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Lack of exercise is a major cause of chronic diseases – PMC

 

Its editors are known as Wikipedians. Wikipedia is the largest and most-read reference work in history. Sanger coined its name as a blend of ” wiki ” and ” encyclopedia. Its combined editions comprise more than 59 million articles, attracting around 2 billion unique device visits per month and more than 17 million edits per month 1.

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Citing fears of commercial advertising and lack of control, users of the Spanish Wikipedia http://replace.me/13380.txt from Wikipedia to create Enciclopedia Libre in February Though the English Wikipedia reached three million microsoft word 2016 merupakan program brainly free download in Augustthe growth of the edition, in terms of the numbers of new articles and of editors, appears to have peaked around early In Novembera researcher at the Rey Juan Carlos University in Madrid found that the English Wikipedia had lost 49, editors during the first three months of ; in comparison, it lost only 4, editors during the same period in In the same interview, he also claimed the number of editors was “stable and sustainable”.

The number of active English Wikipedia editors has since remained steady after a long period of decline. In JanuaryWikipedia first became one of the ten most popular websites in the US, downloav to Comscore Networks. With This marked a significant increase over Januarywhen Wikipedia ranked 33rd, with around Init received eight billion page views every ;rogram. On January 20,Subodh Varma reporting for The Economic Times indicated that not only had Wikipedia’s growth stalled, it “had lost nearly ten percent downloaad its page views last year.

There was a decline of about two billion between December and December Its most popular versions на этой странице leading the slide: page-views of mfrupakan English Wikipedia declined by twelve percent, those of German version slid by 17 percent and the Japanese fre lost nine percent.

In JanuaryWikipediaan asteroidwas named after Wikipedia; in OctoberWikipedia was honored with the Wikipedia Monument ; and, in Julyof the 7, page volumes of Wikipedia became available as Print Wikipedia.

In Aprilmicdosoft Israeli lunar landerBeresheetcrash landed on the surface of the Moon carrying mdrupakan copy of nearly all of the English Wikipedia engraved on thin nickel plates; experts say the plates likely survived the crash. Unlike traditional encyclopedias, Wikipedia follows the procrastination principle [note 3] regarding the security of its content.

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Each article’s History page links to each revision. Anyone can view the latest changes to articles, and anyone registered may maintain a “watchlist” of articles that interest them so they can be notified of changes. Ineconomics Ph. Any change or edit that ссылка на страницу content in a way that deliberately compromises Wikipedia’s integrity is considered vandalism. The most common and obvious types of vandalism include additions of obscenities and crude microsoft word 2016 merupakan program brainly free download it can also include advertising and other types of spam.

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Sord vandalism is generally easy to remove from Wikipedia articles; the median time to detect and fix it is a few minutes. In the Seigenthaler biography incidentan anonymous editor introduced false information into microsoft word 2016 merupakan program brainly free download biography of American political figure John Seigenthaler in Mayfalsely presenting him as a suspect in the assassination of John F.

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When conduct is not impersonation or anti-social, but rather anti-consensus or in violation of editing policies, remedies tend to be limited to warnings. Each article and each user of Wikipedia has an associated doenload page. These form the primary communication channel for editors to discuss, coordinate and debate.

Wikipedia’s community has been described as cultlike[] although not always with entirely negative connotations. Wikipedians sometimes award one another “virtual barnstars” for good work. These personalized tokens of appreciation reveal a wide range of valued work extending far beyond simple editing to include social support, administrative actions, and types of articulation work.

Microsoft word 2016 merupakan program brainly free download does not require that its editors and contributors provide identification. The English Wikipedia has 6, articles, 44, registered editors, meerupakanactive editors. An editor is considered active if they have made one or more edits in the past 30 days. Editors who fail to comply with Wikipedia frree rituals, such as signing talk page comments, may implicitly signal that they are Wikipedia outsiders, increasing the odds that Wikipedia insiders may target or discount their contributions.

Becoming a Wikipedia insider involves non-trivial costs: the contributor is expected to learn Wikipedia-specific technological codes, submit to a sometimes convoluted dispute resolution process, and learn a “baffling culture rich with in-jokes and insider references”. A study by researchers from Dartmouth College found that “anonymous and infrequent contributors to Wikipedia A study found that Wikipedians were less agreeable, open, and conscientious than others, frwe [] although a later commentary pointed out serious flaws, including that the data showed higher openness and that the differences with the control group and the samples were small.

Several studies have shown that most Wikipedia contributors are male. Notably, the results of a Wikimedia Foundation survey in showed that only 13 percent of Wikipedia editors were female. Similarly, many of these universities, including Yale and Browngave college credit to students who create or edit an article relating to women in science or technology.

Distribution of the 59, articles in different language editions as of September 13, []. There are currently language editions of Wikipedia also called language versionsor simply Wikipedias.

The latter are both languages of the Philippines. In addition to the top six, twelve other Wikipedias have more than a million articles each RussianSpanishItalianEgyptian ArabicPolishJapaneseChineseVietnameseWarayUkrainianArabic and Portugueseseven more have overarticles PersianCatalanSerbianIndonesianKoreanNorwegian and Finnish44 more have over , and 82 more have over 10, Since Wikipedia is based on the Web and dord worldwide, contributors to the same language edition may use different dialects or may come from different countries as is the case for the English edition.

These differences may lead to some conflicts over spelling differences e. Though the various language editions are held to global policies such as “neutral point of view”, they diverge on some points of policy and practice, most notably on whether images that are not licensed freely may be used under a claim of fair use. Jimmy Wales has described Wikipedia as “an effort to create and distribute a free encyclopedia of the highest programm quality to every single person on the planet in their own language”.

They are coordinated in part by Meta-Wiki, the Wikimedia Foundation’s wiki devoted to maintaining all its projects Wikipedia and others. It is not rare for articles strongly related to a particular language not to have counterparts in another edition. For example, articles about small towns in the United States might be available only in English, even when they meet the notability criteria of other language Wikipedia projects. Translated articles represent only a small portion of articles in most editions, in part because those editions do not allow fully automated translation of детальнее на этой странице. Articles available in more than one language may offer “interwiki links”, which link to the counterpart articles in other editions.

