Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused the COVID-19 pandemic, can still infect populations in many countries around the globe. The Omicron strain is the most ...mutated variant of SARS-CoV-2. The high transmissibility of the strain and its ability to evade immunity necessitate a priority study of its properties in order to quickly create effective means of preventing its spread. The current research aimed to examine the in silico interaction between PIWI-interacting RNAs (piRNAs) and the SARS-CoV-2 genome (gRNA) to identify endogenous piRNAs and propose synthetic piRNAs with strong antiviral activity for drug development. This study used validated bioinformatic approaches regarding the interaction of more than eight million piRNAs with the SARS-CoV-2 genome. The piRNAs' binding sites (BSs) in the 5'UTR were located with overlapping nucleotide sequences termed clusters of BSs. Several BSs clusters have been found in the nsp3, nsp7, RNA-dependent RNA polymerase, endoRNAse, S surface glycoprotein, ORF7a, and nucleocapsid. Sixteen synthetic piRNAs that interact with gRNA have been proposed with free binding energy ranging from -170 kJ/mol to -175 kJ/mol, which can be used to create drugs that suppress the reproduction of SARS-CoV-2.
Parkinson's disease (PD) exhibits the second-highest rate of mortality among neurodegenerative diseases. PD is difficult to diagnose and treat due to its polygenic nature. In recent years, numerous ...studies have established a correlation between this disease and miRNA expression; however, it remains necessary to determine the quantitative characteristics of the interactions between miRNAs and their target genes. In this study, using novel bioinformatics approaches, the quantitative characteristics of the interactions between miRNAs and the mRNAs of candidate PD genes were established. Of the 6,756 miRNAs studied, more than one hundred efficiently bound to mRNA of 61 candidate PD genes. The miRNA binding sites (BS) were located in the 5'-untranslated region (5'UTR), coding sequence (CDS) and 3'-untranslated region (3'UTR) of the mRNAs. In the mRNAs of many genes, the locations of miRNA BS with overlapping nucleotide sequences (clusters) were identified. Such clusters substantially reduced the proportion of nucleotide sequences of miRNA BS in the 5'UTRs, CDSs, and 3'UTRs. The organization of miRNA BS into clusters leads to competition among miRNAs to bind mRNAs. Differences in the binding characteristics of miRNAs to the mRNAs of genes expressed at different rates were identified. Single miRNA BS, polysites for the binding for one miRNA, and multiple BS for two or more miRNAs in one mRNA were identified. Evolutionary changes in the BS of miRNAs and their clusters in 5'UTRs, CDSs and 3'UTRs of mRNA of orthologous candidate PD genes were established. Based on the quantitative characteristics of the interactions between miRNAs and mRNAs candidate PD genes, several associations recommended as markers for the diagnosis of PD.
The purpose of the study is to explore existing literature on quality management tools applicable in higher education and identify major critical factors of TQM adapted from the business sector. A ...major part of the research focuses on an exploratory literature review of the most well-known existing business quality management tools applicable to higher education.Design/methodology/approach – An exploratory literature review was conducted using a well-known, highly respected database “Web of Science Core Collection”.Findings – The presented study offers a deep literature analysis of effective practices for implementing quality management tools in higher education.The practical value of the paper is university administrators and quality managers can apply it as guidelines in selecting the best cases of quality techniques applicable in their organizations for strategic development, university performance and quality improvement.The originality of the paper - is it can serve as a theoretical guideline for regional academics, scholars and university managers and administrators to define an appropriate quality management tool to meet requirements of external stakeholders (employers).
Stroke is the second leading cause of death and the third leading cause of disability worldwide and its burden is increasing rapidly in low-income and middle-income countries, many of which are ...unable to face the challenges it imposes. In this Health Policy paper on primary stroke prevention, we provide an overview of the current situation regarding primary prevention services, estimate the cost of stroke and stroke prevention, and identify deficiencies in existing guidelines and gaps in primary prevention. We also offer a set of pragmatic solutions for implementation of primary stroke prevention, with an emphasis on the role of governments and population-wide strategies, including task-shifting and sharing and health system re-engineering. Implementation of primary stroke prevention involves patients, health professionals, funders, policy makers, implementation partners, and the entire population along the life course.
Multiple sclerosis (MS) is a common inflammatory demyelinating disease with a high mortality rate. MS is caused by many candidate genes whose specific involvement has yet to be established. The aim ...of our study was to identify endogenous miRNAs and piRNAs involved in the regulation of MS candidate gene expression using bioinformatic methods. A program was used to quantify the interaction of miRNA and piRNA nucleotides with mRNA of the target genes. We used 7310 miRNAs from three databases and 40,000 piRNAs. The mRNAs of the candidate genes revealed miRNA binding sites (BSs), which were located separately or formed clusters of BSs with overlapping nucleotide sequences. The miRNAs from the studied databases were generally bound to mRNAs in different combinations, but miRNAs from only one database were bound to the mRNAs of some genes. For the first time, a direct interaction between the complete sequence of piRNA nucleotides and the nucleotides of their mRNA BSs of target genes was shown. One to several clusters of BSs of miRNA and piRNA were identified in the mRNA of
and
MS candidate genes. These piRNAs form the expression regulation system of the MS candidate genes to coordinate the synthesis of their proteins. Based on these findings, associations of miRNAs, piRNAs, and candidate genes for MS diagnosis are recommended.
