Dysregulation of long non-coding RNA gene expression pathways in monocytes of type 2 diabetes patients with cardiovascular disease.

BACKGROUND: Monocytes play a central role in the pathophysiology of cardiovascular complications in type 2 diabetes (T2D) patients through different mechanisms. We investigated diabetes-induced changes in lncRNA genes from T2D patients with cardiovascular disease (CVD), long-duration diabetes, and poor glycemic control. METHODS: We performed paired-end RNA sequencing of monocytes from 37 non-diabetes controls and 120 patients with T2D, of whom 86 had either macro or microvascular disease or both. Monocytes were sorted from peripheral blood using flow cytometry; their RNA was purified and sequenced. Alignments and gene counts were obtained with STAR to reference GRCh38 using Gencode (v41) annotations followed by batch correction with CombatSeq. Differential expression analysis was performed with EdgeR and pathway analysis with IPA software focusing on differentially expressed genes (DEGs) with a p-value < 0.05. Additionally, differential co-expression analysis was done with csdR to identify lncRNAs highly associated with diabetes-related expression networks with network centrality scores computed with Igraph and network visualization with Cytoscape. RESULTS: Comparing T2D vs. non-T2D, we found two significantly upregulated lncRNAs (ENSG00000287255, FDR = 0.017 and ENSG00000289424, FDR = 0.048) and one significantly downregulated lncRNA (ENSG00000276603, FDR = 0.017). Pathway analysis on DEGs revealed networks affecting cellular movement, growth, and development. Co-expression analysis revealed ENSG00000225822 (UBXN7-AS1) as the highest-scoring diabetes network-associated lncRNA. Analysis within T2D patients and CVD revealed one lncRNA upregulated in monocytes from patients with microvascular disease without clinically documented macrovascular disease. (ENSG00000261654, FDR = 0.046). Pathway analysis revealed DEGs involved in networks affecting metabolic and cardiovascular pathologies. Co-expression analysis identified lncRNAs strongly associated with diabetes networks, including ENSG0000028654, ENSG00000261326 (LINC01355), ENSG00000260135 (MMP2-AS1), ENSG00000262097, and ENSG00000241560 (ZBTB20-AS1) when we combined the results from all patients with CVD. Similarly, we identified from co-expression analysis of diabetes patients with a duration ≥ 10 years vs. <10 years two lncRNAs: ENSG00000269019 (HOMER3-AS10) and ENSG00000212719 (LINC02693). The comparison of patients with good vs. poor glycemic control also identified two lncRNAs: ENSG00000245164 (LINC00861) and ENSG00000286313. CONCLUSION: We identified dysregulated diabetes-related genes and pathways in monocytes of diabetes patients with cardiovascular complications, including lncRNA genes of unknown function strongly associated with networks of known diabetes genes.

Mobilization of per- and poly-fluoroalkyl substances (PFAS) in soils with different organic matter contents.

There is considerable interest in addressing soils contaminated with per- and polyfluoroalkyl substances (PFAS) because of the PFAS in the environment and associated health risks. The neutralization of PFAS in situ is challenging. Consequently, mobilizing the PFAS from the contaminated soils into an aqueous solution for subsequent handling has been pursued. Nonetheless, the efficiency of mobilization methods for removing PFAS can vary depending on site-specific factors, including the types and concentrations of PFAS compounds, soil characteristics. In the present study, the removal of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) from artificially contaminated soils was investigated in a 2D laboratory setup using electrokinetic (EK) remediation and hydraulic flushing by applying a hydraulic gradient (HG) for a duration of 15 days. The percent removal of PFOA by EK was consistent (∼80%) after a 15-day treatment for all soils. The removal efficiency of PFOS by EK significantly varied with the OM content, where the PFOS removal increased from 14% at 5% OM to 60% at 50% OM. With HG, the percent removal increased for both PFOA and PFOS from about 20% at 5% OM up to 80% at 75% OM. Based on the results, the mobilization of PFAS from organic soil would be appropriate using both hydraulic flushing and EK considering their applicability and advantages over each other for site-specific factors and requirements.

