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Hypothesis-generating epidemiological research has suggested that cancer burden is reduced in diabetics treated with metformin and experimental work has raised questions regarding the role of direct adenosine monophosphate-activated protein kinase (AMPK)-mediated antineoplastic effects of metformin as compared with indirect effects attributable to reductions in circulating insulin levels in the host. We treated both tumor LKB1 expression and host diet as variables, and observed that metformin inhibited tumor growth and reduced insulin receptor activation in tumors of mice with diet-induced hyperinsulinemia, independent of tumor LKB1 expression. In the absence of hyperinsulinemia, metformin inhibited only the growth of tumors transfected with short hairpin RNA against LKB1, a finding attributable neither to an effect on host insulin level nor to activation of AMPK within the tumor. Further investigation in vitro showed that cells with reduced LKB1 expression are more sensitive to metformin-induced adenosine triphosphate depletion owing to impaired ability to activate LKB1-AMPK-dependent energy-conservation mechanisms. Thus, loss of function of LKB1 can accelerate proliferation in contexts where it functions as a tumor suppressor, but can also sensitize cells to metformin. These findings predict that any clinical utility of metformin or similar compounds in oncology will be restricted to subpopulations defined by host insulin levels and/or loss of function of LKB1.

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The prevalence of workplace bullying (around 10%) was found to be high in this study as well was the impact of this major job-related stressor on sleep disturbances. Although no conclusion about causality could be drawn from this cross-sectional study, the findings suggest that the contribution of workplace bullying to the burden of sleep disturbances may be substantial.

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Study objective-Concordant results have been reported in several studies for the eVects of job stress on cardiovascular disease, but the potential mechanisms of these eVects have seldom been explored. The aim of this study was therefore to examine, in women and men, the cross sectional relations between psychosocial work variables (psychological demands, decision latitude, and social support) and cardiovascular risk factors (hypertension, hyperlipidaemia, diabetes, overweight, smoking, and alcohol consumption). Design-Data were based on replies to this questionnaire. Three psychosocial work environment exposure scores were used to assess psychological demands, decision latitude, and social support at work respectively. The main outcome measures were the prevalence of hypertension, hyperlipidaemia, and diabetes within the previous 12 months, overweight, smoking, and alcohol consumption. Main results-Psychosocial work factors were significantly associated with hypertension, hyperlipidaemia, overweight, smoking, and alcohol consumption, but not with diabetes. In men, low decision latitude was associated with hypertension, high decision latitude and high social support with overweight, low decision latitude with alcohol consumption. Moreover, the risk of hyperlipidaemia increased in men exposed to both high psychological demands and low social support. In women, low decision latitude was related to hyperlipidaemia, high psychological demands with overweight, high psychological demands and high decision latitude with smoking, and low social support with alcohol consumption. Conclusions-These cross sectional results underline the potential eVects of psychosocial work characteristics on cardiovascular risk factors and the diVerences between the eVects of job stress in men and women, and confirm the direct mechanisms (through physiological variables) and indirect mechanisms (through behavioural risk factors) potentially involved in the relation between psychosocial work characteristics and cardiovascular disease. Participants-The

AimTo examine the associations between psychosocial work factors and general health outcomes, taking into account other occupational risk factors, within the national French working population. MethodsThe study was based on a large national sample of 24 486 women and men of the French working population who filled in a self-administered questionnaire in 2003 (response rate: 96.5%). Psychosocial work exposures included psychological demands, decision latitude, social support, workplace bullying and violence from the public. The three health indicators studied were self-reported health, long sickness absence (.8 days of absence) and work injury. Adjustment was made for covariates: age, occupation, work status, working hours, time schedules, physical, ergonomic, biological and chemical exposures. Men and women were studied separately. ResultsLow levels of decision latitude, and of social support, and high psychological demands were found to be risk factors for poor self-reported health and long sickness absence. High demands were also found to be associated with work injury. Workplace bullying and/or violence from the public also increased the risk of poor health, long sickness absence and work injury.Conclusion Psychosocial work factors were found to be strong risk factors for health outcomes; the results were unchanged after adjustment for other occupational risk factors. Preventive efforts should be intensified towards reducing these psychosocial work exposures.

Psychosocial factors at work have been found to be associated with having potential risk for adverse health effects. The main instrument used to measure these factors and their impact is the Job Content Questionnaire (JCQ) by Karasek. The objective of this study was to evaluate the psychometric properties of the French version of the JCQ, and in particular to assess its internal coherence and consistency, as well as the factorial and convergent validity of psychological demands, decisional latitude and social support at work based upon the SUMER survey, which was the first French national survey of its kind to include the JCQ. The study was based on a sample of 24, 486 workers who answered the JCQ in 2003 (96.5% response rate). Internal consistency was satisfactory, as Cronbach's alpha coefficients were observed as being higher than 0.65. Confirmatory factor analysis showed that the best model was composed of 5 latent variables: demands and pressures, the two dimensions of latitude (utilization of skills and autonomous decision-making), and the two dimensions of support (from supervisors and from colleagues). Convergent validity tests confirmed the expected association with key variables, which were: age, work status, sector of activity, occupation, job satisfaction, perception of job stress, and intent to change job. This study demonstrated satisfactory psychometric properties of Karasek's JCQ scales for the French working population.