C5 methylation confers accessibility, stability and selectivity to picrotoxinin.

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.

Trauma Healing Club: Utilizing Culturally Responsive Processes in the Implementation of an After-School Group Intervention to Address Trauma Among African Refugees.

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.

Perceptions of emotional and physical wellness among African American men as predictors of perceived overall health.

African American are at risk for adverse emotional health. However, due to the intersection of their racial and gender identities which heightens their masculinity, emotional wellness is not always considered a priority by and for these men. This study aimed to examine African American men's emotional and physical health in relation to their overall health. An exploratory cross-sectional study was conducted to examine self-reported responses regarding emotional and physical health as predictors of overall wellness among a convenience sample of 115 African American men. The Wellness Self-Perception Questionnaire (WSPQ), a 15-item scale, was used to assess emotional and physical wellness. Overall health was assessed by a single item.Of the 115 study participants, the majority reported a positive perception of their overall health. Linear regression analyses revealed that both reported emotional wellness and physical wellness predicted better overall wellness, even when controlling for men's education and income. A review of the literature indicates this is the first study to assess emotional and physical wellness as predictors of overall health for African American men. Since African American men tend to utilize physical health services even for mental health concerns, implications for physicians are also discussed.