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Moza Alishaq,1 Hanaa Nafady-Hego,2 Andrew Jeremijenko,3 Jameela Ali Al Ajmi,4 Mohamed Elgendy,5 Naser Ali Asad Al Ansari,4 Hamed Elgendy,4,6 Abdul-Badi Abou-Samra,1,3 Adeel A Butt4,7,8 1Department of Quality and Clinical Transformation, Hamad Medical Corporation, Doha, Qatar; 2Microbiology and Immunology Department, Faculty of Medicine, Assiut University, Assiut, Egypt; 3Department of Medicine, Hamad Medical Corporation, Doha, Qatar; 4Hamad Medical Corporation, Doha, Qatar; 5Faculty of Medicine, Universiti Sains of Malaysia, Kelantan, Malaysia; 6Anesthesia Department, Faculty of Medicine, Assiut University, Assiut, Egypt; 7Departments of Medicine and Population Health Sciences, Weill Cornell Medical College, New York, NY, USA; 8Departments of Medicine and Population Health Sciences, Weill Cornell Medical College, Doha, QatarCorrespondence: Adeel A Butt, Department of Medicine, Hamad Medical Corporation, PO Box 3050, Doha, Qatar, Email aabutt@hamad.qaObjective: To determine the prevalence of SARS-CoV-2 virus infection among female workers who were restricted to working from home compared with those who continued to attend in-person work.Methods: As part of national surveillance program, serum samples for SARS-CoV-2 antibody testing and nasopharyngeal swabs for SARS-CoV-2 PCR were obtained on 1636 female school staff and salon/spa workers who were restricted to work remotely (restricted group) and 1190 female health-care workers who continued in-person work (unrestricted group).Results: Seropositivity rate was 5.1% among the restricted and 22.7% among the unrestricted group (P < 0.0001). Presence of symptoms at baseline (adjusted odds ratio [aOR], 2.88; 95% CI 2.09– 3.97), contact with a confirmed case (aOR 2.34; 95% CI 1.37– 3.98), and unrestricted work type (aOR 4.71; 95% CI 3.24– 6.86) were associated with a higher risk of infection, while increasing age was associated with a lower risk of infection.Conclusion: Prevalence of SARS-CoV-2 infection as determined by seropositivity was higher among women who were not subject to workplace restrictions.Keywords: SARS-CoV-2, COVID-19, work-place restrictions, women, infections, Qatar

Objectives: Mass gathering events may facilitate the transmission of foodborne diseases. We determined the presentations and causative organisms of gastrointestinal illness among the attendees of the Fédération Internationale de Football Association Football World Cup 2022 (FIFA 2022)., Methods: The study was conducted at Hamad Medical Corporation in Qatar, which served as the national reference laboratory for all microbiology testing. We retrieved all stool testing data from the attendees of FIFA 2022 from October 1 to December 31, 2022. Stool microscopy for ova and parasite and cultures were performed on all samples. Polymerase chain reaction testing was performed for cases of suspected foodborne outbreaks or when a rapid result was required for public health response., Results: Among 2179 samples tested, one or more organisms were identified in 424 cases. The most common reasons for testing were acute diarrhea/gastroenteritis (51.4%), abdominal pain (11.5%), screening/surveillance of contacts (10.6%), and fever (7.6%). Bacteria were identified in 92.5% (Salmonella spp. 40%, Escherichia coli 25.7%, and Shigella spp. 8.8%), viruses in 7.8%, and parasites in 2.8% of the samples., Conclusions: The number of individuals who underwent stool testing during the FIFA 2022 was low. The yield of stool testing was higher for those with acute diarrhea/gastroenteritis and fever but not for those with abdominal pain or for surveillance/screening., Competing Interests: Dr. Butt has received investigator-initiated grant funding from Gilead Sciences and Merck and Company (to the institution), which is unrelated to the work presented here. The remaining authors declare no financial conflict of interest regarding the content of this article., (© 2024 The Author(s).)

Using the VA COVID-19 National Database, we created matched pairs of previously uninfected vaccinated (≥2 doses of an mRNA vaccine) and previously infected unvaccinated individuals. The incidence rate (per 1000 person-days) of breakthrough infection among vaccinated individuals (0.30, 95% CI 0.29-0.32) was similar to reinfection rate among unvaccinated individuals (0.31, 95% CI 0.30-0.32; p=0.5). The incidence rate of hospitalization/death was higher after reinfection (7.31, 95% CI 6.66-8.03) compared with rate after breakthrough infection (4.69, 95% CI 4.06-5.42; P<0.0001). Conclusion: The incidence of hospitalization/death is significantly higher after reinfection among unvaccinated individuals compared with breakthrough infection after vaccination., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Type 1 diabetes mellitus (T1DM) is associated with adverse maternal and fetal outcomes. Continuous glucose monitoring (CGM) during pregnancy is associated with better glycemic control in women with T1DM. However, no clear benefits have been demonstrated in reducing adverse feto-maternal outcomes in pregnant women with T1DM., Design and Methods: This is a retrospective, single-center study of pregnant women with T1DM to evaluate the impact of CGM use on glycemic control and feto-maternal outcomes in pregnant women with T1DM., Results: Of 265 women with T1DM, 92 (34.7%) used CGM, and 173 (65.3%) were managed with capillary blood glucose (CBG) monitoring. The mean (SD) age and BMI at the first visit were 29.4 (4.7) years and 27.2 (5.2) kg/m 2, respectively. The mean (SD) HbA1c at the first-trimester visit was 63 (1) mmol/mol, and in the last trimester was 51 (1%). There was no difference in the mean changes in HbA1c between the two groups. Women using CGM had lower insulin requirements (1.02 + 0.37 vs. 0.87 + 0.04 units/kg, p = 0.01). The two groups had no significant differences in maternal or fetal outcomes., Conclusion: CGM use in pregnant T1DM women is not associated with improved fetomaternal outcomes.

Objective: This study investigated the association between Coronavirus Disease 2019 mRNA vaccination and stroke in Qatar., Methods: Between December 1, 2020, and April 11, 2023, a matched case-control study was conducted to investigate the association between 3036 acute stroke cases and 3036 controls drawn from the entire population of Qatar., Results: The adjusted odds ratio (aOR) for vaccination among cases compared to controls was 0.87 (95% CI: 0.75-1.00). The aOR was 0.74 (95% CI: 0.45-1.23) for a single vaccine dose, 0.87 (95% CI: 0.73-1.04) for primary-series vaccination (two doses), and 0.91 (95% CI: 0.66-1.25) for booster vaccination (three or more doses). The aOR was 0.87 (95% CI: 0.72-1.04) for BNT162b2 and 0.86 (95% CI: 0.67-1.11) for mRNA-1273. Subgroup analyses, considering different durations since vaccination, also demonstrated no association. Subgroup analyses based on nationality, age, number of coexisting conditions, or prior infection status yielded similar results. Subgroup analysis, stratified by stroke type, suggested an association between vaccination and cerebral venous sinus thrombosis (aOR of 2.50 [95% CI: 0.97-6.44]), but it did not reach statistical significance., Conclusion: There was no evidence of an increased risk of stroke following vaccination, both in the short term and in the long term, extending beyond a year after receiving the vaccine., Competing Interests: Declarations of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Dr. Butt has received institutional grant funding from Gilead Sciences unrelated to the work presented in this paper. Otherwise, we declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Obesity stands as a formidable global health challenge, predisposing individuals to a plethora of chronic illnesses such as cardiovascular disease, diabetes, and cancer. A confluence of genetic polymorphisms, suboptimal dietary choices, and sedentary lifestyles significantly contribute to the elevated incidence of obesity. This multifaceted health issue profoundly disrupts homeostatic equilibrium at both organismal and cellular levels, with marked alterations in gut permeability as a salient consequence. The intricate mechanisms underlying these alterations have yet to be fully elucidated. Still, evidence suggests that heightened inflammatory cytokine levels and the remodeling of tight junction (TJ) proteins, particularly claudins, play a pivotal role in the manifestation of epithelial barrier dysfunction in obesity. Strategic targeting of proteins implicated in these pathways and metabolites such as short-chain fatty acids presents a promising intervention for restoring barrier functionality among individuals with obesity. Nonetheless, recognizing the heterogeneity among affected individuals is paramount; personalized medical interventions or dietary regimens tailored to specific genetic backgrounds and allergy profiles may prove indispensable. This comprehensive review delves into the nexus of obesity, tight junction remodeling, and barrier dysfunction, offering a critical appraisal of potential therapeutic interventions., (© 2024 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Over the years, several international guidelines have been developed by specialist organizations for the diagnosis of gestational diabetes mellitus (GDM). However, these guidelines vary and lack consensus on what level of glycemia defines GDM and worryingly, there is now evidence of over- or- under-diagnosis of women with GDM by current criteria. Towards this end, the National Priorities Research Program (NPRP) funded a program of research aimed at elucidating the problem with GDM diagnosis. It was determined, on completion of the project, that the solution required diagnosis of graded levels of dysglycemia in pregnancy and not just a diagnosis of presence or absence of GDM. A new diagnostic criterion (called the NPRP criterion) was created based on a single numerical summary of the three readings from the oral glucose tolerance test (GTT) that diagnosed women in pregnancy into four levels: normal, impaired, GDM and high risk GDM. This paper now examines existing GDM criteria vis-à-vis the NPRP criterion. It is noted that no significant change has happened over the years for existing criteria except for a gradual reduction in the threshold values of individual time-points or the number of time points, bringing us towards over-diagnosis of GDM in pregnancy. The new criterion unifies all readings from the GTT into one numerical value and, because it results in four levels of glycemia, represents a new way forwards for GDM diagnosis and can potentially reduce the rates of under diagnosis and over diagnosis of GDM., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Insulin resistance (IR) and beta cell dysfunction are the major drivers of type 2 diabetes (T2D). Genome-Wide Association Studies (GWAS) on IR have been predominantly conducted in European populations, while Middle Eastern populations remain largely underrepresented. We conducted a GWAS on the indices of IR (HOMA2-IR) and beta cell function (HOMA2-%B) in 6,217 non-diabetic individuals from the Qatar Biobank (QBB; Discovery cohort; n = 2170, Replication cohort; n = 4047) with and without body mass index (BMI) adjustment. We also developed polygenic scores (PGS) for HOMA2-IR and compared their performance with a previously derived PGS for HOMA-IR (PGS003470). We replicated 11 loci that have been previously associated with HOMA-IR and 24 loci that have been associated with HOMA-%B, at nominal statistical significance. We also identified a novel locus associated with beta cell function near VEGFC gene, tagged by rs61552983 ( P = 4.38 × 10 -8 ). Moreover, our best performing PGS (Q-PGS4; Adj R 2 = 0.233 ± 0.014; P = 1.55 x 10 -3 ) performed better than PGS003470 (Adj R 2 = 0.194 ± 0.014; P = 5.45 x 10 -2 ) in predicting HOMA2-IR in our dataset. This is the first GWAS on HOMA2 and the first GWAS conducted in the Middle East focusing on IR and beta cell function. Herein, we report a novel locus in VEGFC that is implicated in beta cell dysfunction. Inclusion of under-represented populations in GWAS has potentials to provide important insights into the genetic architecture of IR and beta cell function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Aliyu, Umlai, Toor, Elashi, Al-Sarraj, Abou−Samra, Suhre and Albagha.)

