Assessment of genetic and clinical factors in T2D susceptibility among patients with hypertension.

AIMS: Hypertension (HTN) and Type 2 Diabetes (T2D) often coexist, therefore understanding the relationship between both diseases is imperative to guide targeted prevention/therapy. This study aims to explore the relationship between HTN and T2D using genome-wide association study (GWAS) analysis and biochemical data to understand the implication of both clinical and genetic factors in these pathologies. METHODS: A total of 2,876 patients were enrolled. Using GWAS and biochemical data, patients with both T2D and HTN were compared to patients with only HTN. Specificity was confirmed by testing the detected genetic variants for associations with HTN development in T2D patients, or with HTN in healthy subjects. Regression models were applied to examine the association of T2D in patients with HTN with cardiovascular risk factors. Replication was performed using UK Biobank dataset with 31,170 subjects. RESULTS: Data showed that females with HTN are at higher risk of developing T2D due to dyslipidemia, while males faced higher risk due to high BMI (body mass index) and family history of T2D. GWAS identified Single Nucleotide Polymorphisms (SNPs) linked to T2D in patients with HTN. Notably, rs7865889, rs7756992, and rs10896290 were positively associated with T2D, whereas rs12737517 yielded negative association. Three SNPs were replicated in the UK Biobank (rs10896290, rs7865889, and rs7756992). CONCLUSION: Incorporating clinical and genetic screening into risk assessment is important for the detection and prevention of T2D in patients with HTN. The detected SNPs (rs7865889, rs12737517, and rs10896290), especially the protective SNP (rs12737517), provide an opportunity for better diagnosis, prevention, and therapy of patients with T2D and HTN.

Coronary artery disease patients with rs7904519 (TCF7L2) are at a persistent risk of type 2 diabetes.

AIMS: Type 2 diabetes (T2D) and coronary artery disease (CAD) often coexist and share genetic factors.This study aimed to investigate the common genetic factors underlying T2D and CAD in patients with CAD. METHODS: A three-step association approach was conducted: a) a discovery step involving 943 CAD patients with T2D and 1,149 CAD patients without T2D; b) an eliminating step to exclude CAD or T2D specific variants; and c) a replication step using the UK Biobank data. RESULTS: Ten genetic loci were associated with T2D in CAD patients. Three variants were specific to either CAD or T2D. Five variants lost significance after adjusting for covariates, while two SNPs remained associated with T2D in CAD patients (rs7904519*G: TCF7L2 and rs17608766*C: GOSR2). The T2D susceptibility rs7904519*G was associated with increased T2D risk, while the CAD susceptibility rs17608766*C was negatively associated with T2D in CAD patients. These associations were replicated in a UK Biobank data, confirming the results. CONCLUSIONS: No significant common T2D and CAD susceptibility genetic association was demonstrated indicating distinct disease pathways. However, CAD patients carrying the T2D susceptibility gene TCF7L2 remain at higher risk for developing T2D emphasizing the need for frequent monitoring in this subgroup.

Impact of silver ions and silver nanoparticles on biochemical parameters and antioxidant enzyme modulations in Saccharomyces cerevisiae under co-exposure to static magnetic field: a comparative investigation.

The increase in simultaneous exposure to magnetic fields and other hazardous compounds released from industrial applications poses multiple stress conditions on the ecosystems and public human health. In this work, we investigated the effects of co-exposure to a static magnetic field (SMF) and silver ions (AgNO3) on biochemical parameters and antioxidant enzyme activities in the yeast Saccharomyces cerevisiae. Sub-chronic exposure to AgNO3 (0.5 mM) for 9 h resulted in a significant decrease in antioxidant enzyme activity, including glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and glutathione transferase (GST). The total glutathione (GSH) level increased in yeast cells exposed to Ag. Additionally, a notable elevation in malondialdehyde (MDA) levels and protein carbonyl content was observed in both the AgNP and AgNO3 groups compared to the control group. Interestingly, the SMF alleviated the oxidative stress induced by silver nitrate, normalizing antioxidant enzyme activities by reducing cellular ROS formation, MDA levels, and protein carbonylation (PCO) concentrations.

Clinical Manifestations and Genomic Evaluation of Melioidosis Outbreak among Children after Sporting Event, Australia.

