Suppression of epithelial-mesenchymal transition and apoptotic pathways by miR-294/302 family synergistically blocks let-7-induced silencing of self-renewal in embryonic stem cells.

The embryonic stem cell (ESC)-enriched miR-294/302 family and the somatic cell-enriched let-7 family stabilizes the self-renewing and differentiated cell fates, respectively. The mechanisms underlying these processes remain unknown. Here we show that among many pathways regulated by miR-294/302, the combinatorial suppression of epithelial-mesenchymal transition (EMT) and apoptotic pathways is sufficient in maintaining the self-renewal of ESCs. The silencing of ESC self-renewal by let-7 was accompanied by the upregulation of several EMT regulators and the induction of apoptosis. The ectopic activation of either EMT or apoptotic program is sufficient in silencing ESC self-renewal. However, only combined but not separate suppression of the two programs inhibited the silencing of ESC self-renewal by let-7 and several other differentiation-inducing miRNAs. These findings demonstrate that combined repression of the EMT and apoptotic pathways by miR-294/302 imposes a synergistic barrier to the silencing of ESC self-renewal, supporting a model whereby miRNAs regulate complicated cellular processes through synergistic repression of multiple targets or pathways.

Transitional care of the long-term care patient.

This article reviews the literature on transitional care to and from the LTC environment, highlighting strategies to improve the quality of care transitions. Several factors are vital in the improvement of systems of care dealing with transitions. Key factors include communication with and among health care providers, effective medication reconciliation, advanced discharge planning, and timely use of palliative care.

Factors associated with use of calcium and calcium/vitamin D supplements in older Mexican Americans: Results of the Hispanic EPESE study.

BACKGROUND: Current studies indicate that older Mexican Americans take fewer calcium or calcium/vitamin D supplements than do older non-Hispanic whites. Factors associated with calcium supplement use are not completely understood in this ethnic group. OBJECTIVE: The purpose of this article was to determine the prevalence of calcium or calcium/vitamin D supplementation and factors associated with their use in older Mexican Americans. METHODS: A cross-sectional survey was conducted in a random sample of older Mexican Americans residing in the southwestern United States who had participated in the Hispanic Established Populations for the Epidemiologic Study of the Elderly. Self-identified Mexican Americans >or=75 years of age were enrolled through household interviews in 2004-2005. Each subject was asked to bring all prescription and nonprescription medications that they had used regularly during the previous 2 weeks to allow the interviewer to record the product names. Dosages were not recorded. Subjects were assigned to 1 of 3 categories based on their use of calcium or calcium/vitamin D supplements during the previous 2 weeks: (1) calcium supplement only, (2) calcium/vitamin D supplement, or (3) vitamin D supplement only. The subjects' sociodemographic and cultural factors, self-reported health and functional status, cognitive status, number of comorbidities, and use of antiosteoporosis medications were recorded. RESULTS: A total of 2069 older Mexican Americans (1272 women, 797 men; mean age, 81.9 years) were enrolled. The overall prevalence of calcium supplement use was 10.6% (weighted). Calcium supplements were used more often by women (odds ratio [OR] = 1.76; 95% CI, 1.17-2.63), subjects with multiple comorbidities (OR = 1.29; 95% CI, 1.10-1.50), those who interviewed in English (OR = 1.59; 95% CI, 1.06-2.40), and those who used antiosteoporosis medications (OR = 3.57; 95% CI, 1.85-6.89). CONCLUSIONS: Use of calcium or calcium/vitamin D supplements was low (<60%) among this group of older Mexican Americans. Men are particularly at risk. More should be done to raise awareness regarding the benefits of calcium supplementation in this ethnic group.

Prevalence and characteristics associated with self-reported gall bladder disease in Mexican American elders: results from the Hispanic Established Populations for Epidemiologic Studies in the Elderly (H-EPESE).

