<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Arthrofibrosis and can you explain it in depth? [/INST] Arthrofibrosis (from Greek: arthro- joint, fibrosis – scar tissue formation) has been described in most joints like knee, hip, ankle, foot joints, shoulder (frozen shoulder, adhesive capsulitis), elbow (stiff elbow), wrist, hand joints as well as spinal vertebrae. It can occur after injury or surgery or may arise without an obvious cause. There is excessive scar tissue formation within the joint and/or surrounding soft tissues leading to painful restriction of joint motion that persists despite physical therapy and rehabilitation. The scar tissue may be located inside the knee joint or may involve the soft tissue structures around the knee joint, or both locations.
The pathology that causes arthrofibrosis also causes other forms of fibrosis. Injury and inflammation activates fibroblasts and other cell types, turning them into myofibroblasts which create scar tissue and more inflammation.

Arthrofibrosis of the knee (frozen knee)
Arthrofibrosis of the knee, also known as "frozen knee", has been one of the more studied joints as a result of its frequency of occurrence.  Arthrofibrosis can follow knee injury and knee surgeries like arthroscopic knee surgery or knee replacement. Scar tissue can cause structures of the knee to become contracted, restricting normal motion.  Depending on the site of scarring, knee cap mobility and/or joint range of motion (i.e. flexion, extension, or both) may be affected.  Symptoms experienced as a result of arthrofibrosis of the knee include stiffness, pain, limping, heat, swelling, crepitus, and/or weakness.  Clinical diagnosis may also include the use of magnetic resonance imaging (or MRI) to visualize the knee compartments affected. The consequent pain may lead to the cascade of quadriceps weakness, patellar tendon shortening and scarring in the tissues around the knee cap—with an end stage of permanent patella infera—where the knee cap is pulled down into an abnormal position where it becomes vulnerable to joint surface damage.

Arthrofibrosis after knee injury, knee arthroscopy or other surgeries
The first step in treating arthrofibrosis is appropriately directed physical therapy with a focus on icing and elevating and passive stretching exercises such as continuous passive motion (CPM). Passive stretching can increase range of motion if conducted frequently and carefully so that tissues are not torn. There are a number of treatment options and treatment varies depending on the knowledge of the treating clinician and on the cause and duration of the fibrosis. Often physical therapy is used as an attempt at conservative management. Knowledge of the role of inflammation in arthrofibrosis has led a cautionary approach to exercise, because exercise increases inflammation. Advice to AF patients now typically consists of "listen to your knee" and stop, or reduce, activities that increase pain during and after exercise. Aggressive exercise of the affected limb may cause permanent damage.
If physical therapy fails options include manipulation under anaesthesia (MUA), arthroscopic lysis of adhesions and open lysis of adhesions. Although MUA and surgery can be successful, the resulting increase in inflammation may cause scar tissue to rapidly return and symptoms can worsen.Pharmacological interventions such as anti-inflammatory medications and supplements are increasingly used to treat arthrofibrosis. Biologics that reduce the signalling of the major inflammatory cytokines TNF-α (Simponi, Humira) and IL-1β (anakinra) are promising treatments. Consultation with a rheumatologist can help to determine appropriate medications.

After knee replacement
Arthrofibrosis can occur after total knee replacement or partial knee replacement, when excessive scar tissue (collagen fibril) deposition occurs in and around the knee. This can be accompanied by shortening of the patellar tendon (patella baja/infera) which can also contribute to limited flexion. The rates of AF after TKA vary widely in the literature as there is no standard definition </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Oil acne and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Pulmonary alveolar microlithiasis and can you explain it in depth? [/INST] Pulmonary alveolar microlithiasis (PAM) is a rare, inherited disorder of lung phosphate balance that is associated with small stone formation in the airspaces of the lung. Mutations in the gene SLC34A2 result in loss of a key sodium, phosphate co-transporter (called Npt2b), known to be expressed in distal alveolar type II cells, as well as in the mammary gland, and to a lesser extent in intestine, kidney, skin, prostate and testes. As the disease progresses, the lung fields become progressively more dense (white) on the chest xray, and low oxygen level, lung inflammation and fibrosis, elevated pressures in the lung blood vessels, and respiratory failure ensue, usually in middle age. The clinical course of PAM can be highly variable, with some patients remaining asymptomatic for decades, and others progressing more rapidly. There is no effective treatment, and the mechanisms of stone formation, inflammation and scarring are not known.

Signs and symptoms
Patients typically have no symptoms until the third or fourth decade of life. In most cases, the disease is discovered incidentally on routine chest Xray. The most common symptoms include the following:
dyspnea
dry cough
chest pain
sporadic hemoptysis
asthenia
pneumothoraces

Genetics
PAM is hereditary and another involved family member can be identified in 36% to 61% of cases. Impaired activity of the SLC34A2 gene is responsible for PAM.The SLC34A2 gene encodes a membrane protein that is expressed primarily in the apical portions of alveolar type II cells and is the most abundant phosphate carrier in the lungs.

Pathogenesis
Type II alveolar cells have many important functions in the lung, including the production of pulmonary surfactant, maintenance of fluid balance and composition in the airspace. Phospholipids that make up pulmonary surfactant are broken down by macrophages, releasing phosphate into the alveolar lining fluid. The loss of the Npt2b phosphate transported eliminates the ability of alveolar type II cells to pump phosphorus ions from the alveolar space back into the bloodstream, and leads to microlith formation.Epithelial deletion of Npt2b in mice results in an authentic mimic of the human condition, including accumulation of calcium phosphate microliths in the lung tissue and progressive diffuse radiographic opacities. The mouse model provides a useful platform for preclinical studies, including therapeutic trials of EDTA lavage and low phosphate diet/phosphate binders.

Pathology
PAM may be confined to certain areas or show diffuse distribution through the lungs. Lung biopsy and autopsy specimens demonstrate characteristic intra-alveolar lamellar microliths. Calcium deposits in the alveoli begin in the lower lobes and spread over a period of years throughout the lungs.

Diagnosis
PAM is usually diagnosed on the basis of a typical radiological pattern, namely a very fine, sand-like micronodulation of calcific density diffusely involving both lungs, with basal predominance. Many authors argue that this pattern precludes the need for a lung biopsy in most cases. After PAM is diagnosed in a given patient, family members should be screened by chest radiography, and parents should be counseled that future children are also at risk of developing the disease.

Radiology
Chest radiographs of patients with PAM usually reveal bilateral diffuse micronodular calcifications, producing a "sandstorm” appearance that first involves the inferior portions and then the middle and upper portions of the lungs.

High-resolution computed tomography
The most common findings on HRCT are diffuse hyperdense ground-glass attenuation and subpleural linear calcifications, often most predominant in the inferior and posterior portions of the lungs. Additionally, the medial aspects of the lungs appear to be more heavily involved than the lateral aspects </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Gastrocutaneous syndrome and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Arthritis and can you explain it in depth? [/INST] Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In some types of arthritis, other organs are also affected. Onset can be gradual or sudden.There are over 100 types of arthritis. The most common forms are osteoarthritis (degenerative joint disease) and rheumatoid arthritis. Osteoarthritis usually occurs with age and affects the fingers, knees, and hips. Rheumatoid arthritis is an autoimmune disorder that often affects the hands and feet. Other types include gout, lupus, fibromyalgia, and septic arthritis. They are all types of rheumatic disease.Treatment may include resting the joint and alternating between applying ice and heat. Weight loss and exercise may also be useful. Recommended medications may depend on the form of arthritis. These may include pain medications such as ibuprofen and paracetamol (acetaminophen). In some circumstances, a joint replacement may be useful.Osteoarthritis affects more than 3.8% of people, while rheumatoid arthritis affects about 0.24% of people. Gout affects about 1–2% of the Western population at some point in their lives. In Australia about 15% of people are affected by arthritis, while in the United States more than 20% have a type of arthritis. Overall the disease becomes more common with age. Arthritis is a common reason that people miss work and can result in a decreased quality of life. The term is derived from arthr- (meaning joint) and -itis (meaning inflammation).

Classification
There are several diseases where joint pain is primary, and is considered the main feature. Generally when a person has "arthritis" it means that they have one of these diseases, which include:

Osteoarthritis
Rheumatoid arthritis
Gout and pseudo-gout
Septic arthritis
Ankylosing spondylitis
Juvenile idiopathic arthritis
Stills disease
Psoriatic arthritisJoint pain can also be a symptom of other diseases. In this case, the arthritis is considered to be secondary to the main disease; these include:

Psoriasis
Reactive arthritis
Ehlers–Danlos syndrome
Iron overload
Hepatitis
Lyme disease
Sjögrens disease
Hashimotos thyroiditis
Celiac disease
Non-celiac gluten sensitivity
Inflammatory bowel disease (including Crohns disease and ulcerative colitis)
Henoch–Schönlein purpura
Hyperimmunoglobulinemia D with recurrent fever
Sarcoidosis
Whipples disease
TNF receptor associated periodic syndrome
Granulomatosis with polyangiitis (and many other vasculitis syndromes)
Familial Mediterranean fever
Systemic lupus erythematosus
An undifferentiated arthritis is an arthritis that does not fit into well-known clinical disease categories, possibly being an early stage of a definite rheumatic disease.

