High-Risk Outreach for COVID-19 Mortality Reduction in an Indigenous Community.

Indigenous populations have been disproportionally affected by COVID-19, particularly those in rural and remote locations. Their unique environments and risk factors demand an equally unique public health response. Our rural Native American community experienced one of the highest prevalence outbreaks in the world, and we developed an aggressive management strategy that appears to have had a considerable effect on mortality reduction. The results have implications far beyond pandemic response, and have reframed how our community addresses several complicated health challenges. (Am J Public Health. 2021;111(11):1939-1941. https://doi.org/10.2105/AJPH.2021.306472).

Relationship between membrane physical properties and secretory phospholipase A2 hydrolysis kinetics in S49 cells during ionophore-induced apoptosis.

During apoptosis, changes occur in lymphocyte membranes that render them susceptible to hydrolysis by secretory phospholipase A(2) (sPLA(2)). To study the relevant mechanisms, a simplified model of apoptosis using a calcium ionophore was applied. Kinetic and flow cytometry experiments provided key observations regarding ionophore treatment: the initial rate of hydrolysis was elevated at all enzyme concentrations, the total amount of reaction product was increased fourfold, and adsorption of the enzyme to the membrane surface was unaltered. Analysis of these results suggested that susceptibility during calcium-induced apoptosis is limited by availability of substrate rather than adsorption of enzyme. Fluorescence experiments identified three membrane alterations during apoptosis that might affect substrate access to the sPLA(2) active site. First, intercalation of merocyanine 540 into the membrane was improved, suggesting an increase in lipid spacing. Second, laurdan detected increased solvation of the lower headgroup region of the membrane. Third, the rate at which fluorescent lipids could be removed from the membrane by albumin was enhanced, implying greater vertical mobility of phospholipids. Thus, it is proposed that the membranes of apoptotic cells become susceptible to sPLA(2) through a reduction in lipid-neighbor interactions that facilitates migration of phospholipids into the enzyme active site.