my (M.A.H.A.); irekeola@student.usm.my (A.A.I.); hanimkk@usm.my (R.H.S.)Abstract: Epstein-Barr virus (EBV) is the causative agent of many diseases including infectious mononucleosis (IM), and it is associated with different subtypes of lymphoma, sarcoma and carcinoma such as Hodgkin's lymphoma, non-Hodgkin's lymphoma, nasopharyngeal carcinoma, and gastric carcinoma. With the advent of improved laboratory tests for EBV, a timelier and accurate diagnosis could be made to aid better prognosis and effective treatment. For histopathological lesions, the in situ hybridization (ISH) of EBV-encoded RNA (EBER) in biopsy tissues remains the gold standard for detecting EBV. Methods such as the heterophile antibody test, immunofluorescence assays, enzyme immunoassays, Western blot, and polymerase chain reaction (PCR) are also employed in the detection of EBV in different types of samples. The determination of EBV viral load using PCR, however, is gaining more prominence in the diagnosis of EBV-associated diseases. Given the challenge of false positive/negative results that are sometimes experienced during the detection of EBV, variability in results from different laboratories, and the impact of factors such as sample type and the immunological status of patients from whom samples are collected, the need to critically examine these present methods is invaluable. This review thus presents current advances in the detection of EBV, detailing the advantages and disadvantages of the various techniques. In addition, fundamental virological concepts are highlighted to enhance the greater understanding, the proper application, and the interpretation of EBV tests.Pathogens 2020, 9, 226 2 of 17 EBV can infect a wide range of cells and tissues including T and B lymphocytes, nasopharynx and oropharynx squamous epithelial cells, salivary and stomach glands, thyroid glandular epithelial cells, smooth muscle, and follicular dendritic cells [4]. However, EBV primarily infects and replicates in the stratified squamous epithelium of the oropharynx, followed by a latent infection of B lymphocytes [4]. It has been suggested that the EBV infection of B lymphocytes occurs in the oropharyngeal lymphoid organs [2]. In normal carriers, the virus persists in circulating memory B cells and initiates the production of immunoglobulins [1,2]. Following EBV's infection of B cells, a specific set of latency-related genes and transcripts are expressed, and the virus could remain dormant in resting memory B cells, from which it intermittently reactivates at any mucosal site where B cells are present (Table 1) [4,5]. The reactivation of EBV poses a great and difficult challenge to infected hosts [3]. In healthy adults, it is estimated that for every million B cells in circulation, approximately 1 to 50 are infected with EBV, with the number of latently-infected cells in each individual remaining stable for several years [6]. Therefore, EBV coexists with most human hosts without obvious outcomes. However, in some people, the virus is associated with the develo...

Improper use of antimicrobials has resulted in the emergence of antimicrobial resistance (AMR), including multi-drug resistance (MDR) among bacteria. Recently, a sudden increase in Carbapenem-resistant Enterobacterales (CRE) has been observed. This presents a substantial challenge in the treatment of CRE-infected individuals. Bacterial plasmids include the genes for carbapenem resistance, which can also spread to other bacteria to make them resistant. The incidence of CRE is rising significantly despite the efforts of health authorities, clinicians, and scientists. Many genotypic and phenotypic techniques are available to identify CRE. However, effective identification requires the integration of two or more methods. Whole genome sequencing (WGS), an advanced molecular approach, helps identify new strains of CRE and screening of the patient population; however, WGS is challenging to apply in clinical settings due to the complexity and high expense involved with this technique. The current review highlights the molecular mechanism of development of Carbapenem resistance, the epidemiology of CRE infections, spread of CRE, treatment options, and the phenotypic/genotypic characterisation of CRE. The potential of microorganisms to acquire resistance against Carbapenems remains high, which can lead to even more susceptible drugs such as colistin and polymyxins. Hence, the current study recommends running the antibiotic stewardship programs at an institutional level to control the use of antibiotics and to reduce the spread of CRE worldwide.

