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

Ameliorative Effect of Ashwagandha (Withania somnifera) Root Extract on Brain Oxidative Stress and Depression of Diabetic Rats

Evaluation of the efficacy of ashwagandha root extract to ameliorate the oxidative stress and depression resulting from diabetes in male rats was conducted in the current study. Thirty-six male albino rats were randomly grouped into two main groups: normal (n=18) and diabetic (n=18), diabetes was induced by a single dose of 150 mg/kg BW alloxan injected intraperitoneally. After six weeks, both normal and diabetic groups were further subdivided into six sub-groups; normal control, 100 & 200 mg/kg BW ashwagandha treated normal, diabetic control, 100 and 200 mg/kg BW ashwagandha treated diabetic groups, for another six weeks. The forced swim test was used to assess depression, and serum serotonin levels were measured. In brain tissue homogenates, the glutathione reduced content, superoxide dismutase, and catalase activity were measured, as well as the total antioxidant capacity, total oxidative capacity, and malondialdehyde levels. Moreover, histopathological examination of the brain (cerebral cortex and cerebellum) were conducted. The obtained results revealed that the administration of ashwagandha extract to diabetic rats reduced immobility time during the forced swim test while increasing the serotonin levels significantly when compared with the diabetic group. Similar to this, brain total antioxidant capacity, glutathione reduced content, superoxide dismutase, and catalase activity increased significantly, while brain total oxidative capacity, oxidative stress index, and malondialdehyde levels decreased significantly when compared with the diabetic group. Furthermore, the histopathological changes in brain sections were reversed by ashwagandha root extract. In conclusion, ashwagandha root extract can be used to ameliorate the brain oxidative stress and depression brought on by diabetes mellitus at doses of 100 and 200 mg/kg BW.

Vitamin D mitigates adult onset diseases in male and female mice induced by early-life exposure to endocrine disruptor BPA

Background: During early development, environmental compounds can induce adult onset diseases and disrupt thecirculating vitamin D (VitD) levels.Aim: This study aimed to examine the protective role of VitD against the adverse effects of BPA on male and female mice.Methods: A total of 60 male and female Swiss Albino mice (3 weeks old) were randomly divided into 5 groups; each consisted of 12 mice (6 males and 6 females) and was treated as follows: Group I received no treatment (sham control); Group II, sterile corn oil only (vehicle control); Group III, BPA (400 μg/kg); Group IV, VitD (2,195 IU/kg); and Group V, BPA + VitD. At 10.5 weeks, the animals were sacrificed to conduct histological examinations.Results: BPA-exposed mice were found to have neurobehavioral abnormalities, heart, kidney, and lung diseases with increased apoptotic indices in both sexes. On the other hand, the treatment of BPA mice with VitD altered this scenario with modulated motor activity, enhanced body and organ weights, and preserved the heart, kidney, and lung architecture, alongside a decreased percent apoptotic index.Conclusion: Our findings illustrate that VitD protects mice against BPA-induced heart, kidney, and lung abnormalities

Identification of MiR-125a as a Novel Plasma Diagnostic Biomarker for Chronic Lymphoblastic Leukemia

Background: Chronic lymphocytic leukemia (CLL) is a type of malignancy in which the bone marrow makes too many lymphocytes. MicroRNAs (miRNAs) are endogenous short (~22-nucleotides) non-protein-coding regulatory RNA molecules with key roles in cellular and molecular processes linked to different cancers including CLL. Recently, some investigations have demonstrated that miR-125a downregulation is correlated with the expression of P53, NRG1 and ERBB2. Methods: In this study, samples including 38 patients with CLL and 25 healthy individuals were collected. We used quantitative real-time PCR (qRT-PCR) to assess the expression of miR-125a in plasma of the CLL patients in comparison with healthy controls. Moreover, we used the Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis on miR-125a targets in the DAVID database in order to investigate the potential role of miR-125a in cancer pathways. MiR-125a exerted a variety of roles in the cancer pathway via downregulating target genes including ERBB2. Results: The expression of miR-125a dramatically decreased (~2-fold) in the patients with CLL compared with the healthy controls (p = 0.03). Furthermore, overexpression of miR-125a was associated with different CLL staging and B symptoms (all at p < 0.05). The KEGG pathway enrichment analysis demonstrated the eight statistically related KEGG signaling pathways with miR-125a targetome. Conclusions: The results suggested that the miR-125a expression level could be a novel potential biomarker for CLL prognosis. © 2019 Verlag Klinisches Labor GmbH. All rights reserved

