Tag: nevin manimala

Commun Biol. 2021 Jul 9;4(1):856. doi: 10.1038/s42003-021-02385-7.

ABSTRACT

Mosquito vectors transmit various diseases through blood feeding, required for their egg development. Hence, blood feeding is a major physiological event in their life cycle, during which hundreds of genes are tightly regulated. Blood is a rich source of proteins for mosquitoes, but also contains many other molecules including microRNAs (miRNAs). Here, we found that human blood miRNAs are transported abundantly into the fat body tissue of Aedes aegypti, a key metabolic center in post-blood feeding reproductive events, where they target and regulate mosquito genes. Using an artificial diet spiked with the mimic of an abundant and stable human blood miRNA, hsa-miR-21-5p, and proteomics analysis, we found over 40 proteins showing differential expression in female Ae. aegypti mosquitoes after feeding. Of interest, we found that the miRNA positively regulates the vitellogenin gene, coding for a yolk protein produced in the mosquito fat body and then transported to the ovaries as a protein source for egg production. Inhibition of hsa-miR-21-5p followed by human blood feeding led to a statistically insignificant reduction in progeny production. The results provide another example of the involvement of small regulatory molecules in the interaction of taxonomically vastly different taxa.

PMID:34244602 | DOI:10.1038/s42003-021-02385-7

Nat Med. 2021 Jul 9. doi: 10.1038/s41591-021-01446-y. Online ahead of print.

ABSTRACT

The SARS-CoV-2 pandemic continues to be a global health concern. The mRNA-1273 (Moderna) vaccine was reported to have an efficacy of 94.1% at preventing symptomatic COVID-19 due to infection with ‘wild-type’ variants in a randomized clinical trial. Here, we assess the real-world effectiveness of this vaccine against SARS-CoV-2 variants of concern, specifically B.1.1.7 (Alpha) and B.1.351 (Beta), in Qatar, a population that comprises mainly working-age adults, using a matched test-negative, case-control study design. We show that vaccine effectiveness was negligible for 2 weeks after the first dose, but increased rapidly in the third and fourth weeks immediately before administration of a second dose. Effectiveness against B.1.1.7 infection was 88.1% (95% confidence interval (CI): 83.7-91.5%) ≥14 days after the first dose but before the second dose, and was 100% (95% CI: 91.8-100.0%) ≥14 days after the second dose. Analogous effectiveness against B.1.351 infection was 61.3% after the first dose (95% CI: 56.5-65.5%) and 96.4% after the second dose (95% CI: 91.9-98.7%). Effectiveness against any severe, critical or fatal COVID-19 disease due to any SARS-CoV-2 infection (predominantly B.1.1.7 and B.1.351) was 81.6% (95% CI: 71.0-88.8%) and 95.7% (95% CI: 73.4-99.9%) after the first and second dose, respectively. The mRNA-1273 vaccine is highly effective against B.1.1.7 and B.1.351 infections, whether symptomatic or asymptomatic, and against any COVID-19 hospitalization and death, even after a single dose.

PMID:34244681 | DOI:10.1038/s41591-021-01446-y

Sci Rep. 2021 Jul 9;11(1):14250. doi: 10.1038/s41598-021-93719-2.

ABSTRACT

Triaging and prioritising patients for RT-PCR test had been essential in the management of COVID-19 in resource-scarce countries. In this study, we applied machine learning (ML) to the task of detection of SARS-CoV-2 infection using basic laboratory markers. We performed the statistical analysis and trained an ML model on a retrospective cohort of 5148 patients from 24 hospitals in Hong Kong to classify COVID-19 and other aetiology of pneumonia. We validated the model on three temporal validation sets from different waves of infection in Hong Kong. For predicting SARS-CoV-2 infection, the ML model achieved high AUCs and specificity but low sensitivity in all three validation sets (AUC: 89.9-95.8%; Sensitivity: 55.5-77.8%; Specificity: 91.5-98.3%). When used in adjunction with radiologist interpretations of chest radiographs, the sensitivity was over 90% while keeping moderate specificity. Our study showed that machine learning model based on readily available laboratory markers could achieve high accuracy in predicting SARS-CoV-2 infection.

PMID:34244563 | DOI:10.1038/s41598-021-93719-2

Sci Rep. 2021 Jul 9;11(1):14179. doi: 10.1038/s41598-021-93483-3.

ABSTRACT

The main aim of the study was to assess the risk of falls, and physical fitness in the group of women aged 60 to 65 years of age suffering from an identified osteoporosis in comparison to a similar group of healthy women. The main question was: What is the level of physical fitness and risk of fall among women with osteoporosis compared to healthy women? The research included 262 women aged 60 to 65 of age: 135 with osteoporosis and 127 healthy ones, living in the Małopolskie and the Świętokrzyskie Provinces of Poland. To assess the level of physical fitness, the Senior Fitness Test (SFT) was used, while the Tinetti POMA (Performance Oriented Mobility Assessment) and Timed Up&Go test (TUG) were used to asses the risk of fall. Significant statistical differences in average results of physical fitness assessment were noticed as regards the following aspects: flexibility of the lower body part p < 0.001; flexibility of the upper body part p < 0.001. Essential differences were demonstrated in assessing the risk of falling with p < 0.01. Women with osteoporosis are marked by a lower physical fitness than healthy women. A higher percentage of great and serious risk of fall was demonstrated among women with osteoporosis.

