Digital Commons Network^™

Semi-Quantitative Assay To Measure Urease Activity By Urinary Catheter-Associated Uropathogens, Jesus M Duran Ramirez, Jana Gomez, Chloe L P Obernuefemann, Nathaniel C Gualberto, Jennifer N Walker

2020-Current year OA Pubs

Catheter-associated urinary tract infections (CAUTIs) are one of the most common healthcare-associated infections in the US, accounting for over 1 million cases annually and totaling 450 million USD. CAUTIs have high morbidity and mortality rates and can be caused by a wide range of pathogens, making empiric treatment difficult. Furthermore, when urease-producing uropathogens cause symptomatic CAUTI or asymptomatic catheter colonization, the risk of catheter failure due to blockage increases. The enzyme urease promotes catheter blockage by hydrolyzing urea in urine into ammonia and carbon dioxide, which results in the formation of crystals that coat the catheter surface. If CAUTI is …

Gardnerella Exposures Alter Bladder Gene Expression And Augment Uropathogenic Escherichia Coli Urinary Tract Infection In Mice, Nicole M Gilbert, Valerie P O'Brien, Chevaughn Waller, Ekatherina Batourina, Cathy Lee Mendelsohn, Amanda L Lewis

2020-Current year OA Pubs

The anaerobic actinobacterium

Elevated Axonal Protein Markers Following Repetitive Blast Exposure In Military Personnel, Rany Vorn, Rosanne Naunheim, Chen Lai, Chelsea Wagner, Jessica M Gill

2020-Current year OA Pubs

Blast exposures that occur during training are common in military personnel; however, the biomarkers that relate to these subtle injuries is not well understood. Therefore, the purpose of this study is to identify the acute biomarkers related to blast injury in a cohort of military personnel exposure to blast-related training. Thirty-four military personnel who participated in the training program were included in this study. Blood samples were collected before and after repetitive blast-related training on days 2 (

Glial Dysfunction And Its Contribution To The Pathogenesis Of The Neuronal Ceroid Lipofuscinoses, Keigo Takahashi, Hemanth R Nelvagal, Jenny Lange, Jonathan D Cooper

2020-Current year OA Pubs

While significant efforts have been made in developing pre-clinical treatments for the neuronal ceroid lipofuscinoses (NCLs), many challenges still remain to bring children with NCLs a cure. Devising effective therapeutic strategies for the NCLs will require a better understanding of pathophysiology, but little is known about the mechanisms by which loss of lysosomal proteins causes such devastating neurodegeneration. Research into glial cells including astrocytes, microglia, and oligodendrocytes have revealed many of their critical functions in brain homeostasis and potential contributions to neurodegenerative diseases. Genetically modified mouse models have served as a useful platform to define the disease progression in the …

Multivariate Analysis Of Associations Between Clinical Sequencing And Outcome In Glioblastoma, Peter H Yang, Yu Tao, Jingqin Luo, Mounica Paturu, Hsiang-Chih Lu, Shakti Ramkissoon, Jonathan W Heusel, Eric C Leuthardt, Michael R Chicoine, Joshua L Dowling, Gavin P Dunn, Eric Duncavage, Sonika Dahiya, Arindam R Chattherjee, Albert H Kim

2020-Current year OA Pubs

BACKGROUND: Many factors impact survival in patients with glioblastoma, including age, Karnofsky Performance Status, postoperative chemoradiation,

METHODS: We utilized a widely available diagnostic platform (FoundationOne CDx) to perform high-throughput next-generation sequencing on 185 patients with newly diagnosed glioblastoma in our tertiary care center. We performed multivariate analysis to control for clinical parameters with known impact on survival to elucidate the independent prognostic value of prevalent mutant genes and the independent impact of gross total resection.