Signs and symptoms
Pain, which can vary in severity, is a common symptom in virtually all types of arthritis. Other symptoms include swelling, joint stiffness, redness, and aching around the joint(s). Arthritic disorders like lupus and rheumatoid arthritis can affect other organs in the body, leading to a variety of symptoms. Symptoms may include:
Inability to use the hand or walk
Stiffness in one or more joints
Rash or itch
Malaise and fatigue
Weight loss
Poor sleep
Muscle aches and pains
Tenderness
Difficulty moving the jointIt is common in advanced arthritis for significant secondary changes to occur. For example, arthritic symptoms might make it difficult for a person to move around and/or exercise, which can lead to secondary effects, such as:

Muscle weakness
Loss of flexibility
Decreased aerobic fitnessThese changes, in addition to the primary symptoms, can have a huge impact on quality of life.

Disability
Arthritis is the most common cause of disability in the United States. More than 20 million individuals with arthritis have severe limitations in function on a daily basis. Absenteeism and frequent visits to the physician are common in individuals who have arthritis. Arthritis can make it difficult for individuals to be physically active and some become home bound.
It is estimated that the total cost of arthritis cases is close to $100 billion of which almost 50% is from lost earnings. Each year, arthritis results in nearly 1 million hospitalizations and close to 45 million outpatient visits to health care centers.Decreased mobility, in combination with the above symptoms, can make it difficult for an individual to remain physically active, contributing to an increased risk of obesity, high cholesterol or vulnerability to heart disease. People with arthritis are also at increased risk of depression, which may be a response to numerous factors, including fear of worsening symptoms.

Risk factors
There are common risk factors that increase a persons chance of developing arthritis later in adulthood. Some of these are modifiable while others are not. Smoking has been linked to an increased susceptibility of developing arthritis, particularly rheumatoid arthritis.

Diagnosis
Diagnosis is made by clinical examination from an appropriate health professional, and may be supported by other tests such as radiology and blood tests, depending on the type of suspected arthritis. All arthritides potentially feature pain. Pain patterns may differ depending on the arthritides and the location. Rheumatoid arthritis is generally worse in the morning and associated with stiffness lasting over 30 minutes. However, in the early stages, patients may have no symptoms after a warm shower. Osteoarthritis, on the other hand, tends to be associated with morning stiffness which eases relatively quickly with movement and exercise. In the aged and children, pain might not be the main presenting feature; the aged patient simply moves less, the infantile patient refuses to use the affected limb.

Elements of the history of the disorder guide diagnosis. Important features are speed and time of onset, pattern of joint involvement, symmetry of symptoms, early morning stiffness, tenderness, gelling or locking with inactivity, aggravating and relieving factors, and other systemic symptoms. Physical examination may confirm the diagnosis or may indicate systemic disease. Radiographs are often used to follow progression or help assess severity.Blood tests and X-rays of the affected joints often are performed to make the diagnosis. Screening blood tests are indicated if certain arthritides are suspected. These might include: rheumatoid factor, antinuclear factor (ANF), extractable nuclear antigen, and specific antibodies.

Osteoarthritis
Osteoarthritis is the most common form of arthritis. It affects humans and other animals, notably dogs, but also occurs in cats and horses. It can affect both the larger and the smaller joints of the body. In humans, this includes the hands, wrists, feet, back, hip, and knee. In dogs, this includes the elbow, hip, stifle (knee), shoulder, and back. The disease is essentially one acquired from daily wear and tear of the joint; however, osteoarthritis can also occur as a result of injury.  Osteoarthritis begins in the cartilage and eventually causes the two opposing bones to erode into each other. The condition starts with minor pain during physical activity, but soon the pain can be continuous and even occur while in a state of rest. The pain can be debilitating and prevent one from doing some activities. In dogs, this pain can significantly affect quality of life and may include difficulty going up and down stairs, struggling to get up after lying down, trouble walking on slick floors, being unable to hop in and out of vehicles, difficulty jumping on and off furniture, and behavioral changes (e.g., aggression, difficulty squatting to toilet). Osteoarthritis typically affects the weight-bearing joints, such as the back, knee and hip. Unlike rheumatoid arthritis, osteoarthritis is most commonly a disease of the elderly. The strongest predictor of osteoarthritis is increased age, likely due to the declining ability of chondrocytes to maintain the structural integrity of cartilage. More than 30 percent of women have some degree of osteoarthritis by age 65. Other risk factors for osteoarthritis include prior joint trauma, obesity, and a sedentary lifestyle.

Rheumatoid arthritis
Rheumatoid arthritis (RA) is a disorder in which the bodys own immune system starts to attack body tissues. The attack is not only directed at the joint but to many other parts of the body. In rheumatoid arthritis, most damage occurs to the joint lining and cartilage which eventually results in erosion of two opposing bones. RA often affects joints in the fingers, wrists, knees and elbows, is symmetrical (appears on both sides of the body), and can lead to severe deformity in a few years if not treated. RA occurs mostly in people aged 20 and above. In children, the disorder can present with a skin rash, fever, pain, disability, and limitations in daily activities. With earlier diagnosis and aggressive treatment, many individuals can lead a better quality of life than if going undiagnosed for long after RAs onset. The risk factors with the strongest association for developing rheumatoid arthritis are the female sex, a family history of rheumatoid arthritis, age, obesity, previous joint damage from an injury, and exposure to tobacco smoke.Bone erosion is a central feature of rheumatoid arthritis. Bone continuously undergoes remodeling by actions of bone resorbing osteoclasts and bone forming osteoblasts. One of the main triggers of bone erosion in the joints in rheumatoid arthritis is inflammation of the synovium, caused in part by the production of pro-inflammatory cytokines and receptor activator of nuclear factor kappa B ligand (RANKL), a cell surface protein present in Th17 cells and osteoblasts. Osteoclast activity can be directly induced by osteoblasts through the RANK/RANKL mechanism.

Lupus
Lupus is a common collagen vascular disorder that can be present with severe arthritis. Other features of lupus include a skin rash, extreme photosensitivity, hair loss, kidney problems, lung fibrosis and constant joint pain.

Gout
Gout is caused by deposition of uric acid crystals in the joints, causing inflammation. There is also an uncommon form of gouty arthritis caused by the formation of rhomboid crystals of calcium pyrophosphate known as pseudogout. In the early stages, the gouty arthritis usually occurs in one joint, but with time, it can occur in many joints and be quite crippling. The joints in gout can often become swollen and lose function. Gouty arthritis can become particularly painful and potentially debilitating when gout cannot successfully be treated. When uric acid levels and gout symptoms cannot be controlled with standard gout medicines that decrease the production of uric acid (e.g., allopurinol) or increase uric acid elimination from the body through the kidneys (e.g., probenecid), this can be referred to as refractory chronic gout.

Comparison of types
Other
Infectious arthritis is another severe form of arthritis. It presents with sudden onset of chills, fever and joint pain. The condition is caused by bacteria elsewhere in the body. Infectious arthritis must be rapidly diagnosed and treated promptly to prevent irreversible joint damage.Psoriasis can develop into psoriatic arthritis. With psoriatic arthritis, most individuals develop the skin problem first and then the arthritis. The typical features are continuous joint pains, stiffness and swelling. The disease does recur with periods of remission but there is no cure for the disorder. A small percentage develop a severely painful and destructive form of arthritis which destroys the small joints in the hands and can lead to permanent disability and loss of hand function.

Treatment
There is no known cure for arthritis and rheumatic diseases. Treatment options vary depending on the type of arthritis and include physical therapy, exercise and diet, orthopedic bracing, and oral and topical medications. Joint replacement surgery may be required to repair damage, restore function, or relieve pain.

Physical therapy
In general, studies have shown that physical exercise of the affected joint can noticeably improve long-term pain relief. Furthermore, exercise of the arthritic joint is encouraged to maintain the health of the particular joint and the overall body of the person.Individuals with arthritis can benefit from both physical and occupational therapy. In arthritis the joints become stiff and the range of movement can be limited. Physical therapy has been shown to significantly improve function, decrease pain, and delay the need for surgical intervention in advanced cases. Exercise prescribed by a physical therapist has been shown to be more effective than medications in treating osteoarthritis of the knee. Exercise often focuses on improving muscle strength, endurance and flexibility. In some cases, exercises may be designed to train balance. Occupational therapy can provide assistance with activities. Assistive technology is a tool used to aid a persons disability by reducing their physical barriers by improving the use of their damaged body part, typically after an amputation. Assistive technology devices can be customized to the patient or bought commercially.

Medications
There are several types of medications that are used for the treatment of arthritis. Treatment typically begins with medications that have the fewest side effects with further medications being added if insufficiently effective.Depending on the type of arthritis, the medications that are given may be different. For example, the first-line treatment for osteoarthritis is acetaminophen (paracetamol) while for inflammatory arthritis it involves non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen. Opioids and NSAIDs may be less well tolerated. However, topical NSAIDs may have better safety profiles than oral NSAIDs. For more severe cases of osteoarthritis, intra-articular corticosteroid injections may also be considered.The drugs to treat rheumatoid arthritis (RA) range from corticosteroids to monoclonal antibodies given intravenously. Due to the autoimmune nature of RA, treatments may include not only pain medications and anti-inflammatory drugs, but also another category of drugs called disease-modifying antirheumatic drugs (DMARDs). Treatment with DMARDs is designed to slow down the progression of RA by initiating an adaptive immune response, in part by CD4+ T helper (Th) cells, specifically Th17 cells. Th17 cells are present in higher quantities at the site of bone destruction in joints and produce inflammatory cytokines associated with inflammation, such as interleukin-17 (IL-17).

