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Abstract Hypoglycemia in type 1 diabetes associates with changes in the pancreatic islet α cells, where the receptor for advanced glycation end products (RAGE) is highly expressed. This study compared islet RAGE expression in donors without diabetes, those at risk of, and those with type 1 diabetes. Laser-dissected islets were subject to RNA bioinformatics and adjacent pancreatic tissue were assessed by confocal microscopy. We found that islets from type 1 diabetes donors had differential expression of the RAGE gene (AGER) and its correlated genes, based on glucagon expression. Random forest machine learning revealed that AGER was the most important predictor for islet glucagon levels. Conversely, a generalized linear model identified that glucagon expression could be predicted by expression of RAGE signaling molecules, its ligands and enzymes that create or clear RAGE ligands. Confocal imaging co-localized RAGE, its ligands and signaling molecules to the α cells. Half of the type 1 diabetes cohort comprised of adolescents and a patient with history of hypoglycemia—all showed an inverse relationship between glucagon and RAGE. These data confirm an association between glucagon and islet RAGE, its ligands and signaling pathways in type 1 diabetes, which warrants functional investigation into a role for RAGE in hypoglycemia.

Nirmin F Juber,1 Abdishakur Abdulle,1 Abdulla AlJunaibi,2 Abdulla AlNaeemi,3 Amar Ahmad,1 Andrea Leinberger-Jabari,1 Ayesha S Al Dhaheri,4 Eiman AlZaabi,5 Fatma Al-Maskari,6,7 Fatme AlAnouti,8 Habiba Alsafar,9– 11 Juma Alkaabi,12 Laila Abdel Wareth,13 Mai Aljaber,14 Marina Kazim,15 Michael Weitzman,16 Mohammad Al-Houqani,17 Mohammed Hag-Ali,18 Naima Oumeziane,15 Scott Sherman,19 Syed M Shah,6 Wael Almahmeed,20 Youssef Idaghdour,1 Tom Loney,21 Omar El-Shahawy,19 Raghib Ali1,22 1Public Health Research Center, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates; 2Department of Pediatrics, Zayed Military Hospital, Abu Dhabi, United Arab Emirates; 3Department of Cardiology, Zayed Military Hospital, Abu Dhabi, United Arab Emirates; 4Department of Nutrition and Health, College of Medicine and Health Sciences, UAE University, Al-Ain, United Arab Emirates; 5Department of Pathology, Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates; 6Institute of Public Health, College of Medicine and Health Sciences, UAE University, Al-Ain, United Arab Emirates; 7Zayed Center for Health Sciences, UAE University, Al-Ain, United Arab Emirates; 8College of Natural and Health Sciences, Zayed University, Abu Dhabi, United Arab Emirates; 9Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates; 10Department of Genetics and Molecular Biology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates; 11Department of Biomedical Engineering, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates; 12Department of Internal Medicine, College of Medicine and Health Sciences, UAE University, Al-Ain, United Arab Emirates; 13The National Reference Laboratory, Abu Dhabi, United Arab Emirates; 14Healthpoint Hospital, Abu Dhabi, United Arab Emirates; 15Abu Dhabi Blood Bank Services, SEHA, Abu Dhabi, United Arab Emirates; 16Department of Environmental Medicine, New York University of Medicine, New York, NY, USA; 17Department of Medicine, College of Medicine and Health Sciences, UAE University, Al-Ain, United Arab Emirates; 18Faculty of Health Sciences, Higher Colleges of Technology, Abu Dhabi, United Arab Emirates; 19Department of Population Health, New York University School of Medicine, New York, NY, USA; 20Heart and Vascular Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates; 21College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates; 22MRC Epidemiology Unit, University of Cambridge, Cambridge, UKCorrespondence: Nirmin F Juber, Public Health Research Center, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates, Tel +971-2-6287631, Email nirmin.juber@nyu.eduPurpose: This study aimed to assess the prevalence of self-reported polycystic ovary syndrome (PCOS) among Emiratis and examine bi-directional associations of PCOS with self-reported chronic diseases, namely: diabetes, asthma, high cholesterol, and high blood pressure.Patients and Methods: A cross-sectional analysis was performed using the UAE Healthy Future Study (UAEHFS) data collected from February 2016 to April 2022 involving 1040 Emirati women aged 25– 67 years from recruitment centers in the United Arab Emirates (UAE). The bi-directional associations between self-reported PCOS and self-reported chronic diseases were evaluated by establishing temporality based on reported age-at-diagnoses. Firstly, the associations between PCOS (diagnosed at ≥ 25 years) and chronic diseases (diagnosed at < 25 years) were examined, followed by PCOS (diagnosed at < 25 years) and chronic diseases (diagnosed at ≥ 25 years). Finally, a Poisson regression under unadjusted and age-and-body mass index (BMI) adjusted models was performed to obtain the risk ratio (RR) and its 95% confidence interval (CI).Results: The prevalence of PCOS in this study was 25.9%. Those with asthma and high cholesterol diagnosed at < 25 years had increased risks of PCOS diagnosed at ≥ 25 years (RR = 1.79, 95% CI: 1.17– 2.76 for asthma; and RR = 1.61, 95% CI: 1.01– 2.59 for high cholesterol), compared to those respective healthier counterparts, after adjusting for age and BMI. No significant association was observed between PCOS diagnosed at < 25 years and respective chronic diseases diagnosed at ≥ 25 years.Conclusion: PCOS prevalence among Emirati women was high. Asthma and high cholesterol in earlier life were associated with PCOS in later life. Understanding how chronic disease conditions and PCOS are associated in bi-directional ways may improve the surveillance of chronic disease conditions among women with PCOS and may also contribute to more targeted PCOS prevention strategies.Keywords: polycystic ovary syndrome, self-reported diagnosis, epidemiology, women’s health, United Arab Emirates, UAE Healthy Future Study

