Introduction: There is a scarcity of information on the incidence and outcomes of acute kidney injury (AKI) in COVID-19 patients in India. Therefore, we analyzed the correlation of AKI risk factors, ...ventilatory support, and renal replacement therapy and compared the outcomes of first and second COVID-19 waves in this tertiary care center. Methods: We retrospectively analyzed the patients' medical records with a positive RT-PCR for COVID-19 between July 2020 and May 2021. We looked at the clinical outcomes of the first and second COVID-19 waves and documented the frequency, risk factors for AKI, and the relationship between AKI and in-hospital mortality. Univariate and multivariate binomial logistic regression yielded odds ratios for the risk variables of AKI. Risk differences and age-adjusted odds ratios, as well as 99.5% confidence intervals, were used to compare COVID-19 outcomes between the first and second waves. Results: Of the 1260 hospitalized patients with COVID-19, 86 (6.8%) presented with AKI and 8 (0.7%) patients required dialysis. The most common comorbidity was diabetes mellitus (55.2%), hypertension (42.1%), hypothyroidism (11.3%), and coronary artery disease (8.1%). A total of 229 (18.17%) patients were admitted to ICU, 574 (45.5%) received ventilation, and 26 (2.0%) required mechanical ventilation. The incidence of in-hospital death in the patients with AKI as per the stage from 1 to 3 was 9 (15.8%), 7 (35%), and 5 (55.6%), respectively. Compared to the first wave, the second wave cohort had a lower risk of AKI (adj OR: 0.426; CI: 0.232-0.782) and mortality (adj OR: 0.252; CI: 0.090-0.707). Conclusions: In our study, AKI prevalence was 6.8%, the need for ventilation was 45.5%, ECMO 0.2%, and the mortality rate 2.9%. Second wave of COVID-19 exhibits improved clinical outcomes compared to the first wave.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The standard view of adaptation to larval crowding in fruitflies, built on results from 25 years of multiple experimental evolution studies on
Drosophila melanogaster
, was that enhanced competitive ...ability evolves primarily through increased larval feeding and foraging rate, and increased larval tolerance to nitrogenous wastes, at the cost of efficiency of food conversion to biomass. These results were at odds from the predictions of classical
K
-selection theory, notably the expectation that selection at high density should result in the increase of efficiency of conversion of food to biomass, and were better interpreted through the lens of
α
-selection. We show here that populations of
D. ananassae
and
D. n. nasuta
subjected to extreme larval crowding evolve greater competitive ability and pre-adult survivorship at high density, primarily through a combination of reduced larval duration, faster attainment of minimum critical size for pupation, greater time efficiency of food conversion to biomass and increased pupation height, with a relatively small role of increased urea/ammonia tolerance, if at all. This is a very different suite of traits than that seen to evolve under similar selection in
D
.
melanogaster
, and seems to be closer to the expectations from the canonical theory of
K
-selection. We also discuss possible reasons for these differences in results across the three species. Overall, the results reinforce the view that our understanding of the evolution of competitive ability in fruitflies needs to be more nuanced than before, with an appreciation that there may be multiple evolutionary routes through which higher competitive ability can be attained.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The aggregation of α-synuclein (Syn or S) to form insoluble fibrils is important in the pathogenesis of Parkinson's disease, but key risk factors remain ill-defined. We have developed Fluorescence ...Resonance Energy Transfer (FRET)-based assays for α-synuclein aggregation, using Green Fluorescent Protein variants Cerulean (C) or Venus (V), fused to each other (CV, VC) or to human synuclein (SC, SV etc). Bacterially expressed proteins were purified to homogeneity, and C-terminal fusions SC and SV largely retained their ability to aggregate in vitro. FRET signals from mixtures of SC and SV were used to monitor aggregation. These fusion genes were linked to the C. elegans unc-54 myosin promoter to generate integrated transgenic strains. Increased FRET signals, indicative of S aggregation, were observed following treatment of unc-54::SC + unc-54::SV double transgenic worms with low concentrations of mercury or chlorpyrifos, or with RNAi against hsp-70 and hip-1. Opposite changes in Yellow Fluorescent Protein (YFP) fluorescence in an unc-54::SV strain (NL5901) are likely to reflect FRET from Yellow Fluorescent Protein to aggregates of Syn fusion protein. This could provide the basis for a high throughput screening assay, which could be used for studying the effects of toxic chemicals and environmental pollutants on the aggregation of proteins such as Syn in vivo.
