptoms. Imaging features are in general obtained to support rather than make the diagnosis." This is especially true for cases of occult tethered cord, where the patient has the symptoms of tethered cord syndrome but MRI reveals the conus to be above the L2 level.   Clinical evaluation may include a simple rectal examination and may also include invasive or non-invasive urological examination.  "Bladder dysfunction occurs in ~40% of patients affected by tethered cord syndrome. ... [I]t may be the earliest sign of the syndrome."

Treatment
Because neurological deficits are generally irreversible, early surgery is recommended when symptoms begin to worsen. In children, early surgery is recommended to prevent further neurological deterioration, including but not limited to chronic urinary incontinence.
In adults, surgery to detether (free) the spinal cord can reduce the size and further development of cysts in the cord and may restore some function or alleviate other symptoms. Although detethering is the common surgical approach to TCS, another surgical option for adults is a spine-shortening vertebral osteotomy. A vertebral osteotomy aims to indirectly relieve the excess tension on the spinal cord by removing a portion of the spine, shortening it. This procedure offers a unique benefit in that the spinal cord remains fixated to the spine, preventing retethering and spinal cord injury as possible surgical complications. However, its complexity and limited “track record” presently keeps vertebral osteotomies reserved as an option for patients who have failed in preventing retethering after detethering procedure(s).Other treatment is symptomatic and supportive.  Medications such as NSAIDs, opiates, synthetic opiates, COX-2 inhibitors, and off-label applications of tricyclic antidepressants combined with anti-seizure compounds have yet to prove they are of value in treatment of this afflictions pain manifestations.  There is anecdotal evidence that TENS units may benefit some patients.
Treatment may be needed in adults who, while previously asymptomatic, begin to experience pain, lower back degeneration, scoliosis, neck and upper back problems and bladder control issues. Surgery on adults with minimal symptoms is somewhat controversial. For example, a website from the Columbia University Department of Neurosurgery says, "For the child that has reached adult height with minimal if any symptoms, some neurosurgeons would advocate careful observation only." However, surgery for those who have worsening symptoms is less controversial. If the only abnormality is a thickened, shortened filum, then a limited lumbosacral laminectomy with division of the filum may be sufficient to relieve the symptoms.This syndrome was first noticed in the late 19th century. While information has been available for years, little widespread blind research has been done </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Aortic rupture and explain in detail? [/INST] Aortic rupture is the rupture or breakage of the aorta, the largest artery in the body. Aortic rupture is a rare, extremely dangerous condition. The most common cause is an abdominal aortic aneurysm that has ruptured spontaneously </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Retrolisthesis and explain in detail? [/INST] A retrolisthesis is a posterior displacement of one vertebral body with respect to the subjacent vertebra to a degree less than a luxation (dislocation). Retrolistheses are most easily diagnosed on lateral x-ray views of the spine. Views where care has been taken to expose for a true lateral view without any rotation offer the best diagnostic quality.
Retrolistheses are found most prominently in the cervical spine and lumbar region but can also be seen in the thoracic area.

Classification
Retrolisthesis can be classified as a form of spondylolisthesis, since spondylolisthesis is often defined in the literature as displacement in any direction. Yet, medical dictionaries usually define spondylolisthesis specifically as the forward or anterior displacement of a vertebra over the vertebra inferior to it (or the sacrum). Retrolisthesis is also called retrospondylolisthesis.

Signs and symptoms
Retrolisthesis may lead to symptoms of greatly varying intensity and distribution. This is because of the variable nature of the impact on nerve tissue and of the mechanical impact on the spinal joints themselves.Structural instability may be experienced as a local uneasiness through to a more far reaching structural compensatory distortion involving the whole spine. If the joints are stuck in a retrolisthesis configuration there may also be changes to range of motion.Pain may be experienced as a result of irritation to the sensory nerve roots by bone depending on the degree of displacement and the presence of any rotatory positioning of the individual spinal motion segments. The soft tissue of the disc is often caused to bulge in retrolistheses. These cannot be determined by plain films, as the x-ray passes through the soft tissue. A study by Giles et al., stated that sixteen of the thirty patients (53%) had retrolisthesis of L5 on S1 ranging from 2–9 mm; these patients had either intervertebral disc bulging or protrusion on CT examination ranging from 3–7 mm into the spinal canal. Fourteen patients (47%) without retrolisthesis (control group) did not show any retrolisthesis and the CT did not show any bulge/protrusion. On categorizing x-ray and CT pathology as being present or not, the well positioned i.e. true lateral plain x-ray film revealed a sensitivity and specificity of 100% ([95% Confidence Interval. = [89%–100%]) for bulge/protrusion in this preliminary study.” (7)Spinal cord compressions are also possible with patients experiencing pain, rigidity and neurologic signs that may follow some distance along nerves to cause symptoms at some distance from the location of the retrolisthesis.