Bhupesh Pokhrel,1 Eun Kwang Choi,1 Omer Khalid,2 Kumar Sandrasegaran,3 Evan L Fogel,1 Lee McHenry,1 Stuart Sherman,1 James Watkins,1 Gregory A Cote,1 Henry A Pitt,4 Nicholas J Zyromski,4 Beth Juliar,1 Glen A Lehman11Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, 2Department of Gastroenterology, St Louis University School of Medicine, St Louis, MO, 3Department of Radiology, 4Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USABackground: A preliminary study has shown increased pancreatic fat in patients with idiopathic pancreatitis and sphincter of Oddi dysfunction. In this study, we aimed to determine if an increased quantity of pancreatic fat is an independent risk factor for pancreatitis post-endoscopic retrograde cholangiopancreatography (ERCP).Methods: In this case control study, we retrospectively reviewed a local radiological and ERCP database to identify patients who had had abdominal magnetic resonance imaging (MRI) followed by ERCP no more than 60 days later between September 2003 and January 2011. Percentage of fat was determined by recording signal intensity in the in-phase (Sin) and out-of-phase (Sout) T1-weighted gradient sequences, and calculation of the fat fraction as (Sin - Sout)/(Sin) × 2 by an abdominal radiologist blinded to clinical history. Controls matched for age, gender, and other pancreatobiliary disease were selected from a group with no post-ERCP pancreatitis (before fat content of the pancreas was analyzed).Results: Forty-seven patients were enrolled. Compared with controls, subjects with post-ERCP pancreatitis were similar in terms of age (41.4 years versus 41.1 years), gender (21.2% versus 20.2% males), pancreatobiliary disease characteristics, and most ERCP techniques. Measurements of pancreatic head, body, and tail fat and body mass index were similar in patients and controls.Conclusion: Increased pancreatic fat on MRI criteria is not an independent predictor of post-ERCP pancreatitis.Keywords: magnetic resonance imaging, obesity, pancreatic fat, post-ERCP pancreatitis, sphincter of Oddi dysfunction

Ehud Halperin,1 Tal Engel,2 Shany Sherman,2 Dan Justo2,31Department of Internal Medicine D, Sourasky Medical Center, Tel-Aviv, 2Department of Internal Medicine E, Sheba Medical Center, Tel-Hashomer, 3Department of Geriatrics, Sourasky Medical Center, Tel-Aviv, IsraelBackground: In this study, we investigated if low admission Norton scale scores (ANSS) are associated with falls, fractures, hospitalizations, and death, after rehabilitation in the elderly with hip fractures.Methods: This prospective historical study followed consecutive elderly patients (≥65 years) who were admitted for rehabilitation following hip fracture surgery during 2009 and followed up in January or February 2012. The incidence of falls, number of falls, incidence of fractures, number of hospitalizations, and death rates were compared between patients with low (≤14) and high (≥15) ANSS.Results: The final cohort included 174 patients of mean age 83.6 ± 6.2 years, with 133 (76.4%) being women. Fifty-seven (27.0%) patients died during follow-up. Of the remaining 127 patients, 44 (34.6%) fell at least once and 15 (11.8%) suffered fractures. Overall, 81 (46.6%) patients had a low ANSS. Relative to patients with a high ANSS, they had a higher incidence of falls (odds ratio 3.3, 95% confidence interval 1.5–7.1; P = 0.002) and fell more times (1.2 ± 1.8 versus 0.6 ± 1.7; P = 0.002). Regression analysis showed that ANSS (as a parametric variable) as well as a low ANSS (as a nonparametric variable) were independently associated with falls (P = 0.002 and P = 0.009, respectively). There were no differences between patients with low and high ANSS in terms of incidence of fractures, number of hospitalizations, and death rates.Conclusion: The Norton scoring system may be used for predicting falls long after rehabilitation in the elderly with hip fractures.Keywords: falls, hip fracture, Norton scale, rehabilitation

Pyramidal cells in cortical Layers 5 and 6 are the only cells in the cerebral cortex with axons that leave the cortex to influence the thalamus. Layer 6 cells provide modulatory feedback input to all thalamic nuclei. Layer 5 cells provide driving input to higher-order thalamic nuclei and do not innervate first-order nuclei, which get their driving inputs from subcortical sources. Higher-order nuclei innervated by Layer 5 cells thus seem to be involved with cortico-thalamo-cortical communication. The Layer 5 axons branch to also target additional subcortical structures that mediate interactions with the external environment. These corticofugal pathways represent the only means by which the cortex influences the rest of the neuraxis and thus are essential for proper cortical function and species survival. Here we review current understanding of the corticofugal pathways from Layers 5 and 6 and speculate on their functional contributions to neural processing and behavior.