A study published by PLOS One in also estimated the share of contributions to different editions of Wikipedia from different regions of the world. On March 1,The Economistin an article titled “The Future of Wikipedia”, cited a trend analysis concerning data published by the Wikimedia Foundation stating that “[t]he number of editors for the English-language version has fallen by a third in seven years.

 

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Ross et al. Likewise, a greater percentage loss in VAT percentage than in body weight occurred after 12 months in a moderate-intensity exercise intervention study of sedentary, overweight, postmenopausal women. VAT loss was exercise dose-dependent A 6-month study examined the dose-response relationship for exercise volume-VAT mass in men and women whose BMI’s ranged from 25—35 Gain by visceral and abdominal fat depots in non-exercising group while 6 months of exercise training produced loss in these fat depots.

Data are presented as change in A visceral abdominal fat, B subcutaneous abdominal fat, and C total abdominal fat on the y axis.

Remarkably, the non-treatment group no exercise had an 8. Kraus et al. Sedentary lifestyle reveals an obesity phenotype that is primarily prevented by enhanced physical activity. A second study replicated the primary preventative effect of physical activity. Adolescents meeting the daily physical activity recommendations overcame the effect of the FTO rs AA polymorphism on obesity-related BMI, body fat, and waist circumference traits seen in sedentary subjects High physical activity levels in additional studies were associated with attenuated BMI and waist-circumference obesity traits for two additional FTO polymorphisms [rs and rs ].

Women with the FTO allele rs only have obesity risk if they are less active 5. In summary then, physical inactivity is required to elicit the phenotype of obesity with polymorphisms predisposing to obesity for the human FTO gene.

Obesity is primarily prevented in at least two genetically modified, obese rodent models by allowing natural, instinctive voluntary running. Voluntary running prevented obesity and its comorbidities [T2D and non-alcoholic fatty liver disease] with no significant reductions of food intake in cholecytokinin-1 receptor OLETF rats having a mutant cholecystokinin gene 37 , , , Mice lacking expression of the melanocortin-4 receptor MC4-R exhibit maturity-onset obesity with hyperphagia, hyperinsulinemia, and hyperglycemia, that is prevented by providing access to wheels for voluntary running Lack of voluntary wheel running reveals the obesity phenotypes.

Physical inactivity, as one of the two components in the caloric balance equation, is an actual cause of positive caloric balance, i.

The most effective control of obesity is primary prevention of physical inactivity by moderate levels of physical activity, rather than secondary or tertiary prevention of obesity associated co-morbidities. Physical inactivity is a primary cause to VAT and whole-body obesities. Primary prevention of obesity is possible today for almost all able-bodied individuals able to exercise.

Risks for the following conditions increase with physical inactivity: Coronary heart disease, T2D, cancers endometrial, breast, and colon , hypertension, dyslipidemia for example, high total cholesterol or high levels of triglycerides , stroke, liver and gallbladder disease, sleep apnea and respiratory problems, osteoarthritis, and gynecological problems abnormal menses, infertility.

Poor fitness or low PA in physically unfit individuals is a greater all-cause and cardiovascular mortality risk than obesity in physically fit individual Physical inactivity is a cause of some obesity co-morbidities.

Thus, even if primary prevention for the loss in body fat fails, primary prevention of some, but not all, of obesity’s co-morbidities is possible with physical activity. A summary of the medical literature describing U. Both of these conditions increase risk for the development of type 2 diabetes. Diminished ability of skeletal muscle and liver cells to respond to the action of a given dose of insulin by transporting glucose from the bloodstream into these tissues, or by reducing glucose production, respectively B to D in Fig.

Insulin secretion is presented as a function of insulin sensitivity. Insulin secretion rises as insulin sensitivity falls when physically active individual point A becomes sedentary point B. A failure of insulin secretion to compensate for fall in insulin sensitivity is noted when both insulin secretion and insulin sensitivity decline from point B to point C, indicating prediabetes.

The upper axis for increased and decreased levels of physical activity implies bidirectionality of the two arrows for glucose intolerance and insulin resistance. The leftward enlarging two arrows illustrate increasing glucose intolerance and insulin resistance with 2—3 days of decreased physical activity.

The clinical significant is that low levels of physical activity produce a permissive environment for prediabetes. In opposite direction, high levels of daily physical activity markedly diminish the permission state to develop prediabetes. The distinction between the two arrows is based upon variability in Masters athlete’s responses to stopping training as shown in figure 2 of ref in which 4 subjects had lesser increases in blood insulin insulin resistance arrow at 30 min into an oral glucose tolerance test as compared to 10 other subjects glucose intolerance arrow.

A continued decline in both insulin secretion and insulin sensitivity at point D is where overt type 2 diabetes is present. Reproduced with permission from Bergman’s original figure ref A hyperbolic relationship between insulin sensitivity and insulin secretion has been defined as by Bergman As insulin resistance and compensatory hyperinsulinemia progress, the pancreatic islets in certain individuals are unable to sustain the hyperinsulinemic state.

Impaired glucose tolerance, characterized by elevations in postprandial glucose, then develops Points B to C. A further decline in insulin secretion and an increase in hepatic glucose production lead to overt diabetes with fasting hyperglycemia Point D.

Ultimately, beta cell failure may ensue We have further modified Harrisons’ redrawing of Bergman’s original figure to indicate that Point A is representative of a daily physically active human and point B is an occasionally active human. Based on a number of studies we propose that increases and decreases in daily physical activity over a time frame of hours to a few days places subjects between Points A and B.

Thus, daily physical activity prevents the progression to Point B, making it impossible to continue from Point B, to Point C and Point D, overt diabetes. Therefore, only if continual physical inactivity is present can the progression to Point C, impaired glucose tolerance, and eventually into Point D, overt diabetes, occur. Diabetes prevalence has risen from 1. We will propose the notion that proper volumes of physical activity would essentially primarily prevent most of T2D, as illustrated by maintaining at point A in Fig.

