<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 Periodontal disease and can you explain it in depth? [/INST] Periodontal disease, also known as gum disease, is a set of inflammatory conditions affecting the tissues surrounding the teeth. In its early stage, called gingivitis, the gums become swollen and red and may bleed. It is considered the main cause of tooth loss for adults worldwide. In its more serious form, called periodontitis, the gums can pull away from the tooth, bone can be lost, and the teeth may loosen or fall out. Bad breath may also occur.Periodontal disease is generally due to bacteria in the mouth infecting the tissue around the teeth. Factors that increase the risk of disease include smoking, diabetes, HIV/AIDS, family history, and certain medications. Diagnosis is by inspecting the gum tissue around the teeth both visually and with a probe and X-rays looking for bone loss around the teeth.Treatment involves good oral hygiene and regular professional teeth cleaning. Recommended oral hygiene include daily brushing and flossing. In certain cases antibiotics or dental surgery may be recommended. Clinical trials show that smoking cessation and dietary improvements improve disease outcomes. Globally 538 million people were estimated to be affected in 2015 and has been known to affect 10-15% of the population generally. In the United States nearly half of those over the age of 30 are affected to some degree, and about 70% of those over 65 have the condition. Males are affected more often than females.

Signs and symptoms
In the early stages, periodontitis has very few symptoms, and in many individuals the disease has progressed significantly before they seek treatment.
Symptoms may include:

Redness or bleeding of gums while brushing teeth, using dental floss or biting into hard food (e.g., apples) (though this may also occur in gingivitis, where there is no attachment loss gum disease )
Gum swelling that recurs
Spitting out blood after brushing teeth
Halitosis, or bad breath, and a persistent metallic taste in the mouth
Gingival recession, resulting in apparent lengthening of teeth (this may also be caused by heavy-handed brushing or with a stiff toothbrush)
Deep pockets between the teeth and the gums (pockets are sites where the attachment has been gradually destroyed by collagen-destroying enzymes, known as collagenases)
Loose teeth, in the later stages (though this may occur for other reasons, as well)Gingival inflammation and bone destruction are largely painless. Hence, people may wrongly assume painless bleeding after teeth cleaning is insignificant, although this may be a symptom of progressing periodontitis in that person.

Associated conditions
Periodontitis has been linked to increased inflammation in the body, such as indicated by raised levels of C-reactive protein and interleukin-6. It is associated with an increased risk of stroke, myocardial infarction, atherosclerosis and hypertension. It also linked in those over 60 years of age to impairments in delayed memory and calculation abilities. Individuals with impaired fasting glucose and diabetes mellitus have higher degrees of periodontal inflammation, and often have difficulties with balancing their blood glucose level owing to the constant systemic inflammatory state, caused by the periodontal inflammation. Although no causal association was proven, there is an association between chronic periodontitis and erectile dysfunction, inflammatory bowel disease, heart disease, and pancreatic cancer.

Diabetes and Periodontal Disease
A positive correlation between raised levels of glucose within the blood and the onset or progression of periodontal disease has been shown in the current literature.
Data has also shown that there is a significant increase in the incidence or progression of periodontitis in patients with uncontrolled diabetes compared to those who do not have diabetes or have well-controlled diabetes. In uncontrolled diabetes, the formation of reactive oxygen species can damage cells such as those in the connective tissue of the periodontal ligament, resulting in cell necrosis or apoptosis. Furthermore, individuals with uncontrolled diabetes mellitus who have frequent exposure to periodontal pathogens have a greater immune response to these bacteria. This can subsequently cause and/or accelerate periodontal tissue destruction leading to periodontal disease.Oral Cancer and Periodontal Disease
Current literature suggests a link between periodontal disease and oral cancer. Studies have confirmed an increase in systemic inflammation markers such as C-Reactive Protein and Interleukin-6 to be found in patients with advanced periodontal disease. The link between systemic inflammation and oral cancer has also been well established.
Both periodontal disease and cancer risk are associated with genetic susceptibility and it is possible that there is a positive association by a shared genetic susceptibility in the two diseases.
Due to the low incidence rate of oral cancer, studies have not been able to conduct quality studies to prove the association between the two, however future larger studies may aid in the identification of individuals at a higher risk.Systemic implications
Periodontal disease (PD) can be described as an inflammatory condition affecting the supporting structures of the teeth. Studies have shown that PD is associated with higher levels of systemic inflammatory markers such as Interleukin-6 (IL-6), C-Reactive Protein (CRP) and Tumor Necrosis Factor (TNF). To compare, elevated levels of these inflammatory markers are also associated with cardiovascular disease and cerebrovascular events such as ischemic strokes.The presence of a wide spectrum inflammatory oral diseases can increase the risk of an episode of stroke in an acute or chronic phase. Inflammatory markers, CRP, IL-6 are known risk factors of stroke. Both inflammatory markers are also biomarkers of PD and found to be an increased level after daily activities, such as mastication or toothbrushing, are performed. Bacteria from the periodontal pockets will enter the bloodstream during these activities and the current literature suggests that this may be a possible triggering of the aggravation of the stroke process.Other mechanisms have been suggested, PD is a known chronic infection. It can aid in the promotion of atherosclerosis by the deposition of cholesterol, cholesterol esters and calcium within the subendothelial layer of vessel walls. Atherosclerotic plaque that is unstable may rupture and release debris and thrombi that may travel to different parts of the circulatory system causing embolization and therefore, an ischemic stroke. Therefore, PD has been suggested as an independent risk factor for stroke.
A variety of cardiovascular diseases can also be associated with periodontal disease. Patients with higher levels of inflammatory markers such as TNF, IL-1, IL-6 and IL-8 can lead to progression of atherosclerosis and the development and perpetuation of atrial fibrillation, as it is associated with platelet and coagulation cascade activations, leading to thrombosis and thrombotic complications.
Experimental animal studies have shown a link between periodontal disease, oxidative stress and cardiac stress. Oxidative stress favours the development and progression of heart failure as it causes cellular dysfunction, oxidation of proteins and lipids, and damage to the deoxyribonucleic acid (DNA), stimulating fibroblast proliferation and metalloproteinases activation favouring cardiac remodelling.

Clinical Significance
Inadequate Nutrition and Periodontal Disease
Periodontal disease is multifactorial, and nutrition can significantly affect its prognosis. Studies have shown that a healthy and well-balanced diet is crucial to maintaining periodontal health. Nutritional deficiencies can lead to oral manifestations such as those in scurvy and rickets disease.
Different vitamins will play a different role in periodontal health:

Vitamin C: Deficiencies may lead to gingival inflammation and bleeding, subsequently advancing periodontal disease
Vitamin D: Deficiencies may lead to delayed post-surgical healing
Vitamin E: Deficiencies may lead to impaired gingival wound healing
Vitamin K: Deficiencies may lead to gingival bleedingNutritional supplements of vitamins have also been shown to positively affect healing after periodontal surgery and many of these vitamins can be found in a variety of food that we eat within a regular healthy diet.
Therefore, vitamin intakes (particularly vitamin C) and dietary supplements not only play a role in improving periodontal health, but also influence the rate of bone formation and periodontal regeneration. However, studies supporting the correlation between nutrition and periodontal health are limited, and more long-term research is required to confirm this.