BACKGROUND AND AIMS: To identify the prevalence and characteristics of gall bladder disease (GBD) that has been self-reported in Mexican American Elders. METHODS: A prospective survey of a regional probability sample of self-identified Mexican Americans aged 65 and over. The Hispanic Established Population for the Epidemiologic Studies of the Elderly (H-EPESE), a probability sample of non-institutionalized, Mexican Americans, aged 65 and over, residing in Southwestern states of Texas, New Mexico, Colorado, Arizona, and California. In 1993- 1994 (Wave 1), 3050 Mexican Americans, aged 65 and over, were selected at baseline as a weighted probability sample. In 1995-1996 (Wave 2), 2895 remained. Sample weights were used to extrapolate to the estimated 498,176 older Mexican Americans residing in the Southwest United States. Self-reported GBD was collected via in-home interviews. RESULTS: The prevalence of self-reported GBD in Mexican American elders was found to be 18.8% with an average age of 75.05 years. The findings indicate that older Mexican Americans have an increased rate of GBD if they are female, have history of arthritis or hypertension and have more acculturation to the United States. However, the rate decreases when they score poorly on the Mini Mental State Exam. One major limitation was reliance on self-report, as GBD and other co-morbid illnesses may be under-, or overestimated. CONCLUSIONS: Age is not protective in the prevalence of GBD in elder Mexican Americans. Persistent underlying genetics and dietary habits most likely attribute to this consistent high percentage, even in the elderly.

Characteristics of hip fractures among hospitalized elder Mexican American Black and White Medicare beneficiaries in the Southwestern United States.

BACKGROUND AND AIMS: Hip fractures are a major cause of morbidity and mortality in the older adult population. The evidence of the incidence of morbidity and mortality in Mexican Americans compared to other ethnic groups is mixed. This study aims to examine characteristics and utilization patterns of older Mexican Americans compared to Whites and Blacks, hospitalized for hip fracture in the Southwestern United States. METHODS: Retrospective analysis of the Medicare and Medicaid claims data for the southwestern states of California, Arizona, Colorado, New Mexico and Texas. All Medicare beneficiaries aged 65 and above, hospitalized for non-pathologic hip fractures, participated in the study. Mexican Americans were directly identified from the H-EPESE database. The primary outcome measures were length of stay, total charges and number of diagnoses. RESULTS: The total proportion of hospital encounters related to hip fractures within each ethnic group was 3.7% for Whites, 2.0% for Mexican Americans and 1.2% for Blacks. The mean patient age for the hip fracture was 82.5 years while the non-hip fractures encounters had a mean age of 76.6 years. A higher percentage of Mexican Americans who suffered fracture were female. Although length of stay for Mexican Americans was equivalent to Whites, comparative total charges for Mexican Americans were lower. Mexican Americans also have lower mean number of diagnoses at admission than the other groups (MA=5.5, B=6.2, W=5.9: p<0.001). CONCLUSIONS: Mexican American elders in the southwestern United States who are hospitalized for hip fractures are more likely to be female, relatively healthier, and have lower health care costs when compared to Whites and especially to Blacks in the same region.

Loss of mammary epithelial prolactin receptor delays tumor formation by reducing cell proliferation in low-grade preinvasive lesions.

Top quartile serum prolactin levels confer a twofold increase in the relative risk of developing breast cancer. Prolactin exerts this effect at an ill defined point in the carcinogenic process, via mechanisms involving direct action via prolactin receptors within mammary epithelium and/or indirect action through regulation of other hormones such as estrogen and progesterone. We have addressed these questions by examining mammary carcinogenesis in transplants of mouse mammary epithelium expressing the SV40T oncogene, with or without the prolactin receptor, using host animals with a normal endocrine system. In prolactin receptor knockout transplants the area of neoplasia was significantly smaller (7 versus 17%; P < 0.001 at 22 weeks and 7 versus 14%; P = 0.009 at 32 weeks). Low-grade neoplastic lesions displayed reduced BrdU incorporation rate (11.3 versus 17% P = 0.003) but no change in apoptosis rate. Tumor latency increased (289 days versus 236 days, P < 0.001). Tumor frequency, growth rate, morphology, cell proliferation and apoptosis were not altered. Thus, prolactin acts directly on the mammary epithelial cells to increase cell proliferation in preinvasive lesions, resulting in more neoplasia and acceleration of the transition to invasive carcinoma. Targeting of mammary prolactin signaling thus provides a strategy to prevent the early progression of neoplasia to invasive carcinoma.

Integrated microelectrode array and microfluidics for temperature clamp of sensory neurons in culture.

A device for cell culture is presented that combines MEMS technology and liquid-phase photolithography to create a microfluidic chip that influences and records electrical cellular activity. A photopolymer channel network is formed on top of a multichannel microelectrode array. Preliminary results indicated successful local thermal control within microfluidic channels and control of lamina position over the electrode array. To demonstrate the biological application of such a device, adult dissociated dorsal root ganglion neurons with a subpopulation of thermally-sensitive cells are attached onto the electrode array. Using laminar flow, dynamic control of local temperature of the neural cells was achieved while maintaining a constant chemical culture medium. Recording the expected altered cellular activity confirms the success of the integrated device.