Surgery
A number of rheumasurgical interventions have been incorporated in the treatment of arthritis since the 1950s. Arthroscopic surgery for osteoarthritis of the knee provides no additional benefit to optimized physical and medical therapy.

Adaptive aids
People with hand arthritis can have trouble with simple activities of daily living tasks (ADLs), such as turning a key in a lock or opening jars, as these activities can be cumbersome and painful. There are adaptive aids or assistive devices (ADs) available to help with these tasks, but they are generally more costly than conventional products with the same function. It is now possible to 3-D print adaptive aids, which have been released as open source hardware to reduce patient costs. Adaptive aids can significantly help arthritis patients and the vast majority of those with arthritis need and use them.

Alternative medicine
Further research is required to determine if transcutaneous electrical nerve stimulation (TENS) for knee osteoarthritis is effective for controlling pain.Low level laser therapy may be considered for relief of pain and stiffness associated with arthritis. Evidence of benefit is tentative.Pulsed electromagnetic field therapy (PEMFT) has tentative evidence supporting improved functioning but no evidence of improved pain in osteoarthritis. The FDA has not approved PEMFT for the treatment of arthritis. In Canada, PEMF devices are legally licensed by Health Canada for the treatment of pain associated with arthritic conditions.

Epidemiology
Arthritis is predominantly a disease of the elderly, but children can also be affected by the disease. Arthritis is more common in women than men at all ages and affects all races, ethnic groups and cultures. In the United States a CDC survey based on data from 2013 to 2015 showed 54.4 million (22.7%) adults had self-reported doctor-diagnosed arthritis, and 23.7 million (43.5% of those with arthritis) had arthritis-attributable activity limitation (AAAL). With an aging population, this number is expected to increase. Adults with co-morbid conditions, such as heart disease, diabetes, and obesity, were seen to have a higher than average prevalence of doctor-diagnosed arthritis (49.3%, 47.1%, and 30.6% respectively).Disability due to musculoskeletal disorders increased by 45% from 1990 to 2010. Of these, osteoarthritis is the fastest increasing major health condition. Among the many reports on the increased prevalence of musculoskeletal conditions, data from Africa are lacking and underestimated </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Pesticide poisoning and can you explain it in depth? [/INST] A pesticide poisoning occurs when pesticides, chemicals intended to control a pest, affect non-target organisms such as humans, wildlife, plant, or bees. There are three types of pesticide poisoning. The first of the three is a single and short-term very high level of exposure which can be experienced by individuals who commit suicide, as well as pesticide formulators. Type two poisoning is long-term high-level exposure, which can occur in pesticide formulators and manufacturers. The third type of poisoning is a long-term low-level exposure, which individuals are exposed to from sources such as pesticide residues in food as well as contact with pesticide residues in the air, water, soil, sediment, food materials, plants and animals.In developing countries, such as Sri Lanka, pesticide poisonings from short-term very high level of exposure (acute poisoning) is the most worrisome type of poisoning. However, in developed countries, such as Canada, it is the complete opposite: acute pesticide poisoning is controlled, thus making the main issue long-term low-level exposure of pesticides.

Cause
The most common exposure scenarios for pesticide-poisoning cases are accidental or suicidal poisonings, occupational exposure, by-stander exposure to off-target drift, and the general public who are exposed through environmental contamination.

Accidental or suicidal
Self-poisoning with agricultural pesticides represents a major hidden public health problem accounting for approximately one-third of all suicides worldwide. It is one of the most common forms of self-injury in the Global South. The World Health Organization estimates that 300,000 people die from self-harm each year in the Asia-Pacific region alone. Most cases of intentional pesticide poisoning appear to be impulsive acts undertaken during stressful events, and the availability of pesticides strongly influences the incidence of self poisoning. Pesticides are the agents most frequently used by farmers and students in India to commit suicide.

Occupational
Pesticide poisoning is an important occupational health issue because pesticides are used in a large number of industries, which puts many different categories of workers at risk.  Extensive use puts agricultural workers in particular at increased risk for pesticide illnesses. Exposure can occur through inhalation of pesticide fumes, and often occurs in settings including greenhouse spraying operations and other closed environments like tractor cabs or while operating rotary fan mist sprayers in facilities or locations with poor ventilation systems.
Workers in other industries are at risk for exposure as well.  For example, commercial availability of pesticides in stores puts retail workers at risk for exposure and illness when they handle pesticide products. The ubiquity of pesticides puts emergency responders such as fire-fighters and police officers at risk, because they are often the first responders to emergency events and may be unaware of the presence of a poisoning hazard.  The process of aircraft disinsection, in which pesticides are used on inbound international flights for insect and disease control, can also make flight attendants sick.Different job functions can lead to different levels of exposure.  Most occupational exposures are caused by absorption through exposed skin such as the face, hands, forearms, neck, and chest.  This exposure is sometimes enhanced by inhalation in settings including spraying operations in greenhouses and other closed environments, tractor cabs, and the operation of rotary fan mist sprayers.

Residential
The majority of households in Canada use pesticides while taking part in activities such as gardening. In Canada, 96 percent of households report having a lawn or a garden. 56 percent of the households who have a lawn or a garden utilize fertilizer or pesticide. This form of pesticide use may contribute to the third type of poisoning, which is caused by long-term low-level exposure. As mentioned before, long-term low-level exposure affects individuals from sources such as pesticide residues in food as well as contact with pesticide residues in the air, water, soil, sediment, food materials, plants and animals.

Pathophysiology
Organochlorines
The organochlorine pesticides, like DDT, aldrin, and dieldrin, are extremely persistent and accumulate in fatty tissue.  Through the process of bioaccumulation (lower amounts in the environment get magnified sequentially up the food chain), large amounts of organochlorines can accumulate in top species like humans.  There is substantial evidence to suggest that DDT, and its metabolite DDE, act as endocrine disruptors, interfering with hormonal function of estrogen, testosterone, and other steroid hormones.

Anticholinesterase compounds
Cholinesterase-inhibiting pesticides, also known as organophosphates, carbamates, and anticholinesterases, are most commonly reported in occupationally related pesticide poisonings globally. Besides acute symptoms including cholinergic crisis, certain organophosphates have long been known to cause a delayed-onset toxicity to nerve cells, which is often irreversible.  Several studies have shown persistent deficits in cognitive function in workers chronically exposed to pesticides.

Diagnosis
Most pesticide-related illnesses have signs and symptoms that are similar to common medical conditions, so a complete and detailed environmental and occupational history is essential for correctly diagnosing a pesticide poisoning.  A few additional screening questions about the patients work and home environment, in addition to a typical health questionnaire, can indicate whether there was a potential pesticide poisoning.If one is regularly using carbamate and organophosphate pesticides, it is important to obtain a baseline cholinesterase test. Cholinesterase is an important enzyme of the nervous system, and these chemical groups kill pests and potentially injure or kill humans by inhibiting cholinesterase. If one has had a baseline test and later suspects a poisoning, one can identify the extent of the problem by comparison of the current cholinesterase level with the baseline level.

Prevention
Accidental poisonings can be avoided by proper labeling and storage of containers.  When handling or applying pesticides, exposure can be significantly reduced by protecting certain parts of the body where the skin shows increased absorption, such as the scrotal region, underarms, face, scalp, and hands. Safety protocols to reduce exposure include the use of personal protective equipment, washing hands and exposed skin during as well as after work, changing clothes between work shifts, and having first aid trainings and protocols in place for workers.Personal protective equipment for preventing pesticide exposure includes the use of a respirator, goggles, and protective clothing, which have all have been shown to reduce risk of developing pesticide-induced diseases when handling pesticides. A study found the risk of acute pesticide poisoning was reduced by 55% in farmers who adopted extra personal protective measures and were educated about both protective equipment and pesticide exposure risk. Exposure can be significantly reduced when handling or applying pesticides by protecting certain parts of the body where the skin shows increased absorption, such as the scrotal region, underarms, face, scalp, and hands. Using chemical-resistant gloves has been shown to reduce contamination by 33–86%.Use of genetically modified crops led to significant reduction of pesticide poisoning as these require significantly less pesticide application. In India alone reduction of 2.4–9 million cases per year was observed after widespread adoption of Bt cotton, with similar reductions reported in China, Pakistan and other countries.

