CHOP Mediates Endoplasmic Reticulum Stress-Induced Apoptosis in Gimap5-Deficient T Cells

Gimap5 (GTPase of the immunity-associated protein 5) has been linked to the regulation of T cell survival, and polymorphisms in the human GIMAP5 gene associate with autoimmune disorders. The BioBreeding diabetes-prone (BBDP) rat has a mutation in the Gimap5 gene that leads to spontaneous apoptosis of peripheral T cells by an unknown mechanism. Because Gimap5 localizes to the endoplasmic reticulum (ER), we hypothesized that absence of functional Gimap5 protein initiates T cell death through disruptions in ER homeostasis. We observed increases in ER stress-associated chaperones in T cells but not thymocytes or B cells from Gimap5−/− BBDP rats. We then discovered that ER stress-induced apoptotic signaling through C/EBP-homologous protein (CHOP) occurs in Gimap5−/− T cells. Knockdown of CHOP by siRNA protected Gimap5−/− T cells from ER stress-induced apoptosis, thereby identifying a role for this cellular pathway in the T cell lymphopenia of the BBDP rat. These findings indicate a direct relationship between Gimap5 and the maintenance of ER homeostasis in the survival of T cells

Assessing Causality in the Relationship Between Adolescents’ Risky Sexual Online Behavior and Their Perceptions of this Behavior

The main aim of this study was to investigate the causal nature of the relationship between adolescents’ risky sexual behavior on the internet and their perceptions of this behavior. Engagement in the following online behaviors was assessed: searching online for someone to talk about sex, searching online for someone to have sex, sending intimate photos or videos to someone online, and sending one’s telephone number and address to someone exclusively known online. The relationship between these behaviors and adolescents’ perceptions of peer involvement, personal invulnerability, and risks and benefits was investigated. A two-wave longitudinal study among a representative sample of 1,445 Dutch adolescents aged 12–17 was conducted (49% females). Autoregressive cross-lagged structural equation models revealed that perceived peer involvement, perceived vulnerability, and perceived risks were all significant predictors of risky sexual online behavior 6 months later. No reverse causal paths were found. When the relationships between perceptions and risky sexual online behavior were modeled simultaneously, only perceived peer involvement was a determinant of risky sexual online behavior. Findings highlight the importance of addressing peer involvement in future interventions to reduce adolescents’ risky sexual online behavior

Training Primary Care Physicians to Employ Self-Efficacy-Enhancing Interviewing Techniques: Randomized Controlled Trial of a Standardized Patient Intervention

BACKGROUND: Primary care providers (PCPs) have few tools for enhancing patient self-efficacy, a key mediator of myriad health-influencing behaviors. OBJECTIVE: To examine whether brief standardized patient instructor (SPI)-delivered training increases PCPs’ use of self-efficacy-enhancing interviewing techniques (SEE IT). DESIGN: Randomized controlled trial. PARTICIPANTS: Fifty-two family physicians and general internists from 12 primary care offices drawn from two health systems in Northern California. INTERVENTIONS: Experimental arm PCPs received training in the use of SEE IT training during three outpatient SPI visits scheduled over a 1-month period. Control arm PCPs received a single SPI visit, during which they viewed a diabetes treatment video. All intervention visits (experimental and control) were timed to last 20 min. SPIs portrayed patients struggling with self-care of depression and diabetes in the first 7 min, then delivered the appropriate intervention content during the remaining 13 min. MAIN MEASURES: The primary outcome was provider use of SEE IT (a count of ten behaviors), coded from three audio-recorded standardized patient visits at 1–3 months, again involving depression and diabetes self-care. Two five-point scales measured physician responses to training: Value (7 items: quality, helpfulness, understandability, relevance, feasibility, planned use, care impact), and Hassle (2 items: personal hassle, flow disruption). KEY RESULTS: Pre-intervention, study PCPs used a mean of 0.7 behaviors/visit, with no significant between-arm difference (P = 0.23). Post-intervention, experimental arm PCPs used more of the behaviors than controls (mean 2.7 vs. 1.0 per visit; adjusted difference 1.7, 95 % CI 1.1–2.2; P < 0.001). Experimental arm PCPs had higher training Value scores than controls (mean difference 1.05, 95 % CI 0.68–1.42; P < 0.001), and similarly low Hassle scores. CONCLUSIONS: Primary care physicians receiving brief SPI-delivered training increased their use of SEE IT and found the training to be of value. Whether patients visiting SEE IT-trained physicians experience improved health behaviors and outcomes warrants study. CLINICALTRIALS.GOV IDENTIFIER: NCT01618552 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11606-016-3644-z) contains supplementary material, which is available to authorized users

The Effect of Teach One Reach One (TORO) on Youth Acceptance of Couple Violence

This study evaluated the impact of the Teach One Reach One intervention, a community-based participatory research project designed to address the co-occurrence of adolescent risk behaviors on acceptance of teen dating violence. Data were derived from 331 rural African American youth between 10–14 years of age who participated in caregiver-youth dyads as either: 1) peer lay health advisor dyads, or Ambassadors, 2) caregiver-youth dyads recruited by Ambassadors, or Allies, or 3) comparison dyads. The following study focuses on participating youth only and our results indicated that: 1) Ambassadors and Allies reported less acceptance of couple violence than youth within the comparison group, and 2) less family cohesion, greater family conflict, and greater knowledge of healthy dating behaviors predicted greater acceptance of couple violence. Our findings highlight the efficaciousness of the TORO intervention, which directly engaged participants in prevention efforts through community-based participatory research methods and the use of lay heath advisors