Association between nurses' personal, professional and work characteristics, and engagement in hospital-based clinical research.

PURPOSE: The purpose of this study was to assess the associations between demographic, professional and other personal nurse characteristics, social support factors and comfort in conducting research with nurses' level of active participation in clinical research. DESIGN: A prospective, cross-sectional, correlational design was used. METHODS: Clinical nurses working in a multihospital healthcare system were recruited by email to complete an anonymous survey that used multiple valid and reliable scales to assess demographic and professional work characteristics, curiosity, grit, locus of control, perceived social support (for research activities), comfort in conducting research, and level of being research-active. Univariate and multivariable analyses were completed. RESULTS: Of 310 participants, 274 (88.4%) were female and mean (SD) age was 42.9 (13.1) years. After condensing 11 levels of research activity to four categories, 179 (57.7%) were not research-active, and 91 (29.4%), 26 (8.3%) and 14 (4.5%) were engaged at low, moderate, and high levels, respectively. Of 78 factors, 69 (88.5%) were associated with being research-active in univariate analyses. In multivariable analysis that adjusted for age, personal experience as a patient, years as a nurse and hours in direct patient care, professionalism characteristics, higher curiosity, internal locus of control, grit perseverance, support of a nurse scientist and nurse friends, and comfort in conducting research remained associated with higher levels of being research-active (all p < 0.01). CONCLUSION: Research-active nurses were more likely to be engaged professionally in hospital-based activities beyond their work roles and displayed higher levels of positive psychological characteristics and mentorship that supported research capacity. CLINICAL RELEVANCE: Research-active nurses were more likely to have internal factors and external resources that promoted higher levels of being research-active. A strong professional governance model may enhance clinical nurses research activities.

C5aR plus MEK inhibition durably targets the tumor milieu and reveals tumor cell phagocytosis.

Plexiform neurofibromas (PNFs) are nerve tumors caused by loss of NF1 and dysregulation of RAS-MAPK signaling in Schwann cells. Most PNFs shrink in response to MEK inhibition, but targets with increased and durable effects are needed. We identified the anaphylatoxin C5a as increased in PNFs and expressed largely by PNF m acrophages. We defined pharmacokinetic and immunomodulatory properties of a C5aR1/2 antagonist and tested if peptide antagonists augment the effects of MEK inhibition. MEK inhibition recruited C5AR1 to the macrophage surface; short-term inhibition of C5aR elevated macrophage apoptosis and Schwann cell death, without affecting MEK-induced tumor shrinkage. PNF macrophages lacking C5aR1 increased the engulfment of dying Schwann cells, allowing their visualization. Halting combination therapy resulted in altered T-cell distribution, elevated Iba1+ and CD169+ immunoreactivity, and profoundly altered cytokine expression, but not sustained trumor shrinkage. Thus, C5aRA inhibition independently induces macrophage cell death and causes sustained and durable effects on the PNF microenvironment.

Strategies for recruiting adolescents in rural areas in firearm injury research.

BACKGROUND: Participant recruitment is a central aspect of human sciences research. Barriers to participant recruitment can be categorised into participant, recruiter and institutional factors. Firearm injury research poses unique barriers to recruitment. This is especially true for rural adolescents, who are at high risk for firearm-related injury and death, and whose voice is often absent in firearms research. In particular, recruitment strategies targeting adolescents should align with developmental changes occurring during this life stage. Identifying strategies to address recruitment barriers tailored to firearm-related research can help future researchers engage rural adolescents in injury prevention efforts. PURPOSE: The purpose of the current methodology paper is to outline barriers and provide strategies for recruiting rural adolescents in firearms research informed by the Youth Experiences in Rural Washington: Research on Firearm Safety project, a mixed-methods, community-based participatory research study of 13-18 year-olds residing in rural Washington. STRATEGIES: Recruitment barriers and related strategies were organised by participant-related and recruiter-related/institutional-related factors. While carrying out the study, key considerations or strategies which addressed multiple participant and recruiter/institutional factors, emerged with potential to enhance firearm-related research with rural adolescents more broadly. Key considerations included logistics (ie, scheduling flexibility, adequate and aligned incentives), use of a community-based participatory research approach and accounting for developmental stage. CONCLUSION: Reducing the burden of firearm injury and death for rural adolescents and developing effective interventions requires understanding and navigating recruitment barriers. Strategies used in the current project can guide future qualitative or mixed methods data collection informing firearm injury prevention.

A SINE-VNTR-Alu at the LRIG2 locus is associated with proximal and distal gene expression in CRISPR and population models.

SINE-VNTR-Alu (SVA) retrotransposons represent mobile regulatory elements that have the potential to influence the surrounding genome when they insert into a locus. Evolutionarily recent mobilisation has resulted in loci in the human genome where a given retrotransposon might be observed to be present or absent, termed a retrotransposon insertion polymorphism (RIP). We previously observed that an SVA RIP ~ 2 kb upstream of LRIG2 on chromosome 1, the 'LRIG2 SVA', was associated with differences in local gene expression and methylation, and that the two were correlated. Here, we have used CRISPR-mediated deletion of the LRIG2 SVA in a cell line model to validate that presence of the retrotransposon is directly affecting local expression and provide evidence that is suggestive of a modest role for the SVA in modulating nearby methylation. Additionally, in leveraging an available Hi-C dataset we observed that the LRIG2 SVA was also involved in long-range chromatin interactions with a cluster of genes ~ 300 kb away, and that expression of these genes was to varying degrees associated with dosage of the SVA in both CRISPR cell line and population models. Altogether, these data support a regulatory role for SVAs in the modulation of gene expression, with the latter potentially involving chromatin looping, consistent with the model that RIPs may contribute to interpersonal differences in transcriptional networks.