Treatment
Specific treatments for acute pesticide poisoning are often dependent on the pesticide or class of pesticide responsible for the poisoning. However, there are basic management techniques that are applicable to most acute poisonings, including skin decontamination, airway protection, gastrointestinal decontamination, and seizure treatment.Decontamination of the skin is performed while other life-saving measures are taking place.  Clothing is removed, the patient is showered with soap and water, and the hair is shampooed to remove chemicals from the skin and hair.  The eyes are flushed with water for 10–15 minutes.  The patient is intubated and oxygen administered, if necessary.  In more severe cases, pulmonary ventilation must sometimes be supported mechanically. Seizures are typically managed with lorazepam, phenytoin and phenobarbitol, or diazepam (particularly for organochlorine poisonings).Gastric lavage is not recommended to be used routinely in pesticide poisoning management, as clinical benefit has not been confirmed in controlled studies; it is indicated only when the patient has ingested a potentially life-threatening amount of poison and presents within 60 minutes of ingestion.   An orogastric tube is inserted and the stomach is flushed with saline to try to remove the poison.  If the patient is neurologically impaired, a cuffed endotracheal tube inserted beforehand for airway protection.  Studies of poison recovery at 60 minutes have shown recovery of 8–32%.  However, there is also evidence that lavage may flush the material into the small intestine, increasing absorption.  Lavage is contra-indicated in cases of hydrocarbon ingestion.Activated charcoal is sometimes administered as it has been shown to be successful with some pesticides </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Scleroderma and can you explain it in depth? [/INST] Scleroderma is a group of autoimmune diseases that may result in changes to the skin, blood vessels, muscles, and internal organs. The disease can be either localized to the skin or involve other organs, as well. Symptoms may include areas of thickened skin, stiffness, feeling tired, and poor blood flow to the fingers or toes with cold exposure. One form of the condition, known as CREST syndrome, classically results in calcium deposits, Raynauds syndrome, esophageal problems, thickening of the skin of the fingers and toes, and areas of small, dilated blood vessels.The cause is unknown, but it may be due to an abnormal immune response. Risk factors include family history, certain genetic factors, and exposure to silica. The underlying mechanism involves the abnormal growth of connective tissue, which is believed to be the result of the immune system attacking healthy tissues. Diagnosis is based on symptoms, supported by a skin biopsy or blood tests.While no cure is known, treatment may improve symptoms. Medications used include corticosteroids, methotrexate, and non-steroidal anti-inflammatory drugs (NSAIDs). Outcome depends on the extent of disease. Those with localized disease generally have a normal life expectancy. In those with systemic disease, life expectancy can be affected, and this varies based on subtype. Death is often due to lung, gastrointestinal, or heart complications.About three per 100,000 people per year develop the systemic form. The condition most often begins in middle age. Women are more often affected than men. Scleroderma symptoms were first described in 1753 by Carlo Curzio and then well documented in 1842. The term is from the Greek skleros meaning "hard" and derma meaning "skin".

Signs and symptoms
Potential signs and symptoms include:
Cardiovascular: Raynauds phenomenon (is the presenting symptom in 30% of affected persons, occurs in 95% of affected individuals at some time during their illness); healed pitting ulcers on the fingertips; skin and mucosal telangiectasis; palpitations, irregular heart rate and fainting due to conduction abnormalities, hypertension, and congestive heart failure
Digestive: gastroesophageal reflux disease, bloating, indigestion, loss of appetite, diarrhoea alternating with constipation, sicca syndrome and its complications, loosening of teeth, and hoarseness (due to acid reflux).
Pulmonary: progressive worsening of shortness of breath, chest pain (due to pulmonary artery hypertension) and dry, persistent cough due to interstitial lung disease
Musculoskeletal: joint, muscle aches, loss of joint range of motion, carpal tunnel syndrome, and muscle weakness
Genitourinary: erectile dysfunction, dyspareunia, kidney problems, or kidney failure
Other: facial pain due to trigeminal neuralgia, hand paresthesias, headache, stroke, fatigue, calcinosis, and weight loss

Cause
Scleroderma is caused by genetic and environmental factors. Mutations in HLA genes seem to play a crucial role in the pathogenesis of some cases; likewise silica, aromatic and chlorinated solvents, ketones, trichloroethylene, welding fumes, and white spirits exposure seems to contribute to the condition in a small proportion of affected persons.

Pathophysiology
It is characterised by increased synthesis of collagen (leading to the sclerosis), damage to small blood vessels, activation of T lymphocytes, and production of altered connective tissue. Its proposed pathogenesis is the following:
It begins with an inciting event at the level of the vasculature, probably the endothelium. The inciting event is yet to be elucidated, but may be a viral agent, oxidative stress, or autoimmune. Endothelial cell damage and apoptosis ensue, leading to the vascular leakiness that manifests in early clinical stages as tissue oedema. At this stage, it is predominantly a Th1- and Th17-mediated disease.
After this, the vasculature is further compromised by impaired angiogenesis and impaired vasculogenesis (fewer endothelial progenitor cells), likely related to the presence of antiendothelinal cell antibodies (AECA). Despite this impaired angiogenesis, elevated levels of pro-angiogenic growth factors such as PDGF and VEGF is often seen in persons with the condition. The balance of vasodilation and vasoconstriction becomes askew, and the net result is vasoconstriction. The damaged endothelium then serves as a point of origin for blood-clot formation and further contributes to ischaemia-reperfusion injury and the generation of reactive oxygen species. These later stages are characterised by Th2 polarity.
The damaged endothelium upregulates adhesion molecules and chemokines to attract leucocytes, which enables the development of innate and adaptive immune responses, including loss of tolerance to various oxidised antigens, which includes topoisomerase I. B cells mature into plasma cells, which furthers the autoimmune component of the condition. T cells differentiate into subsets, including Th2 cells, which play a vital role in tissue fibrosis. Anti–topoisomerase 1 antibodies, in turn, stimulate type I interferon production.
Fibroblasts are recruited and activated by multiple cytokines and growth factors to generate myofibroblasts. Dysregulated transforming growth factor β (TGF-β) signalling in fibroblasts and myofibroblasts has been observed in multiple studies of scleroderma-affected individuals. Activation of fibroblasts and myofibroblasts leads to excessive deposition of collagen and other related proteins, leading to fibrosis. B cells are implicated in this stage, IL-6 and TGF-β produced by the B cells decrease collagen degradation and increase extracellular matrix production. Endothelin signalling is implicated in the pathophysiology of fibrosis.Vitamin D is implicated in the pathophysiology of the disease. An inverse correlation between plasma levels of vitamin D and scleroderma severity has been noted, and vitamin D is known to play a crucial role in regulating (usually suppressing) the actions of the immune system.

Diagnosis
Typical scleroderma is classically defined as symmetrical skin thickening, with about 70% of cases also presenting with Raynauds phenomenon, nail-fold capillary changes, and antinuclear antibodies. Affected individuals may experience systemic organ involvement. No single test for scleroderma works all of the time, hence diagnosis is often a matter of exclusion. Atypical scleroderma may show any variation of these changes without skin changes or with finger swelling only.Laboratory testing can show antitopoisomerase antibodies, like anti-scl70 (causing a diffuse systemic form), or anticentromere antibodies (causing a limited systemic form and the CREST syndrome). Other autoantibodies can be seen, such as anti-U3 or anti-RNA polymerase.
Antidouble-stranded DNA  autoantibodies are likely to be present in serum.

Differential
Diseases that are often in the differential include:
Eosinophilia is a condition in which too many eosinophils  (a type of immune cell that attacks parasites and is involved in certain allergic reactions) are present in the blood.
Eosinophilia-myalgia syndrome is a form of eosinophilia caused by L-tryptophan supplements.
Eosinophilic fasciitis affects the connective tissue surrounding skeletal muscles, bones, blood vessels, and nerves in the arms and legs.
Graft-versus-host disease is an autoimmune condition that occurs as a result of bone-marrow transplants in which the immune cells from the transplanted bone marrow attack the hosts body.
Mycosis fungoides is a type of cutaneous T cell lymphoma, a rare cancer that causes rashes all over the body.
Nephrogenic systemic fibrosis is a condition usually caused by kidney failure that results in fibrosis (thickening) of the tissues.
Primary biliary cirrhosis is an autoimmune disease of the liver.
Primary pulmonary hypertension
Complex regional pain syndrome

Classification
Scleroderma is characterised by the appearance of circumscribed or diffuse, hard, smooth, ivory-colored areas that are immobile and which give the appearance of hidebound skin, a disease occurring in both localised and systemic forms:

Treatment
No cure for scleroderma is known, although relief of symptoms is often achieved; these include the:
Raynauds phenomenon with vasodilators such as calcium channel blockers, alpha blockers, serotonin receptor antagonists, angiotensin II receptor inhibitors, statins, local nitrates or iloprost
Digital ulcers with phosphodiesterase 5 inhibitors (e.g., sildenafil) or iloprost
Prevention of new digital ulcers with bosentan
Malnutrition, secondary to intestinal flora overgrowth with tetracycline antibiotics such as tetracycline
Interstitial lung disease with cyclophosphamide, azathioprine with or without corticosteroids
Pulmonary arterial hypertension with endothelin receptor antagonists, phosphodiesterase 5 inhibitors, and prostanoids
Gastrooesophageal reflux disease with antacids or prokinetics
Kidney crises with angiotensin converting enzyme inhibitors and angiotensin II receptor antagonistsSystemic disease-modifying treatment with immunosuppressants is often used. Immunosuppressants used in its treatment include azathioprine, methotrexate, cyclophosphamide, mycophenolate, intravenous immunoglobulin, rituximab, sirolimus, alefacept, and the tyrosine kinase inhibitors, imatinib, nilotinib, and dasatinib.Experimental therapies under investigation include endothelin receptor antagonists, tyrosine kinase inhibitors, beta-glycan peptides, halofuginone, basiliximab, alemtuzumab, abatacept, and haematopoietic stem cell transplantation.

