Interplay of cell-cell contacts and RhoA/MRTF-A signaling regulates cardiomyocyte identity.

Cell-cell and cell-matrix interactions guide organ development and homeostasis by controlling lineage specification and maintenance, but the underlying molecular principles are largely unknown. Here, we show that in human developing cardiomyocytes cell-cell contacts at the intercalated disk connect to remodeling of the actin cytoskeleton by regulating the RhoA-ROCK signaling to maintain an active MRTF/SRF transcriptional program essential for cardiomyocyte identity. Genetic perturbation of this mechanosensory pathway activates an ectopic fat gene program during cardiomyocyte differentiation, which ultimately primes the cells to switch to the brown/beige adipocyte lineage in response to adipogenesis-inducing signals. We also demonstrate by in vivo fate mapping and clonal analysis of cardiac progenitors that cardiac fat and a subset of cardiac muscle arise from a common precursor expressing Isl1 and Wt1 during heart development, suggesting related mechanisms of determination between the two lineages

Process evaluation of the context, reach and recruitment of participants and delivery of dementia-specific case conferences (WELCOME-IdA) in nursing homes (FallDem): a mixed-methods study

Abstract Background A system of dementia-specific case conferences (WELCOME-IdA) was evaluated using a stepped-wedge design in six nursing homes (NHs) to enable nursing staff to analyse properly the behavioural and psychological symptoms (BPSD) of residents with dementia. A process evaluation of the context, the recruitment and target populations reached (residents and nursing staff) and the delivery of the intervention and implementation strategy was carried out to explore the lack of effectiveness of WELCOME-IdA on the residents’ prevalence of BPSD. Methods This study was part of a larger process evaluation using a mixed-methods design. Standardised questionnaires, semi-structured interviews, attendance lists, standardised protocols and written self-reports were used to collect the data. The quantitative data were analysed by calculating descriptive statistics. The qualitative interviews were analysed using deductive content analysis and the self-reports were analysed using a documentary analysis. Results None of the NHs had prior experience with dementia-specific case conferences on a specific concept related to BPSD. The number of residents for whom a dementia-specific case conference was held was lower than expected. The number of nursing staff reached was high, although as defined in the study protocol, core nursing teams continuously participating in all components of the intervention were not established throughout the study. An analysis of the delivery of the intervention showed a reduction in the frequency of dementia-specific case conferences and deviations in the process structure and role structure of WELCOME-IdA. The strategy used to facilitate the implementation of WELCOME-IdA was mostly followed. An analysis of the recruitment of residents indicated that the variation in which residents were included in the study sample was high and that the intended sample size required to achieve a power >80% was not reached. Conclusion An analysis of the process evaluation data indicated that there were inaccuracies in the implementation of WELCOME-IdA and there were methodological limitations within the design of the effectiveness trial, both of which could explain the lack of effectiveness of WELCOME-IdA. To optimise the process structure of WELCOME-IdA, an assessment of BPSD and a pre-selection of possible domains for the behavioural analysis could be conducted prior to a dementia-specific case conference. Trial registration ISRCTN20203855. Registered on 10 July 2013