Diabetes Is Associated with Worse Postoperative Mortality and Morbidity in Bariatric Surgery, Regardless of the Procedure.

Background/Objectives: Bariatric surgery is a central cornerstone in obesity treatment. We aimed to assess the impact of diabetes on the postoperative outcomes of bariatric surgery and compare three techniques: sleeve gastrectomy, Roux-en-Y, and gastric banding. Methods: We extracted data from the National Inpatient Sample (2015-2019) using ICD codes. The primary outcome was postoperative mortality. Secondary outcomes were major bleeding, atrial fibrillation, and acute renal failure. Results: Among patients who underwent sleeve gastrectomy, diabetes was associated with a higher adjusted risk of mortality (aOR 2.07 [1.36-3.16]), atrial fibrillation, and acute renal failure, but a similar risk of bleeding. Among patients who underwent Roux-en-Y, diabetes did not increase mortality and bleeding risk. Still, it was associated with a higher risk of atrial fibrillation and acute renal failure. Among patients who underwent gastric banding, diabetes was only associated with a higher risk of bleeding. When comparing the three techniques in diabetes patients, Roux-en-Y was significantly associated with higher mortality and acute renal failure risk when compared to the other procedures. Bleeding was more common in Roux-en-Y than in Sleeve. Conclusions: In total, diabetes is associated with worse postoperative outcomes in bariatric surgery, regardless of the technique. Among diabetes patients, Roux-en-Y was associated with the highest mortality and morbidity.

Enhancing the Thermal Mineralization of Perfluorooctanesulfonate on Granular Activated Carbon Using Alkali and Alkaline-Earth Metal Additives.

Thermal treatment has emerged as a promising approach for either the end-of-life treatment or regeneration of granular activated carbon (GAC) contaminated with per- and polyfluoroalkyl substances (PFAS). However, its effectiveness has been limited by the requirement for high temperatures, the generation of products of incomplete destruction, and the necessity to scrub HF in the flue gas. This study investigates the use of common alkali and alkaline-earth metal additives to enhance the mineralization of perfluorooctanesulfonate (PFOS) adsorbed onto GAC. When treated at 800 °C without an additive, only 49% of PFOS was mineralized to HF. All additives tested demonstrated improved mineralization, and Ca(OH)2 had the best performance, achieving a mineralization efficiency of 98% in air or N2. Its ability to increase the reaction rate and shift the byproduct selectivity suggests that its role may be catalytic. Moreover, additives reduced HF in the flue gas by instead reacting with the additive to form inorganic fluorine (e.g., CaF2) in the starting waste material. A hypothesized reaction mechanism is proposed that involves the electron transfer from O2- defect sites of CaO to intermediates formed during the thermal decomposition of PFOS. These findings advocate for the use of additives in the thermal treatment of GAC for disposal or reuse, with the potential to reduce operating costs and mitigate the environmental impact associated with incinerating PFAS-laden wastes.

Loss of the TRPM4 channel in humans causes immune dysregulation with defective monocyte migration.

BACKGROUND: TRPM4 is a broadly expressed, calcium-activated, monovalent cation channel that regulates immune cell function in mice and cell lines. Clinically, however, partial loss- or gain-of-function mutations in TRPM4 lead to arrhythmia and heart disease, with no documentation of immunologic disorders. OBJECTIVE: To characterize functional cellular mechanisms underlying the immune dysregulation phenotype in a proband with a mutated TRPM4 gene. METHODS: We employed a combination of biochemical, cell biological, imaging, omics analyses, flow cytometry, and gene editing approaches. RESULTS: We report the first human cases to our knowledge with complete loss of the TRPM4 channel, leading to immune dysregulation with frequent bacterial and fungal infections. Single-cell and bulk RNA sequencing point to altered expression of genes affecting cell migration, specifically in monocytes. Inhibition of TRPM4 in T cells and the THP-1 monocyte cell line reduces migration. More importantly, primary T cells and monocytes from TRPM4 patients migrate poorly. Finally, CRISPR knockout of TRPM4 in THP-1 cells greatly reduces their migration potential. CONCLUSION: Our results demonstrate that TRPM4 plays a critical role in regulating immune cell migration, leading to increased susceptibility to infections.