Prognosis
As of 2012, the five-year survival rate for systemic scleroderma was about 85%, whereas the 10-year survival rate was just under 70%. This varies according to the subtype; while localized scleroderma rarely results in death, the systemic form can, and the diffuse systemic form carries a worse prognosis than the limited form. The major scleroderma-related causes of death are: pulmonary hypertension, pulmonary fibrosis, and scleroderma renal crisis. People with scleroderma are also at a heightened risk for contracting cancers (especially liver, lung, haematologic, and bladder cancers), and perhaps, cardiovascular disease.According to a study of an Australian cohort, between 1985 and 2015, the average life expectancy of a person with scleroderma increased from 66 years to 74 years (around 8 years less than the average Australian life expectancy of 82 years).

Epidemiology
Scleroderma most commonly first presents between the ages of 20 and 50 years, although any age group can be affected </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Pulmonary hyalinizing granuloma and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Netherton syndrome and can you explain it in depth? [/INST] Netherton syndrome is a severe, autosomal recessive form of ichthyosis associated with mutations in the SPINK5 gene. It is named after Earl W. Netherton (1910–1985), an American dermatologist who discovered it in 1958.

Signs and symptoms
Netherton syndrome is characterized by chronic skin inflammation, universal pruritus (itch), severe dehydration, and stunted growth. Patients with this disorder tend to have a hair shaft defect (trichorrhexis invaginata), also known as "bamboo hair". The disrupted skin barrier function in affected individuals also presents a high susceptibility to infection and allergy, leading to the development of scaly, reddish skin similar to atopic dermatitis. In severe cases, these atopic manifestations persist throughout the individuals life, and consequently post-natal mortality rates are high. In less severe cases, this develops into the milder ichthyosis linearis circumflexa.Netherton syndrome has recently been characterised as a primary immunodeficiency, which straddles the innate and acquired immune system, much as does Wiskott–Aldrich syndrome.  A group of Netherton patients have been demonstrated to have altered immunoglobulin levels (typically high IgE and low to normal IgG) and immature natural killer cells. These Natural Killer cells have a reduced lytic function; which can be improved with regular infusions of immunoglobulin (see Treatment); although the mechanism for this is not clear.Patients are more prone than healthy people to infections of all types, especially recurrent skin infections with staphylococcus.  They may have more severe infections; but are not as vulnerable to opportunistic pathogens as patients with true Natural Killer cell deficiency-type SCID.

Cause
Netherton syndrome is an autosomal recessive disorder associated with mutations in the SPINK5 gene, which encodes the serine protease inhibitor lympho-epithelial Kazal-type-related inhibitor (LEKTI). These mutations result in a dysfunctional protein that has a reduced capacity to inhibit serine proteases expressed in the skin. Potential endogenous targets of LEKTI include KLK5, KLK7 and KLK14. These enzymes are involved in various aspects of epidermal remodelling, including desquamation, PAR-2 activation and degradation of lipid hydrolases, suggesting a potential mechanism for the development of atopic manifestations characteristic of Netherton syndrome.Disease severity is determined by the level of LEKTI expression and, consequently, serine protease activity. Complete SPINK5 gene deletions have been linked to severe cases, while mutations which induce alternate splicing or create premature stop codons may lead to varying levels of severity. Furthermore, LEKTI-knockout mice exhibit a phenotype similar to Netherton syndrome in humans.

Diagnosis
Treatment
There is no known cure at the moment but there are several things that can be done to relieve the symptoms </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Congenital hepatic fibrosis and can you explain it in depth? [/INST]  </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Polycythemia and can you explain it in depth? [/INST] Polycythemia (also known as polycythaemia, polyglobulia and Erythrocytosis) is a disease state in which the hematocrit (the volume percentage of red blood cells in the blood) and/or hemoglobin concentration are elevated in peripheral blood.
It can be due to an increase in the number of red blood cells ("absolute polycythemia") or to a decrease in the volume of plasma ("relative polycythemia"). Polycythemia is sometimes called erythrocytosis, but the terms are not synonymous, because polycythemia describes any increase in red blood mass (whether due to an erythrocytosis or not), whereas erythrocytosis is a documented increase of red cell count.
The emergency treatment of polycythemia (e.g., in hyperviscosity or thrombosis) is by phlebotomy (removal of blood from the circulation). Depending on the underlying cause, phlebotomy may also be used on a regular basis to reduce the hematocrit. Myelosuppressive medications such as hydroxyurea are sometimes used for long-term management of polycythemia.

Absolute polycythemia
The overproduction of red blood cells may be due to a primary process in the bone marrow (a so-called myeloproliferative syndrome), or it may be a reaction to chronically low oxygen levels or, rarely, a malignancy. Alternatively, additional red blood cells may have been received through another process—for example, being over-transfused (either accidentally or, as blood doping, deliberately) or being the recipient twin in a pregnancy, undergoing twin-to-twin transfusion syndrome.

Primary polycythemia
Primary polycythemias are due to factors intrinsic to red cell precursors. Polycythemia vera (PCV), polycythemia rubra vera (PRV), or erythremia, occurs when excess red blood cells are produced as a result of an abnormality of the bone marrow.  Often, excess white blood cells and platelets are also produced. PCV is classified as a myeloproliferative disease. Symptoms include headaches and vertigo, and signs on physical examination include an abnormally enlarged spleen and/or liver. In some cases, affected individuals may have associated conditions including high blood pressure or formation of blood clots. Transformation to acute leukemia is rare. Phlebotomy is the mainstay of treatment. A hallmark of polycythemia is an elevated hematocrit, with Hct > 55% seen in 83% of cases. A somatic (non-hereditary) mutation (V617F) in  the JAK2 gene, also present in other myeloproliferative disorders, is found in 95% of cases.Primary familial polycythemia, also known as primary familial and congenital polycythemia (PFCP), exists as a benign hereditary condition, in contrast with the myeloproliferative changes associated with acquired PCV. In many families, PFCP is due to an autosomal dominant mutation in the EPOR erythropoietin receptor gene. PFCP can cause an increase of up to 50% in the oxygen-carrying capacity of the blood; skier Eero Mäntyranta had PFCP, which is considered to have given him a large advantage in endurance events.

Secondary polycythemia
Secondary polycythemia is caused by either natural or artificial increases in the production of erythropoietin, hence an increased production of erythrocytes. In secondary polycythemia,  6 to 8 million and occasionally 9 million erythrocytes may occur per cubic millimeter of blood. Secondary polycythemia resolves when the underlying cause is treated.Secondary polycythemia in which the production of erythropoietin increases appropriately is called physiologic polycythemia.
Conditions which may result in a physiologically appropriate polycythemia include:

Altitude related – This physiologic polycythemia is a normal adaptation to living at high altitudes (see altitude sickness). Many athletes train at high altitude to take advantage of this effect, which can be considered a legal form of blood doping. Some individuals believe athletes with primary polycythemia may have a competitive advantage due to greater stamina. However, this has yet to be proven due to the multifaceted complications associated with this condition.
Hypoxic disease-associated – for example in cyanotic heart disease where blood oxygen levels are reduced significantly, may also occur as a result of hypoxic lung disease such as COPD and as a result of chronic obstructive sleep apnea.
Iatrogenic – Secondary polycythemia can be induced directly by phlebotomy (blood letting) to withdraw some blood, concentrate the erythrocytes, and return them to the body.
Genetic – Heritable causes of secondary polycythemia also exist and are associated with abnormalities in hemoglobin oxygen release. This includes patients who have a special form of hemoglobin known as Hb Chesapeake, which has a greater inherent affinity for oxygen than normal adult hemoglobin. This reduces oxygen delivery to the kidneys, causing increased erythropoietin production and a resultant polycythemia </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Velopharyngeal insufficiency and can you explain it in depth? [/INST] Velopharyngeal insufficiency  is a disorder of structure that causes a failure of the velum (soft palate) to close against the posterior pharyngeal wall (back wall of the throat) during speech in order to close off the nose (nasal cavity) during oral speech production. This is important because speech requires sound (from the vocal folds) and airflow (from the lungs) to be directed into the oral cavity (mouth) for the production of all speech sound with the exception of nasal sounds (m, n, and ng). If complete closure does not occur during speech, this can cause hypernasality (a resonance disorder) and/or audible nasal emission during speech (a speech sound disorder). In addition, there may be inadequate airflow to produce most consonants, making them sound weak or omitted.The terms "velopharyngeal insufficiency" "velopharyngeal incompetence, "velopharyngeal inadequacy" and "velopharyngeal dysfunction" have often been used interchangeably, although they do not mean the same thing. "Velopharyngeal dysfunction" now refers to abnormality of the velopharyngeal valve, regardless of cause. Velopharyngeal insufficiency includes any structural defect of the velum or mechanical interference with closure. Causes include a history of
cleft palate, adenoidectomy, irregular adenoids, cervical spine anomalies, or oral/pharyngeal tumor removal. In contrast, "velopharyngeal incompetence" refers to a neurogenic cause of inadequate velopharyngeal closure. Causes may include stroke, traumatic brain injury, cerebral palsy, or neuromuscular disorders. It is important that the term "velopharyngeal insufficiency" is used if it is an anatomical defect and not a neurological problem.

