How Medical Compliance Solutions Can Save Your Practice Time and Money

Medical compliance solutions are essential for guaranteeing that healthcare professionals follow the many rules and guidelines established by regulatory organizations. These solutions support the preservation of patient data's availability, confidentiality, and integrity as well as the compliance of medical procedures with legal and ethical requirements.

Healthcare businesses may guarantee that they adhere to all legal and ethical standards of practice, safeguard patient information, and satisfy all regulatory obligations by putting thorough compliance procedures into place. By doing this, the organization is protected from legal action while simultaneously boosting public and patient confidence in the healthcare system.

Adherence to laws such as HIPAA (Health Insurance Portability and Accountability Act) in the United States, which mandates the protection of patient health information. Also, compliance with GDPR (General Data Protection Regulation) in Europe for the protection of personal data. Putting strong cybersecurity safeguards in place to protect patient data against hacks and illegal access and employing tight access controls, encryption, and regular security audits.

Furthermore, make certain that only authorized people have access to patient data granting autonomy over their data, encompassing access and decision-making over sharing and usage. Also, keeping complete and accurate records of all contacts and treatments with patients. Reporting regularly to regulatory agencies to prove compliance. Staff members should participate in regular training sessions to stay latest on best practices and new requirements.

Hence, supplying tools and encouragement for ongoing medical compliance education. It is also very important to ensure adherence to all applicable rules and regulations by conducting internal and external audits. Compliance procedures are continuously monitored, and any ongoing problems are fixed right away.  To recognize, evaluate, and reduce the risks connected to non-compliance.

Therefore, creating and putting into practice risk management plans to address possible infractions of the law. You may have several benefits and challenges in this way. The privacy of patient data builds trust and avoids fines and penalties associated with non-compliance. Simplified compliance procedures can raise healthcare operations' general effectiveness. Keeping up with the continuously changing regulatory landscape is the biggest problem.

Investment and resources of a considerable amount may be needed for the implementation and upkeep of compliance solutions. Medical compliance can be intimidating due to its complexity, particularly for smaller healthcare providers.

 

Low energy and stubborn belly fat Diet

I understand that you're concerned about low energy and stubborn belly fat. However, I can share some general information that may be helpful.

Low energy:

Many things can contribute to low energy levels, including:

• Diet: Not eating enough calories or not getting enough nutrients can lead to fatigue.
• Lack of sleep: Most adults need around 7-8 hours of sleep per night.
• Medical conditions: Certain medical conditions, such as anemia, thyroid problems, and depression, can cause fatigue.
• Medications: Some medications can cause fatigue as a side effect.

If you're concerned about your low energy levels, it's important to see a doctor to rule out any underlying medical conditions.

Stubborn belly fat:

Belly fat, also known as visceral fat, is stored around your organs and is more dangerous than fat stored under your skin. Losing belly fat can be difficult, but it is possible with a healthy diet and exercise.

Here are some general tips for losing belly fat:

• Eat a healthy diet: Focus on eating plenty of fruits, vegetables, and whole grains. Choose lean protein sources and limit unhealthy fats, processed foods, and sugary drinks.
• Reduce your calorie intake: You'll need to create a calorie deficit to lose weight. This means eating fewer calories than you burn each day.
• Get regular exercise: Aim for at least 30 minutes of moderate-intensity exercise most days of the week.

Here are some additional tips that may be helpful:

• Drink plenty of water: Water can help you feel full and energized.
• Get enough sleep: When you're well-rested, you're more likely to have more energy and make healthy choices.
• Manage stress: Stress can contribute to weight gain and make it harder to lose weight. Find healthy ways to manage stress, such as yoga, meditation, or spending time in nature.
• Be patient: Losing weight and belly fat takes time and effort. Don't get discouraged if you don't see results immediately.

If you're concerned about your weight or have any questions about how to lose belly fat, it's always best to talk to a doctor or registered dietitian. They can help you create a personalized plan that is safe and effective for you. If you are in struggling off, then try a five super-nutrients with clinical proof that can rejuvenate and purify your liver while also significantly enhancing your general well-being and vitality.

Planks helps to strengthen your core arms, legs, tones your buttocks, builds abs.

 

What is HYSTERIA?