Background: We investigated the spectrum of infection and risk factors for invasive fungal disease due to Candida auris (CA) in Qatar., Methods: We performed structured chart reviews on individuals with any positive CA culture between May 2019 and December 2022 at three tertiary care hospitals in Qatar. Invasive CA disease (ICAD) was defined as a positive sterile site culture, or any positive culture for CA with appropriate antifungal prescription. Main outcomes included proportion of individuals who developed ICAD among those with positive cultures, and 30-day/in-hospital mortality., Results: Among 331 eligible individuals, median age was 56 years, 83.1% were male, 70.7% were non-Qataris, and 37.5% had ≥ 3 comorbidities at baseline. Overall, 86.4% were deemed to have colonization and 13.6% developed ICAD. Those with ICAD were more likely to have invasive central venous or urinary catheterization and mechanical ventilation. Individuals with ICAD had longer prior ICU stay (16 vs 26 days, P = 0.002), and longer hospital length of stay (63 vs. 43 days; P = 0.003), and higher 30-day mortality (38% vs. 14%; P<0.001). In multivariable regression analysis, only mechanical ventilation was associated with a higher risk of ICAD (OR 3.33, 95% CI 1.09-10.17)., Conclusion: Invasive Candida auris Disease is associated with longer hospital stay and higher mortality. Severely ill persons on mechanical ventilation should be especially monitored for development of ICAD., Competing Interests: Dr. Butt has received investigator-initiated grant funding from Gilead Sciences and Merck and Company (to the institution, Veterans Health Foundation of Pittsburgh) which are unrelated to the work presented here. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Al Ajmi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The genetic basis of type 2 diabetes (T2D) is under-investigated in the Middle East, despite the rapidly growing disease prevalence. We aimed to define the genetic determinants of T2D in Qatar., Methods: Using whole genome sequencing of 11,436 participants (2765 T2D cases and 8671 controls) from the population-based Qatar Biobank (QBB), we conducted a genome-wide association study (GWAS) of T2D with and without body mass index (BMI) adjustment., Results: We replicated 93 known T2D-associated loci in a BMI-unadjusted model, while 96 known loci were replicated in a BMI-adjusted model. The effect sizes and allele frequencies of replicated SNPs in the Qatari population generally concurred with those from European populations. We identified a locus specific to our cohort located between the APOBEC3H and CBX7 genes in the BMI-unadjusted model. Also, we performed a transethnic meta-analysis of our cohort with a previous GWAS on T2D in multi-ancestry individuals (180,834 T2D cases and 1,159,055 controls). One locus in DYNC2H1 gene reached genome-wide significance in the meta-analysis. Assessing polygenic risk scores derived from European- and multi-ancestries in the Qatari population showed higher predictive performance of the multi-ancestry panel compared to the European panel., Conclusion: Our study provides new insights into the genetic architecture of T2D in a Middle Eastern population and identifies genes that may be explored further for their involvement in T2D pathogenesis., (© 2024. The Author(s).)

Background: Diabetes in pregnancy (DIP) is associated with adverse fetal and maternal outcomes. DIP is classified as either pre-existing or new-onset diabetes mellitus (DM), which is classified into gestational DM (GDM) and newly detected type 2 (N-T2D). All pregnant women in Qatar who are not known to have pre-existing DM are offered screening for DIP during the first antenatal care visit and after 24 weeks gestation. The study aims to report the DIP screening rates, the prevalence of DIP, and the impact of the universal screening program on adverse pregnancy outcomes., Methods: This retrospective study included all women who gave birth in Hamad Medical Corporation (HMC) hospitals between 2019 and 2022. New-onset DIP was defined using the WHO-2013 criteria. The primary outcomes were the screening rates and the prevalence of DIP in Qatar. The secondary outcomes were the difference in preterm delivery, C-section, macrosomia, large for gestational age (LGA), small for gestational age (SGA), and intra-uterine fetal death (IUFD) between women with or without GDM., Findings: We included 94,422 women who gave birth to 96,017 neonates (85.7%) out of 112,080 neonates born nationwide. The number of women with pre-existing diabetes was 2496 women. Of 91,926 eligible women, 77,372 (84.2%) were screened for DIP. The prevalence of GDM is 31.6% (95% CI: 31.3-32.0%); N-T2D is 2.2% (95% CI: 2.1-2.3%), and pre-existing Type 2 DM and Type 1 DM was 2.6% (95% CI: 0.8-3.0%) and 0.2% (0.19-0.25), respectively. Compared to the non-GDM group, women with GDM were older (30.8 ± 5.3 versus 29.7 ± 5.2 years, p < 0.001). After adjusting for age, women with GDM had lower risk of IUFD and SGA (0.63 [95% CI 0.50-0.80, p < 0.001], 0.88 [95% CI 0.84-0.92, p < 0.001] respectively) but higher risk of C-section and LFD (1.07 [95% CI 1.04-1.10, p < 0.001], 1.09 [95% CI 1.01-1.15, p = 0.01], respectively, compared to women with no-GDM., Interpretation: Of the women eligible for screening, 84.2% were screened by the DIP program in Qatar. The prevalence of DIP in Qatar is 36.9%. Integrated care is critical for the screening and management of diabetes during pregnancy., Fundings: The authors did not receive any funding for this project., Competing Interests: The study did not receive any funds. The authors have no relevant affiliations or financial involvement with any organisation or entity with a financial interest in or conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants, patents received or pending, or royalties., (© 2024 The Authors.)