Diagnosis
Complete Retrolisthesis - The body of one vertebra is posterior to both the vertebral body of the segment of the spine above as well as below.Stairstepped Retrolisthesis - The body of one vertebra is posterior to the body of the spinal segment above, but is anterior to the one below.Partial Retrolisthesis - The body of one vertebra is posterior to the body of the spinal segment either above or below. (3)

Grading
Since the vertebral body in a retrolisthesis moves in a posterior direction, the grading used for spondylolistheses is of little use. It is however useful to divide the anterior to posterior dimension of the intervertebral foramina (IVF) (4) into four equal units. A posterior displacement of up to ¼ of the IVF is graded as Grade 1, ¼ to ½ as Grade 2, ½ to ¾ as Grade 3, ¾ to total occlusion of the IVF as Grade 4. Alternatively, a measurement of the amount of displacement can also made by measuring the bone displacement in millimetres.Retrolistheses can be caused by injury and the resulting instability of the connecting soft tissues especially ligaments, discs, muscles, tendons and fascia. They may also involve muscles through spasm as a result of nerve malfunction due to pressure caused by the posterior displacement of the vertebra encroaching on the contents of the IVF. The IVFs contents include spinal (sensory and motor) nerves, arteries, veins and lymphatic vessels which cater to the nutritional and waste removal needs of the spinal cord.Degenerative spinal changes are often seen at the levels where a retrolisthesis is found. These changes are more pronounced as time progresses after injury, and are evidenced by end plate osteophytosis, disc damage, disc narrowing, desiccation and disc bulging. “A retrolisthesis hyperloads at least one disc and puts shearing forces on the anterior longitudinal ligament, the annular rings, nucleus pulposus, cartilage end plates and capsular ligaments. The bulging, twisting and straining tissues attached to the endplates pull, push and stretch it. It is worsened with time, becoming irreversible.”  This is the etiology of degenerative joint disease. (5)
Associated radiological findings include a vacuum phenomenon (in the nucleus pulposis of the adjacent intervertebral disc), reduction of disc height with corresponding loss of the disc space, marginal sclerosis of the adjacent vertebral bodies, osteophyte formation and apophyseal joint instability. With a retrolisthesis there is always a less than ideal positioning of spinal segments. There is also always a reduced anterior to posterior dimension of the spinal canal compared to the way it is supposed to be. The greater the posterior displacement, the more significant it is for producing a dysfunctional spinal cord or even a cauda equina syndrome.

Joint stability
Joint stability is easily evaluated by the use of flexion and extension lateral x-ray views of the spine.
A summary of part of the DRE tables (6) give a guide as to the implications of the joint instability </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Bicornuate uterus and explain in detail? [/INST] A bicornuate uterus or bicornate uterus (from the Latin cornū, meaning "horn"), is a type of mullerian anomaly in the human uterus, where there is a deep indentation at the fundus (top) of the uterus.

Pathophysiology
A bicornuate uterus develops during embryogenesis. It occurs when the proximal (upper) portion of the paramesonephric ducts does not fuse, but the distal portion that develops into the lower uterine segment, cervix, and upper vagina fuses normally.

Diagnosis
Diagnosis of bicornuate uterus typically involves imaging of the uterus with 2D or 3D ultrasound, hysterosalpingography, or magnetic resonance imaging (MRI). On imaging, a bicornuate uterus can be distinguished from a septate uterus by the angle between the cornua (intercornual angle): less than 75 degrees in a septate uterus, and greater than 105 degrees in a bicornuate uterus. Measuring the depth of the cleft between the cornua (fundal cleft) may also assist in diagnosis; a cleft of over 1 centimetre (0.39 in) is indicative of bicornuate uterus.

