Association of polygenic scores with chronic kidney disease phenotypes in a longitudinal study of older adults

Risk of chronic kidney disease (CKD) is influenced by environmental and genetic factors and increases sharply in individuals 70 years and older. Polygenic scores (PGS) for kidney disease-related traits have shown promise but require validation in well-characterized cohorts. Here, we assessed the performance of recently developed PGSs for CKD-related traits in a longitudinal cohort of healthy older individuals enrolled in the Australian ASPREE randomized controlled trial of daily low-dose aspirin with CKD risk at baseline and longitudinally. Among 11,813 genotyped participants aged 70 years or more with baseline eGFR measures, we tested associations between PGSs and measured eGFR at baseline, clinical phenotype of CKD, and longitudinal rate of eGFR decline spanning up to six years of follow-up per participant. A PGS for eGFR was associated with baseline eGFR, with a significant decrease of 3.9 mL/min/1.73m2 (95% confidence interval -4.17 to -3.68) per standard deviation (SD) increase of the PGS. This PGS, as well as a PGS for CKD stage 3 were both associated with higher risk of baseline CKD stage 3 in cross-sectional analysis (Odds Ratio 1.75 per SD, 95% confidence interval 1.66-1.85, and Odds Ratio 1.51 per SD, 95% confidence interval 1.43-1.59, respectively). Longitudinally, two separate PGSs for eGFR slope were associated with significant kidney function decline during follow-up. Thus, our study demonstrates that kidney function has a considerable genetic component in older adults, and that new PGSs for kidney disease-related phenotypes may have potential utility for CKD risk prediction in advanced age

Lean Body Mass and Muscle Cross-Sectional Area Adaptations Among College Age Males with Different Strength Levels across 11 Weeks of Block Periodized Programmed Resistance Training

The block periodization training paradigm has been shown to produce enhanced gains in strength and power. The purpose of this study is to assess resistance training induced alterations in lean body mass and cross-sectional area using a block periodization training model among individuals (n = 15) of three differing strength levels (high, moderate and low) based on one repetition maximum back squat relative to body weight. A 3 × 5 mixed-design ANOVA was used to examine within-and between-subject changes in cross-sectional area (CSA), lean body mass (LBM), lean body mass adjusted (LBMadjusted) and total body water (TBW) over an 11-week resistance training program. LBMadjusted is total body water subtracted from lean body mass. The ANOVA revealed no statistically significant between-group differences in any independent variable (p > 0.05). Within-group effects showed statistically significant increases in cross-sectional area (p < 0.001), lean body mass (p < 0.001), lean body mass adjusted (p ˂ 0.001) and total body water (p < 0.001) from baseline to post intervention: CSA: 32.7 cm2 ± 8.6; 36.3 cm2 ± 7.2, LBM: 68.0 kg ± 9.5; 70.6 kg ± 9.4, LBMadjusted: 20.4 kg ± 3.1; 21.0 kg ± 3.3 and TBW: 49.8 kg ± 6.9; 51.7 kg ± 6.9. In conclusion, the results of this study suggest subjects experienced an increase in both lean body mass and total body water, regardless of strength level, over the course of the 11-week block periodized program. Gains in lean body mass and cross-sectional area may be due to edema at the early onset of training

The Effect of Training Status on Adaptations to 11 Weeks of Block Periodization Training

This work is licensed under a Creative Commons Attribution 4.0 International License.Some controversy exists as to the most efficacious method of training to achieve enhanced levels of sport performance. Controversy concerning the efficacy of periodization and especially block periodization (BP) likely stems from the use of poorly or untrained subjects versus trained who may differ in their responses to a stimulus. The purpose of this study was to investigate the effect of training status on performance outcomes resulting from 11 weeks of BP training. Fifteen males were recruited for this study and placed into strong (age = 24.3 ± 1.9 years., body mass (BM) = 87.7 ± 8.7 kg, squat: body mass = 1.96 ± 0.16), moderate (age = 25.3 ± 2.7 years., body mass = 100.2 ± 15.5 kg, squat: body mass = 1.46 ± 0.14), or weak (age = 23.2 ± 3.9 yrs., body mass = 83.5 ± 17.1 kg, squat: body mass = 1.17 ± 0.07) groups based on relative strength. Testing was completed at baseline, and after each block which consisted of 1 repetition maximum (1RM) squat, 0 kg static jump (SJ), 0 kg countermovement jump (CMJ), 20 kg SJ, and 20 kg CMJ. Absolute and relative strength were strongly correlated with rates of improvement for absolute strength, relative strength, 0 kg, and 20 kg vertical jumps. All subjects substantially improved back squat (p < 0.001), relative back squat (p < 0.001) with large–very large effect sizes between groups for percent change favoring the weak group over the moderate and strong group for all performance variables. All subjects showed statistically significant improvements in 0 kg SJ (p < 0.001), 0 kg CMJ (p < 0.001), 20 kg SJ (p = 0.002), and 20 kg CMJ (p < 0.001). Statistically significant between group differences were noted for both 20 kg SJ (p = 0.01) and 20 kg CMJ (p = 0.043) with the strong group statistically greater jump heights than the weak group. The results of this study indicate BP training is effective in improving strength and explosive ability. Additionally, training status may substantially alter the response to a resistance training program

Lean Body Mass and Muscle Cross-Sectional Area Adaptations Among College Age Males With Different Strength Levels Across 11 Weeks of Block Periodized Programmed Resistance Training

