A review of treatment programs for offenders with co-occurring addictive and mental disorders: support for booster interventions

Background: Treatment interventions are essential in supporting psychosocial skills, health promotion and successful reintegration to community living for incarcerated persons. Booster interventions are presumed to be important methods for maintaining the effects of treatment effects for persons with addiction and mental disorders, but there has been remarkably little empirical attention to this assumption. Objectives: This review aims are: (1) to describe existing literature on treatment programs for offenders with addiction and mental disorders in the reentry process, and, (2) to add to the literature on this topic by evaluating the impact of booster interventions upon maintenance of treatment effects and outcomes - specifically, a reduction in symptoms, reduced substance abuse, medication adherence, coping, independent functioning and decreased depressive symptoms. Methods: Electronic databases were searched for systematic reviews from January 2004 through January 2014 to include: CINAHL PubMed, and PsycINFO using selected keywords. Inclusion criteria were adult offenders, a treatment intervention in prison, jail, or forensic psychiatric hospital with a reentry focus for offenders with addiction and mental disorder. The AMSTAR was utilized to assess quality of the reviews. Results: Three systematic reviews were identified to examine treatment interventions for offenders with addiction and mental disorders. Little empirical evidence is available to demonstrate the contribution of booster interventions to overall treatment effects among justice-involved persons. Conclusion: Although evidence is not available, clinically it seems reasonable to expect booster interventions for offenders to reinforce treatment gains, strengthen self-care skills, and manage symptoms. Implications: Research designed specifically to study booster interventions are needed. Keywords: offender reentry, correctional institutions, offenders, treatment programs, mental illness, booster program

Measuring Time Costs in Interventions Designed to Reduce Behavior Problems Among Children and Youth

The economic evaluation of psychosocial interventions is a growing area of research. Though time costs are central to the economist’s understanding of social costs, these costs generally have been ignored by prevention scientists. This article highlights the need to measure such costs and then reviews the principles economists use in valuing time. It then considers the specific time costs that often arise in interventions designed to reduce behavior problems among children and youth. These include classroom time devoted to program activities, the time of parents or other caregivers, the time of teachers (outside of the classroom), and the time of volunteers. We consider the economic principles that govern how economists value these inputs and then apply these principles to data from an evaluation of a prominent intervention in the field, the Incredible Years Program. We find that the time costs are potentially rather large and consider the implications for public policy of ignoring them

A Calcium-dependent Tyrosine Kinase Splice Variant in Human Monocytes: ACTIVATION BY A TWO-STAGE PROCESS INVOLVING ADHERENCE AND A SUBSEQUENT INTRACELLULAR SIGNAL

Freshly isolated human monocytes do not express p125(FAK) but upon adherence to substrata activate the highly related calcium-dependent tyrosine kinase (CADTK), also known as Pyk2, CAKbeta, RAFTK, and FAK2. The monocyte CADTK was 5 kDa smaller than protein from epithelial cells; isolation and sequencing of the monocyte CADTK cDNA revealed a predicted 42-amino acid deletion between the two proline-rich domains of the enzyme. The nucleic acid sequence suggests that the deletion is caused by alternative RNA splicing. This species was also found in T and B lymphocytes and appears to be the predominant form of cytoskeletal associated tyrosine kinase in non-neoplastic, circulating, hematopoietic cells. CADTK was not activated when monocytes maintained in suspension were treated with agents that produce an intracellular calcium (thapsigargin) or protein kinase C (phorbol 12-myristate 13-acetate) signal including a chemokine, RANTES, that binds to the HIV co-receptor, CCK5. In contrast, monocyte adherence to tissue culture plastic-stimulated CADTK tyrosine phosphorylation, a process that was enhanced by thapsigargin, phorbol 12-myristate 13-acetate, and RANTES but that was completely blocked by preincubation with cytochalasin D. When compared with plastic, adherence to fibronectin- or collagen-coated surfaces produced only minimal CADTK activation but permitted significant stimulation by added thapsigargin. These data suggest that in a cell type that lacks p125(FAK), CADTK plays an early role in post-adherence signaling. Its activation involves two stages, cytoskeletal engagement, which is permissive, and co-stimulatory signals (calcium or protein kinase C) generated by extensive cell surface engagement, agonists, or inflammatory chemokines

An Intracellular Calcium Signal Activates p70 but Not p90 Ribosomal S6 Kinase in Liver Epithelial Cells