Genome Engineering as a Therapeutic Approach in Cancer Therapy: A Comprehensive Review.

Cancer is one of the foremost causes of mortality. The human genome remains stable over time. However, human activities and environmental factors have the power to influence the prevalence of certain types of mutations. This goes to the excessive progress of xenobiotics and industrial development that is expanding the territory for cancers to develop. The mechanisms involved in immune responses against cancer are widely studied. Genome editing has changed the genome-based immunotherapy process in the human body and has opened a new era for cancer treatment. In this review, recent cancer immunotherapies and the use of genome engineering technology are largely focused on.

T-cell lymphocytes' aging clock: telomeres, telomerase and aging.

Aging is the decline of physiological capabilities required for life maintenance and reproduction over time. The human immune cells, including T-cells lymphocytes, undergo dramatic aging-related changes, including those related to telomeres and telomerase. It was demonstrated that telomeres and telomerase play crucial roles in T-cell differentiation, aging, and diseases, including a well-documented link between short telomeres and telomerase activation demonstrated in several T-cells malignancies. Herein, we provide a comprehensive review of the literature regarding T-cells' telomeres and telomerase in health and age related-diseases.

Epigenetic age acceleration in surviving versus deceased COVID-19 patients with acute respiratory distress syndrome following hospitalization.

BACKGROUND: Aging has been reported as a major risk factor for severe symptoms and higher mortality rates in COVID-19 patients. Molecular hallmarks such as epigenetic alterations and telomere attenuation reflect the biological process of aging. Epigenetic clocks have been shown to be valuable tools for measuring biological age in various tissues and samples. As such, these epigenetic clocks can determine accelerated biological aging and time-to-mortality across various tissues. Previous reports have shown accelerated biological aging and telomere attrition acceleration following SARS-CoV-2 infection. However, the effect of accelerated epigenetic aging on outcome (death/recovery) in COVID-19 patients with acute respiratory distress syndrome (ARDS) has not been well investigated. RESULTS: In this study, we measured DNA methylation age and telomere attrition in 87 severe COVID-19 cases with ARDS under mechanical ventilation. Furthermore, we compared dynamic changes in epigenetic aging across multiple time points until recovery or death. Epigenetic age was measured using the Horvath, Hannum, DNAm skin and blood, GrimAge, and PhenoAge clocks, whereas telomere length was calculated using the surrogate marker DNAmTL. Our analysis revealed significant accelerated epigenetic aging but no telomere attrition acceleration in severe COVID-19 cases. In addition, we observed epigenetic age deceleration at inclusion versus end of follow-up in recovered but not in deceased COVID-19 cases using certain clocks. When comparing dynamic changes in epigenetic age acceleration (EAA), we detected higher EAA using both the Horvath and PhenoAge clocks in deceased versus recovered patients. The DNAmTL measurements revealed telomere attrition acceleration in deceased COVID-19 patients between inclusion and end of follow-up and a significant change in dynamic telomere attrition acceleration when comparing patients who recovered versus those who died. CONCLUSIONS: EAA and telomere attrition acceleration were associated with treatment outcomes in hospitalized COVID-19 patients with ARDS. A better understanding of the long-term effects of EAA in COVID-19 patients and how they might contribute to long COVID symptoms in recovered individuals is urgently needed.

Overweight and obesity are associated with better survival in STEMI patients with diabetes.

