Interplay of serum biomarkers bilirubin and γ-glutamyltranspeptidase in predicting cardiovascular complications in type-2 diabetes mellitus.

This editorial synthesizes insights from a series of studies examining the interplay between metabolic and oxidative stress biomarkers in cardiovascular disease (CVD), focusing particularly on type-2 diabetes mellitus (T2DM) and acute coronary syndrome (ACS). The central piece of this synthesis is a study that investigates the balance between oxidative stress and antioxidant systems in the body through the analysis of serum bilirubin and γ-glutamyltranspeptidase (γ-GGT) levels in T2DM patients with ACS. This study highlights serum bilirubin as a protective antioxidant factor, while elevated γ-GGT levels indicate increased oxidative stress and correlate with major adverse cardiovascular events.

Uncovering myocardial infarction genetic signatures using GWAS exploration in Saudi and European cohorts.

Genome-wide association studies (GWAS) have yielded significant insights into the genetic architecture of myocardial infarction (MI), although studies in non-European populations are still lacking. Saudi Arabian cohorts offer an opportunity to discover novel genetic variants impacting disease risk due to a high rate of consanguinity. Genome-wide genotyping (GWG), imputation and GWAS followed by meta-analysis were performed based on two independent Saudi Arabian studies comprising 3950 MI patients and 2324 non-MI controls.

Gut microbiota analyses of Saudi populations for type 2 diabetes-related phenotypes reveals significant association.

Background: Large-scale gut microbiome sequencing has revealed key links between microbiome dysfunction and metabolic diseases such as type 2 diabetes (T2D). To date, these efforts have largely focused on Western populations, with few studies assessing T2D microbiota associations in Middle Eastern communities where T2D prevalence is now over 20%. We analyzed the composition of stool 16S rRNA from 461 T2D and 119 non-T2D participants from the Eastern Province of Saudi Arabia.

Prevalence of carriers in Saudi ischemic stroke patients and the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup.

Objectives: To mitigate the incidence of recurrent stroke in patients, dual antiplatelet therapy comprising aspirin and clopidogrel is usually administered. Clopidogrel is a prodrug and its bioactivation is catalyzed by cytochrome P450 (CYP)2C19. The main objective of this work was to determine the prevalence of carriers in Saudi ischemic stroke patients and assess the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup.

Bedside testing of CYP2C19 vs. conventional clopidogrel treatment to guide antiplatelet therapy in ST-segment elevation myocardial infarction patients.

Background: ST-segment elevation myocardial infarction (STEMI) patients are treated with dual antiplatelet therapy comprising aspirin and a P2Y inhibitor. Clopidogrel is widely used in these patients in several areas worldwide, such as Middle East, but is associated to sub-optimal platelet inhibition in up to 1/3 of treated patients. We investigated a CYP2C19 genotype-guided strategy to select the optimal P2Y inhibitor.

Faculty readiness for online teaching at Imam Abdulrahman Bin Faisal University during the COVID-19 crisis: a cross-sectional study.

The outbreak of the COVID-19 pandemic has affected the education sector around the world. In order to control the spread of the virus, eLearning practice has been introduced in Saudi higher education. Such online communication has become an important tool to narrow the teaching practice gap.

Prevalence of carriers in Saudi ischemic stroke patients and the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup.

Objectives: To mitigate the incidence of recurrent stroke in patients, dual antiplatelet therapy comprising aspirin and clopidogrel is usually administered. Clopidogrel is a prodrug and its bioactivation is catalyzed by cytochrome P450 (CYP)2C19. The main objective of this work was to determine the prevalence of carriers in Saudi ischemic stroke patients and assess the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup.

Evaluating the molecular diagnostic yield of joint genotyping-based approach for detecting rare germline pathogenic and putative loss-of-function variants.

Purpose: Cohort-based germline variant characterization is the standard approach for pathogenic variant discovery in clinical and research samples. However, the impact of cohort size on the molecular diagnostic yield of joint genotyping is largely unknown.

Methods: Head-to-head comparison of the molecular diagnostic yield of joint genotyping in two cohorts of 239 cancer patients in the absence and then in the presence of 100 additional germline exomes.

Adeno-Associated Viral Transfer of Glyoxalase-1 Blunts Carbonyl and Oxidative Stresses in Hearts of Type 1 Diabetic Rats.

Accumulation of methylglyoxal (MG) arising from downregulation of its primary degrading enzyme glyoxalase-1 (Glo1) is an underlying cause of diabetic cardiomyopathy (DC). This study investigated if expressing Glo1 in rat hearts shortly after the onset of Type 1 diabetes mellitus (T1DM) would blunt the development of DC employing the streptozotocin-induced T1DM rat model, an adeno-associated virus containing Glo1 driven by the endothelin-1 promoter (AAV2/9-Endo-Glo1), echocardiography, video edge, confocal imaging, and biochemical/histopathological assays. After eight weeks of T1DM, rats developed DC characterized by a decreased E:A ratio, fractional shortening, and ejection fraction, and increased isovolumetric relaxation time, E: e' ratio, and circumferential and longitudinal strains.

Bedside testing of CYP2C19 gene for treatment of patients with PCI with antiplatelet therapy.

Background: To mitigate the risk of stent thrombosis, patients treated by percutaneous coronary intervention (PCI) are administered dual anti-platelet therapy comprising aspirin and a platelet P2Y receptor inhibitor. Clopidogrel is a prodrug requiring activation by the cytochrome P450 enzyme, CYP2C19. In Saudi Arabia, it has been reported that approximately 26% of the population carries CYP2C19*2 and/or *3 loss-of-function polymorphisms in addition to a high prevalence of CVD.

