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Nevin Manimala Statistics

Pilot trial of vitamin D3 and calcifediol in healthy vitamin D deficient adults: does it change the fecal microbiome?

J Clin Endocrinol Metab. 2021 Aug 3:dgab573. doi: 10.1210/clinem/dgab573. Online ahead of print.

ABSTRACT

PURPOSE: To determine whether correcting vitamin D deficiency with cholecalciferol (vitamin D3, D3) or calcifediol (25-hydroxyvitamin D3, 25(OH)D3) changes gut microbiome composition.

METHODS: 18 adults with vitamin D deficiency (25-hydroxyvitamin D [25(OH)D] <20 ng/ml) received 60 mcg/day of D3 or 20 mcg/day of 25(OH)D3 for 8 weeks. Changes in serum 25(OH)D, 1,25-diydroxyvitamin D (1,25(OH)2D), and 24,25-dihydroxyvitamin D (24,25(OH)2D) were assessed. We characterized composition of the fecal microbiota using 16S rRNA gene sequencing, and examined changes in α-diversity (Chao 1, Faith’s Phylogenetic Diversity, Shannon Index), β-diversity (DEICODE), and genus-level abundances (DESeq2).

RESULTS: Vitamin D3 and 25(OH)D3 groups were similar. After 8 weeks of vitamin D3, mean 25(OH)D and 24,25(OH)2D increased significantly, but 1,25(OH)2D did not (25(OH)D: 17.8 to 30.1 ng/ml [p=0.002]; 24,25(OH)2D: 1.1 to 2.7 ng/ml [p=0.003]; 1,25(OH)2D: 49.5 to 53.0 pg/ml [p=0.9]). After 8 weeks of 25(OH)D3, mean 25(OH)D, 24,25(OH)2D, and 1,25(OH)2D increased significantly (25(OH)D: 16.7 to 50.6 ng/ml [p<0.0001]; 24,25(OH)2D: 1.3 to 6.2 ng/ml [p=0.0001]; 1,25(OH)2D: 56.5 to 74.2 pg/ml [p=0.05]). Fecal microbial α-diversity and β-diversity did not change with D3 or 25D3 supplementation. Mean relative abundance of Firmicutes increased and mean relative abundance of Bacterioidetes decreased from baseline to four weeks, but returned to baseline by study completion. DESeq2 analysis did not confirm any statistically significant taxonomic changes.

MAIN CONCLUSIONS: In a small sample of healthy adults with vitamin D deficiency, restoration of vitamin D sufficiency with vitamin D3 or 25(OH)D3 did not lead to lasting changes in the fecal microbiota.

PMID:34343292 | DOI:10.1210/clinem/dgab573

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Nevin Manimala Statistics

Excess mortality due to Covid-19? A comparison of total mortality in 2020 with total mortality in 2016 to 2019 in Germany, Sweden and Spain

PLoS One. 2021 Aug 3;16(8):e0255540. doi: 10.1371/journal.pone.0255540. eCollection 2021.

ABSTRACT

INTRODUCTION: Excess mortality is a suitable indicator of health consequences of COVID-19 because death from any cause is clearly defined contrary to death from Covid-19. We compared the overall mortality in 2020 with the overall mortality in 2016 to 2019 in Germany, Sweden and Spain. Contrary to other studies, we also took the demographic development between 2016 and 2020 and increasing life expectancy into account.

METHODS: Using death and population figures from the EUROSTAT database, we estimated weekly and cumulative Standardized Mortality Ratios (SMR) with 95% confidence intervals (CI) for the year 2020. We applied two approaches to calculate weekly numbers of death expected in 2020: first, we used mean weekly mortality rates from 2016 to 2019 as expected mortality rates for 2020, and, second, to consider increasing life expectancy, we calculated expected mortality rates for 2020 by extrapolation from mortality rates from 2016 to 2019.