Background A long distance and time spent traveling to a hemodialysis (HD) center and other factors, such as comorbidities, can significantly impact HD patient compliance, satisfaction, and cost. Uncertainty about HD-dependent patients' geographical location may lead to inappropriate distribution of HD centers. The present study investigates travel time, distance, and nonspatial factors affecting HD center accessibility within a 30-km radius in the State of Qatar. Materials and methods The study included all HD-dependent patients residing in Qatar between March 1, 2020, and December 31, 2021. There were 921 patients dialyzed in six HD centers across Qatar. Our methodology incorporated descriptive and analytical cross-sectional designs to accurately identify the shortest routes and quickest travel times. We used two applications (Maptive {Vancouver, WA: BatchGeo LLC} and Google Maps {Mountain View, CA: Google LLC}) and marked a driving distance of 30 km as the main assessment scale and measurement standard, allowing optimum spatial accessibility determination. Results On average, patients traveled approximately 19±4.2 km, requiring almost 17.6±3.4 minutes to reach the assigned HD center three times per week. Based on geographic-spatial accessibility analysis, patients living in Umm Salal drove 31.4±3.5 km in 32.4±4.7 minutes, Al Daayen patients drove 30.2 km in 25.3 minutes, and others even drove more than 70 km to access HD sessions. Approximately 37.8% of Qatar's municipalities had no HD centers within their boundaries, but nearly 47% of HD-dependent patients lived in those municipalities. Additionally, some municipalities had HD centers; however, their general population density was less than 100 inhabitants/km 2 , and they had relatively few patients requiring regular HD. We noted a statistically significant correlation between the patients' residences and the locations of HD centers, whether they were located within or outside municipalities. Also, nonspatial factors may have affected the likelihood of reaching a hemodialysis center within a 30-km distance, including two or more comorbid conditions, having HD for at least five years, living in a municipality with more than 1,000 inhabitants/km 2 , being female, and attending dialysis centers that are more than 30 km away. Conclusion Although the available HD centers were sufficient for the present number of patients requiring HD, HD center locations did not match the patients' distribution, leading to difficulties for some patients. Understanding the impact of this geographic mismatch, population density, and other spatial factors helps significantly improve patient care and satisfaction at minimal cost. Furthermore, considering all these factors is crucial when planning new centers to achieve higher satisfaction and compliance as well as better health care., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Al Halabi et al.)

Extracellular vesicles (EVs) are nano-sized, membranous structures secreted into the extracellular space. They exhibit diverse sizes, contents, and surface markers and are ubiquitously released from cells under normal and pathological conditions. Human serum is a rich source of these EVs, though their isolation from serum proteins and non-EV lipid particles poses challenges. These vesicles transport various cellular components such as proteins, mRNAs, miRNAs, DNA, and lipids across distances, influencing numerous physiological and pathological events, including those within the tumor microenvironment (TME). Their pivotal roles in cellular communication make EVs promising candidates for therapeutic agents, drug delivery systems, and disease biomarkers. Especially in cancer diagnostics, EV detection can pave the way for early identification and offers potential as diagnostic biomarkers. Moreover, various EV subtypes are emerging as targeted drug delivery tools, highlighting their potential clinical significance. The need for non-invasive biomarkers to monitor biological processes for diagnostic and therapeutic purposes remains unfulfilled. Tapping into the unique composition of EVs could unlock advanced diagnostic and therapeutic avenues in the future. In this review, we discuss in detail the roles of EVs across various conditions, including cancers (encompassing head and neck, lung, gastric, breast, and hepatocellular carcinoma), neurodegenerative disorders, diabetes, viral infections, autoimmune and renal diseases, emphasizing the potential advancements in molecular diagnostics and drug delivery., (© 2024. The Author(s).)

There is variability in the metabolic health status among individuals presenting with obesity; some may be metabolically healthy, while others may have developed the metabolic syndrome, a cluster including insulin resistance, hypertension, dyslipidemia, and increased risk of cardiovascular disease and type 2 diabetes. The mechanisms contributing to this metabolic heterogeneity are not fully understood. To address this question, plasma samples from 48 individuals with BMI ≥ 35 kg/m 2 were examined (27 with and 21 without metabolic syndrome). Fasting plasma samples were subjected to Olink proteomics analysis for 184 cardiometabolic and inflammation-enriched proteins. Data analysis showed a clear differentiation between the two groups with distinct plasma protein expression profiles. Twenty-four proteins were differentially expressed (DEPs) between the two groups. Pathways related to immune cell migration, leukocyte chemotaxis, chemokine signaling, mucosal inflammatory response, tissue repair and remodeling were enriched in the group with metabolic syndrome. Functional analysis of DEPs revealed upregulation of 15 immunological pathways. The study identifies some of the pathways that are altered and reflect metabolic health in individuals with obesity. This provides valuable insights into some of the underlying mechanisms and can lead to identification of therapeutic targets to improve metabolic health in individuals with obesity., (© 2023. The Author(s).)

Background: Chronic Urticaria (CU) is a complex skin disease that appears as recurrent raised itchy rash/angioedema or both for more than six weeks. The pathophysiology of CU is complex and has yet to be understood entirely. It is predominantly a mast cell-driven disease with the possible involvement of type 2 inflammation. Current evidence largely favors mast cell activation by an IgE-mediated autoallergic mechanism or an autoimmune mechanism by IgG autoantibodies to IgE/ high-affinity receptor of IgE. MicroRNAs (miRNA) are small coding RNAs regulating gene expression at the post-transcription level. This study aimed to investigate the circulating miRNA as potential biomarkers in CU patients compared to healthy controls. Methods: The miRNA gene expression was done in seven patients with CU and seven healthy controls. The expression of miRNA is done using TaqMan openArray human advanced miRNA Panel. ExpressionSuite Software (Thermo Fischer Scientific, Waltham, MA, USA) is used for data analysis to quantify the miRNA expressions. P<0.05 is considered to be statistically significant. Results: A significant upregulation (p<0.05) in the miR-451a, miR-9-5p, miR-150-5p, miR-296-5p, and miR-182-5p was observed in CU compared to controls. Dysregulation of miR-451a is identified as an early biomarker in allergic diseases. Functional enrichment analysis with the KEGG pathway and disease ontology databases showed that these miRNAs were associated with skin diseases and inflammation. The differentially expressed miRNAs contribute to determining the genes regulated in CU. miRNA-based therapies that target different genes in a given pathway might be a potential candidate for treating CU. Conclusion: miRNA field has grown steadily over the past few years, but the role of circulating miRNAs in CU remains relatively unexplored. This study showed that the upregulated circulating miRNA might play an essential role in CU pathogenesis and inflammation. Also, our study highlights the importance of miRNAs as a future biomarker and potential therapeutic target to be investigated., (© 2023 Jerobin, Ali, Khalil, Ramanjaneya, Betahi, Samra, Al-Nesf, licensee HBKU Press.)

Body contouring surgery enhances physical appearance by means of surgical subcutaneous fat removal (SSFR). However, it remains unclear how SSFR may affect glucose metabolism and its broader effects on the endocrine system, especially in individuals who have undergone obesity (bariatric) surgery. This study aimed to evaluate the impact of SSFR on glucose excursion and insulin resistance in such patients, by examining them over three visits (within 1 week before surgery, 1 week after surgery, and 6 weeks after surgery). The independent impact of SSFR and history of obesity surgery on glucose homeostasis was evaluated in 29 participants, of whom ten patients (34%) had a history of obesity surgery. Indices of glucose metabolism were evaluated using cluster robust-error logistic regression. Results indicated that SSFR led to a gross improvement in insulin resistance at 6 weeks after the surgery in all patient's irrespective of BMI, type 2 diabetes mellitus (T2D) status, or history of obesity surgery (OR 0.22; p = 0.042). However, no effect was observed on glucose excursion except for a transient increase at visit 2 (1 week after surgery) in those without prior obesity surgery. Interestingly, participants with a history of obesity surgery had approximately half the odds being in the upper tertile for HOMA-IR (OR 0.44; p = 0.142) and ten-folds lower odds of having severely abnormal glucose excursion (OR 0.09; p = 0.031), irrespective of their BMI, T2D status, or time post SSFR. In conclusion, this study showed that body contouring surgery through SSFR resulted in (at least) short-term improvement in insulin resistance (independent of the participant's BMI, T2D status, or history of obesity surgery) without affecting glucose excursion under the GTT. On the contrary, obesity surgery may have a long-term effect on glucose excursion, possibly due to sustained improvement of pancreatic ß-cell function.

Standard cell therapy equipment, including the gold standard cell processor to purify human islets for clinical transplantation, is rarely refrigerated, potentially exposing cells to elevated temperatures during the centrifugation step. Custom cooling systems have a direct benefit on human islet viability and function. The current study was designed to test the effectiveness of a newly developed, readily available cooled cell processor system requiring minimal modifications and to evaluate its impact on human cell viability and the GMP cleanroom environment. The cooler system, a mechanically refrigerated heat exchanger set at -30 °C was used to deliver cooled medical grade dry air to the cell processor bowl through a hole drilled in the centrifuge cover. With the limited availability of pancreas donors in Qatar, system validation was done with continuous density gradient purification of pooled human bone marrow buffy coat. Sterility, turbulence, and particle count were measured in class C and class B clean room environments. No turbulence developed around the cooled cell processor, and no excess 0.5 µm and 5 µm airborne particulates were generated as per cleanroom GMP standards. At the beginning and end of the collection steps, the temperature rose respectively to 21.50 °C ± 0.34 °C and 21.93 °C ± 0.20 °C in the non-cooled cell processor and to only 10.9 °C ± 0.17 °C and 11.16 °C ± 0.35 °C in the cooled- cell processor (p <0.05). The cooled cell processor led to both improved recovery (98%) of the mononuclear cell fraction and viability (100% ± 2%) post-processing. The new cooling system effectively reduces the heat produced by the cell processor while having no particulate impact on the GMP clean room environment. The cooled cell processor described here is an inexpensive ($16,000 without including taxes, customs clearance, and transportation) and minimally invasive method to provide robust cooling. Currently, this technology in the GMP cell therapy facility is being applied to human islet cell isolation and transplantation for the clinical program.

