Much is known about the prevalence and correlates of dating violence, especially the perpetration of physical dating violence, among older adolescents. However, relatively little is known about the prevalence and correlates of the perpetration of cyber dating abuse, particularly among early adolescents. In this study, using a predominantly ethnic-minority sample of sixth graders who reported ever having had a boyfriend/girlfriend (n = 424, 44.2 % female), almost 15 % reported perpetrating cyber dating abuse at least once during their lifetime. Furthermore, using a cross-sectional design, across multiple levels of the socio-ecological model, the individual-level factors of (a) norms for violence for boys against girls, (b) having a current boyfriend/girlfriend, and (c) participation in bullying perpetration were correlates of the perpetration of cyber dating abuse. Collectively, the findings suggest that dating violence interventions targeting these particular correlates in early adolescents are warranted. Future studies are needed to establish causation and to further investigate the relative importance of correlates of the perpetration of cyber dating abuse among early adolescents that have been reported among older adolescents.
Purpose: MET-signaling has been suggested a potential role in malignant peripheral nerve sheath tumors (MPNSTs). Here, MET function and blockade were preclinically assessed. Experimental Design: Expression levels of MET, its ligand HGF, and phosphorylated MET (pMET) were examined in a clinically annotated MPNST tissue microarray incorporating univariable and multivariable statistical analyses. Human MPNST cells were studied in vitro and in vivo; WB and ELISA were used to evaluate MET and HGF expression, activation, and downstream signaling. Cell culture assays tested the impact of HGF-induced MET activation and anti-MET-specific siRNA inhibition on cell proliferation, migration, and invasion; in vivo gelfoam assays were used to evaluate angiogenesis. Cells stably transduced with anti-MET shRNA constructs were tested for growth and metastasis in SCID mice. The effect of the tyrosine kinase inhibitor XL184 (Exelixis) targeting MET/VEGFR2 on local and metastatic MPNST growth was examined in vivo. Results: All three markers were expressed in MPNST human samples; pMET expression was an independent prognosticator of poor patient outcome. Human MPNST cell lines expressed MET, HGF, and pMET. MET activation increased MPNST cell motility, invasion, angiogenesis, and induced MMP2 and VEGF expression; MET knockdown had inverse effects in vitro and markedly decreased local and metastatic growth in vivo. XL184 abrogated human MPNST xenograft growth and metastasis in SCID mice. Conclusions: Informative prognosticators and novel therapies are crucially needed to improve MPNST management and outcomes. We demonstrate an important role for MET in MPNST, supporting continued investigation of novel anti-MET therapies in this clinical context.
Histone deacetylase inhibitors (HDACi) show promise as cancer therapeutics; however, the full scope of their utility remains unknown. Here we report findings that strongly rationalize clinical evaluation of HDACis in malignant peripheral nerve sheath tumors (MPNST), a class of highly aggressive, therapeutically resistant, and commonly fatal malignancies that occur sporadically or in patients with the inherited neurofibromatosis type-1 (NF1) syndrome. We evaluated the effects of the chemical HDACis PCI-24781, suberoylanilide hydroxamic acid, and MS-275 on a panel of human NF1-associated and sporadic MPNSTs in vitro and in vivo. A subset of MPNSTs was found to be highly sensitive to HDACis, especially to PCI-24781. All cell lines in this group were NF1-associated. Significant proapoptotic effects were noted in vitro and in vivo and were independent of p53 mutational status. In contrast, as a group the sporadic -MPNST cells were markedly resistant to HDACi treatment. HDACis were found to induce productive autophagy in MPNST cells. Genetic and/or pharmacologic autophagy blockade resulted in significant HDACi-induced apoptosis in cells defined as resistant or sensitive, leading to abrogated growth of primary tumors and lung metastases in tumor xenograft assays. Among autophagy-associated genes expressed in response to HDACi, the immunity-related GTPase family, M was validated as a critical target in mediating HDACi-induced autophagy and enhanced apoptosis. Taken together, our findings strongly support the evaluation of HDACi currently in clinical trials as an important new therapeutic strategy to treat MPNST, including in combination with autophagy blocking combination regimens in particular for patients with sporadic MPNST. Cancer Res; 71(1); 185-96. Ó2010 AACR.
Objectives. To test the efficacy of Me & You, a multilevel technology-enhanced adolescent dating violence (DV) intervention, in reducing DV perpetration and victimization among ethnic-minority early adolescent youths. We assessed secondary impact for specific DV types and psychosocial outcomes. Methods. We conducted a group-randomized controlled trial of 10 middle schools from a large urban school district in Southeast Texas in 2014 to 2015. We used multilevel regression modeling; the final analytic sample comprised 709 sixth-grade students followed for 1 year. Results. Among the total sample, odds of DV perpetration were lower among intervention students than among control students (adjusted odds ratio = 0.46; 95% confidence interval = 0.28, 0.74). Odds of DV victimization were not significantly different. There were significant effects on some specific DV types. Conclusions. Me & You is effective in reducing DV perpetration and decreasing some forms of DV victimization in early middle-school ethnic-minority students.
Methods Data from a nationally representative sample of 4,069 U.S. veterans in 2019–2020 were used to examine the prevalence of full and subthreshold PTSD in veterans with a history of homelessness; identify characteristics associated with PTSD; examine the proportion of veterans who reported homelessness as an index trauma event and screened positive for PTSD. Results Among veterans with a history of homelessness, lifetime prevalence of full and subthreshold PTSD was 33.0% and 32.0%; and past‐month prevalence of full and subthreshold PTSD was 5.6% and 12.7%. These prevalence estimates were more than five times higher than nonhomeless veterans. Among veterans with a history of homelessness, 14.1% reported that homelessness was their “worst” traumatic event which was associated with a fivefold greater odds of current PTSD and nearly threefold greater odds of subthreshold PTSD even after adjustment for other trauma exposures. Conclusions Veterans who have been homeless have extensive trauma histories and both events that occur during homelessness and the experience of homelessness itself may be traumatic and lead to PTSD, substantiating efforts to provide trauma‐informed care for this population.
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