PMID:34244566 | DOI:10.1038/s41598-021-93483-3

Sci Rep. 2021 Jul 9;11(1):14229. doi: 10.1038/s41598-021-93503-2.

ABSTRACT

Recent studies suggested that cerebrovascular micro-occlusions, i.e. microstokes, could lead to ischemic tissue infarctions and cognitive deficits. Due to their small size, identifying measurable biomarkers of these microvascular lesions remains a major challenge. This work aims to simulate potential MRI signatures combining arterial spin labeling (ASL) and multi-directional diffusion-weighted imaging (DWI). Driving our hypothesis are recent observations demonstrating a radial reorientation of microvasculature around the micro-infarction locus during recovery in mice. Synthetic capillary beds, randomly- and radially-oriented, and optical coherence tomography (OCT) angiograms, acquired in the barrel cortex of mice (n = 5) before and after inducing targeted photothrombosis, were analyzed. Computational vascular graphs combined with a 3D Monte-Carlo simulator were used to characterize the magnetic resonance (MR) response, encompassing the effects of magnetic field perturbations caused by deoxyhemoglobin, and the advection and diffusion of the nuclear spins. We quantified the minimal intravoxel signal loss ratio when applying multiple gradient directions, at varying sequence parameters with and without ASL. With ASL, our results demonstrate a significant difference (p < 0.05) between the signal-ratios computed at baseline and 3 weeks after photothrombosis. The statistical power further increased (p < 0.005) using angiograms measured at week 4. Without ASL, no reliable signal change was found. We found that higher ratios, and accordingly improved significance, were achieved at lower magnetic field strengths (e.g., B0 = 3T) and shorter echo time TE (< 16 ms). Our simulations suggest that microstrokes might be characterized through ASL-DWI sequence, providing necessary insights for posterior experimental validations, and ultimately, future translational trials.

PMID:34244549 | DOI:10.1038/s41598-021-93503-2

Sci Rep. 2021 Jul 9;11(1):14180. doi: 10.1038/s41598-021-92964-9.

ABSTRACT

High resistance towards traditional antibiotics has urged the development of new, natural therapeutics against methicillin-resistant Staphylococcus aureus (MRSA). Prenylated (iso)flavonoids, present mainly in the Fabaceae, can serve as promising candidates. Herein, the anti-MRSA properties of 23 prenylated (iso)flavonoids were assessed in-vitro. The di-prenylated (iso)flavonoids, glabrol (flavanone) and 6,8-diprenyl genistein (isoflavone), together with the mono-prenylated, 4′-O-methyl glabridin (isoflavan), were the most active anti-MRSA compounds (Minimum Inhibitory Concentrations (MIC) ≤ 10 µg/mL, 30 µM). The in-house activity data was complemented with literature data to yield an extended, curated dataset of 67 molecules for the development of robust in-silico prediction models. A QSAR model having a good fit (R²_adj 0.61), low average prediction errors and a good predictive power (Q²) for the training (4% and Q²_LOO 0.57, respectively) and the test set (5% and Q²_test 0.75, respectively) was obtained. Furthermore, the model predicted well the activity of an external validation set (on average 5% prediction errors), as well as the level of activity (low, moderate, high) of prenylated (iso)flavonoids against other Gram-positive bacteria. For the first time, the importance of formal charge, besides hydrophobic volume and hydrogen-bonding, in the anti-MRSA activity was highlighted, thereby suggesting potentially different modes of action of the different prenylated (iso)flavonoids.

PMID:34244528 | DOI:10.1038/s41598-021-92964-9

RMD Open. 2021 Jul;7(2):e001724. doi: 10.1136/rmdopen-2021-001724.

ABSTRACT

AIM: The objective was to examine the prevalence of atherosclerotic cardiovascular disease (ASCVD) and its risk factors among patients with RA with diabetes mellitus (RA-DM) and patients with RA without diabetes mellitus (RAwoDM), and to evaluate lipid and blood pressure (BP) goal attainment in RA-DM and RAwoDM in primary and secondary prevention.

METHODS: The cohort was derived from the Survey of Cardiovascular Disease Risk Factors in Patients with Rheumatoid Arthritis from 53 centres/19 countries/3 continents during 2014-2019. We evaluated the prevalence of cardiovascular disease (CVD) among RA-DM and RAwoDM. The study population was divided into those with and without ASCVD, and within these groups we compared risk factors and CVD preventive treatment between RA-DM and RAwoDM.