In the rat liver epithelial cell lines GN4 and WB, angiotensin II (Ang II) activates the Gq class of regulatory G-proteins, increasing intracellular calcium, protein kinase C activity, and protein tyrosine phosphorylation. We compared the ability of Ang II and other compounds that increase intracellular calcium (i.e. the calcium ionophore A23187 and thapsigargin) or protein kinase C activity (the phorbol ester 12-O-tetradecanoylphorbol-13-acetate) to activate p70 ribosomal S6 kinase (p70(S6K)) and p90 ribosomal S6 kinase (p90(RSK)). In GN4 cells, increasing intracellular calcium stimulated p70(S6K) activity in a rapamycin- and wortmannin- sensitive manner, but did not affect p90(RSK) activity. In contrast, 12-O-tetradecanoylphorbol-13-acetate strongly activated p90(RSK) but only weakly stimulated p70(S6K). The ability of calcium to activate p70(S6K) was confirmed by blocking the A23187-dependent activation through chelation of extracellular calcium with EGTA; the effect of thapsigargin was inhibited by the cell permeant chelator bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetraacetoxymethyl ester (BAPTA-AM). Similarly, BAPTA-AM prevented the activation of p70(S6K) by Ang II, suggesting that this signal was largely calcium-dependent. In contrast, the Ang II-dependent activation of mitogen-activated protein kinase and p90(RSK) was not inhibited but was enhanced by BAPTA-AM. These results show that in GN4 cells, Ang II selectively activates p70(S6K) through effects on calcium, p90(RSK) through effects on protein kinase C. The activation of p70(S6K) by calcium stimuli or Ang II was independent of calmodulin but correlated well with the activation of the recently identified, nonreceptor calcium-dependent tyrosine kinase (CADTK)/PYK-2. Both calcium- and Ang II-dependent activation of p70(S6K) were attenuated by the tyrosine kinase inhibitor genistein, and activation of p70(S6K) was higher in GN4 than WB cells, correlating with the increased expression and activation of CADTK/PYK-2 in GN4 cells. In summary, these results demonstrate that intracellular calcium selectively activates p70(S6K) in GN4 cells, consistent with increased CADTK/PYK-2 signaling in these cells

Predictors of activity level and retention among African American lay health advisors (LHAs) from The National Witness Project: ...

Background Lay health advisor (LHA) programs are increasingly being implemented in the USA and globally in the context of health promotion and disease prevention. LHAs are effective in addressing health disparities when used to reach medically underserved populations, with strong evidence among African American and Hispanic women. Despite their success and the evidence supporting implementation of LHA programs in community settings, there are tremendous barriers to sustaining LHA programs and little is understood about their implementation and sustainability in “real-world” settings. The purpose of this study was to (1) propose a conceptual framework to investigate factors at individual, social, and organizational levels that impact LHA activity and retention; and (2) use prospective data to investigate the individual, social, and organizational factors that predict activity level and retention among a community-based sample of African American LHAs participating in an effective, evidence-based LHA program (National Witness Project; NWP). Methods Seventy-six LHAs were recruited from eight NWP sites across the USA. Baseline predictor data was collected from LHAs during a telephone questionnaire administered between 2010 and 2011. Outcome data on LHA participation and program activity levels were collected in the fall of 2012 from NWP program directors. Chi-square and ANOVA tests were used to identify differences between retained and completely inactive LHAs, and LHAs with high/moderate vs. low/no activity levels. Multivariable logistic regression models were conducted to identify variables that predicted LHA retention and activity levels. Results In multivariable models, LHAs based at sites with academic partnerships had increased odds of retention and high/moderate activity levels, even after adjusting for baseline LHA activity level. Higher religiosity among LHAs was associated with decreased odds of being highly/moderately active. LHA role clarity and self-efficacy were associated with retention and high/moderate activity in multivariable models unadjusted for baseline LHA activity level. Conclusions Organizational and role-related factors are critical in influencing the retention and activity levels of LHAs. Developing and fostering partnerships with academic institutions will be important strategies to promote successful implementation and sustainability of LHA programs. Clarifying role expectations and building self-efficacy during LHA recruitment and training should be further explored to promote LHA retention and participation

Discovery of Macrocyclic Pyrimidines as MerTK-Specific Inhibitors

Macrocycles have attracted significant attention in drug discovery recently. In fact, a few de novo designed macrocyclic kinase inhibitors are currently in clinical trials with good potency and selectivity for their intended target. In this study, we successfully engaged a structure-based drug design approach to discover macrocyclic pyrimidines as potent Mer tyrosine kinase (MerTK)-specific inhibitors. An enzyme-linked immunosorbent assay (ELISA) in 384-well format was employed to evaluate the inhibitory activity of macrocycles in a cell-based assay assessing tyrosine phosphorylation of MerTK. Through structure-activity relationship (SAR) studies, analogue 11 [UNC2541; (S)-7-amino-N-(4-fluorobenzyl)-8-oxo-2,9,16-triaza-1(2,4)-pyrimidinacyclohexadecaphane-1-carboxamide] was identified as a potent and MerTK-specific inhibitor that exhibits sub-micromolar inhibitory activity in the cell-based ELISA. In addition, an X-ray structure of MerTK protein in complex with 11 was resolved to show that these macrocycles bind in the MerTK ATP pocket