Objectives: Accurate determination of the immediate causes of death in patients with COVID-19 is important for optimal care and mitigation strategies., Methods: All deaths in Qatar between March 01, 2020, and August 31, 2022, flagged for likely relationship to COVID-19 were reviewed by two independent, trained reviewers using a standardized methodology to determine the immediate and contributory causes of death., Results: Among 749 flagged deaths, the most common admitting diagnoses were respiratory tract infection (91%) and major adverse cardiac event (MACE, 2.3%). The most common immediate causes of death were COVID-19 pneumonia (66.2%), MACE (7.1%), hospital-associated pneumonia (HAP, 6.8%), bacteremia (6.3%), disseminated fungal infection (DFI, 5.2%), and thromboembolism (4.5%). After COVID-19 pneumonia, MACE was the predominant cause of death in the first 2 weeks but declined thereafter. No death occurred due to bacteremia, HAP, or DFI in the first week after hospitalization, but became increasingly common with increased length of stay in the hospital accounting for 9%, 12%, and 10% of all deaths after 4 weeks in the hospital, respectively., Conclusion: Nearly one-third of patients with COVID-19 infection die of non-COVID-19 causes, some of which are preventable. Mitigation strategies should be instituted to reduce the risk of such deaths., Competing Interests: Declaration of competing interest Dr. Butt has received investigator-initiated grant funding from Gilead Sciences and Merck and Company (to the institution, Veterans Health Foundation of Pittsburgh) which is unrelated to the work presented here. Other authors declare no financial conflict of interest regarding the content of this article., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To examine the hypothesis that obesity complicated by the metabolic syndrome, compared to uncomplicated obesity, has distinct molecular signatures and metabolic pathways., Methods: We analyzed a cohort of 39 participants with obesity that included 21 with metabolic syndrome, age-matched to 18 without metabolic complications. We measured in whole blood samples 754 human microRNAs (miRNAs), 704 metabolites using unbiased mass spectrometry metabolomics, and 25,682 transcripts, which include both protein coding genes (PCGs) as well as non-coding transcripts. We then identified differentially expressed miRNAs, PCGs, and metabolites and integrated them using databases such as mirDIP (mapping between miRNA-PCG network), Human Metabolome Database (mapping between metabolite-PCG network) and tools like MetaboAnalyst (mapping between metabolite-metabolic pathway network) to determine dysregulated metabolic pathways in obesity with metabolic complications., Results: We identified 8 significantly enriched metabolic pathways comprising 8 metabolites, 25 protein coding genes and 9 microRNAs which are each differentially expressed between the subjects with obesity and those with obesity and metabolic syndrome. By performing unsupervised hierarchical clustering on the enrichment matrix of the 8 metabolic pathways, we could approximately segregate the uncomplicated obesity strata from that of obesity with metabolic syndrome., Conclusions: The data suggest that at least 8 metabolic pathways, along with their various dysregulated elements, identified via our integrative bioinformatics pipeline, can potentially differentiate those with obesity from those with obesity and metabolic complications., (© 2023. The Author(s).)

Although obesity is a preventable disease, maintaining a normal body weight can be very challenging and difficult, which has led to a significant increase in the demand for surgical subcutaneous fat removal (SSFR) to improve physical appearance. The need for SSFR is further exacerbated because of the global rise in the number of bariatric surgeries, which is currently the single most durable intervention for mitigating obesity. Fat tissue is now recognized as a vital endocrine organ that produces several bioactive proteins. Thus, SSFR-mediated weight (fat) loss can potentially have significant metabolic effects; however, currently, there is no consensus on this issue. This review focuses on the metabolic sequelae after SSFR interventions for dealing with cosmetic body appearance. Data was extracted from existing systematic reviews and the diversity of possible metabolic changes after SSFR are reported along with gaps in the knowledge and future directions for research and practice. We conclude that there is a potential for metabolic sequelae after SSFR interventions and their clinical implications for the safety of the procedures as well as for our understanding of subcutaneous adipose tissue biology and insulin resistance are discussed.

Background: Skeletal muscle is the main site for insulin-dependent glucose disposal. The hyperinsulinemic euglycemic clamp (HIEC) is the gold standard for the assessment of insulin sensitivity (IS). We have previously shown that insulin sensitivity, measured by HIEC, varied widely among a group of 60 young healthy men with normoglycemia. The aim of this study was to correlate the proteomic profile of skeletal muscles to insulin sensitivity., Methods: Muscle biopsies from 16 subjects having the highest (M ≥ 13; n = 8, HIS) and lowest (M ¾ 6, n = 8, LIS) IS were obtained at baseline and during insulin infusion after stabilization of the blood glucose level and glucose infusion rate at the end of the HIEC. The samples were processed using a quantitative proteomic analysis approach., Results: At baseline, 924 proteins were identified in the HIS and LIS groups. Among the 924 proteins detected in both groups, three were suppressed and three were increased significantly in the LIS subjects compared with the HIS subjects. Following insulin infusion, 835 proteins were detected in both groups. Among the 835 proteins, two showed differential responsiveness to insulin; ATP5F1 protein was decreased, and MYLK2 was higher in the LIS group compared with that in the HIS group. Our data suggest that alteration in mitochondrial proteins and an increased number of proteins involved in fast-twitch fiber correlate to insulin sensitivity in healthy young Arab men., Conclusions: These results suggest a change in a small number of differentially expressed proteins. A possible reason for this small change could be our study cohorts representing a homogeneous and healthy population. Additionally, we show differences in protein levels from skeletal muscle in low and high insulin sensitivity groups. Therefore, these differences may represent early events for the development of insulin resistance, pre-diabetes, and type 2 diabetes., Competing Interests: Authors IB, RK, NS, MR, JJ, SH, MA, IA, AI and AA-S are employed by the Hamad Medical Corporation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bettahi, Krishnankutty, Jaganjac, Suleiman, Ramanjaneya, Jerobin, Hassoun, Alkasem, Abdelhakam, Iskandarani, Samra, Mohamed-Ali and Abou-Samra.)

Accurate determination of mortality attributable to SARS-CoV-2 vaccination is critical in allaying concerns about their safety. We reviewed every death in Qatar that occurred within 30 days of any SARS-CoV-2 vaccine administration between January 1, 2021 and June 12, 2022. Probability of association with SARS-CoV-2 vaccination was determined by four independent trained reviewers using a modified WHO algorithm. Among 6,928,359 doses administered, 138 deaths occurred within 30 days of vaccination; eight had a high probability (1.15/1,000,000 doses), 15 had intermediate probability (2.38/1,000,000 doses), and 112 had low probability or no association with vaccination. The death rate among those with high probability of relationship to SARS-CoV-2 vaccination was 0.34/100,000 unique vaccine recipients, while death rate among those with either high or intermediate probability of relationship to SARS-CoV-2 vaccination was 0.98/100,000 unique vaccine recipients. In conclusion, deaths attributable to SARS-CoV-2 vaccination are extremely rare and lower than the overall crude mortality rate in Qatar., (© 2023. The Author(s).)

