Manimbulu Nlooto

Background: Long waiting times have a negative impact on patients, including loss of income, reduced medication adherence, the risk of drug resistance, and deterioration of their health

Background: The use of quality indicators in healthcare systems is one of the factors that improve the quality of health services. However, indicators for assessing HIV clinical care in the context of low- and middle-income countries are not fully explored. Some existing indicators were established within the context of developed countries and are primarily defined for community care, with limited emphasis on the hospital setting. Additionally, these indicators often do not account for the local practicality and relevance of quality measures in the context of low- and middle-income countries. Aim: To assess the clinical significance and practical applicability of these indicators from the perspective of healthcare professionals specialising in HIV care in South Africa and Democratic Republic of Congo. Methods: After performing a systematic review of quality indicators employed in the evaluation of clinical care for individuals with HIV, we conducted an observational, cross-sectional study. In this research, 30 physicians filled out two questionnaires with a core set of indicators, to establish the most pertinent and practically indicators for evaluation of the HIV clinical care. A Likert scale was used to rank the indicators. Kendall’s tau-B rank correlation analysis was also performed. Results: From the initial list of 88 quality indicators, 43 were identified as the most relevant and practical in HIV clinical care. Healthcare professionals deemed the monitoring and therapy domain to be the most pertinent and useful indicators out of the seven different clinical domains, followed by the functional organisational structure domain. Conclusion: This instrument may be a tool for healthcare professionals and hospital administrators to improve the quality of HIV clinical care.

The main proteinase (Mpro), or 3CLpro, is a critical enzyme in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lifecycle and is responsible for breaking down and releasing vital functional viral proteins crucial for virus development and transmission. As a catalytically active dimer, its dimerization interface has become an attractive target for antiviral drug development. Recent research has extensively investigated the enzymatic activity of Mpro, focusing on its role in regulating the coronavirus replication complex and its significance in virus maturation and infectivity. Computational investigations have identified four druggable pockets, suggesting potential allosteric sites beyond the substrate-binding region. Empirical validation through site-directed alanine mutagenesis has targeted residues in both the active and allosteric regions and corroborated these predictions. Structural studies of drug target proteins can inform therapeutic approaches, with metadynamics simulations shedding light on the role of H163 in regulating Mpro function and providing insights into its dynamic equilibrium to the wild-type enzyme. Despite the efficacy of vaccines and drugs in mitigating SARS-CoV-2 spread, its ongoing viral evolution, selective pressures, and continued transmission pose challenges, potentially leading to resistant mutations. Phylogenetic analyses have indicated the existence of several resistant variations predating drug introduction to the human population, emphasizing the likelihood of drug spread. Hydrogen/deuterium-exchange mass spectrometry reveals the structural influence of the mutation. At the same time, clinical trials on 3CLPro inhibitors underscore the clinical significance of reduced enzymatic activity and offer avenues for future therapeutic exploration. Understanding the implications of 3CLPro mutations holds promise for shaping forthcoming therapeutic strategies against COVID-19. This review delves into factors influencing mutation rates and identifies areas warranting further investigation, providing a comprehensive overview of Mpro mutations, categorization, and terminology. Moreover, we examine their associations with clinical outcomes, illness severity, unresolved issues, and future research prospects, including their impact on vaccine efficacy and potential therapeutic targeting.

The main proteinase (Mpro), or 3CLpro, is a critical enzyme in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lifecycle and is responsible for breaking down and releasing vital functional viral proteins crucial for virus development and transmission. As a catalytically active dimer, its dimerization interface has become an attractive target for antiviral drug development. Recent research has extensively investigated the enzymatic activity of Mpro, focusing on its role in regulating the coronavirus replication complex and its significance in virus maturation and infectivity. Computational investigations have identified four druggable pockets, suggesting potential allosteric sites beyond the substrate-binding region. Empirical validation through site-directed alanine mutagenesis targeted residues in both the active and allosteric regions corroborated these predictions. Structural studies of drug target proteins can inform therapeutic approaches, with metadynamics simulations shedding light on the role of H163 in regulating Mpro function and providing insights into its dynamic equilibrium to the wild-type enzyme. Despite the efficacy of vaccines and drugs in mitigating SARS-CoV-2 spread, ongoing viral evolution, selective pressures, and continued transmission pose challenges, potentially leading to resistance mutations. Phylogenetic analyses indicated the existence of several resistance variations predating drug introduction to the human population, emphasizing the likelihood of drug spread. Hydrogen/deuterium-exchange mass spectrometry reveals the structural influence of the mutation, while clinical trials on 3CLPro inhibitors underscore the clinical significance of reduced enzymatic activity and offer avenues for future therapeutic exploration. Understanding the implications of 3CLPro mutations holds promise for shaping forthcoming therapeutic strategies against COVID-19. This review delves into factors influencing mutation rates and identifies areas warranting further investigation, providing a comprehensive overview of Mpro mutations, their categorization, and terminology. Moreover, we examined their associations with clinical outcomes, illness severity, unresolved issues, and future research prospects, including their impact on vaccine efficacy and potential therapeutic targeting.