Melioidosis, caused by the environmental gram-negative bacterium Burkholderia pseudomallei, usually develops in adults with predisposing conditions and in Australia more commonly occurs during the monsoonal wet season. We report an outbreak of 7 cases of melioidosis in immunocompetent children in Australia. All the children had participated in a single-day sporting event during the dry season in a tropical region of Australia, and all had limited cutaneous disease. All case-patients had an adverse reaction to oral trimethoprim/sulfamethoxazole treatment, necessitating its discontinuation. We describe the clinical features, environmental sampling, genomic epidemiologic investigation, and public health response to the outbreak. Management of this outbreak shows the potential benefits of making melioidosis a notifiable disease. The approach used could also be used as a framework for similar outbreaks in the future.

Homocysteine levels, H-Hypertension, and the MTHFR C677T genotypes: A complex interaction.

Background and objectives: High homocysteine levels are associated with increased risk of hypertension and stroke. Homocysteine is metabolized by the methylenetetrahydrofolate reductase (MTHFR). We aimed to investigate the levels of homocysteine and their association with hypertension, stroke, and antihypertensive medication usage in patients with different MTHFR C677T genotypes. Methods and results: Genotype frequency of MTHFR polymorphism was performed, and plasma homocysteine levels were measured in 2,640 adult Lebanese patients. Hypertension, history of stroke, and list of medications were documented, among other clinical and demographic parameters. The TT mutant genotype and the T mutant allele of MTHFR were more prevalent in hyperhomocysteinemia (HHcy) and H-hypertensive (H-HTN, defined as hypertension with hyperhomocysteinemia) patients when compared to non-HHcy subjects and non H-HTN patients respectively. Homocysteine levels were significantly higher in hypertensive patients specifically among those on diuretics. A higher level of homocysteine was found in hypertensive patients with the MTHFR T allele compared to patients carrying the C allele. Among the T allele carriers, the average plasma homocysteine level was 13.3 ± 0.193 µmol/L for hypertensive subjects compared to 11.9 ± 0.173 µmol/L (non-hypertensives). Furthermore, homocysteine levels significantly correlated with stroke risk in patients with the T alleles. Conclusions: We found an association of homocysteine with hypertension, hypertensive medication, and stroke risk among patients with the MTHFR T allele and the TT genotype. The association of diuretics therapy with higher homocysteine levels calls for routine measurements and therapeutic control of homocysteine in patients on diuretic, to improve health-related outcomes.

The impact of forced displacement: trauma, increased levels of inflammation and early presentation of diabetes in women Syrian refugees.

BACKGROUND: Forced displacement and war trauma cause high rates of post-traumatic stress, anxiety disorders and depression in refugee populations. We investigated the impact of forced displacement on mental health status, gender, presentation of type 2 diabetes (T2D) and associated inflammatory markers among Syrian refugees in Lebanon. METHODS: Mental health status was assessed using the Harvard Trauma Questionnaire (HTQ) and the Hopkins Symptom Checklist-25 (HSCL-25). Additional metabolic and inflammatory markers were analyzed. RESULTS: Although symptomatic stress scores were observed in both men and women, women consistently displayed higher symptomatic anxiety/depression scores with the HSCL-25 (2.13 ± 0.58 versus 1.95 ± 0.63). With the HTQ, however, only women aged 35-55 years displayed symptomatic post-traumatic stress disorder (PTSD) scores (2.18 ± 0.43). Furthermore, a significantly higher prevalence of obesity, prediabetes and undiagnosed T2D were observed in women participants (23.43, 14.91 and 15.18%, respectively). Significantly high levels of the inflammatory marker serum amyloid A were observed in women (11.90 ± 11.27 versus 9.28 ± 6.93, P = 0.036). CONCLUSIONS: Symptomatic PTSD, anxiety/depression coupled with higher levels of inflammatory marker and T2D were found in refugee women aged between 35 and 55 years favoring the strong need for psychosocial therapeutic interventions in moderating stress-related immune dysfunction and development of diabetes in this subset of female Syrian refugees.

Genetic Variants in PHACTR1 & LPL Mediate Restenosis Risk in Coronary Artery Patients.