Background: Bariatric surgery averts obesity-induced insulin resistance and the metabolic syndrome. By contrast, surgical fat removal is considered merely an esthetic endeavor. The aim of this article was to establish whether surgical fat removal, similar to bariatric surgery, exerts measurable, lasting metabolic benefits., Methods: PubMed, Embase, and Scopus were searched using the Polyglot Search Translator to find studies examining quantitative expression of metabolic markers. Quality assessment was done using the MethodologicAl STandard for Epidemiological Research scale. The robust-error meta-regression model was employed for this synthesis., Results: Twenty-two studies with 493 participants were included. Insulin sensitivity improved gradually with a maximum reduction in fasting insulin and homeostatic model assessment for insulin resistance of 17 pmol/L and 1 point, respectively, at postoperative day 180. Peak metabolic benefits manifest as a reduction of 2 units in body mass index, 3 kg of fat mass, 5 cm of waist circumference, 15 µg/L of serum leptin, 0.75 pg/ml of tumor necrosis factor-alpha, 0.25 mmol/L of total cholesterol, and 3.5 mmHg of systolic and diastolic blood pressure that were observed at day 50 but were followed by a return to preoperative levels by day 180. Serum high-density lipoproteins peaked at 50 days post-surgery before falling below the baseline. No significant changes were observed in lean body mass, serum adiponectin, resistin, interleukin-6, C-reactive protein, triglyceride, low-density lipoproteins, free fatty acids, and fasting blood glucose., Conclusion: Surgical fat removal exerts several metabolic benefits in the short term, but only improvements in insulin sensitivity last beyond 6 months., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2022 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Patients with end-stage kidney disease (ESKD) are at increased risk for SARS-CoV-2 infection and its complications compared with the general population. Several studies evaluated the effectiveness of COVID-19 vaccines in the dialysis population but showed mixed results. The aim of this study was to determine the effectiveness of COVID-19 mRNA vaccines against confirmed SARS-CoV-2 infection in hemodialysis (HD) patients in the State of Qatar. We included all adult ESKD patients on chronic HD who had at least one SARS-CoV-2 PCR test done after the introduction of the COVID-19 mRNA vaccines on 24 December 2020. Vaccinated patients who were only tested before receiving any dose of their COVID-19 vaccine or within 14 days after receiving the first vaccine dose were excluded from the study. We used a test-negative case−control design to determine the effectiveness of the COVID-19 vaccination. Sixty-eight patients had positive SARS-CoV-2 PCR tests (cases), while 714 patients had negative tests (controls). Ninety-one percent of patients received the COVID-19 mRNA vaccine. Compared with the controls, the cases were more likely to be older (62 ± 14 vs. 57 ± 15, p = 0.02), on dialysis for more than one year (84% vs. 72%, p = 0.03), unvaccinated (46% vs. 5%, p < 0.0001), and symptomatic (54% vs. 21%, p < 0.0001). The effectiveness of receiving two doses of COVID-19 mRNA vaccines against confirmed SARS-CoV-2 infection was 94.7% (95% CI: 89.9−97.2) in our HD population. The findings of this study support the importance of using the COVID-19 mRNA vaccine in chronic HD patients to prevent SARS-CoV-2 infection in such a high-risk population.

Maturity-onset diabetes of the young (MODY) is a rare monogenic form of diabetes mellitus. In this study, we estimated the prevalence and genetic spectrum of MODY in the Middle Eastern population of Qatar using whole-genome sequencing (WGS) of 14,364 subjects from the population-based Qatar biobank (QBB) cohort. We focused our investigations on 14 previously identified genes ascribed to the cause of MODY and two potentially novel MODY-causing genes, RFX6 and NKX6-1 . Genetic variations within the 16 MODY-related genes were assessed for their pathogenicity to identify disease-causing mutations. Analysis of QBB phenotype data revealed 72 subjects (0.5%) with type 1 diabetes, 2915 subjects (20.3%) with type 2 diabetes and 11,377 (79.2%) without diabetes. We identified 22 mutations in 67 subjects that were previously reported in the Human Genetic Mutation Database (HGMD) as disease-causing (DM) or likely disease causing (DM?) for MODY. We also identified 28 potentially novel MODY-causing mutations, predicted to be among the top 1% most deleterious mutations in the human genome, which showed complete (100%) disease penetrance in 34 subjects. Overall, we estimated that MODY accounts for around 2.2-3.4% of diabetes patients in Qatar. This is the first population-based study to determine the genetic spectrum and estimate the prevalence of MODY in the Middle East. Further research to characterize the newly identified mutations is warranted.

Hypoglycemia, as a complication of type 2 diabetes (T2D), causes increased morbidity and mortality but the physiological response underlying hypoglycemia has not been fully elucidated. Small noncoding microRNA (miRNA) have multiple downstream biological effects. This pilot exploratory study was undertaken to determine if induced miRNA changes would persist and contribute to effects seen 24 h post-hypoglycemia. A parallel, prospective study design was employed, involving T2D (n = 23) and control (n = 23) subjects. The subjects underwent insulin-induced hypoglycemia (2 mmol/L; 36 mg/dL); blood samples were drawn at baseline, upon the induction of hypoglycemia, and 4 h and 24 h post-hypoglycemia, with a quantitative polymerase chain reaction analysis of miRNA undertaken. The baseline miRNAs did not differ. In the controls, 15 miRNAs were downregulated and one was upregulated (FDR < 0.05) from the induction of hypoglycemia to 4 h later while, in T2D, only four miRNAs were altered (downregulated), and these were common to both cohorts (miR-191-5p; miR-143-3p; let-7b-5p; let-7g-5p), correlated with elevated glucagon levels, and all were associated with energy balance. From the induction of hypoglycemia to 24 h, 14 miRNAs were downregulated and 5 were upregulated (FDR < 0.05) in the controls; 7 miRNAs were downregulated and 7 upregulated (FDR < 0.05) in T2D; a total of 6 miRNAs were common between cohorts, 5 were downregulated (miR-93-5p, let-7b-5p, miR-191-5p, miR-185-5p, and miR-652-3p), and 1 was upregulated (miR-369-3p). An ingenuity pathway analysis indicated that many of the altered miRNAs were associated with metabolic and coagulation pathways; however, of the inflammatory proteins expressed, only miR-143-3p at 24 h correlated positively with tumor necrosis factor-α (TNFa; p < 0.05 and r = 0.46) and negatively with toll-like receptor-4 (TLR4; p < 0.05 and r = 0.43). The MiRNA levels altered by hypoglycemia reflected changes in counter-regulatory glucagon and differed between cohorts, and their expression at 24 h suggests miRNAs may potentiate and prolong the physiological response. Trial registration: ClinicalTrials.gov NCT03102801.

Type 2 diabetes (T2D) has a heterogeneous etiology influencing its progression, treatment, and complications. A data driven cluster analysis in European individuals with T2D previously identified four subtypes: severe insulin deficient (SIDD), severe insulin resistant (SIRD), mild obesity-related (MOD), and mild age-related (MARD) diabetes. Here, the clustering approach was applied to individuals with T2D from the Qatar Biobank and validated in an independent set. Cluster-specific signatures of circulating metabolites and proteins were established, revealing subtype-specific molecular mechanisms, including activation of the complement system with features of autoimmune diabetes and reduced 1,5-anhydroglucitol in SIDD, impaired insulin signaling in SIRD, and elevated leptin and fatty acid binding protein levels in MOD. The MARD cluster was the healthiest with metabolomic and proteomic profiles most similar to the controls. We have translated the T2D subtypes to an Arab population and identified distinct molecular signatures to further our understanding of the etiology of these subtypes., (© 2022. The Author(s).)

Background Shortening the patient experience time (PET) in the emergency department (ED) improves patient quality and satisfaction and reduces mortality and morbidity. Worldwide, the PET target in the ED is ≤ 6 hours; however, the PET awaiting admission to inpatient Medicine at Hamad General Hospital (HGH) in the Qatar State, through ED is currently 15.3±6.4 (mean ± SD) hours. Aim Identify solutions to reduce the PET duration at HGH-ED to the international target. Method A cohort study was done using the Discrete-event simulation (DES) model, utilizing a commercial simulation software package (Process Model Inc., Utah, version 5.2.0). One-year data, January 1, 2019 - December 30, 2019, was analyzed and found to follow seven subprocesses. The duration of each subprocess was recorded, and the average time was calculated. A computer simulation scheme was developed for all the subprocesses of the actual PET duration. The simulated PET was validated, and scenarios were proposed and assessed for each subprocess separately and in combination, A constructed simulatory design using an iterative process involving a construction model. This model starts with the logical organization of submitted tasks based on their cycle times. A subject-matter expert interview was conducted to determine the appropriateness and frequency of actions. The duration of each activity in the considered process was defined using a triangular distribution. Results The actual PET duration for the Medical Department was 15.3±6.4 (mean + SD) hours. The three most prolonged PET subprocess durations were in the referral to internal medicine, the decision to admit, and finding a free bed; these represent 17.9%, 53.8%, and 16.7% of the PET, respectively. Adding two physicians to each shift, which shortens the subprocess of the decision to admit, reduced the PET duration by 27.5%. Moreover, creating a new admitting team (unit) that takes care of new patients admitted to the ED reduced PET duration by another 12.5%. Combining these two scenarios reduced the average PET duration to only 10.2±0.5 hours. In addition to these scenarios, the PET can be further decreased to six hours by increasing the number of inpatient beds. Conclusions The simulated scenarios indicated that restructuring the medical teams, adding two physicians to each shift, and creating an admissions team dedicated to the ED would reduce the total PET duration to 10.2 hours, Furthermore, PET's further reduction to six hours is predictable by increasing the bed number., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Al Halabi et al.)