Classification
Bicornuate uterus is typically classified based on whether or not the division extends to the external cervical os. Bicornuate uteri with a division above the os are called bicornuate unicollis and those with a divided os are called bicornuate bicollis. There is a continuous range of the degree and location of the fusion of the paramesonephric ducts, and existence of a spectrum, rather than a fixed number of types corresponding to strict medical definitions.
Two processes that occur during the embryonic development of the paramesonephric ducts — fusion and reabsorption — can be affected to different degrees.There is also a hybrid bicornuate uterus: External fundal depressions of variable depths associated with a septate uterus can be seen by laparoscopy, indicating the coexistence of the two anomalies. These cases are candidates for hysteroscopic metroplasty under appropriate sonographic and/or laparoscopic monitoring.An obstructed bicornuate uterus showing uni or bilateral obstruction might also be possible. The unilateral obstruction is more difficult to diagnose than the bilateral obstructive. A delay in the diagnosis can be problematic and compromise the reproductive abilities of those cases.

Treatment
Bicornuate uterus typically requires no treatment. In those who do need treatment, metroplasty is the surgical correction of choice. Women who have recurrent miscarriage with no other explanation may benefit from surgery.

Epidemiology
The occurrence of all types of paramesonephric duct abnormalities in women is estimated around 0.4%. A bicornuate uterus is estimated to occur in 0.1–0.6% of women in the US </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Skull fracture and explain in detail? [/INST] A skull fracture is a break in one or more of the eight bones that form the cranial portion of the skull, usually occurring as a result of blunt force trauma.  If the force of the impact is excessive, the bone may fracture at or near the site of the impact and cause damage to the underlying structures within the skull such as the membranes, blood vessels, and brain.
While an uncomplicated skull fracture can occur without associated  physical or neurological damage and is in itself usually not clinically significant, a fracture in healthy bone indicates that a substantial amount of force has been applied and increases the possibility of associated injury. Any significant blow to the head results in a concussion, with or without loss of consciousness.
A fracture in conjunction with an overlying laceration that tears the epidermis and the meninges, or runs through the paranasal sinuses and the middle ear structures, bringing the outside environment into contact with the cranial cavity is called a compound fracture. Compound fractures can either be clean or contaminated.
There are four major types of skull fractures: linear, depressed, diastatic, and basilar. Linear fractures are the most common, and usually require no intervention for the fracture itself. Depressed fractures are usually comminuted, with broken portions of bone displaced inward—and may require surgical intervention to repair underlying tissue damage. Diastatic fractures widen the sutures of the skull and usually affect children under three. Basilar fractures are in the bones at the base of the skull.

Types
Linear fracture
Linear skull fractures are breaks in the bone that transverse the full thickness of the skull from the outer to inner table. They are usually fairly straight with no bone displacement. The common cause of injury is blunt force trauma where the impact energy transferred over a wide area of the skull.Linear skull fractures are usually of little clinical significance unless they parallel in close proximity or transverse a suture, or they involve a venous sinus groove or vascular channel. The resulting complications may include suture diastasis, venous sinus thrombosis, and epidural hematoma. In young children, although rare, the possibility exists of developing a growing skull fracture especially if the fracture occurs in the parietal bone.

Depressed fracture
A depressed skull fracture is a type of fracture usually resulting from blunt force trauma, such as getting struck with a hammer, rock or getting kicked in the head. These types of fractures—which occur in 11% of severe head injuries—are comminuted fractures in which broken bones displace inward. Depressed skull fractures present a high risk of increased pressure on the brain, or a hemorrhage to the brain that crushes the delicate tissue.Compound depressed skull fractures occur when there is a laceration over the fracture, putting the internal cranial cavity in contact with the outside environment, increasing the risk of contamination and infection. In complex depressed fractures, the dura mater is torn. Depressed skull fractures may require surgery to lift the bones off the brain if they are pressing on it by making burr holes on the adjacent normal skull.

Diastatic fracture
Diastatic fractures occur when the fracture line transverses
one or more sutures of the skull causing a widening of the suture. While this type of fracture is usually seen in infants and young children as the sutures are not yet fused it can also occur in adults. When a diastatic fracture occurs in adults it usually affects the lambdoidal suture as this suture does not fully fuse in adults until about the age of 60. Most adult diastatic fractures are caused by severe head injuries. Due to the trauma, diastatic fracture occurs with the collapse of the surrounding head bones. It crushes the delicate tissue, similarly to a depressed skull fracture.Diastatic fractures can occur with different types of fractures and it is also possible for diastasis of the cranial sutures to occur without a concomitant  fracture. Sutural diastasis may also occur in various congenital disorders such as cleidocranial dysplasia and osteogenesis imperfecta.