Dynamic control of extracellular environment in in vitro neural recording systems.

A technique is presented for rapid fabrication of microfluidic channels on top of multichannel in vitro neural recording electrode arrays. The channels allow dynamic control of transient flow over localized areas of the array. Dorsal root ganglion neurons were integrated into the system. The device was used to demonstrate precise control of the extracellular microenvironment of individual cells on the array. Because the methods presented here are not specific to a particular cell type or neural recording system, the technique is amenable to a wide range of applications within the neuroscience field.

Television viewing and low participation in vigorous recreation are independently associated with obesity and markers of cardiovascular disease risk: EPIC-Norfolk population-based study.

OBJECTIVE: This study describes the associations between sedentary behaviour (television viewing) and participation in vigorous recreational activity with obesity and with biomarkers of cardiovascular disease (CVD) risk profile. DESIGN: Cross-sectional analysis of the EPIC-Norfolk cohort study. SETTING: The study is a population-based study of participants living in Norfolk, UK. SUBJECTS: A total of 15 515 men and women aged between 45 and 74 y, recruited through General Practice lists, who completed the detailed physical activity questionnaire. RESULTS: Following exclusion of those with self-reported myocardial infarction, stroke and diabetes, 14 189 participants remained for the analysis. Self-reported television viewing was positively and participation in vigorous activity negatively associated with markers of obesity, blood pressure and plasma lipids. In multiple regression analysis, adjusting for age, alcohol, smoking, treatment for hypertension, vigorous and total physical activity, these associations remained significant. For women who participated in more than 1 h/week of vigorous activity and who watched fewer than 2 h of television each day, the adjusted mean body mass index was 1.92 kg/m(2) less than for women who reported participating in no vigorous activity and who watched more than 4 h of television each day (P<0.001). The equivalent figure for men was 1.44 kg/m(2) (P<0.001). In a similar analysis, with blood pressure as the outcome, mean diastolic blood pressure difference between the extreme groups of vigorous activity and television viewing was 3.6 mmHg in men (P<0.001) and 2.7 mmHg (P=0.001) in women. CONCLUSIONS: These data suggest that time spent participating in vigorous recreational physical activity and television viewing, an indicator of a sedentary lifestyle, are associated with obesity and markers of CVD disease risk independent of total reported physical activity. Whether these observations represent the true underlying aetiological relations or are a manifestation of the different precision with which the subdimensions of activity are measured remains uncertain.

Residential area deprivation predicts smoking habit independently of individual educational level and occupational social class. A cross sectional study in the Norfolk cohort of the European Investigation into Cancer (EPIC-Norfolk).

OBJECTIVES: To investigate the independent association between individual and area based measures of socioeconomic status and cigarette smoking habit. DESIGN AND SETTING: Cross sectional, population based study. PARTICIPANTS AND METHODS: 12 579 men and 15 132 women aged 39-79 years living in the general community participating in the EPIC-Norfolk Study in 1993-1997. The association between social class, educational status, Townsend residential deprivation level, and cigarette smoking status was examined. MAIN OUTCOME MEASURES: Cigarette smoking status at baseline survey. RESULTS: Social class, educational level, and residential deprivation level independently related to cigarette smoking habit in both men and women. Multivariate age adjusted odds ratios for current smoking in men were 1.62 (95% CI 1.45 to 1.81) for manual compared with non-manual social class, 1.32 (95% CI 1.17 to 1.48) for those with educational level less than O level compared with those with O level qualifications or higher and 1.84 (95% CI 1.62 to 2.08) for high versus low area deprivation level. For women, the odds ratios for current smoking for manual social class were 1.14 (95% CI 1.03 to 1.27); 1.31 (95% CI 1.18 to 1.46) for low educational level and 1.68 (95% CI 1.49 to 1.90) for high residential deprivation respectively. CONCLUSIONS: Residential deprivation level using the Townsend score, individual social class, and educational level all independently predict smoking habit in both men and women. Efforts to reduce cigarette smoking need to tackle not just individual but also area based factors. Understanding the specific factors in deprived areas that influence smoking habit may help inform preventive efforts.

Cross-sectional association between total level and type of alcohol consumption and glycosylated haemoglobin level: the EPIC-Norfolk Study.