Blair, and Church hypothesized that the most proximal behavioral cause of insulin resistance is physical inactivity. Highly endurance trained men’s high insulin sensitivity returns to sedentary levels after cessation of training for 38 hrs or 60 hrs 72 as measured by euglycemic-hyperinsulimic clamp. Measured 12, 60, and hrs after the last exercise bout, peripheral tissue glucose disposal dropped from Similarly, 14, 38, 86, and hr after the last exercise bout by endurance trained athletes glucose disposal declined from 9.

Therefore, only days after ceasing exercise training, endurance athletes the same insulin sensitivity as long-term sedentary subjects. Like humans, rats who cease 3 weeks of voluntary wheel running drop their submaximal insulin-stimulated glucose uptake to sedentary values on the 2 nd day of no running in skeletal muscle normally recruited during wheel running Two days of bed rest did not affect insulin resistance A single bout of muscle contraction increases insulin sensitivity in perfused hindquarters of healthy animals , , and in the whole body of healthy humans , Resistance training also enhances insulin sensitivity and improves glucose tolerance in a wide range of human subjects A systemic review of 20 studies found that supervised resistance training improved glycemic control and insulin sensitivity in adults with T2D Independent of insulin action, exercise acts to prevent hyperglycemia by improving glucose uptake in animal skeletal muscle primarily by independently activating the translocation of glucose transporter, GLUT4, from intracellular locations to the plasma membrane of rats , , and also by increasing transcription in mice and translation in rats of GLUT4 leading to greater GLUT4 protein content.

In human subjects, a positive correlation exists between GLUT4 protein content in the vastus lateralis muscle with insulin sensitivity in both sexes The relationship remained in men after adjustment for overall adiposity, regional adiposity, and CRF Conversely, much less effort has gone into investigating the mechanisms through which lack of physical activity decreases insulin sensitivity. Although low-grade inflammation can worsen insulin resistance in a variety of models circulating inflammatory markers were unchanged, while insulin resistance increased during 5 days of bed rest, implying that systemic inflammation is not a mechanism for initial insulin resistance Reduced mitochondrial content or dysfunction has also been postulated to cause insulin resistance by leading to an increased accumulation of lipid intermediates in skeletal muscle The lipid intermediates putatively activate serine kinases that reduce insulin signaling ultimately leading to reduced insulin stimulated GLUT4 translocation to the plasma membrane.

However, the links between insulin resistance and an accumulation of lipid intermediates are associative at this time, and an increasing number of reports have found that the relationship does not always hold true Another possibility is oxidative stress.

Anderson et al. Insulin sensitivity in rat epitrochlearis muscle declines at a time 2 days after stopping 3 weeks of voluntary wheel running when the mitochondrial marker, citrate synthase activity, remains unchanged and elevated from the wheel running No differences in skeletal muscle mitochondria and insulin sensitivity existed between non-obese sedentary controls and hyperphagic, voluntary running in OLETF rats.

Rector et al. However, acute exercise prior to insulin stimulation can restore insulin stimulated glucose transport in muscle from obese Zucker rats , without improving signaling through the insulin-signaling pathway. The links between the contraction-induced energy flux and insulin action are at this time unknown, however according to a comprehensive review of the topic, the molecule Akt substrate may play an integral role as it is activated by both insulin and muscle contraction and plays a major role in activation of GLUT4 translocation to the plasma membrane Global mRNA analysis of human vastus lateralis muscle identified transcripts changing after development of insulin resistance following 9 days of continuous bed rest in 20 healthy young men 8.

Vaag and coauthors 8 emphasized that they could not exclude the possibility that down-regulation of oxidation phosphorylation as well as other genes may have occurred as a result of — not as a causal factor for — skeletal muscle insulin resistance during bed rest.

Furthermore, increased reactive-oxygen species generation and endoplasmic reticulum stress were also identified as potential mechanisms of inactivity induced insulin resistance 8. Physical inactivity is a primary cause of loss of insulin sensitivity in skeletal muscle, and thus whole-body.

Primary prevention of almost all of insulin resistance by high levels of daily physical activity is possible for almost all humans up their seventh decade of life Continued long-term reductions in physical activity are a primary cause of insulin resistance.

By a direct cause of insulin resistance, physical inactivity indirectly, directly, or both in some cases endothelial dysfunction causes all of the aforementioned. It is estimated that 57 million people have prediabetes in the U. Prediabetes is a condition in which blood glucose levels are higher than normal, but not high enough to be classified as T2D. Prediabetics have an increased risk of developing T2D, and T2D’s-associated comorbidities of heart disease, and stroke.

However, to our knowledge, no large RCTs have been performed to test whether a physically active lifestyle over time primarily prevents prediabetes in healthy individuals as compared to healthy inactive individuals. While early prediabetes, late prediabetes, and diabetes are in a continuum, they differ in success of primary prevention by physical activity. For instance, daily physical can reverse insulin resistance in healthy individuals points B to A in the modified Bergman Fig.

However, microvascular retinopathy, neuropathy, nephropathy damage in T2D seems to be non-repairable by physical activity Nearly 24 million people in the U. Today the number is likely even higher. The estimated lifetime risk of developing diabetes for babies born in is The CDC Website states that progression to diabetes among those with prediabetes is not inevitable The National Physical Activity Guidelines Advisory Committee Report NPAGCR 1 states that usage of physical activity questionnaires in large prospective cohort and cross-sectional observational studies all show that increased physical activity levels show associations with reduced risk for developing T2D.

A systemic review of follow-up, case—control or cross-sectional studies by Fogelholm concludes for individuals with BMI of 25—35 having high BMI even with high physical activity were at a greater risk for the incidence of T2D and the prevalence of cardiovascular and diabetes risk factors, compared with normal BMI with low physical activity.

