Iron bioavailability and cardiopulmonary function during ascent to very high altitude

Lette

Comparing genomic variant identification protocols for Candida auris.

Genomic analyses are widely applied to epidemiological, population genetic and experimental studies of pathogenic fungi. A wide range of methods are employed to carry out these analyses, typically without including controls that gauge the accuracy of variant prediction. The importance of tracking outbreaks at a global scale has raised the urgency of establishing high-accuracy pipelines that generate consistent results between research groups. To evaluate currently employed methods for whole-genome variant detection and elaborate best practices for fungal pathogens, we compared how 14 independent variant calling pipelines performed across 35 Candida auris isolates from 4 distinct clades and evaluated the performance of variant calling, single-nucleotide polymorphism (SNP) counts and phylogenetic inference results. Although these pipelines used different variant callers and filtering criteria, we found high overall agreement of SNPs from each pipeline. This concordance correlated with site quality, as SNPs discovered by a few pipelines tended to show lower mapping quality scores and depth of coverage than those recovered by all pipelines. We observed that the major differences between pipelines were due to variation in read trimming strategies, SNP calling methods and parameters, and downstream filtration criteria. We calculated specificity and sensitivity for each pipeline by aligning three isolates with chromosomal level assemblies and found that the GATK-based pipelines were well balanced between these metrics. Selection of trimming methods had a greater impact on SAMtools-based pipelines than those using GATK. Phylogenetic trees inferred by each pipeline showed high consistency at the clade level, but there was more variability between isolates from a single outbreak, with pipelines that used more stringent cutoffs having lower resolution. This project generated two truth datasets useful for routine benchmarking of C. auris variant calling, a consensus VCF of genotypes discovered by 10 or more pipelines across these 35 diverse isolates and variants for 2 samples identified from whole-genome alignments. This study provides a foundation for evaluating SNP calling pipelines and developing best practices for future fungal genomic studies

Aerobic training protects cardiac function during advancing age: a meta-analysis of four decades of controlled studies

In contrast to younger athletes, there is comparatively less literature examining cardiac structure and function in older athletes. However, a progressive accumulation of studies during the past four decades offers a body of literature worthy of systematic scrutiny. We conducted a systematic review, meta-analysis and meta-regression of controlled echocardiography studies comparing left ventricular (LV) structure and function in aerobically trained older athletes (> 45 years) with age-matched untrained controls, in addition to investigating the influence of chronological age. statistic. , 95% CI 0.05-1.86, p = 0.04). Meta-regression for chronological age identified that athlete-control differences, in the main, are maintained during advancing age. Athletic older men have larger cardiac dimensions and enjoy more favourable cardiac function than healthy, non-athletic counterparts. Notably, the athlete groups maintain these effects during chronological ageing

Left ventricular speckle tracking-derived cardiac strain and cardiac twist mechanics in athletes: a systematic review and meta-analysis of controlled studies

Background: The athlete’s heart is associated with physiological remodeling as a consequence of repetitive cardiac loading. The effect of exercise training on left ventricular (LV) cardiac strain and twist mechanics are equivocal, and no meta-analysis has been conducted to date. Objective: The objective of this systematic review and meta-analysis was to review the literature pertaining to the effect of different forms of athletic training on cardiac strain and twist mechanics and determine the influence of traditional and contemporary sporting classifications on cardiac strain and twist mechanics. Methods: We searched PubMed/MEDLINE, Web of Science, and ScienceDirect for controlled studies of aged-matched male participants aged 18–45 years that used two-dimensional (2D) speckle tracking with a defined athlete sporting discipline and a control group not engaged in training programs. Data were extracted independently by two reviewers. Random-effects meta-analyses, subgroup analyses, and meta-regressions were conducted. Results: Our review included 13 studies with 945 participants (controls n = 355; athletes n = 590). Meta-analyses showed no athlete–control differences in LV strain or twist mechanics. However, moderator analyses showed greater LV twist in high-static low-dynamic athletes (d = –0.76, 95% confidence interval [CI] –1.32 to –0.20; p < 0.01) than in controls. Peak untwisting velocity (PUV) was greater in high-static low-dynamic athletes (d = –0.43, 95% CI –0.84 to –0.03; p < 0.05) but less than controls in high-static high-dynamic athletes (d = 0.79, 95% CI 0.002–1.58; p = 0.05). Elite endurance athletes had significantly less twist and apical rotation than controls (d = 0.68, 95% CI 0.19–1.16, p < 0.01; d = 0.64, 95% CI 0.27–1.00, p = 0.001, respectively) but no differences in basal rotation. Meta-regressions showed LV mass index was positively associated with global longitudinal (b = 0.01, 95% CI 0.002–0.02; p < 0.05), whereas systolic blood pressure was negatively associated with PUV (b = –0.06, 95% CI –0.13 to –0.001; p = 0.05). Conclusion: Echocardiographic 2D speckle tracking can identify subtle physiological differences in adaptations to cardiac strain and twist mechanics between athletes and healthy controls. Differences in speckle tracking echocardiography-derived parameters can be identified using suitable sporting categorizations