RESULTS: In the first approach, the cumulative SMRs show that in Germany and Sweden there was no or little excess mortality in 2020 (SMR = 0.976 (95% CI: 0.974-0.978), and 1.030 (1.023-1.036), respectively), while in Spain the excess mortality was 14.8% (1.148 (1.144-1.151)). In the second approach, the corresponding SMRs for Germany and Sweden increased to 1.009 (1.007-1.011) and 1.083 (1.076-1.090), respectively, whereas results for Spain were virtually unchanged.

CONCLUSION: In 2020, there was barely any excess mortality in Germany for both approaches. In Sweden, excess mortality was 3% without, and 8% with consideration of increasing life expectancy.

PMID:34343210 | DOI:10.1371/journal.pone.0255540

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Nevin Manimala Statistics

A systematic review and meta-analysis of measurement properties of objective structured clinical examinations used in physical therapy licensure and a structured review of licensure practices in countries with well-developed regulation systems

PLoS One. 2021 Aug 3;16(8):e0255696. doi: 10.1371/journal.pone.0255696. eCollection 2021.

ABSTRACT

BACKGROUND: The Objective Structured Clinical Examination (OSCE) is a commonly used tool internationally to assess clinical competency. Physical therapy (PT) licensure processes vary internationally. The OSCE is the tool used in Canada to assess clinical competency for PT graduates seeking licensure. Previous studies that examined the measurement properties of OSCEs present contradictory results.

OBJECTIVES: The first objective was to investigate the reliability and validity of OSCEs when administered to PTs during their education or as part of a licensure process. The second objective was to conduct a structured review to report PT educational and licensing components and policies in 17 countries with well-developed PT regulation systems.

METHODS: An electronic search was performed in four databases from inception to 31st March 2021 to identify relevant articles. Two reviewers performed the critical appraisal of the included studies using a validated quality assessment tool. We deployed a random effects meta-analysis on reliability and validity estimates of OSCEs and examined sources of heterogeneity with univariate meta-regressions. We searched websites of professional regulatory bodies and associations for data on educational and licencing components and policies. Educational and licensing components across countries were synthesized descriptively.

RESULTS: A pooled estimate of Cronbach’s alpha of 0.55, (95% CI: 0.41, 0.67) was determined for OSCEs. The pooled estimate of Intraclass Correlation Coefficient (ICC) between assessors was 0.77 (95% CI: 0.70, 0.83). The pooled estimate of Pearson Correlation between multiple OSCE stations’ scores was 0.27 (95% CI: 0.15, 0.39); and between each station score and the total score was 0.71 (95% CI: 0.61, 0.79). The pooled estimates for kappa Coefficients were 0.75 (95% CI: 0.58, 0.86) and 0.84, (95% CI: 0.72, 0.91) for intra-rater and inter-rater reliability of the standardised patient respectively. From the 17 included countries, Canada (excluding Quebec) was the only country that required both a clinical and written competency exam following graduation from an accredited PT program. Two countries (USA, UAE) required a written competency exam. The remaining 14 countries did not require an additional competency examination after completion of degree requirements from an accredited program.

CONCLUSIONS: We found weak evidence that OSCE examinations items are internally consistent when used to assess PTs. Canada (excluding Quebec) is the only country out of 17 implementing a national clinical competency examination for their PT graduates to achieve licensure after completing professional degree requirements.

PMID:34343213 | DOI:10.1371/journal.pone.0255696

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Nevin Manimala Statistics

SuMO-Fil: Supervised multi-omic filtering prior to performing network analysis

PLoS One. 2021 Aug 3;16(8):e0255579. doi: 10.1371/journal.pone.0255579. eCollection 2021.

