Apoptosis of t(14;18)-positive lymphoma cells by a Bcl-2 interacting small molecule

Overexpression of Bcl-2 protein occurs via both t(14;18)-dependent and independent mechanisms and contributes to the survival and chemoresistance of non-Hodgkin lymphomas. HA14–1 is a nonpeptidic organic small molecule, which has been shown to inhibit the interaction of Bcl-2 with Bax, thereby interfering with the antiapoptotic function of Bcl-2. In this study, we sought to determine the in vitro efficacy of HA14–1 as a therapeutic agent for non-Hodgkin lymphomas expressing Bcl-2. Assessment of cell viability demonstrated that HA14–1 induced a dose- (IC50 = 10 μM) and time-dependent growth inhibition of a cell line (SudHL-4) derived from a t(14;18)-positive, Bcl-2-positive, non-Hodgkin lymphoma. HA14–1 effectively induced apoptosis via a caspase 3-mediated pathway but did not affect either the p38 MAPK or p44/42 MAPK pathways. Western blot analyses of Bcl-2 family proteins and other cell cycle-associated proteins were performed to determine the molecular sequelae of HA14–1-induced apoptosis. The results show down-regulation of Mcl-1 but up-regulation of p27kip1, Bad, Bcl-xL, and Bcl-2 proteins, without change in Bax levels during HA14–1-mediated apoptosis. Our findings further elucidate the cellular mechanisms accompanying Bcl-2 inhibition and demonstrate the potential of Bcl-2 inhibitors as therapeutic agents for the treatment of non-Hodgkin lymphomas

Advancing a Conceptual Model of Evidence-Based Practice Implementation in Public Service Sectors

Implementation science is a quickly growing discipline. Lessons learned from business and medical settings are being applied but it is unclear how well they translate to settings with different historical origins and customs (e.g., public mental health, social service, alcohol/drug sectors). The purpose of this paper is to propose a multi-level, four phase model of the implementation process (i.e., Exploration, Adoption/Preparation, Implementation, Sustainment), derived from extant literature, and apply it to public sector services. We highlight features of the model likely to be particularly important in each phase, while considering the outer and inner contexts (i.e., levels) of public sector service systems

The Effect of Bullying and Victimization on Cognitive Empathy Development During the Transition to Middle School

Background Interventions aimed at reducing bullying behavior commonly target the development of empathy. Yet, few longitudinal studies have investigated how empathy levels vary with bullying and victimization over time, especially during the transition to middle school. Objective To that end, the purpose of the present study was to: (1) examine the naturally-occurring changes in cognitive empathy during the transition from elementary to middle school, and (2) explore the effect of bullying and victimization involvement on changes in cognitive empathy over time, and specifically during this school transition. Methods Latent growth curve modeling was used to examine growth trajectories in empathy over time and the effects of bullying involvement on this growth among a sample of 431 students (52 % female, 52 % Latino, 10.18 years old at baseline), using data collected during the spring semester of the 4th grade, the fall and spring semesters of 5th grade, and the spring semester of 6th grade. Results Cognitive empathy decreased over time, and a linear trajectory was the best fitting shape for these data. Bullying and victimization were both associated with lower levels of cognitive empathy throughout the study. However, the effect of victimization was small and it became non-significant when both were added to the model. Several notable participant-related differences were found