Basilar fracture
Basilar skull fractures are linear fractures that occur in the floor of the cranial vault (skull base), which require more force to cause than other areas of the neurocranium. Thus they are rare, occurring as the only fracture in only 4% of severe head injury patients.
Basilar fractures have characteristic signs: blood in the sinuses; cerebrospinal fluid rhinorrhea (CSF leaking from the nose) or from the ears (cerebrospinal fluid otorrhea); periorbital ecchymosis  often called raccoon eyes (bruising of the orbits of the eyes that result from blood collecting there as it leaks from the fracture site); and retroauricular ecchymosis known as "Battles sign" (bruising over the mastoid process).

Growing fracture
A growing skull fracture (GSF) also known as a craniocerebral erosion or leptomeningeal cyst due to the usual development of a cystic mass filled with cerebrospinal fluid is a rare complication of head injury usually associated with linear skull fractures of the parietal bone in children under 3. It has been reported in older children in atypical regions of the skull such as the basioccipital and the base of the skull base and in association with other types of skull fractures. It is characterized by a diastatic enlargement of the fracture.Various factors are associated with the development of a GSF. The primary causative factor is a tear in the dura mater. The skull fracture enlarges due, in part, to the rapid physiologic growth of the brain that occurs in young children, and brain cerebrospinal fluid (CSF) pulsations in the underlying leptomeningeal cystic mass.

Cranial burst fracture
A cranial burst skull fracture, usually occurring with severe injuries in infants less than 1 year of age, is a closed, diastatic skull fracture with cerebral extrusion beyond the outer table of the skull under the intact scalp.Acute scalp swelling is associated with this type of fracture. In equivocal cases without immediate scalp swelling the diagnosis may be made via the use of magnetic resonance imaging thus insuring more prompt treatment and avoiding the development of a "growing skull fracture".

Compound fracture
A fracture in conjunction with an overlying laceration that tears the epidermis and the meninges—or runs through the paranasal sinuses and the middle ear structures, putting the outside environment in contact with the cranial cavity—is a compound fracture.Compound fractures may either be clean or contaminated. Intracranial air (pneumocephalus) may occur in compound skull fractures.The most serious complication of compound skull fractures is infection. Increased risk factors for infection include visible contamination, meningeal tear, loose bone fragments and presenting for treatment more than eight hours after initial injury.

Compound elevated fracture
A compound elevated skull fracture is a rare type of skull fracture where the fractured bone is elevated above the intact outer table of the skull. This type of skull fracture is always compound in nature. It can be caused during an assault with a weapon where the initial blow penetrates the skull and the underlying meninges and, on withdrawal, the weapon lifts the fractured portion of the skull outward. It can also be caused by the skull rotating while being struck in a case of blunt force trauma, the skull rotating while striking an inanimate object as in a fall, or it may occur during transfer of a patient after an initial compound head injury.

Anatomy
The human skull is anatomically divided into two parts: the neurocranium, formed by eight cranial bones that houses and protect the brain—and the facial skeleton (viscerocranium) composed of fourteen bones, not including the three ossicles of the inner ear.  The term skull fracture typically means fractures to the neurocranium, while fractures of the facial portion of the skull are facial fractures, or if the jaw is fractured, a mandibular fracture.The eight cranial bones  are separated by sutures : one frontal bone, two parietal bones, two temporal bones, one occipital bone, one sphenoid bone, and one ethmoid bone.The bones of the skull are in three layers: the hard compact layer of the external table (lamina externa), the diploë (a spongy layer of red bone marrow in the middle, and the compact layer of the inner table (Lamina interna).Skull thickness is variable, depending on location </s>


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


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


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Pseudomyxoma peritonei and explain in detail? [/INST] Pseudomyxoma peritonei (PMP) is a clinical condition caused by cancerous cells (mucinous adenocarcinoma) that produce abundant mucin or gelatinous ascites. The tumors cause fibrosis of tissues and impede digestion or organ function, and if left untreated, the tumors and mucin they produce will fill the abdominal cavity.  This will result in compression of organs and will destroy the function of the colon, small intestine, stomach, or other organs. Prognosis with treatment in many cases is optimistic, but the disease is lethal if untreated, with death occurring via cachexia, bowel obstruction, or other types of complications.
This disease is most commonly caused by an appendiceal primary cancer (cancer of the appendix); mucinous tumors of the ovary have also been implicated, although in most cases ovarian involvement is favored to be a metastasis from an appendiceal or other gastrointestinal source. Disease is typically classified as low- or high-grade (with signet ring cells).  When disease presents with low-grade histologic features the cancer rarely spreads through the lymphatic system or through the bloodstream.

