EMERGENCE OF NEW STRAINS OF SARS-COV-2: AFRICA’S FATE AND ITS PREPAREDNESS AGAINST COVID-19 INFECTION WAVES

Background: Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2) has infected over 100million individuals worldwide with diverse impacts on nations. The rising cases of new strains and resultant infection waves create an urgent need to assess the readiness of countries especially in Africa to mitigate the impact on community transmission. This paper delivers a brief synopsis of the novel SARS-CoV-2, emerging cases of new variants reported worldwide, and implications for genetic surveillance of disease transmission in low-and middle-income countries (LMICs) especially Africa. Materials and Methods: Literature search used keywords like SARS-CoV-2; COVID-19 epidemiology; pandemic waves; corona outbreak, clinical syndromes, treatments, prevention and control. Cross-sectional and observational studies published on COVID-19 from 2019 till date of study provided main information sources. Databases such as Web of Science, Embase, PubMed and Google Scholar were utilised. Main findings: Over 220 countries have documented COVID-19 cases with varied severity till date. Before the spikes in resurgence, a highly virulent mutated (>90% fatality rate) novel strain of COVID-19 had been documented. There is very little data to ascertain the impact of the COVID-19 infection waves in LMICs. Discussion: LMICs especially African countries still grapple with significant challenges like inefficient surveillance mechanisms, inadequate vaccination coverage, inadequate enforcement of environmental health strategies, poor health systems etc. Hence, Africa’s fate remains dicey in the face of the dynamic evolution of the SARS-CoV-2 and other identified challenges. Conclusion:  The adoption of a multidisciplinary approach to mitigate the impact of emergence of mutant SARS-CoV-2 variants and resurgence of infection spike is recommende

Enhancing the Effectiveness of Vertical Water Injection Wells With Inflow Control Devices (ICDs): Design, Simulation and Economics

Water injector completion techniques used traditionally, such as frac packs or openhole standalone screens, were judged to be incapable of meeting all completion objectives and have been reported to loose injectivity over time coupled with the issue of long term injection conformance due to plugging. Another major challenge is to achieve even distribution of the injected water into all zones along the wellbore. Permeability contrasts, formation damage, creation of thief fractures, and changes in wellbore injectivity need to be managed to avoid early breakthrough in adjacent production wells. This study presents the application of inflow control devices (ICDs), fined tuned by reservoir simulations for balancing the water injection profile into various sand formation zones in an open–hole completed injector well in Flo-Z6, a stratified Niger Delta reservoir with communicating layers.The solution targeted at developing a screening tool for deciding candidate layers in Flo-Z6 reservoir and installing special flow control devices, tailor-made for injection wells and with correct nozzle sizes for this particular case.The results from this study show that, the installation of ICDs with different nozzle configuration in the injector wells tailored to equalize the water outflow (for better sweep efficiency), improved the field oil recovery by 11.9% (6.6MMstb). Economic indicators used to validate the profitability of the investment further showed that completing the injectors with different ICD nozzle configuration was more profitable, with an NPV@10% of $192.5million, profit per dollar invested of$6.6, DCF-ROR of 81% and a pay-out period of 1.2 year which is relatively short

TGF-beta(2)- and H2O2-Induced Biological Changes in Optic Nerve Head Astrocytes Are Reduced by the Antioxidant Alpha-Lipoic Acid

Background/Aims: The goal of the present study was to determine whether transforming growth factor-beta(2) (TGF-beta(2))- and oxidative stress-induced cellular changes in cultured human optic nerve head (ONH) astrocytes could be reduced by pretreatment with the antioxidant alpha-lipoic acid (LA). Methods: Cultured ONH astrocytes were treated with 1.0 ng/ml TGF-beta(2) for 24 h or 200 mu M hydrogen peroxide (H2O2) for 1 h. Lipid peroxidation was measured by a decrease in cis-pari-naric acid fluorescence. Additionally, cells were pretreated with different concentrations of LA before TGF-beta 2 or H2O2 exposure. Expressions of the heat shock protein (Hsp) alpha B-crystallin and Hsp27, the extracellular matrix (ECM) component fibronectin and the ECM-modulating protein connective tissue growth factor (CTGF) were examined with immunohistochemistry and real-time PCR analysis. Results: Both TGF-beta(2) and H2O2 increased lipid peroxidation. Treatment of astrocytes with TGF-beta(2) and H2O2 upregulated the expression of alpha B-crystallin, Hsp27, fibronectin and CTGF. Pretreatment with different concentrations of LA reduced the TGF-beta(2)- and H2O2-stimulated gene expressions. Conclusion: We showed that TGF-beta(2)- and H2O2-stimulated gene expressions could be prevented by pretreatment with the antioxidant LA in cultured human ONH astrocytes. Therefore, it is tempting to speculate that the use of antioxidants could have protective effects in glaucomatous optic neuropathy. Copyright (C) 2012 S. Karger AG, Base