Causes
Periodontitis is an inflammation of the periodontium, i.e., the tissues that support the teeth. The periodontium consists of four tissues:

gingiva, or gum tissue,
cementum, or outer layer of the roots of teeth,
alveolar bone, or the bony sockets into which the teeth are anchored, and
periodontal ligaments (PDLs), which are the connective tissue fibers that run between the cementum and the alveolar bone.
The primary cause of gingivitis is poor or ineffective oral hygiene, which leads to the accumulation of a mycotic and bacterial matrix at the gum line, called dental plaque. Other contributors are poor nutrition and underlying medical issues such as diabetes. Diabetics must be meticulous with their homecare to control periodontal disease. New finger prick tests have been approved by the Food and Drug Administration in the US, and are being used in dental offices to identify and screen people for possible contributory causes of gum disease, such as diabetes.
In some people, gingivitis progresses to periodontitis – with the destruction of the gingival fibers, the gum tissues separate from the tooth and deepened sulcus, called a periodontal pocket. Subgingival microorganisms (those that exist under the gum line) colonize the periodontal pockets and cause further inflammation in the gum tissues and progressive bone loss. Examples of secondary causes are those things that, by definition, cause microbic plaque accumulation, such as restoration overhangs and root proximity.

Smoking is another factor that increases the occurrence of periodontitis, directly or indirectly, and may interfere with or adversely affect its treatment. It is arguably the most important environmental risk factor for periodontitis. Research has shown that smokers have more bone loss, attachment loss and tooth loss compared to non-smokers. This is likely due to several effects of smoking on the immune response including decreased wound healing, suppression of antibody production, and the reduction of phagocytosis by neutrophilsEhlers–Danlos syndrome and Papillon–Lefèvre syndrome (also known as palmoplantar keratoderma) are also risk factors for periodontitis.
If left undisturbed, microbial plaque calcifies to form calculus, which is commonly called tartar. Calculus above and below the gum line must be removed completely by the dental hygienist or dentist to treat gingivitis and periodontitis. Although the primary cause of both gingivitis and periodontitis is the microbial plaque that adheres to the tooth surfaces, there are many other modifying factors. A very strong risk factor is ones genetic susceptibility. Several conditions and diseases, including Down syndrome, diabetes, and other diseases that affect ones resistance to infection, also increase susceptibility to periodontitis.
Periodontitis may be associated with higher stress. Periodontitis occurs more often in people from the lower end of the socioeconomic scale than people from the upper end of the socioeconomic scale.Genetics appear to play a role in determining the risk for periodontitis. It is believed genetics could explain why some people with good plaque control have advanced periodontitis, whilst some others with poor oral hygiene are free from the disease. Genetic factors which could modify the risk of a person developing periodontitis include:

Defects of phagocytosis: person may have hypo-responsive phagocytes.
Hyper-production of interleukins, prostaglandins and cytokines, resulting in an exaggerated immune response.
Interleukin 1 (IL-1) gene polymorphism: people with this polymorphism produce more IL-1, and subsequently are more at risk of developing chronic periodontitis.Diabetes appears to exacerbate the onset, progression, and severity of periodontitis. Although the majority of research has focused on type 2 diabetes, type 1 diabetes appears to have an identical effect on the risk for periodontitis. The extent of the increased risk of periodontitis is dependent on the level of glycaemic control. Therefore, in well managed diabetes there seems to be a small effect of diabetes on the risk for periodontitis. However, the risk increases exponentially as glycaemic control worsens. Overall, the increased risk of periodontitis in diabetics is estimated to be between two and three times higher. So far, the mechanisms underlying the link are not fully understood, but it is known to involve aspects of inflammation, immune functioning, neutrophil activity, and cytokine biology.

Mechanism
As dental plaque or biofilm accumulates on the teeth near and below the gums there is some dysbiosis of the normal oral microbiome. As of 2017 it was not certain what species were most responsible for causing harm, but gram-negative anaerobic bacteria, spirochetes, and viruses have been suggested; in individual people it is sometimes clear that one or more species is driving the disease. Research in 2004 indicated three gram negative anaerobic species: Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Bacteroides forsythus and Eikenella corrodens.Plaque may be soft and uncalcified, hard and calcified, or both; for plaques that are on teeth the calcium comes from saliva; for plaques below the gumline, it comes from blood via oozing of inflamed gums.The damage to teeth and gums comes from the immune system as it attempts to destroy the microbes that are disrupting the normal symbiosis between the oral tissues and the oral microbe community. As in other tissues, Langerhans cells in the epithelium take up antigens from the microbes, and present them to the immune system, leading to movement of white blood cells into the affected tissues. This process in turn activates osteoclasts which begin to destroy bone, and it activates matrix metalloproteinases that destroy ligaments. So, in summary, it is bacteria which initiates the disease, but key destructive events are brought about by the exaggerated response from the hosts immune system.

Classification
There were several attempts to introduce an agreed-upon classification system for periodontal diseases: in 1989, 1993, 1999, and 2017.

1999 classification
The 1999 classification system for periodontal diseases and conditions listed seven major categories of periodontal diseases, of which 2–6 are termed destructive periodontal disease, because the damage is essentially irreversible. The seven categories are as follows:

Gingivitis
Chronic periodontitis
Aggressive periodontitis
Periodontitis as a manifestation of systemic disease
Necrotizing ulcerative gingivitis/periodontitis
Abscesses of the periodontium
Combined periodontic-endodontic lesionsMoreover, terminology expressing both the extent and severity of periodontal diseases are appended to the terms above to denote the specific diagnosis of a particular person or group of people.

Severity
The "severity" of disease refers to the amount of periodontal ligament fibers that have been lost, termed "clinical attachment loss". According to the 1999 classification, the severity of chronic periodontitis is graded as follows:
Slight: 1–2 mm (0.039–0.079 in) of attachment loss
Moderate: 3–4 mm (0.12–0.16 in) of attachment loss
Severe: ≥ 5 mm (0.20 in) of attachment loss

Extent
The "extent" of disease refers to the proportion of the dentition affected by the disease in terms of percentage of sites. Sites are defined as the positions at which probing measurements are taken around each tooth and, generally, six probing sites around each tooth are recorded, as follows:

Mesiobuccal
Mid-buccal
Distobuccal
Mesiolingual
Mid-lingual
DistolingualIf up to 30% of sites in the mouth are affected, the manifestation is classified as "localized"; for more than 30%, the term "generalized" is used.