Signs and symptoms
Signs and symptoms of pseudomyxoma peritonei may include abdominal or pelvic pain and/or bloating, distension, digestive disorders, weight changes, increased girth, and infertility.

Cause
The primary tumor appears to arise from the MUC2 expressing goblet cells and most commonly from these cells in the appendix. The K-Ras and p53 genes may be involved in the oncogenesis. It may be diagnosed with a range of conditions. While the majority of these cases are associated with appendiceal carcinomas, other conditions may also be found, including disseminated peritoneal adenomucinosis (DPAM), peritoneal carcinomas, several mucinous tumors (mucinous adenocarcinoma, mucinous cystadenoma, and mucinous cystadenocarcinoma), as well as other disease states. Other primary sites that have been reported include colon, rectum, stomach, gallbladder, bile ducts, small intestine, urinary bladder, lung, breast, fallopian tubes, and the pancreas.

Diagnosis
This disease is often discovered during surgery for other conditions, e.g., hernia repair, following which an experienced pathologist can confirm the diagnosis. Advanced stages may present as tumors palpable on the abdomen or distention of the belly ("jelly belly" is sometimes used as a slang term for the condition).  Due to the rarity of this disease, it is important to obtain an accurate diagnosis so that appropriate treatment may be obtained from a Gastro intestinal cancer surgeon.  Diagnostic tests may include CT scans, examination of tissue samples obtained through laparoscopy, and the evaluation of tumor markers. In most cases a colonoscopy is unsuitable as a diagnostic tool because in most cases appendix cancer invades the abdominal cavity but not the colon (however, spread inside the colon is occasionally reported). PET scans may be used to evaluate high-grade mucinous adenocarcinoma, but this test is not reliable for detecting low-grade tumors because those do not take up the dye which shows up on scans.  New MRI procedures are being developed for disease monitoring, but standard MRIs are not typically used as a diagnostic tool.  Diagnosis is confirmed through pathology.

Classification
There is substantial debate regarding histopathologic classification of pseudomyxoma peritonei. In 1995, Ronnett et al. proposed separating pseudomyxoma peritonei cases into two diagnostic categories: adenoma (disseminated peritoneal adenomucinosis, DPAM) or carcinoma (peritoneal mucinous carcinomatosis, PMCA) with a third category reserved for cases with intermediate features.  In this classification system, cases of DPAM were characterized by peritoneal lesions composed of abundant extracellular mucin containing scant simple to focally proliferative mucinous epithelium with little cytologic atypia or mitotic activity (in other words, most cells looked fairly normal and there was no evidence of mitosis which would indicate that cells were rapidly dividing), with or without an associated appendiceal mucinous adenoma.  Cases of PMCA were characterized by peritoneal lesions composed of more abundant mucinous epithelium with the architectural and cytologic features of carcinoma (irregular cells, evidence that cells were rapidly dividing, and other criteria), with or without an associated primary mucinous adenocarcinoma.  Bradley et al. (2007) argued that continued use of non-malignant terms, i.e., adenoma, for those frequent cases with low-grade features (such as DPAM), is misleading because pseudomyxoma peritonei is a disease state that results from invasion of the abdominal cavity by cells with uncontrolled growth.  Bradley states that an adenoma, by definition, is a tumor confined to the appendiceal mucosa with absolutely no evidence of invasion beyond the muscularis mucosae.
The term mucinous adenocarcinoma is used in different contexts depending on the reference material used by the pathologist for disease classification.  For example, neoplasms characterized by high-grade features, invasive glands and or signet ring cells, are termed adenocarcinoma in pathology literature. However, some pathologists (e.g., Odze and Goldblum, Surgical Pathology of the GI Tract, Liver, Biliary Tract and Pancreas, 2nd ed.) also use the term mucinous adenocarcinoma when referring to low-grade, well-differentiated tumors lacking high-grade features.  Low-grade mucinous adenocarcinoma is used by the American Joint Committee on Cancer and World Health Organization and is nearly or completely synonymous with the DPAM designation. For low-grade mucinous adenocarcinoma, disease may be designated as "benign" because tumors do not invade deeply into tissue and rarely metastasize to parenchyma of organs; this designation may be misleading and confusing to the layperson because pseudomyxoma peritonei is not a harmless condition, fatal if untreated.  High-grade or poorly differentiated mucinous adenocarcinoma has a generally poorer prognosis, though surgical treatment with heated intra-peritoneal chemotherapy (HIPEC) is yielding promising outcomes (see surgical treatment).

