26,480 research outputs found

    Association of maternal prenatal copper concentration with gestational duration and preterm birth: a multicountry meta-analysis

    Get PDF
    Background Copper (Cu), an essential trace mineral regulating multiple actions of inflammation and oxidative stress, has been implicated in risk for preterm birth (PTB). Objectives This study aimed to determine the association of maternal Cu concentration during pregnancy with PTB risk and gestational duration in a large multicohort study including diverse populations. Methods Maternal plasma or serum samples of 10,449 singleton live births were obtained from 18 geographically diverse study cohorts. Maternal Cu concentrations were determined using inductively coupled plasma mass spectrometry. The associations of maternal Cu with PTB and gestational duration were analyzed using logistic and linear regressions for each cohort. The estimates were then combined using meta-analysis. Associations between maternal Cu and acute-phase reactants (APRs) and infection status were analyzed in 1239 samples from the Malawi cohort. Results The maternal prenatal Cu concentration in our study samples followed normal distribution with mean of 1.92 ÎĽg/mL and standard deviation of 0.43 ÎĽg/mL, and Cu concentrations increased with gestational age up to 20 wk. The random-effect meta-analysis across 18 cohorts revealed that 1 ÎĽg/mL increase in maternal Cu concentration was associated with higher risk of PTB with odds ratio of 1.30 (95% confidence interval [CI]: 1.08, 1.57) and shorter gestational duration of 1.64 d (95% CI: 0.56, 2.73). In the Malawi cohort, higher maternal Cu concentration, concentrations of multiple APRs, and infections (malaria and HIV) were correlated and associated with greater risk of PTB and shorter gestational duration. Conclusions Our study supports robust negative association between maternal Cu and gestational duration and positive association with risk for PTB. Cu concentration was strongly correlated with APRs and infection status suggesting its potential role in inflammation, a pathway implicated in the mechanisms of PTB. Therefore, maternal Cu could be used as potential marker of integrated inflammatory pathways during pregnancy and risk for PTB

    Extreme drought impacts have been underestimated in grasslands and shrublands globally

    No full text
    Climate change is increasing the frequency and severity of short-term (~1 y) drought events—the most common duration of drought—globally. Yet the impact of this intensification of drought on ecosystem functioning remains poorly resolved. This is due in part to the widely disparate approaches ecologists have employed to study drought, variation in the severity and duration of drought studied, and differences among ecosystems in vegetation, edaphic and climatic attributes that can mediate drought impacts. To overcome these problems and better identify the factors that modulate drought responses, we used a coordinated distributed experiment to quantify the impact of short-term drought on grassland and shrubland ecosystems. With a standardized approach, we imposed ~a single year of drought at 100 sites on six continents. Here we show that loss of a foundational ecosystem function—aboveground net primary production (ANPP)—was 60% greater at sites that experienced statistically extreme drought (1-in-100-y event) vs. those sites where drought was nominal (historically more common) in magnitude (35% vs. 21%, respectively). This reduction in a key carbon cycle process with a single year of extreme drought greatly exceeds previously reported losses for grasslands and shrublands. Our global experiment also revealed high variability in drought response but that relative reductions in ANPP were greater in drier ecosystems and those with fewer plant species. Overall, our results demonstrate with unprecedented rigor that the global impacts of projected increases in drought severity have been significantly underestimated and that drier and less diverse sites are likely to be most vulnerable to extreme drought

    From TgO/GABA-AT, GABA, and T-263 Mutant to Conception of Toxoplasma

    No full text
    Summary: Toxoplasma gondii causes morbidity, mortality, and disseminates widely via cat sexual stages. Here, we find T. gondii ornithine aminotransferase (OAT) is conserved across phyla. We solve TgO/GABA-AT structures with bound inactivators at 1.55 Å and identify an inactivator selective for TgO/GABA-AT over human OAT and GABA-AT. However, abrogating TgO/GABA-AT genetically does not diminish replication, virulence, cyst-formation, or eliminate cat’s oocyst shedding. Increased sporozoite/merozoite TgO/GABA-AT expression led to our study of a mutagenized clone with oocyst formation blocked, arresting after forming male and female gametes, with “Rosetta stone”-like mutations in genes expressed in merozoites. Mutations are similar to those in organisms from plants to mammals, causing defects in conception and zygote formation, affecting merozoite capacitation, pH/ionicity/sodium-GABA concentrations, drawing attention to cyclic AMP/PKA, and genes enhancing energy or substrate formation in TgO/GABA-AT-related-pathways. These candidates potentially influence merozoite’s capacity to make gametes that fuse to become zygotes, thereby contaminating environments and causing disease