Prospective studies implicating physical inactivity as a risk factor in the development of T2D. Modified from Table 1 in Ref Prediabetic individuals who incorporate lifestyle modification including increases in their physical activity prevent or delay the onset of T2D by returning their elevated blood glucose levels to normal. In the U. The result led Knowler et al. However, intent-to-treat does not separate behavioral from biological mechanisms. Thus, the biological effectiveness of diet and exercise, independent of behavior, is underestimated due to lower compliance rates in the lifestyle versus metformin groups.

Primary prevention of T2D without weight loss has major public health importance due to media and medical emphasis on weight loss.

To determine the effect of leisure-time physical activity on the occurrence of T2D in prediabetics of the Finnish DPS, subjects filled out a 1-yr questionnaire for leisure-time activity and then were followed for an additional 4. DPP, a follow-up analysis was made for those subjects who made one goal, but not a second goal. A recent review describes available evidence suggesting that exercise primarily acts to lower hyperglycemia by improving glucose sensitivity and mechanisms that interfere directly with endothelial metabolism 4.

Another review indicates that it is likely that one of the mechanisms by which physical fitness and activity reduce health risk associated with high BMI is by decreasing fat-to-lean mass ratio and also by decreasing visceral-to-subcutaneous fat ratio. Physical activity also improves glucose-induced insulin secretion in pancreatic beta cells, likely through enhanced gastric inhibitory protein GIP secretion Snyder at al. Contemporary hypotheses are that many individual rare gene variants play a much larger role in the genetic predisposition to T2D , but currently there is little data to support this speculation.

Physical inactivity is an actual cause of insulin resistance and of prediabetes, and therefore, according to disease progression of T2D, itself.

T2D is primarily prevented by primary prevention of insulin resistance prevents movement from point A to B in the modified Bergman figure Fig. T2D is estimated to cost men NAFLD is a progressive disease first apparent by benign fatty liver steatosis , which can evolve to non-alcoholic steatohepatitis NASH that adds inflammation to steatosis.

Later progression leads to steatosis with inflammation and mild to advanced fibrosis, to steatosis with fibrosis alone, to cirrhosis and finally to end-stage liver disease.

Serious outcomes of NAFLD include cirrhosis, hepatocellular carcinoma, coronary heart disease, and diabetes NAFLD is recognized as the leading cause of chronic liver disease in adults and children Gorge et al.

A second study reported a low level of habitual physical activity was associated with higher intrahepatic fat content in healthy, nonalcoholic males and females ages 19—62 OLETF rats have a spontaneous mutation that inactivates cholecystokinin receptor 1 protein to signal satiety. Without the satiety signal, hyperphagia leads to concurrent obesity and NAFLD between the ages of 5 and 8 wks old, which progress to T2D Morphologically, livers of runners had both fewer and smaller lipid droplets compared non-runners.

Habitual leisure-time physical activity, especially anaerobic, may play a protective role in NAFLD by a reduced rate of abdominal obesity in 24—yr old human subjects Further, only the association with resistance physical activity remained significant with further adjustment for BMI. Maintaining or increasing physical activity provides health benefits for patients with fatty liver, independent of changes in weight Targeting weight loss by energy restriction alone or in combination with exercise training has been shown to reduce NAFLD pathology.

In patients with and without NAFLD, nine months of diet and exercise intervention led to three important outcomes: 1 reduction in liver fat was approximately twice reduction of VAT; 2 subjects who resolved NAFLD tended to have higher CRF at prior to the intervention; and 3 VO 2 max at baseline was a predictor of change in liver fat, independently of total- and VAT mass The study indicated that CRF fitness and liver fat are related to each other.

Two approaches were tested. The times for hepatic metabolic adaptations to occur with stoppage of running were: 2 days malonyl-CoA protein increased while phospho-acetyl-CoA carboxylase ACC decreased and 7 days fatty acid synthase increased and cytochrome oxidase activity and fatty acid oxidation decreased.

CVD includes all diseases that affect heart and blood vessels. The American Heart Association lists major CVDs as: of subclinical atherosclerosis, coronary heart disease, acute coronary syndrome myocardial ischemia , angina pectoris, stroke cerebrovascular disease , high blood pressure, congenital cardiovascular defects, cardiomyopathy and heart failure, and other less prevalent CVDs.

Physical inactivity increases the prevalence of all major CVDs. Of the identified CVD risk factors, modest percentage changes occur with habitual physical activity. Mora and Lee presented an analysis that showed that almost one-half of risk factors by which physical activity lowers CVDs are not identified. Physical activity predicts lower CVD risk independent of obesity Increased physical activity levels in women with elevated BMI considerably reduce the risk of coronary heart disease However, the risk is not completely eliminated, reinforcing the importance of being lean and physically active Their suggestions for additional risk factor candidates that are improved by habitual physical activity include:.

CVD is a complex disease. Physical inactivity adaptations in gene expression are very complex, varying by tissue type and time. Thus CVD x physical inactivity interaction promises to be highly individualized, depending on the degree of accuracy of the desired prediction. The strategy for the presentation of individual cardiovascular diseases follows. The order of cardiovascular diseases presented will be coronary heart disease, peripheral artery disease, hypertension, stroke, and congestive heart failure.

Cross-references: Chronic cardiac disease. CHD is a disease of the heart and the coronary arteries that is characterized by atherosclerotic arterial deposits that block blood flow to the heart, causing myocardial infarction.

In , an estimated , Americans will have a myocardial infarction, and approximately , will have a recurrent attack. Using those individuals with 4 MET maximal aerobic exercise capacity as a reference value of 1. Positive effects of chronic exercise on primary prevention of CHD could be explained by several mechanisms including: increased nitric oxide and antioxidants, decreased pro-inflammatory cytokine levels in blood by decreasing production from multiple tissues, and increased regenerative capacity of endothelium expressed by an increased number of circulating endothelial precursor cells, according to a recent comprehensive review of the topic However, these mechanisms do not totally explain the primary prevention of CHD.

