Does a Crossover Age Effect Exist for African American and Hispanic Binge Drinkers? Findings from the 2010 to 2013 National Study on Drug Use and Health.

BACKGROUND: Among general population studies, lower rates of binge drinking tend to be found among African Americans and Hispanics compared to Whites. However, among older adult populations, minority groups have been shown to be at higher risk for binge drinking, suggesting the presence of a crossover effect from low to high risk as a function of age. To date, limited research has examined the crossover effect among African American and Hispanic populations compared to non-Hispanic Whites across large developmental time frames or explored variation in risk based on income or gender. This study aimed to fill these gaps in the literature. METHODS: Data were compiled from the 2010 to 2013 National Survey on Drug Use and Health surveys, which provide annual, nationally representative data on substance use behaviors among individuals aged 12 and older. Hispanic, non-Hispanic African American, and non-Hispanic White respondents were included (N = 205,198) in the analyses. RESULTS: A crossover effect was found for African American males and females among the lowest income level (i.e., incomes less than $20,000). Specifically, after controlling for education and marital status, compared to Whites, risk for binge drinking was lower for African American males at ages 18 to 24 and for females at ages 18 to 34, but higher for both African American males and females at ages 50 to 64. No crossover effect was found for Hispanic respondents. CONCLUSIONS: Although African Americans are generally at lower risk for binge drinking, risk appears to increase disproportionately with age among those who are impoverished. Explanatory factors, such as social determinants of health prevalent within low-income African American communities (e.g., lower education, violence exposure, housing insecurity) and potential areas for intervention programming are discussed.

Examining Risk for Frequent Cocaine Use: Focus on an African American Treatment Population.

BACKGROUND: Cocaine use and its consequences are disproportionately higher and more severe among African Americans compared to other ethnic/racial groups. OBJECTIVES: The aims of this study were to examine a risk model specific for African American users and assess whether risk varies as a function of sex. METHODS: 270 African American adults in a residential drug treatment facility completed measurements assessing first and past year crack/cocaine use frequency, childhood trauma, and stress reactivity. Multiple linear regression analysis was used to examine the unique effect of each predictor variable on past year crack/cocaine frequency. Sex was included as a moderator variable in the regression analysis. RESULTS: All predictor variables were positively correlated with past year crack/cocaine use. However, sex differences were also observed: females reported higher rates of childhood emotional abuse, childhood sexual abuse, and stress reactivity-as well as past year crack use and cocaine use-than males. Regression analyses were performed with sex, first year use, and stress reactivity emerging as the only significant predictors for frequency of crack and cocaine use among all study participants. Moreover, sex differences were observed in the influence of first year crack use frequency on past year crack use frequency, such that the effect was stronger for males than for females. Conclusion/Importance: This study offers a clearer understanding of the risk factors for crack and cocaine abuse specific to African Americans, as well as sex specific pathways to risk, providing useful implications for future prevention and treatment efforts.

A randomized controlled trial of the community-friendly health recovery program (CHRP) among high-risk drug users in treatment.

Existing evidence-based HIV risk reduction interventions have not been designed for implementation within clinical settings, such as methadone maintenance programs, where many high-risk drug users seek treatment services. We therefore systematically developed an adapted, significantly shortened, version of a comprehensive evidence-based intervention called the Community-friendly Health Recovery Program (CHRP) which has demonstrated preliminary evidence of efficacy in a feasibility/acceptability study already published. In a randomized controlled trial reported here, we tested the efficacy of the CHRP intervention among high-risk drug users newly enrolled in drug treatment at an inner-city methadone maintenance program. The CHRP intervention produced improvements in drug risk reduction knowledge as well as demonstrated sex- and drug-risk reduction skills. Support was found for the IMB model of health behavior change. Implications for future intervention research and practice are considered.

Relative influence of landscape vs. local factors on plant community assembly in restored wetlands.

Ecological restoration often involves only the manipulation of abiotic factors at the local scale. However, processes external to a restoration site determine the range of local conditions within the site, constraining the level of restoration progress that can be achieved by on-site manipulations. We examined the relationship of landscape and local explanatory variables to plant species composition in 28 restored wetlands in Illinois, USA. Using constrained ordination combined with variation partitioning, we determined the independent and joint effects of three spatially hierarchical sets of variables: (1) macroscale landscape features reflecting site setting within regional landscapes, (2) mesoscale landscape features reflecting nearby propagule sources and buffers from disturbances, and (3) local environmental factors. Because the relative influence of landscape- vs. local-scale factors on restoration success may depend on particular restoration goals, we repeated the analyses using three multivariate plant community responses that represented three frequently stated goals: (1) replicating species composition, (2) restoring a particular wetland community type, and (3) constructing sites with high value for plant conservation. Explanatory variables at landscape and local scales had independent and nearly equally strong relationships to plant species composition. In contrast, when species were aggregated based on plant traits, the independent contribution of local predictors was greater than the independent contributions of macroscale or mesoscale landscape predictors, reflecting convergence of plant trait composition in sites with similar local conditions. Local predictors explained a significant amount of variation in plant conservation value among sites, but much of the variation could be explained by large-scale landscape setting, indicating that landscape constraints on local environmental conditions limited the level of floristic conservation value achievable. The appropriate scale at which to focus restoration efforts will vary depending upon restoration objectives. Restoration of particular wetland community types might be successfully achieved through manipulation of local abiotic factors. In contrast, restoration of a particular species assemblage or reconstruction of wetlands with high value for conservation requires consideration of landscape processes and available species pools.