Anatomy
Diagnosis
Speech analysis
Velopharyngeal insufficiency can be diagnosed by a speech pathologist through a perceptual speech assessment. Speech characteristics of VPI include hypernasality (too much sound in the nasal cavity during speech) and/or audible nasal emission of air during speech. Nasal emission can also cause the consonants to be very weak in intensity and pressure. The patient may develop compensatory productions for consonants, where the sounds are produced in the pharynx (throat area) where there is adequate airflow.

Nasometry
Nasometry is a method of measuring the acoustic correlates of resonance and velopharyngeal function through a computer-based instrument. Nasometry testing gives the speech pathologist a nasalance score, which is the percentage of nasal sound of the total (nasal plus oral) sound during speech. This score can be compared to normative values for the speech passage. Nasometry is useful in the evaluation of hypernasality because it provides objective measurements of the function of the velopharyngeal valve. As such, it is often used for pre-and post-surgical comparisons and to determine speech outcomes as a result of certain surgical interventions.

Nasopharyngoscopy
Nasopharyngoscopy is endoscopic technique in which the physician or speech pathologist passes a small scope through the patients nose to the nasopharynx. The nasal cavity is typically numbed before the procedure, so there is minimal discomfort. Nasopharyngoscopy provides a view of the velum (soft palate) and pharyngeal walls (walls of the throat) during nasal breathing and during speech. The advantage of this technique over videofluoroscopy is that the examiner can see the size, location, and cause of the velopharyngeal opening very clearly and without harm (e.g., radiation) to the patient. Even very small openings can be visualized. This information is helpful in determining appropriate surgical or prosthetic management for the patient. The disadvantage of this technique is that the vertical level velar elevation is less obvious than with videofluoroscopy, although this is not a big concern.

Videofluoroscopy
Multiview videofluoroscopy is a radiographic technique to view the length and movement of the velum (soft palate) and the posterior and lateral pharyngeal (throat) walls during speech. The advantage of this technique is that the entire posterior pharyngeal wall can be visualized. Disadvantages include the following: 1. This procedure requires radiation, which is a particular concern for children. 2. It is not well tolerated by some children because it requires injection of barium into the nasopharynx through a nasal catheter. 3. The resolution (clarity of the image) is not nearly as good as nasopharyngoscopy. 4. Small or unilateral openings cannot be seen because the X-ray beam takes a sum of all the parts. 5. It only provides a two-dimensional view, and therefore, multiple views are needed to see the entire velopharyngeal mechanism.   Comparison between multiview videofluoroscopy and nasoendoscopy of velopharyngeal movements."/>  This diagnosis method is useful in assessing velopharyngeal (VP) closure in healthy individuals vs individuals who experience velar backed articulation (BA); given that it was found that healthy individuals had VP closure  occur before tongue movement, whereas individuals with BA had VP closure occur after tongue movement when articulating words.

Magnetic resonance imaging
A relatively new approach in the diagnosis is magnetic resonance imaging (MRI), which is noninvasive. MRI uses the property of nuclear magnetic resonance to image nuclei of atoms inside the body. MRI is non-radiographic and therefore can be repeated more often in short periods of time. In addition, different studies show that the MRI is better as an imaging tool than videofluoroscopy for visualizing the anatomy of the velopharynx. There are some limitations of the MRI however. Unlike videofluoroscopy and nasopharyngoscopy, MRI does not show the movement of the velopharyngeal structures during speech. In addition, artifacts can be shown on the images when the patient moves while imaging or if the patient has orthodontic appliances. MRI is limited in children who are claustrophobic. Finally, MRI is much more expensive than videofluoroscopy or nasopharyngoscopy. Because of these limits, MRI is currently not widely used for clinical diagnostic purposes.

Treatment
Speech pathology
Speech therapy will not correct velopharyngeal insufficiency. The condition results from abnormal structure and requires physical management (surgery, or a prosthetic device if surgery cannot be done). Speech therapy is appropriate to correct the compensatory articulation productions that develop as a result of velopharyngeal insufficiency. Speech therapy is most successful after correction of velopharyngeal insufficiency. Speech pathologists who are associated with a cleft palate/craniofacial team are most qualified for this type of therapy.

Operation techniques
In patients with cleft palate, the palate must be repaired through a palatoplasty for normal velopharyngeal function. Despite the palatoplasty, 20-30% of these patients will still have some degree of velopharyngeal insufficiency, which will require surgical (or prosthetic) management for correction. Therefore, a secondary operation is necessary.
There is not one single operative approach to surgical correction of VPI. The surgical approach typically depends on the size of the velopharyngeal opening, its location, and the cause.  With diagnostic tools the surgeon is able to decide which technique should be used based on the anatomical situation of the individual. The goal of every operation is to achieve the best possible result with the technique assigned to each individual case, without causing upper airway obstruction and sleep apnea.Nowadays the procedure that is chosen the most from the palatoplasties is the pharyngeal flap or sphincter palatoplasty.

Pharyngeal flap
When a pharyngeal flap is used, a flap of the posterior wall is attached to the posterior border of the soft palate. The flap consists of mucosa and the superior pharyngeal constrictor muscle. The muscle stays attached to the pharyngeal wall at the upper side (superior flap) or at the lower side (inferior flap). The function of the muscle is to obstruct the pharyngeal port at the moment that the pharyngeal lateral walls move towards each other. It is important that the width and the level of insertion of the flap are properly constructed, because if the flap is too wide, the patient can have problems with breathing through the nose, which can result in sleep apnea. Alternatively, a postoperative situation can be created with the same symptoms as before surgery. Some complications are possible; for example, the flaps width can change because of contraction of the flap. This results in a situation with the same symptoms of hypernasality after a few weeks of surgery. Also a fistula can occur in 2.4% of the cases.

Sphincter palatoplasty
When the sphincter pharyngoplasty is used, both sides of the superior-based palatopharyngeal mucosa and muscle flaps are elevated. Because the distal parts (posterior tonsillar pillars, which the palatopharyngeal muscles are attached to) are sutured to the other side of the posterior wall, the pharyngeal port will become smaller. As a result, the tissue flaps cross each other, leading to a smaller port in the middle and a shorter distance between the palate and posterior pharyngeal wall.There are a few advantages with using this technique. First of all the procedure is relatively easy to execute. This makes the operation cheaper, also because of a reduced anesthesia time. Secondly the dynamic sphincter can be moved as result of a remaining neuromuscular innervation, which gives a better function of the velopharyngeal port. Finally there is a lower complication rate, although obstructive sleep apnoea syndrome (OSAS) is associated.Both techniques are used often, but there is no standard operation. Pharyngeal flap surgery is not better than sphincter palatoplasty. It is more upon the surgeons experience, knowledge and preference which operation will be done. Also the patient’s age, and the size and nature of the velopharyngeal defect, contribute to which technique is used.

Posterior wall augmentation
Another option for diminishing the velopharyngeal port is posterior wall augmentation. This technique is not often used. Additionally this technique can only be used for small gaps. When this operation is performed there are several advantages. It is possible to narrow down the velopharyngeal port without modifying the function of the velum or lateral walls. Furthermore, the chance of obstructing the airway is lower, because the port can be closed more precisely. Many materials have been used for this closure: petroleum jelly, paraffin, cartilage, adjacent soft tissue, silastic, fat, Teflon and proplast </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Emphysema and can you explain it in depth? [/INST] Emphysema, or pulmonary emphysema, is a lower respiratory tract disease, characterised by air-filled spaces (pneumatoses) in the lungs, that can vary in size and may be very large. The spaces are caused by the breakdown of the walls of the alveoli and they replace the spongy lung parenchyma. This reduces the total alveolar surface available for gas exchange leading to a reduction in oxygen supply for the blood. Emphysema usually affects the middle aged or older population because it takes time to develop with the effects of tobacco smoking, and other risk factors. Alpha-1 antitrypsin deficiency is a genetic risk factor that may lead to the condition presenting earlier.When associated with significant airflow limitation, emphysema is a major subtype of chronic obstructive pulmonary disease (COPD), a progressive lung disease characterized by long-term breathing problems and poor airflow. Without COPD, the finding of emphysema on a CT lung scan still confers a higher mortality risk in tobacco smokers. In 2016 in the United States there were 6,977 deaths from emphysema – 2.2 per 100,000 of the population. Globally it accounts for 5% of all deaths. A study on the effects of tobacco and cannabis smoking showed that a possibly cumulative toxic effect could be a risk factor for developing emphysema, and spontaneous pneumothorax.There are four types of emphysema, three of which are related to the anatomy of the lobules of the lung – centrilobular or centriacinar, panlobular or panacinar, and paraseptal or distal acinar emphysema, and are not associated with fibrosis (scarring). The fourth type is known as paracicatricial emphysema or irregular emphysema that  involves the acinus irregularly and is associated with fibrosis. Though the different types can be seen on imaging they are not well-defined clinically. There are also a number of associated conditions including bullous emphysema, focal emphysema, and Ritalin lung. Only the first two types of emphysema – centrilobular, and panlobular are associated with significant airflow obstruction, with that of centrilobular emphysema around 20 times more common than panlobular. Centrilobular emphysema is the only type associated with smoking.Osteoporosis is often a comorbidity of emphysema. The use of systemic corticosteroids for treating exacerbations is a significant risk factor for osteoporosis, and their repeated use is recommended against.