2017 classification
The 2017 classification of periodontal diseases is as follows:Periodontal health, gingival disease and conditions

Periodontal health and gingival health
Clinical gingival health on an intact periodontium
Clinical gingival health on an intact periodontium
Stable periodontitis
Non periodontitis person
Gingivitis - Dental biofilm induced
Associated with the dental biofilm alone
Mediated by systemic and local risk factors
Drug induced gingival enlargement.
Gingival diseases - Non dental biofilm induced
Genetic/developmental disorders
Specific infections
Inflammatory and immune conditions
Reactive processes
Neoplasms
Endocrine, nutritional and metabolic
Traumatic lesions
Gingival pigmentation.Periodontitis

Necrotizing periodontal diseases
Necrotizing Gingivitis
Necrotizing Periodontitis
Necrotizing Stomatitis
Periodontitis as a manifestation of systemic disease
PeriodontitisOther conditions affecting the periodontium
(Periodontal Manifestations of Systemic Diseases and Developmental and Acquired Conditions)

Systemic disease of conditions affecting the periodontal support tissues
Other Periodontal Conditions
Periodontal abscesses
Endodontic- periodontal lesions
Mucogingival deformities and conditions
Gingival Phenotype
Gingival/Soft Tissue Recession
Lack of Gingiva
Decreased Vestibular Depth
Aberrant Frenum/muscle position
Gingival Excess
Abnormal Color
Condition of the exposed root surface
Traumatic occlusal forces
Primary Occlusal Trauma
Secondary Occlusal Trauma
Tooth and prosthesis related factors
Localized tooth-related factors
Localized dental prostheses-related factorsPeri-implant diseases and conditions

Peri-implant health
Peri-implant mucositis
Peri-implantitis
Peri-implant soft and hard tissue deficiencies

Staging
The goals of staging periodontitis is to classify the severity of damage and assess specific factors that may affect management.According to the 2017 classification, periodontitis is divided into four stages; after considering a few factors such as:

Amount and percentage bone loss radiographically
Clinical attachment loss, probing depth
Presence of furcation
Vertical bony defects
History of tooth loss related to periodontitis
Tooth hypermobility due to secondary occlusal trauma

Grading
According to the 2017 classification, the grading system for periodontitis consists of three grades:
Grade A: Slow progression of disease; no evidence of bone loss over last five years
Grade B: Moderate progression; < 2mm of bone loss over last five years
Grade C: Rapid progression or future progression at high risk; ≥ 2mm bone loss over five yearsRisk factors affecting which grade a person is classified into include:
Smoking
Diabetes

Prevention
Daily oral hygiene measures to prevent periodontal disease include:

Brushing properly on a regular basis (at least twice daily), with the person attempting to direct the toothbrush bristles underneath the gumline, helps disrupt the bacterial-mycotic growth and formation of subgingival plaque.
Flossing daily and using interdental brushes (if the space between teeth is large enough), as well as cleaning behind the last tooth, the third molar, in each quarter
Using an antiseptic mouthwash: Chlorhexidine gluconate-based mouthwash in combination with careful oral hygiene may cure gingivitis, although they cannot reverse any attachment loss due to periodontitis.
Regular dental check-ups and professional teeth cleaning as required: Dental check-ups serve to monitor the persons oral hygiene methods and levels of attachment around teeth, identify any early signs of periodontitis, and monitor response to treatment.Clinical trials show that smoking cessation abd dietary improvements improve disease outcomes.Typically, dental hygienists (or dentists) use special instruments to clean (debride) teeth below the gumline and disrupt any plaque growing below the gumline. This is a standard treatment to prevent any further progress of established periodontitis. Studies show that after such a professional cleaning (periodontal debridement), microbial plaque tends to grow back to precleaning levels after about three to four months. Nonetheless, the continued stabilization of a persons periodontal state depends largely, if not primarily, on the persons oral hygiene at home, as well as on the go. Without daily oral hygiene, periodontal disease will not be overcome, especially if the person has a history of extensive periodontal disease.

Management
The cornerstone of successful periodontal treatment starts with establishing excellent oral hygiene. This includes twice-daily brushing with daily flossing. Also, the use of an interdental brush is helpful if space between the teeth allows. For smaller spaces, products such as narrow picks with soft rubber bristles provide excellent manual cleaning. Persons with dexterity problems, such as with arthritis, may find oral hygiene to be difficult and may require more frequent professional care and/or the use of a powered toothbrush. Persons with periodontitis must realize it is a chronic inflammatory disease and a lifelong regimen of excellent hygiene and professional maintenance care with a dentist/hygienist or periodontist is required to maintain affected teeth.

Initial therapy
Removal of microbial plaque and calculus is necessary to establish periodontal health. The first step in the treatment of periodontitis involves nonsurgical cleaning below the gum line with a procedure called "root surface instrumentation" or "RSI", this causes a mechanical disturbance to the bacterial biofilm below the gumline. This procedure involves the use of specialized curettes to mechanically remove plaque and calculus from below the gumline, and may require multiple visits and local anesthesia to adequately complete. In addition to initial RSI, it may also be necessary to adjust the occlusion (bite) to prevent excessive force on teeth that have reduced bone support. Also, it may be necessary to complete any other dental needs, such as replacement of rough, plaque-retentive restorations, closure of open contacts between teeth, and any other requirements diagnosed at the initial evaluation. It is important to note that RSI is different to scaling and root planing: RSI only removes the calculus, while scaling and root planing removes the calculus as well as underlying softened dentine, which leaves behind a smooth and glassy surface, which is not a requisite for periodontal healing. Therefore, RSI is now advocated over root planing.

Reevaluation
Nonsurgical scaling and root planing are usually successful if the periodontal pockets are shallower than 4–5 mm (0.16–0.20 in). The dentist or hygienist must perform a re-evaluation four to six weeks after the initial scaling and root planing, to determine if the persons oral hygiene has improved and inflammation has regressed. Probing should be avoided then, and an analysis by gingival index should determine the presence or absence of inflammation. The monthly reevaluation of periodontal therapy should involve periodontal charting as a better indication of the success of treatment, and to see if other courses of treatment can be identified. Pocket depths of greater than 5–6 mm (0.20–0.24 in) which remain after initial therapy, with bleeding upon probing, indicate continued active disease and will very likely lead to further bone loss over time. This is especially true in molar tooth sites where furcations (areas between the roots) have been exposed.

Surgery
If nonsurgical therapy is found to have been unsuccessful in managing signs of disease activity, periodontal surgery may be needed to stop progressive bone loss and regenerate lost bone where possible. Many surgical approaches are used in the treatment of advanced periodontitis, including open flap debridement and osseous surgery, as well as guided tissue regeneration and bone grafting. The goal of periodontal surgery is access for definitive calculus removal and surgical management of bony irregularities which have resulted from the disease process to reduce pockets as much as possible. Long-term studies have shown, in moderate to advanced periodontitis, surgically treated cases often have less further breakdown over time and, when coupled with a regular post-treatment maintenance regimen, are successful in nearly halting tooth loss in nearly 85% of diagnosed people.

Local drug delivery
Local drug deliveries in periodontology has gained acceptance and popularity compared to systemic drugs due to decreased risk in development of resistant flora and other side effects. A meta analysis of local tetracycline found improvement. Local application of statin may be useful.

Systemic drug delivery
Systemic drug delivery in conjunction with non-surgical therapy may be used as a means to reduce the percentage of the bacterial plaque load in the mouth. Many different antibiotics and also combinations of them have been tested; however, there is yet very low-certainty evidence of any significant difference in the short and long term compared to non-surgical therapy alone. It may be beneficial to limit the use of systemic drugs, since bacteria can develop antimicrobial resistance and some specific antibiotics might induce temporary mild adverse effects, such as nausea, diarrhoea and gastrointestinal disturbances.

