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Objective: Early prostate cancer micrometastatic foci undergo a mesenchymal to epithelial reverting transition, not only aiding seeding and colonization, but also rendering the tumor cells generally chemoresistant. We previously found that upregulated E-cadherin in the epithelial micrometastases activated canonical survival pathways, including PI3K-Akt, that protected the tumor cells from death; however, the extent of protection from blocking the pathway in its entirety was modest, because different isoforms may have alternately affected cell functioning. Here, we characterized Akt isoform expressions in primary and metastatic prostate cancers, as well as their individual contributions to chemoresistance., Methods: Akt isoforms and E-cadherin were manipulated with drugs, knocked down, and over expressed. Tumor cell killing was determined in vitro and in vivo . Overall survival was calculated from patient records and specimens., Results: Pan-Akt inhibition sensitized tumor cells to chemotherapy, and specific blockade of Akt1 or/and Akt2 caused cells to be more chemoresponsive. Overexpression of Akt3 induced apoptosis. A low dose of Akt1 or Akt2 inhibitor enabled standard chemotherapies to significantly eradicate metastatic prostate tumors in a mouse model, acting as chemosensitizers. In human specimens, we found Akt1 and Akt2 positively correlated, whereas Akt3 inversely correlated, with the overall survival of prostate cancer patients. Akt1high/Akt2high/Akt3low tumors had the worst outcomes., Conclusions: E-cadherin-induced activation of Akt1/2 isoforms was the essential mechanism of chemoresistance, whereas Akt3 made cells more fragile. These findings emphasized the need to target Akt1/2, rather than pan-Akt, as a rational therapeutic approach., Competing Interests: No potential conflicts of interest are disclosed., (Copyright © 2021 Cancer Biology & Medicine.)

A systematic review was conducted to identify determinants (barriers and facilitators) of implementing evidence-based psychosocial interventions for children and youth who experience emotional or behavioral difficulties due to trauma exposure. Determinants were coded, abstracted, and synthesized using the Exploration, Preparation, Implementation, and Sustainment framework. Twenty-three articles were included, all of which examined implementation of Trauma-Focused Cognitive Behavioral Therapy or Cognitive-Behavioral Intervention for Trauma in Schools. This review identified multilevel and multiphase determinants that can be addressed by implementation strategies to improve implementation and clinical outcomes, and suggests how future studies might address gaps in the evidence base.

Background: Adolescents involved with child welfare system are disproportionately at risk for underage drinking. Little empirical evidence has informed interventions targeting child welfare caregivers to prevent alcohol consumption among adolescents involved with the system., Methods: The present study addressed this gap by examining modifiable caregiver characteristics most predictive of future underage drinking in a cohort of adolescents (N = 1205) in a nationally representative child welfare dataset. We used dominance analyses to examine direct contributions of each caregiver predictor to the overall variance of future alcohol use. This is the first study to apply the reputable Turrisi and Jaccard (2001) framework of familial processes affecting underage drinking to the child welfare population., Results: Findings highlight the role of caregiver-adolescent relational quality and communications for predicting underage alcohol use, and downplay the role of caregiver monitoring., Conclusions: Child welfare service systems may help prevent underage drinking by systematically training and motivating caregivers to foster trusting, helping relationships and regular communications with the adolescents in their care., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In generalizability theory (G theory), one-facet models are specified to be additive, which is equivalent to the assumption that subject-by-facet interaction effects are absent. In this article, the authors first derive estimators of variance components (VCs) for nonadditive models and show that, in some cases, they are different from their counterparts in additive models. The authors then demonstrate and later confirm with a simulation study that when the subject-by-facet interaction exists, but the additive-model formulas are used, the VC of subjects is underestimated. Consequently, generalizability coefficients are also underestimated. Thus, depending on the nature of interaction effects, an appropriate model, either additive or nonadditive, should be used in applications of G theory. The nonadditive G theory developed in this article generalizes current G theory and uses data at hand to determine when additive or nonadditive models should be used to estimate VCs. Finally, the implications of the findings are discussed in light of an analysis of real data., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

It has been suggested that cannabinoid agonists increase dopamine (DA) transmission in the mesolimbic dopamine system. However, evidence for such an effect is inconsistent. Prepulse inhibition (PPI) of the acoustic startle reflex is a behavioural paradigm that is modulated by an increase of mesolimbic dopamine. This study sought to ascertain whether or not a cannabinoid agonist, CP 55,940, mimicked the effects of amphetamine (a drug which increases dopamine release) on PPI. The first experiment measured the PPI of 16 male Wistar rats injected (i.p.) with different doses of CP 55,940 in a Latin-square design. A second experiment replicated the effects of the first experiment in a between-subjects design, and also examined the effects of using a 5% alcohol solution as a solvent for cannabinoid agonists, in comparison to the more inert detergent, Tween 80. In both experiments, CP 55,940 in Tween 80 significantly reduced basal activity, increased startle onset latencies and increased PPI, effects opposite to those of amphetamine. These results suggest that the net behavioural effects of cannabinoids are opposite to those of amphetamine. In addition, it was found that 1 ml/kg of a 5% alcohol solution has significant behavioural effects on its own, and reverses the effects of CP 55,940 on PPI.

Primary Objective: Evaluate the effects of a point-of-dispensing (POD) pharmaceutical care model on outcomes of self-monitored blood glucose (SMBG) results, SMBG frequency, and medication adherence rates for patients with diabetes., Secondary Objective: Measure the rate at which physicians implemented therapy recommendations made by community pharmacists., Design: 12-month, noncrossover, single-group trial., Setting: Two independent community pharmacies in Richmond, Va., Patients: 101 patients were initially identified as potential participants; of the 82 that elected to participate in the study, 62 (76%) completed the first 6 months and 52 (63%) completed the entire 12-month study period., Intervention: This pharmaceutical care program was integrated into the dispensing function: subjective and objective data related to diabetes care were gathered with each prescription refill. Recommendations were made to patients and their physicians., Main Outcome Measures: SMBG values and frequency at baseline, 6, and 12 months. Diabetic medication adherence rates for 1 year before and during participation were evaluated. Community pharmacist recommendations and implementation status were followed over the 12-month period., Results: Average morning blood glucose values (n = 27) decreased from 178.6 mg/dL to 159.3 mg/dL, from baseline to 6 months, respectively (p = .07). Blood glucose values (n = 23) at baseline and 12 months decreased from 179.0 mg/dL to 149.7 mg/dL, respectively (p < .05). There was no statistical difference in SMBG frequency. A diabetes medication adherence rate of 90% was maintained over the 12-month study period. Physicians implemented 15 of 20 (75%) recommendations., Conclusion: This model offers an effective and efficient mechanism for providing pharmaceutical care for patients with diabetes.