Background: The prevalence of type 2 diabetes mellitus (T2DM) has increased worldwide, including in Saudi Arabia. Objective: To systematically review the available literature and assess the pooled prevalence of T2DM in Saudi Arabia between 2000 and 2020. Methods: Observational studies that reported quantitative estimates of the prevalence of T2DM as their main outcome, included the general population of Saudi Arabia, and were published between 2000–2020 and in English were retrieved using three electronic databases (namely, CINAHL, Medline via PubMed, and Web of Science). Retrieved studies were screened, and relevant data were extracted. The Joanna Briggs Institute Critical Appraisal guideline was used to assess the methodological quality of included studies. A random-effects model was used to estimate the prevalence of T2DM. Results: Twenty-three studies were included in the systematic review, of which 19 were included in the meta-analysis (total pooled population: 258,283). The overall pooled prevalence of T2DM in Saudi Arabia was 16.4% (95% CI: 11.6–17.5). However, there was heterogeneity in the results of the studies [I2 = 99.31%, P < 0.0001] and the summary values varied from 3.18% (95% CI: 1.46–5.95) to 94.34% (95% CI: 89.53–97.38). Although the prevalence of T2DM by age varied across studies, in most studies, it was higher among the older age groups. In addition, the prevalence of diabetes widely varied across the different geographical regions of Saudi Arabia. Conclusions: This is the first meta-analysis that determined the pooled prevalence of T2DM in Saudi Arabia, and it revealed a high prevalence over the past two decades. However, owing to data collection inconsistencies in the identified studies, neither the modifiable (such as obesity, educational status, emotional support, etc.) nor the non-modifiable (such as gender and age) risk factors of T2DM could be determined, thereby indicating the need for a nationally collective effort in determining these factors.

Background The EBV-associated epithelial tumours consist 80% of all EBV-associated cancer, where the nasopharyngeal cancer (NPC) and EBV-associated gastric carcinoma (EBVaGC) are considered as the most frequent EBV-associated epithelial tumours. It has been shown that the BART-encoded miRNAs are abundantly expressed in EBV-associated epithelial tumours, hence, these miRNAs may serve as diagnostic and prognostic biomarkers for EBV-associated epithelial tumours. Therefore, the purpose of this systematic review and meta-analysis is to assess these EBV miRNAs as prognostic biomarkers for NPC and GC. Method This systematic review was developed based on PRISMA guidelines and utilizing PubMed, Web of Science, Scopus, Cochrane, and Google scholar databases. The retrieved articles were thoroughly screened in accordance with the selection criteria. The hazard ratio (HR) and 95% confidence interval (CI) for patient survival outcomes were used to evaluate EBV miRNA expression levels. To assess the risk of bias, funnel plot symmetry and Egger’s bias test were employed. Result Eleven studies met the selection criteria for inclusion, and four were included in the meta-analysis. Most of the articles considered in this study were from China, with one study from South Korea. The overall pooled effect size estimation (HR) for upregulated EBV miRNAs was 3.168 (95% CI: 2.020–4.969), demonstrating that upregulated EBV miRNA expression enhanced the mortality risk in NPC and GC patients by three times. Conclusion To the best of our knowledge, this is the first meta-analysis that investigates the significance of EBV miRNAs as prognostic biomarkers in NPC and GC patients. The pooled effect estimates of HR of the various studies revealed that higher EBV miRNA expression in NPC and GC may result in a worse survival outcome. To assess the clinical significance of EBV miRNAs as prognostic biomarkers, larger-scale prospective studies are needed.

Coronavirus disease 2019 (COVID-19) has shaken the world and triggered drastic changes in our lifestyle to control it. Despite the non-typical efforts, COVID-19 still thrives and plagues humanity worldwide. The unparalleled degree of infection has been met with an exceptional degree of research to counteract it. Many drugs and therapeutic technologies have been repurposed and discovered, but no groundbreaking antiviral agent has been introduced yet to eradicate COVID-19 and restore normalcy. As lethality is directly correlated with the severity of disease, hospitalized severe cases are of the greatest importance to reduce, especially the cytokine storm phenomenon. This severe inflammatory phenomenon characterized by elevated levels of inflammatory mediators can be targeted to relieve symptoms and save the infected patients. One of the promising therapeutic strategies to combat COVID-19 is nucleic acid-based therapeutic approaches, including microRNAs (miRNAs). This work is an up-to-date review aimed to comprehensively discuss the current nucleic acid-based therapeutics against COVID-19 and their mechanisms of action, taking into consideration the emerging SARS-CoV-2 variants of concern, as well as providing potential future directions. miRNAs can be used to run interference with the expression of viral proteins, while endogenous miRNAs can be targeted as well, offering a versatile platform to control SARS-CoV-2 infection. By targeting these miRNAs, the COVID-19-induced cytokine storm can be suppressed. Therefore, nucleic acid-based therapeutics (miRNAs included) have a latent ability to break the COVID-19 infection in general and quell the cytokine storm in particular.