Adjunctive systemic antimicrobial treatment
There is currently low-quality evidence suggesting if adjunctive systemic antimicrobials are beneficial for the non-surgical treatment of periodontitis. It is not sure whether some antibiotics are better than others when used alongside scaling and root planing).

Maintenance
Once successful periodontal treatment has been completed, with or without surgery, an ongoing regimen of "periodontal maintenance" is required. This involves regular checkups and detailed cleanings every three months to prevent repopulation of periodontitis-causing microorganisms, and to closely monitor affected teeth so early treatment can be rendered if the disease recurs. Usually, periodontal disease exists due to poor plaque control resulting from inappropriate brushing. Therefore, if the brushing techniques are not modified, a periodontal recurrence is probable.

Other
Most alternative "at-home" gum disease treatments involve injecting antimicrobial solutions, such as hydrogen peroxide, into periodontal pockets via slender applicators or oral irrigators. This process disrupts anaerobic micro-organism colonies and is effective at reducing infections and inflammation when used daily. A number of other products, functionally equivalent to hydrogen peroxide, are commercially available, but at substantially higher cost. However, such treatments do not address calculus formations, and so are short-lived, as anaerobic microbial colonies quickly regenerate in and around calculus.
Doxycycline may be given alongside the primary therapy of scaling (see § initial therapy). Doxycycline has been shown to improve indicators of disease progression (namely probing depth and attachment level). Its mechanism of action involves inhibition of matrix metalloproteinases (such as collagenase), which degrade the teeths supporting tissues (periodontium) under inflammatory conditions. To avoid killing beneficial oral microbes, only small doses of doxycycline (20 mg) are used.Phage therapy may be a new therapeutic alternative.

Prognosis
Dentists and dental hygienists measure periodontal disease using a device called a periodontal probe. This thin "measuring stick" is gently placed into the space between the gums and the teeth, and slipped below the gumline. If the probe can slip more than 3 mm (0.12 in) below the gumline, the person is said to have a gingival pocket if no migration of the epithelial attachment has occurred or a periodontal pocket if apical migration has occurred. This is somewhat of a misnomer, as any depth is, in essence, a pocket, which in turn is defined by its depth, i.e., a 2-mm pocket or a 6-mm pocket. However, pockets are generally accepted as self-cleansable (at home, by the person, with a toothbrush) if they are 3 mm or less in depth. This is important because if a pocket is deeper than 3 mm around the tooth, at-home care will not be sufficient to cleanse the pocket, and professional care should be sought. When the pocket depths reach 6 to 7 mm (0.24 to 0.28 in) in depth, the hand instruments and ultrasonic scalers used by the dental professionals may not reach deeply enough into the pocket to clean out the microbial plaque that causes gingival inflammation. In such a situation, the bone or the gums around that tooth should be surgically altered or it will always have inflammation which will likely result in more bone loss around that tooth. An additional way to stop the inflammation would be for the person to receive subgingival antibiotics (such as minocycline) or undergo some form of gingival surgery to access the depths of the pockets and perhaps even change the pocket depths so they become 3 mm or less in depth and can once again be properly cleaned by the person at home with his or her toothbrush.
If people have 7-mm or deeper pockets around their teeth, then they would likely risk eventual tooth loss over the years. If this periodontal condition is not identified and people remain unaware of the progressive nature of the disease, then years later, they may be surprised that some teeth will gradually become loose and may need to be extracted, sometimes due to a severe infection or even pain.
According to the Sri Lankan tea laborer study, in the absence of any oral hygiene activity, approximately 10% will experience severe periodontal disease with rapid loss of attachment (>2 mm/year). About 80% will experience moderate loss (1–2 mm/year) and the remaining 10% will not experience any loss.

Epidemiology
Periodontitis is very common, and is widely regarded as the second most common dental disease worldwide, after dental decay, and in the United States has a prevalence of 30–50% of the population, but only about 10% have severe forms.
Chronic periodontitis affects about 750 million people or about 10.8% of the world population as of 2010.Like other conditions intimately related to access to hygiene and basic medical monitoring and care, periodontitis tends to be more common in economically disadvantaged populations or regions. Its occurrence decreases with a higher standard of living. In Israeli population, individuals of Yemenite, North-African, South Asian, or Mediterranean origin have higher prevalence of periodontal disease than individuals from European descent. Periodontitis is frequently reported to be socially patterned, i.e. people from the lower end of the socioeconomic scale are affected more often than people from the upper end of the socioeconomic scale.

History
An ancient hominid from 3 million years ago had gum disease. Records from China and the Middle East, along with archaeological studies, show that mankind has had Periodontal disease for at least many thousands of years. In Europe and the Middle East archaeological research looking at ancient plaque DNA, shows that in the ancient hunter-gatherer lifestyle there was less gum disease, but that it became more common when more cereals were eaten. The Otzi Iceman was shown to have had severe gum disease. Furthermore, research has shown that in the Roman era in the UK, there was less periodontal disease than in modern times. The researchers suggest that smoking may be a key to this.

Society and culture
Etymology
The word "periodontitis" (Greek: περιοδοντίτις) comes from the Greek peri, "around", odous (GEN odontos), "tooth", and the suffix -itis, in medical terminology "inflammation" </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 Pernicious anemia and can you explain it in depth? [/INST] Pernicious anemia is a type of vitamin B12 deficiency anemia, a disease in which not enough red blood cells are produced due to the malabsorption of vitamin B12. Malabsorption in pernicious anemia results from the lack or loss of intrinsic factor needed for the absorption of vitamin B12. Anemia is defined as a condition in which the blood has a lower than normal amount of red blood cells or hemoglobin. The disease may come on slowly and insidiously.The most common initial symptoms are tiredness, and weakness. Other signs and symptoms of anemia include breathlessness, dizziness, a sore red tongue, lightheadedness, headaches, poor ability to exercise, cold hands and feet, low blood pressure, pale or yellow skin, chest pain, and an irregular heartbeat. The digestive tract may also be disturbed giving symptoms that can include nausea and vomiting, heartburn, upset stomach and loss of appetite. Pernicious anemia can cause osteoporosis and may lead to bone fractures. Symptoms of severe vitamin B12 deficiency can include tingling or numbness in the hands and feet, memory problems, blurred vision, unsteady walking, poor balance, muscle weakness, impaired sense of taste and smell, poor reflexes, clumsiness, depression, and confusion. Without treatment, some of these problems may become permanent.Pernicious anemia occurs due to an autoimmune response that produces antibodies that attack the parietal cells in the stomach lining and prevents them from creating intrinsic factor. Malabsorption may also result from the surgical removal of all or part of the stomach or small intestine; from an inherited disorder or from certain drugs or illnesses that damage the stomach lining. Other causes of low vitamin B12 include not enough dietary intake (which can be a risk in a vegan diet), celiac disease, or tapeworm infection. When suspected, diagnosis is made by blood tests initially a complete blood count, and occasionally, bone marrow tests. Blood tests may show fewer but larger red blood cells, low numbers of young red blood cells, low levels of vitamin B12, and antibodies to intrinsic factor.Pernicious anemia can be treated with intramuscular injections or pills of vitamin B12. Nasal sprays and gels are also available for those who have trouble swallowing pills. Treatment may need to be lifelong.Pernicious anemia due to autoimmune problems occurs in about one per 1000 people in the USA. Among those over the age of 60, about 2% have the condition. It more commonly affects people of northern European descent. Women are more commonly affected than men. With proper treatment, most people live normal lives. Due to a higher risk of stomach cancer, those with pernicious anemia should be checked regularly for this. The first clear description was by Thomas Addison in 1849. The term "pernicious" means "deadly", and this term came into use because before the availability of treatment the disease was often fatal.