Background and Objective: Coronary artery disease (CAD) is a major cause of death worldwide. Revascularization via stent placement or coronary artery bypass grafting (CABG) are standard treatments for CAD. Despite a high success rate, these approaches are associated with long-term failure due to restenosis. Risk factors associated with restenosis were investigated using a case-control association study design. Methods: Five thousand two hundred and forty-two patients were enrolled in this study and were assigned as follows: Stenosis Group: 3570 patients with CAD >50% without a prior stent or CABG (1394 genotyped), and Restenosis Group: 1672 patients with CAD >50% and prior stent deployment or CABG (705 genotyped). Binomial regression models were applied to investigate the association of restenosis with diabetes, hypertension, and dyslipidemia. The genetic association with restenosis was conducted using PLINK 1.9. Results: Dyslipidemia is a major risk factor (Odds Ratio (OR) = 2.14, P-value <0.0001) for restenosis particularly among men (OR = 2.32, P < 0.0001), while type 2 diabetes (T2D) was associated with an increased risk of restenosis in women (OR = 1.36, P = 0.01). The rs9349379 (PHACTR1) and rs264 (LPL) were associated with an increased risk of restenosis in our patients. PHACTR1 variant was associated with increased risk of restenosis mainly in women and in diabetic patients, while the LPL variant was associated with increased risk of restenosis in men. Conclusion: The rs9349379 in PHACTR1 gene is significantly associated with restenosis, this association is more pronounced in women and in diabetic patients. The rs264 in LPL gene was associated with increased risk of restenosis in male patients.

Elevated Lp(a) Levels Correlate with Severe and Multiple Coronary Artery Stenotic Lesions.

Backgrounds and Aims: The role of Lipoprotein(a) (Lp(a)) in increasing the risk of cardiovascular diseases is reported in several populations. The aim of this study is to investigate the correlation of high Lp(a) levels with the degree of coronary artery stenosis. Methods: Two hundred and sixty-eight patients were enrolled for this study. Patients who underwent coronary artery angiography and who had Lp(a) measurements available were included in this study. Binomial logistic regressions were applied to investigate the association between Lp(a) and stenosis in the four major coronary arteries. The effect of LDL and HDL Cholesterol on modulating the association of Lp(a) with coronary artery disease (CAD) was also evaluated. Multinomial regression analysis was applied to assess the association of Lp(a) with the different degrees of stenosis in the four major coronary arteries. Results: Our analyses showed that Lp(a) is a risk factor for CAD and this risk is significantly apparent in patients with HDL-cholesterol ≥35 mg/dL and in non-obese patients. A large proportion of the study patients with elevated Lp(a) levels had CAD even when exhibiting high HDL serum levels. Increased HDL with low Lp(a) serum levels were the least correlated with stenosis. A significantly higher levels of Lp(a) were found in patients with >50% stenosis in at least two major coronary vessels arguing for pronounced and multiple stenotic lesions. Finally, the derived variant (rs1084651) of the LPA gene was significantly associated with CAD. Conclusion: Our study highlights the importance of Lp(a) levels as an independent biological marker of severe and multiple coronary artery stenosis.

Three-Country Snapshot of Ornithine Transcarbamylase Deficiency.

X-linked ornithine transcarbamylase deficiency (OTCD) is the most common urea cycle defect. The disease severity ranges from asymptomatic carrier state to severe neonatal presentation with hyperammonaemic encephalopathy. We audited the diagnosis and management of OTCD, using an online 12-question-survey that was sent to 75 metabolic centres in Turkey, France and the UK. Thirty-nine centres responded and 495 patients were reported in total. A total of 208 French patients were reported, including 71 (34%) males, 86 (41%) symptomatic and 51 (25%) asymptomatic females. Eighty-five Turkish patients included 32 (38%) males, 39 (46%) symptomatic and 14 (16%) asymptomatic females. Out of the 202 UK patients, 66 (33%) were male, 83 (41%) asymptomatic and 53 (26%) symptomatic females. A total of 19%, 12% and 7% of the patients presented with a neonatal-onset phenotype in France, Turkey and the UK, respectively. Vomiting, altered mental status and encephalopathy were the most common initial symptoms in all three countries. While 69% in France and 79% in Turkey were receiving protein restriction, 42% were on a protein-restricted diet in the UK. A total of 76%, 47% and 33% of patients were treated with ammonia scavengers in Turkey, France and the UK, respectively. The findings of our audit emphasize the differences and similarities in manifestations and management practices in three countries.

"Involve Me and I Learn": Active Learning in a Hybrid Medical Biochemistry First Year Course on an American-Style MD Program in the UAE.

Perceived as a subject with abstract jargon, requiring extensive memorization of complex metabolic pathways, chemical structures, and names, students lose sight of the significance of biochemistry on their MD journey (Afshar M, Han Z. Teaching and learning medical biochemistry: Perspectives from a student and an educator. Med Sci Educ. 2014;24:339-41.). A disconnect between what is taught in the classroom and its application to clinical settings arises through over emphasis on the need to pass board exams, documented to be a poor measure of core competencies. Employing active learning strategies with meaningful activities with clinical applications, centered around the curriculum, cognitively engages students and is a deviation from the didactic way in which biochemistry is traditionally taught.