Creating Acceptable Tablets 3D (CAT 3D): A Feasibility Study to Evaluate the Acceptability of 3D Printed Tablets in Children and Young People

3D printing (3DP) has been proposed as a novel approach for personalising dosage forms for children and young people (CYP). Owing to its low cost and the lack of need for finishing steps, fused deposing modelling (FDM) 3DP has been heavily researched in solid dosage forms (SDFs) manufacturing. However, the swallowability and overall acceptability of 3D printed dosage forms are yet to be established. This work is the first to evaluate the acceptability of different sized 3D printed placebo SDFs in CYP (aged 4–12 years). All participants had previously participated in a feasibility study (CAT study) that assessed the swallowability and acceptability of different sized GMP manufactured placebo conventional film-coated tablets, and therefore only attempted to swallow one 3D printed tablet. The participants assessed the swallowability, acceptability, mouthfeel, volume of water consumed, and taste of the sample using a 5-point hedonic facial scale on a partic-ipant questionnaire. A total of 30 participants were recruited, 87% of whom successfully swallowed the 3D printed tablet that they attempted to take. Attributes of the 3D printed tablets were scored as acceptable by the following percentage of participants—swallowability (80%), mouthfeel/texture (87%), the volume of water consumed (80%), taste (93%), and overall acceptability (83%). Overall, 77% of children reported they would be happy to take the tablet every day if it was a medicine. Participants were also asked which tablets felt better in the mouth—the film-coated tablets or the 3D printed tablets, and the most popular response (43%) was that both were acceptable. This study shows that FDM-based 3D printed SDFs may be a suitable dosage form for children aged 4–12 years. The results from this feasibility study will be used to inform a larger, definitive study looking at the acceptability of 3D printed tablets in children

Mitochondrial DNA Polymorphism A4917G Is Independently Associated with Age-Related Macular Degeneration

The objective of this study was to determine if MTND2*LHON4917G (4917G), a specific non-synonymous polymorphism in the mitochondrial genome previously associated with neurodegenerative phenotypes, is associated with increased risk for age-related macular degeneration (AMD). A preliminary study of 393 individuals (293 cases and 100 controls) ascertained at Vanderbilt revealed an increased occurrence of 4917G in cases compared to controls (15.4% vs.9.0%, p = 0.11). Since there was a significant age difference between cases and controls in this initial analysis, we extended the study by selecting Caucasian pairs matched at the exact age at examination. From the 1547 individuals in the Vanderbilt/Duke AMD population association study (including 157 in the preliminary study), we were able to match 560 (280 cases and 280 unaffected) on exact age at examination. This study population was genotyped for 4917G plus specific AMD-associated nuclear genome polymorphisms in CFH, LOC387715 and ApoE. Following adjustment for the listed nuclear genome polymorphisms, 4917G independently predicts the presence of AMD (OR = 2.16, 95%CI 1.20–3.91, p = 0.01). In conclusion, a specific mitochondrial polymorphism previously implicated in other neurodegenerative phenotypes (4917G) appears to convey risk for AMD independent of recently discovered nuclear DNA polymorphisms

Genetic polymorphism of the iron-regulatory protein-1 and -2 genes in age-related macular degeneration

Iron can be involved in the pathogenesis of AMD through the oxidative stress because it may catalyze the Haber–Weiss and Fenton reactions converting hydrogen peroxide to free radicals, which can induce cellular damage. We hypothesized that genetic polymorphism in genes related to iron metabolism may predispose individuals to the development of AMD and therefore we checked for an association between the g.32373708 G>A polymorphism (rs867469) of the IRP1 gene and the g.49520870 G>A (rs17483548) polymorphism of the IRP2 gene and AMD risk as well as the modulation of this association by some environmental and life-style factors. Genotypes were determined in DNA from blood of 269 AMD patients and 116 controls by the allele-specific oligonucleotide-restriction fragment length polymorphism and the polymerase chain reaction-restriction fragment length polymorphism. An association between AMD, dry and wet forms of AMD and the G/G genotype of the g.32373708 G>A-IRP1 polymorphism was found (OR 3.40, 4.15, and 2.75). On the other hand, the G/A genotype reduced the risk of AMD as well as its dry or wet form (OR 0.23, 0.21, 0.26). Moreover, the G allele of the g.49520870 G>A-IRP2 polymorphism increased the risk of the dry form of the disease (OR 1.51) and the A/A genotype and the A allele decreased such risk (OR 0.43 and 0.66). Our data suggest that the g.32373708 G>A-IRP1 and g.49520870 G>A-IRP2 polymorphisms may be associated with increased risk for AMD

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome