Global health security and universal health coverage: from a marriage of convenience to a strategic, effective partnership.

Global health security and universal health coverage have been frequently considered as "two sides of the same coin". Yet, greater analysis is required as to whether and where these two ideals converge, and what important differences exist. A consequence of ignoring their individual characteristics is to distort global and local health priorities in an effort to streamline policymaking and funding activities. This paper examines the areas of convergence and divergence between global health security and universal health coverage, both conceptually and empirically. We consider analytical concepts of risk and human rights as fundamental to both goals, but also identify differences in priorities between the two ideals. We support the argument that the process of health system strengthening provides the most promising mechanism of benefiting both goals.

Early mitochondrial dysfunction leads to altered redox chemistry underlying pathogenesis of TPI deficiency.

Triose phosphate isomerase (TPI) is responsible for the interconversion of dihydroxyacetone phosphate to glyceraldehyde-3-phosphate in glycolysis. Point mutations in this gene are associated with a glycolytic enzymopathy called TPI deficiency. This study utilizes a Drosophila melanogaster model of TPI deficiency; TPI(sugarkill) is a mutant allele with a missense mutation (M80T) that causes phenotypes similar to human TPI deficiency. In this study, the redox status of TPI(sugarkill) flies was examined and manipulated to provide insight into the pathogenesis of this disease. Our data show that TPI(sugarkill) animals exhibit higher levels of the oxidized forms of NAD(+), NADP(+) and glutathione in an age-dependent manner. Additionally, we demonstrate that mitochondrial redox state is significantly more oxidized in TPI(sugarkill) animals. We hypothesized that TPI(sugarkill) animals may be more sensitive to oxidative stress and that this may underlie the progressive nature of disease pathogenesis. The effect of oxidizing and reducing stressors on behavioral phenotypes of the TPI(sugarkill) animals was tested. As predicted, oxidative stress worsened these phenotypes. Importantly, we discovered that reducing stress improved the behavioral and longevity phenotypes of the mutant organism without having an effect on TPI(sugarkill) protein levels. Overall, these data suggest that reduced activity of TPI leads to an oxidized redox state in these mutants and that the alleviation of this stress using reducing compounds can improve the mutant phenotypes.