Urinary Angiotensinogen-Melatonin Ratio in Gestational Diabetes and Preeclampsia.

Background: A large research portfolio indicates that an activated renal renin-angiotensin system or a deficit on melatonin is associated with several cardiovascular pathologies. In this observational clinical study, we hypothesized that alterations in urinary melatonin or angiotensinogen levels may be altered in two common conditions, preeclampsia and gestational diabetes. Our study's primary objective was to assess melatonin and angiotensinogen as novel disease biomarkers detectable and quantifiable in the urine of pregnant women with or without pregnancy complications. Methods: This was a concurrent cohort study of pregnant women with selected obstetric pathologies (gestational diabetes, preeclampsia, hypertension and obesity with hypertension). A group of healthy controls was also included. Urinary 6-sulfatoxymelatonin and angiotensinogen were measured by sensitive and specific ELISAs in first morning void urine samples. The patients were included in the cohort consecutively, and the diagnosis was blinded at the level of urine collection. Urinary 6-sulfatoxymelatonin and angiotensinogen levels were investigated in the patients included in the cohort. Results: Urinary levels of angiotensinogen were significantly higher in the gestational diabetes [angiotensinogen/creatinine ratio median (25th, 75th): 0.11 (0.07, 0.18)] and preeclampsia [0.08 (0.06, 0.18)] groups than in those with healthy pregnancy [0.05(0.04, 0.06]; 6-sulfatoxymelatonin levels were significantly lower in the gestational diabetes [ug/h: median (25th, 75th): 0.12(0.08, 0.17)] and preeclampsia [0.12 (0.09, 0.15)] groups than in those with healthy pregnancy [0.20 (0.15, 0.27]. Neither morning void protein/creatinine ratio nor 24-h urine protein estimate were significantly different between the study groups. Conclusion: These results suggest that urinary angiotensinogen levels may indicate an intrarenal RAS activation while melatonin production appears to be defective in gestational diabetes or hypertension. An angiotensinogen/melatonin ratio is suggested as an early biomarker for identification of gestational diabetes or hypertension. This report provides a basis for the potential use of melatonin for the treatment of preeclampsia. A prospective study in a larger number of patients to determine the operative characteristics of these markers as potential diagnostic tests is justified.

The Study to Investigate COVID-19 Infection in People Living in Ireland (SCOPI): A seroprevalence study, June to July 2020.

BackgroundRobust data on SARS-CoV-2 population seroprevalence supplement surveillance data in providing evidence for public health action.AimTo conduct a SARS-CoV-2 population-based seroprevalence survey in Ireland.MethodsUsing a cross-sectional study design, we selected population samples from individuals aged 12-69 years in counties Dublin and Sligo using the Health Service Executive Primary Care Reimbursement Service database as a sampling frame. Samples were selected with probability proportional to the general population age-sex distribution, and by simple random sampling within age-sex strata. Antibodies to SARS-CoV-2 were detected using the Abbott Architect SARS-CoV-2 IgG Assay and confirmed using the Wantai Assay. We estimated the population SARS-CoV-2 seroprevalence weighted for age, sex and geographic area.ResultsParticipation rates were 30% (913/3,043) and 44% (820/1,863) in Dublin and Sligo. Thirty-three specimens had detectable SARS-CoV-2 antibodies (1.9%). We estimated weighted seroprevalences of 3.12% (95% confidence interval (CI): 2.05-4.53) and 0.58% (95% CI: 0.18-1.38) for Dublin and Sligo, and 1.69% (95% CI: 1.13-2.41) nationally. This equates to an estimated 59,482 (95% CI: 39,772-85,176) people aged 12-69 years nationally having had infection with SARS-CoV-2, 3.0 (95% CI: 2.0-4.3) times higher than confirmed notifications. Ten participants reported a previous laboratory-confirmed SARS-CoV-2 -infection; eight of these were antibody-positive. Twenty-five antibody-positive participants had not reported previous laboratory-confirmed infection.ConclusionThe majority of people in Ireland are unlikely to have been infected with SARS-CoV-2 by June-July 2020. Non-pharmaceutical public health measures remained key pending widespread availability of vaccination, and effective treatments.

Novel static magnetic field effects on green chemistry biosynthesis of silver nanoparticles in Saccharomyces cerevisiae.