Valve movement behaviour and byssal formation of the mussel, Mytilus edulis in relation to environmental toxins

The present investigation was undertaken to determine behavioural responses of mussel, Mytilus edulis, to sub-lethal concentrations of lindane and atrazine. Behaviour effects that have been studied in mussels were byssus formation, valve movement and valve gape. Lindane was more toxic, causing a 46% reduction of byssal formation, compared to control, after 7 days exposure to 0.9 mg/l. However, atrazine caused 50% reduction of byssal formation after 14 days exposure to 3.585 mg/l atrazine. The sensitivity of the tests increased with increasing the exposure time. Measurements of valve movement and gape showed that increasing exposure and accumulation of lindane increased the proportion of time spent resting (a closed to open ratio of 1.31 at 56 days, compared to a value of 0.05 in the controls). On the other hand, with atrazine the valves did not shut completely (valve closed to open time ratio of 0.3 at 56 days compared with a control value of 0.08) but were observed to have a smaller gape (average gape at 56 days 8.7 mm) than control mussels (average gape at 56 days 25.5 mm). The data of valve movement indicate that the rest period has increased by increasing the concentration and the time of exposure to lindane. Byssus formation in M. edulis was progressively reduced with time of exposure to the 1/2 LC50 of the two pesticides. The byssogenesis test was proved to be a sensitive test in mussels and is suggested as a convenient and rapid technique for bioassay of potential pollutants. KEY WORDS: Mussels, valve movement, byssal formation, lindane and atrazine. Egyptian Journal of Biology Vol.3(2) 2001: 63-7

Rhodamine (B) photocatalysis under solar light on high crystalline ZnO films grown by home-made DC sputtering

ZnO thin films were deposited by home-made DC sputtering of zinc target under mixed gases (Argon, Oxygen) plasma on glass substrates. Films were deposited by varying oxygen partial pressure (PO2) from 0.09 to 1.3 mbar in the deposition chamber, at a fixed substrate temperature of 100 °C. The samples were characterized by photoluminescence (PL), X-ray diffraction (XRD), optical transmissions (UV–vis), scanning electron microscopy (SEM) and electrical (Hall effect) measurements. The results indicate that by varying the oxygen pressure in the deposition chamber, the films show a precise and well defined photoluminescence emissions for each range of pressure covering almost the entire visible domain (UV, UV-Violet, Violet, Blue, and Red) with high intensities. Moreover, the deposited films have different defects levels. The XRD analysis indicates that the films are well grown along the c-axis peak, but with different crystalline quality. Optical measurements reveal a high transmission, up to 90%, in the spectral region between 400 and 2500 nm and a large variation of the optical band gap (3.16–4.34 eV). As an application of the deposited ZnO films, the photo-catalytic degradation of a synthetic solution of Rhodamine B (RhB) poured on a ZnO thin film was successfully achieved and an elimination rate of 38% was obtained after exposing the film to solar light for 3 h

Valve movement behaviour and byssal formation of the mussel, Mytilus edulis in relation to environmental toxins

ABSTRACT The present investigation was undertaken to determine behavioural responses of mussel, Mytilus edulis, to sub-lethal concentrations of lindane and atrazine. Behaviour effects that have been studied in mussels were byssus formation, valve movement and valve gape. Lindane was more toxic, causing a 46% reduction of byssal formation, compared to control, after 7 days exposure to 0.9 mg/l. However, atrazine caused 50% reduction of byssal formation after 14 days exposure to 3.585 mg/l atrazine. The sensitivity of the tests increased with increasing the exposure time. Measurements of valve movement and gape showed that increasing exposure and accumulation of lindane increased the proportion of time spent resting (a closed to open ratio of 1.31 at 56 days, compared to a value of 0.05 in the controls). On the other hand, with atrazine the valves did not shut completely (valve closed to open time ratio of 0.3 at 56 days compared with a control value of 0.08) but were observed to have a smaller gape (average gape at 56 days 8.7 mm) than control mussels (average gape at 56 days 25.5 mm). The data of valve movement indicate that the rest period has increased by increasing the concentration and the time of exposure to lindane. Byssus formation in M. edulis was progressively reduced with time of exposure to the 1/2 LC 50 of the two pesticides. The byssogenesis test was proved to be a sensitive test in mussels and is suggested as a convenient and rapid technique for bioassay of potential pollutants