OBJECTIVE: The relationship between obesity and in-hospital outcomes in individuals with type 2 diabetes mellitus (T2DM) who develop an ST-elevation myocardial infarction (STEMI) was assessed. METHODS: Data from the National Inpatient Sample (NIS) from 2008 to 2017 were analyzed. Patients with STEMI and T2DM were classified as being underweight or having normal weight, overweight, obesity, and severe obesity. The temporal trend of those BMI ranges and in-hospital outcomes among different obesity groups were assessed. RESULTS: A total of 74,099 patients with T2DM and STEMI were included in this analysis. In 2008, 35.8% of patients had obesity, and 37.3% had severe obesity. However, patients with obesity accounted for most of the study population in 2017 (57.8%). During the observation period, mortality decreased in underweight patients from 18.1% to 13.2% (p < 0.001). Still, it gradually increased in all other BMI ranges, along with cardiogenic shock, atrial fibrillation, and ventricular fibrillation (p < 0.001 for all). After the combination of all patients during the observation period, mortality was lower in patients with overweight and obesity (adjusted odds ratio = 0.625 [95% CI 0.499-0.784]; 0.606 [95% CI 0.502-0.733], respectively). CONCLUSIONS: A U-shaped association governs the relationship between BMI and mortality in STEMI patients with diabetes, with those having overweight and obesity experiencing better survival.

Type 2 diabetes and in-hospital sudden cardiac arrest in ST-elevation myocardial infarction in the US.

Aims: We aimed to assess the impact of diabetes on sudden cardiac arrest (SCA) in US patients hospitalized for ST-elevation myocardial infarction (STEMI). Methods: We used the National Inpatient Sample (2005-2017) data to identify adult patients with STEMI. The primary outcome was in-hospital SCA. Secondary outcomes included in-hospital mortality, ventricular tachycardia (VT), ventricular fibrillation (VF), cardiogenic shock (CS), acute renal failure (ARF), and the revascularization strategy in SCA patients. Results: SCA significantly increased from 4% in 2005 to 7.6% in 2018 in diabetes patients and from 3% in 2005 to 4.6% in 2018 in non-diabetes ones (p < 0.001 for both). Further, diabetes was associated with an increased risk of SCA [aOR = 1.432 (1.336-1.707)]. In SCA patients with diabetes, the mean age (SD) decreased from 68 (13) to 66 (11) years old, and mortality decreased from 65.7% to 49.3% during the observation period (p < 0.001). Compared to non-diabetes patients, those with T2DM had a higher adjusted risk of mortality, ARF, and CS [aOR = 1.72 (1.62-1.83), 1.52 (1.43-1.63), 1.25 (1.17-1.33); respectively] but not VF or VT. Those patients were more likely to undergo revascularization with CABG [aOR = 1.197 (1.065-1.345)] but less likely to undergo PCI [aOR = 0.708 (0.664-0.754)]. Conclusion: Diabetes is associated with an increased risk of sudden cardiac arrest in ST-elevation myocardial infarction. It is also associated with a higher mortality risk in SCA patients. However, the recent temporal mortality trend in SCA patients shows a steady decline, irrespective of diabetes.

Field fluorometers for assessing oil dispersion at sea.

Oil dispersion by the application of chemical dispersants is an important tool in oil spill response, but it is difficult to quantify in the field in a timely fashion that is useful for coordinators and decision-makers. One option is the use of rugged portable field fluorometers that can deliver essentially instantaneous results if access is attainable. The United States Coast Guard has suggested, in their Special Monitoring of Applied Response Technologies (SMART) protocols, that successful oil dispersion can be identified by a five-fold increase in oil fluorescence. Here we test three commercial fluorometers with different excitation/emission windows (SeaOWL, Cyclops 7FO, and Cyclops 7F-G) that might prove useful for such applications. Results show that they have significantly different dynamic ranges for detecting oil and that using them (or similar instruments) in combination is probably the best option for successfully assessing the effectiveness of oil dispersion operations. Nevertheless, the rapid dilution of dispersed oil means that measurements must be made within an hour or two of dispersion, suggesting that one feasible scenario would be monitoring ship-applied dispersants by vessels following close behind the dispersant application vessel. Alternatively, autonomous submersibles might be pre-deployed to monitor aerial dispersant application, although the logistical challenges in a real spill would be substantial.

Primary hyperaldosteronism is associated with increased mortality and morbidity in patients with hypertension and diabetes.

