SUMMARYPhagocytic cell NADPH oxidase (NOX) generates reactive oxygen species (ROS) as part of innate immunity. Unfortunately, ischemia can also induce this pathway and inflict damage on native cells. Here we show that NOX–mediated damage can be inhibited by suppression of the voltage-gated proton channel, Hv1. Hv1 is required for full NOX activity since it compensates for loss of NOX–exported charge. We show that Hv1 is required for NOX–dependent ROS generation in brain microglia in situ and in vivo. Mouse and human brain microglia, but not neurons or astrocytes, express large Hv1-mediated currents. Mice lacking Hv1 were protected from NOX–mediated neuronal death and brain damage 24 hours after stroke. These results demonstrate that Hv1–dependent ROS production is responsible for a significant fraction of brain damage at early time points after ischemic stroke and provide a rationale for Hv1 as a therapeutic target for the treatment of ischemic stroke.

Maternal midgestation vitamin D deficiency was associated with increased risk of severe preeclampsia. Vitamin D deficiency may be a modifiable risk factor for severe preeclampsia.

Background Vitamin D deficiency may contribute to impaired glucose metabolism. There are sparse data regarding vitamin D and the development of gestational diabetes (GDM). The objective of this study was to assess if first-trimester vitamin D deficiency is more prevalent in women later diagnosed with GDM compared with women with uncomplicated pregnancies. Methods We conducted a nested case-control study of pregnant women who had previously given blood for routine genetic multiple marker screening and subsequently delivered at a tertiary hospital between November 2004 and July 2009. From an overall cohort of 4225 women, 60 cases of GDM were matched by race/ethnicity with 120 women delivering at term (≥37 weeks) with uncomplicated pregnancies. Banked maternal serum was used to measure maternal 25-hydroxyvitamin D [25(OH)D]. Results The prevalence of first-trimester maternal vitamin D deficiency (defined as 25(OH)D <50 nmol/L) was comparable among women with GDM compared with controls (5/60 vs 8/120, p = 0.90). The median 25(OH)D level for all subjects was 89 nmol/L (interquartile range, 73–106 nmol/L). Seventy three percent (117/160) of the cohort had 25(OH)D levels ≥75 nmol/L. Conclusions In a cohort of pregnant women with mostly sufficient levels of serum 25(OH)D, vitamin D deficiency was not associated with GDM. Further studies are warranted with larger cohorts, especially in populations with lower levels of vitamin D.

Masters athletic records in track and field events, published in September 1999, were analyzed to evaluate the percentage decline in maximum physiological performance with increasing age. Records were normalized using the 30s age records as the baseline and studied through to the 90s age range. Track running records declined with age in a curvilinear fashion [y = 1-exp((T-T0)/tau)] whereas the walking and field events declined in a linear manner [y = alpha (T-T'0)]. There were significant differences in the rates of percentage decline in the running events over various distances for both males and females, and significant differences between males and females. Decline with aging was greater for females, and for the longer or endurance running events. There were no differences in the rates of declining function for any of the walking events, and the only jumping event to show a significant difference was the high jump performance, which showed the slowest decline. The walking events declined more slowly than the running events, which declined more slowly than the jumping events. Because of the changes in the weights, heights, and distances at different ages, for both males and females, it was not possible to directly compare rates of decline in the various throwing and hurdling events. The strength-dependent throwing events and the pole vault showed the greatest rates of decline with age. In general terms, men's performance declined to 75% of peak performance in sprint events by the early 70s, in the longer track distances by mid to late 60s, and in field events by mid to late 50s. Women's performance declined to a similar extent by their mid 60s in track events, and by late 40s to early 50s in field events. Some of these differences may be due to differences in training effort and/or other competitive aspects, such as the numbers of athletes involved in the sport, and such differences may be reduced in the future with a more professional approach to these events.

We assessed if first-trimester vitamin D deficiency is more prevalent in women who experienced a spontaneous preterm birth compared with women who delivered at term. We conducted a nested case-control study of pregnant women who had previously given blood for first-trimester combined screening for trisomy 21 and subsequently delivered at a tertiary hospital between November 2004 and July 2009. From an overall cohort of 4225 women, 40 cases of spontaneous preterm birth (≥23 0/7 and ≤34 6/7 weeks) were matched by race/ethnicity with 120 women delivering at term (≥37 0/7 weeks) with uncomplicated pregnancies. Banked maternal serum was used to measure maternal 25-hydroxyvitamin D [25(OH)D]. The prevalence of first-trimester maternal vitamin D deficiency [25(OH)D <50 nmol/L] was comparable among women who subsequently delivered preterm compared with controls (7.5% versus 6.7%, p=0.90). The median 25(OH)D level for all subjects was 89 nmol/L (interquartile range, 73 to 106 nmol/L). Seventy-three percent (117/160) of the cohort had sufficient vitamin D levels [25(OH)D ≥75 nmol/L]. In a cohort of pregnant women with mostly sufficient levels of first-trimester serum 25(OH)D, vitamin D deficiency was not associated with spontaneous preterm birth.

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Introduction: There is mixed evidence in the literature on the role of inflammation in major depressive disorder. Contradictory findings are attributed to lack of rigorous characterization of study subjects, to the presence of concomitant medical illnesses, to the small sample sizes, and to the limited number of cytokines tested.Methods: Subjects aged 18-70 years, diagnosed with major depressive disorder and presenting with chronic course of illness, as well as matched controls (n = 236), were evaluated by trained raters and provided blood for cytokine measurements. Cytokine levels in EDTA plasma were measured with the MILLIPLEX Multi-Analyte Profiling Human Cytokine/ Chemokine Assay employing Luminex technology. The Wilcoxon rank-sum test was used to compare cytokine levels between major depressive disorder subjects and healthy volunteers, before (interleukin [IL]-1β, IL-6, and tumor necrosis factor-α) and after Bonferroni correction for multiple comparisons (IL-1α, IL-2, IL-3, IL-4, IL-5, IL-7, IL-8, IL-10, IL-12(p40), IL-12(p70), IL-13, IL-15, IFN-γ-inducible protein 10, Eotaxin, interferon-γ, monotype chemoattractant protein-1, macrophage inflammatory protein-1α, granulocyte-macrophage colony-stimulating factor and vascular endothelial growth factor).Results: There were no significant differences in cytokine levels between major depressive disorder subjects and controls, both prior to and after correction for multiple analyses (significance set at p ⩽ 0.05 and p ⩽ 0.002, respectively). Conclusion:Our well-characterized examination of cytokine plasma levels did not support the association of major depressive disorder with systemic inflammation. The heterogeneity of major depressive disorder, as well as a potential sampling bias selecting for non-inflammatory depression, might have determined our findings discordant with the literature.