HYSTERIA is a morbid state of the nervous system in which clinical manifestations present a wonderful variety of symptoms closely simulating organic disease. There is often increased physical irritability; the condition manifests in neuralgic pains, hyperesthesias, hallucinations, and convulsive and paralytic phenomena. It may be considered a brain affection - a mild mental illness. Among the causes of hysteria, heredity plays a significant role.

There may be direct transmission of the hysterical temperament from parent to child or other nervous manifestations in the family and its branches. These manifestations include epilepsy, chorea, neuralgia, insanity, etc. It occurs more frequently in women, but it is much more common in men than believed; it occurs in boys and girls at a tender age or about puberty. Briquet found that one-eighth of his cases were for children under 10. Anything that lowers the general tone of the nervous system may contribute to it in predisposed persons.

Haemorrhages, severe illness, poor food, anaemia, overwork in uncongenial occupations, anxiety, fright, jealousy, and disappointments, make a profound impression; so does an education that fosters and stimulates inherited instability. Women's enforced social restrictions often inflicted upon their young children, with lack of proper exercise for physical development and artificial and premature education and habits heighten this predisposition. Accidents are a frequent cause of hysteria, as Charcot clearly pointed out. _ The disease may occur in young girls who have witnessed attacks elsewhere.

To understand hysteria symptoms, it must be remembered that there are two classes of phenomena. These have been termed the psychological stigmata and the menial accidents. The stigmata are anesthesias (loss of sensation), amnesias (forgetfulness), abulias (loss if will power), motor disturbances, and modifications of character. These are the cardinal symptom groups that characterize the hysteric's mental state. Any or all mental accidents may also be noted — suggestibility and sub-conscious acting, fixed ideas, ecstasy, automatism, convulsive movements, sleepwalking, deliriums, etc.

The occurrence of these constitutes substantial corroborative evidence of hysteria. While not found in all hysterics, they may be very common symptoms. Hysterical persons often complain of some of the symptoms found in neurasthenia — neuralgic pains in various parts and hyperesthetic areas about the abdomen, chest, or back, frequently in the neighborhood of the ovary, mammary gland, etc. There may be anaesthetic patches in various parts of the body. In addition, there may be a complete loss of sensation on one side associated with mucous membrane anaesthesia.

The special senses on that side are involved — sight, taste, and hearing. There may be irritations of the bladder and urethra; and pain in the joints, which may be mistaken for joint disease. In some cases, the senses are exceedingly acute. Persons notice odors imperceptible to others; are often made sick by odors that do not affect normal individuals; and may like odors and substances disagreeable to others. Perverted sense is shown in abnormal tastes, soap, slate, pencils, etc. Hysterical manifestations are simply emotional exaggerations; they laugh and cry without cause.

In serious attacks, there may be various hysterical manifestations. Occasionally tactile sensibility is disturbed and the muscular sense may be abolished. The anaesthesia may affect the mucous membranes of the mouth, pharynx, and nose, abolishing reflexes. Secretions may be diminished or stopped. Spasmodic convulsions and paralytic phenomena may occur. The spasmodic attack may be rhythmic; may simulate organic disease trembling; may be confined to one member or involve the entire half of the body; may coarse, as in disseminated sclerosis, or a fine tremor, as in paralysis agitans, or the tremor may simulate organic brain disease.

It may occur in any muscle or group of muscles; and may manifest itself as contracture, which may be intermittent or last continuously for months or years. Contracture may be confined to the strong jaw muscles and other muscles in their vicinity, resulting in trismus. Spasms of the glottis may cause severe difficulty breathing or of the pharynx, causing difficulty swallowing. Globus hystericus is a constant symptom but it is not as frequent as often thought.

Persistent and severe vomiting often occurs, but nutritionists rarely suffer materially from these attacks. Retention of urine is frequent, owing to sphincter spasms, and a catheter may have to be used for months. Paralysis occurs in these cases; it is variable in distribution and may come on suddenly after a convulsive attack or without it; it may be flaccid or associated with contracture; it may come on slowly; it may be confined to one limb or hemiplegic in type. Hysterics are easily affected by pleasurable or painful impressions and crave sympathy and attention.