Aims: Primary hyperaldosteronism (PA) is a common cause of hypertension. It is more prevalent in patients with diabetes. We assessed the cardiovascular impact of PA in patients with established hypertension and diabetes. Methods: Data from the National Inpatient Sample (2008-2016) was used to identify adults with PA with hypertension and diabetes comorbidities and then compared to non-PA patients. The primary outcome was in-hospital death. Secondary outcomes included ischemic stroke, hemorrhagic stroke, acute renal failure, atrial fibrillation, and acute heart failure. Results: A total of 48,434,503 patients with hypertension and diabetes were included in the analysis, of whom 12,850 (0.03%) were diagnosed with primary hyperaldosteronism (PA). Compared to patients with hypertension and diabetes but no PA, those with PA were more likely to be younger [63(13) vs. 67 (14), male (57.1% vs. 48.3%), and African-Americans (32% vs. 18.5%) (p<0.001 for all). PA was associated with a higher risk of mortality (adjusted OR 1.076 [1.076-1.077]), ischemic stroke [adjusted OR 1.049 (1.049-1.05)], hemorrhagic stroke [adjusted OR 1.05 (1.05-1.051)], acute renal failure [adjusted OR 1.058 (1.058-1.058)], acute heart failure [OR 1.104 (1.104-1.104)], and atrial fibrillation [adjusted OR 1.034 (1.033-1.034)]. As expected, older age and underlying cardiovascular disease were the strongest predictors of mortality. However, the female gender conferred protection [OR 0.889 (0.886-0.892]. Conclusion: Primary hyperaldosteronism in patients with hypertension and diabetes is associated with increased mortality and morbidity.

Post-Formation of Oil Particle Aggregates: Breakup and Biodegradation.

Spilled oil slicks are likely to break into droplets in the subtidal and intertidal zones of seashores due to wave energy. The nonliving suspended fine particles in coastal ecosystems can interact with the dispersed oil droplets, resulting in the formation of Oil Particle Aggregates (OPAs). Many investigations assumed that these aggregates will settle due to the particles' high density. Recent studies, however, reported that some particles penetrate the oil droplets, which results in further breakup while forming smaller OPAs that remain suspended in the water column. Here, we investigated the interaction of crude oil droplets with intertidal and subtidal sediments, as well as artificial pure kaolinite, in natural seawater. Results showed that the interaction between oil droplets and intertidal sediments was not particularly stable, with an Oil Trapping Efficiency (OTE) < 25%. When using subtidal sediments, OTE reached 56%. With artificial kaolinite, OPA formation and breakup were more significant (OTE reaching up to 67%) and occurred faster (within 12 h). Oil chemistry analysis showed that the biodegradation of oil in seawater (half-life of 485 h) was significantly enhanced with the addition of sediments, with half-lives of 305, 265, and 150 h when adding intertidal sediments, subtidal sediments, and pure kaolinite, respectively. Such results reveal how the sediments' shape and size affect the various oil-sediment interaction mechanisms, and the subsequent impact on the microbial degradation of petroleum hydrocarbons. Future studies should consider investigating the application of fine (several microns) and sharp (elongated-sheeted) sediments as a nondestructive and nontoxic technique for dispersing marine oil spills.

Influence of Age, Sex, and Wait Times on Public Online Ratings of Glaucoma Physicians in the United States.

PRCIS: Glaucoma surgeons are highly rated by the general public. Physicians with shorter wait times and who are younger are more likely to have higher ratings. Female glaucoma physicians are less likely to have higher ratings. PURPOSE: Find what characteristics of glaucoma physicians are associated with higher online ratings. METHODS: All American members of the American Glaucoma Society were queried on Healthgrades, Vitals, and Yelp. Ratings, medical school ranking, region of practice, sex, age, and wait times were recorded. RESULTS: One thousand one hundred six (78.2%) of American Glaucoma Society members had at least 1 review across the 3 platforms. The average score among glaucoma surgeons was 4.160 (0.898 SD). Female physicians were associated with lower online ratings [adjusted odds ratio (aOR): 0.536; 95% CI 0.354-0.808]. Physicians with <30 minutes of wait time had higher ratings: 15-30 minutes wait time (aOR: 2.273; 95% CI: 1.430-3.636) and <15 minutes wait time (aOR: 3.102; 95% CI: 1.888-5.146). Older physicians had lower ratings (aOR: 0.384; 95% CI: 0.255-0.572). CONCLUSIONS: Public online ratings of glaucoma specialists in the United States seem to favor those of younger age, men, and those with shorter wait times.