RESULTS: The study population comprised of 10 543 patients with RA, of whom 1381 (13%) had DM. ASCVD was present in 26.7% in RA-DM compared with 11.6% RAwoDM (p<0.001). The proportion of patients with a diagnosis of hypertension, hyperlipidaemia and use of lipid-lowering or antihypertensive agents was higher among RA-DM than RAwoDM (p<0.001 for all). The majority of patients with ASCVD did not reach the lipid goal of low-density lipoprotein cholesterol <1.8 mmol/L. The lipid goal attainment was statistically and clinically significantly higher in RA-DM compared with RAwoDM both for patients with and without ASCVD. The systolic BP target of <140 mm Hg was reached by the majority of patients, and there were no statistically nor clinically significant differences in attainment of BP targets between RA-DM and RAwoDM.

CONCLUSION: CVD preventive medication use and prevalence of ASCVD were higher in RA-DM than in RAwoDM, and lipid goals were also more frequently obtained in RA-DM. Lessons may be learnt from CVD prevention programmes in DM to clinically benefit patients with RA .

PMID:34244381 | DOI:10.1136/rmdopen-2021-001724

Aging (Albany NY). 2021 Jul 9;13. doi: 10.18632/aging.203252. Online ahead of print.

ABSTRACT

Previous studies have provided limited evidence for the effect of tomato intake on bladder cancer incidence. This study aimed to evaluate the association between dietary tomato or lycopene consumption and bladder cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression model adjusting for confounders. After a median of 12.5 years of follow-up, 774 incident bladder cancer cases were identified. We found no statistically significant association between dietary intake of raw tomatoes and bladder cancer risk (Adjusted model: HR_{Q5 VS Q1} = 1.20, 95% CI: 0.95-1.52; P for trend = 0.243). Dietary intakes of tomato catsup, tomato salsa and tomato juice were also not associated with the risk of bladder cancer (all P for trend > 0.05). There was no statistically significant association between dietary consumption of lycopene and bladder cancer risk (Adjusted model: HR_{Q5 vs. Q1} = 1.04, 95% CI 0.82-1.33; P for trend = 0.590). In summary, analysis of the PLCO study suggested that dietary consumption of tomato or lycopene was not associated with the risk of bladder cancer.

PMID:34244460 | DOI:10.18632/aging.203252

Sci Rep. 2021 Jul 9;11(1):14206. doi: 10.1038/s41598-021-93091-1.

ABSTRACT

We consider a velocity field with linear viscous interactions defined on a one dimensional lattice. Brownian baths with different parameters can be coupled to the boundary sites and to the bulk sites, determining different kinds of non-equilibrium steady states or free-cooling dynamics. Analytical results for spatial and temporal correlations are provided by analytical diagonalisation of the system’s equations in the infinite size limit. We demonstrate that spatial correlations are scale-free and time-scales become exceedingly long when the system is driven only at the boundaries. On the contrary, in the case a bath is coupled to the bulk sites too, an exponential correlation decay is found with a finite characteristic length. This is also true in the free cooling regime, but in this case the correlation length grows diffusively in time. We discuss the crucial role of boundary driving for long-range correlations and slow time-scales, proposing an analogy between this simplified dynamical model and dense vibro-fluidized granular materials. Several generalizations and connections with the statistical physics of active matter are also suggested.

PMID:34244527 | DOI:10.1038/s41598-021-93091-1

BMJ Mil Health. 2021 Jul 9:bmjmilitary-2021-001791. doi: 10.1136/bmjmilitary-2021-001791. Online ahead of print.

ABSTRACT

INTRODUCTION: Military studies have investigated acute injuries associated with parachute jumps, but the literature does not address paratroopers’ cumulative microtraumatic (CMT) injury risk, nor does it compare injury risks between paratroopers and the rest of the military population. This study determined whether US active duty Army paratroopers experienced greater injury risks than their non-paratrooper soldier counterparts and whether their injuries cost more to treat suggesting greater injury severity.

METHODS: This retrospective study evaluated electronic medical records (2016-2018) for 31 621 paratroopers and a randomly selected comparison group of 170 715 non-paratrooper soldiers. Analyses included univariate and multivariate regression to quantify odds of injuries associated with risk variables and additional descriptive statistics.

RESULTS: Paratroopers had a 57% increase in the odds of experiencing one or more injuries (OR=1.57, 95% CI: 1.52 to 1.62) after controlling for sex, race and age, with a greater proportion of acute injuries (OR=1.38, 95% CI: 1.34 to 1.42), relative to comparison group soldiers. Injury types proportionally higher among paratroopers included head trauma and shoulder injuries. Average injury cost among paratroopers was 13% lower than for non-paratroopers ($2470 vs $2830 per injury). Among both populations, acute injury costs were notably higher than for CMT injuries (paratroopers, $1710/$630; non-paratroopers, $1860/$880 per injury).

CONCLUSIONS: Paratroopers were more likely to incur injury, especially an acute injury, than non-paratroopers. However, paratroopers’ average injury costs were less. This may be due to higher return-to-duty motivations, fitness levels, and/or facility-specific cost of care. Future studies should investigate causes of injuries found to be proportionally higher among paratroopers.

PMID:34244378 | DOI:10.1136/bmjmilitary-2021-001791