RESULTS: When controlling for factors with known prognostic significance including

CONCLUSIONS: This study verifies the independent prognostic value of several mutant genes in glioblastoma. Six …

Combination Tigit/Pd-1 Blockade Enhances The Efficacy Of Neoantigen Vaccines In A Model Of Pancreatic Cancer, Hui Peng, Lijin Li, Chong Zuo, Michael Y Chen, Xiuli Zhang, Nancy B Myers, Graham D Hogg, David G Denardo, S Peter Goedegebuure, William G Hawkins, William E Gillanders

2020-Current year OA Pubs

BACKGROUND: Cancer neoantigens are important targets of cancer immunotherapy and neoantigen vaccines are currently in development in pancreatic ductal adenocarcinoma (PDAC) and other cancer types. Immune regulatory mechanisms in pancreatic cancer may limit the efficacy of neoantigen vaccines. Targeting immune checkpoint signaling pathways in PDAC may improve the efficacy of neoantigen vaccines.

METHODS: We used KPC4580P, an established model of PDAC, to test whether neoantigen vaccines can generate therapeutic efficacy against PDAC. We focused on two immunogenic neoantigens associated with genetic alterations in the CAR12 and CDK12 genes. We tested a neoantigen vaccine comprised of two 20-mer synthetic long peptides …

Mechanisms Of Persistent Atrial Fibrillation And Recurrences Within 12 Months Post-Ablation: Non-Invasive Mapping With Electrocardiographic Imaging, Ramya Vijayakumar, Mitchell N Faddis, Phillip S Cuculich, Yoram Rudy

2020-Current year OA Pubs

INTRODUCTION: Catheter ablation of persistent AF has not been consistently successful in terminating AF or preventing arrhythmia recurrences. Non-invasive Electrocardiographic Imaging (ECGI) can help to understand recurrences by mapping the mechanisms of pre-ablation AF and comparing them with the patterns of recurrent arrhythmias in the same patient.

METHODS: Seventeen persistent AF patients underwent ECGI before their first catheter ablation. Time-domain activation maps and phase progression maps were obtained on the bi-atrial epicardium. Location of arrhythmogenic drivers were annotated on the bi-atrial anatomy. Activation and phase movies were examined to understand the wavefront dynamics during AF. Eight patients recurred within 12 …

Implicating Genes, Pleiotropy, And Sexual Dimorphism At Blood Lipid Loci Through Multi-Ancestry Meta-Analysis, Stavroula Kanoni, Adam E. Locke, E Warwick Daw, Mary F. Feitosa, Mary K. Wojczynski, Bernhard Banas, Carsten A. Boger, Bettina Jung, D C. Rao, Michael A. Province, Et Al.

2020-Current year OA Pubs

No abstract provided.

Postnatal Osterix But Not Dmp1 Lineage Cells Significantly Contribute To Intramembranous Ossification In Three Preclinical Models Of Bone Injury, Evan G Buettmann, Susumu Yoneda, Pei Hu, Jennifer A Mckenzie, Matthew J Silva

2020-Current year OA Pubs

Murine models of long-bone fracture, stress fracture, and cortical defect are used to discern the cellular and molecular mediators of intramembranous and endochondral bone healing. Previous work has shown that Osterix (Osx

Protocol For A Proof-Of-Concept Study Evaluating Systematic Quality Improvement With Realtime Event Support (Squires), Arianna Montes De Oca, Thaddeus P. Budelier, Rachel C. Wolfe, Teresa M. Murray-Torres, Melissa Milbrandt, Ryan Guffey, Alex Kronzer, Mara L. Bollini, Brian A. Torres, Bernadette Henrichs, Arbi Ben Abdallah, Sherry L. Mckinnon, Ivan Kangrga, Andrea Reidy, Paul W. Kerby, Michael S. Avidan, Troy S. Wildes

2020-Current year OA Pubs

No abstract provided.

Cost And Value In Contemporary Heart Failure Clinical Guidance Documents, John W. Ostrominski, Sameer Hirji, Ankeet S. Bhatt, Javed Butler, Mona Fiuzat, Gregg C. Fonarow, Paul A. Heidenreich, James L. Januzzi, Carolyn S. P. Lam, Thomas M. Maddox, Christopher M. O'Connor, Muthiah Vaduganathan

2020-Current year OA Pubs

OBJECTIVES: This study sought to evaluate the frequency and nature of cost/value statements in contemporary heart failure (HF) clinical guidance documents (CGDs).

BACKGROUND: In an era of rising health care costs and expanding therapeutic options, there is an increasing need for formal consideration of cost and value in the development of HF CGDs.