OBJECTIVE: To investigate the association between total level and type of alcohol consumed and glycaemia. DESIGN: Cross-sectional study. SETTING: The EPIC-Norfolk Study, a population-based cohort study of diet and chronic disease. SUBJECTS AND METHODS: Non-diabetic men (n=2842) and women (n=3572), aged 40-78 y. Alcohol intake was assessed by self-reported questionnaire, and glycaemia measured by glycosylated haemoglobin (HbA(1c)). RESULTS: Ten percent of men and 18% of women reported drinking no alcohol. Among drinkers, median alcohol intake was 8 units/week for men and 3 units/week for women. In analyses stratified by sex and adjusted for age, total energy intake, education, fruit and vegetable intake, smoking, family history of diabetes, physical activity, body mass index and waist:hip ratio, alcohol intake was inversely associated with HbA(1c) in men and women, although the association was stronger in women. A 1 unit/week increase in alcohol intake was associated with 0.0049% (s.e.=0.00223; P-value=0.028) and 0.017% (s.e.=0.00343; P-value <0.001) reduction in HbA(1c) in men and women respectively. In similar multivariate analyses, wine intake was inversely associated with HbA(1c) in men, and wine, spirits and beer intake were inversely associated with HbA(1c) in women. When also adjusted for total alcohol intake, only the association between wine intake and HbA(1c) in men remained significant. CONCLUSION: Alcohol intake was associated with lower HbA(1c) level, an association not explained by confounding. The distinction between type of alcohol consumed was particularly important in men.

Frequency of eating and concentrations of serum cholesterol in the Norfolk population of the European prospective investigation into cancer (EPIC-Norfolk): cross sectional study.

OBJECTIVES: To examine the relation between self reported eating frequency and serum lipid concentrations in a free living population. DESIGN: Cross sectional population based study. SETTING: Norfolk, England. PARTICIPANTS: 14 666 men and women aged 45-75 years from the Norfolk cohort of the European prospective investigation into cancer (EPIC-Norfolk). MAIN OUTCOME MEASURES: Concentrations of blood lipids. RESULTS: Mean concentrations of total cholesterol and low density lipoprotein cholesterol decreased in a continuous relation with increasing daily frequency of eating in men and women. No consistent relation was observed for high density lipoprotein cholesterol, body mass index, waist to hip ratio, or blood pressure. Mean cholesterol concentrations differed by about 0.25 mmol/l between people eating more than six times a day and those eating once or twice daily; this difference was reduced to 0.15 mmol/l after adjustment for possible confounding variables, including age, obesity, cigarette smoking, physical activity, and intake of energy and nutrients (alcohol, fat, fatty acids, protein, and carbohydrate). CONCLUSIONS: Concentrations of total cholesterol and low density lipoprotein cholesterol are negatively and consistently associated with frequency of eating in a general population. The effects of eating frequency on lipid concentrations induced in short term trials in animals and human volunteers under controlled laboratory conditions can be observed in a free living general population. We need to consider not just what we eat but how often we eat.

Fat consumption and HbA(1c) levels: the EPIC-Norfolk study.

OBJECTIVE: To describe the relationship between total dietary fat and the pattern of fat intake and HbA(1c). RESEARCH DESIGN AND METHODS: In this cross-sectional study, 2,759 men and 3,464 women (40-78 years of age) without a previous diagnosis of type 2 diabetes were recruited from a population-based sampling frame. Diet was assessed using a self-reported semiquantitative food frequency questionnaire. RESULTS: The HbA(1c) level was negatively associated with the polyunsaturated fat-to-saturated fat ratio (P:S ratio) of the diet (beta = -0.0338 HbA(1c)% per SD change in P:S ratio; P < 0.001) and positively associated with the total level of fat intake (beta = 0.0620 HbA(1c)% per SD change in total fat intake; P < 0.001), adjusted for age and total energy intake. The associations remained significant when adjusted for each other and for total energy, protein, age, sex, family history of diabetes, BMI, waist-to-hip ratio, physical activity, and smoking (for P:S ratio, beta = -0.0200 HbA(1c)% per SD change in P:S ratio, P = 0.013; for total fat, beta = 0.420% HbA(1c)% per SD change in total fat intake, P < 0.001). The benefits from a high P:S ratio were attributed to a lower saturated fat intake. CONCLUSIONS: These findings demonstrate independent associations between HbA(1c) concentration across the normal range of HbA(1c) and both total fat intake and the pattern of dietary fat intake. They provide further support to efforts promoting modifications in the intake of dietary fat.

Nutritional methods in the European Prospective Investigation of Cancer in Norfolk.