ABSTRACT

Multi-omic analyses that integrate many high-dimensional datasets often present significant deficiencies in statistical power and require time consuming computations to execute the analytical methods. We present SuMO-Fil to remedy against these issues which is a pre-processing method for Supervised Multi-Omic Filtering that removes variables or features considered to be irrelevant noise. SuMO-Fil is intended to be performed prior to downstream analyses that detect supervised gene networks in sparse settings. We accomplish this by implementing variable filters based on low similarity across the datasets in conjunction with low similarity with the outcome. This approach can improve accuracy, as well as reduce run times for a variety of computationally expensive downstream analyses. This method has applications in a setting where the downstream analysis may include sparse canonical correlation analysis. Filtering methods specifically for cluster and network analysis are introduced and compared by simulating modular networks with known statistical properties. The SuMO-Fil method performs favorably by eliminating non-network features while maintaining important biological signal under a variety of different signal settings as compared to popular filtering techniques based on low means or low variances. We show that the speed and accuracy of methods such as supervised sparse canonical correlation are increased after using SuMO-Fil, thus greatly improving the scalability of these approaches.

PMID:34343218 | DOI:10.1371/journal.pone.0255579

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Nevin Manimala Statistics

Unveiling a key role of oxaloacetate-glutamate interaction in regulation of respiration and ROS generation in nonsynaptic brain mitochondria using a kinetic model

PLoS One. 2021 Aug 3;16(8):e0255164. doi: 10.1371/journal.pone.0255164. eCollection 2021.

ABSTRACT

Glutamate plays diverse roles in neuronal cells, affecting cell energetics and reactive oxygen species (ROS) generation. These roles are especially vital for neuronal cells, which deal with high amounts of glutamate as a neurotransmitter. Our analysis explored neuronal glutamate implication in cellular energy metabolism and ROS generation, using a kinetic model that simulates electron transport details in respiratory complexes, linked ROS generation and metabolic reactions. The analysis focused on the fact that glutamate attenuates complex II inhibition by oxaloacetate, stimulating the latter’s transformation into aspartate. Such a mechanism of complex II activation by glutamate could cause almost complete reduction of ubiquinone and deficiency of oxidized form (Q), which closes the main stream of electron transport and opens a way to massive ROS generating transfer in complex III from semiquinone radicals to molecular oxygen. In this way, under low workload, glutamate triggers the respiratory chain (RC) into a different steady state characterized by high ROS generation rate. The observed stepwise dependence of ROS generation on glutamate concentration experimentally validated this prediction. However, glutamate’s attenuation of oxaloacetate’s inhibition accelerates electron transport under high workload. Glutamate-oxaloacetate interaction in complex II regulation underlies the observed effects of uncouplers and inhibitors and acceleration of Ca2+ uptake. Thus, this theoretical analysis uncovered the previously unknown roles of oxaloacetate as a regulator of ROS generation and glutamate as a modifier of this regulation. The model predicted that this mechanism of complex II activation by glutamate might be operative in situ and responsible for excitotoxicity. Spatial-time gradients of synthesized hydrogen peroxide concentration, calculated in the reaction-diffusion model with convection under a non-uniform local approximation of nervous tissue, have shown that overproduction of H2O2 in a cell causes excess of its level in neighbor cells.

PMID:34343196 | DOI:10.1371/journal.pone.0255164

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Nevin Manimala Statistics

Temporal deposition of copper and zinc in the sediments of metal removal constructed wetlands

PLoS One. 2021 Aug 3;16(8):e0255527. doi: 10.1371/journal.pone.0255527. eCollection 2021.

ABSTRACT

The objective of this study was to explore the effects of time, seasons, and total carbon (TC) on Copper (Cu) and Zinc (Zn) deposition in the surface sediments. This study was performed at the H-02 constructed wetland on the Savannah River Site (Aiken, SC, USA). Covering both warm (April-September) and cool (October-March) seasons, several sediment cores were collected twice a year from the H-02 constructed wetland cells from 2007 to 2013. Total concentrations of Cu and Zn were measured in the sediments. Concentrations of Cu and Zn (mean ± standard deviation) in the surface sediments over 7 years of operation increased from 6.0 ± 2.8 and 14.6 ± 4.5 mg kg-1 to 139.6 ± 87.7 and 279.3 ± 202.9 mg kg-1 dry weight, respectively. The linear regression model explained the behavior and the variability of Cu deposition in the sediments. On the other hand, using the generalized least squares extension with the linear regression model allowed for unequal variance and thus produced a model that explained the variance properly, and as a result, was more successful in explaining the pattern of Zn deposition. Total carbon significantly affected both Cu (p = 0.047) and Zn (p < 0.001). Time effect on Cu deposition was statistically significant (p = 0.013), whereas Zn was significantly affected by the season (p = 0.009).

