ABSTRACT
Despite high rates of intimate partner violence (IPV) among teens who are pregnant or parenting, the field is lacking evidence-based prevention programs designed for this population. The purpose of this study was to comprehensively adapt the evidence-based Safe Dates IPV prevention program and conduct a pilot study of the adapted program with female teens who were pregnant or parenting. We completed formative research including a literature review, focus groups, and pre-testing of adapted content to inform the revised curriculum. We then conducted a randomized controlled trial with 32 teens (average age = 17) to compare the adapted program to the original program on implementation characteristics and outcomes, including IPV perpetration and victimization. Directions of effect favored the adapted program over the original program for 18 out of 21 implementation outcomes for which models could be estimated and for 11 of 12 participant outcomes. The strongest effects, all favoring the adapted program, were found for observer-reported adherence to the curriculum, participant ratings of the relevance of characters and scenarios, participant knowledge of ways to get help for abuse, and attitudes toward IPV. These findings demonstrate the feasibility and acceptability of the adapted program for this target population and suggest that the program may be efficacious when evaluated in a larger study.
ABSTRACT
High-dose chemotherapy regimens using cyclophosphamide (CY) are frequently associated with cardiotoxicity that could lead to myocyte damage and congestive heart failure. However, the mechanisms regulating the cardiotoxic effects of CY remain unclear. Because CY is converted to an unsaturated aldehyde acrolein, a toxic, reactive CY metabolite that induces extensive protein modification and myocardial injury, we examined the role of glutathione S-transferase P (GSTP), an acrolein-metabolizing enzyme, in CY cardiotoxicity in wild-type (WT) and GSTP-null mice. Treatment with CY (100-300 mg/kg) increased plasma levels of creatine kinase-MB isoform (CK · MB) and heart-to-body weight ratio to a significantly greater extent in GSTP-null than WT mice. In addition to modest yet significant echocardiographic changes following acute CY-treatment, GSTP insufficiency was associated with greater phosphorylation of c-Jun and p38 as well as greater accumulation of albumin and protein-acrolein adducts in the heart. Mass spectrometric analysis revealed likely prominent modification of albumin, kallikrein-1-related peptidase, myoglobin and transgelin-2 by acrolein in the hearts of CY-treated mice. Treatment with acrolein (low dose, 1-5 mg/kg) also led to increased heart-to-body weight ratio and myocardial contractility changes. Acrolein induced similar hypotension in GSTP-null and WT mice. GSTP-null mice also were more susceptible than WT mice to mortality associated with high-dose acrolein (10-20 mg/kg). Collectively, these results suggest that CY cardiotoxicity is regulated, in part, by GSTP, which prevents CY toxicity by detoxifying acrolein. Thus, humans with low cardiac GSTP levels or polymorphic forms of GSTP with low acrolein-metabolizing capacity may be more sensitive to CY toxicity.