Mesenchymal stem cells-derived secretome and extracellular vesicles: perspective and challenges in cancer therapy and clinical applications.

Stem cell-based therapies have been foreshowed as a promising therapeutic approach for the treatment of several diseases. However, in the cancer context, results obtained from clinical studies were found to be quite limited. Deeply implicated in inflammatory cues, Mesenchymal, Neural, and Embryonic Stem Cells have mainly been used in clinical trials as a vehicle to deliver and stimulate signals in tumors niche. Although these stem cells have shown some therapeutical promises, they still face several challenges, including their isolation, immunosuppression potential, and tumorigenicity. In addition, regulatory and ethical concerns limit their use in several countries. Mesenchymal stem cells (MSC) have emerged as a gold standard adult stem cell medicine tool due to their distinctive characteristics, such as self-renewal and potency to differentiate into numerous cell types with lower ethical restrictions. Secreted extracellular vesicles (EVs), secretomes, and exosomes play a crucial role in mediating cell-to-cell communication to maintain physiological homeostasis and influence pathogenesis. Due to their low immunogenicity, biodegradability, low toxicity, and ability to transfer bioactive cargoes across biological barriers, EVs and exosomes were considered an alternative to stem cell therapy through their immunological features. MSCs-derived EVs, exosomes, and secretomes showed regenerative, anti-inflammatory, and immunomodulation properties while treating human diseases. In this review, we provide an overview of the paradigm of MSCs derived exosomes, secretome, and EVs cell-free-based therapies, we will focus on MSCs-derived components in anti-cancer treatment with decreased risk of immunogenicity and toxicity. Astute exploration of MSCs may lead to a new opportunity for efficient therapy for patients with cancer.

Effect of clay content on the mobilization efficiency of per- and polyfluoroalkyl substances (PFAS) from soils by electrokinetics and hydraulic flushing.

The need for the efficient remediation of soils impacted by per- and polyfluoroalkyl substances (PFAS) is substantially growing because of the notable upsurge in societal and regulatory awareness of this class of chemicals. To remediate PFAS-contaminated soils using mobilization approaches, the choice of appropriate techniques highly depends on the soil's composition, particularly the clay content, which significantly affects the soil's permeability. Here, we investigated the PFAS mobilization efficiency from soils with different clay contents by using two techniques: electrokinetic (EK) remediation and hydraulic flushing. Artificial kaolinite was added to a loamy sand soil to prepare four soil blends with clay contents of 5, 25, 50, and 75%, each contaminated with perfluorooctanoic acid (PFOA) and perfulorooctanesulfonic acid (PFOA) at 10,000 µg/kg. EK remediation was conducted by applying a low voltage (30 V) with a current of 100 mA, and hydraulic flushing was carried out by applying a hydraulic gradient (HG) with a slope of 6.7%. Results show that, with a 14-day treatment duration, the EK-mobilization efficiency was enhanced substantially with the increase of clay content (removal of PFOS increased from 20% at 5% clay to 80% at 75% clay), most likely due to the increase of electroosmotic flow due to the higher content of particles having a zeta potential (i.e., clay). For HG, increasing the clay content significantly suppressed the mobilization of PFAS (removal of PFOS decreased from 40% at 5% clay to 10% at 75% clay) due to a notable decrease in the soil's permeability. Based on the results, applying hydraulic flushing and washing techniques for mobilizing PFAS would be appropriate when treating permeable soils with a maximum clay content of about 25%; otherwise, other suitable mobilization techniques such as EKs should be considered.