Physical inactivity is a cause of at least 1 of 3 deaths from CHD. Sufficient physical activity primarily prevents CHD. Narrowed arteries reduce blood flow to limbs, sometimes causing leg pain, generally referred to as claudication when walking. Cross-reference: Exercise and peripheral arterial insufficiency: Control of blood flow to cardiac and skeletal muscle during exercise.

PAD affects affects 8—12 million people million in the U. However, the Report does find support that physical inactivity contributes to accelerated disease progression in those who have PAD. A recent review concludes that the magnitude of effect from a supervised exercise program exceeds that achieved with any of the pharmacologic agents available to treat PAD Mechanisms by which physical activity is primary prevention of PAD are potentially similar to those given for coronary artery disease.

Physical inactivity may be a factor increasing the risk of PAD. PAD is a strong predictor of myocardial infraction, stroke, and death due to vascular causes. As atherosclerosis is by far the most common etiology of PAD, and as physical activity primarily prevents coronary artery disease, speculation could be made that physical activity could also primarily prevent PAD. However, insufficient large RCT studies have been performed. Some tertiary preventive evidence exists in PAD patients that walking performed 3 times or more weekly have less functional decline during the next year and that greater than light physical activity reduces mortality Cross-reference: Peripheral Circulation.

Eicher et al. Physical activity is one of a number of primary preventive measures against hypertension. Stroke is a sudden diminution or loss of consciousness, sensation, and voluntary motion caused by rupture or obstruction as by a clot of a blood vessel of the brain.

Thirteen of articles satisfied all eligibility criteria to be included in a meta-analysis. No significant risk reduction associated with moderate physical activity in women A meta-analysis of 33 prospective cohort studies and 10 case-control studies found that physical activity reduces the relative risk of 0.

The reduction of risk was only statistically significant for men Reimers et al. They include: antihypertensive effect, beneficial effect on lipid metabolism, and improved endothelial function increased endothelial NOS activity and extracellular superoxide dismutase expression.

Other mechanisms that may play a role include a lowered blood viscosity, a tendency toward platelet aggregation, increased fibrinolysis, reduced plasma fibrinogen, increased activity of plasma tissue plasminogen activator activity, and higher of HDL-cholesterol.

Physical inactivity causes deteriorations in multiple mechanisms that cause stroke, as mentioned above.

The heart fails to pump adequate amounts of blood through arteries to tissues, which causes blood to back up and accumulate in other parts of the body, such as lungs and feet. CHF is often accompanied by distension of the ventricles, peripheral and pulmonary causing shortness of breath edema.

RCTs for prevention of congestive heart failure are not available. Observational data supports the notion that habitual endurance training is primary prevention against development of CHF.

Levine and co-authors 16 have concluded that prolonged, sustained endurance training preserves ventricular compliance with aging and may be an important approach to reduce the probability of heart failure with aging.

Preservation of ventricular compliance with endurance training probably includes preservation of viscoelastic myocardial properties absence of increased ventricular stiffening and eccentric ventricular hypertrophy a balanced enlargement of ventricular mass and dimensions These adaptations lead to profoundly improved cardiac performance without apparent change in contractility, which thus is largely explained by enhanced diastolic filling due to low stiffness Together these are coupled with endurance training prevention of arterial stiffening with aging result in preserving ventricular-vascular coupling of compliance, lowering afterload on the left ventricle Physical inactivity contributes development of CHF.

Physical activity can primarily prevent some CHF. Endothelial dysfunction is characterized by vascular endothelium exhibiting reduced vasodilation along with greater proinflammatory and prothrombic markers The list of associations would now have to include physical inactivity since the list is out-of-date.

Sedentary men at ages of 50—76 years of age have impaired endothelium-dependent dilation in response to both acetylcholine and increased shear stress in humans In contrast, 50—76 yr-old, long-term, exercise-trained men do not show age impairment as they have similar endothelium-dependent dilation to acetylcholine-mediated vasodilation as healthy, 22—yr old men have , Davigon and Ganz contend that endothelial dysfunction is an early marker for atherosclerosis and can be detected before structural changes to the vessel wall are evident.

If, as claimed by Davigon and Ganz , endothelial dysfunction is an early marker for atherosclerosis and can be detected before structural changes to the vessel wall are evident, then a prevention of endothelial dysfunction by a lifetime of physical activity would therefore also prevent most of atherosclerosis reaching a clinical level at the age of 50—76 yrs in men , or even initiation of aerobic physical activity within lifestyle Expression levels for subunits nox1, p47phox and p67phox were increased, which suggests increased oxidative stress.

A tissue that is not involved in limb movement of running or cycling is the penis. Treadmill training of diabetic rats restored impaired endothelial-dependent and neurogenic nitrergic relaxation in corpus cavernosum The exercise training increased depressed plasma superoxide dismutase SOD levels of sedentary diabetic rats.

The paper hypothesized that nitric oxide bioavailability to corporal smooth muscle was increased by plasma’s SOD’s antioxidant action. Lack of shear stress from transient bouts of exercise initiates a cascade of unhealthy events that can be inferred if the sedentary group in exercise studies is considered Physical inactivity is a cause of endothelial dysfunction by lack of increased blood flow by exercise in sedentary condition. Exercise signals a beneficial endothelial cell phenotype, at least in part through changes in shear stress and wall stretch in the arteries.

Atherogenic dyslipidemia is defined as the presence of abnormally low serum concentrations of high-density lipoprotein cholesterol HDL-C and elevated concentrations of high triglycerides and small, dense low-density lipoprotein cholesterol LDL-C.

Threshold volumes are from 7 to 15 miles per week of regular aerobic exercise equating to an approximate to MET-minutes , with no sex differences The change for HDL-C was not significant. Physical inactivity contributes to worsening of atherogenic dyslipidemia. Exercise improves blood lipid values.

Lakka and Laaksonen caution not to underestimate the clinical significance of small changes in plasma LDL-C, HDL-C, and TG concentrations with aerobic exercise training because they occur concurrently with benefits on other cardiovascular and metabolic risk factors.