Background The emergence of new variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with mutations in the spike protein has raised concerns regarding their potential implications on the effectiveness of vaccines and therapeutics. In silico studies have emerged as a powerful tool for predicting the impact of mutations on the structure and function of proteins, including the spike protein of SARS-CoV-2. This systematic review and meta-analysis aims to assess the structural and functional consequences of SARS-CoV-2 spike protein mutations through an evaluation of the available in silico studies. Methods/Design A comprehensive search of multiple databases including PubMed, Scopus, Web of Science, and Google Scholar will be conducted to identify relevant studies. In silico studies that investigate the structural and functional consequences of SARS-CoV-2 spike protein mutations will be included. The primary outcome of interest will be the effects of mutations on the binding affinity of the spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor, which is essential for virus entry into host cells. The quality of the studies will be assessed using established criteria, and a meta-analysis will be conducted to combine the results of the studies into a single estimate of the effects of the mutations. The analysis of data will be carried out by utilizing two software tools - Review Manager software (version 5.3.5) and R software (version 3.6.1). To determine statistical heterogeneity, a standard chi-square test will be applied with a significance level of P < 0.10. Potential biases related to study size (such as publication bias) will be examined through the application of several techniques, including funnel plots, Egger's test, Begg's test, as well as Trim and Fill analysis. Results and conclusion The findings of this systematic review and meta-analysis will provide a comprehensive evaluation of the structural and functional consequences of SARS-CoV-2 spike protein mutations, highlighting the potential implications of these mutations for the development of effective interventions against the virus. The results of the review will contribute to our understanding of the impact of these mutations on the binding affinity of the spike protein to the ACE2 receptor, informing the development of new interventions to combat the virus and its variants. The review will also identify gaps in knowledge and highlight areas for future research, providing a valuable resource for researchers and practitioners in the field of vaccine and drug development. Ethics and Dissemination: Since the data to be analysed in this study has already been published, there will be no involvement of human subjects and no data will be collected directly from them. Therefore, the study will not require ethical clearance. Registration Details: This protocol has been registered with the International Prospective Registry of Systematic Reviews (PROSPERO) registration number “CRD42023409682” (https://www.crd.york.ac.uk/prospero/display_record.asp?ID=CRD42023409682).

Hypertensive disorders associated with pregnancy are a major health concern and a leading cause of maternal indisposition and transience. The main objective of this study was to assess the prevalence of hypertension in pregnancy as well as antihypertensive therapy and pregnancy outcomes among pregnant women at Tamale Teaching Hospital (TTH) in Ghana. This was a retrospective study conducted using data from the folders of pregnant hypertensive patients. The study was conducted at the maternity ward of TTH from 1 June 2018 to 31 May 2019. Participants were all pregnant women with a diagnosis of hypertensive disorders. The prevalence of hypertensive disorders in pregnancy was 12.5%. The most common antihypertensive medication prescribed was sustained-release oral nifedipine, which was prescribed for 548 (81.4%) participants either alone or with methyldopa, followed by oral methyldopa: 506 (75.2%), intravenous hydralazine: 94 (14.0%), intravenous labetalol: 28 (4.2%) and diuretics: 10 (1.5%). Thirty-eight (5.7%) babies died before delivery, whereas 635 (94.3%) babies were born alive. Twenty-six out of the 38 dead babies (68.4%) were babies of pregnant women with elevated BP, whereas 12 (31.6%) were babies of those with normal BP. There was a statistically significant association between BP control and delivery outcomes. The study observed adherence to antihypertensive medicines recommended by the standard treatment guidelines of Ghana for the management of hypertensive disorders in pregnancy. The BPs of about two-thirds of the study participants were well controlled with the antihypertensive therapy. The majority of the study participants with well-controlled BP had positive delivery outcomes.

The search for new chemotherapeutics against leukemia is of great interest to researchers, owing to the limitation of the current drugs. In this research, new drug candidates against leukemia were probed through liquid chromatography-mass spectrometer (LC-MS) analysis of three traditional herbal concoctions, that provide the phytochemical profile of the samples. The identified compounds from the LC-MS were modeled for the analysis of their antileukemia activities, by using five different consensus methods, to combine the seven docking scores. The consensus methods are used to combine the docking scores to avoid losing promising drug candidates, due to a poor reproducibility of the docking scores across the different packages, due to differences in the scoring functions and training sets across the docking packages. The libraries of the potential drug candidates from the concoctions were constructed by searching the NIST database for molecules with a similar MS fragmentation. Venetoclax and gilteritinib, that target FLT3 and BCL-2 were ranked among the top hits, indicating the efficiency of this protocol without missing any potential drug. The results ranked rescinnamine and bisacodyl as new potential antileukemia agents that targets FLAT3, and BCL-2, including the mutated BCL-2 G101V receptor, that is known to be resistant to treatment with venetoclax.