A Meta-analysis on the Effectiveness of Trauma-informed Practice

This study looked at past research on trauma informed practice to analyze its effectiveness.. There is sufficient research portraying the helpfulness of the trauma-informed approach; however, there is little research on whether it is effective as a theoretical intervention. The study looked at how different trauma-informed interventions have helped in diminishing the effect of trauma on different populations. The populations considered in the analysis include: women that have experienced domestic violence, children, individuals with Post-Traumatic Stress Disorder (PTSD), and youth that reside in neighborhoods with high levels of crime. Since trauma-informed care is currently considered a broad theoretical framework for practice, with this meta-analysis, we aim to establish it as a concrete evidence-based practice

Pharmacokinetics and pharmacodynamics of orally administered acetylenic tricyclic <i>bis</i>(cyanoenone), a highly potent Nrf2 activator with a reversible covalent mode of action

AbstractThe acetylenic tricyclic bis(cyanoenone) TBE-31 is a highly potent cysteine targeting compound with a reversible covalent mode of action; its best-characterized target being Kelch-like ECH-associated protein-1 (Keap1), the cellular sensor for oxidants and electrophiles. TBE-31 reacts with cysteines of Keap1, impairing its ability to target nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) for degradation. Consequently, Nrf2 accumulates and orchestrates cytoprotective gene expression. In this study we investigated the pharmacokinetic and pharmacodynamic properties of TBE-31 in C57BL/6 mice. After a single oral dose of 10 μmol/kg (∼200 nmol/animal), the concentration of TBE-31 in blood exhibited two peaks, at 22.3 nM and at 15.5 nM, 40 min and 4 h after dosing, respectively, as determined by a quantitative stable isotope dilution LC-MS/MS method. The AUC0–24h was 195.5 h/nmol/l, the terminal elimination half-life was 10.2 h, and the kel was 0.068 h−1. To assess the pharmacodynamics of Nrf2 activation by TBE-31, we determined the enzyme activity of its prototypic target, NAD(P)H:quinone oxidoreductase 1 (NQO1) and found it elevated by 2.4- and 1.5-fold in liver and heart, respectively. Continuous feeding for 18 days with diet delivering the same daily doses of TBE-31 under conditions of concurrent treatment with the immunosuppressive agent azathioprine had a similar effect on Nrf2 activation without any indications of toxicity. Together with previous reports showing the cytoprotective effects of TBE-31 in animal models of carcinogenesis, our results demonstrate the high potency, efficacy and suitability for chronic administration of cysteine targeting reversible covalent drugs