Mental health clinician perspectives regarding factors impacting implementation of evidence-based psychotherapies in Veterans Health Administration community-based outpatient clinics.

OBJECTIVE: Uptake of Evidence-Based Psychotherapies (EBPs) by mental health (MH) clinicians, especially in community settings, remains highly variable. This formative pilot study aimed to understand the attitudes and practices of Veterans Health Administration community-based MH clinicians regarding EBPs and to identify multi-level factors that enable and hinder EBP implementation in this unique context. METHODS: Semi-structured interviews were conducted with MH clinicians (N = 40) working in community-based outpatient clinics (CBOCs) in metro/urban (n = 20) and non-metro/rural (n = 20) locations. Interviews were guided by the Consolidated Framework for Implementation Research and were analyzed using rapid content analysis. Results were organized by system-, clinician-, patient-, and innovation-levels. RESULTS: EBPs were consistently perceived as important to delivering quality MH care, with most clinicians having received training in at least one VHA EBP. However, limited EBP training and consultation opportunities, inadequate autonomy to schedule EBP sessions, high and complex caseloads, and feelings of isolation at CBOCs decreased EPB use. Social workers perceived disparities in EBP training access relative to psychologists. Some barriers were more salient in non-metro/rural settings (e.g., patient-level privacy concerns). CONCLUSIONS: Increased EBP training opportunities- particularly for social workers-, greater flexibility over schedules and caseloads, and more mechanisms for consultation and professional development may increase EBP uptake in community-based clinics.

Influence of pubertal development on urinary oxidative stress biomarkers in adolescent girls in the New York LEGACY cohort.

Puberty is a time of intense growth and differentiation of breast tissue and a window of susceptibility (WOS) for breast cancer. Although oxidative stress markers have been associated with breast cancer risk, it is unclear whether oxidative stress levels are different during the pubertal WOS, and if so, whether these differences are related to breast cancer susceptibility. We measured urinary biomarkers of whole body oxidative stress (urinary F2-Isoprostanes and 8-oxodeoxyguanosine (8-oxodG)) in 158 girls (ages 6-13 years), 71 with and 87 without a breast cancer family history (BCFH) from a cohort of adolescent girls from the New York site of the LEGACY cohort (Lessons in Epidemiology and Genetics in Adults Cancer from Youth). We compared levels of urinary oxidative stress biomarkers (F2-Isoprostanes and 8-oxodG) across the pubertal window, defined by Tanner Stage (TS) of breast development, both cross-sectionally and longitudinally within girls over an 18-month follow up period. Urinary oxidative stress biomarkers were unrelated to pubertal stages in cross-sectional analyses after considering adjustments for body mass index (BMI) and BCFH. In our longitudinal analysis, we found that urinary 8-oxodG levels, but not F2-Isoprostane levels, increased with age in BCFH + girls (ß = 6.12, 95% CI = 0.08-12.16) compared to BCFH-girls. Higher BMI was associated with higher level of F2-Isoprostane in both cross-sectional (ß = 0.02, 95% CI = 0.0004-0.05) and longitudinal analysis (ß = 0.02, 95% CI = 0.0002-0.05). These findings support that higher BMI increases oxidative stress biomarkers over the pubertal window and that there are changes in 8-oxodG oxidative stress biomarkers in girls with a BCFH compared to girls without a BCFH.

Cognitive and Adaptive Skills in Toddlers Who Meet Criteria for Autism in DSM-IV but not DSM-5.

The current study compared adaptive and cognitive skills, and autism severity of toddlers with an autism spectrum disorder (ASD) diagnosis under DSM-IV but not DSM-5 criteria (DSM-IV only group) to those who met autism criteria under both diagnostic systems (DSM-5 group) and to those without ASD (non-ASD group). The toddlers in the DSM-IV only group were less delayed on various domains of adaptive (Communication, Socialization) and cognitive (Expressive and Receptive language, Fine Motor, Visual Reception) skills, and had less severe symptoms of ASD than the DSM-5 group. Thus, they might have the best potential for successful intervention. The DSM-IV only group did not differ from the non-ASD group in any adaptive or cognitive skills except for socialization skills, the hallmark of ASD.

Human single-domain neutralizing intrabodies directed against Etk kinase: a novel approach to impair cellular transformation.

Etk, the 70-kDa member of the Tec family of nonreceptor protein tyrosine kinases, is expressed in a variety of hematopoietic, epithelial, and endothelial cells and was shown to be involved in several cellular processes, including proliferation, differentiation, and motility. In this study, we describe a novel approach using a human single-domain antibody phage display library for the generation of intrabodies directed against Etk. These single-domain antibodies bind specifically to recombinant Etk and efficiently block its kinase activity. When expressed in transformed cells, these antibodies associated tightly with Etk, leading to significant blockade of Etk enzymatic activity and inhibition of clonogenic cell growth in soft agar. Our results indicate that Etk may play a role in Src-induced cellular transformation and thus may represent a good target for cancer intervention. Furthermore, our single-domain antibody-based intrabody system proves to be an excellent tool for future intracellular targeting of other signaling molecules.

Involvement of the VEGF receptor 3 in tubular morphogenesis demonstrated with a human anti-human VEGFR-3 monoclonal antibody that antagonizes receptor activation by VEGF-C.

In this report we utilize a novel antagonist antibody to the human VEGFR-3 to elucidate the role of this receptor in in vitro tubular morphogenesis of bovine and human endothelial cells (EC cells) induced by VEGF-C. The antibody hF4-3C5 was obtained by panning a human phage display library on soluble human VEGFR-3. The binding affinity constant of hF4-3C5 significantly exceeds that of the interaction of VEGFR-3 with VEGF-C. hF4-3C5 strongly inhibits the binding of soluble VEGFR-3 to immobilized VEGF-C and abolishes the VEGF-C-mediated mitogenic response of cells that expresses a chimeric human VEGFR-3-cFMS receptor. In fluorescence experiments, hF4-3C5 reactivity is observed with human lymphatic endothelial cells (LECs) and human umbilical vein endothelial cells (HUVECs). Binding of hF4-3C5 shows that about half of bovine aortic endothelial (BAE) cells express VEGFR-3 and cells in this subpopulation are primarily responsible for the chemotactic response to the mature form of VEGF-C (VEGF-C(DeltaNDeltaC)). This response was strongly inhibited by the addition of hF4-3C5. In vitro tube formation by BAE cells induced by VEGF-C(DeltaNDeltaC) was reduced by greater than 60% by hF4-3C5 whereas the response to VEGF(165) was unaffected. Addition of hF4-3C5 together with an antagonist antibody to VEGFR-2 completely abolished the response to VEGF-C(DeltaNDeltaC). Similar results were obtained with HUVECs. Together, these findings point to a role for VEGFR-3 in vascular tubular morphogenesis and highlight the utility of hF4-3C5 as a tool for the investigation of the biology of VEGFR-3.