"Frequency of A Very Rare 35delG Mutation in Two Ethnic Groups of Iranian Populations "

The 35delG mutation in the Connexin 26 gene (Cx26), at the DNFB1 locus is the most common mutation in the patients with autosomal recessive non-syndromic hearing loss (ARNSHL). We have studied a total of 224 deaf cases from 189 families in two populations of Iran (Sistan va Bluchestan and Hormozgan provinces) by prescreening nested PCR, polyacrylamide gel electrophoresis and consequent direct sequencing method for all cases. The aim of the present work was to find prevalence of GJB2 mutations in the populations studied. Four different GJB2 mutations including 35delG, W24X, R127H and (V27I + E114 G) were identified in 11 of 189 families (5.8%). Two polymorphisms (V27I and V153I) also were detected in 14 families. A polymorphism S86T was determined in all cases. Homozygote 35delG mutation was found only in 1 of 189 families (0.5%).The rate of Cx26 mutations found in this study was lower than other Iranian populations. So the cause of deafness in the populations studied remains to be detected in other loci or genes

Assessment of anti-factor Xa activity of enoxaparin for venous thromboembolism prophylaxis in morbidly obese surgical patients

Background: Venous thromboembolism (VTE) can be encountered by 60% of hospitalized patients. Anticoagulants have been recommended to reduce the risk of VTE in patients with risk factors. However, no specific dosing recommendations for obese patients are provided in the current practice guidelines. The purpose of this study was to determine the efficacy and safety of weight-based dosing of enoxaparin for VTE prophylaxis among morbidly obese patients undergoing surgery. Methods: Adult patients were enrolled if they have a body mass index (BMI) of ≥35 kg/m2 and were scheduled for surgery. These patients were prescribed enoxaparin (0.5 mg/kg subcutaneously [SC] once daily). Peak anti-factor Xa levels were measured 4 h after the third dose of enoxaparin. The primary outcome measure was to determine whether a weight-based dosing of enoxaparin of 0.5 mg/kg produce the anticipated peak anti-Xa levels (0.2–0.6 IU/m) among obese patients undergoing surgery. Secondary outcomes include the incidence of VTE, the incidence of minor or major bleeding, and the incidence of heparin-induced thrombocytopenia (HIT). Results: Fifty patients were enrolled in the study. The mean age was 53 ± 16 years, 74% of the patients were female. The mean BMI was 40.5 ± 5, and the average enoxaparin dose was 50 ± 9.8 SC daily. Nearly 88% of the patients reached the target anti-factor Xa (0.427 ± 0.17). None of the patients developed HIT or VTE. There was no incidence of major or minor bleeding. Conclusions: Weight-based enoxaparin dose led to the anticipated peak anti-Xa levels (0.2–0.6 IU/mL) in most of the morbidly obese study patients undergoing surgery without any evidence of major side effects. The weight-based dosing of enoxaparin was also effective in preventing VTE in all patients. Although these results are promising, further comparative trials are needed in the setting of morbidly obese surgical patients

"Two Novel Mutations and Predominant 35delG Mutation in the Connexin 26 Gene (GJB2) in Iranian Populations"

Mutations in the GJB2 gene encoding Connexin 26 (Cx26) protein are a major cause for autosomal recessive non syndromic and sporadic deafness in many populations. In this study we have investigated the prevalence of the GJB2 gene mutations using nested PCR pre screening strategy and direct sequencing method. Two hundred and sixty autosomal recessive non syndromic and sporadic deaf subjects from 199 families in two provinces of Iran (Gilan and Khorasan) were studied. Altogether 14 different genetic variants were identified from which 2 were novel variant (327delG+G109G and 431insC). Eight GJB2 mutations including 35delG, 235delC, W77X, R127H, M34T, V27I+E114G, L90P and delE120 were also found in 54 of 199 families (27%). Four polymorphysms V27I, S86T, V153I and G160S also were detected. Thirty two of 199 families were observed to have GJB2 mutations in both alleles (16%). The most common mutation was 35delG so that 43 out of 55 GJB2 mutations (78.2%) contained 35delG mutation