Hemostasis is the arrest of bleeding either by physiological properties of vasoconstriction and coagulation or by surgical means. In a review, physical inactivity had been associated with the following: low plasma volume, high hematocrit, high plasma fibrinogen, elevated blood viscosity, increased platelet aggregation, and diminished fibrinolysis Low physical fitness and self-reported sedentary lifestyle have been associated with a pro-thrombotic blood profile in middle-aged women with CHD Regular physical exercise has beneficial long-term effects on hemostasis in studies including male subjects See for refs.

Numerous reviews suggest that physical activity has long-term healthy benefits on hemostasis 2 , 28 , , DVT is caused by physical inactivity. The clinical significance of DVT results when a clot breaks off as an embolus and flows to the lung where it blocks a portion of pulmonary blood flow, causing lack of gas exchange in pulmonary capillaries.

Cognitive decline is considered an aging disease with two of the most severe forms being Alzheimer’s and dementia. Thus, cognitive function can arbitrarily be divided into studies of developing cognition and of primary prevention of the decline in cognition. Cross-reference: Dementia and Alzheimer’s disease; Effects of exercise on brain function and cognitive development. Research in exercise and prevention of cognitive decline is relatively new and moving rapidly.

Recent reviews exist , Aerobic exercise and physical activity improve cognitive health across the lifespan Dutch men, but not women, who were physically active at a young age 15—25 yrs old , had less of a decline in informational processing capabilities versus individuals physically inactivity early in life Women who reported being physically active at any point in life had a lower likelihood of cognitive impairment in late life Women who began physical activity later in life after inactive teenage years also had lower rates of cognitive impairment in late life.

Of the four ages examined, teenage physical activity appeared to be most strongly related to better cognitive function and lower prevalence of cognitive impairment in old age Chaddock et al. Children who have low physical activity levels have poorer academic achievement scores and inferior cognitive performance as compared to physically fit children 70 , 84 , 91 , 92 , , , , , , , , , A review concluded that exercise facilitates children’s executive function, i.

Further, an association between better cardiovascular fitness at age 18 yrs, a higher socioeconomic status, and educational attainment later in life existed.

Aerobic exercise had an overall effect size of 0. Moderate and high levels of physical activity were associated with significantly lower risks for Alzheimer disease and for dementia of any type An inverse relationship between physical activity levels and dementia was found in men and women aged 65 years and older Higher VO 2 peak was associated positively with preservation of cognitive function over a 6-year period in subjects over the age of 55 Increased aerobic fitness can be neuroprotective and can enhance cognitive function , , Kramer et al.

Resistance exercise also had a positive impact on cognitive function in 65—yr-old males A meta-analysis was performed on fitness effect sizes from subjects from 37 studies prior to Etnier et al. Rather across the same 37 studies designed to test the effects of fitness on cognition, the summary statistic indicated that a positive association existed between physical activity and cognitive performance , confirming the findings of three previous meta-analytic reviews of this literature , , To date, no RCT has been performed to show that regular physical activity prevents dementia Highly cardiorespiratory-fit or aerobically-trained individuals had reduced activation of the anterior cingulated cortex concomitantly with lower indecision that arises when multiple conflicting responses are elicited in response to a stimulus during a task that required variable amounts of executive control, relative to untrained individuals Fit and trained subjects also had greater task-related activity in regions of the prefrontal and parietal cortices that are involved in spatial selection and inhibitory functioning Reductions in hippocampus volume are associated with a decline in memory performance, specifically acquisition and recall measures hippocampal volume is positively correlated with physical fitness in adults and children yr olds 91 , and can be increased by aerobic training of both schizophrenic and healthy subjects’ Likewise, a 6-month aerobic exercise intervention increased grey matter volume in the frontal and superior temporal lobes Further, results suggest that aerobic fitness does not have a general impact on the volume of all structures in the brain in children Exercise increases neurogenesis in the dentrate gyrus, a hippocampal region that is important for spatial recognition.

Van Praag et al. Another study found that improved spatial pattern separation in 3-month-old mice was tightly correlated with increased neurogenesis and vasculature in the dentate gryus after 10 weeks of voluntary wheel running Another anatomical change associated with improved cognitive is improvements is brain blood flow.

Voluntary wheel running can increase blood vessel density, blood flow, and capillary perfusion of the motor cortex in rats 42 , Potential mechanisms include the increased density of microvessels , angiopoietin 1 , VEGF protein , or endothelial proliferation , Angiogenesis in the brain is associated with enhanced improvement in a functional outcome like water maze time , but not the ability to activate the motor limbs Physical activity can induce local and systemic expression of many growth factors that protect the brain from physical inactivity-related declines in function.

Brain-derived neurotrophic factor BDNF plays an important role in the growth, development, maintenance, and function of several neuronal systems Whether 1 day would have the same effects is unknown. Another critical growth factor for neuroprotection and brain health is IGF A number of studies show that IGF-1 increases in the brain following exercise. Infusion of IGF-1 mimicked the effects of exercise. Blocking hippocampal IGF-I receptors, but abolished the effect of exercise on augmenting recall in rats during 5 days of wheel running Anti-IGF-I antibody can also abrogate the protective effects of exercise in many types of brain lesions Blockage of peripheral VEGF prevents the increase in BrdU-positive cells and mitosis in immature neurons of exercising animals only Polymorphisms in the APOE4 genotype have been examined in relationship to physical activity, with mixed results For instance in cross-sectional studies examining physical activity by questionnaire, two studies suggest that carriers of APOE4 benefit from physical activity , , while one does not However, higher aerobic fitness levels in older women having the APOE4 genotype had better cognitive function in another cross-sectional study , suggesting that physical activity levels that are capable of increasing aerobic fitness are needed to improve cognitive function in those with APOE4 genotypes.

Animal studies support this. Epidemiological, interventions, and mechanistic insights from human and rodent studies all suggest that physical inactivity can accelerate declines in cognitive function; a decline that be attenuated or potentially reversed by physical activity. However, questions remain regarding the best-practice for mode, duration, intensity, the long lasting effects, potential gender specific effects, and the interaction with genetic components.

