Folic acid supplementation and chronic kidney disease progression

In contrast to prior studies demonstrating no benefit or even increased harm from B vitamin supplementation in patients with chronic kidney disease, a large randomized trial from China recently demonstrated small but statistically significant reductions in the risk of first stroke and chronic kidney disease progression with the addition of folic acid to enalapril in adults with hypertension. Differences in the study population and study intervention may explain these discordant results

Prevalence of Kidney Disease in HIV-Infected and Uninfected Rwandan Women

Background: In the United States, HIV-related kidney disease disproportionately affects individuals of African descent; however, there are few estimates of kidney disease prevalence in Africa. We evaluated the prevalence of kidney disease among HIV-infected and uninfected Rwandan women. Methods: The Rwandan Women's Interassociation Study and Assessment prospectively enrolled 936 women. Associations with estimated glomerular filtration rate (eGFR)<60 mL/min/1.73 m$^2$ and proteinuria were assessed in separate logistic regression models. Results: Among 891 non-pregnant women with available data, 2.4% had an eGFR<60 mL/min/1.73 m$^2$ (calculated by the Modification of Diet in Renal Disease equation, MDRD eGFR) and 8.7% had proteinuria $\ge$1+. The prevalence of decreased eGFR varied markedly depending on the estimating method used, with the highest prevalence by Cockcroft-Gault. Regardless of the method used to estimate GFR, the proportion with decreased eGFR or proteinuria did not differ significantly between HIV-infected and -uninfected women in unadjusted analysis. After adjusting for age and blood pressure, HIV infection was associated with significantly higher odds of decreased MDRD eGFR but not proteinuria. Conclusion: In a well-characterized cohort of Rwandan women, HIV infection was associated with decreased MDRD eGFR. The prevalence of decreased eGFR among HIV-infected women in our study was lower than that previously reported in African-Americans and in other Central and East African HIV populations, although there was substantial variability depending on the equation used to estimate GFR. Future studies are needed to optimize GFR estimates and to determine the impact of antiretroviral therapy on kidney disease in this population

Assaying sensory ciliopathies using calcium biosensor expression in zebrafish ciliated olfactory neurons

Background: Primary cilia mediate signal transduction by acting as an organizing scaffold for receptors, signalling proteins and ion channels. Ciliated olfactory sensory neurons (OSNs) organize olfactory receptors and ion channels on cilia and generate a calcium influx as a primary signal in odourant detection. In the zebrafish olfactory placode, ciliated OSNs and microvillus OSNs constitute the major OSN cell types with distinct odourant sensitivity. Methods: Using transgenic expression of the calcium biosensor GCaMP5 in OSNs, we analysed sensory cilia-dependent odour responses in live zebrafish, at individual cell resolution. oval/ift88 mutant and ift172 knockdown zebrafish were compared with wild-type siblings to establish ciliated OSN sensitivity to different classes of odourants. Results: oval/ift88 mutant and ift172 knockdown zebrafish showed fewer and severely shortened OSN cilia without a reduction in OSN number. The fraction of responding OSNs and response amplitudes to bile acids and food odour, both sensed by ciliated OSNs, were significantly reduced in ift88 mutants and ift172-deficient embryos, while the amino acids responses were not significantly changed. Conclusions: Our approach presents a quantitative model for studying sensory cilia signalling using zebrafish OSNs. Our results also implicate ift172-deficiency as a novel cause of hyposmia, a reduced sense of smell, highlighting the value of directly assaying sensory cilia signalling in vivo and supporting the idea that hyposmia can be used as a diagnostic indicator of ciliopathies. Electronic supplementary material The online version of this article (10.1186/s13630-018-0056-1) contains supplementary material, which is available to authorized users

Changes in proteinuria and albuminuria with initiation of antiretroviral therapy: data from a randomized trial comparing tenofovir disoproxil fumarate/emtricitabine versus abacavir/lamivudine

