Rumen microbiome and fat deposition in sheep: insights from a bidirectional mendelian randomization study.

Rumen microbiotas are known to influence the fat deposition (FD) in sheep, but controversy over causality remains unresolved. Here, we performed microbiome-wide association studies (MWAS), microbiome genome-wide association analysis (mbGWAS) and bidirectional mendelian randomization (MR) analyses on 1,150 sheep with genotype data from whole-genome resequencing, 16S rRNA sequencing and multilevel FD-traits data. We quantified the proportion of individual variation in FD-traits explained by host genetics, rumen microbiota, and their interaction effects.

Identification of the Biotransformation Pathways of a Potential Oral Male Contraceptive, 11β-Methyl-19-Nortestosterone (11β-MNT) and Its Prodrugs: An In Vitro Study Highlights the Contribution of Polymorphic Intestinal UGT2B17.

11β-Methyl-19-nortestosterone dodecylcarbonate (11β-MNTDC) is a prodrug of 11β-MNT and is being considered as a promising male oral contraceptive candidate in clinical development. However, the oral administration of 11β-MNTDC exhibits an ~200-fold lower serum concentration of 11β-MNT compared to 11β-MNTDC, resulting in the poor bioavailability of 11β-MNT. To elucidate the role of the first-pass metabolism of 11β-MNT in its poor bioavailability, we determined the biotransformation products of 11β-MNT and its prodrugs in human in vitro models.

Comparison of Relative Activity versus Relative Expression Factors (RAF versus REF) in Predicting Glucuronidation Mediated Drug Clearance Using Recombinant UGTs.

Purpose: Predicting the quantitative fraction of glucuronidation (f) by individual UDP-glucuronosyltransferase enzymes (UGTs) is challenging due to the lack of selective inhibitors and inconsistent activity of recombinant UGT systems (rUGTs). Our study compares the relative expression versus activity factors (REF versus RAF) to predict f based on rUGT data to human liver and intestinal microsomes (HLM and HIM).

Methods: REF scalars were derived from a previous in-house proteomics study for eleven UGT enzymes (UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT1A10, UGT2B4, UGT2B7, UGT2B10, UGT2B15, and UGT2B17), whereas RAF was calculated by measuring activities in rUGTs to microsomes of selective UGT probe substrates.

Modeling Plutonium Decorporation in a Female Nuclear Worker Treated with Ca-DTPA after Inhalation Intake.

The present work models plutonium (Pu) biokinetics in a female former nuclear worker. Her bioassay measurements are available at the US Transuranium and Uranium Registries. The worker was internally exposed to a plutonium-americium mixture via acute inhalation at a nuclear weapons facility.

A qualitative assessment of influenza vaccine uptake among children in Kenya.

Background: Influenza is a significant contributor to acute respiratory infections (ARI), and children < 5 years are at increased risk of severe influenza disease. In Kenya the influenza vaccine is not included in the Kenya Expanded Programme on Immunization (KEPI). To inform roll-out of a national influenza vaccination program, we implemented an influenza vaccine demonstration project in Nakuru and Mombasa counties in Kenya from 2019 to 2021 and set out to establish factors driving influenza vaccine acceptance and hesitancy among caregivers of children aged 6-23 months.

Ontogeny of Human Liver Aldehyde Oxidase: Developmental Changes and Implications for Drug Metabolism.

Despite the increasing importance of aldehyde oxidase (AO) in the drug metabolism of clinical candidates, ontogeny data for AO are limited. The objective of our study was to characterize the age-dependent AO content and activity in the human liver cytosolic fraction (HLC) and human hepatocytes (HH). HLC ( = 121 donors) and HH ( = 50 donors) were analyzed for (1) AO protein content by quantitative proteomics and (2) enzyme activity using carbazeran as a probe substrate.

Reduced Opioid Use Among Patients Who Received Liposomal Bupivacaine Brachial Plexus Block for Total Shoulder Arthroplasty.

Purpose This retrospective cohort explores the efficacy of regional shoulder blocks using Exparel™ in patients undergoing total shoulder arthroplasty (TSA)/reverse total shoulder arthroplasty (RSA) to reduce total opioid prescription, refills, and length of stay in the acute care setting. Methods Patients who underwent TSA/RSA by a single surgeon in a three-year period were evaluated. Patients in the case group received liposomal bupivacaine 1.

Seroconversion and seroprevalence of TORCH infections in a pregnant women cohort study, Mombasa, Kenya, 2017-2019.

Women infected during pregnancy with TORCH (Toxoplasmosis, Other, Rubella, Cytomegalovirus, and Herpes simplex viruses) pathogens have a higher risk of adverse birth outcomes including stillbirth / miscarriage because of mother-to-child transmission. To investigate these risks in pregnant women in Kenya, we analyzed serum specimens from a pregnancy cohort study at three healthcare facilities. A sample of 481 participants was selected for TORCH pathogen antibody testing to determine seroprevalence.

Costs of seasonal influenza vaccine delivery in a pediatric demonstration project for children aged 6-23 months - Nakuru and Mombasa Counties, Kenya, 2019-2021.