Background: Obesity coexists with variable features of metabolic syndrome, which is associated with dysregulated metabolic pathways. We assessed potential associations between serum metabolites and features of metabolic syndrome in Arabic subjects with obesity. Methods: We analyzed a dataset of 39 subjects with obesity only (OBO, n = 18) age-matched to subjects with obesity and metabolic syndrome (OBM, n = 21). We measured 1069 serum metabolites and correlated them to clinical features. Results: A total of 83 metabolites, mostly lipids, were significantly different (p < 0.05) between the two groups. Among lipids, 22 sphingomyelins were decreased in OBM compared to OBO. Among non-lipids, quinolinate, kynurenine, and tryptophan were also decreased in OBM compared to OBO. Sphingomyelin is negatively correlated with glucose, HbA1C, insulin, and triglycerides but positively correlated with HDL, LDL, and cholesterol. Differentially enriched pathways include lysine degradation, amino sugar and nucleotide sugar metabolism, arginine and proline metabolism, fructose and mannose metabolism, and galactose metabolism. Conclusions: Metabolites and pathways associated with chronic inflammation are differentially expressed in subjects with obesity and metabolic syndrome compared to subjects with obesity but without the clinical features of metabolic syndrome.

Short Summary: Severe acute respiratory syndrome coronavirus 2 infection from the Omicron variant in children/adolescents is less severe than infection from the Delta variant. Those 6 to <18 years also have less severe disease than those <6 years old., Background: There are limited data assessing coronavirus 2019 (COVID-19) disease severity in children/adolescents infected with the Omicron variant., Methods: We identified children and adolescents <18 years of age with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with Delta and propensity score-matched controls with Omicron variant infection from the National COVID-19 Database in Qatar. Primary outcome was disease severity, determined by hospital admission, admission to the intensive care unit (ICU), or mechanical ventilation within 14 days of diagnosis, or death within 28 days., Results: Among 1735 cases with Delta variant infection between 1 June and 6 November 2021, and 32 635 cases with Omicron variant infection between 1 January and 15 January 2022, who did not have prior infection and were not vaccinated, we identified 985 propensity score-matched pairs. Among those who were Delta infected, 84.2% had mild, 15.7% had moderate, and 0.1% had severe/critical disease. Among those who were Omicron infected, 97.8% had mild, 2.2% had moderate, and none had severe/critical disease (P < .001). Omicron variant infection (vs Delta) was associated with significantly lower odds of moderate or severe/critical disease (adjusted odds ratio [AOR], 0.12; 95% confidence interval [CI], .07-.18). Those aged 6-11 and 12 to <18 years had lower odds of developing moderate or severe/critical disease compared with those younger than age 6 years (aOR, 0.47; 95% CI, .33-.66 for 6-11 year olds; aOR, 0.45; 95% CI, .21-.94 for 12 to <18 year olds)., Conclusions: Omicron variant infection in children/adolescents is associated with less severe disease than Delta variant infection as measured by hospitalization rates and need for ICU care or mechanical ventilation. Those 6 to <18 years of age also have less severe disease than those <6 years old., Competing Interests: Potential conflicts of interest. A. A. B. has received investigator-initiated grant funding from Gilead Sciences (to the institution, Veterans Health Foundation of Pittsburgh) that is unrelated to the work presented here. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The genetic factors associated with insulin resistance (IR) are not well understood. Clinical studies on first-degree relatives of type 2 diabetic (T2D) patients, which have the highest genetic predisposition to T2D, have given insights into the role of IR in T2D pathogenesis. Induced pluripotent stem cells (iPSCs) are excellent tools for disease modeling as they can retain the genetic imprint of the disease. Therefore, in this study, we aimed to investigate the genetic perturbations associated with insulin resistance (IR) in the offspring of T2D parents using patient-specific iPSCs., Methods: We generated iPSCs from IR individuals (IR-iPSCs) that were offspring of T2D parents as well as from insulin-sensitive (IS-iPSCs) individuals. We then performed transcriptomics to identify key dysregulated gene networks in the IR-iPSCs in comparison to IS-iPSCs and functionally validated them., Results: Transcriptomics on IR-iPSCs revealed dysregulated gene networks and biological processes indicating that they carry the genetic defects associated with IR that may lead to T2D. The IR-iPSCs had increased lactate secretion and a higher phosphorylation of AKT upon stimulation with insulin. IR-iPSCs have increased cellular oxidative stress indicated by a high production of reactive oxygen species and higher susceptibility to H 2 O 2 -induced apoptosis., Conclusions: IR-iPSCs generated from offspring of diabetic patients confirm that oxidative stress and increased lactate secretion, associated with IR, are inherited in this population, and may place them at a high risk of T2D. Overall, our IR-iPSC model can be employed for T2D modeling and drug screening studies that target genetic perturbations associated with IR in individuals with a high risk for T2D., (© 2022. The Author(s).)

Objective: Hypoglycemia in type 2 diabetes (T2D) increases morbidity and mortality but the underlying physiological response is still not fully understood, though physiological changes are still apparent 24 hours after the event. Small noncoding microRNA (miRNA) have multiple downstream biological effects that may respond rapidly to stress. We hypothesized that hypoglycemia would induce rapid miRNA changes; therefore, this pilot exploratory study was undertaken., Methods: A pilot prospective, parallel study in T2D (n=23) and controls (n=23). Insulin-induced hypoglycemia (2mmol/l: 36mg/dl) was induced and blood sampling performed at baseline and hypoglycemia. Initial profiling of miRNA was undertaken on pooled samples identified 96 miRNA that were differentially regulated, followed by validation on a custom designed 112 miRNA panel., Results: Nine miRNAs differed from baseline to hypoglycemia in control subjects; eight were upregulated: miR-1303, miR-let-7e-5p, miR-1267, miR-30a-5p, miR-571, miR-661, miR-770-5p, miR-892b and one was downregulated: miR-652-3p. None of the miRNAs differed from baseline in T2D subjects., Conclusion: A rapid miRNA response reflecting protective pathways was seen in control subjects that appeared to be lost in T2D, suggesting that mitigating responses to hypoglycemia with blunting of the counter-regulatory response in T2D occurs even in patients with short duration of disease., Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03102801?term=NCT03102801&draw=2&rank=1, identifier NCT03102801., Competing Interests: Authors MR, RP, MB,JJ and AA-S were employed by Hamad Medical Corporation The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ramanjaneya, Priyanka, Bensila, Jerobin, Pawar, Sathyapalan, Abou-Samra, Halabi, Moin, Atkin and Butler.)

Aim: Encouraging patients to improve their self-management behavior based on a strict definition of the intervention is important for a standardized delivery but, until recently, there was no consensus on the core attributes that define such an intervention. The purpose of this study is to generate a core-attribute based and stakeholder-informed problem-based curriculum for promotion of type 2 diabetes self-management structured around five core attributes derived from a previous concept analysis that defined the intervention., Methods: Using a Delphi process for consensus achievement, physicians, clinical epidemiologists and allied health care professionals completed eleven rounds of online meetings over 6 months., Results: Core self-management skills were identified by consensus for each of the five attributes and then used to design a model case and interactions of a problem-based self-management education intervention for delivery in a health care setting. Five model cases and associated interactions were developed by consensus for delivery in group-based and problem-based learning sessions., Conclusions: The final structured curriculum will be useful to inform and standardize diabetes self-management based on a clear conceptual definition of the intervention and can thus help make the latter more effective tools for encouraging persons with type 2 diabetes to self manage their condition., (Copyright © 2022 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Background: Obesity-associated dysglycemia is associated with metabolic disorders. MicroRNAs (miRNAs) are known regulators of metabolic homeostasis. We aimed to assess the relationship of circulating miRNAs with clinical features in obese Qatari individuals., Methods: We analyzed a dataset of 39 age-matched patients that includes 18 subjects with obesity only (OBO) and 21 subjects with obesity and metabolic syndrome (OBM). We measured 754 well-characterized human microRNAs (miRNAs) and identified differentially expressed miRNAs along with their significant associations with clinical markers in these patients., Results: A total of 64 miRNAs were differentially expressed between metabolically healthy obese (OBO) versus metabolically unhealthy obese (OBM) patients. Thirteen out of 64 miRNAs significantly correlated with at least one clinical trait of the metabolic syndrome. Six out of the thirteen demonstrated significant association with HbA1c levels; miR-331-3p, miR-452-3p, and miR-485-5p were over-expressed, whereas miR-153-3p, miR-182-5p, and miR-433-3p were under-expressed in the OBM patients with elevated HbA1c levels. We also identified, miR-106b-3p, miR-652-3p, and miR-93-5p that showed a significant association with creatinine; miR-130b-5p, miR-363-3p, and miR-636 were significantly associated with cholesterol, whereas miR-130a-3p was significantly associated with LDL. Additionally, miR-652-3p's differential expression correlated significantly with HDL and creatinine., Conclusions: MicroRNAs associated with metabolic syndrome in obese subjects may have a pathophysiologic role and can serve as markers for obese individuals predisposed to various metabolic diseases like diabetes., Competing Interests: Authors FM, AI, TS, AP, MA, IA, and A-BA-S were employed by HMC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mir, Mall, Iskandarani, Ullah, Samra, Cyprian, Parray, Alkasem, Abdalhakam, Farooq and Abou-Samra.)

