The acceptance and use of the e-Health instrument 'The personal health check' in four Dutch municipalities:Lessons learned

This pilot study assessed the acceptance and use of the e-Health instrument “the Personal Health Check” (PHC) among clients and professionals in primary care settings. By filling in the online PHC instrument, participants were provided insights into their health and lifestyle. When results revealed an increased health risk, participants were advised to undertake additional lab tests measuring blood pressure and haemaglobin levels. Based on the online questionnaire and optional lab tests, participants then received a report that included individually-tailored feedback from the e-Health application about personal health risks and suggestions for health interventions. The PHC was implemented in 2016 in four Dutch municipalities that determined which neighbourhood(s) the PHC targeted and how participants were invited. The Unified Theory of Acceptance and Use of Technology was used as a theoretical framework to address our research questions. Methods used to assess acceptance were: PHC instrument data, data from additional questionnaires completed by PHC participants, focus groups with PHC participants and professionals in primary care, and telephone interviews with non-responders to the invitation to participate in the online PHC. Of the 21,735 invited, 12% participated. Our results showed that participants and professionals in this pilot were predominantly positive about the PHC. Participants reported that they made an effort to apply the PHC lifestyle advice they received. Almost all had the knowledge and resources needed to use the PHC online instrument. Invitations from general practitioners almost doubled participation relative to invitations from the sponsoring municipalities. The overall low response rate, however, suggests that the PHC is unsuitable as a foundation on which to develop local public health policy

Splicing factors control triple-negative breast cancer cell mitosis through SUN2 interaction and sororin intron retention

BackgroundTriple negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited therapeutic opportunities. Recently, splicing factors have gained attention as potential targets for cancer treatment. Here we systematically evaluated the role of RNA splicing factors in TNBC cell proliferation.MethodsIn this study, we performed an RNAi screen targeting 244 individual splicing factors to systematically evaluate their role in TNBC cell proliferation. For top candidates, mechanistic insight was gained using amongst others western blot, PCR, FACS, molecular imaging and cloning. Pulldown followed by mass spectrometry were used to determine protein-protein interactions and patient-derived RNA sequencing data was used relate splicing factor expression levels to proliferation markers.ResultsWe identified nine splicing factors, including SNRPD2, SNRPD3 and NHP2L1, of which depletion inhibited proliferation in two TNBC cell lines by deregulation of sister chromatid cohesion (SCC) via increased sororin intron 1 retention and down-regulation of SMC1, MAU2 and ESPL1. Protein-protein interaction analysis of SNRPD2, SNRPD3 and NHP2L1 identified that seven out of the nine identified splicing factors belong to the same spliceosome complex including novel component SUN2 that was also critical for efficient sororin splicing. Finally, sororin transcript levels are highly correlated to various proliferation markers in BC patients.ConclusionWe systematically determined splicing factors that control proliferation of breast cancer cells through a mechanism that involves effective sororin splicing and thereby appropriate sister chromatid cohesion. Moreover, we identified SUN2 as an important new spliceosome complex interacting protein that is critical in this process. We anticipate that deregulating sororin levels through targeting of the relevant splicing factors might be a potential strategy to treat TNBC.Cancer Signaling networks and Molecular Therapeutic