Signs and symptoms
Pernicious anemia often presents slowly, and can cause harm insidiously and unnoticeably. Untreated, it can lead to neurological complications, and in serious cases, death. It can take several years for pernicious anemia to appear, and the disease often goes unrecognized, as the body becomes used to feeling unwell.
The onset may be vague and slow, as the same symptoms are often also present with anemia; in 81.1% of cases of cobalamin deficiency, pernicious anemia is not observed. Pernicious anemia may be present without a person experiencing symptoms at first, over time, feeling tired and weak, lightheadedness, dizziness, headaches, rapid or irregular heartbeat, breathlessness, glossitis (a sore red tongue), poor ability to exercise, low blood pressure, cold hands and feet, pale or yellow skin, easy bruising and bleeding, low-grade fevers, shakiness, cold sensitivity, chest pain, upset stomach, nausea, loss of appetite, heartburn, weight loss, diarrhea, constipation, severe joint pain, feeling abnormal sensations including tingling or numbness to the fingers and toes (pins and needles), and tinnitus, may occur. Anemia may present with a number of further common symptoms, including hair thinning and loss, early greying of the hair, mouth ulcers, bleeding gums, angular cheilitis, a look of exhaustion with pale and dehydrated or cracked lips and dark circles around the eyes, as well as brittle nails.In more severe or prolonged cases of pernicious anemia, nerve cell damage may occur, which can lead to more severe symptoms, including sense loss, difficulty in proprioception, neuropathic pain, unsteady walking (ataxia), poor balance, loss of sensation in the feet, muscle weakness, blurred vision (either due to retinopathy or optic neuropathy), impaired urination, fertility problems, decreased sense of taste and smell, decreased level of consciousness, changes in reflexes, memory loss, mood swings, depression, irritability, slurred speech, cognitive impairment, confusion, anxiety, clumsiness, psychosis, and, in more severe cases, dementia. Anemia may also lead to cardiac murmurs and/or altered blood pressure (low or high). The deficiency may also present with thyroid disorders. In severe cases, the anemia may cause congestive heart failure. A complication of severe chronic PA is subacute combined degeneration of spinal cord, which leads to distal sensory loss (posterior column), absent ankle reflex, increased knee reflex response, and extensor plantar response. Other than anemia, hematological symptoms may include cytopenias, intramedullary hemolysis, and pseudothrombotic microangiopathy. Vitamin B12 deficiency, which is reversible, is occasionally confused with acute myeloid leukemia, which is an irreversible autoimmune condition presenting with some of the same hematological symptoms, including hypercellular bone marrow with blastic differentiation and hypersegmented neutrophils. Pernicious anemia can contribute to a delay in physical growth in children, and may also be a cause for delay in puberty for adolescents.

Causes
Vitamin B12 cannot be produced by the human body, and must be obtained from the diet. When foods containing B12 are eaten, the vitamin is usually bound to protein and is released by proteases released by the pancreas into the small bowel. Following its release, most B12 is absorbed by the body in the small bowel (ileum) after binding to a protein known as intrinsic factor. Intrinsic factor is produced by parietal cells of the gastric mucosa (stomach lining) and the intrinsic factor-B12-complex is absorbed by enterocytes in the ileums cubam receptors. PA is characterised by B12 deficiency caused by the absence of intrinsic factor. Other disorders that can disrupt the absorption of vitamin B12 in the small intestine include celiac disease, surgical removal of crohns disease, and HIV.

PA may be considered as an end stage of autoimmune atrophic gastritis, a disease characterised by stomach atrophy and the presence of antibodies to parietal cells and intrinsic factor. Autoimmune atrophic gastritis, is localised to the body of the stomach, where parietal cells are located. Antibodies to intrinsic factor and parietal cells cause the destruction of the oxyntic gastric mucosa, in which the parietal cells are located, leading to the subsequent loss of intrinsic factor synthesis. Without intrinsic factor, the ileum can no longer absorb the B12. Atrophic gastritis is often a precursor to gastric cancer.Although the exact role of Helicobacter pylori infection in PA remains controversial, evidence indicates H. pylori is involved in the pathogenesis of the disease. A long-standing H. pylori infection may cause gastric autoimmunity by a mechanism known as molecular mimicry. Antibodies produced by the immune system can be cross-reactive and may bind to both H. pylori antigens and those found in the gastric mucosa. The antibodies are produced by activated B cells that recognise both pathogen and self-derived peptides. The autoantigens believed to cause the autoreactivity are the alpha and beta subunits of the sodium-potassium pump. In a study, B12 deficiency caused by Helicobacter pylori was positively correlated with CagA positivity and gastric inflammatory activity, rather than gastric atrophy. Less commonly, H. pylori and Zollinger-Ellison syndrome may cause a form of nonautoimmune gastritis that can lead to pernicious anemia.Impaired B12 absorption can also occur following gastric removal (gastrectomy) or gastric bypass surgery. In these surgeries, either the parts of the stomach that produce gastric secretions are removed or they are bypassed. This means intrinsic factor, as well as other factors required for B12 absorption, are not available. However, B12 deficiency after gastric surgery does not usually become a clinical issue. This is probably because the body stores many years worth of B12 in the liver and gastric surgery patients are adequately supplemented with the vitamin.Although no specific PA susceptibility genes have been identified, a genetic factor likely is involved in the disease. Pernicious anemia is often found in conjunction with other autoimmune disorders, suggesting common autoimmune susceptibility genes may be a causative factor. In spite of that, previous family studies and case reports focusing on PA have suggested that there is a tendency of genetic heritance of PA in particular, and close relatives of the PA patients seem to have higher incidence of PA and associated PA conditions. Moreover, it was further indicated that the formation of antibodies to gastric cells was autosomal dominant gene determined, and the presence of antibodies to the gastric cells might not be necessarily related to the occurrence of atrophic gastritis related to PA.

Pathophysiology
Although the healthy body stores three to five years worth of B12 in the liver, the usually undetected autoimmune activity in ones gut over a prolonged period of time leads to B12 depletion and the resulting anemia; pernicious anemia refers to one of the hematologic manifestations of chronic auto-immune gastritis, in which the immune system targets the parietal cells of the stomach or intrinsic factor itself, leading to decreased absorption of vitamin B12.
B12 is required by enzymes for two reactions: the conversion of methylmalonyl-CoA to succinyl-CoA, and the conversion of homocysteine to methionine. In the latter reaction, the methyl group of levomefolic acid is transferred to homocysteine to produce tetrahydrofolate and methionine. This reaction is catalyzed by the enzyme methionine synthase with B12 as an essential cofactor. During B12 deficiency, this reaction cannot proceed, which leads to the accumulation of levomefolic acid. This accumulation depletes the other types of folate required for purine and thymidylate synthesis, which are required for the synthesis of DNA. Inhibition of DNA replication in maturing red blood cells results in the formation of large, fragile megaloblastic erythrocytes. The neurological aspects of the disease are thought to arise from the accumulation of methylmalonyl- CoA due to the requirement of B12 as a cofactor to the enzyme methylmalonyl-CoA mutase.