Introduction: Complement factors mediate the recruitment and activation of immune cells and are associated with metabolic changes during pregnancy. The aim of this study was to determine whether complement factors in the maternal serum and follicular fluid (FF) are associated with in vitro fertilization (IVF) outcomes in overweight/obese women., Methods: Forty overweight/obese (BMI = 30.8 ± 5.2 kg/m 2 ) female patients, 33.6 ± 6.3 years old, undergoing IVF treatment for unexplained infertility were recruited. Baseline demographic information, including biochemical hormonal, metabolic, and inflammatory markers, and pregnancy outcome, was collected. Levels of 14 complement markers (C2, C4b, C5, C5a, C9, adipsin, mannose-binding lectin, C1q, C3, C3b/iC3b, C4, factor B, factor H, and properdin) were assessed in the serum and FF and compared to IVF outcome, inflammatory, and metabolic markers using multivariate and univariate models., Results: Out of 40 IVF cycles, 14 (35%) resulted in pregnancy. Compared to women with failed pregnancies, women with successful pregnancies had higher levels of adipsin in the serum and FF ( p = 0.01) but lower C5a levels ( p = 0.05). Serum adipsin levels were positively correlated with circulating levels of vitamin D ( R = 0.5, p = 0.02), glucagon ( R = 0.4, p = 0.03), leptin ( R = 0.4, p = 0.01), resistin ( R = 0.4, p = 0.02), and visfatin ( R = 0.4, p = 0.02), but negatively correlated with total protein ( R = -0.5, p = 0.03). Higher numbers of top-quality embryos were associated with increased levels of C3, properdin, C1q, factors H and B, C4, and adipsin, but with reduced C2 and C5a levels ( p ≤ 0.01)., Conclusions: Higher adipsin and lower C5a levels in the maternal serum during implantation are potential markers of successful outcome in obese women undergoing IVF-assisted pregnancies., Competing Interests: Authors MR, TA, MS, MA, HB, and AA-S were employed by Hamad Medical Corporation. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ramanjaneya, Diboun, Rizwana, Dajani, Ahmed, Butler, Almarzooqi, Shahata, Al Bader, Elgassim, Burjaq, Atkin, Abou-Samra and Elrayess.)

Background: Understanding the disease severity associated with the Omicron variant of the SARS-CoV-2 virus is important in determining appropriate management strategies at the individual and population levels. We determined the severity of SARS-CoV-2 infection in persons infected with the Omicron vs the Delta variant., Methods: We identified individuals with SARS-CoV-2 infection with Delta and propensity-score matched controls with Omicron variant infection from the National COVID-19 Database in Qatar. We excluded temporary visitors to Qatar, those with a prior documented infection, those ≤18 years old, and those with <14 days of follow up after the index test positive date. We determined the rates of admission to the hospital, admission to intensive care unit, mechanical ventilation, or death among those infected with the Delta or Omicron variants., Results: Among 9763 cases infected with the Delta variant and 11 310 cases infected with the Omicron variant, we identified 3926 propensity-score matched pairs. Among 3926 Delta infected, 3259 (83.0%) had mild, 633 (16.1%) had moderate and 34 (0.9%) had severe/critical disease. Among 3926 Omicron infected, 3866 (98.5%) had mild, 59 (1.5%) had moderate, and only 1 had severe/critical disease (overall P < 0.001). Factors associated with less moderate or severe/critical disease included infection with Omicron variant (aOR = 0.06; confidence interval (CI) = 0.05-0.09) and vaccination including a booster (aOR = 0.30; 95% CI = 0.09-0.99)., Conclusions: Omicron variant infection is associated with significantly lower severity of disease compared with the Delta variant. Vaccination continues to offer strong protection against severe/critical disease., Competing Interests: Competing interests: Dr Butt has received investigator-initiated grant funding from Gilead Sciences (to the institution, Veterans Health Foundation of Pittsburgh) which is unrelated to the work presented here. The other authors completed the ICMJE Declaration of Interest Form (available upon request from the corresponding author), and declare no further conflicts of interest., (Copyright © 2022 by the Journal of Global Health. All rights reserved.)

Background: Mobile health (mHealth) is increasingly advocated for diabetes management. It is unclear if mobile applications are effective in improving glycaemic control, clinical outcomes, quality of life and overall patient satisfaction in patients with type 2 diabetes (T2DM). A new mobile application was specifically built for people with T2DM with the help of the local expertise. The objective of the study was to evaluate the effectiveness of the mobile app., Methods: The planned study is an ongoing open-label randomised controlled trial in which adults living with T2DM treated with insulin will be randomised 1:1 to the use of this diabetes application versus current standard care. The primary outcome will be the difference in mean HbA1c from baseline to 6 months. Other outcome measures include anthropometric measures, hypoglycaemic events, medication adjustments, number of clinical interactions and missed appointments and patient perceptions of their disease and diabetes self-management. The study will randomise 180 subjects for assessment of the primary outcome., Discussion: We hypothesise that the diabetes-specific mobile application will improve glycaemic control, increase patient empowerment for self-management of diabetes and improve interaction between patients and healthcare providers. If the Qatar Diabetes Mobile Application Trial (QDMAT) demonstrates this, it will inform clinical services for the future self-management of T2DM., Trial Registration: ClinicalTrials.gov Identifier: NCT03998267 . Registered on 26 June 2019., (© 2022. The Author(s).)

Background:  The Staff Medical Clinic (SMC) of the Hamad Medical Corporation (HMC) serves the staff members who require healthcare services, but in a crowded environment, the SMC can only meet 75% of that demand. Overcrowding reduces productivity and service quality and increases waiting time. Furthermore, overcrowding in healthcare facilities decreases the experience and satisfaction of patients and healthcare providers., Aim: The main objective of this study was to use simulation modeling to evaluate interventions that could improve SMC waiting time and efficiency., Method:  Eighteen months of data on SMC patient flow, staffing, and clinical sessions were collected (January 2018 to June 2019). The patient's journey through the SMC was modeled as a series of processes with assigned durations defined mathematically using the appropriate probability distribution. A simulation flow model was developed considering the locations of the staff and nearby main hospital facilities. An intervention was proposed and evaluated through a simulation. The intervention involved redistributing 25% of the SMC staff into three main satellite clinics located at the facilities where most of the SMC patients came.  Results: The proposed intervention decreased crowding by 37%, reduced staffing requirements by 28%, and increased the number of patient slots by 22%, resulting in a net increase in the number of patients served by an average of 1250 monthly, without the need for hiring new additional staffing., Conclusion:  Redistribution of the available medical staff to three new satellite clinics reduces workload pressure at all sites and increases clinic capacity without additional costs., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Habas et al.)

Background: Humanin and the mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) are mitochondrial encoded peptides involved in energy metabolism, cytoprotection, longevity, insulin sensitivity and their expression decrease with age. Levels of these molecules have been shown to respond to acute exercise, however little is known about their modulation under different chronic exercise conditions. In this study, we aim to compare levels of Humanin and MOTS-c in non-athletes vs professional (moderate and high endurance) athletes., Methods: Serum samples were collected from 30 non-athlete controls and 75 professional athletes (47 low/moderate endurance and 28 high endurance athletes). Levels of Humanin and MOTS-c were measured by the enzyme linked immunosorbent aaasy (ELISA) and linear models were generated to compare the effect of different levels of endurance exercise on these factors in different age groups. Spearman correlation was used to assess the correlation between these factors in athletes and non-athletes., Results: We showed that professional athletes had lower levels of MOTS-c and higher levels of Humanin than sedentary controls. Within the athletic groups, high endurance athletes had lower levels of Humanin than low/moderate endurance athletes of the same gender/age groups, whereas MOTS-c levels did not change between the subgroups. Humanin and MOTS-c levels were highly correlated in athletes, but not in sedentary controls., Conclusions: This pilot data suggests that serum levels of the mitochondrial proteins MOTS-c and Humanin change in response to chronic exercise with implications on energy metabolism and performance., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2022 The Author(s). Published by IMR Press.)