OBJECTIVE: To describe methods and dietary habits of a large population cohort. DESIGN: Prospective assessment of diet using diet diaries and food-frequency questionnaires, and biomarkers of diet in 24-h urine collections and blood samples. SETTING: Free living individuals aged 45 to 75 years living in Norfolk, UK. SUBJECTS: Food and nutrient intake from a food-frequency questionnaire on 23 003 men and women, and from a 7-day diet diary from 2117 men and women. Nitrogen, sodium and potassium excretion was obtained from single 24-h urine samples from 300 individuals in the EPIC cohort. Plasma vitamin C was measured for 20 846 men and women. RESULTS: The food-frequency questionnaire (FFQ) and the food diary were able to determine differences in foods and nutrients between the sexes and were reliable as judged by repeated administrations of each method. Plasma vitamin C was significantly higher in women than men. There were significant differences in mean intake of all nutrients measured by the two different methods in women but less so in men. The questionnaire overestimated dairy products and vegetables in both men and women when compared with intakes derived from the diary, but underestimated cereal and meat intake in men. There were some consistent trends with age in food and nutrient intakes assessed by both methods, particularly in men. Correlation coefficients between dietary intake assessed from the diary and excretion of nitrogen and potassium in a single 24-h urine sample ranged from 0.36 to 0.47. Those comparing urine excretion and intake assessed from the FFQ were 0.09 to 0.26. The correlations between plasma vitamin C and dietary intake from the first FFQ, 24-h recall or diary were 0.28, 0.35 and 0.40. CONCLUSIONS: EPIC Norfolk is one of the largest epidemiological studies of nutrition in the UK and the largest on which plasma vitamin C has been obtained. Methods for obtaining food and nutrient intake are described in detail. The results shown here for food and nutrient intakes can be compared with results from other population studies utilising different methods of assessing dietary intake. The utility of different methods used in different settings within the main EPIC cohort is described. The FFQ is to be used particularly in pooled analyses of risk from diet in relation to cancer incidence within the larger European EPIC study, where measurement error is more likely to be overcome by large dietary heterogeneity on an international basis. Findings in the UK, where dietary variation between individuals is smaller and hence the need to use a more accurate individual method greater, will be derived from the 7-day diary information on a nested case-control basis. 24-h recalls can be used in the event that diary information should not be forthcoming from some eventual cases. Combinations of results utilising all dietary methods and biomarkers may also be possible.

Cigarette smoking and glycaemia: the EPIC-Norfolk Study. European Prospective Investigation into Cancer.

BACKGROUND: Previous prospective studies have suggested that cigarette smoking may be associated with an increased risk of type 2 diabetes, but the possibility of confounding, particularly by dietary factors has not been fully examined. METHODS: Cross-sectional analysis of the association between cigarette smoking and HbA(1C), a marker of long-term glucose homeostasis in 2704 men and 3385 women, aged 45--74 years who were recruited to a population-based study of diet and chronic disease. RESULTS: Twelve per cent of men and 11% of women reported being current smokers. Mean HbA(1C) was lowest in never smokers, intermediate in former smokers and highest in current smokers. There was a dose-response relationship between HbA(1C) levels and number of cigarettes smoked per day and a positive association with total smoking exposure as measured by pack-years. The unadjusted increase in HbA(1C) for 20 pack-years of smoking was 0.12% (95% CI : 0.09--0.16) in men and 0.12% (95% CI : 0.08--0.17) in women. After adjustment for possible confounders including dietary variables, the values were 0.08% (95% CI : 0.04--0.12) and 0.07% (95% CI : 0.02--0.12) for men and women, respectively. Mean HbA(1C) was inversely related to time since quitting smoking in men. CONCLUSIONS: These results add support to the hypothesis that smoking has long-term effects on glucose homeostasis, an association that cannot be explained by confounding by dietary factors as measured in this study.

Fruit and vegetable intake and population glycosylated haemoglobin levels: the EPIC-Norfolk Study.