Exome sequencing of Saudi Arabian patients with ADPKD.

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive development of kidney cysts and enlargement and dysfunction of the kidneys. The Consortium of Radiologic Imaging Studies of the Polycystic Kidney Disease (CRISP) cohort revealed that 89.1% had either a or mutation.

Identification of on-target mutagenesis during correction of a beta-thalassemia splice mutation in iPS cells with optimised CRISPR/Cas9-double nickase reveals potential safety concerns.

Precise and accurate gene correction is crucial for enabling iPSC-based therapies, and Cas9-Nickase based approaches are increasingly considered for correction of diseases such as beta-thalassemia. Here, we generate footprint-free induced pluripotent stem cells from a patient with a beta-thalassemia mutation IVSII-1 G > A) and employ a double Cas9nickase-mediated correction strategy combined with a transposon-modified donor vector for gene correction. Our approach further aimed to minimize the formation of adjacent single-strand breaks at the targeted allele through the destruction of the binding site for one guide and the use of a synonymous protospacer adjacent motif blocking mutation (canonical PAM sequence 5'-NGG-3' is changed to 5'-NCG-3', where N indicates any nucleobase) for the other guide.

Perspective: A Novel Prognostic for Sickle Cell Disease.

Sickle hemoglobin (αβ ) polymerization drives disease pathophysiology in sickle cell anemia. Fetal hemoglobin (αγ) restricts disease severity by inhibiting the polymerization of sickle hemoglobin in a concentration-dependent manner. Clinical decision-making relies on diagnostic technologies evaluating fetal hemoglobin as mean percent or mean quantity in blood.

Assessing known chronic kidney disease associated genetic variants in Saudi Arabian populations.

Background: Genome wide association studies of patients with European descent have identified common variants associated with risk of reduced estimated glomerular filtration rate (eGFR). A panel of eight variants were selected to evaluate their association and prevalence in a Saudi Arabian patient cohort with chronic kidney disease (CKD).

Methods: Eight genetic variants in four genes (SHROOM3, MYH9, SLC7A9, and CST3) were genotyped in 160 CKD patients and 189 ethnicity-matched healthy controls.

Existence of HbF Enhancer Haplotypes at Intergenic Region in Transfusion-Dependent Saudi -Thalassemia Patients.

. -Thalassemia and sickle cell disease are genetic disorders characterized by reduced and abnormal -globin chain production, respectively. The elevation of fetal hemoglobin (HbF) can ameliorate the severity of these disorders.

Psychometrics of Multiple Choice Questions with Non-Functioning Distracters: Implications to Medical Education.

Objectives: The functionality of distracters in a multiple choice question plays a very important role. We examined the frequency and impact of functioning and non-functioning distracters on psychometric properties of 5-option items in clinical disciplines.

Methods: We analyzed item statistics of 1115 multiple choice questions from 15 summative assessments of undergraduate medical students and classified the items into five groups by their number of non-functioning distracters.

Exome-Wide Association Analysis of Coronary Artery Disease in the Kingdom of Saudi Arabia Population.

Coronary Artery Disease (CAD) remains the leading cause of mortality worldwide. Mortality rates associated with CAD have shown an exceptional increase particularly in fast developing economies like the Kingdom of Saudi Arabia (KSA). Over the past twenty years, CAD has become the leading cause of death in KSA and has reached epidemic proportions.

Concept and design of a genome-wide association genotyping array tailored for transplantation-specific studies.

Background: In addition to HLA genetic incompatibility, non-HLA difference between donor and recipients of transplantation leading to allograft rejection are now becoming evident. We aimed to create a unique genome-wide platform to facilitate genomic research studies in transplant-related studies. We designed a genome-wide genotyping tool based on the most recent human genomic reference datasets, and included customization for known and potentially relevant metabolic and pharmacological loci relevant to transplantation.

IκΒα inhibits apoptosis at the outer mitochondrial membrane independently of NF-κB retention.

IκBα resides in the cytosol where it retains the inducible transcription factor NF-κB. We show that IκBα also localises to the outer mitochondrial membrane (OMM) to inhibit apoptosis. This effect is especially pronounced in tumour cells with constitutively active NF-κB that accumulate high amounts of mitochondrial IκBα as a NF-κB target gene.

Lack of MERS coronavirus neutralizing antibodies in humans, eastern province, Saudi Arabia.

We used a lentiviral vector bearing the viral spike protein to detect neutralizing antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV) in persons from the Eastern Province of Saudi Arabia. None of the 268 samples tested displayed neutralizing activity, which suggests that MERS-CoV infections in humans are infrequent in this province.

β2-adrenergic receptor gene polymorphisms in normal and asthmatic individuals in the Eastern Province of Saudi Arabia.

Background And Objectives: Several polymorphisms of the β2-adrenergic receptor (β2-AR) gene have been identified, including the amino acid substitution from arginine (Arg) to glycine (Gly) at codon 16 and from glutamine (Gln) to glutamic acid (Glu) at codon 27. These substitutions affect receptor function and show significantly more agonist-promoted receptor down-regulation than cells expressing the Arg 16/Gln 27 variants. Although the ethnic dependency of this polymorphism has been described in other populations, no studies investigating its relationship to asthma have been conducted in the Saudi population .

Academic job satisfaction questionnaire: Construction and validation in Saudi Arabia.

Background: Colleges and universities are becoming increasingly accountable for teaching outcomes in order to meet rigorous accreditation standards. Job satisfaction (JS) seems more difficult to measure in the academic field in view of the complexity of roles, duties and responsibilities.

Objectives: To compile and determine the psychometric properties of a proposed Academic Job Satisfaction Questionnaire (AJSQ) suitable for university faculty, and amenable to future upgrading.