Prolonged job strain reduces time-domain heart rate variability on both working and resting days among cardiovascular-susceptible nurses

Introduction Modifications of hearth rate variability (HRV) constitute a marker of the autonomic nervous system (ANS) deregulation, a promising pathway linking job strain (JS) and cardiovascular diseases (CVD). The study objective is to assess whether exposures to recent and prolonged JS reduce time-domain HRV parameters on working days (WD) among CVD-susceptible nurses and whether the association also persists on resting days (RD). Material and methods 313 healthy nurses were investigated twice with one year interval to assess JS based on the demand-control and the effort-reward models. 36, 9 and 16 CVD-susceptible nurses were classified as low JS in both surveys (stable low strain – SLS), recent high JS (high JS at the second screening only-RHS) and prolonged high JS (high strain in both surveys-PHS), respectively. In 9, 7 and 10 of them, free from comorbidities/treatments interfering with HRV, two 24-h ECG recordings were performed on WD and RD. Differences in the time domain HRV metrics among JS categories were assessed using ANCOVA, adjusted for age and smoking. Results In the entire sample (mean age: 39 years, 83% females) the prevalence of high job strain was 38.7% in the second survey. SDNN (standard deviation of all normal RR intervals) on WD significantly declined among JS categories (p = 0.02), with geometric mean values of 169.1, 145.3 and 128.9 ms in SLS, RHS, PHS, respectively. In the PHS group, SDNN remained lower on RD as compared to the low strain subjects (142.4 vs. 171.1 ms, p = 0.02). Similar findings were found for the SDNN_Index, while SDANN (standard deviation of average RR intervals in all 5 min segments of registration) mean values reduced in the PHS group during WD only. Conclusions Our findings suggest that persistent JS lowers HRV time-domain parameters, supporting the hypothesis that the ANS disorders may play an intermediate role in the relationship between work stress and CVD

The CRACK programme: a scientific alliance for bridging healthcare research and public health policies in Italy

Healthcare utilisation databases, and other secondary data sources, have been used with growing frequency to assess health outcomes and healthcare interventions worldwide. Their increased popularity as a research tool is due to their timely availability, the large patient populations covered, low cost, and applicability for studying real-world clinical practice. Despite the need to measure Italian National Health Service performance both at regional and national levels, the wealth of good quality electronic data and the high standards of scientific research in this field, healthcare research and public health policies seem to progress along orthogonal dimensions in Italy. The main barriers to the development of evidence-based public health include the lack of understanding of evidence-based methodologies by policy makers, and of involvement of researchers in the policy process. The CRACK programme was launched by some academics from the Lombardy Region. By extensively using electronically stored data, epidemiologists, biostatisticians, pharmacologists and clinicians applied methods and evidence to several issues of healthcare research. The CRACK programme was based on their intention to remove barriers that thwart the process of bridging methods and findings from scientific journals to public health practice. This paper briefly describes aim, articulation and management of the CRACK programme, and discusses why it might find articulated application in Italy

Determinants of social inequalities in stroke incidence across Europe:a collaborative analysis of 126 635 individuals from 48 cohort studies

Knowledge on the origins of the social gradient in stroke incidence in different populations is limited. This study aims to estimate the burden of educational class inequalities in stroke incidence and to assess the contribution of risk factors in determining these inequalities across Europe

Tolerogenic IL-10-engineered dendritic cell-based therapy to restore antigen-specific tolerance in T cell mediated diseases

Tolerogenic dendritic cells play a critical role in promoting antigen-specific tolerance via dampening of T cell responses, induction of pathogenic T cell exhaustion and antigen-specific regulatory T cells. Here we efficiently generate tolerogenic dendritic cells by genetic engineering of monocytes with lentiviral vectors co-encoding for immunodominant antigen-derived peptides and IL-10. These transduced dendritic cells (designated DCIL-10/Ag) secrete IL-10 and efficiently downregulate antigen-specific CD4+ and CD8+ T cell responses from healthy subjects and celiac disease patients in vitro. In addition, DCIL-10/Ag induce antigen-specific CD49b+LAG-3+ T cells, which display the T regulatory type 1 (Tr1) cell gene signature. Administration of DCIL-10/Ag resulted in the induction of antigen-specific Tr1 cells in chimeric transplanted mice and the prevention of type 1 diabetes in pre-clinical disease models. Subsequent transfer of these antigen-specific T cells completely prevented type 1 diabetes development. Collectively these data indicate that DCIL-10/Ag represent a platform to induce stable antigen-specific tolerance to control T-cell mediated diseases

Roles of allostatic load, lifestyle and clinical risk factors in mediating the association between education and coronary heart disease risk in Europe

Background Previous studies have shown that differential exposure to lifestyle factors may mediate the association between education and coronary heart diseases (CHD). However, few studies have examined the potential roles of allostatic load (AL) or differential susceptibility. Methods 25 310 men and 26 018 women aged 35\u201374 and CHD free at baseline were identified from 21 European cohorts and followed for a median of 10 years, to investigate the mediating role of AL, as well as of smoking, alcohol use and body mass index (BMI), on educational differences in CHD incidence, applying marginal structural models and three-way decomposition. Results AL is a mediator of the association between educational status and CHD incidence, with the highest proportion mediated observed among women and largely attributable to differential exposure, (28% (95% CI 19% to 44%)), with 8% (95% CI 0% to 16%) attributable to differential susceptibility. The mediating effects of smoking, alcohol and BMI, compared with AL, were relatively small for both men and women. Conclusion Overall, the educational inequalities in CHD incidence were partially mediated through differential exposure to AL. By contrast, the mediation of the educational gradient in CHD by investigated lifestyle risk factors was limited. As differential susceptibility in men was found to have a predominant role in the accumulation of AL in low educational classes, the investigation of AL-related risk factors is warranted