Burden of cardiovascular disease attributable to particulate matter pollution in the eastern Mediterranean region: analysis of the 1990-2019 global burden of disease.

AIMS: Particulate matter pollution is the most important environmental mediator of global cardiovascular morbidity and mortality. Air pollution evidence from the Eastern Mediterranean Region (EMR) is limited, owing to scarce local studies, and the omission from multinational studies. We sought to investigate trends of particulate matter (PM2.5)-related cardiovascular disease (CVD) burden in the EMR from 1990 to 2019. METHODS AND RESULTS: We used the 1990-2019 global burden of disease methodology to investigate total PM2.5, ambient PM2.5, and household PM2.5-related CVD deaths and disability-adjusted life years (DALYs) and cause-specific CVD mortality in the EMR. The average annual population-weighted PM2.5 exposure in EMR region was 50.3 µg/m3 [95% confidence interval (CI):42.7-59.0] in 2019, which was comparable with 199 048.1 µg/m3 (95% CI: 36.5-65.3). This was despite an 80% reduction in household air pollution (HAP) sources since 1990. In 2019, particulate matter pollution contributed to 25.67% (95% CI: 23.55-27.90%) of total CVD deaths and 28.10% (95% CI: 25.75-30.37%) of DALYs in the region, most of which were due to ischaemic heart disease and stroke. We estimated that 353 071 (95% CI: 304 299-404 591) CVD deaths in EMR were attributable to particulate matter in 2019, including 264 877 (95% CI: 218 472-314 057) and 88 194.07 (95% CI: 60 149-119 949) CVD deaths from ambient PM2.5 pollution and HAP from solid fuels, respectively. DALY's in 2019 from CVD attributable to particulate matter was 28.1% when compared with 26.69% in 1990. The age-standardized death and DALY rates attributable to air pollution was 2122 per 100 000 in EMR in 2019 and was higher in males (2340 per 100 000) than in females (1882 per 100 000). CONCLUSION: The EMR region experiences high PM2.5 levels with high regional heterogeneity and attributable burden of CVD due to air pollution. Despite significant reductions of overall HAP in the past 3 decades, there is continued HAP exposure in this region with rising trend in CVD mortality and DALYs attributable to ambient sources. Given the substantial contrast in disease burden, exposures, socio-economic and geo-political constraints in the EMR region, our analysis suggests substantial opportunities for PM2.5 attributable CVD burden mitigation.

Diabetes outcomes in heart failure patients with hypertrophic cardiomyopathy.

Aims: We aimed to assess diabetes outcomes in heart failure (HF) patients with hypertrophic cardiomyopathy (HCM). Methods: The National Inpatient Sample database was analyzed to identify records from 2005 to 2015 of patients hospitalized for HF with concomitant HCM. We examined the prevalence of diabetes in those patients, assessed the temporal trend of in-hospital mortality, ventricular fibrillation, atrial fibrillation, and cardiogenic shock and compared diabetes patients to their non-diabetes counterparts. Results: Among patients with HF, 0.26% had HCM, of whom 29.3% had diabetes. Diabetes prevalence increased from 24.8% in 2005 to 32.7% in 2015. The mean age of patients with diabetes decreased from 71 ± 13 to 67.6 ± 14.2 (p < 0.01), but the prevalence of cardiovascular risk factors significantly increased. In-hospital mortality decreased from 4.3% to 3.2% between 2005 and 2015. Interestingly, cardiogenic shock, VF, and AF followed an upward trend. Age (OR = 1.04 [1.03-1.05]), female gender (OR = 1.50 [0.72-0.88]), and cardiovascular risk factors were associated with a higher in-hospital mortality risk in diabetes. Compared to non-diabetes patients, the ones with diabetes were younger and had more comorbidities. Unexpectedly, the adjusted risks of in-hospital mortality (aOR = 0.88 [0.76-0.91]), ventricular fibrillation (aOR = 0.79 [0.71-0.88]) and atrial fibrillation (aOR 0.80 [0.76-0.85]) were lower in patients with diabetes, but not cardiogenic shock (aOR 1.01 [0.80-1.27]). However, the length of stay was higher in patients with diabetes, and so were the total charges per stay. Conclusion: In total, we observed a temporal increase in diabetes prevalence among patients with HF and HCM. However, diabetes was paradoxically associated with lower in-hospital mortality and arrhythmias.