Immunohistochemistry
Immunohistochemical features:

Diffuse expression of SATB2, CK20, CDX2, and mCEA
Sometimes patchy CK7; negative PAX8
High-grade neoplasms may show loss of DPC4 (10%)

Treatment
Treatment is variable, both due to its rarity and to its frequently slow-growing nature. Treatment ranges from watchful waiting to debulking and hyperthermic intraperitoneal chemotherapy (HIPEC, also called intraperitoneal hyperthermic chemotherapy, IPHC) with cytoreductive surgery.

Surgical
The standard of care for mucinous adenocarcinoma with clinical condition PMP involves cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC), performed by surgical oncologists who specialize in treating PMP.  Some surgeons also apply early post-operative intraperitonial chemotherapy (EPIC), adjunct to surgical cytoreduction and HIPEC.  In situations where surgery is not required immediately, patients can be monitored via CT scans, tumor marker laboratory tests, and physical symptoms, to determine when, and if, surgery is warranted. Although some surgical procedures may be rather extensive, patients can and do recover from surgery, and the majority of these patients can and do live productive lives.In debulking, the surgeon attempts to remove as much tumor as possible. CRS or cytoreductive surgery involves surgical removal of the peritoneum and any adjacent organs which appear to have tumor seeding. Since the mucus tends to pool at the bottom of the abdominal cavity, it is common to remove the ovaries, fallopian tubes, uterus, and parts of the large intestine.  Depending upon the spread of the tumor, other organs might be removed, including but not limited to the gallbladder, spleen, and portions of the  small intestine and/or stomach.  For organs that cannot be removed safely (like the liver), the surgeon strips off the tumor from the surface.

Chemotherapy
Chemotherapy (typically utilising the chemotherapeutic agent Mitomycin C) may be infused directly into the abdominal cavity after cytoreductive surgery (surgery removing all visible disease to kill remaining microscopic cancerous tumors and free floating cells). The heated chemotherapy (HIPEC) is perfused throughout the abdominal cavity for an hour or two as the last step in the surgery, or ports are installed to allow circulation and/or drainage of the chemicals for one to five days after surgery, known as early postoperative intraperitoneal chemotherapy (EPIC). EPIC may be given in multiple cycles for several months after surgery.Systemic chemotherapy may be administered as additional or adjuvant treatment </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Pronator teres syndrome and explain in detail? [/INST] Pronator teres syndrome is a compression neuropathy of the median nerve at the elbow.
It is rare compared to compression at the wrist (carpal tunnel syndrome) or isolated injury of the anterior interosseous branch of the median nerve (anterior interosseous syndrome).

Symptoms
Compression of the median nerve in the region of the elbow or proximal part of the forearm can cause pain and/or numbness in the distribution of the distal median nerve, and weakness of the muscles innervated by the anterior interosseous nerve: the flexor pollicis longus ("FPL"), the flexor digitorum profundus of the index finger ("FDP IF"), and the pronator quadratus ("PQ").
The pain tends to be at the wrist joint, in the distribution of the terminal branch of the anterior interosseous nerve, and is exacerbated by sustained pronation (i.e., wrist down).
The weakness of the FPL and FDP IF is painless, but causes people to "drop things" and have a sense of loss of dexterity </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Variegate porphyria and explain in detail? [/INST] Variegate porphyria, also known by several other names, is an autosomal dominant porphyria that can have acute (severe but usually not long-lasting) symptoms along with symptoms that affect the skin. The disorder results from low levels of the enzyme responsible for the seventh step in heme production. Heme is a vital molecule for all of the bodys organs. It is a component of hemoglobin, the molecule that carries oxygen in the blood.

