Long-Term Effects From A School-Based Trial Comparing Interpersonal Psychotherapy-Adolescent Skills Training To Group Counseling

Adolescence represents a vulnerable developmental period for depression and an opportune time for prevention efforts. In this study, 186 adolescents with elevated depressive symptoms (M age = 14.01, SD = 1.22; 66.7% female; 32.2% racial minority) were randomized to receive either Interpersonal Psychotherapy–Adolescent Skills Training (IPT-AST; n = 95) delivered by research clinicians or group counseling (GC; n = 91) delivered by school counselors. We previously reported the short-term outcomes of this school-based randomized controlled trial: IPT-AST youth experienced significantly greater improvements in depressive symptoms and overall functioning through 6-month follow-up. Here, we present the long-term outcomes through 24 months postintervention. We examined differences in rates of change in depressive symptoms and overall functioning and differences in rates of depression diagnoses. Youth in both conditions showed significant improvements in depressive symptoms and overall functioning from baseline to 24-month follow-up, demonstrating the efficacy of school-based depression prevention programs. However, the two groups did not differ in overall rates of change or in rates of depression diagnoses from baseline to 24-month follow-up. Although IPT-AST demonstrated advantages over GC in the short term, these effects dissipated over long-term follow-up. Specifically, from 6- to 24-month follow-up, GC youth showed continued decreases in depressive symptoms, whereas IPT-AST youth showed a nonsignificant increase in symptoms. GC youth remained relatively stable in overall functioning, whereas IPT-AST youth experienced a small but statistically significant worsening in functioning. This study highlights the potential of school-based depression prevention efforts and the need for further research

Genomic profiling reveals the potential role of TCL1A and MDR1 Deficiency in chemotherapy-induced cardiotoxicity

Background: Anthracyclines, such as doxorubicin (Adriamycin), are highly effective chemotherapeutic agents, but are well known to cause myocardial dysfunction and life-threatening congestive heart failure (CHF) in some patients. Methods: To generate new hypotheses about its etiology, genome-wide transcript analysis was performed on whole blood RNA from women that received doxorubicin-based chemotherapy and either did, or did not develop CHF, as defined by ejection fractions (EF)≤40%. Women with non-ischemic cardiomyopathy unrelated to chemotherapy were compared to breast cancer patients prior to chemo with normal EF to identify heart failure-related transcripts in women not receiving chemotherapy. Byproducts of oxidative stress in plasma were measured in a subset of patients. Results: The results indicate that patients treated with doxorubicin showed sustained elevations in oxidative byproducts in plasma. At the RNA level, women who exhibited low EFs after chemotherapy had 260 transcripts that differed \u3e2-fold (pIn vitro studies confirmed that inhibition of MDR1 by verapamil in rat H9C2 cardiomyocytes increased their susceptibility to doxorubicin-induced toxicity. Conclusions: It is proposed that chemo-induced cardiomyopathy may be due to a reduction in TCL1A levels, thereby causing increased apoptotic sensitivity, and leading to reduced cardiac MDR1 levels, causing higher cardiac levels of doxorubicin and intracellular free radicals. If so, screening for TCL1A and MDR1 SNPs or expression level in blood, might identify women at greatest risk of chemo-induced heart failure

Non-monotonic variation with salt concentration of the second virial coefficient in protein solutions

The osmotic virial coefficient $B_2$ of globular protein solutions is calculated as a function of added salt concentration at fixed pH by computer simulations of the ``primitive model''. The salt and counter-ions as well as a discrete charge pattern on the protein surface are explicitly incorporated. For parameters roughly corresponding to lysozyme, we find that $B_2$ first decreases with added salt concentration up to a threshold concentration, then increases to a maximum, and then decreases again upon further raising the ionic strength. Our studies demonstrate that the existence of a discrete charge pattern on the protein surface profoundly influences the effective interactions and that non-linear Poisson Boltzmann and Derjaguin-Landau-Verwey-Overbeek (DLVO) theory fail for large ionic strength. The observed non-monotonicity of $B_2$ is compared to experiments. Implications for protein crystallization are discussed.Comment: 43 pages, including 17 figure

Adsorption of mono- and multivalent cat- and anions on DNA molecules

Adsorption of monovalent and multivalent cat- and anions on a deoxyribose nucleic acid (DNA) molecule from a salt solution is investigated by computer simulation. The ions are modelled as charged hard spheres, the DNA molecule as a point charge pattern following the double-helical phosphate strands. The geometrical shape of the DNA molecules is modelled on different levels ranging from a simple cylindrical shape to structured models which include the major and minor grooves between the phosphate strands. The densities of the ions adsorbed on the phosphate strands, in the major and in the minor grooves are calculated. First, we find that the adsorption pattern on the DNA surface depends strongly on its geometrical shape: counterions adsorb preferentially along the phosphate strands for a cylindrical model shape, but in the minor groove for a geometrically structured model. Second, we find that an addition of monovalent salt ions results in an increase of the charge density in the minor groove while the total charge density of ions adsorbed in the major groove stays unchanged. The adsorbed ion densities are highly structured along the minor groove while they are almost smeared along the major groove. Furthermore, for a fixed amount of added salt, the major groove cationic charge is independent on the counterion valency. For increasing salt concentration the major groove is neutralized while the total charge adsorbed in the minor groove is constant. DNA overcharging is detected for multivalent salt. Simulations for a larger ion radii, which mimic the effect of the ion hydration, indicate an increased adsorbtion of cations in the major groove.Comment: 34 pages with 14 figure

Pain coping skills training for African Americans with osteoarthritis (STAART): study protocol of a randomized controlled trial

Background: African Americans bear a disproportionate burden of osteoarthritis (OA), with higher prevalence rates, more severe pain, and more functional limitations. One key barrier to addressing these disparities has been limited engagement of African Americans in the development and evaluation of behavioral interventions for management of OA. Pain Coping Skills Training (CST) is a cognitive-behavioral intervention with shown efficacy to improve OA-related pain and other outcomes. Emerging data indicate pain CST may be a promising intervention for reducing racial disparities in OA symptom severity. However, there are important gaps in this research, including incorporation of stakeholder perspectives (e.g. cultural appropriateness, strategies for implementation into clinical practice) and testing pain CST specifically among African Americans with OA. This study will evaluate the effectiveness of a culturally enhanced pain CST program among African Americans with OA. Methods/Design: This is a randomized controlled trial among 248 participants with symptomatic hip or knee OA, with equal allocation to a pain CST group and a wait list (WL) control group. The pain CST program incorporated feedback from patients and other stakeholders and involves 11 weekly telephone-based sessions. Outcomes are assessed at baseline, 12 weeks (primary time point), and 36 weeks (to assess maintenance of treatment effects). The primary outcome is the Western Ontario and McMaster Universities Osteoarthritis Index, and secondary outcomes include self-efficacy, pain coping, pain interference, quality of life, depressive symptoms, and global assessment of change. Linear mixed models will be used to compare the pain CST group to the WL control group and explore whether participant characteristics are associated with differential improvement in the pain CST program. This research is in compliance with the Helsinki Declaration and was approved by the Institutional Review Boards of the University of North Carolina at Chapel Hill, Durham Veterans Affairs Medical Center, East Carolina University, and Duke University Health System. Discussion: This culturally enhanced pain CST program could have a substantial impact on outcomes for African Americans with OA and may be a key strategy in the reduction of racial health disparities.Funded by Patient-Centered Outcomes Research Institute (PCORI) Award (AD-1408-19519)

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