***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: Abstract The longitudinal observations for ten years on 5209 men and women aged 30–62 in Framingham , Massachusetts , have been used for a prospect i ve investigation of the epidemiology of gallbladder disease . ‘ Definite ’ gallbladder disease was diagnosed in 427 persons on the evidence of pathology reports , surgery , X-ray and hospital admissions and 116 were ‘ doubtful ’ , having only the diagnosis suggested by a physician without further verification . The overall incidence of gallbladder disease was about twice as high in women as in men , and it increased with age in both sexes without any evidence of an excess in the forties . Gallbladder disease was not related to ‘ fairness ’ as measured by national origin . Increase in weight and number of pregnancies were each associated with increased incidence . Despite the presence of cholesterol in many gallstones and the elevation of serum cholesterol often noted with obesity and during pregnancy , no relationship was demonstrated between serum cholesterol level and gallbladder disease . Hemoglobin level was also not related in the population studied . Women with lower systolic blood pressures showed a somewhat reduced risk of gallbladder disease , but the possibility that a mutual relationship to weight could explain this has not been excluded . Slight negative correlations were noted between the disease incidence and height , and alcohol and cigarette consumption . These were small and in general not statistically significant .  Dietary fat , protein and cholesterol intake , level of physical activity , age at menopause , marital status and precinct of residence were not related to gallbladder disease . Nor was an excess incidence noted in persons whose spouses had gallbladder disease . Persons entering the study with gallbladder disease showed no excess mortality . It is not yet clear whether such persons develop coronary heart disease at an excess rate . Potent environmental factors influencing the rate of development of gallbladder disease have yet to be identified . On the basis of present evidence , it would appear that more attention should be devoted to the anatomy and pathological physiology of the biliary tract in seeking a better underst and ing of the pathogenesis of gallbladder disease Ten healthy volunteers ( six men and four women , aged 22 - 41 years ) were studied in a crossover trial . The study was divided into three one week periods . During each period the subjects either ran on a treadmill , cycled on a bicycle ergometer , or rested in a chair for 1 hour every day . The exercise was performed at two thirds predicted maximum heart rate ( equivalent to 50 % VO2 max ) . The sequences were rotated ; no studies were performed in the perimenstrual period . Transit was measured by the method of measuring the excretion of a single dose of radio-opaque markers ; all stools were collected , weighed , and x rayed after the ingestion of radio-opaque markers .  Dietary fibre and fluid intake were measured on the fourth day of each test period by 24 hour record . Lifestyle was otherwise unchanged . Transit time was dramatically accelerated by moderate exercise ( both jogging and cycling ) ; however , stool weight , defecation frequency , dietary fibre intake , and fluid intake did not change significantly . Whole gut transit changed from 51.2 hours ( 95 % confidence intervals 41.9 to 60.5 ) at rest to 36.6 hours ( 31.6 to 39.2 ) when riding and 34.0 hours ( 28.8 to 39.2 ) when jogging . Riding and running both differed significantly from resting ( p less than 0.01 ) ; the difference between riding and running was not significant PURPOSE Regular exercise reduces cardiovascular risk in humans by reducing cholesterol levels , but the underlying mechanisms have not been fully explored . Exercise might provoke changes in cholesterol and bile acid metabolism and thereby reduce cardiovascular risk . We examined whether voluntary wheel running in mice modulates cholesterol and bile acid metabolism . METHODS Male mice ( 10 wk old ) were r and omly assigned to have access to a voluntary running wheel for 2 wk ( RUN group ) or remained sedentary ( SED group ) . Running wheel activity was recorded daily . In a first experiment , fecal sterol outputs , fecal bile acid profiles , plasma parameters , and expression levels of genes involved in cholesterol and bile acid metabolism were determined . In a second experiment , bile flow , biliary bile acid profile , and biliary secretion rates of