Signs and symptoms
When symptoms occur, they can include acute attacks (similar to acute intermittent porphyria) or skin damage. Acute attacks usually begin in adulthood and cause abdominal pain, vomiting, diarrhoea and constipation. During an attack, a person may also experience muscle weakness, seizures, and mental changes such as anxiety and hallucinations. These signs and symptoms are triggered by nongenetic factors such as certain drugs, dieting or fasting, certain hormones and stress.Some people with variegate porphyria have skin that is overly sensitive to sunlight (photosensitive). Areas of skin exposed to the sun develop severe blistering, scarring, changes in pigmentation, and increased hair growth. Exposed skin becomes fragile and is easily damaged.Rarely, the signs and symptoms of variegate porphyria can begin in infancy or early childhood. In such cases, the signs and symptoms are usually more severe than those starting later in life.

Genetics
Mutations in the PPOX gene cause variegate porphyria. The PPOX gene makes a membrane bound mitochondrial enzyme called protoporphyrinogen oxidase, which is critical to the chemical process that leads to heme production </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Mauriac syndrome and explain in detail? [/INST] Mauriac syndrome is a rare complication of type 1 diabetes characterized by extreme liver enlargement due to glycogen deposition, along with growth failure and delayed puberty. It occurs in some children and adolescents with type 1 diabetes irrespective of their glycemic control.

History
Mauriac syndrome was first described in 1930 by Pierre Mauriac. It was described as a syndrome of growth failure and delayed puberty in children with poorly-controlled type I diabetes.

Signs and symptoms
Patients with Mauriac syndrome may present with obesity, hepatomegaly, cushingoid facies, and elevated liver enzymes. Patients usually have growth failure and delayed puberty, which should warn the physician about insufficient management of the patients diabetes. These symptoms can be reversed with good glycemic control.

Genetics
Abnormally high blood sugar levels are relatively common among patients with type I diabetes, but Mauriac syndrome is rare </s>


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


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Dextrocardia and explain in detail? [/INST] Dextrocardia (from Latin dextro, meaning "right hand side," and Greek kardia, meaning "heart") is a rare congenital condition in which the apex of the heart is located on the right side of the body, rather than the more typical placement towards the left. There are two main types of dextrocardia:  dextrocardia of embryonic arrest (also known as isolated dextrocardia) and dextrocardia situs inversus.  Dextrocardia situs inversus is further divided.

Classification
Dextrocardia of embryonic arrest
In this form of dextrocardia, the heart is simply placed further right in the thorax than is normal.  It is commonly associated with severe defects of the heart and related abnormalities including pulmonary hypoplasia.

Dextrocardia situs solitus
Dextrocardia refers to a heart positioned in the right side of the chest </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Natural killer cell enteropathy and explain in detail? [/INST] Natural killer cell enteropathy, also termed  NK cell enteropathy (NKCE), and a closely related disorder, lymphomatoid gastropathy (LG), are non-malignant diseases in which one type of lymphocyte, the natural killer cell (i.e. NK cell), proliferates excessively in  the gastrointestinal tract (GI tract). This proliferation causes red, sore-like spots, raised lesions, erosions, and ulcers in the mucosal layer surrounding the GI tract lumen. Both disorders cause either no or only vague symptoms of GI tract disturbances such as nausea, vomiting, and bleeding.In 2006, a persistent but apparently benign disease that involved the proliferation of NK cells at multiple sites throughout the intestines was described. This disorder appeared similar to and easily mistaken for a highly malignant disease, extranodal NK/T-cell lymphoma, nasal type. In 2010, a similarly non-malignant disorder that involved the proliferation of NK cells in the stomach was described. The disease mimicked gastrointestinal lymphomas. Since these first descriptions, several case series and case reports have been published on these enteropathies.The two NK cell proliferation diseases have been termed NK cell enteropathy and lymphomatoid gastropathy with NKCE being seen mostly in the United States and Korea and LG being seen mostly in Japan. Besides this geographical difference, the only other critical difference between the two diseases is that the lesions in NKCE occur in the small intestine, colon, stomach, and/or esophagus while those of LG are limited to the stomach. Since the pathophysiological features of the two diseases are virtually identical, NKCE and LG are now commonly viewed as manifestations of the same disease.Only 36 patients with NKCE or LG have been reported as of January 2019. Nonetheless, these diseases are emerging as important clinical entities because they 1) are newly described and likely to be diagnosed more often as they become better known and 2) have been mistaken for, and treated as, various types of pre-malignant and malignant lymphomas of the GI tract. Given the radical differences in the prognoses and treatments of NKCE and LG compared to the lymphomas that they can mimic, the evaluation of many lymphocyte-proliferating disorders of the GI tract must consider and rule out the possibility that they are NKCE or LG rather than a pre-malignant disorder or malignant lymphoma.