PMID:34343201 | DOI:10.1371/journal.pone.0255527

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Nevin Manimala Statistics

Factors of surface thermal variation in high-mountain lakes of the Pyrenees

PLoS One. 2021 Aug 3;16(8):e0254702. doi: 10.1371/journal.pone.0254702. eCollection 2021.

ABSTRACT

Thermal variables are crucial drivers of biological processes in lakes and ponds. In the current context of climate change, determining which factors better constrain their variation within lake districts become of paramount importance for understanding species distribution and their conservation. In this study, we describe the regional and short-term interannual variability in surface water temperature of high mountain lakes and ponds of the Pyrenees. And, we use mixed regression models to identify key environmental factors and to infer mean and maximum summer temperature, accumulated degree-days, diel temperature ranges and three-days’ oscillation. The study is based on 59 lake-temperature series measured from 2001 to 2014. We found that altitude was the primary explicative factor for accumulated degree-days and mean and maximum temperature. In contrast, lake area showed the most relevant effect on the diel temperature range and temperature oscillations, although diel temperature range was also found to decline with altitude. Furthermore, the morphology of the catchment significantly affected accumulated degree-days and maximum and mean water temperatures. The statistical models developed here were applied to upscale spatially the current thermic conditions across the whole set of lakes and ponds of the Pyrenees.

PMID:34343195 | DOI:10.1371/journal.pone.0254702

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Nevin Manimala Statistics

Application of endocrine biomarkers to update information on reproductive physiology in gray whale (Eschrichtius robustus)

PLoS One. 2021 Aug 3;16(8):e0255368. doi: 10.1371/journal.pone.0255368. eCollection 2021.

ABSTRACT

Most of our knowledge on reproductive biology of gray whales dates back to scientific research conducted during commercial whaling in the late 1950s and 1960s. The goal of the present study was to provide updated insights on reproductive physiology of gray whales, using progesterone and testosterone as biomarkers. We measured hormone concentrations using enzyme immunoassay (EIA) techniques in blubber biopsies collected from 106 individual whales from March to November over a span of 12 years (2004-2016) between California and Alaska. We found testosterone concentrations in males to increase significantly with age (P = 0.03). Adult males showed significantly elevated testosterone concentrations when sampled in the fall compared to the summer (P = 0.01), likely indicating physiological preparation for mating. We measured testosterone concentrations in females of different age classes, but no statistical differences were found. We found significantly higher progesterone concentrations in pregnant females compared to non-pregnant females and adult males (P< 0.001), indicating progesterone is a valid biomarker for pregnancy in gray whales. Both female and male calves had elevated progesterone concentrations, suggesting maternal transfer via lactation. We fit a mixture of two normal distributions to progesterone data from all non-calf females to identify clusters of high and low progesterone and estimated the probability of being pregnant for whales of unknown reproductive status. With this approach we identified likely pregnant and non-pregnant animals. This study represents an important milestone on reproductive profiles in this population, that can be used to estimate more accurate and precise reproductive parameters to be used for better understanding population dynamics of gray whales.

PMID:34343192 | DOI:10.1371/journal.pone.0255368

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Nevin Manimala Statistics

Applicability of TIVAP versus PICC in non-hematological malignancies patients: A meta-analysis and systematic review

PLoS One. 2021 Aug 3;16(8):e0255473. doi: 10.1371/journal.pone.0255473. eCollection 2021.

ABSTRACT

BACKGROUND: Applicability of totally implantable venous access port (TIVAP) and peripherally inserted central venous catheter (PICC) in non-hematological malignancies patients remains controversial.