cholesterol , phospholipids , and bile acids were determined . RESULTS The RUN group ran an average of 10 km.d and displayed lower plasma cholesterol compared with SED ( P = 0.030 ) . Fecal bile acid loss was induced by approximately 30 % in running mice compared with SED ( P = 0.0012 ) . A approximately 30 % increase in fecal cholesterol output in RUN ( P = 0.014 ) was consistent with changes in parameters of cholesterol absorption , such as reduced plasma plant sterol-cholesterol ratio ( P = 0.044 ) and decreased jejunal expression of Npc1l1 ( P = 0.013 ) . Supportive of an increased cholesterol synthesis to compensate for fecal sterol loss were increased hepatic mRNA levels of HMGCoA reductase ( P = 0.006 ) and an increased plasma lathosterol-cholesterol ratio ( P = 0.0011 ) in RUN . CONCLUSIONS Voluntary wheel running increased cholesterol turnover in healthy mice owing to an increased fecal bile acid excretion and a decreased intestinal cholesterol absorption . Enhanced cholesterol turnover may contribute to the established reduction of cardiovascular risk induced by regular exercise Despite the high prevalence of gallbladder disease in industrialized countries , little is known about the predictors of the disease , especially in men . The authors prospect ively studied 16,785 alumni of Harvard University , aged 15 - 24 years , who were followed for up to 61 years . The health characteristics of these men were ascertained from their  college entrance physical examination done in 1916 - 1950 , and up date d via mailed question naires in 1962 or 1966 ( 1962/1966 ) . Alumni subsequently self-reported physician-diagnosed gallbladder disease on further mailed question naires in 1972 or 1977 . Between college time and 1962/1966 , 371 gallbladder disease cases occurred . An additional 314 cases occurred after 1962/1966 . With respect to college characteristics , after adjustment for potential confounders , the authors found that body mass index ( BMI ) , smoking , physical activity , blood pressure , and consumption of alcohol , coffee , or tea were unrelated to risk . However , BMI in 1962/1966 was directly related to risk of subsequent gallbladder disease , as was BMI gain since college ( p , trend = 0.002 and 0.013 , respectively ) . Compared with men with BMI < 22.0 , men with BMI > or = 27.0 had a rate ratio of 2.71 ( 95 % confidence interval ( CI ) 1.57 - 4.66 ) for risk of contracting the disease . Men who gained > or = 6.0 BMI units since college had a rate ratio of 1.46 ( 95 % CI 0.86 - 2.46 ) compared with men who gained -0.9 to + 0.9 BMI units . Compared with never smokers , men who smoked pipes or cigars or < 1 pack of cigarettes daily in 1962/1966 had a rate ratio of 1.43 ( 95 % CI 1.00 - 2.06 ) , while heavier cigarette smokers had a rate ratio of 1.52 ( 95 % CI 1.03 - 2.24 ) . Neither physical activity nor physician-diagnosed hypertension or diabetes mellitus in 1962/1966 predicted risk Background Animal experiments have shown a protective effect of vitamin C on the formation of gallstones . Few data in humans suggest an association between reduced vitamin C intake and increased prevalence of gallstone disease . The aim of this study was to assess the possible association of regular vitamin C supplementation with  gallstone prevalence . Methods An observational , population -based study of 2129 subjects aged 18 - 65 years r and omly selected from the general population in southern Germany was conducted . Abdominal ultrasound examination , completion of a st and ardized question naire , compilation of  anthropometric data  and  blood tests  were used . Data were collected in November and December 2002 . Data analysis was conducted between December 2005 and January 2006 . Results Prevalence of gallstones in the study population was 7.8 % ( 167/2129 ) . Subjects reporting vitamin C supplementation showed a prevalence of 4.7 % ( 11/232 ) , whereas in subjects not reporting regular vitamin C supplementation , the prevalence was 8.2 % ( 156/1897 ) . Female gender , hereditary predisposition , increasing age and body-mass index ( BMI ) were associated with increased prevalence of gallstones . Logistic regression with backward elimination adjusted for these factors showed reduced gallstone prevalence  for vitamin C supplementation ( odds ratio , OR 0.34 ; 95 % confidence interval , CI 0.14 to 0.81 ; P = 0.01 ) , increased physical activity ( OR 0.62 ; 95 % CI , 0.42 to 0.94 ; P = 0.02 ) , and higher total cholesterol ( OR 0.65 ; 95 % CI , 0.52 to 0.79 ; P < 0.001 ) . Conclusion Regular vitamin C supplementation and , to a lesser extent , increased physical activity and total cholesterol levels are associated with a reduced prevalence of gallstones .  