The bacteriocidal properties of silver nanoparticles (AgNPs) depend on their average diameter (toxicity increases with decreasing diameter). In the present work, we describe novel green chemistry biosynthesis of AgNPs from AgNO3 added to cell-free culture medium of baker's yeast, Saccharomyces cerevisiae, yielding nanoparticles in the range 11-25 nm. However, when yeast was grown in a moderate static magnetic field, AgNPs obtained from the resulting cell-free culture medium, were significantly smaller (2-12 nm) than those obtained without magnetic field. These latter nanoparticles were highly crystalline, stable and near-uniform shape. Furthermore, the antibacterial activity of AgNPs obtained from static magnetic fields were greater than those from control cultures. Static magnetic fields show a promising ability to generate biocidal nanoparticles via this novel green chemistry approach.

Hematuria in a 3-month-old filly with an internal umbilical abscess and internal iliac artery aneurysm.

A 3-month-old foal with a history of acute hematuria was evaluated. Hydronephrosis and hydroureter were visualized upon renal ultrasonography of the left kidney. Cystoscopy identified a blood clot occluding the left ureter. Computed tomography (CT) revealed a large retroperitoneal abscess at the level of the aortic bifurcation and a left internal iliac aneurysm. Due to the severity of the lesions and the poor prognosis, the filly was euthanized and the clinical findings were confirmed by post-mortem examination. This report emphasizes the value of obtaining a precise diagnosis via CT in order to avoid unviable treatment approaches when confronted with this unusual secondary complication of omphaloarteritis. Key clinical message: Umbilical complications are routinely diagnosed in equine neonatal medicine, and commonly lead to septicemia, physitis, and septic arthritis; severe internal umbilical abscessation, and subsequent vascular and urinary disorders are uncommon sequelae.

Hématurie chez une pouliche de 3 mois avec abcès ombilical interne et anévrisme de l'artère iliaque interne. Un poulain de 3 mois ayant des antécédents d'hématurie aiguë a été évalué. L'hydronéphrose et l'hydro-uretère ont été visualisés par échographie rénale du rein gauche. La cystoscopie a identifié un caillot sanguin obstruant l'uretère gauche. La tomodensitométrie (TDM) a révélé un gros abcès rétropéritonéal au niveau de la bifurcation aortique et un anévrisme iliaque interne gauche. En raison de la gravité des lésions et du mauvais pronostic, la pouliche a été euthanasiée et les résultats cliniques ont été confirmés par un examen post-mortem. Ce rapport souligne l'intérêt d'obtenir un diagnostic précis par TDM afin d'éviter des approches thérapeutiques non-viables face à cette complication secondaire inhabituelle de l'omphalo-artérite.Message clinique clé :Les complications ombilicales sont couramment diagnostiquées en néonatalogie équine et conduisent généralement à une septicémie, une épiphysite et une arthrite septique; un abcès ombilical interne sévère et des troubles vasculaires et urinaires subséquents sont des séquelles peu fréquentes.(Traduit par Dr Serge Messier).

Lessons Learned Transitioning from Traditional Premedical and Medical Education to E-learning Platforms during the COVID-19 Pandemic within the United Arab Emirates.

Educational systems across the globe were disrupted by the COVID-19 pandemic, and faculty, staff, and students had to rapidly transition to e-learning platforms. These groups had little preparation to cope with the challenges of this newly adopted system. However, as we begin to emerge from the COVID-19 era, efforts are being made to assess the impact of this transition and develop a framework of best practices to help educators prepare for possible future disruptions. This commentary aims to discuss some of the challenges associated with the rapid transition to the new academic environment, including the modes of instruction employed, technical obstacles encountered, student responses to change and efforts made to evaluate didactic and practical aspects of the curriculum in the contexts of premedical and medical education, at the newly established College of Medicine at Khalifa University of Science and Technology in the United Arab Emirates.

Challenges Faculty Faced Transitioning to e-Learning Platforms during the Current Pandemic in the United Arab Emirates.

The authors recount the challenges they overcame to deliver lecture content and assessments while engaging students at their newly established medical school. Faculty must multitask in new and added ways to achieve the same goal in e-learning platforms. Online course delivery introduces additional barriers to engaging students, atypical of face-to-face sessions. We received valuable feedback, adjusted our delivery, and allowed our students to access lecture recordings at their convenience. Our sessions with students were more than just a lecture but a way to help people through a unprecedented time. Remote learning platforms also provided faculty with opportunities to develop new pedagogical skills and alternative assessments.