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Small extracellular vesicles (sEVs) play a central role in cell-to-cell communication in normal physiology and in disease, including gestational diabetes mellitus (GDM). The goal of the present study was to test the hypothesis that chronic administration of sEVs isolated from GDM causes glucose intolerance in healthy pregnant mice. Small EVs were isolated from plasma between 24 and 28 weeks gestation from healthy pregnant women (controls) and GDM, and infused intravenously for 4 days in late pregnant mice using a mini-osmotic pump. Subsequently in vivo glucose tolerance was assessed, and muscle and adipose tissue insulin sensitivity and islet glucose stimulated insulin secretion (GSIS) were determined in vitro. Mice infused with sEVs from GDM developed glucose intolerance. Administration of sEVs from controls, but not sEVs from GDM women, stimulated islet GSIS and increased fasting insulin levels in pregnant mice. Neither infusion of sEVs from controls nor from GDM women affected muscle insulin sensitivity, placental insulin or mTOR signaling, placental and fetal weight. Moreover, these results were not associated with immunomodulatory effects as human sEVs did not activate mouse T cells in vitro. We suggest that circulating sEVs regulate maternal glucose homeostasis in pregnancy and may contribute to the attenuated islet insulin secretion and more pronounced glucose intolerance in GDM as compared with healthy pregnancy.

BackgroundThere are limited studies evaluating the impact of COVID-19-related interruptions on hepatitis B virus (HBV) screening in endemic countries in Sub-Saharan Africa.MethodsWe conducted a retrospective study of HBV testing in a community pharmacy in Freetown, Sierra Leone, from October 1, 2019, through September 30, 2022. We compared participant characteristics using Pearson’s chi-square test. We evaluated trends in HBV screening and diagnosis using one-way ANOVA with Tukey’s or Dunnett’s post-test.FindingsOf 920 individuals screened, 161 had detectable HBsAg (seroprevalence 17.5% [95% CI 14.9-20.4]). There was a 100% decrease in HBV screening during January-June of 2020; however, screening increased by 27% and 23% in the first and second year after COVID-19, respectively. Mean quarterly tests showed a significant upward trend: 55 ± 6 tests during January-March (baseline), 74 ± 16 tests during April-June, 101 ± 3 tests during July-September, and 107 ± 17 tests during October-December (one-way ANOVA test for trend, F=7.7, p = 0.0254) but not the mean quarterly number of people diagnosed with HBV (F = 0.34, p = 0.7992).InterpretationCommunity-based HBV screening dramatically improved following temporary disruptions related to COVID-19. Seasonal variation in HBV screening, but not HBV diagnosis, may have implications for HBV elimination efforts in Sierra Leone and other West African countries.

Hepatitis B virus (HBV) infection is a major public health problem in Sierra Leone, yet reliable estimates of cases are lacking. This study aimed to provide an estimate of the national prevalence of chronic HBV infection in the general population and select groups in Sierra Leone. We used the electronic databases PubMed/MEDLINE, Embase, Scopus, ScienceDirect, Web of Science, Google Scholar, and African Journals Online to systematically review articles reporting hepatitis B infection surface antigen seroprevalence estimates in Sierra Leone during 1997–2022. We estimated pooled HBV seroprevalence rates and assessed potential sources of heterogeneity. Of 546 publications screened, 22 studies with a total sample size of 107,186 people were included in the systematic review and meta-analysis. The pooled prevalence of chronic HBV infection was 13.0% (95% CI, 10.0–16.0) (I2 = 99%; Pheterogeneity < 0.01). During the study period, the HBV prevalence rates were as follows: 17.9% (95% CI, 6.7–39.8) before 2015, 13.3% (95% CI, 10.4–16.9) during 2015–2019, and 10.7% (95% CI, 7.5–14.9) during 2020–2022. The use of the 2020–2022 HBV prevalence estimates corresponded to 870,000 cases of chronic HBV infection (uncertainty interval, 610,000–1,213,000), or approximately one in nine people. The highest HBV seroprevalence estimates were among adolescents aged 10–17 years (17.0%; 95% CI, 8.8–30.5), Ebola survivors (36.8%; 95% CI, 26.2–48.8), people living with HIV (15.9%; 95% CI, 10.6–23.0), and those in the Northern Province (19.0%; 95% CI, 6.4–44.7) and Southern Province (19.7%; 95% CI, 10.9–32.8) regions. These findings may help inform national HBV program implementation in Sierra Leone.

ObjectivesPeople living with HIV (PWH) are at increased risk of COVID-19 related morbidity and mortality, yet less is known about COVID-19 vaccination uptake and hesitancy, especially in sub-Saharan Africa. We aimed to evaluate COVID-19 vaccine uptake and hesitancy among PWH in Sierra Leone.MethodsWe conducted a cross-sectional study in a convenience sample of PWH in routine care at Connaught Hospital in Freetown, Sierra Leone from April through June 2022. We collected sociodemographic and health-related data. We used the VAX Scale, a validated instrument to assess attitudes towards COVID-19 vaccination. From the responses, we constructed hesitancy (VAX) scores, with higher scores implying negative attitudes towards vaccination. We used generalized linear models to identify factors associated with vaccine hesitancy.ResultsA total of 490 PWH were enrolled (71.4% female, median age 38 years, median CD4 count 412 cells/mm3, 83.9% virologically suppressed). About 17.3% had received at least one dose of a COVID-19 vaccine. The mean VAX score was 43.14 ± 7.05, corresponding to 59.9% participants classified as vaccine hesitant. Preference for natural immunity (65.8%) and concerns about commercial profiteering (64.4%) were the commonest reasons for hesitancy, followed by mistrust of vaccine benefits (61.4%) and worries about future side effects (48.0%). In adjusted regression analysis, being Muslim (β = 2.563, p < 0.001) and residence in urban areas (β = 1.709, p = 0.010) were associated with greater vaccine hesitancy, while having tested ever for COVID-19 was associated with lesser vaccine hesitancy (β = -3.417, p = 0.027).ConclusionWe observed a low COVID-19 vaccine uptake and high hesitancy among PWH in Sierra Leone. Our findings underscore the need to address vaccine hesitancy as a critical element of efforts to boost COVID-19 vaccine uptake among this population in Sierra Leone.