Diagnosis
Pernicious anemia is thought mainly to be an autoimmune disorder that attacks the gastric parietal cells that produce intrinsic factor resulting in impaired absorption of B12.  However, pernicious anemia may also have a genetic component, potentially running in families. Pernicious anemia may be suspected when a blood smear shows large, brittle, immature, erythrocytes, known as megaloblasts. To make a diagnosis a full blood count, and blood smear, with the following tests included is needed:
A complete blood count and blood smear evaluates the mean corpuscular volume (MCV) and the mean corpuscular hemoglobin concentration (MCHC) to demonstrate  megaloblastic anemia. PA is identified with a high MCV (macrocytic anemia) and a normal MCHC (normochromic anemia). Ovalocytes are also typically seen on the blood smear, and a pathognomonic feature of megaloblastic anemias (which include PA and others) is hypersegmented neutrophils.
Vitamin B12 serum levels are used to detect its deficiency, but do not distinguish its causes. Vitamin B12 levels can be falsely high or low and data for sensitivity and specificity vary widely. Normal serum levels may be found in cases of deficiency where myeloproliferative disorders, liver disease, transcobalamin II deficiency, or small intestinal bacterial overgrowth are present.
Intrinsic factor and parietal cell antibodies – the blood is checked for antibodies against IF and parietal cells in the stomach. The presence of antibodies to gastric parietal cells and IF is common in PA. Parietal cell antibodies are found in other autoimmune disorders and also in up to 10% of healthy individuals. However, around 85% of PA patients have parietal cell antibodies, which means they are a sensitive marker for the disease. Intrinsic factor antibodies are much less sensitive than parietal cell antibodies, but they are much more specific. They are found in about half of PA patients and are very rarely found in other disorders. These antibody tests can distinguish between PA and food-B12 malabsorption.
Methylmalonic acid and/or homocysteine  – vitamin B12 plays an important role in metabolic processes and cellular functions. Therefore, its deficiency leads to the accumulation of some metabolic products. Methylmalonic acid and/or homocysteine is one of the metabolic products that can be measured in the blood. as the increase in the levels of both helps differentiate between vitamin B12 deficiency and folic acid deficiency, because homocysteine alone increases in the latter.Elevated gastrin levels can be found in around 80–90% of PA cases, but they may also be found in other forms of gastritis. Decreased pepsinogen I levels or a decreased pepsinogen I to pepsinogen II ratio may also be found, although these findings are less specific to PA and can be found in food-B12 malabsorption and other forms of gastritis.The diagnosis of atrophic gastritis type A should be confirmed by gastroscopy and stepwise biopsy. About 90% of individuals with PA have antibodies for parietal cells; however, only 50% of all individuals in the general population with these antibodies have pernicious anemia.Forms of vitamin B12 deficiency other than PA must be considered in the differential diagnosis of megaloblastic anemia. For example, a B12-deficient state which causes megaloblastic anemia and which may be mistaken for classical PA may be caused by infection with the tapeworm Diphyllobothrium latum, possibly due to the parasites competition with host for vitamin B12.The classic test for PA, the Schilling test, is no longer widely used, as more efficient methods are available. This historic test consisted, in its first step, of taking an oral dose of radiolabelled vitamin B12, followed by quantitation of the vitamin in the patients urine over a 24-hour period via measurement of the radioactivity. A second step of the test repeats the regimen and procedure of the first step, with the addition of oral intrinsic factor. A patient with PA presents lower than normal amounts of intrinsic factor; hence, addition of intrinsic factor in the second step results in an increase in vitamin B12 absorption (over the baseline established in the first). The Schilling test distinguished PA from other forms of B12 deficiency, specifically, from Imerslund–Gräsbeck syndrome, a B12-deficiency caused by mutations in CUBN that codes for cubilin the cobalamin receptor.

Treatment
Pernicious anemia may not be diagnosed at first. More in-depth diagnosis may be required. Pernicious anemia caused by a loss of intrinsic factor cannot be prevented. If there are other, reversible causes of low vitamin B12 levels, the cause must be treated. Pernicious anemia is usually easily treated by providing the necessary level of vitamin B12 supplementation. Severe cases can be treated with intramuscular injections of vitamin B12. Less severe cases may be treated with high doses of oral supplemenation of vitamin B12. A nasal spray, gel, and sublingual preparation are also available for people who may have difficulty in swallowing. Folate supplementation may affect the course and treatment of pernicious anemia, therefore vitamin B12 replacement is often recommended initially. In some severe cases of anemia, a blood transfusion may be needed to resolves haematological effects. Often treatment will be needed for life.

Prognosis
A person with well-treated PA can live a healthy life. Failure to diagnose and treat in time, however, may result in permanent neurological damage, excessive fatigue, depression, memory loss, and other complications. In severe cases, the neurological complications of pernicious anemia can lead to death – hence the name, "pernicious", meaning deadly.There is an increased risk of gastric cancer in those with pernicious anemia linked to the common feature of atrophic gastritis.

Epidemiology
PA is estimated to affect 0.1% of the general population and 1.9% of those over 60, accounting for 20–50% of B12 deficiency in adults. A review of literature shows that the prevalence of PA is higher in Northern Europe, especially in Scandinavian countries, and among people of African descent, and that increased awareness of the disease and better diagnostic tools might play a role in apparently higher rates of incidence.

History
A case of anemia with a first recognition of associated atrophic gastritis a feature of pernicious anemia, was first described in 1824 by James Combe. This was fully investigated in 1849, by British physician Thomas Addison, from which it acquired the common name of Addisons anemia. In 1871, the first accurate description of the disease in Europe was by Michael Anton Biermer, a German physician who referred to the insidious course of the condition, and because it was untreatable and fatal at the time, he first referred to it as "pernicious" anemia. In 1900 Russell coined the term subacute combined degeneration of spinal cord.In 1907, Richard Clarke Cabot reported on a series of 1200 patients with PA; their average survival was between one and  three years. Pernicious anemia was a fatal disease before about the year 1920, until the importance of the liver in hematopoiesis was recognized, the treatment of pernicious anemia was unsuccessful and arbitrary. It may have motivated George Whipple, who had a keen interest in liver diseases, to investigate the livers role in hematopoiesis. Whipple began evaluating the effects of treatments for anemia caused by chronic blood loss. Whipple, Huber, and Robchett have studied the effects on hemoglobin and blood regeneration of a variety of treatments – among which only raw liver has shown real promise. Serendipity is said to have played a role in this discovery. Whipple observed that blood regeneration was poor in dogs fed cooked liver after chronic blood loss, had it not been that a lazy laboratory technician had given the dogs raw liver, the much more dramatic response might not have been discovered at that point in history.