They may show moral perversion; may lie, steal, quarrel with, and intrigue against their own family; may form and change attachments and dislikes without obvious reason; may manifest aversions, to frogs, spiders, mice, cats, etc.; may deceive for deception's sake or to excite wonder. Some are painfully depressed; they have forebodings or are compelled to do certain acts. It is here that hysterical insanities and imperative conceptions as well as neurasthenias are discussed. Hystero-epileptic attacks in their greatest severity are often preceded by general discomfort or hallucinations of vision and hearing. Usually sudden, they may be preceded by an "aura," globus hystericus, singing in the ear, etc.

Breathing is spasmodic; consciousness is obscured; convulsions may be similar to mild epilepsy. In some cases, the body is thrown into all sorts of contortions. Extreme opisthotonos may be present, the body bent backward, resting on the head and heels. Gestures and noises are made. Sometimes religious ideas influence attitudes assumed; sometimes demonic possession. In milder forms, recovery is the rule. In grave cases, and when there is a strong neuronopathic tendency, the person will probably pass from one hysterical manifestation to another.

Treatment.

In cases where physical health deteriorates, tonics, and a nutritious diet should be given. Hydrotherapy improves nutrition and mental state. Many drugs have been recommended, but they are all uncertain about their action, giving a result and failing at another. Convulsive attacks may be stopped by applying a cold douche to the spine. Isolation from the family circle is of the utmost importance in treating these cases. Every effort should be made to discover the psychic shock that triggered the attack. Only the patient may know this and will not often reveal it. There is no disease whose treatment is harder to describe. Suggestion therapy gives the fastest results, but the great difficulty is that successful results are rarely permanent.

Intermittent Fasting

Intermittent fasting should be another part of the whole program you have decided to use in your quest for better health.
Considering the discomfort that you have to endure when fasting especially if you are a beginner, it must have crossed your mind why do you even need to fast. The benefits are just too numerous to list out, but I will give you a few.

- Your metabolism is increased during the process.
- The fat deposits around your body are used up quite fast.
- You can control your urge to eat.
- Your blood pressure is reduced to normal healthy levels.
- The levels of your blood sugar are maintained at optimal levels.
- Your heart functions just as it should.

So before you embark on this program, you should be quite aware of the foundations on which it was built. You should have a dedicated mindset, have an unshifting view of attaining your goal no matter how tough it may be, focus on giving your body the very best and also have it at the forefront of all your
actions that you have to incorporate regular exercise into the program. Intermittent fasting does not require you stocking up on a particular group of food. Instead, you should eat mindfully having it in mind that what you eat will eventually have an impact on your health either negative or positive. So if you decide to be holistic about your eating habits, it will be easier for your fasting program to yield and maintain the results you seek. So are you ready for your first steps towards fasting?

A running retreat or running school

Imagine a week or a weekend during which you didn’t have to work. Days were spent running, meeting good people, eating, sleeping, and learning. In addition, you find yourself motivated for months afterward. This is the essence of what we do during our Galloway running retreats. Many of our participants tell me that the retreat was their reward for staying with their running program for three months, six months a year.

Others needed motivation improves after a layoff. More than a few times a year, Barbara and I conduct beach weekend retreats at Blue Mountain Beach, FL. Not only is there a beautiful white sand beach, but due to its location, there is a series of state parks and a forest preserve, which means hundreds of miles of beautiful trails that wind through pine forests. More often than not during the middle of July, we conduct a weeklong program in the Lake Tahoe area of California.

During each retreat, there are clinics on building endurance, nutrition, fat-burning, getting faster, motivation, shoes, strength, and more. Individual questions are asked constantly, and problem-solving situations are welcomed. Interacting with others results in new friendships and a lot of fun.

Joy Johnson is one of our long-term friends who inspire us every year. She has won her age group many times in the Boston and New York marathons. But that’s not the main source of inspiration. Last year, while on a hike, Joy slipped and hurt her leg so badly that she didn’t know that she would be able to run again.

When one is over eighty, the healing is much slower, but Joy was determined. One year later, Joy was back at Tahoe, training for the next marathon. She is also a beautiful person with a lot of determination. Each participant can receive an individualized running form evaluation. Suggestions are given for those who have challenges. Several form drills are taught to help improve running mechanics. Running schools are three-hour to five-hour focused sessions that cover the content areas taught at running retreats.

These are held in about twenty locations around the United States each year. During each session, I can cut through the conflicting advice, help design a focused training program, and deal with individual problems. I personally conduct each of these sessions. Sign up now and you’ll be motivated leading up to the retreat/school, with a boost for months afterward.

