Detection of FXIII gene V34L and fibrinogen β-gene -455G/A polymorphisms among Saudi Arabia population via polymerase chain reaction-reverse hybridization technique

FXIII gene Val34Leu variant appears to be associated with decreased risk of myocardial infarction and venous thromboembolism as well as with increased risk of intracerebral hemorrhage. Fibrinogen β-gene SNP -455G/A are associated with differences in the plasma levels of fibrinogen and severity of arterial disease. The aim of the present work was to study the prevalence of FXIII gene V34L and Fibrinogen β-gene -455G/A SNPs in Saudi population. Among 200 blood samples randomly collected from unrelated healthy Saudi subjects, FXIII gene V34L and Fibrinogen β-gene -455G/A SNPs were genotyped via cardiovascular disease (CVD) StripAssay (ViennaLab, Austria. Homozygous (V/V) and heterozygous (V/L) genotypes were detected with 96 and 4%, respectively, among FXIII gene V34L genotypes, whereas (L/L) genotype was not found. The allele frequency was 0.98 for V allele and 0.02 for L allele. Three genotypes of Fibrinogen β-gene -455G/A SNP (GG, GA and AA) were obtained and its prevalence (%) was 70, 25 and 5, respectively. The frequency of G allele was 0.825 and 0.175 for A allele. Prevalence of FXIII gene Vl34L polymorphism and its allele frequency are in line with other Asian populations. Distribution of β-gene -455G/A genotypes and allele frequency are in accordance with previous reports in different ethnic groups. This is the first time to report these polymorphisms in Saudi Arabia population. This study provides valuable information on Saudi genetic background in comparison with other populations. In addition, it serves as a template for future clinical research involving cardiovascular and cerebrovascular diseases.Key words: FXIII gene V34L, fibrinogen β-gene -455G/A, polymorphisms, Saudi Arabia

Association between polymorphisms of SLC6A3 and DRD1 genes and autism among Saudi Arabia Taif population using PCR-restriction fragment length polymorphism (PCR- RFLP)

The prevalence of autism in Saudi Arabia is 18 per 10,000, higher than the 13 per 10,000 reported in developed  countries. The etiology of autism is still not completely understood. Different studies support the involvement  of dopaminergic neurotransmitter system in the etiology of autism. Several lines of evidences suggest the role of some dopamine related genes, such as DRD1 and SLC6A3 in the etiology of autism. The aim of the present  work was to study the possible role of rs2550936 A/C polymorphism at SLC6A3 locus as well as rs4532 A/G  polymorphism at DRD1 locus in the etiology of autism among Saudi population. The polymorphisms of DRD1  and LC6A3 were genotyped in the case-control study using polymerase chain reaction-restriction fragment  length polymorphism (PCR-RFLP) technique. Significant association as risk factor was found between autism  and GA genotype of DRD1 [OR = 3.5 CI (1.04, 12.41*)] as well as CA genotype of SLC6A3 [OR = 2.53 CI  (1.03, 6.26*)], while CC genotype of SLC6A3 revealed protective effect. In conclusion, possible risk  genotypes  for autism in the DRD1 and SLC6A3 genes were observed. This is the first report in Saudi Arabia  population and Arab world. Therefore further investigations of these markers and other SNPs of SLC6A3 and  DRD1 genes are considered in large replication samples with other causal factors to enable positive  identification of risk genotypes and generalize obtained results.Key words: Etiology, polymorphism, autism, genotype

Protease activity of some mesophilic streptomycetes isolated from Egyptian habitats

Different streptomycetes (317 isolates) were obtained from several sources and areas in Egypt and were screened for proteolytic activity. Thirty nine of them produced proteases and were subjected to identification. Streptomyces anulatus formed the most abundant portion of the isolates. This species deserves special attention because it is a good candidate for biotechnological applications

Exome-wide association study to identify rare variants influencing COVID-19 outcomes : Results from the Host Genetics Initiative

Publisher Copyright: Copyright: © 2022 Butler-Laporte et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75–10.05, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.Peer reviewe

Global prevalence and genotype distribution of hepatitis C virus infection in 2015 : A modelling study

Publisher Copyright: © 2017 Elsevier LtdBackground The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate hepatitis C virus (HCV) infection by 2030, which can become a reality with the recent launch of direct acting antiviral therapies. Reliable disease burden estimates are required for national strategies. This analysis estimates the global prevalence of viraemic HCV at the end of 2015, an update of—and expansion on—the 2014 analysis, which reported 80 million (95% CI 64–103) viraemic infections in 2013. Methods We developed country-level disease burden models following a systematic review of HCV prevalence (number of studies, n=6754) and genotype (n=11 342) studies published after 2013. A Delphi process was used to gain country expert consensus and validate inputs. Published estimates alone were used for countries where expert panel meetings could not be scheduled. Global prevalence was estimated using regional averages for countries without data. Findings Models were built for 100 countries, 59 of which were approved by country experts, with the remaining 41 estimated using published data alone. The remaining countries had insufficient data to create a model. The global prevalence of viraemic HCV is estimated to be 1·0% (95% uncertainty interval 0·8–1·1) in 2015, corresponding to 71·1 million (62·5–79·4) viraemic infections. Genotypes 1 and 3 were the most common cause of infections (44% and 25%, respectively). Interpretation The global estimate of viraemic infections is lower than previous estimates, largely due to more recent (lower) prevalence estimates in Africa. Additionally, increased mortality due to liver-related causes and an ageing population may have contributed to a reduction in infections. Funding John C Martin Foundation.publishersversionPeer reviewe

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

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

Protease activity of some mesophilic streptomycetes isolated from Egyptian habitats

Different streptomycetes (317 isolates) were obtained from several sources and areas in Egypt and were screened for proteolytic activity. Thirty nine of them produced proteases and were subjected to identification. Streptomyces anulatus formed the most abundant portion of the isolates. This species deserves special attention because it is a good candidate for biotechnological applications

The effect of fluoride on the distribution of some minerals in the surface water of an Egyptian lagoon at the Mediterranean Sea

The seasonal fluoride distribution in surface waters along Lake Edku and in the supplying land drains, as well as its effect on the formation of carbonated and fluoridated minerals were investigated. The data revealed that fluoride’s content was affected by the chlorinity value of two feeding sources of water in Lake Edku, which were the seawater from El-Maadiya inlet and drainage water from land drains. Fluoride in surface water showed average contents of 0.62–1.59, 0.44–1.53, 0.13–1.07 and 0.23–1.17 mg/l in winter, spring, summer and autumn, respectively, with an annual average concentration of 0.8 ± 0.1 mg/l. The annual average of the saturation index (SI) of carbonated (calcite, aragonite and dolomite) and fluorapatite minerals along Lake Edku had values that exceeded the unity and referred to the over saturation of the lake water in respect to these minerals. In contrast, the average annual SI of fluorite and sellaïte gave values lower than unity. That indicated the under saturation in respect to these two minerals. The high saturation index values for fluorapatite may be related to the low solubility of calcite in apatite supernatants in alkaline conditions. Interestingly, the formation of the fluorapatite mineral leaves a small concentration of it, and that protects Lake Edku’s ecosystem from the destructive impact of fluoride pollution