Global perspectives on CYP2D6 associations with primaquine metabolism and Plasmodium vivax radical cure.

Clinical trial and individual patient treatment outcomes have produced accumulating evidence that effective primaquine (PQ) treatment of Plasmodium vivax and P. ovale liver stage hypnozoites is associated with genetic variation in the human cytochrome P450 gene, CYP2D6. Successful PQ treatment of individual and population-wide infections by the Plasmodium species that generate these dormant liver stage forms is likely to be necessary to reach elimination of malaria caused by these parasites globally. Optimizing safe and effective PQ treatment will require coordination of efforts between the malaria and pharmacogenomics research communities.

CLEC4E (Mincle) genetic variation associates with pulmonary tuberculosis in Guinea-Bissau (West Africa).

Tuberculosis (TB) is the leading cause of death from a single infectious agent. According to the WHO, 85% of cases in 2018 were pulmonary tuberculosis (PTB), making it the most prevalent form of the disease. Although the bacillus responsible for disease, Mycobacterium tuberculosis (MTB), is estimated to infect 1.7 billion people worldwide, only a small portion of those infected (5-10%) will transition into active TB. Because such a small fraction of infected people develop active disease, we hypothesized that underlying host genetic variation associates with developing active pulmonary disease. Variation in CLEC4E has been of interest in previous association studies showing either no effect or protection from PTB. For our study we assessed 60 SNPs in 11 immune genes, including CLEC4E, using a case-control study from Guinea-Bissau. The 289 cases and 322 controls differed in age, sex, and ethnicity all of which were included in adjusted models. Initial association analysis with unadjusted logistic regression revealed putative association with seven SNPs (p < 0.05). All SNPs were then assessed in an adjusted model. Of the six SNPs that remained significant, three of them were assigned to the CLEC4E gene (rs12302046, rs10841847, and rs11046143). Of these, only rs10841847 passed FDR adjustment for multiple testing. Adjusted regression analyses showed that the minor allele at rs10841847 associated with higher risk of developing PTB (OR = 1.55, CI = 1.22-1.96, p-value = 0.00036). Based on these initial association tests, CLEC4E seemed to be the predictor of interest for PTB risk in this population. Haplotype analysis (2-SNP and 3-SNP windows) showed that minor alleles in segments including rs10841847 were the only ones to pass the threshold of global significance, compared to other haplotypes (p-value < 0.05). Linkage disequilibrium patterns showed that rs12302046 is in high LD with rs10841847 (r2 = 0.67), and all other SNPs lost significance when adjusted for rs10841847 effects. These findings indicate that rs10841847 in CLEC4E is the single best predictor of pulmonary tuberculosis risk in our study population. These results provide evidence for the hypothesis that genetic variation of CLEC4E influences risk to TB in Guinea-Bissau.

Faith in Fat: A Multisite Examination of University Students' Perceptions of Fat in the Diet.

Despite recent relaxation of restrictions on dietary fat consumption in dietary guidelines, there remains a collective "fear of fat". This study examined college students' perceptions of health among foods with no fat relative to foods with different types of fats (unsaturated and saturated). Utilizing a multisite approach, this study collected data from college students at six university dining halls throughout the United States. Data were available on 533 students. Participants were 52% male and consisted largely of first-year students (43%). Across three meal types, the no-fat preparation option was chosen 73% of the time, the unsaturated fat option was selected 23% of the time, and the saturated fat option was chosen 4% of the time. Students chose the no-fat option for all meal types 44% of the time. Findings suggest that college students lack knowledge regarding the vital role played by the type and amount of fats within a healthy diet. Nutrition education and food system reforms are needed to help consumers understand that type of fat is more important than total amount of fat. Efforts across various sectors can encourage incorporating, rather than avoiding, fats within healthy dietary patterns.

Enzyme Immobilization and Mediation with Osmium Redox Polymers.

Enzymatic electrodes are becoming increasingly common for energy production and sensing applications. Research over the past several decades has addressed a major issue that can occur when using these biocatalysts, i.e., slow heterogeneous electron transfer, by incorporation of a redox active species to act as an electron shuttle. There are several advantages to immobilizing both the enzyme and mediator at the enzyme surface, including increased electron transfer rates, decreased enzyme leaching, and minimized diffusion limitations. Redox polymers consisting of a redox active center attached to a polymer backbone are a particularly attractive option because they have high self-exchange rates for electron transfer and tunable redox potential. Osmium (Os) polymers are the most well studied of this type of polymer for bioelectrocatalysis. Here, we describe the methods to synthesize one of the most common Os redox polymers and how it can be used to fabricate glucose oxidase electrodes. Procedures are also outlined for evaluating the enzymatic electrodes.