The P8 proteoglycolipid complex (P8 PGLC) is a glyconjugate expressed by Leishmania mexicana complex parasites. We previously have shown that vaccination with P8 PGLC provides protection against cutaneous leishmaniasis in susceptible BALB/c mice. However, the biological importance of this complex remains unknown. Here we show that P8 PGLC localizes to the surface of Leishmania pifanoi amastigotes and that upon exposure to macrophages, P8 PGLC binds and induces inflammatory cytokine and chemokine mRNAs such as tumor necrosis factor alpha and RANTES early after stimulation. Our studies indicate that cytokine and chemokine induction is dependent upon Toll-like receptor 4 (TLR4). Interestingly, key inflammatory cytokines and chemokines (such as interleukin-6 [IL-6], macrophage inflammatory protein 1␤, and beta interferon [IFN-␤]) that can be induced through TLR4 activation were not induced or only slightly upregulated by P8 PGLC. Activation by P8 PGLC does not occur in the presence of TLR4 alone and requires both CD14 and myeloid differentiation protein 2 for signaling; this requirement may be responsible for the limited TLR4 response. This is the first characterization of a TLR4 ligand for Leishmania. In vitro experiments indicate that L. pifanoi amastigotes induce lower levels of cytokines in macrophages in the absence of TLR4; however, notably higher IL-10/IFN-␥ ratios were found for TLR4-deficient mice than for BALB/c mice. Further, increased levels of parasites persist in BALB/c mice deficient in TLR4. Taken together, these results suggest that TLR4 recognition of Leishmania pifanoi amastigotes is important for the control of infection and that this is mediated, in part, through the P8 PGLC.

One of the major problems facing Nigeria's vaccine supply chain is the lack of adequate vaccine storage facilities. Despite the introduction of solar-powered refrigerators and the use of new tools to monitor supply levels, this problem persists. Using data on vaccine supply for 2011-14 from Nigeria's National Primary Health Care Development Agency, we created a simulation model to explore the effects of variance in supply and demand on storage capacity requirements. We focused on the segment of the supply chain that moves vaccines inside Nigeria. Our findings suggest that 55 percent more vaccine storage capacity is needed than is currently available. We found that reorganizing the supply chain as proposed by the National Primary Health Care Development Agency could reduce that need to 30 percent more storage. Storage requirements varied by region of the country and vaccine type. The Nigerian government may want to consider the differences in storage requirements by region and vaccine type in its proposed reorganization efforts.

Few studies have examined the relationship between education and diabetes among men in the United States and whether this relationship differs by race/ethnicity. This study examined whether racial disparities in diabetes existed by educational attainment in 336,746 non-Hispanic White, non-Hispanic Black, and Hispanic men 18 years of age and older in the United States. Logistic regression models were specified to examine the odds of reporting diabetes by educational attainment. Within race/ethnicity, both White and Hispanic men who had less than a high school education (odds ratio [OR] = 1.42, 95% confidence interval [CI] = [1.19, 1.69], and OR = 1.64, 95% CI = [1.22, 2.21], respectively) had consistently higher odds of diabetes than men with a bachelor’s degree or higher level of educational attainment. Educational attainment did not appear to be associated with reporting a diagnosis of diabetes in non-Hispanic Black men. Identifying why educational attainment is associated with diabetes outcomes in some racial/ethnic groups but not others is essential for diabetes treatment and management.

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