METHODS: A systematic studies search in the public databases PubMed, EMBASE, Wan Fang, CNKI (China National Knowledge Infrastructure), the Cochrane Library and Google Scholar (updated to May 1, 2020) was performed to identify eligible researches. All statistical tests in this meta-analysis were performed using Stata 12.0 software (Stata Corp, College Station, TX). A P value less than 0.05 was considered statistically significant.

RESULTS: Thirteen studies were included in this final meta-analysis. The pooled data showed that compared with PICC, TIVAP was associated with a higher first-puncture success rate (OR:2.028, 95%CI:1.25-3.289, P<0.05), a lower accidental removal rate (OR:0.447, 95%CI:0.225-0.889, P<0.05) and lower complication rates, including infection (OR:0.570, 95%CI: 0.383-0.850, P<0.05), occlusion (OR:0.172, 95%CI:0.092-0.324, P<0.05), malposition (OR:0.279, 95%CI:0.128-0.608, P<0.05), thrombosis (OR:0.191, 95%CI, 0.111-0.329, P<0.05), phlebitis (OR:0.102, 95%CI, 0.038-0.273, P<0.05), allergy (OR:0.155, 95%CI:0.035-0.696, P<0.05). However, no difference was found in catheter life span (P>0.05) and extravasation (P>0.05). Moreover, TIVAP is more expensive compared with PICC in six-month use (weighted mean difference:3.132, 95%CI:2.434-3.83, P<0.05), but is much similar in 12 months use (P>0.05).

CONCLUSION: For the patients with non-hematological malignancies, TIVAP was superior to PICC in the data related to placement and the incidence of complications. Meanwhile, TIVAP is more expensive compared with PICC in six-month use, but it is much similar in twelve-month use.

PMID:34343193 | DOI:10.1371/journal.pone.0255473

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Nevin Manimala Statistics

Relationships between subendocardial perfusion impairment, arterial stiffness and orthostatic hypotension in hospitalized elderly individuals

J Hypertens. 2021 Aug 2. doi: 10.1097/HJH.0000000000002944. Online ahead of print.

ABSTRACT

BACKGROUND: Orthostatic hypotension is an independent risk factor for cardiovascular morbidity and mortality. Arterial stiffness has been shown to be a pathophysiological mechanism linking orthostatic hypotension and increased cardiovascular risk. This study aims to evaluate the relationship between arterial stiffness, orthostatic hypotension and subendocardial viability ratio (SEVR) and moreover to identify the main predictors of orthostatic hypotension, carotid-femoral pulse wave velocity (PWV-cf) and SEVR.

METHODS: Seventy-five patients were enrolled (mean age 82.95 ± 6.45) in Verona’s AOUI Geriatric ward. They underwent blood pressure, heart rate, body weight measurements and also comorbidity, arterial stiffness (PWV-cf measured by applanation tonometry), SEVR and biochemical indexes.

RESULTS: Prevalence of orthostatic hypotension was 46.6%. Even after adjustment for age, sex, glomerular filtration rate and mean arterial pressure, SEVR values corrected for arterial oxygen and haemoglobin content were statistically lower in orthostatic hypotension patients (P = 0.05) and PWV-cf values were statistically higher in orthostatic hypotension individuals (P = 0.042). In a binary logistic regression, PWV-cf was the only significant predictor of orthostatic hypotension (odds ratio 1.123; P = 0.039; confidence interval = 1.006–1.17).In a backward logistic regression model sex, creatinine clearance and orthostatic hypotension were significant predictors of SEVR corrected for O2 content. Mean arterial pressure, creatinine clearance and orthostatic hypotension were significant predictors of PWV-cf.

CONCLUSION: This study shows that orthostatic hypotension is related to increased arterial stiffness, confirming its higher prevalence in elderly patients. Orthostatic hypotension was also associated with reduced values of corrected SEVR, showing a relevant consequence of orthostatic hypotension on subendocardial perfusion impairment.

PMID:34343144 | DOI:10.1097/HJH.0000000000002944