Age-related dehydration etiology

Age-related dehydration etiology - Reduced fluid intake and increased fluid loss in older adults put them at risk of dehydration. Water deprivation reduces thirst in even healthy older adults. Dehydration is reflected both in low thirst scores during dehydration and in reduced water intake after dehydration. 

It has been shown in several studies that older subjects are unable to return to their baseline plasma osmolality or sodium concentration even when water is freely available. Naloxone, an opiate antagonist, modifies fluid intake in young subjects, but not in older subjects, suggesting that the opioid receptor system in older individuals may be deficient, contributing to hypodypsia. Furthermore, presbynephrosis occurs as the elderly age, which contributes to their weakened ability to defend against dehydration as a result of renal concentrating capacity reduction. 

Aging seems to cause a multifactorial but specific problem with water homeostasis. Aldosterone and plasma renin levels diminish with age, as does the ability to respond appropriately to sodium deprivation by increasing aldosterone and plasma renin levels. However, plasma antidiuretic hormone (ADH) and arginine vasopressin (AVP) levels are higher in older dehydrated individuals compared to young people, indicating that this volume and tonicity defense mechanism does not diminish as we age. 

However, healthy older adults are not different from younger adults when it comes to responding to hypertonicity (induced by intravenous infusion of hypertonic saline). The aging process seems to have more to do with how the body senses volume than how it senses tonicity. The osmolality of plasma and the extracellular fluid volume was altered simultaneously by both dehydration and hypertonic saline infusion until recently, however. 

To address this question, a recent study used head-out water immersion, which increases hydrostatic pressure outside the body and drives blood into the thoracic cavity, thus expanding central blood volume by about 700 ml and leading to increased cardiac filling pressure and heart volume without altering plasma osmolality. The increased central volume seems to activate cardiac stretch receptors, attenuating thirst and drinking; this effect is markedly diminished in healthy older subjects, despite a comparable, or greater, increase in central blood volume and atrial natriuretic peptide. 

This experiment suggests that a centrally mediated response to volume, but not to osmolality, is reduced with aging. The changes listed above seem to be physiologic since they occur in healthy older subjects in the absence of chronic diseases. However, many degenerative age-related diseases worsen the tendency towards dehydration in older persons. 

These include delirium, dementia, diuretic use, swallowing problems, laxative abuse, and problems with hand dexterity or ambulation. In addition, dehydration is a common complication of acute illness in older persons. For example, among Medicare beneficiaries in the USA hospitalized with dehydration, 28% had pneumonia or influenza, 25% had a urinary tract infection and 10% had gastroenteritis.

Nursing Care

If someone in your family needs regular nursing care, their doctor may be able to arrange for a community or district nurse to visit them at home. This will not, of course, be a sleeping-in arrangement but simply involves a qualified nurse calling round when necessary. If you want more concentrated home nursing you will have to go through a private agency. 

Consultus can sometimes supply trained nurses. Additionally, there are many specialist agencies that can arrange hourly, daily or living-in nurses on a temporary or longer-term basis. Terms of employment vary considerably. Some nurses will literally undertake nursing duties only – and nothing else; and may even expect to have their meals provided. Others will do light housework and act as nurse companions. 

Fees vary throughout the country, with London inevitably being most expensive. Private health insurance can sometimes be claimed against part of the cost, but this is generally only in respect of qualified nurses. Your local health centre or social services department should be able to give you names and addresses of local agencies. 

There may come a time when you feel that it is no longer safe to live entirely on your own. One possibility is to engage a companion or housekeeper on a permanent basis but such arrangements are normally very expensive. Permanent help can also sometimes be provided by agencies (such as those listed under ‘Temporary living-in help’), who will supply continuous four-weekly placements. 

This is an expensive option and the lack of continuity can at times be distressing for elderly people, particularly at the change-over point. But it can also lead to a happier atmosphere as the housekeeper comes fresh to the job and neither party has time to start getting on each other’s nerves.

Diagnosis of malignant mesothelioma

A definitive pathological diagnosis of malignant pleural mesothelioma usually requires a tissue (biopsy) specimen to demonstrate that the lesion has a mesothelial phenotype and that it shows neoplastic invasion, as opposed to benign entrapment of mesothelium as part of a fibro-inflammatory process. 