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Structural study of DNA duplex containing an N-(2-deoxy-β-d-erythro-pentofuranosyl) formamide frameshift by NMR and restrained molecular dynamics

The presence of an N-(2-deoxy-β-d-erythro-pentofuranosyl) formamide (F) residue, a ring fragmentation product of thymine, in a frameshift context in the sequence 5′-d-(AGGACCACG)·d(CGTGGFTCCT) has been studied by (1)H and (31)P nuclear magnetic resonance (NMR) and molecular dynamics. Two-dimensional NMR studies show that the formamide residue, whether the cis or trans isomer, is rotated out of the helix and that the bases on either side of the formamide residue in the sequence, G14 and T16, are stacked over each other in a way similar to normal B-DNA. The cis and trans isomers were observed in the ratio 3:2 in solution. Information extracted from (31)P NMR data reveal a modification of the phosphodiester backbone conformation at the extrahelical site, which is also observed during the molecular dynamics simulations

Speckle tracking echocardiographic analysis of left ventricular systolic and diastolic function in young elite rugby players.

International audienceLittle evidence exists in the literature on the effects of mixed-type training on the left ventricle (LV). This study focused on the effects of training on the morphological and functional characteristics of the left ventricle. This study investigated the effects of training on LV function using Speckle Tracking Imaging (STI) in high-level, young rugby players. Prospective and longitudinal cohort study. CA Brive Correze Limousin rugby club (France) and JA Isle rugby club (France). Ten young controls and 24 young rugby players (13 high-level rugby players; 11 amateur rugby players) were included in the study. Standard Tissue Doppler Imaging Echocardiography and STI were performed in this study before and after the season. LV mass and pulsed wave Doppler inflow recording of the LV, including early and atrial waves, were carried out in 2-3-4 chamber views. We assessed three normal strains, rotation, and torsion in the LV. The main results of this study demonstrated that no differences existed between the three groups in LV functional parameters, the longitudinal circumferential and radial strain indices, and rotation and torsion indices. In the professional group, a significantly higher end- diastolic diameter (p<0.001), septal (p<0.05) and posterior (p<0.01) wall thickness, and LV mass (p<0.01) was observed. There were no differences in diastolic function. This study confirmed that young, elite rugby players have normal LV remodeling and normal LV function under resting conditions

Screening for natural polymorphisms in genes involved in Candida albicans azoles and echinocandins resistance and description of new mutations for azole resistance in clinical isolates

International audienceBackground: Azoles and echinocandins are the 2 main classes of antifungal agents used to treat candidiasis. Resistance of Candida albicans isolates is a major cause of breakthrough infections. C. albicans is a diploid yeast which displays a high genetic polymorphism. Point mutations found in genes involved in the resistance of C. albicans to antifungals could either be natural polymorphisms or can confer phenotypic resistance. Objective: Our objective was to establish a comprehensive repertoire of the non-synonymous polymorphisms (natural polymorphisms and/ or mutations of resistance) in genes involved in resistance to azoles and echinocandins. Methods: Two collections of C. albicans clinical isolates were used. The first one consists of 151 epidemiologically-unrelated strains susceptible to antifungal agents. The second collection consists of 24 isolates with a high level of resistance to fluconazole (MIC > 256 μg/mL, n = 21/24) and/or caspofungin (n = 5/24). The resistant isolates were obtained sequentially over a period of up to 8 years from 7 Chronic Mucocutaneous Candidiasis patients. The whole genome sequencing of these 2 strain collections was performed on an Illumina HiSeq 2000, generating 100 bp reads (roughly 100× coverage on average). The reads were mapped to the SC5314 reference genome (Assembly 22) using the BWA alignment tool. Then SNPs were detected by GATK and selected with the recommended filters. Using homemade scripts we analyzed the sequences of 5 genes involved in the resistance to azoles (ERG11, TAC1, MRR1 and UPC2) and echinocandins (FKS1) and compared them to the sequences of reference strain SC5314. Results: Among the 151 antifungal susceptible strains we identified 126 distinct natural amino acid substitutions, including 38 substitutions in Tac1p, 20 in Erg11p, 15 in Upc2p, 33 in Mrr1p and 20 in Fks1p. Novel substitutions were found; respectively 37% (14/38), 50% (10/20), 67% (10/15) and 73% (24/33). Whereas, from the 24 resistant strains we identified 20 amino acid substitutions, in addition to the above-mentioned natural polymorphisms, affecting Erg11p (n = 9), Tac1p (n = 7), Upc2p (n = 3) and Fks1p (n = 1). From the latter, 9 of these mutations have already been associated to azoles or echinocandins resistance. However, the remaining 11 substitutions are novel putative azoles resistance mutations. To confirm that these mutations are indeed responsible for the resistance phenotype, direct mutagenesis experiments are in progress. Conclusion: Whole genome sequencing of numerous antifungal susceptible C. albicans strains allowed us to determine a repertoire of the natural polymorphisms within the main genes involved in the resistance to azoles and echinocandins. Using this repertoire as a guide, 11 new putative mutations conferring resistance where identified. Thus this repertoire can serve as a major tool helping to rapidly unveil mutations potentially linked to antifungal resistance