Context: Recent studies have shown that beta-blocker (BB) users have a decreased risk of fracture and higher bone mineral density (BMD) compared to nonusers, likely due to the suppression of ...adrenergic signaling in osteoblasts, leading to increased BMD. There is also variability in the effect size of BB use on BMD in humans, which may be due to pharmacogenomic effects. Objective: To investigate potential single-nucleotide variations (SNVs) associated with the effect of BB use on femoral neck BMD, we performed a cross-sectional analysis using clinical data, dual-energy x-ray absorptiometry, and genetic data from the Framingham Heart Study's (FHS) Offspring Cohort. We then sought to validate our top 4 genetic findings using data from the Rotterdam Study, the BPROOF Study, the Malta Osteoporosis Fracture Study (MOFS), and the Hertfordshire Cohort Study. Methods: We used sex-stratified linear mixed models to determine SNVs that had a significant interaction effect with BB use on femoral neck (FN) BMD across 11 gene regions. We also evaluated the association of our top SNVs from the FHS with microRNA (miRNA) expression in blood and identified potential miRNA-mediated mechanisms by which these SNVs may affect FN BMD. Results: One variation (rs11124190 in HDAC4) was validated in females using data from the Rotterdam Study, while another (rs12414657 in ADRB1) was validated in females using data from the MOFS. We performed an exploratory meta-analysis of all 5 studies for these variations, which further validated our findings. Conclusion: This analysis provides a starting point for investigating the pharmacogenomic effects of BB use on BMD measures. Key Words: beta-blocker, beta blocker, bone, pharmacogenomics, miRNA, genomics
Abstract
Context
Recent studies have shown that β-blocker (BB) users have a decreased risk of fracture and higher bone mineral density (BMD) compared to nonusers, likely due to the suppression of ...adrenergic signaling in osteoblasts, leading to increased BMD. There is also variability in the effect size of BB use on BMD in humans, which may be due to pharmacogenomic effects.
Objective
To investigate potential single-nucleotide variations (SNVs) associated with the effect of BB use on femoral neck BMD, we performed a cross-sectional analysis using clinical data, dual-energy x-ray absorptiometry, and genetic data from the Framingham Heart Study’s (FHS) Offspring Cohort. We then sought to validate our top 4 genetic findings using data from the Rotterdam Study, the BPROOF Study, the Malta Osteoporosis Fracture Study (MOFS), and the Hertfordshire Cohort Study.
Methods
We used sex-stratified linear mixed models to determine SNVs that had a significant interaction effect with BB use on femoral neck (FN) BMD across 11 gene regions. We also evaluated the association of our top SNVs from the FHS with microRNA (miRNA) expression in blood and identified potential miRNA-mediated mechanisms by which these SNVs may affect FN BMD.
Results
One variation (rs11124190 in HDAC4) was validated in females using data from the Rotterdam Study, while another (rs12414657 in ADRB1) was validated in females using data from the MOFS. We performed an exploratory meta-analysis of all 5 studies for these variations, which further validated our findings.
Conclusion
This analysis provides a starting point for investigating the pharmacogenomic effects of BB use on BMD measures.
Hybrid Optical Packet Switching is a prominent solution for boosting a Data Centers' performance. We reaffirm this hypothesis by studying network latencies and showing that hybrid switching delivers ...the best performance compared to all-electronic one.
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