• Evidence of malignant mesothelioma on cytological examination of pleural effusion fluid should be confirmed by tissue biopsy or, if a biopsy is considered inadvisable, impractical, or unnecessary, the cyst diagnosis should be supported by clinical and radiological data as a surrogate for the histological demonstration of invasion. 

• The anatomical location and extent of the pleural tumor should be ascertained by imaging studies. 

• The histological appearances of malignant pleural mesothelioma can vary widely, from epithelioid, to sarcomatoid and biphasic mesotheliomas – together with distinctive subtypes – and such variation occurs not only from one mesothelioma to another but sometimes within single mesothelioma. 

• Recognition of the histological subtype can facilitate diagnosis and provides important prognostic information. 

• Immunohistochemistry is essential for the diagnosis and differential diagnosis of malignant pleural mesothelioma and should include positive and negative (carcinoma-related) markers.

The diagnosis of malignant mesothelioma can be difficult, with symptoms and clinical findings that can mimic and be mimicked by other diseases. Pleural mesothelioma patients may present with dyspnoea, chest pain (pleuritic or non-pleuritic), cough, weight loss, or any combinations of these symptoms. Initial clinical and radiological examination usually reveals a pleural effusion, often massive. 

Rarely, patients are asymptomatic at the time when a radiological abnormality is demonstrated, and patients seldom present with metastatic disease. Some patients with malignant mesothelioma experience a long interval between the first onset of symptoms and subsequent diagnosis, but whether a long interval signifies enhanced or diminished survival following diagnosis is unclear. 

Most patients with malignant pleural mesothelioma have a background of asbestos exposure, and some may have had antecedent symptoms associated with the benign asbestos-related disease – for example, symptoms related to asbestosis or benign asbestos pleuritis with effusion. Others may have radiological evidence of past asbestos exposure, such as pleural plaques. 

In general, biopsy, immunohistochemical analysis, and correlation with radiological and clinical features are needed for the diagnosis of mesothelioma. When immunohistochemical findings are non-diagnostic or discordant, electron microscopy – including electron microscopic examination of tissue retrieved from blocks of paraffin embedded biopsy tissue or cytology cell blocks – can be used, but electron microscopy is not recommended for ‘routine’ diagnosis of mesothelioma. 

Although several cytological and histological findings may raise varying levels of suspicion of malignant pleural mesothelioma a current requirement for the definitive clinicopathological diagnosis of malignant pleural mesothelioma is the demonstration of neoplastic invasion – for example, infiltration into subpleural fat, chest wall skeletal muscle, rib or lung – by histological examination or by imaging studies, and by the clinical exclusion of alternative causes for an atypical mesothelial proliferation. 

A component of malignant mesothelioma in situ can be diagnosed when invasion has been demonstrated in the same or different biopsy or by imaging studies. This applies specifically to epithelioid malignant mesotheliomas. Sarcomatoid malignant mesotheliomas are rarely diagnosable from effusion fluid cytology and are usually identified histologically, by the demonstration of invasion or overtly sarcomatoid areas.

What are Cyanogenic Glycosides?

Cyanogenic glycosides are chemical compounds that occur naturally in many plants, including species of Prunus (wild cherry), Sambucus (elderberry), Manihot (cassava), and Linum (flax), Bambusa (bamboo), and Sorghum (sorghum). Chemically, they are defined as glycosides of the a-hydroxynitriles. 

These compounds are potentially toxic as they are readily broken down by enzymic hydrolysis to liberate hydrogen cyanide when the plant suffers physical damage. Occurrence in Foods There are approximately 25 known cyanogenic glycosides, and a number of these can be found in the edible parts of some important food plants. 

These include amygdalin (almonds), dhurrin (sorghum), lotaustralin (cassava), linamarin (cassava, lima beans), prunasin (stone fruit), and taxiphyllin (bamboo shoots). Some of the main food sources of cyanogenic glycosides and their estimated potential yield of hydrogen cyanide are released on hydrolysis. Bitter apricot kernels have been marketed as a health food in the UK and elsewhere. They can contain high levels of the cyanogenic glycoside amygdalin.