Signs and symptoms
Emphysema is a respiratory disease of the lower respiratory tract. It is commonly caused by tobacco smoking but a significant number of people are affected who either do not smoke, or have never smoked. The presence of emphysema is a clear risk factor for the development of lung cancer, made stronger in those who smoke.Early symptoms of emphysema may vary from person to person. Symptoms can include a cough (with or without sputum), wheezing, a fast breathing rate, breathlessness on exertion, and a feeling of tightness in the chest. There may be frequent cold or flu infections. Other symptoms may include anxiety, depression, fatigue, sleep problems and weight loss. Since these symptoms could also relate to other lung conditions or other health problems, emphysema is often under diagnosed. The shortness of breath caused by emphysema can increase over time and develop into chronic obstructive pulmonary disease.
A sign of emphysema in smokers is the finding of a higher number of alveolar macrophages sampled from the bronchoalveolar lavage (BAL) in the lungs. The number can be four to six times greater in those who smoke than in non-smokers.

Types
There are four main types of emphysema, three of which are related to the anatomy of the lobules of the lung – centrilobular or centriacinar, panlobular or panacinar, and paraseptal or distal acinar and are not associated with fibrosis (scarring). Although fibrosis is not a normal feature of these subtypes, repair strategies in end-stage emphysema may lead to pulmonary fibrosis. The fourth subtype is known as paracicatricial emphysema or irregular emphysema, involves the acinus irregularly and is associated with fibrosis.Only the first two types of emphysema – centrilobular, and panlobular are associated with significant airflow obstruction, with that of centrilobular emphysema around 20 times more common than panlobular. The subtypes can be  seen on imaging but are not well-defined clinically.
There are also a number of associated conditions including bullous emphysema, focal emphysema, and Ritalin lung.

Centrilobular
Centrilobular emphysema also called centriacinar emphysema, affects the centre of a pulmonary lobule (centrilobular) in the lung, the area around the terminal bronchiole, and the first respiratory bronchiole, and can be seen on imaging as an area around the tip of the visible pulmonary artery. Centrilobular emphysema is the most common type usually associated with smoking, and with chronic bronchitis. The disease progresses from the centrilobular portion, leaving the lung parenchyma in the surrounding (perilobular) region preserved. Usually the upper lobes of the lungs are affected.

Panlobular
Panlobular emphysema also called panacinar emphysema affects all of the alveoli in a lobule and can involve the whole lung or mainly the lower lobes. This type of emphysema is associated with alpha-1 antitrypsin deficiency (A1AD or AATD), and Ritalin lung, and is not related to smoking.

Complications
Likely complications of centrilobular, and panlobular emphysema, some of which are life-threatening, include: respiratory failure, pneumonia, respiratory infections, pneumothorax, interstitial emphysema, pulmonary heart disease, and respiratory acidosis.

Paraseptal
Paraseptal emphysema also called distal acinar emphysema relates to emphysematous change next to a pleural surface, or to a fissure. The cystic spaces known as blebs or bullae that form in paraseptal emphysema typically occur in just one layer beneath the pleura. This distinguishes it from the honeycombing of small cystic spaces seen in fibrosis that typically occurs in layers. This type of emphysema is not associated with airflow obstruction.

Bullous
When the subpleural bullae are significant, the emphysema is called bullous emphysema. Bullae can become extensive and combine to form giant bullae. These can be large enough to take up a third of a hemithorax, compress the lung parenchyma, and cause displacement. The emphysema is now termed giant bullous emphysema, more commonly called vanishing lung syndrome due to the compressed parenchyma. A bleb or bulla may sometimes rupture and cause a pneumothorax.

Paracicatricial
Paracicatricial emphysema, also known as irregular emphysema, is seen next to areas of fibrosis (scarring) as large spaces. The scarring is most often a result of silicosis, granulomatous  infection, tuberculosis, or pulmonary infarction. It can be difficult to differentiate from the honeycombing of pulmonary fibrosis.

HIV associated
Classic lung diseases are a complication of HIV/AIDS with emphysema being a source of disease. HIV is cited as a risk factor for the development of emphysema, and COPD regardless of smoking status. Around 20 percent of those with HIV have increased emphysematous changes. This has suggested that an underlying mechanism related to HIV is a contributory factor in the development of emphysema. HIV associated emphysema occurs over a much shorter time than that associated with smoking; an earlier presentation is also seen in emphysema caused by alpha-1 antitrypsin deficiency. Both of these conditions predominantly show damage in the lower lungs which suggests a similarity between the two mechanisms.

Alpha-1 related
Emphysema may develop in some people with alpha-1 antitrypsin deficiency, the only genotype of chronic obstructive pulmonary disease. This usually occurs a lot earlier, as does HIV associated emphysema than other types.

Ritalin lung
The intravenous use of methylphenidate, commonly marketed as Ritalin and widely used as a stimulant drug in the treatment of attention deficit hyperactivity disorder, can lead to emphysematous changes known as Ritalin lung. The mechanism underlying this link is not clearly understood. Ritalin tablets contain talc as a filler, and these need to be crushed and dissolved for injecting. It has been suggested that the talc exposure causes granulomatosis leading to alveolar destruction. However, other intravenous drugs also contain talc and there is no associated emphysematous change. High resolution CT scanning shows the emphysema to be panlobular.

CPFE
Combined pulmonary fibrosis and emphysema (CPFE) is a rare syndrome that shows upper-lobe emphysema, together with lower-lobe interstitial fibrosis. This is diagnosed by CT scan. This syndrome presents a marked susceptibility for the development of pulmonary hypertension.

Congenital lobar
Congenital lobar emphysema (CLE), also known as congenital lobar overinflation and infantile lobar emphysema, is a neonatal condition associated with enlarged air spaces in the lungs of newborn infants. It is diagnosed around the time of birth or in the first 6 months of life, occurring more often in boys than girls. CLE affects the upper lung lobes more than the lower lobes, and the left lung more often than the right lung. CLE is defined as the hyperinflation of one or more lobes of the lung due to the partial obstruction of the bronchus. This causes symptoms of pressure on the nearby organs. It is associated with several cardiac abnormalities such as patent ductus arteriosus, atrial septal defect, ventricular septal defect, and tetralogy of Fallot. Although CLE may be caused by the abnormal development of bronchi, or compression of airways by nearby tissues, no cause is identified in half of cases. CT scan of the lungs is useful in assessing the anatomy of the lung lobes and status of the neighbouring lobes on whether they are hypoplastic or not. Contrast-enhanced CT is useful in assessing vascular abnormalities and mediastinal masses.

Focal
Focal emphysema, is a localized region of emphysema in the lung that is larger than alveoli, and often associated with coalworkers pneumoconiosis. This is also known as localized pulmonary emphysema. Blebs and bullae may also be included as focal emphysema. These can be differentiated from the other type of enclosed air space known as a lung cyst by their size and wall thickness. A bleb or bulla  has a wall thickness of less than 1 mm, and are smaller.

Occupational
A number of occupations are associated with the development of emphysema due to the inhalation of varied gases and particles. In the US uranium mining that releases radon gas and particles has been shown to be a cause of emphysema deaths; the figures in the study included some miners who also smoked. Uranium mining and milling was found to create environmental pollution.The inhalation of coal mine dust that can result in coalworkers pneumoconiosis is an independent risk factor for the development of emphysema. Focal emphysema is associated with the coal macule, and this extends into progressive centrilobular emphysema. Less commonly a variant of panlobular emphysema develops.Silicosis results from the inhalation of silica particles, and the formation of large silica nodules is associated with paracicatricial emphysema, with or without bullae.

Ozone-induced emphysema
Ozone is another pollutant that can affect the respiratory system. Long-term exposure to ozone can result in emphysema.

Osteoporosis
Osteoporosis is a major comorbidity of emphysema. Both conditions are associated with a low body mass index. There is an association between treating emphysema, and osteoporosis; the use of systemic corticosteroids for treating exacerbations is a significant risk factor for osteoporosis, and their repeated use is not recommended.

Other terms
Compensatory emphysema, is overinflation of part of a lung in response to either removal by surgery of another part of the lung or decreased size of another part of the lung.Pulmonary interstitial emphysema (PIE) is a collection of air outside of the normal air space of the alveoli, found as pneumatoses inside the connective tissue of the peribronchovascular sheaths, interlobular septa, and visceral pleura.

Lung volume reduction
Lung volume reduction may be offered to those with advanced emphysema. When other treatments fail, and the emphysema is located in the upper lobes a surgical option may be possible.  A number of minimally invasive bronchoscopic procedures are increasingly used to reduce lung volume.