Regular vitamin C supplementation might exert a protective effect on the development of gallstones BACKGROUND Gallstones are a highly prevalent condition ; however , the nutritional and lifestyle risk factors of this disease are not well understood . OBJECTIVE We evaluated the association between  diet , physical activity  , and incident cases of gallstones diagnosed by ultrasound in a population -based , case-control study . DESIGN One hundred patients with newly diagnosed gallstones and 290 r and omly selected control subjects without gallstones were enrolled in the study . The presence of gallstones was determined by ultrasonography . Both patients and control subjects completed a question naire about their usual diet and physical activity for the 12 mo before the ultrasonography . The association between  diet and physical activity and risk of gallstone formation was analyzed by using multiple logistic regression . RESULTS Body mass index and intake of refined sugars were directly associated with risk of gallstone formation , whereas physical activity , dietary monounsaturated fats , dietary cholesterol , and dietary fibers from cellulose  were inversely associated with risk of gallstone formation . Saturated fats were a risk factor for gallstone formation and the association appeared to be stronger for men than for women . CONCLUSION These findings suggest that a sedentary lifestyle and a diet rich in animal fats and refined sugars and poor in vegetable fats and fibers are significant risk factors for gallstone formation By means of loxiglumide , a potent and highly specific antagonist for cholecystokinin ( CCK ) , the effects of blocking CCK receptors on gastrointestinal motility were investigated in a placebo-controlled study in healthy young men ( aged 21 - 39 , mean 24 years ) . Gallbladder contraction stimulated by ingestion of a liquid test meal was completely abolished by oral administration of loxiglumide 30 min before the test meal . Gastric emptying of radio-opaque markers ingested with the test meal was significantly accelerated by loxiglumide ( area under the curve [ markers x h ] 33.3 [ SEM 3.8 ] vs 17.9 [ 2.7 ] after placebo ) . No effect of loxiglumide was found on small-bowel transit time , but 7 days ' treatment with oral loxiglumide ( 800 mg three times daily ) significantly shortened colonic transit time ( 29.4 [ 4.1 ] h after placebo , 15.0 [ 3.4 ] h after loxiglumide ) . It is concluded that CCK is an important mediator of meal-induced gallbladder contraction and is involved in the regulation of gastrointestinal motility in man Background The effects of vegetable preference and leisure-time physical activity ( LPA ) on cancer have been inconsistent . We examined the effects of dietary preference and physical activity , as well as their combined effect on cancer risk . Methods This prospect i ve cohort study included 444,963 men , older than 40 years , who participated in a national health examination program begun in 1996 . Based on the answer to the question " What kind of dietary preference do you have ? " we categorized dietary preference as ( 1 ) vegetables , ( 2 ) mixture of vegetables and meat , and ( 3 ) meats . We categorized LPA as low ( < 4 times/wk , < 30 min/session ) , moderate ( 2–4 times/wk , ≥ 30 min/session or ≥ 5 times/wk , < 30 min/session ) , or high ( ≥ 5 times/wk , ≥ 30 min/session ) . We obtained cancer incidence data for 1996 through 2002 from the Korean Central Cancer Registry . We used a st and ard Poisson regression model with a log link function and person-time offset 
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Results The impact of physical activity upon gallbladder function remains unclear ; acute activity could augment emptying by stimulating cholecystokinin release , and one of two training experiments found a small increase in gallbladder motility .
The largest and most recent cross-sectional and case-control trials show a reduced risk of gallbladder disease in active individuals .
Conclusions Although there remains a need for further research , regular physical activity seems likely to reduce the risk of both gallstones and gallbladder cancer .
A substantial number of individuals must be persuaded to exercise in order to avoid one case of gallbladder disease , but the attempt appears warranted because of the other health benefits of regular physical activity