Effects on Health

The toxicity of a cyanogenic plant depends largely on the amount of hydrogen cyanide that could be released on consumption of the plant. Adequate processing or preparation is required to ensure that detoxification of the food is complete before consumption. However, if the processing or preparation is insufficient to ensure detoxification, the potential hydrogen cyanide concentration released during consumption can be high. 

Upon consumption of the food, the enzyme b-glycosidase will be released and hydrolysis of the cyanogenic glycoside will commence, resulting in hydrogen cyanide formation. Certain gut microflora also produces b-glycosidases, which can contribute to the breakdown of cyanogenic glycosides into hydrogen cyanide. Hydrogen cyanide is cytotoxic and blocks the activity of cytochrome oxidase – an enzyme critical for cellular respiration. 

When cytochrome oxidase is blocked, ATP production stops, and cellular organelles cease to function. However, cyanide is readily detoxified in animals as all animal tissues contain the enzyme rhodanese – a thiosulfate sulfurtransferase enzyme that converts cyanide to thiocyanate, which is then excreted in the urine. Acute poisoning only occurs when this detoxification mechanism is overwhelmed. 

The symptoms of acute cyanide poisoning include rapid breathing, drop in blood pressure, raised pulse rate, dizziness, headache, stomach pains, vomiting, diarrhea, confusion, twitching, and convulsions. In extreme cases, death may occur. The minimum lethal dose of hydrogen cyanide taken orally is approximately 0.5–3.5 mg/kg body weight or 35–245mg for a person weighing 75 kg. The chronic effects of cyanide consumption are associated with regular long-term consumption of foods containing cyanogenic glycosides in individuals with poor nutrition. 

These effects are most notable in the tropics, where cassava, and to a lesser extent, sorghum, bamboo shoots, and lima beans are staple components of human diets. 

Malnutrition, growth retardation, diabetes, congenital malformations, neurological disorders, and myelopathy are all associated with cassava-eating populations subject to chronic cyanide intake. There are a number of documented cases of poisoning caused by the consumption of apricot kernels. One report concerned a 41-year-old female found comatose after eating approximately 30 bitter apricot kernels, who eventually recovered after treatment. 

There are also case reports of children being poisoned after consumption of wild apricot kernels and where the kernels were made into sweets without proper processing. The UK Committee on Toxicity recommended in March 2006 that a tolerable daily intake (TDI) of 20 mg cyanide/kg BW/day be applied, which is the equivalent of 1–2 bitter apricot kernels per day. There are over 2500 known species of plants that produce cyanogenic glycosides, usually in combination with a corresponding hydrolytic enzyme – a beta-glycosidase. 

When the cell structure of the plant is disrupted in some way, for example by predation, the beta-glycosidase is brought into contact with its substrate – the cyanogenic glycoside. This leads to the breakdown of the glycoside into sugar and a cyanohydrin, which rapidly decomposes to release hydrogen cyanide. The purpose of the reaction is to protect the plant from predation. Stability in Foods Cyanogenic glycosides break down when the cells of the plant are damaged, for example during preparation and processing, and release hydrogen cyanide. Hydrogen cyanide itself is not heated and stable and does not survive boiling and cooking processes. 

It can also be eliminated by fermentation. Processing Adequate processing of cyanogenic glycoside-containing plants should be sufficient to significantly reduce or remove the toxic agents prior to consumption. Processing procedures, such as peeling and slicing disrupt the cell structure of the plant so that b-glycosidases are released and the cyanogenic glycosides are hydrolyzed. 

Hydrogen cyanide is thus released and can be removed by cooking processes such as baking, boiling, or roasting. Fermentation is also used to remove hydrogen cyanide. These methods are particularly suitable for products such as cassava and bamboo shoots. There are two main types of cassava – bitter cassava and sweet cassava. The sweet variety contains a significantly lower concentration of cyanogenic glycosides than the bitter variety, and it is the sweet variety that is used commercially. 

Cassava is consumed largely as cassava flour, cassava chips, and tapioca pearls, all of which are processed products with a long history of safe consumption. Treatments for removing cyanogenic compounds from flaxseed include boiling in water, dry and wet autoclaving, and acid treatment followed by autoclaving. Solvent extraction has also been used to remove cyanogenic glycosides from flaxseed and oil. 