The emergence of the COVID-19 pandemic has significantly impacted global healthcare systems and this may affect stroke care and outcomes. This study examines the changes in stroke epidemiology and ...care during the COVID-19 pandemic in Zanjan Province, Iran.
This study is part of the CASCADE international initiative. From February 18, 2019, to July 18, 2020, we followed ischemic and hemorrhagic stroke hospitalization rates and outcomes in Valiasr Hospital, Zanjan, Iran. We used a Bayesian hierarchical model and an interrupted time series analysis (ITS) to identify changes in stroke hospitalization rate, baseline stroke severity measured by the National Institutes of Health Stroke Scale (NIHSS), disability measured by the modified Rankin Scale (mRS), presentation time (last seen normal to hospital presentation), thrombolytic therapy rate, median door-to-needle time, length of hospital stay, and in-hospital mortality. We compared in-hospital mortality between study periods using Cox-regression model.
During the study period, 1,026 stroke patients were hospitalized. Stroke hospitalization rates per 100,000 population decreased from 68.09 before the pandemic to 44.50 during the pandemic, with a significant decline in both Bayesian Beta: -1.034; Standard Error (SE): 0.22, 95% CrI: -1.48, -0.59 and ITS analysis (estimate: -1.03, SE = 0.24, p < 0.0001). Furthermore, we observed lower admission rates for patients with mild (NIHSS < 5) ischemic stroke (p < 0.0001). Although, the presentation time and door-to-needle time did not change during the pandemic, a lower proportion of patients received thrombolysis (-10.1%; p = 0.004). We did not see significant changes in admission rate to the stroke unit and in-hospital mortality rate; however, disability at discharge increased (p < 0.0001).
In Zanjan, Iran, the COVID-19 pandemic has significantly impacted stroke outcomes and altered the delivery of stroke care. Observed lower admission rates for milder stroke may possibly be due to fear of exposure related to COVID-19. The decrease in patients treated with thrombolysis and the increased disability at discharge may indicate changes in the delivery of stroke care and increased pressure on existing stroke acute and subacute services. The results of this research will contribute to a similar analysis of the larger CASCADE dataset in order to confirm findings at a global scale and improve measures to ensure the best quality of care for stroke patients during the COVID-19 pandemic.
Background and purpose
Early this century, the high risk strategy of primary stroke and cardiovascular disease (CVD) prevention for individuals shifted away from identifying (and treating, as ...appropriate) all at‐risk individuals towards identifying and treating individuals who exceed arbitrary thresholds of absolute CVD risk. The public health impact of this strategy is uncertain.
Methods
In our systematic scoping review, the electronic databases (Scopus, MEDLINE, Embase, Google Scholar, Cochrane Library) were searched to identify and appraise publications related to primary CVD/stroke prevention strategies and their effectiveness published in any language from January 1990 to August 2023.
Results
No published randomized controlled trial was found on the effectiveness of the high CVD risk strategy for primary stroke/CVD prevention. Targeting high CVD risk individuals excludes a large proportion of the population from effective blood‐pressure‐lowering and lipid‐lowering treatment and effective CVD prevention. There is also evidence that blood pressure lowering and lipid lowering are beneficial irrespective of blood pressure and cholesterol levels and irrespective of absolute CVD risk and that risk‐stratified pharmacological management of blood pressure and lipids to only high CVD risk individuals leads to significant underuse of blood‐pressure‐lowering and lipid‐lowering medications in individuals otherwise eligible for such treatment.
Conclusions
Primary stroke and CVD prevention needs to be done in all individuals with increased risk of CVD/stroke. Pharmacological management of blood pressure and blood cholesterol should not be solely based on the high CVD risk treatment thresholds. International guidelines and global strategies for primary CVD/stroke prevention need to be revised.
The purpose of the article is to assess the financial sustainability of the household sector of the Republic of Kazakhstan and its impact on the real and financial sector in the context of minimizing ...the credit risks of the regulated banks of the Republic of Kazakhstan. The paper analyzes various points of view on assessing the financial sustainability of the household sector, makes a successful attempt to assess at a macroeconomic level the financial sustainability of households and the drawing potential of households in Kazakhstan using the OECD and IMF methods. The work made a holistic analysis of the financial condition and solvency of households in Kazakhstan, a forecasted VAR-model for assessing the impact of household financial sustainability on the state of the real sector of the economy has been developed; a regression model for assessing the impact of financial stability of households on the financial sector of Kazakhstan has been developed.
Human capital occupies a leading position in economic development and determines the importance of education as a system responsible for its production. Attention has increasingly been paid in recent ...years to the role of education in the economic growth of countries. Researchers began to study the impact of education on economic growth in the 19th century and continue to this day. Hence, the growth in the number of publications and scientific studies studying the importance of education in economic growth actualizes the need to use bibliometric analysis methods to identify patterns and trends studied by scientists from various countries around the world. The article examines the works of economists who formulated theories emphasizing the importance of education for economic development. This study reviews scientific works to determine the underlying concepts in the field of the role of education in economic growth. The purpose of this research is to analyze the structure and dynamics of academic research aimed at studying the role of education in economic growth. A bibliometric analysis of the literature was carried out using the VOSviewer software. The sample consists of 2,432 publications from the WoS database. A result of the analysis is a compiled bibliometric map of five clusters. The research outcomes apply to both local higher education establishments and governmental bodies responsible for state educational oversight.