Assessing the genetic burden of familial hypercholesterolemia in a large middle eastern biobank.

BACKGROUND: The genetic architecture underlying Familial Hypercholesterolemia (FH) in Middle Eastern Arabs is yet to be fully described, and approaches to assess this from population-wide biobanks are important for public health planning and personalized medicine. METHODS: We evaluate the pilot phase cohort (n = 6,140 adults) of the Qatar Biobank (QBB) for FH using the Dutch Lipid Clinic Network (DLCN) criteria, followed by an in-depth characterization of all genetic alleles in known dominant (LDLR, APOB, and PCSK9) and recessive (LDLRAP1, ABCG5, ABCG8, and LIPA) FH-causing genes derived from whole-genome sequencing (WGS). We also investigate the utility of a globally established 12-SNP polygenic risk score to predict FH individuals in this cohort with Arab ancestry. RESULTS: Using DLCN criteria, we identify eight (0.1%) 'definite', 41 (0.7%) 'probable' and 334 (5.4%) 'possible' FH individuals, estimating a prevalence of 'definite or probable' FH in the Qatari cohort of ~ 1:125. We identify ten previously known pathogenic single-nucleotide variants (SNVs) and 14 putatively novel SNVs, as well as one novel copy number variant in PCSK9. Further, despite the modest sample size, we identify one homozygote for a known pathogenic variant (ABCG8, p. Gly574Arg, global MAF = 4.49E-05) associated with Sitosterolemia 2. Finally, calculation of polygenic risk scores found that individuals with 'definite or probable' FH have a significantly higher LDL-C SNP score than 'unlikely' individuals (p = 0.0003), demonstrating its utility in Arab populations. CONCLUSION: We design and implement a standardized approach to phenotyping a population biobank for FH risk followed by systematically identifying known variants and assessing putative novel variants contributing to FH burden in Qatar. Our results motivate similar studies in population-level biobanks - especially those with globally under-represented ancestries - and highlight the importance of genetic screening programs for early detection and management of individuals with high FH risk in health systems.

DNA methylation predicts the outcome of COVID-19 patients with acute respiratory distress syndrome.

BACKGROUND: COVID-19 infections could be complicated by acute respiratory distress syndrome (ARDS), increasing mortality risk. We sought to assess the methylome of peripheral blood mononuclear cells in COVID-19 with ARDS. METHODS: We recruited 100 COVID-19 patients with ARDS under mechanical ventilation and 33 non-COVID-19 controls between April and July 2020. COVID-19 patients were followed at four time points for 60 days. DNA methylation and immune cell populations were measured at each time point. A multivariate cox proportional risk regression analysis was conducted to identify predictive signatures according to survival. RESULTS: The comparison of COVID-19 to controls at inclusion revealed the presence of a 14.4% difference in promoter-associated CpGs in genes that control immune-related pathways such as interferon-gamma and interferon-alpha responses. On day 60, 24% of patients died. The inter-comparison of baseline DNA methylation to the last recorded time point in both COVID-19 groups or the intra-comparison between inclusion and the end of follow-up in every group showed that most changes occurred as the disease progressed, mainly in the AIM gene, which is associated with an intensified immune response in those who recovered. The multivariate Cox proportional risk regression analysis showed that higher methylation of the "Apoptotic execution Pathway" genes (ROC1, ZNF789, and H1F0) at inclusion increases mortality risk by over twofold. CONCLUSION: We observed an epigenetic signature of immune-related genes in COVID-19 patients with ARDS. Further, Hypermethylation of the apoptotic execution pathway genes predicts the outcome. TRIAL REGISTRATION: IMRPOVIE study, NCT04473131.