OBJECTIVE: To investigate whether self-reported frequency of fruit and vegetable consumption was associated with HbA(1C) levels in individuals not known to have diabetes, and what dietary and lifestyle factors might explain this association. DESIGN: Cross-sectional study. SETTING: The EPIC-Norfolk Study, a population-based cohort study of diet and chronic disease. SUBJECTS AND METHODS: A total of 2678 men and 3318 women (45-74 y) not known to have diabetes reported weekly consumption of fruit, green leafy vegetables and other vegetables. RESULTS: Among men, 274 (10.2%) reported seldom or never eating fruit and 127 (4.7%) seldom or never eating green leafy vegetables. Corresponding numbers in women were 157 (4.7%) and 92 (2.8%), respectively. Participants who reported never or seldom having both fruit and green leafy vegetables had higher mean (s.d.) HbA(1C) measurements (5.43% (0.71)) than those who reported more frequent consumption (5.34% (0.67); P=0.046). Differences by category of fruit or green leafy vegetable consumption were not substantially changed after adjustment for saturated fat, dietary fibre and plasma vitamin C. CONCLUSION: These findings support the hypothesis that high intake of fruit and green leafy vegetables may influence glucose metabolism independent of dietary fibre or vitamin C alone and that increased consumption may contribute to the prevention of diabetes.

Relation between plasma ascorbic acid and mortality in men and women in EPIC-Norfolk prospective study: a prospective population study. European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Ascorbic acid (vitamin C) might be protective for several chronic diseases. However, findings from prospective studies that relate ascorbic acid to cardiovascular disease or cancer are not consistent. We aimed to assess the relation between plasma ascorbic acid and subsequent mortality due to all causes, cardiovascular disease, ischaemic heart disease, and cancer. METHODS: We prospectively examined for 4 years the relation between plasma ascorbic acid concentrations and mortality due to all causes, and to cardiovascular disease, ischaemic heart disease, and cancer in 19 496 men and women aged 45-79 years. We recruited individuals by post using age-sex registers of general practices. Participants completed a health and lifestyle questionnaire and were examined at a clinic visit. They were followed-up for causes of death for about 4 years. Individuals were divided into sex-specific quintiles of plasma ascorbic acid. We used the Cox proportional hazard model to determine the effect of ascorbic acid and other risk factors on mortality. FINDINGS: Plasma ascorbic acid concentration was inversely related to mortality from all-causes, and from cardiovascular disease, and ischaemic heart disease in men and women. Risk of mortality in the top ascorbic acid quintile was about half the risk in the lowest quintile (p<0.0001). The relation with mortality was continuous through the whole distribution of ascorbic acid concentrations. 20 micromol/L rise in plasma ascorbic acid concentration, equivalent to about 50 g per day increase in fruit and vegetable intake, was associated with about a 20% reduction in risk of all-cause mortality (p<0.0001), independent of age, systolic blood pressure, blood cholesterol, cigarette smoking habit, diabetes, and supplement use. Ascorbic acid was inversely related to cancer mortality in men but not women. INTERPRETATION: Small increases in fruit and vegetable intake of about one serving daily has encouraging prospects for possible prevention of disease.

Patterns of physical activity and ultrasound attenuation by heel bone among Norfolk cohort of European Prospective Investigation of Cancer (EPIC Norfolk): population based study.

OBJECTIVES: To study associations between patterns of physical activity and ultrasound attenuation by the heel bone in men and women. DESIGN: Cross sectional, population based study. SETTING: Norfolk. PARTICIPANTS: 2296 men and 2914 women aged 45-74 registered with general practices participating in European Prospective Investigation into Cancer (EPIC Norfolk). RESULTS: Self reported time spent in high impact physical activity was strongly and positively associated with ultrasound attenuation by the heel bone, independently of age, weight, and other confounding factors. Men who reported participating in >/=2 hours/week of high impact activity had 8.44 dB/MHz (95% confidence interval 4.49 to 12.40) or 9.5%, higher ultrasound attenuation than men who reported no activity of this type. In women, the difference in ultrasound attenuation between those reporting any high impact activity and those reporting none was 2.41 dB/MHz (0.45 to 4.37) or 3.4% higher. In women this effect was similar in size to that of an age difference of four years. Moderate impact activity had no effect. However, climbing stairs was strongly independently associated with ultrasound attenuation in women (0.64 dB/MHz (0.19 to 1.09) for each additional five flights of stairs). There was a significant negative association in women between time spent watching television or video and heel bone ultrasound attenuation, which decreased by 0.08 dB/MHz (0.02 to 0.14) for each additional hour of viewing a week. CONCLUSIONS: High impact physical activity is independently associated with ultrasound attenuation by the heel bone in men and women. As low ultrasound attenuation has been shown to predict increased risk of hip fracture, interventions to promote participation in high impact activities may help preserve bone density and reduce the risk of fracture. However, in older people such interventions may be inappropriate as they could increase the likelihood of falls.