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Minor changes to complex structures can exert major influences on synthesis strategy and functional properties. Here we explore two parallel series of picrotoxinin (PXN, 1) analogs and identify leads with selectivity between mammalian and insect ion channels. These are the first SAR studies of PXN despite its >100-year history and are made possible by advances in total synthesis. We observe a remarkable stabilizing effect of a C5 methyl, which completely blocks C15 alcoholysis via destabilization of an intermediate twist-boat conformer; suppression of this secondary hydrolysis pathway increases half-life in plasma. C5 methylation also decreases potency against vertebrate ion channels (γ-Aminobutyric acid type A (GABAA) receptors) but maintains or increases antagonism of homologous invertebrate GABA-gated chloride channels (resistance to dieldrin (RDL) receptors). Optimal 5MePXN analogs appear to change the PXN binding pose within GABAARs by disruption of a hydrogen bond network. These discoveries were made possible by the lower synthetic burden of 5MePXN (2) and were illuminated by the parallel analog series, which allowed characterization of the role of the synthetically simplifying C5 methyl in channel selectivity. These are the first SAR studies to identify changes to PXN that increase the GABAA-RDL selectivity index. Minor changes to complex structures can exert major influences on synthesis strategy and functional properties but synthetic difficulties can obstruct the exploration of natural product function. Here the authors explore two parallel series of picrotoxinin analogs and identify leads with selectivity between mammalian and insect ion channels. [ABSTRACT FROM AUTHOR]

The State of Tennessee granted appropriations to an urban university in the West Tennessee region to address the needs of at-risk African refugee children and families who have experienced Adverse Childhood Experiences (ACEs). Action oriented research efforts were conducted to address the needs of youth in the local region by developing, implementing, and evaluating a community-based intervention that was not only trauma responsive but culturally competent. The Trauma Healing Club was a treatment package developed and researched for this purpose and offered in an after school support program. This identified intervention utilized an existing evidence-based trauma intervention framework that was adapted to include more culturally responsive processes such as pyramid mentoring and African drumming. This work aimed to evaluate the effectiveness of an integrated trauma-informed practice model for community-based programming and the effectiveness of adapting an existing intervention to better fit the community needs. Results indicated that the adaptation of the trauma-responsive intervention was effective and supportive of the child-participant and his/her family needs –both culturally and as it relates to improved participant functioning post intervention. [ABSTRACT FROM AUTHOR]

This article reports that urban inner-city African American male youth residing in communities of color are at-risk and warrant interventions custom tailored to meet their unique cultural needs. This article describes a promising community and school-based intervention and prevention program utilizing Washington's (J Soc Work Gr 2006:14, ) pyramid mentoring model designed to foster the positive development of this group, prevent violence, and to reduce contacts with the juvenile and criminal justice system. It discusses and presents African drumming, Spir-rhythms as a Afrocentric cultural arts tool to engage, establish rapport, and provide pyramid group mentoring experiences for African American male youth. [ABSTRACT FROM AUTHOR]