Presentation
Most cases of NKCE and LG have been reported in middle-aged or older individuals. Patients diagnosed with NKCE (medium age 46 years) have presented with vague abdominal pain, indigestion, vomiting, diarrhea, constipation, weight loss, anemia, and/or GI bleeding. Two patients complained of biliary colic (i.e. gallbladder pain) and were found to have typical lesions of NKCE in their cystic ducts. These two cases indicate that NKCE involvement is not totally limited to the alimentary canal. Three of 15 individuals diagnosed with NKCE disease reported no symptoms, their disease being found on endoscopy conducted for screening purposes. Typically, patients diagnosed with LG (medium age 58 years) have been asymptomatic at presentation with their disease being detected during GI tract examinations done for other reasons. Three of twenty patients diagnosed with LG complained of pain or discomfort in the upper abdominal region. Symptomatic individuals with either disease generally have a long history of persistent or intermittent symptoms.

Pathophysiology
NK cells normally occupy the GI tract where they contribute to innate immunity by becoming active in killing pathogen-infected and cancerous cells. The proliferating lymphocytes in NKCE and LG express CD56 and CD7 proteins on their cell surface membrane, CD3γ protein in their cytoplasm, and granzyme B, perforin, and T-cell intracellular antigen-1 cytotoxic proteins within their cytoplasmic granules. This pattern of protein expression identifies these cells as NK cells that, because of their expression of the cytotoxic granule-bound proteins, have been activated. However, the cause(s) for the activation of these cells as wells as for their rapid proliferation to produce NKCE and LG is unknown. To date, no evidence of NK cell clonality (i.e. cells developing from a single precursor) or for these cells to bear gene mutations or chromosome abnormalities have been reported in NKCE or LG. These findings help distinguish LB and NKCE from many lymphomas and support the conclusion that neither disease is malignant. The NK cells in LG and NKCE are not infected with the Epstein-Barr virus (EBV), as evidenced by their failure to express this viruss latency proteins and latency ncRNAs. This finding indicates that EBV is not the cause for the NK cell activation and excessive proliferation seen in NKCE and LG and distinguishes these diseases from malignant diseases they can mimic such as extranodal NK/T-cell lymphoma, nasal type. In isolated reports, LG has occurred in individuals with Helicobacter pylori infection of the stomach or a history of stomach cancer, while NKCE has been reported to occur in patients with gluten sensitivity or circulating anti-gliadin antibodies. Both of the latter conditions are associated with the development of GI tract lymphomas. However, the relationship of any of these findings to the etiology of LB and NKCE is unclear.

Histology
Biopsies of NKCE tissues reveal atypical medium to large lymphocytes identified by immunohistochemistry to be NK cells that are multiplying at a moderately rapid rate and that lack evidence of being infected by the Epstein-Barr virus. These cells are located primarily in the lamina propria, i.e. loose connective tissue lying just below the epithelium lining the GI tract. There is generally little invasion of these cells into the epithelium, submucosa, or glands of the GI tract, and the lesions almost always show a complete absence of vascular injury due to invasion by these cells. The lesions in LG closely resemble those of NKCE.

Diagnosis
The diagnoses of NKCE and LG depends on clinical and pathological findings indicating that the two diseases: a) are indolent and non-malignant; b) usually manifested by mild, vague, or no symptoms; c) localize to the GI tract without involvement of the head, neck, or organs such as the liver and spleen; d) consist of one or more lesions localized primarily to the lamina propria of the esophagus, stomach, small intestine, and/or large intestine (for NKCE} or to the stomach (for LG); and e) involve lesions which contain medium-to large-sized, atypical, and non-clonal lymphocytes that are activated NK cells (see Pathophysiology section) which proliferate at moderately rapid rates (as gauged by, e.g. analysis of their Ki-67 protein levels), lack evidence of Epstein-Barr virus infection, gene mutations, or chromosome abnormalities, and show little evidence of centering around, and destroying, blood vessels.

Differential diagnosis
In early studies, aggressive chemotherapy with or without bone marrow translanton and gastric resections were used to treat NKCE and LG, respectively, based on the assumptions that these diseases were malignant </s>