Heavy Metals Can either Aid or Oppose the Protective Function of the Placental Barrier

BACKGROUND: In developing countries, toxic heavy metals are a threatening catastrophe to human health, particularly in the vulnerable group of pregnant mothers and their fetuses. Fortunately, the placenta can be a protective barrier to the fetuses. AIM: To explore the relationship between serum lead, cadmium and arsenic levels in pregnant mothers and their newborns, to address the placental barrier in this situation. METHODS: A cross-sectional study was conducted on 100 pregnant mothers at the time of labour and their newborns. Serum cadmium, lead, and arsenic levels were measured using the Inductively Coupled Plasma Mass Spectrometry. RESULTS: All the studied heavy metals concentrations showed a significant elevation in the maternal blood relative to the cord blood. There was a significant association between the maternal lead and both fetal lead and arsenic. Meanwhile, a negative but insignificant correlation was recorded between the maternal cadmium and each of the fetal cadmium, lead, and arsenic. CONCLUSION: The study findings indicated a weak relation between maternal and fetal blood heavy metals, except for the influence of maternal lead, so it can be assumed that the placental barriers are partially protective against those toxic pollutants, putting into consideration the influence of their different natures

An open-source framework for automated high-throughput cell biology experiments

Modern data analysis methods, such as optimization algorithms or deep learning have been successfully applied to a number of biotechnological and medical questions. For these methods to be efficient, a large number of high-quality and reproducible experiments needs to be conducted, requiring a high degree of automation. Here, we present an open-source hardware and low-cost framework that allows for automatic high-throughput generation of large amounts of cell biology data. Our design consists of an epifluorescent microscope with automated XY stage for moving a multiwell plate containing cells and a perfusion manifold allowing programmed application of up to eight different solutions. Our system is very flexible and can be adapted easily for individual experimental needs. To demonstrate the utility of the system, we have used it to perform high-throughput Ca2+ imaging and large-scale fluorescent labeling experiments

Tetherin antagonism by SARS-CoV-2 ORF3a and spike protein enhances virus release

The antiviral restriction factor, tetherin, blocks the release of several different families of enveloped viruses, including the Coronaviridae. Tetherin is an interferon‐induced protein that forms parallel homodimers between the host cell and viral particles, linking viruses to the surface of infected cells and inhibiting their release. We demonstrate that SARS‐CoV‐2 infection causes tetherin downregulation and that tetherin depletion from cells enhances SARS‐CoV‐2 viral titres. We investigate the potential viral proteins involved in abrogating tetherin function and find that SARS‐CoV‐2 ORF3a reduces tetherin localisation within biosynthetic organelles where Coronaviruses bud, and increases tetherin localisation to late endocytic organelles via reduced retrograde recycling. We also find that expression of Spike protein causes a reduction in cellular tetherin levels. Our results confirm that tetherin acts as a host restriction factor for SARS‐CoV‐2 and highlight the multiple distinct mechanisms by which SARS‐CoV‐2 subverts tetherin function

Discovery of novel oxazole-based macrocycles as anti-coronaviral agents targeting SARS-CoV-2 main protease

Peer reviewedPostprin

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security

Dietary Supplementation with a Combination of Fibrolytic Enzymes and Probiotics Improves Digestibility, Growth Performance, Blood Metabolites, and Economics of Fattening Lambs

This study was conducted to evaluate the effects of adding different levels of the combination of fibrolytic enzymes and probiotics (a mixture of bacteria and yeast) on the performance of fattening lambs. Thirty-two male Ossimi lambs (weighing 39 ± 0.24 kg) were divided into four groups randomly (eight animals each). The first group (control ration, G1) was fed on a ration of 60% concentrate feed mixture (CFM), 20% Egyptian clover (EC), and 20% wheat straw (WS). The second (G2), third (G3), and fourth (G4) groups were fed a control ration supplemented with Calfo Care® at concentrations of 0.5, 1, and 2 kg/ton diet of dry matter (DM). Results showed that the G2 and G3 rations significantly (p ≤ 0.05) increased the DM, organic matter, crude protein, crude fiber, and ether extract digestibility compared with the G1 and G4 rations. Moreover, the G2 and G3 rations increased (p ≤ 0.05) the percentages of total digestible nutrients (TDN), starch values (SV), and digestible crude protein (DCP) compared with the G1 and G4 rations. Both the G2 and G3 rations significantly (p ≤ 0.05) increased the TDN, SV, and DCP as kg/day or g/kg w0.75 and kg or g/100 kg body weight compared with the G1 and G4 rations. Conversely, the G1 ration significantly decreased the feed conversion of DM, TDN, SV, and DCP compared with the experimental groups. Furthermore, the G2, G3, and G4 rations significantly (p ≤ 0.05) increased the total weight gain by 25.34%, 52.20%, and 3.79%, respectively, compared with the G1 ration. The G2, G3, and G4 rations also (p ≤ 0.05) increased the concentrations of most hematological parameters, including triiodothyronine, total protein, albumin, and glucose, compared with the G1 ration. Finally, the best net profit was recorded with the G3 ration, followed by the G2, G4, and G1 rations