BACKGROUND: Antiretroviral therapy (ART) is associated with improved kidney function; however, the nucleotide reverse transcriptase inhibitor (NRTI) tenofovir disoproxil fumarate (TDF) has been associated with decreased kidney function and proteinuria. METHODS: We examined changes in urine protein:creatinine (UPCR) and urine albumin:creatinine (UACR) ratios in 245 ART-naive participants in A5202 randomized in a substudy to blinded NRTI (abacavir/lamivudine, ABC/3TC, n = 124 or TDF/emtricitabine, TDF/FTC, n = 121) with open-label protease inhibitor (PI) atazanavir/ritonavir or nonnucleoside reverse transcriptase inhibitor (NNRTI) efavirenz. RESULTS: At baseline, 18% of participants had clinically significant proteinuria (UPCR ≥200 mg/g), and 11% had clinically significant albuminuria (UACR ≥30 mg/g). The prevalence of clinically significant proteinuria and albuminuria decreased from baseline to week 96 in all treatment groups. In intention-to-treat analyses, there was a significant effect of NRTI component on fold change in UPCR (P = 0.011) and UACR (P = 0.018) from baseline to week 96, with greater improvements in participants randomized to ABC/3TC. There was no significant effect of NNRTI/PI component on fold change in UPCR (P = 0.23) or UACR (P = 0.88), and no significant interactions between NRTI and NNRTI/PI components. CONCLUSIONS: In this prespecified secondary analysis, ART initiation was associated with improvements in proteinuria and albuminuria, with significantly greater improvements in participants randomized to ABC/3TC versus TDF/FTC. These are the first data from a randomized trial to suggest that initiation of TDF/FTC may not be associated with the same degree of improvement in proteinuria and albuminuria that have been reported with other regimens. Future studies should consider the long-term clinical significance of these findings

Targeting Mycobacterium tuberculosis CoaBC through Chemical Inhibition of 4'-Phosphopantothenoyl-l-cysteine Synthetase (CoaB) Activity.

Coenzyme A (CoA) is a ubiquitous cofactor present in all living cells and estimated to be required for up to 9% of intracellular enzymatic reactions. Mycobacterium tuberculosis (Mtb) relies on its own ability to biosynthesize CoA to meet the needs of the myriad enzymatic reactions that depend on this cofactor for activity. As such, the pathway to CoA biosynthesis is recognized as a potential source of novel tuberculosis drug targets. In prior work, we genetically validated CoaBC as a bactericidal drug target in Mtb in vitro and in vivo. Here, we describe the identification of compound 1f, a small molecule inhibitor of the 4'-phosphopantothenoyl-l-cysteine synthetase (PPCS; CoaB) domain of the bifunctional Mtb CoaBC, and show that this compound displays on-target activity in Mtb. Compound 1f was found to inhibit CoaBC uncompetitively with respect to 4'-phosphopantothenate, the substrate for the CoaB-catalyzed reaction. Furthermore, metabolomic profiling of wild-type Mtb H37Rv following exposure to compound 1f produced a signature consistent with perturbations in pantothenate and CoA biosynthesis. As the first report of a direct small molecule inhibitor of Mtb CoaBC displaying target-selective whole-cell activity, this study confirms the druggability of CoaBC and chemically validates this target

Design of the Prevention of Adult Caries Study (PACS): A randomized clinical trial assessing the effect of a chlorhexidine dental coating for the prevention of adult caries