The block periodization training paradigm has been shown to produce enhanced gains in strength and power. The purpose of this study is to assess resistance training induced alterations in lean body mass and cross-sectional area using a block periodization training model among individuals (n = 15) of three differing strength levels (high, moderate and low) based on one repetition maximum back squat relative to body weight. A 3 × 5 mixed-design ANOVA was used to examine within-and between-subject changes in cross-sectional area (CSA), lean body mass (LBM), lean body mass adjusted (LBMadjusted) and total body water (TBW) over an 11-week resistance training program. LBMadjusted is total body water subtracted from lean body mass. The ANOVA revealed no statistically significant between-group differences in any independent variable (p \u3e 0.05). Within-group effects showed statistically significant increases in cross-sectional area (p \u3c 0.001), lean body mass (p \u3c 0.001), lean body mass adjusted (p \u3c 0.001) and total body water (p \u3c 0.001) from baseline to post intervention: CSA: 32.7 cm2 ± 8.6; 36.3 cm2 ± 7.2, LBM: 68.0 kg ± 9.5; 70.6 kg ± 9.4, LBMadjusted: 20.4 kg ± 3.1; 21.0 kg ± 3.3 and TBW: 49.8 kg ± 6.9; 51.7 kg ± 6.9. In conclusion, the results of this study suggest subjects experienced an increase in both lean body mass and total body water, regardless of strength level, over the course of the 11-week block periodized program. Gains in lean body mass and cross-sectional area may be due to edema at the early onset of training

Agglutination of benthic foraminifera in relation to mesoscale bathymetric features in the abyssal NE Atlantic (Porcupine Abyssal Plain)

Abyssal hills, small topographic features rising above the abyssal seafloor (< 1000 m altitude), have distinct environmental characteristics compared to abyssal plains, notably the presence of coarser-grained sediments. As a result, they are a major source of habitat heterogeneity in the deep sea. The aim of this study was to investigate whether there is a link between abyssal hills and the test characteristics of selected agglutinated benthic foraminiferal species. We analysed 1) the overall morphometry, and 2) the granulometric and chemical (elemental) characteristics of the agglutinated tests of ten common foraminiferal species (Adercotryma glomerata, Ammobaculites agglutinans, Cribrostomoides subglobosus, Lagenammina sp.1, Nodulina dentaliniformis, Portatrochammina murrayi, three Reophax sp. and Recurvoides sp. 9) at four sites (two on top of abyssal hills and two on the adjacent plain) in the area of the Porcupine Abyssal Plain Sustained Observatory, northeast Atlantic. The foraminiferal test data were compared with the particle size distribution and elemental composition of sediments from the study sites in order to explore possible grain size and mineral selectivity. We found differences in the visual appearance of the tests (i.e. the degree of irregularity in their shape), which was confirmed by morphometric analyses, related to seafloor topography. The agglutinated foraminifera selected different sized particles on hills and plains, reflecting the distinct granulometric characteristics of these settings. These characteristics (incorporation of coarse particles, test morphometry) could provide evidence for the recognition of ancient abyssal hill environments, as well as other palaeoceanographic settings that were characterised by enhanced current flow. Furthermore, analyses of sediment samples from the hill and plain sites using wavelength dispersive X-ray fluorescence (WD-XRF) yielded different elemental profiles from the plains, probably a result of winnowing on the hills, although all samples were carbonate-rich. In contrast, the majority of the agglutinated tests were rich in silica, suggesting a preferential selection for quartz

Chronic kidney disease and arrhythmias: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

Patients with chronic kidney disease (CKD) are predisposed to heart rhythm disorders, including atrial fibrillation (AF)/atrial flutter, supraventricular tachycardias, ventricular arrhythmias, and sudden cardiac death (SCD). While treatment options, including drug, device, and procedural therapies, are available, their use in the setting of CKD is complex and limited. Patients with CKD and end-stage kidney disease (ESKD) have historically been under-represented or excluded from randomized trials of arrhythmia treatment strategies,1 although this situation is changing.2 Cardiovascular society consensus documents have recently identified evidence gaps for treating patients with CKD and heart rhythm disorders [...

Determining Roles of Accessory Genes in Denitrification by Mutant Fitness Analyses.

Enzymes of the denitrification pathway play an important role in the global nitrogen cycle, including release of nitrous oxide, an ozone-depleting greenhouse gas. In addition, nitric oxide reductase, maturation factors, and proteins associated with nitric oxide detoxification are used by pathogens to combat nitric oxide release by host immune systems. While the core reductases that catalyze the conversion of nitrate to dinitrogen are well understood at a mechanistic level, there are many peripheral proteins required for denitrification whose basic function is unclear. A bar-coded transposon DNA library from Pseudomonas stutzeri strain RCH2 was grown under denitrifying conditions, using nitrate or nitrite as an electron acceptor, and also under molybdenum limitation conditions, with nitrate as the electron acceptor. Analysis of sequencing results from these growths yielded gene fitness data for 3,307 of the 4,265 protein-encoding genes present in strain RCH2. The insights presented here contribute to our understanding of how peripheral proteins contribute to a fully functioning denitrification pathway. We propose a new low-affinity molybdate transporter, OatABC, and show that differential regulation is observed for two MoaA homologs involved in molybdenum cofactor biosynthesis. We also propose that NnrS may function as a membrane-bound NO sensor. The dominant HemN paralog involved in heme biosynthesis is identified, and a CheR homolog is proposed to function in nitrate chemotaxis. In addition, new insights are provided into nitrite reductase redundancy, nitric oxide reductase maturation, nitrous oxide reductase maturation, and regulation