Surgical
Where there is severe emphysema with significant hyperinflation that has proved unresponsive to other therapies lung volume reduction surgery (LVRS) may be an option. LVRS involves the removal of tissue from the lobe most damaged by emphysema, which allows the other lobes to expand and give improved function. The procedure appears to be particularly effective if the emphysema primarily involves the upper lobes; however, the procedure increases the risk of adverse events and early death in people who have diffuse emphysema.

Bronchoscopic
Minimally invasive bronchoscopic procedures may be carried out to reduce lung volume. These include the use of valves, coils, or thermal ablation. Endobronchial valves are one-way valves that may be used in those with severe hyperinflation resulting from advanced emphysema; a suitable target lobe, and no collateral ventilation are required for this procedure. The placement of one or more valves in the lobe induces a partial collapse of the lobe that ensures a reduction in residual volume that improves lung function, the capacity for exercise, and quality of life.The placement of nitinol coils instead of valves is recommended where there is collateral ventilation that would prevent the use of valves. Nitinol  is a biocompatible shape-memory alloy.
Both of these techniques are associated with adverse effects including persistent air leaks and cardiovascular complications. Bronchoscopic thermal vapor ablation has an improved profile. Heated water vapor is used to target affected lobe regions which leads to permanent fibrosis and volume reduction. The procedure is able to target individual lobe segments, can be carried out regardless of collateral ventilation, and can be repeated with the natural advance of emphysema.

Other surgeries
Lung transplantation – the replacement of either a single lung or both (bilateral) may be considered in end-stage disease. A bilateral transplant is the preferred choice as complications can arise in a remaining single native lung; complications can include hyperinflation, pneumonia, and the development of lung cancer. Careful selection as recommended by the National Emphysema Treatment Trial (NETT) for transplant surgeries is needed as in some cases there will be an increased risk of mortality </s>


<s> [INST] <<SYS>> You are a responsible assistant committed to providing accurate and helpful responses. Avoid sharing harmful or biased content. Clarify any unclear or incorrect questions rather than providing false or misleading information. <</SYS>> What is Essential fatty acid and can you explain it in depth? [/INST] Essential fatty acids, or EFAs, are fatty acids that humans and other animals must ingest because the body requires them for good health but cannot synthesize them.The term "essential fatty acid" refers to fatty acids required for biological processes but does not include the fats that only act as fuel. Essential fatty acids should not be confused with essential oils, which are "essential" in the sense of being a concentrated essence.
Only two fatty acids are known to be essential for humans: alpha-linolenic acid (an omega-3 fatty acid) and linoleic acid (an omega-6 fatty acid). Some other fatty acids are sometimes classified as "conditionally essential", meaning that they can become essential under some developmental or disease conditions; examples include docosahexaenoic acid (an omega-3 fatty acid) and gamma-linolenic acid (an omega-6 fatty acid).
When the two EFAs were discovered in 1923, they were designated "vitamin F", but in 1929, research on rats showed that the two EFAs are better classified as fats rather than vitamins.

Functions
The biological effects of the ω-3 and ω-6 fatty acids are mediated by their mutual interactions, see Essential fatty acid interactions for detail.In the body, essential fatty acids serve multiple functions. In each of these, the balance between dietary ω-3 and ω-6 strongly affects function.

They are modified to make
the classic eicosanoids (affecting inflammation and many other cellular functions)
the endocannabinoids (affecting mood, behavior and inflammation)
the lipoxins which are a group of eicosanoid derivatives formed via the lipoxygenase pathway from ω-6 EFAs and resolvins from ω-3 (in the presence of acetylsalicylic acid, downregulating inflammation)
the isofurans, neurofurans, isoprostanes, hepoxilins, epoxyeicosatrienoic acids (EETs) and neuroprotectin D
They form lipid rafts (affecting cellular signaling)
They act on DNA (activating or inhibiting transcription factors such as NF-κB, which is linked to pro-inflammatory cytokine production)

Fatty acids comprise an aliphatic hydrocarbon chain plus a carboxyl group (–COOH) group at one end, and terminated by a methyl group (–CH3) at the other end. They are almost always straight-chained. The carbon next to the carboxylate is known as α, the next carbon β, and so forth. Since biological fatty acids can be of diverse lengths, the last position is often labelled as a "ω", the last letter in the Greek alphabet. Thus, the ω-3 indicates that the first unsaturated carbon-carbon bond from the terminal end (ω) of then chain is the third one. Typically, the number of carbons and the number of double bonds are also listed in short descriptions of unsaturated fatty acids. For instance, ω-3 18:4, or 18:4 ω-3, or 18:4 n−3 indicates stearidonic acid, an 18-carbon chain with 4 double bonds, and with a double bond between the third and fourth carbon atoms from the CH3 end. Double bonds are cis and separated by a single methylene (CH2) group unless otherwise noted. In free fatty acid form, the chemical structure of stearidonic acid is:

Examples
Polyunsaturated fatty acids with 16- and 18-carbon chains are sometimes classified as short chain polyunsaturated fatty acids (SC-PUFA), as opposed to long-chain polyunsaturated fatty acids (LC-PUFA), which have more than 18 carbon atoms.Both the essential fatty acids are SC-PUFA with an 18-carbon chain:

ω-3 fatty acid:
α-linolenic acid or ALA (18:3n-3)
ω-6 fatty acid:
linoleic acid or LA (18:2n-6)These two fatty acids cannot be synthesized by humans because humans lack the desaturase enzymes required for their production.
They form the starting point for the creation of more desaturated fatty acids, most of which also have a longer carbon chain:

ω-3 fatty acids:
eicosapentaenoic acid or EPA (20:5n-3)
docosahexaenoic acid or DHA (22:6n-3)
ω-6 fatty acids:
gamma-linolenic acid or GLA (18:3n-6)
dihomo-gamma-linolenic acid or DGLA (20:3n-6)
arachidonic acid or AA (20:4n-6)Except for GLA, which has a short 18-carbon chain, these fatty acids have more than 18 carbon atoms and are typically classified as LC-PUFA.ω-9 fatty acids are not essential in humans because they can be synthesized from carbohydrates or other fatty acids.

Essentiality in human diet
Mammals lack the ability to introduce double bonds in fatty acids beyond carbon 9 and 10, hence the omega-6 linoleic acid (18:2n-6; LA) and the omega-3 Alpha-linolenic acid (18:3n-3; ALA) are essential for humans in the diet. However, humans can convert both LA and ALA to fatty acids with longer carbon chains and a larger number of double bonds, by alternative desaturation and chain elongation.
In humans, arachidonic acid (20:4n-6; AA) can be synthesized from LA. In turn, AA can be converted to an even longer fatty acid, the docosapentaenoic acid (22:5n-6; DPA). Similarly, ALA can be converted to docosahexaenoic acid (22:6n-3; DHA), although the latter conversion is limited, resulting in lower blood levels of DHA than through direct ingestion. This is illustrated by studies in vegans and vegetarians. If there is relatively more LA than ALA in the diet it favors the formation of DPA from LA rather than DHA from ALA. This effect can be altered by changing the relative ratio of LA:ALA, but is more effective when total intake of polyunsaturated fatty acids is low.
In preterm infants, the capacity to convert LA to AA and ALA to DHA is limited, and preformed AA and DHA may be required to meet the needs of the developing brain. Both AA and DHA are present in breastmilk and contribute along with the parent fatty acids LA and ALA to meeting the requirements of the newborn infant. Many infant formulas have AA and DHA added to them with an aim to make them more equivalent to human milk.
Essential nutrients are defined as those that cannot be synthesized de novo in sufficient quantities for normal physiological function. This definition is met for LA and ALA but not the longer chain derivatives in adults. The longer chain derivatives particularly, however, have pharmacological properties that can modulate disease processes, but this should not be confused with dietary essentiality.
Between 1930 and 1950, arachidonic acid and linolenic acid were termed essential because each was more or less able to meet the growth requirements of rats given fat-free diets. In the 1950s Arild Hansen showed that in humans: infants fed skimmed milk developed the essential fatty acid deficiency. It was characterized by an increased food intake, poor growth, and a scaly dermatitis, and was cured by the administration of corn oil.
Later work by Hansen randomized 426 children to four treatments: modified cows milk formula, skimmed milk formula, skimmed milk formula with coconut oil, or cows milk formula with corn oil. The infants who received the skimmed milk formula or the formula with coconut oil developed essential fatty acid deficiency signs and symptoms. This could be cured by administration of ethyl linoleate (the ethyl ester of linoleic acid) with about 1% of the energy intake.Collins et al. 1970 were the first to demonstrate linoleic acid deficiency in adults. They found that patients undergoing intravenous nutrition with glucose became isolated from their fat supplies and rapidly developed biochemical signs of essential fatty acid deficiency (an increase in 20:3n-9/20:4n-6 ratio in plasma) and skin symptoms. This could be treated by infusing lipids, and later studies showed that topical application of sunflower oil would also resolve the dermal symptoms. Linoleic acid has a specific role in maintaining the skin water-permeability barrier, probably as constituents of acylglycosylceramides. This role cannot be met by any ω-3 fatty acids or by arachidonic acid.
The main physiological requirement for ω-6 fatty acids is attributed to arachidonic acid </s>