<p>Abstract</p> <p>Background</p> <p>Dental caries is one of the primary causes of tooth loss among adults. It is estimated to affect a majority of Americans aged 55 and older, with a disproportionately higher burden in disadvantaged populations. Although a number of treatments are currently in use for caries prevention in adults, evidence for their efficacy and effectiveness is limited.</p> <p>Methods/Design</p> <p>The Prevention of Adult Caries Study (PACS) is a multicenter, placebo-controlled, double-blind, randomized clinical trial of the efficacy of a chlorhexidine (10% w/v) dental coating in preventing adult caries. Participants (n = 983) were recruited from four different dental delivery systems serving four diverse communities, including one American Indian population, and were randomized to receive either chlorhexidine or a placebo treatment. The primary outcome is the net caries increment (including non-cavitated lesions) from baseline to 13 months of follow-up. A cost-effectiveness analysis also will be considered.</p> <p>Discussion</p> <p>This new dental treatment, if efficacious and approved for use by the Food and Drug Administration (FDA), would become a new in-office, anti-microbial agent for the prevention of adult caries in the United States.</p> <p>Trial Registration Number</p> <p>NCT00357877</p

Citizen-Science for the Future: Advisory Case Studies From Around the Globe

The democratization of ocean observation has the potential to add millions of observations every day. Though not a solution for all ocean monitoring needs, citizen scientists offer compelling examples showcasing their ability to augment and enhance traditional research and monitoring. Information they are providing is increasing the spatial and temporal frequency and duration of sampling, reducing time and labor costs for academic and government monitoring programs, providing hands-on STEM learning related to real-world issues and increasing public awareness and support for the scientific process. Examples provided here demonstrate the wide range of people who are already dramatically reducing gaps in our global observing network while at the same time providing unique opportunities to meaningfully engage in ocean observing and the research and conservation it supports. While there are still challenges to overcome before widespread inclusion in projects requiring scientific rigor, the growing organization of international citizen science associations is helping to reduce barriers. The case studies described support the idea that citizen scientists should be part of an effective global strategy for a sustained, multidisciplinary and integrated observing system

Meta-analysis of the space flight and microgravity response of the Arabidopsis plant transcriptome

15 p.-8 fig.-2 tab.Spaceflight presents a multifaceted environment for plants, combining the effects on growth of many stressors and factors including altered gravity, the influence of experiment hardware, and increased radiation exposure. To help understand the plant response to this complex suite of factors this study compared transcriptomic analysis of 15 Arabidopsis thaliana spaceflight experiments deposited in the National Aeronautics and Space Administration’s GeneLab data repository. These data were reanalyzed for genes showing significant differential expression in spaceflight versus ground controls using a single common computational pipeline for either the microarray or the RNA-seq datasets. Such a standardized approach to analysis should greatly increase the robustness of comparisons made between datasets. This analysis was coupled with extensive cross-referencing to a curated matrix of metadata associated with these experiments. Our study reveals that factors such as analysis type (i.e., microarray versus RNA-seq) or environmental and hardware conditions have important confounding effects on comparisons seeking to define plant reactions to spaceflight. The metadata matrix allows selection of studies with high similarity scores, i.e., that share multiple elements of experimental design, such as plant age or flight hardware. Comparisons between these studies then helps reduce the complexity in drawing conclusions arising from comparisons made between experiments with very different designs.This work was coordinated through the GeneLab Plant Analysis Working Group and was supported by NASA grants 80NSSC19K0126, 80NSSC18K0132 and 80NSSC21K0577 to S.G. and R.B., through NASA 80NSSC19K1481 to S.W., NNX15AG55G to C.W., and NNX15AG56G to L.D. and N.L., from the Spanish Agencia Estatal de Investigación grant RTI2018-099309-B-I00 and ESA 1340112 4000131202/20/NL/PG/pt to R.H. Contributions from P.J. and P.G. were partially supported by funds from the Oregon State University, NSF awards 1127112 and 1340112 and the United States Department of Agriculture, Agriculture Research Service. The Qlik software used in this work is provided under a free-to-use educational license from Qlik Technologies Inc. GeneLab datasets were obtained from https://genelab-data.ndc.nasa.gov/genelab/projects/, maintained by NASA GeneLab, NASA Ames Research Center, Moffett Field, CA 94035.Peer reviewe