Legislation 

A safe level of cyanide in cassava flour for human consumption has been set by the WHO at 10 ppm. Low levels of cyanide are also present in almonds, sweet apricot kernels and in the stones of other fruit such as cherries, as well as in bitter apricot kernels. In the UK, the maximum level of cyanide that can be present as a result of using such materials as flavourings is regulated under the terms of the Flavourings in Food Regulations 1992 (as amended).

Mesothelial progenitor and side population cells

Proliferative tissues such as skin and bone marrow are maintained by a stable population of progenitor cells with self-renewing properties. Tumors are also proliferative tissues, possibly maintained by a self-renewing cancer stem cell population. Therefore leukemia can be viewed as a tumor maintained by a subset of bone marrow progenitor cells that have tumor-initiating properties. Analogously, mesothelioma may be a tumor maintained by a mesothelial progenitor cell population. Normal mesothelium consists of a single layer of simple squamous mesothelial cells of mesodermal origin that function to maintain serosal fluid production in order to provide a frictionless and protective surface for organ movement. 

Mesothelial cells also participate in material transport across the serosal membrane; and mediate regulatory inflammatory, immune, and tissue repair responses (Mutsaers, 2007). There is evidence for a mesothelial progenitor cell population (Herrick, 2004). First, mesothelial cells express characteristics of mesodermal, epithelial and mesenchymal phenotypes- supportive evidence for multipotential differentiation of a progenitor cell population. In addition, mesothelial cells exhibit plasticity by transforming into tissues such as myofibroblasts and vascular grafts under specific growth conditions (Lv, 2011 & Sparks, 2002). 

After mesothelial tissue injury, new mesothelium regenerates from both cells at the wound edge and from the surrounding serosal fluid, which may be mesothelial progenitor cells capable of tissue regeneration. Mesothelial progenitor cells with such stem cell-like properties are potentially a source of a cancer stem cell population in mesothelioma. Another potential cancer stem cell population in mesothelioma is side population (SP) cells. Defined as cells that efflux the DNA-binding dye Hoechst 33342, SP cells can be enriched for using flow cytometry. Side population cells express ATP-binding cassette (ABC) membrane transporters that efflux the Hoechst 33342 dye, and these transporters are also involved in efflux of drugs such as chemotherapeutic. 

Side population cells are found in both normal and malignant tissues. In cancer, SP cells have been considered a potential cancer stem cell population as well as a cell population responsible for resistance to therapy. SP cells have been identified as a potential cancer stem cell population in various tumors, including ovarian carcinoma and osteosarcoma (Fong, 2010 & Murase, 2009). A group that isolated SP cells from human malignant mesothelioma cell lines illustrated that SP cells had enhanced proliferation and higher expression of stem-cell genes (Kiyonori, 2010). However, the SP cells did not have increased tumorigenic potential in immunodeficiant mice. 

A more recent study reported that SP cells isolated from malignant pleural mesothelioma not only expressed stem cell markers, but also showed self-renewal, chemoresistance, and tumorigenicity (Frei, 2011). Further the subset of SP cells characterized as WT1 negative/D2- 40 positive/CD105 (low) were found to be even more tumorigenic. The increased stem cellness of the SP cells isolated from this study by Frei et al. compared to the study by Kiyonori et al. could be due to their isolation from malignant tissue rather than from mesothelioma cell lines. 

Since cancer stem cells remain to be fully characterized and defined, a diversity of cell types- including progenitor cells and side population cells- may qualify as cancer stem cells in tumors (Bjerkvig, 2005). How a normal mesothelial progenitor cell or side population cell transforms into a cancer stem cell remains to be elucidated. 

Traditional thinking of transformation of a normal differentiated cell into a tumor cell requires multiple hits to the genome resulting in genetic instability and a selective survival advantage. Cancer stem cells may be products of a similar transformative process. Human mesothelial cells exposed to asbestos and SV40 virus were reported to transform via an Akt-mediated cell survival mechanism (Cacciotti, 2005). These authors concluded that mesothelioma originates from a subpopulation of transformed stem cells. 

More work illustrating this important concept is necessary and offers potential targets for therapy to abrogate this transformation process. Hypothetically, the advantage for a tumor to arise from a transformed stem cell rather than from a transformed differentiated cell includes the ability for the tumor to have multiple phenotypes for growth in different microenvironments; an additional mechanism for a metastatic phenotype; and resistance to current therapies. Interestingly, mesothelioma exhibits aspects of all three of these tumor characteristics. Diffuse malignant mesothelioma can be classified histologically into three major classes: epithelioid, sarcomatoid, and mixed-type. Epithelioid is the most common phenotype and the mixed-type can be found in 30% of tumors. 