Background: During November 2019-October 2021, a pediatric influenza vaccination demonstration project was conducted in four sub-counties in Kenya. The demonstration piloted two different delivery strategies: year-round vaccination and a four-month vaccination campaign. Our objective was to compare the costs of both delivery strategies.

Comparing performance of year-round and campaign-mode influenza vaccination strategies among children aged 6-23 months in Kenya: 2019-2021.

Introduction: In 2016, the Kenya National Immunization Technical Advisory Group requested additional programmatic and cost effectiveness data to inform the choice of strategy for a national influenza vaccination program among children aged 6-23 months of age. In response, we conducted an influenza vaccine demonstration project to compare the performance of a year-round versus campaign-mode vaccination strategy. Findings from this demonstration project will help identify essential learning lessons for a national program.

Resilience of routine childhood immunization services in two counties in Kenya in the face of the COVID-19 pandemic.

The recently emerged coronavirus disease 2019 (COVID-19) has caused considerable morbidity and mortality worldwide and disrupted health services. We describe the effect of the COVID-19 pandemic on utilization of childhood vaccination services during the pandemic. Using a mixed methods approach combining retrospective data review, a cross-sectional survey, focus group discussions among care givers and key informant interviews among nurses, we collected data between May and September 2021 in Mombasa and Nakuru counties.

Heritability and recursive influence of host genetics on the rumen microbiota drive body weight variance in male Hu sheep lambs.

Background: Heritable rumen microbiota is an important modulator of ruminant growth performance. However, no information exists to date on host genetics-rumen microbiota interactions and their association with phenotype in sheep. To solve this, we curated and analyzed whole-genome resequencing genotypes, 16S rumen-microbiota data, and longitudinal body weight (BW) phenotypes from 1150 sheep.

Dissecting Parameters Contributing to the Underprediction of Aldehyde Oxidase-Mediated Metabolic Clearance of Drugs.

We investigated the effect of variability and instability in aldehyde oxidase (AO) content and activity on the scaling of in vitro metabolism data. AO content and activity in human liver cytosol (HLC) and five recombinant human AO preparations (rAO) were determined using targeted proteomics and carbazeran oxidation assay, respectively. AO content was highly variable as indicated by the relative expression factor (REF; i.

In-depth genome and pan-genome analysis of a metal-resistant bacterium OS-1.

A metal-resistant bacterium OS-1 was isolated from waste-contaminated soil in Ranchi City, India. The isolated strain OS-1 showed its growth at 25-45°C, pH 5.0-9.

Modulation of Polar Auxin Transport Identifies the Molecular Determinants of Source-Sink Carbon Relationships and Sink Strength in Poplar.

Source-to-sink carbon (C) allocation driven by the sink strength, i.e., the ability of a sink organ to import C, plays a central role in tissue growth and biomass productivity.

Annotated genome sequence of a fast-growing diploid clone of red alder (Alnus rubra Bong.).

Red alder (Alnus rubra Bong.) is an ecologically significant and important fast-growing commercial tree species native to western coastal and riparian regions of North America, having highly desirable wood, pigment, and medicinal properties. We have sequenced the genome of a rapidly growing clone.

Near-Complete SARS-CoV-2 Seroprevalence among Rural and Urban Kenyans despite Significant Vaccine Hesitancy and Refusal.

Considering the early inequity in global COVID-19 vaccine distribution, we compared the level of population immunity to SARS-CoV-2 with vaccine uptake and refusal between rural and urban Kenya two years after the pandemic onset. A population-based seroprevalence study was conducted in the city of Nairobi (n = 781) and a rural western county (n = 810) between January and February 2022. The overall SARS-CoV-2 seroprevalence was 90.

Response mechanisms of anaerobic fermentative sludge to zinc oxide nanoparticles during medium-chain carboxylates production from waste activated sludge.

The conversion of waste activated sludge (WAS) into medium chain carboxylates (MCCs) has attracted much attention, while investigations of the impacts of ZnO nanoparticles (NPs) on this process are sparse. The present study showed that 8 mg/g-TSS of ZnO NPs have little effects on all key steps and the activity of anaerobes, and finally leading to unchanged MCCs production. Although 30 mg/g-TSS of ZnO NPs weakly inhibited the hydrolysis, acidogenesis, and chain elongation process, WAS solubilization was enhanced, thus, the improvement was enough to offset inhibition, also resulting in an insignificant impact on overall MCCs production.

Nonmonotonic effect of CuO nanoparticles on medium-chain carboxylates production from waste activated sludge.

The growing applications of CuO nanoparticles (NPs) in industrial and agriculture has increased their concentrations in wastewater and subsequently accumulated in waste activated sludge (WAS), raising concerns about their impact on reutilization of WAS, especially on the medium-chain carboxylates (MCCs) production from anaerobic fermentation of WAS. Here we showed that CuO NPs at 10-50 mg/g-TS can significantly inhibit MCCs production, and reactive oxygen species generation was revealed to be the key factor linked to the phenomena. At lower CuO NPs concentrations (0.