We review the Canadian federal government‘s recently enacted Food Policy for Canada (FPC). Three arguments are developed. First, the development and vision statement of the FPC implies that improving Canadian food security is a specific objective of the policy. Second, if assessed by the measure of food insecurity promulgated by Statistics Canada, the effectiveness of the FPC in reducing Canadian food insecurity will primarily depend on the extent to which it improves household incomes and/or lowers food prices. We evaluate the current programmatic content by these criteria. Third, and related to the second point, we argue that the variation in the severity of food insecurity is an important consideration in assessing the effectiveness of FPC programs in reducing food insecurity as measured by Statistics Canada. Finally, we combine these three arguments into a simple figure/heuristic that can serve as a guide to the assessment and development of FPC programs seeking to enhance food insecurity in Canada.

Background Residual neuromuscular blockade can be avoided with quantitative neuromuscular monitoring. The authors embarked on a professional practice initiative to attain documented train-of-four ratios greater than or equal to 0.90 in all patients for improved patient outcomes through reducing residual paralysis. Methods The authors utilized equipment trials, educational videos, quantitative monitors in all anesthetizing locations, and electronic clinical decision support with real-time alerts, and initiated an ongoing professional practice metric. This was a retrospective assessment (2016 to 2020) of train-of-four ratios greater than or equal to 0.9 that were documented before extubation. Anesthesia records were manually reviewed for neuromuscular blockade management details. Medical charts of surgical patients who received a neuromuscular blocking drug were electronically searched for patient characteristics and outcomes. Results From pre- to postimplementation, more patients were assigned American Society of Anesthesiologists Physical Status III to V, fewer were inpatients, the rocuronium average dose was higher, and more patients had a prereversal train-of-four count less than 4. Manually reviewed anesthesia records (n = 2,807) had 2 of 172 (1%) cases with documentation of train-of-four ratios greater than or equal to 0.90 in November 2016, which was fewer than the cases in December 2020 (250 of 269 [93%]). Postimplementation (February 1, 2020, to December 31, 2020), sugammadex (650 of 935 [70%]), neostigmine (195 of 935 [21%]), and no reversal (90 of 935 [10%]) were used to attain train-of-four ratios greater than or equal to 0.90 in 856 of 935 (92%) of patients. In the electronically searched medical charts (n = 20,181), postimplementation inpatients had shorter postanesthesia care unit lengths of stay (7% difference; median [in min] [25th, 75th interquartile range], 73 [55, 102] to 68 [49, 95]; P < 0.001), pulmonary complications were less (43% difference; 94 of 4,138 [2.3%] to 23 of 1,817 [1.3%]; P = 0.010; −1.0% difference [95% CI, –1.7 to –0.3%]), and hospital length of stay was shorter (median [in days] [25th, 75th], 3 [2, 5] to 2 [1, 4]; P < 0.001). Conclusions In this professional practice initiative, documentation of train-of-four ratios greater than or equal to 0.90 occurred for 93% of patients in a busy clinical practice. Return-of-strength documentation is an intermediate outcome, and only one of many factors contributing to patient outcomes. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

The anti-hyperglycaemic and anti-oxidative effect of Merremia tridentata (Linn) Hallier F ethanol leaf extract (MTELE) was evaluated in this study. Diabetes was induced on male albino wistar rats by a single intra-peritoneal injection of 65mg/kg body weight dose of streptozotocin. The rats were divided into seven groups and treated accordingly with varying doses (50 mg/kg, 75 mg/kg and 100 mg/kg body weight) of MTELE for seven weeks. Body weight and plasma glucose levels were monitored while antioxidant parameters, catalase (CAT), superoxide dismutase (SOD) activities, reduced glutathione (GSH) concentration and levels of thiobarbituric acid reacting substances (TBARS) were determined in the liver and kidney tissues. There was a significant (p

SummaryCold stress is one of the major environmental factors that limit growth and yield of plants. However, it is still not fully understood how plants account for daily temperature fluctuations, nor how these temperature changes are integrated with other regulatory systems such as the circadian clock.We demonstrate that REVEILLE2, a MYB-like transcription factor, exhibits a cold-induced alternative splicing switch from a non-translatable isoform at ambient temperature to a translatable isoform upon cold exposure. We explore the biological function ofREVEILLE2using a combination of molecular genetics, transcriptomics, and physiology.Disruption of theREVEILLE2cooling switch alters regulatory gene expression, impairs circadian timing, and improves photosynthetic capacity. Changes in nuclear gene expression are particularly apparent in the initial hours following chilling, with chloroplast gene expression subsequently up-regulated.TheREVEILLE2cold switch extends our understanding of plants immediate response to cooling. We propose that the circadian componentREVEILLE2restricts plants responses to nocturnal reductions in temperature, thereby enabling appropriate responses to daily environmental changes.Plain language summaryPlants need to respond appropriately to temperature, accounting for the expected daily patterns of reduced temperatures that occur every night relative to the day. Here, we show that a gene expressed at night fulfils this function.