Around 1926, George Minot and William P. Murphy, who learned of Whipples discovery, sought raw liver as a treatment for pernicious anemia. They later suggested a high-protein diet with high amounts of raw liver. This caused a rapid improvement in symptoms and a simultaneous rise in red blood cell counts. Fruit and iron were also part of the diet, and it appears that at this point, Minot and Murphy were not quite sure that the liver was a very important factor. It was thought that iron in liver tissue, not liver juice-soluble factor, cured hemorrhagic anemia in dogs. Thus, the discovery of liver juice as a treatment for pernicious anemia had been by coincidence. However, Minot, Murphy, and Whipple received the joint Nobel Prize for discovering a cure for a previously fatal disease of unknown cause in 1934, becoming the first Americans to be awarded the Nobel Prize in Physiology and Medicine.It is not easy to eat uncooked liver, and extracts were developed as a concentrate of liver juice for intramuscular injection. In 1928, chemist  Edwin Cohn prepared an extract that was 50 to 100 times stronger than obtained from raw liver. This became part of the standard management of pernicious anemia until the 1950s. The active ingredient in the liver remained unknown until 1948. The anti-pernicious anemia factor was only isolated from the liver by Smith, Rex and others. The substance was cobalamin, which the discoverers called "vitamin B12". They showed that giving a few micrograms could prevent relapse in the disease. Dorothy Hodgkin and co-workers went on to use X-ray crystallography to elucidate the structure of cobalamin for which she, too, was awarded a Nobel Prize.Understanding of the pathogenesis of pernicious anaemia increased over subsequent decades. It had long been known that the disease was associated with defects in the gastrointestinal tract: patients had chronic gastritis and lack of acid secretion (achlorhydria) </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 Peroxisomal disorder 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 PID 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 Pinworm infection and can you explain it in depth? [/INST] Pinworm infection (threadworm infection in the UK), also known as enterobiasis, is a human parasitic disease caused by the pinworm. The most common symptom is itching in the anal area. This can make sleeping difficult. The period of time from swallowing eggs to the appearance of new eggs around the anus is 4 to 8 weeks. Some people who are infected do not have symptoms.The disease is spread between people by pinworm eggs. The eggs initially occur around the anus and can survive for up to three weeks in the environment. They may be swallowed following contamination of the hands, food, or other articles. Those at risk are those who go to school, live in a health care institution or prison, or take care of people who are infected. Other animals do not spread the disease. Diagnosis is by seeing the worms which are about one centimetre long or the eggs under a microscope.Treatment is typically with two doses of the medications mebendazole, pyrantel pamoate, or albendazole two weeks apart. Everyone who lives with or takes care of an infected person should be treated at the same time. Washing personal items in hot water after each dose of medication is recommended. Good handwashing, daily bathing in the morning, and daily changing of underwear can help prevent reinfection.Pinworm infections commonly occur in all parts of the world. They are the most common type of worm infection in Western Europe and the United States. School-aged children are the most commonly infected. In the United States about 20% of children will develop pinworm at some point. Infection rates among high-risk groups may be as high as 50%. It is not considered a serious disease. Pinworms are believed to have affected humans throughout history.

Signs and symptoms
One-third of individuals with pinworm infection are totally asymptomatic. The main symptoms are itching in and around the anus and perineum. The itching occurs mainly during the night, and is caused by the female pinworms migrating to lay eggs around the anus. Both the migrating females and the clumps of eggs are irritating, as well as the sticky substance that is produced by the worms when the eggs are laid. The intensity of the itching varies, and it can be described as tickling, crawling sensations, or even acute pain. The itching leads to continuously scratching the area around the anus, which can further result in tearing of the skin and complications such as secondary bacterial infections, including bacterial skin inflammation, and hair follicle inflammation. General symptoms are trouble sleeping, and restlessness. A considerable proportion of children experience loss of appetite, weight loss, irritability, emotional instability, and bed wetting.Pinworms cannot damage the skin, and they do not normally migrate through tissues. However, they may move onto the vulva and into the vagina, from there moving to the external orifice of the uterus, and onwards to the uterine cavity, fallopian tubes, ovaries, and peritoneal cavity. This can cause inflammation of the vulva and vagina. This causes vaginal discharge and itchiness of the vulva. The pinworms can also enter the urethra, and presumably, they carry intestinal bacteria with them. According to Gutierrez (2000), a statistically significant correlation between pinworm infection and urinary tract infections has been shown; however, Burkhart & Burkhart (2005) maintain that the incidence of pinworms as a cause of urinary tract infections remains unknown. One report indicated that 36% of young girls with a urinary tract infection also had pinworms. Painful urination has been associated with pinworm infection.The relationship between pinworm infestation and appendicitis has been researched, but there is a lack of clear consensus on the matter: While Gutiérrez maintains that there exists a consensus that pinworms do not produce the inflammatory reaction, Cook (1994) states that it is controversial whether pinworms are causatively related to acute appendicitis, and Burkhart & Burkhart (2004) state that pinworm infection causes symptoms of appendicitis to surface.

Cause
The cause of a pinworm infection is the worm Enterobius vermicularis.  The entire lifecycle – from egg to adult – takes place in the human gastrointestinal tract of a single human host. This process is two to eight weeks.

Spread
Pinworm infection spreads through human-to-human transmission, by swallowing infectious pinworm eggs. The eggs are hardy and can remain infectious in a moist environment for up to three weeks, though in a warm dry environment they usually last only 1–2 days. They do not tolerate heat well, but can survive in low temperatures: at −8 degrees Celsius (18 °F), two-thirds of the eggs are still viable after 18 hours.After the eggs have been initially deposited near the anus, they are readily transmitted to other surfaces through contamination. The surface of the eggs is sticky when laid, and the eggs are readily transmitted from their initial deposit near the anus to fingernails, hands, night-clothing and bed linen. From here, eggs are further transmitted to food, water, furniture, toys, bathroom fixtures and other objects. Household pets often carry the eggs in their fur, while not actually being infected. Dust containing eggs can become airborne and widely dispersed when dislodged from surfaces, for instance when shaking out bed clothes and linen. Consequently, the eggs can enter the mouth and nose through inhalation, and be swallowed later. Although pinworms do not strictly multiply inside the body of their human host, some of the pinworm larvae may hatch on the anal mucosa, and migrate up the bowel and back into the gastrointestinal tract of the original host. This process is called retroinfection. According to Burkhart (2005), when this retroinfection occurs, it leads to a heavy parasitic load and ensures that the pinworm infestation continues. This statement is contradictory to a statement by Caldwell, who contends that retroinfection is rare and not clinically significant. Despite the limited, 13-week lifespan of individual pinworms, autoinfection (infection from the original host to itself), either through the anus-to-mouth route or through retroinfection, causes the pinworms to inhabit the same host indefinitely.