Background: The complement system is pivotal in host defense mechanisms, protecting against pathogenic infection by regulating inflammation and cell immunity. Complement-related protein activation occurs through three distinct pathways: classical, alternative, and lectin-dependent pathways, which are regulated by cascades of multiple proteins. Complement activation is recognized in polycystic ovary syndrome (PCOS) to be associated with obesity and insulin sensitivity. Exercise reduces insulin resistance and may help reduce obesity, and therefore, this study was undertaken to determine the effect of exercise on the activation of complement-related proteins in PCOS and control women., Subjects and Measurements: In this study, 10 controls and 11 PCOS subjects who were age- and weight-matched underwent an 8-week supervised exercise program at 60% maximal oxygen consumption. Weight was unchanged though insulin sensitivity was increased in PCOS subjects and controls. Fasting baseline and post-exercise samples were collected and 14 complement-related proteins belonging to classical, alternative, and lectin-dependent pathways were measured., Results: Baseline levels of complement C4b and complement C3b/iC3b were higher in PCOS ( P < 0.05) compared with controls. Exercise reduced complement C1q ( P < 0.05), C3 ( P < 0.001), C4 ( P < 0.01), factor B ( P < 0.01), factor H ( P < 0.01), and properdin ( P < 0.05) in controls, but not in PCOS women., Conclusion: Exercise induced complement changes in controls that were not seen in PCOS subjects, suggesting that these pathways remain dysregulated even in the presence of improved insulin sensitivity and not improved by moderate aerobic exercise., Clinical Trial Registration: ISRCTN registry, ISRCTN42448814., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past collaboration with several of the authors (MR, IB, SA, A-BA-S)., (Copyright © 2022 Ramanjaneya, Abdalhakam, Bettahi, Bensila, Jerobin, Aye, Alkasem, Sathyapalan, Atkin and Abou-Samra.)

Objectives: This study examines the levels of knowledge, attitude and practices (KAP) towards diabetes among Qatar nationals and long-term residents and its association with participants' selected demographics., Setting: A cross-sectional study conducted in public areas in all the eight municipalities of Qatar from July to October 2018., Participants: 2400 participants from the general public (nationals and long-term residents) stratified by gender, age and nationality across all geographic locations in Qatar., Primary and Secondary Outcome Measures: Responses were scored from 0% to 100% and KAP scores were classified as low (0%-49%), intermediate (50%-74%) or high (75%-100%). Analyses and comparisons were performed using descriptive statistics and χ 2 test at 5% level., Results: Most participants (54%) had an intermediate overall KAP score, 43% had a low score and only 3% had a high score. The knowledge scores were the lowest among participants, 69% had low, 29% had intermediate and only 2% had high scores. Participants scored better in attitude and practice; the percentages of participants who scored high, intermediate and low were 32%, 55% and 13% for attitude, and 37%, 33% and 30% for practice, respectively. Except for age, level of knowledge significantly varied by gender, nationality and diabetes-related diagnosis (p<0.001); attitude and practice levels differed significantly in all four factors. Areas where participants were deficient include: diabetes types, risk factors, signs and symptoms, complications, recommended daily exercise, normal fasting glucose level, preventive measures, management and control and understanding about complexity of diabetes., Conclusions: Participants generally have intermediate levels of positive attitudes and practices towards diabetes but low knowledge in diabetes-related factors. The data suggest that future communications should focus on educating the public and conduct mass campaigns about diabetes to improve knowledge especially targeting men and women, and both nationals and expatriates., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: The Delta variant is now the predominant circulating SARS-CoV-2 strain worldwide. Severity of illness in persons infected with the SARS-CoV-2 Delta variant compared with the Beta variant is not known., Objective: To directly compare clinical outcomes in persons infected with the SARS-CoV-2 Delta variant vs those infected with the Beta variant in Qatar., Design, Setting, and Participants: This retrospective cohort study used data from the national COVID-19 database in Qatar, which includes information on all individuals who were ever tested for SARS-CoV-2 using a reverse transcriptase-polymerase chain reaction test and all individuals who received any SARS-CoV-2 vaccine in Qatar. Among persons with confirmed SARS-CoV-2 infection between March 22 and July 7, 2021, those infected with the Delta variant were identified and were propensity score matched with control individuals infected with the Beta variant. The variants were ascertained by variant genotyping of the positive samples., Exposures: SARS-CoV-2 infection with the Delta or Beta variant., Main Outcomes and Measures: The main outcomes were admission to the hospital, admission to the intensive care unit, use of supplemental oxygen, use of high-flow oxygen, receipt of mechanical ventilation, or death among those infected with the Delta or Beta variant overall and stratified by vaccination status., Results: Among 1427 persons infected with the Delta variant (252 [55.9%] male; median age, 34 years [IQR, 17-43 years]) and 5353 persons infected with the Beta variant (233 [51.7%] male; median age, 34 years [IQR, 17-45 years]), 451 propensity score-matched pairs were identified. Persons infected with the Delta variant were more likely to be hospitalized (27.3% [95% CI, 23.2%-31.6%] vs 20.0% [95% CI, 16.4-24.0]; P = .01) or to have mild-moderate or severe-critical disease outcomes (27.9% [95% CI, 23.8%-32.3%] vs 20.2% [95% CI, 16.6%-24.2%]; P = .01) compared with persons infected with the Beta variant. Infection with the Delta variant was independently associated with higher odds of experiencing any adverse outcome (adjusted odds ratio [aOR], 2.53; 95% CI, 1.72-3.72). Compared with being unvaccinated, being vaccinated with a second dose more than 3 months before infection was associated with lower odds of any adverse outcome among persons infected with the Delta variant (aOR, 0.11; 95% CI, 0.04-0.26) and among those infected with the Beta variant (aOR, 0.22; 95% CI, 0.05-0.98). Protection was similar among those who received a second vaccine dose less than 3 months before infection, but having received only a single dose was not associated with a lower odds of any severe outcome among those infected with the Delta variant (aOR, 1.12; 95% CI, 0.41-3.06) or those infected with the Beta variant (aOR, 0.74; 95% CI, 0.20-2.72)., Conclusions and Relevance: In this cohort study of persons with COVID-19 in Qatar, infection with the SARS-CoV-2 Delta variant was associated with more severe disease than was infection with the Beta variant. Being unvaccinated was associated with greater odds of severe-critical disease.

Objectives: Diabetes self-management educational (DSME) interventions can vary considerably, and it is unclear what is the operational conceptualization of the ideal delivery to individuals with type 2 diabetes (T2D)., Design: From a search conducted concurrently we extracted and evaluated the 50 most recently published DSME intervention studies. Based on an analysis of these studies, we undertook a concept analysis using the Walker and Avant framework., Results: Five attributes describing the concept were recognized and organized into two groups. Group (a): skills related attributes that included (1) decision making, (2) problem solving and (3) taking action. Group (b): information related attributes that included (4) patient-provider interaction and (5) resource utilization., Conclusions: The outcomes of this study make the operational conceptualization of the ideal DSME intervention measurable through its attributes and hence clarifies its delivery. This will improve the implementation of the key attributes in diabetes self-management intervention programs for T2D., (Copyright © 2021 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Aims: Disagreement about the appropriate criteria for the diagnosis of gestational diabetes mellitus (GDM) persists. This study examines an alternative approach which combines information from all time-points on the glucose tolerance test (GTT) into a single index and expands the GDM spectrum into four categories using data from three geographically and ethnically distinct populations., Methods: A retrospective observational study design was used. Data from Wisconsin, USA (723 women) was used in derivation of the criterion and data from Doha, Qatar (1284 women) and Cape Town, South Africa (220 women) for confirmation. Pregnant women without pre-existing diabetes with a GTT done between 23 and 30 weeks gestation were included. A novel index was derived from the GTT termed the weighted average glucose (wAG). This was categorized into four pre-defined groups (henceforth National Priorities Research Program (NPRP) criterion); i) normal gestational glycemia (NGG), ii) impaired gestational glycemia (IGG), iii) GDM and iv) high risk GDM (hGDM)., Results: In the Doha cohort, compared to the NGG group, the odds of large for gestational age babies increased 1.33 fold (P = 0.432), 2.86 fold (P < 0.001) and 3.35 fold (P < 0.001) in the IGG, GDM and hGDM groups respectively. The odds of pregnancy induced hypertension increased 2.10 fold (P = 0.024) in GDM & hGDM groups compared to the IGG and NGG groups. In the Cape Town cohort, a third of women in the GDM group and two-thirds in the hGDM group progressed to T2DM at 5 years., Conclusions: The NPRP categorization identifies four distinct risk clusters of glycemia in pregnancy which may aid better decision making in routine management, avoid potential over-diagnosis of women at lower risk of complications and assist with diabetes prevention in women at high-risk after an index pregnancy with GDM., (Copyright © 2021. Published by Elsevier Ltd.)