Enhancing Risk Detection Among Homeless Youth: A Randomized Clinical Trial of a Promising Pilot Intervention.

Homeless youth frequently experience victimization, and youth with histories of trauma often fail to detect danger risks, making them vulnerable to subsequent victimization. The current study describes a pilot test of a skills-based intervention designed to improve risk detection among homeless youth through focusing attention to internal, interpersonal, and environmental cues. Youth aged 18 to 21 years ( N = 74) were recruited from a shelter and randomly assigned to receive usual case management services or usual services plus a 3-day manualized risk detection intervention. Pretest and posttest interviews assessed youths' risk detection abilities through vignettes describing risky situations and asking youth to identify risk cues present. Separate 2 (intervention vs. control) × 2 (pretest vs. posttest) mixed ANOVAs found significant interaction effects, as intervention youth significantly improved in overall risk detection compared with control youth. Post hoc subgroup analyses found the intervention had a greater effect for youth without previous experiences of indirect victimization than those with previous indirect victimization experiences.

Commensal Gut Microbiota Immunomodulatory Actions in Bone Marrow and Liver have Catabolic Effects on Skeletal Homeostasis in Health.

Despite knowledge the gut microbiota regulates bone mass, mechanisms governing the normal gut microbiota's osteoimmunomodulatory effects on skeletal remodeling and homeostasis are unclear in the healthy adult skeleton. Young adult specific-pathogen-free and germ-free mice were used to delineate the commensal microbiota's immunoregulatory effects on osteoblastogenesis, osteoclastogenesis, marrow T-cell hematopoiesis, and extra-skeletal endocrine organ function. We report the commensal microbiota has anti-anabolic effects suppressing osteoblastogenesis and pro-catabolic effects enhancing osteoclastogenesis, which drive bone loss in health. Suppression of Sp7(Osterix) and Igf1 in bone, and serum IGF1, in specific-pathogen-free mice suggest the commensal microbiota's anti-osteoblastic actions are mediated via local disruption of IGF1-signaling. Differences in the RANKL/OPG Axis in vivo, and RANKL-induced maturation of osteoclast-precursors in vitro, indicate the commensal microbiota induces sustained changes in RANKL-mediated osteoclastogenesis. Candidate mechanisms mediating commensal microbiota's pro-osteoclastic actions include altered marrow effector CD4+T-cells and a novel Gut-Liver-Bone Axis. The previously unidentified Gut-Liver-Bone Axis intriguingly implies the normal gut microbiota's osteoimmunomodulatory actions are partly mediated via immunostimulatory effects in the liver. The molecular underpinnings defining commensal gut microbiota immunomodulatory actions on physiologic bone remodeling are highly relevant in advancing the understanding of normal osteoimmunological processes, having implications for the prevention of skeletal deterioration in health and disease.

Predictors of Permanent Pacemaker Implantation After Transcatheter Aortic Valve Replacement.

OBJECTIVE: Determine predictors of permanent pacemaker (PPM) implantation after transcatheter aortic valve replacement (TAVR). DESIGN: A retrospective chart review of patients undergoing TAVR at the authors' institution. Extracted data included patient demographics, electrocardiogram, procedural, and echocardiographic data. Multivariate regression was performed to identify associations with PPM implantation. SETTING: Single-center academic hospital. PARTICIPANTS: Patients undergoing TAVR. INTERVENTIONS: This study was retrospective. No interventions were performed on patients. MEASUREMENTS AND MAIN RESULTS: Baseline electrocardiogram, Society of Thoracic Surgeons score, age, and echocardiographic parameters were not predictors of PPM implantation. However, multiple deployments was a risk factor, and degree of paravalvular leak trended toward significance. Ten patients required placement of a 2nd valve, or valve-in-valve (VIV). Of the 10 patients with VIV, 5 (50%) required a PPM, compared with 8 (14%) of 56 patients with a single valve (OR 6.0, p = 0.02). PPM implantation occurred in 5 (42%) patients with no leak, 8 (19%) patients with trace leak, and no patients with mild or moderate leak (p = 0.085). In patients with no or trace leak, VIV increased the likelihood of PPM from 17.4% to 62.5% (OR 7.9, p = 0.006). For the 42 patients with trace leak, VIV increased the likelihood of PPM from 11.4% to 57.1% (OR 10.33, p = 0.005). CONCLUSIONS: The authors found VIV placement, and likely degree of paravalvular leak, to be predictors of PPM placement. VIV and the degree of leak may be useful markers for postoperative prophylactic pacemaker placement.

Electronic case management with homeless youth.

Case management, a widely practiced form of service brokerage, is associated with a variety of positive outcomes for homeless youth, but it may be difficult to implement, as youth face logistical barriers to attending in-person meetings. As part of a larger clinical trial, the current study investigates the feasibility of providing electronic case management (ECM) to homeless youth, using cell-phones, texts, email, and Facebook. Youth were given prepaid cell-phones and a case manager who provided four ECM sessions every 2-3 weeks over a 3-month period. Contact logs were used to record how many youth engaged in ECM, how many attempts were necessary to elicit engagement, and youths' preferred technology methods for engaging. Although engagement in the number of ECM sessions varied, the majority of youth (87.5%) engaged in at least one ECM session. Youth (41%) most commonly needed one contact before they engaged in an ECM session, and the majority responded by the third attempt. While youth most commonly answered calls directly, their chosen method of returning calls was texting. The majority of youth (80%) described ECM positively, reporting themes of convenience, connection, and accountability. The use of ECM, particularly of texting, offers promising implications for providing services to homeless youth.

Insights into the Role of PAX-3 in the Development of Melanocytes and Melanoma.

Melanoma is the deadliest form of skin cancer in the United States with an increasing prevalence. However, the development of melanoma from a melanocyte precursor is still poorly defined. Understanding the molecules responsible for melanoma progression may lead to improved targeted therapy. One potential molecule is the paired box-3 (PAX-3) protein, which has been implicated in the development of melanocytes and malignant melanoma. In melanoma, the expression of PAX-3 is believed to be differentially regulated, and has been linked with malignancies and staging of the disease. The loss of PAX-3 regulation has also been associated with the loss of transforming growth factor-beta (TGF-ß) activity, but its effect on PAX-3 in differentiated melanocytes as well as metastatic melanoma remains unclear. Understanding PAX-3 regulation could potentially shift melanoma to a less aggressive and less metastatic disease. This review summarizes our current knowledge on PAX-3 during melanocyte development, its regulation, and its implications in the development of novel chemo-immunotherapeutics against metastatic melanoma.