Concurrent Inhibition of Pim and FLT3 Kinases Enhances Apoptosis of FLT3-ITD Acute Myeloid Leukemia Cells through Increased Mcl-1 Proteasomal Degradation.

Purpose:fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) is present in 30% of acute myeloid leukemia (AML), and these patients have short disease-free survival. FLT3 inhibitors have limited and transient clinical activity, and concurrent treatment with inhibitors of parallel or downstream signaling may improve responses. The oncogenic serine/threonine kinase Pim-1 is upregulated downstream of FLT3-ITD and also promotes its signaling in a positive feedback loop, suggesting benefit of combined Pim and FLT3 inhibition.Experimental Design: Combinations of clinically active Pim and FLT3 inhibitors were studied in vitro and in vivoResults: Concurrent treatment with the pan-Pim inhibitor AZD1208 and FLT3 inhibitors at clinically applicable concentrations abrogated in vitro growth of FLT3-ITD, but not wild-type FLT3 (FLT3-WT), cell lines. AZD1208 cotreatment increased FLT3 inhibitor-induced apoptosis of FLT3-ITD, but not FLT3-WT, cells measured by sub-G1 fraction, annexin V labeling, mitochondrial membrane potential, and PARP and caspase-3 cleavage. Concurrent treatment with AZD1208 and the FLT3 inhibitor quizartinib decreased growth of MV4-11 cells, with FLT3-ITD, in mouse xenografts, and prolonged survival, enhanced apoptosis of FLT3-ITD primary AML blasts, but not FLT3-WT blasts or remission marrow cells, and decreased FLT3-ITD AML blast colony formation. Mechanistically, AZD1208 and quizartinib cotreatment decreased expression of the antiapoptotic protein Mcl-1. Decrease in Mcl-1 protein expression was abrogated by treatment with the proteasome inhibitor MG132, and was preceded by downregulation of the Mcl-1 deubiquitinase USP9X, a novel mechanism of Mcl-1 regulation in AML.Conclusions: The data support clinical testing of Pim and FLT3 inhibitor combination therapy for FLT3-ITD AML. Clin Cancer Res; 24(1); 234-47. ©2017 AACR.

Monocarbonyl analogs of curcumin inhibit growth of antibiotic sensitive and resistant strains of Mycobacterium tuberculosis.

Tuberculosis (TB) is a major public health concern worldwide with over 2 billion people currently infected. The rise of strains of Mycobacterium tuberculosis (Mtb) that are resistant to some or all first and second line antibiotics, including multidrug-resistant (MDR), extensively drug resistant (XDR) and totally drug resistant (TDR) strains, is of particular concern and new anti-TB drugs are urgently needed. Curcumin, a natural product used in traditional medicine in India, exhibits anti-microbial activity that includes Mtb, however it is relatively unstable and suffers from poor bioavailability. To improve activity and bioavailability, mono-carbonyl analogs of curcumin were synthesized and screened for their capacity to inhibit the growth of Mtb and the related Mycobacterium marinum (Mm). Using disk diffusion and liquid culture assays, we found several analogs that inhibit in vitro growth of Mm and Mtb, including rifampicin-resistant strains. Structure activity analysis of the analogs indicated that Michael acceptor properties are critical for inhibitory activity. However, no synergistic effects were evident between the monocarbonyl analogs and rifampicin on inhibiting growth. Together, these data provide a structural basis for the development of analogs of curcumin with pronounced anti-mycobacterial activity and provide a roadmap to develop additional structural analogs that exhibit more favorable interactions with other anti-TB drugs.

The Age of Initiation of Drug Use and Sexual Behavior May Influence Subsequent HIV Risk Behavior: A Systematic Review.

Researchers examining injection drug users (IDUs) in drug treatment have been trying for decades to determine the optimal way to intervene to prevent the transmission and spread of human immunodeficiency virus (HIV) in this population. Although efficacious HIV risk reduction interventions are widely available, questions remain about what specific factors are most related to HIV risk behavior and defined as unprotected sexual activity and/or high risk drug use. This review involved an evaluation of the research literature in order to better understand the association between drug use and sexual behavior debut on HIV risk behavior. Findings suggest that drug use debut and sexual behavior debut may be related to subsequent HIV risk behavior. Evidence to date implies that intervening at an earlier age to assist youth to avoid or delay these high risk behaviors may be an additional means of reducing subsequent HIV risk.