    Supplementary Tables 1a-3d from A Population-Based Family Case–Control Study of Sun Exposure and Follicular Lymphoma Risk

    No full text
    Supplementary Tables 1a-3d. Supplementary Table 1a: Bayesian information criterion for outdoor hours group-based trajectory model according to number of groups and trajectory outdoor hours. Supplementary Table 1b: Average posterior probability value and odds of correct classification for outdoor hours trajectory groups. Supplementary Table 1c: Estimated probability and the proportion of study members classified in each group according to the maximum posterior probability assignment rule. Supplementary Table 2a: Odds ratios and 95% confidence intervals for FL risk in relation to total lifetime outdoor hours during decade years among cases and related controls.Supplementary Table 2b: Odds ratios and 95% confidence intervals for FL risk in relation to outdoor hours on weekdays, weekends, and holidays at each decade year among cases and related controls. Supplementary Table 2c: Odds ratios and 95% confidence intervals for FL risk in relation to trajectories of outdoor hours across the decade years among cases and related controls. Supplementary Table 2d: Odds ratios and 95% confidence intervals for FL risk in relation to total lifetime outdoor hours during decade years among cases and unrelated controls. Supplementary Table 2e: Odds ratios and 95% confidence intervals for FL risk in relation to outdoor hours on weekdays, weekends, and holidays at each decade year among cases and unrelated controls. Supplementary Table 2f: Odds ratios and 95% confidence intervals for FL risk in relation to trajectories of outdoor hours across the decade years among cases and unrelated controls. Supplementary Table 3a: Bayesian information criterion for outdoor hours group-based trajectory model according to number of groups and trajectory outdoor hours – cases and related controls. Supplementary Table 3b: Bayesian information criterion for outdoor hours group-based trajectory model according to number of groups and trajectory outdoor hours – cases and unrelated controls. Supplementary Table 3c: Average posterior probability value and odds of correct classification for outdoor hours trajectory groups. Supplementary Table 3d: Estimated probability and the proportion of study members classified in each group according to the maximum posterior probability assignment rule.</p

    Burosumab vs conventional therapy in children with X-linked hypophosphatemia:results of the open-label, phase 3 extension period

    Get PDF
    In a randomized, open-label phase 3 study of 61 children aged 1–12 years old with X-linked hypophosphatemia (XLH) previously treated with conventional therapy, changing to burosumab every 2 weeks (Q2W) for 64 weeks improved the phosphate metabolism, radiographic rickets, and growth compared with conventional therapy. In this open-label extension period (weeks 64–88), 21 children continued burosumab Q2W at the previous dose or crossed over from conventional therapy to burosumab starting at 0.8 mg/kg Q2W with continued clinical radiographic assessments through week 88. Efficacy endpoints and safety observations were summarized descriptively for both groups (burosumab continuation, n = 6; crossover, n = 15). At week 88 compared with baseline, improvements in the following outcomes were observed in the burosumab continuation and crossover groups, respectively: mean (SD) RGI-C rickets total score (primary outcome), +2.11 (0.27) and +1.89 (0.35); mean (SD) RGI-C lower limb deformity score, +1.61 (0.91) and +0.73 (0.82); and mean (SD) height Z-score + 0.41 (0.50) and +0.08 (0.34). Phosphate metabolism normalized rapidly in the crossover group and persisted in the continuation group. Mean (SD) serum alkaline phosphatase decreased from 169% (43%) of the upper limit of normal (ULN) at baseline to 126% (51%) at week 88 in the continuation group and from 157% (33%) of the ULN at baseline to 111% (23%) at week 88 in the crossover group. During the extension period, treatment-emergent adverse events (AEs) were reported in all 6 children in the burosumab continuation group and 14/15 children in the crossover group. The AE profiles in the randomized and extension periods were similar, with no new safety signals identified. Improvements from baseline in radiographic rickets continued in the extension period among children with XLH who remained on burosumab. Children who crossed over from conventional therapy to burosumab demonstrated a rapid improvement in phosphate metabolism and improved rickets healing over the ensuing 22 weeks
    • …
    corecore