Life cycle
The life cycle begins with eggs being ingested. The eggs hatch in the duodenum (first part of the small intestine). The emerging pinworm larvae grow rapidly to a size of 140 to 150 micrometres, and migrate through the small intestine towards the colon. During this migration they moult twice and become adults. Females survive for 5 to 13 weeks, and males about 7 weeks. The male and female pinworms mate in the ileum (last part of the small intestine), whereafter the male pinworms usually die, and are passed out with stool. The gravid female pinworms settle in the ileum, caecum (beginning of the large intestine), appendix and ascending colon, where they attach themselves to the mucosa and ingest colonic contents. Almost the entire body of a gravid female becomes filled with eggs. The estimations of the number of eggs in a gravid female pinworm ranges from about 11,000 to 16,000. The egg-laying process begins approximately five weeks after initial ingestion of pinworm eggs by the human host. The gravid female pinworms migrate through the colon towards the rectum at a rate of 12 to 14 centimetres per hour. They emerge from the anus, and while moving on the skin near the anus, the female pinworms deposit eggs either through (1) contracting and expelling the eggs, (2) dying and then disintegrating, or (3) bodily rupture due to the host scratching the worm. After depositing the eggs, the female becomes opaque and dies. The reason the female emerges from the anus is to obtain the oxygen necessary for the maturation of the eggs.

Diagnosis
Diagnosis relies on finding the eggs or the adult pinworms. Individual eggs are invisible to the naked eye, but they can be seen using a low-power microscope. On the other hand, the light-yellowish thread-like adult pinworms are clearly visually detectable, usually during the night when they move near the anus, or on toilet paper. Shining a flashlight on the infected individuals anus about one hour after they fall asleep is one form of detection and may show worms crawling out of the anus. Another form of detection is the use of transparent adhesive tape (e.g. Scotch Tape) applied on the anal area which will pick up deposited eggs, and diagnosis can be made by examining the tape with a microscope. This test is most successful if done every morning for several days, because the females do not lay eggs every day, and the number of eggs varies. A third method of diagnosis is examining a sample from under their fingernails under a microscope as itching around the anal area is common and therefore they may have collected some eggs under their nails as a result.Pinworms do not lay eggs in the feces, but sometimes eggs are deposited in the intestine. As such, routine examination of fecal material gives a positive diagnosis in only 5 to 15% of infected subjects, and is therefore of little practical diagnostic use. In a heavy infection, female pinworms may adhere to stools that pass out through the anus, and they may thus be detected on the surface on the stool. Adult pinworms are occasionally seen during colonoscopy. On a microscopic level, pinworms have an identifying feature of alae (i.e., protruding ridges) running the length of the worm.

Prevention
Pinworm infection cannot be totally prevented under most circumstances. This is due to the prevalence of the parasite and the ease of transmission through soiled night clothes, airborne eggs, contaminated furniture, toys and other objects. Infection may occur in the highest strata of society, where hygiene and nutritional status are typically high. The stigma associated with pinworm infection is hence considered a possible over-emphasis. Counselling is sometimes needed for upset parents who have discovered their children are infected, as they may not realize how prevalent the infection is.Preventive action revolves around personal hygiene and the cleanliness of the living quarters. The rate of reinfection can be reduced through hygienic measures, and this is recommended especially in recurring cases.The main measures are keeping fingernails short, and washing and scrubbing hands and fingers carefully, especially after defecation and before meals. Showering every morning is also highly recommended to wash off any eggs that may be still laying on the skin. Under ideal conditions, bed covers, sleeping garments, and hand towels should be changed daily and clothes and linens should be washed in hot water and then be placed in a hot dryer in order to kill off any eggs. Children can wear gloves while asleep, and the bedroom floor should be kept clean. Regular disinfection of kitchen and bathroom surfaces will help to prevent spread as well. Food should be covered to limit contamination with dust-borne parasite eggs. It is not recommended to shake clothes and bed linen as the eggs may detach and spread or to share clothes and towels. Nail biting and sucking on fingers is also discouraged.

Treatment
Medication is the primary treatment for pinworm infection. However, reinfection is frequent regardless of the medication used. Total elimination of the parasite in a household may require repeated doses of medication for up to a year or more. Because the drugs kill the adult pinworms, but not the eggs, the first retreatment is recommended in two weeks. Also, if one household member spreads the eggs to another, it will be a matter of two or three weeks before those eggs become adult worms and thus amenable to treatment. Asymptomatic infections, often in small children, can serve as reservoirs of infection, and therefore the entire household should be treated regardless of whether or not symptoms are present.The benzimidazole compounds albendazole (brand names e.g., Albenza, Eskazole, Zentel and Andazol) and mebendazole (brand names e.g., Ovex, Vermox, Antiox and Pripsen) are the most effective. They work by inhibiting the microtubule function in the pinworm adults, causing glycogen depletion, thereby effectively starving the parasite. A single 100 milligram dose of mebendazole with one repetition after two weeks, is considered the safest, and is usually effective with cure rate of 96%. Mebendazole has no serious side effects, although abdominal pain and diarrhea have been reported. Pyrantel pamoate (also called pyrantel embonate, brand names e.g., Reeses Pinworm Medicine, Pin-X, Combantrin, Anthel, Helmintox, and Helmex) kills adult pinworms through neuromuscular blockade, and is considered as effective as the benzimidazole compounds and is used as a second-line medication. Pyrantel pamoate is available over the counter and does not require a prescription. Pinworms located in the genitourinary system (in this case, female genital area) may require other drug treatments.

Treatment in Pregnancy and Breastfeeding
The available data on mebendazole, albendazole, and pyrantel pamoate use in pregnancy is limited and they are all assigned to pregnancy category level C. Treatment of a pinworm infection during pregnancy is only recommended for patients with significant symptoms that may be causing adverse effects to the pregnant person such as loss of sleep and weight loss. Pyrantel pamoate is the treatment of choice in pregnancy but should be used only after consultation with a health care practitioner rather than self-treatment. Treatment should be avoided in the first trimester, and if possible done in the third trimester. If the pregnant individual is asymptomatic, then they should be treated after the baby is delivered.Mebendazole has less than 10% of the oral dose absorbed into systemic circulation with a clinically insignificant amount of drug excreted in breastmilk, and therefore treatment should not be withheld during breastfeeding. There is limited data on the use of pyrantel pamoate and albendazole in breastfeeding but WHO also classifies them as compatible with breastfeeding. This is due to the drugs acting mainly in the intestinal system of the mother with only a very small amount of drug being absorbed into the systemic circulation.

Epidemiology
Pinworm infection occurs worldwide, and is the most common helminth (i.e., parasitic worm) infection in the United States and Western Europe. In the United States, a study by the Center of Disease Control reported an overall incidence rate of 11.4% among people of all ages. Pinworms are particularly common in children with approximately 30% of children being infected and most commonly seen in children between 7 and 11 years old. The prevalence rates in children having been reported as high as 61% in India, 50% in England, 39% in Thailand, 37% in Sweden, and 29% in Denmark. Finger sucking has been shown to increase both incidence and relapse rates, and nail biting has been similarly associated. Because it spreads from host to host through contamination, enterobiasis is common among people living in close contact, and tends to occur in all people within a household. The prevalence of pinworms is not associated with gender, nor with any particular social class, race, or culture </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 Pleurodesis and can you explain it in depth? [/INST] Pleurodesis is a medical procedure in which part of the pleural space is artificially obliterated. It involves the adhesion of the visceral and the costal pleura. The mediastinal pleura is spared.

Uses
Pleurodesis is performed to prevent recurrence of spontaneous pneumothorax or pleural effusion, and can be done chemically or mechanically </s>