Sarcomatoid tumors are rare but carry the worst prognosis. There are also rare variants including desmoplastic, undifferentiated and deciduoid types. This wide variety of phenotypes could be explained by a cancer stem cell origin for mesothelioma, such as a transformed mesothelial progenitor cell population that has been shown to differentiate into multiple cell types. Currently, determining the histological subtype is important for diagnosis, prognosis and treatment (Tischoff, 2011). 

If, however, all the histological subtypes are derived from a single stem cell population, earlier diagnosis could be determined before histological differentiation occurs; prognosis could be improved overall; and treatment could be focused on targeting these stem cells. Mesothelioma is an aggressive tumor that often metastasizes. In tumor biology epithelialmesenchymal transition (EMT) is associated with increased tumor invasiveness and metastasis. This transition is reminiscent of the epithelioid versus sarcomatoid type of mesothelioma, and therefore has important implications in the metastastic feature of this tumor. 

EMT is a transdifferentiation program used in normal embryonic development. Activation of this program in carcinogenesis would confer a metastatic phenotype to the tumor cells. Not only can EMT increase cell invasiveness and migration, but it also contributes to additional properties that promote tumor cell survival; such as resistance to apoptosis and senescence, and increased immunosuppression (Thiery, 2009). 

In addition, EMT has been shown to induce stem cell-like properties. Many cancer stem cell traits are consistent with a metastatic phenotype- self-renewal, ability to initiate tumors in a new environment, motility, invasiveness, and resistance to apoptosis (Chaffer, 2011). Evidence of EMT occurring in mesothelioma includes expression of proteins involved in the EMT axis in malignant pleural mesothelioma tissue samples from untreated patients, and expression of the periostin protein in particular by sarcomatoid tumors, which in turn correlated with shorter survival in these patients (Schramm, 2010). 

Successful colonization of metastatic cells to the distant tissues requires activation of genetic and epigenetic programming for survival in the new tissue environment. This area of research is relatively new, but it is believed that the self-renewal property of stem cells offers one explanation for homing success. Once in the new microenvironment, metastatic cells need to successfully utilize the local growth factors and cytokines to gain mitogenic potential and the ability to self-renew. Subsequently the metastatic cells would need to recruit the stroma to aid in cell survival, such as inducing a blood supply (Chambers, 2002). 

Distant metastatic lesions of mesothelioma, amongst other tumors both epithelial and nonepithelial, have been reported to highly express the self-renewal gene Bmi-1, suggesting that a state of self-renewal is linked to metastatic potential (Glinsky, 2005). Whether the metastatic cells in mesothelioma represent a cancer stem cell population derived from the primary tumor, or mesothelioma cells that acquired stem cell-like properties such as selfrenewal en route to and after homing to the distant metastatic site, remains to be studied. However these finding support a role for stem cells in the pathogenesis of mesothelioma. 

Epigenetic mechanisms that do not change the DNA sequence but that do alter gene expression at the mRNA and protein levels are exciting new potential targets for therapy. A number of epigenetic mechanisms have been described in tumors, including microRNA (miRNA) regulation of mRNA expression, histone acetylation/deacetylation, and gene promoter methylation/demethylation. By suppressing expression of tumor suppressor genes or increasing expression of oncogenes, these epigenetic proteins regulate tumorigenesis at an additional level of complexity. 

A study identifying a panel of miRNAs downregulated in malignant pleural mesothelioma tissue samples found redundant miRNA regulators of Wnt signaling, an important pathway in stem cell self renewal (Gee, 2010). Wnt signaling in mesothelioma suggests a cell population with stemness properties, and whose expression appears to be regulated at an epigenetic level. The existence of a cancer stem cell population in mesothelioma is supported by evidence of cells with stem cell-like properties in normal mesothelium, primary mesothelial tumors, and metastatic lesions. 

A definitive cancer stem cell population capable of re-initiating mesotheliomal tumors remains to be identified. If such a cancer stem cell population is discovered, the prospects of earlier diagnosis and novel therapy for malignant mesothelioma would be of utmost importance for further research.