A mood disorder marked especially by sadness, inactivity, difficulty with thinking and concentration, a significant increase or decrease in appetite and time spent sleeping, feelings of dejection and hopelessness, and sometimes with suicidal thoughts or an attempt to commit suicide.

Cross-reference: Depression. An abnormal and overwhelming sense of apprehension and fear often marked by physiological signs as sweating, tension, and increased pulse , by doubt concerning the reality and nature of the threat, and by self-doubt about one’s capacity to cope with it.

Both depression and anxiety are associated with increased risks of many other diseases. Genetic, biological, chemical, hormonal, environmental, psychological, and social factors all likely intersect to contribute to depression in women see or details.

Some of these same factors play a role in men. For anxiety, disorders last at least 6 months and commonly occur along with other mental or physical illnesses, including alcohol or substance abuse. Since , more than population-based observational studies have been completed. Looking at the 28 prospective cohorts allows for examination of physical activity levels before depression symptoms occur.

In 66 of 67 cohort studies, physical inactivity increased the risk of depression. Physical working capacity was found in depressed male patients but not female patients Morgan et al, who noted that both grip strength inversely related to hospital length stay and lower in depressed patients Likewise, lower fitness was found in depressed male patients but not female patients Treatment of depression with exercise has also been shown to be effective.

The NPAGCR , concluded that after examining 4 population-based cross-sectional studies of over , Americans that regular physical activity decreases the odds of an anxiety disorder. Specifically, the national Co-Morbidity study found physical inactivity increased anxiety disorder by 1. Australians reporting no activity were 2. A decline in cognitive function may be a cause of depression. For instance, in over 5, elderly women mostly white , increasing symptoms of depression were associated with reduced cognitive function in each of 3 tests, showing a negative correlation Those with 6 cognitive-impairment symptoms had a relative risk of 2.

While it is unknown whether the mechanisms of increased depression and decreased cognitive function are similar in different populations for example young vs. Potential roles of elevated gluccocorticoids due to a failure to suppress the hypothalamic-pituitary-adrenal HPA axis have also been studied in healthy humans. Physically active individuals have less stress response to the same absolute exercise in terms of cortisol release Furthermore, the most fit group had a diminished release of cortisol in response to intravenous ovine corticotropin-releasing hormone In rats, physical inactivity increases the ACTH levels rather than cortisol in response to a stressor , However, questions remain about the level of physical activity necessary for beneficial HPA adaptations with some studies suggesting intense physical activity can have a detrimental effect Changes in monamines and other circulating markers may also be involved in inactivity-induced increases in depression and anxiety, similar to changes in cognitive function.

Catecholamines, specifically norepinephrine NE signaling and production, is increased with physical activity in the pons medulla, which is where the only NE-producing nerves are found that serve the frontal cortex, hippocampus, thalamus, and cerebellum; a major source of NE-serving nerves to the hypothalamus, amygdala, and spinal cord [reviewed in ].. In addition to increased NE levels at the site of production, microdialysis showed increased levels and turnover of NE where the neurons terminate in the spinal cord is found after just 1 hour of treadmill running in rats Levels of 5-hydroxytryptamine serotonin , an important neurotransmitter for mood, and its receptor are potentially increased by acute treadmill running due to the increased lipolysis and FFA binding to albumin.

By reducing albumin, tryptophan levels are higher in circulation and have an increased entry into the brain, leading to increased synthesis of serotonin In a large twin-population based in the Netherlands, data about leisure-time exercise and anxiety and depression symptoms were measured. Interestingly, in genetically identical twin-pairs, the lack of leisure-time exercise did not increase anxiety or depression symptoms However, this study took a very narrow approach at looking at exercise level, whereby physical activity, such as walking or cycling work, or vocational related physical activity were not considered Lastly, adolescent girls with an allele for high BDNF received no protective effects against depression and anxiety symptoms by avoiding physical inactivity, while those with the allele causing lower BDNF level were protected Counter to the hypothesis, the HCR had more anxiety-like behavior on a maze test and higher levels of cortisol in response to a restraint test Decrease in bone mass with decreased density and enlargement of bone spaces producing porosity and brittleness.

The spaceflight data shows that loading bone gravity is a powerful stimulus to maintenance of bone mass. Non-weight-bearing athletes bicycling had lower bone mineral mass of whole-body and spine than weight-bearing athletes in males , The spinal cord injury and cycling data demonstrate that absence of gravitational loading is a powerful stimulus for loss of bone mass. Inactivity, i. Exercise: the key to bone health through the life span. Peak value for bone mineral density BMD in third decade of life contributes to the age in later life at which threshold for osteoporosis is passed.

The higher the peak value for BMD, the later age in life delays age at which BMD reaches the osteoporosis threshold, below which osteoporosis is diagnosed. The upper line reflects a population that had high bone-loading physical activities throughout lifespan with genes predisposing to high bone strength in contrast to the lower line reflecting low lifetime bone loading with genes predisposing to low bone strength. Adapted from Rizzoli et al. Mixed loading exercise programs combining jogging with other low-impact loading activity and programs mixing impact activity with high-magnitude resistance exercise were effective in reducing postmenopausal bone loss at the hip and spine These findings emphasize the clinical importance of avoiding inactivity in the early post-menopausal period and the specificity of the lack of impact on critical bones with high fracture rates in later life Finally, it is important to emphasize the site-specificity of exercise on bone.

Only bones subject to loading will become stronger as adaptations are site-specific. Physical inactivity results in reduced mechanical, both gravitational and muscle contraction, forces which in turn induces catabolism resorption by promoting osteoclastogenesis with concurrent suppression of both bone formation and osteoblastogenesis.

Dynamic exercise alters the balance between bone formation and resorption to favor anabolism through osteoblast recruitment and activity. Mechanical loading of bone occurs in response to compressive forces from gravity during walking or running, or to in response to muscular forces at the bone attachments during contractions. The implication, then, is that a mechanism must therefore exist to amplify strains from physical activity compressive impact forces from striking surfaces and tensile forces from contracting skeletal muscle at attachment sites to bone to exceed the threshold needed to activate bone cells.

Ozcivici et al. Deformation of skeletal tissues induces pressurization of interstitial fluid, producing a positive pressure gradient from the matrix to the haversian cannels, allowing bone cells perceive changes in their mechanical environment an amplification mechanism Physical inactivity is a primary cause of bone loss in weight-bearing bones.

Physical activity results in both gravitational and muscle-contraction loading of the skeleton and, therefore, is primary prevention of osteoporosis. Degeneration of cartilage and its underlying bone within a joint Cross-reference: Osteoarthritis and exercise: cause and effects.

The type and duration of physical activity is a key factor determining whether exercise is beneficial to joint health or not. Buckwalter wrote,. Participation in sports that cause minimal joint impact and torsional loading by people with normal joints and neuromuscular function may cause osteophyte bony projections that form along joints formation, but it has minimal, if any, effect on the risk of osteoarthritis.

In contrast, participation in sports that subject joints to high levels of impact and torsional loading increases the risk of injury-induced joint degeneration. The small size of this study prevented this difference from reaching statistical significance. The NPAGCR concluded that no evidence presently exists to indicate that regular moderate to vigorous physical activity of 30—60 minutes for general health benefits increases the risk of developing osteoarthritis in those without pre-existing major joint injury.

Primary prevention would be to avoid those sports predisposing to later life development of osteoarthritis. Balance is defined as t he ability to maintain the center of gravity for the body within the base of support that produces minimal postural sway.

Its etiology can be related to lack of usage of nervous system controlling skeletal muscle movement against gravity. For example, living in space for as little as 9 days accelerates problems of equilibrium on standing, walking and coordination on return to Earth caused by inappropriate neurovestibular responses With eyes closed on this platform astronauts complain of having no sensation of falling.

Similar balance dysfunctions occur with aging. It is likely that improper balance upon return to Earth from spaceflight and with aging have a common denominator of insufficient exercise against gravity. Lack of appropriate balance occurs in later life. The NPAGCR concluded that the strong evidence exists in old Americans that the risk of falls is reduced from physical activity programs that emphasize both balance training and muscle-strengthening activity with some aerobic activity, especially walking.

The NPAGCR further indicates that no evidence indicates that planned physical activity reduces falls in adults and older adults who are not at risk for falls. The clinical significance for primary prevention requires exercises that retain normal balance to reduce falls in individuals at risk for falls Bone fracture is defined as a break, rupture, or crack in bone or cartilage.

Physical inactivity, specifically lack of loading bones against gravity, will cause loss in bone density, which increases the risk of bone fracture. Physical inactivity is directly associated with fracture risk, particularly for fractures of the proximal femur i. Based on epidemiologic studies that evaluated present dose-response associations, the minimal levels of physical activity that were significantly associated with reduced fracture risk were at least 9 to Primary prevention with exercises that load bones can reduce falls in those with balance irregularities, fall-related fractures, and several risk factors for falls in individuals with low bone density RA is a chronic autoimmune disease characterized by inflammation of the joints, frequently accompanied by marked deformities, and ordinarily associated with manifestations of a general, or systemic, affliction.

While no preventive measures are currently known, physical activity is critical to not allowing RA to progress. Studies show no harmful effects of physical activity, and some even show a positive effect in the reduction of symptoms High-intensity physical activity is better than low at preventing the worsening of symptoms. The mechanism by which physical activity has a beneficial effect on RA might be its countering the global increase in inflammation that normally occurs during the progression of RA.

A malignant tumor of potentially unlimited growth that expands locally by invasion and systemically by metastasis. Inherited genetic factors make a minor contribution to susceptibility to most types of neoplasms, implying that the environment has the principal role in causing sporadic cancer A review on targets and pathways for cancer prevention exists Physical inactivity increases the prevalence of some site-specific colon, breast, and endometrial cancers , but, to date, not all cancer types.

The specificity of cancer types enhanced by physical inactivity supports a notion that mechanisms of inactivity-induced cancers are specific to each site-specific cancer. Stated in an opposite manner, some cancer types are not caused by physical inactivity. Cross-reference: Cancer. Those cancers whose risk is enhanced by inactivity will be considered next.

A literature review through March found 23 case-control cross-sectional studies and 17 cohort longitudinal studies. The NPAGCR states that RCTs have demonstrated effects of physical activity interventions on cancer risk factors, which further support a role of physical activity in reducing risk for cancer.

Colbert et al. In their first study, 3 weeks of voluntary running followed by 5 weeks of treadmill running did not alter polyp development or serum IGF-I Ju et al. Physical activity is a primary preventer of colon cancer. The effect of physical activity on breast cancer reduction differs between pre- and post-menopausal conditions.

However, much weaker evidence is available for physical activities reduction on risk of premenopausal breast cancer, so no effect existed. Lower levels of steroid hormone binding protein by physical inactivity have been suggested to increase breast cancer risk.

The mechanisms by which long-term physical activity lowers postmenopausal breast cancer risk, however, remain unclear Thompson et al. Hypothesis 1 proposes that inactivity-induced changes in circulating growth factors and hormones activate the mTOR-signaling network to increase proliferation and decrease apoptosis in breast cells while stimulating new blood vessel formation.

Hypothesis 3 says that inactivity increases glucose and glutamine availability in mammary carcinomas, thereby attenuating breast cell apoptosis and, thus, increasing the accumulation of breast tumor masses. Physical activity is a primary preventer of breast cancer. The NPAGCR found growing evidence to support reduced risk of endometrial cancers in physically active versus sedentary persons.

Multiple methodological pitfalls exist in the studies published , so conclusions made about benefits of physical activity on female reproductive health remain for further testing. Nonetheless, the consensus is that exercise can serve as primary prevention during pregnancy , Haima strikes Hong Kong just as it recovers from a day of torrential rain on Wednesday that caused several minor landslides and localised flooding. Indian School Muscat, since its inception has grown steadily with a purpose.

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