METHODS: HF CGDs published by major professional cardiovascular organizations between January 2010 and February 2021 were reviewed for the inclusion of cost/value statements.

RESULTS: Overall, 33 documents were identified, including 5 (15%) appropriate use criteria, 7 (21%) clinical practice guidelines, and 21 (64%) expert consensus documents. Most …

Altered Peroxisome Proliferator-Activated Receptor Alpha Signaling In Variably Diseased Peripheral Arterial Segments, Connor Engel, Rodrigo Meade, Nikolai Harroun, Amanda Penrose, Mehreen Shafqat, Xiaohua Jin, Gayan Desilva, Clay Semenkovich, Mohamed Zayed

2020-Current year OA Pubs

OBJECTIVE: Peripheral atherosclerosis that accumulates in the extracranial carotid and lower extremity arteries can lead to significant morbidity and mortality. However, atherosclerotic disease progression is often not homogenous and is accelerated by diabetes. We previously observed increased phospholipid content in minimally (Min)-diseased arterial segments compared to maximally (Max)-diseased segments. Since Peroxisome Proliferator-Activated Receptor alpha (PPARα) is a key regulator of lipid metabolism, we hypothesized that it may have differential expression and signaling in Min vs. Max-diseased peripheral arterial segments.

METHODS: Eighteen patients who underwent carotid endarterectomy (CEA), and 34 patients who underwent major lower extremity amputation were prospectively enrolled into …

Mitochondrial Fitness And Cancer Risk, Andrew V. Kossenkov, Andrew Milcarek, Faiyaz Notta, Gun-Ho Jang, Julie M. Wilson, Steven Gallinger, Daniel Cui Zhou, Li Ding, Jagadish C. Ghosh, Michela Perego, Annamaria Morotti, Marco Locatelli, Marie E. Robert, Valentina Vaira, Dario C. Altieri

2020-Current year OA Pubs

Changes in metabolism are a hallmark of cancer, but molecular signatures of altered bioenergetics to aid in clinical decision-making do not currently exist. We recently identified a group of human tumors with constitutively reduced expression of the mitochondrial structural protein, Mic60, also called mitofilin or inner membrane mitochondrial protein (IMMT). These Mic60-low tumors exhibit severe loss of mitochondrial fitness, paradoxically accompanied by increased metastatic propensity and upregulation of a unique transcriptome of Interferon (IFN) signaling and Senescence-Associated Secretory Phenotype (SASP). Here, we show that an optimized, 11-gene signature of Mic60-low tumors is differentially expressed in multiple malignancies, compared to normal …

Reconstructing Neural Circuits Using Multiresolution Correlated Light And Electron Microscopy, Karl Friedrichsen, Pratyush Ramakrishna, Jen-Chun Hsiang, Katia Valkova, Daniel Kerschensteiner, Josh L Morgan

2020-Current year OA Pubs

Correlated light and electron microscopy (CLEM) can be used to combine functional and molecular characterizations of neurons with detailed anatomical maps of their synaptic organization. Here we describe a multiresolution approach to CLEM (mrCLEM) that efficiently targets electron microscopy (EM) imaging to optically characterized cells while maintaining optimal tissue preparation for high-throughput EM reconstruction. This approach hinges on the ease with which arrays of sections collected on a solid substrate can be repeatedly imaged at different scales using scanning electron microscopy. We match this multiresolution EM imaging with multiresolution confocal mapping of the aldehyde-fixed tissue. Features visible in lower resolution …

Silver Jubilee: 25 Years Of The First Demonstration Of The Direct Effect Of Phosphate On The Parathyroid Cell, Jordi Bover, Adriana Dusso, Et Al.

2020-Current year OA Pubs

Although phosphorus is an essential element for life, it is not found in nature in its native state but rather combined in the form of inorganic phosphates (PO

Correlating Electroconvulsive Therapy Response To Electroencephalographic Markers: Study Protocol, Subha Subramanian, Alyssa K Labonte, Thomas Nguyen, Anhthi H Luong, Orlandrea Hyche, S Kendall Smith, R Edward Hogan, Nuri B Farber, Ben Julian A Palanca, Mohammadmehdi Kafashan, Cet-Rem Study Group

2020-Current year OA Pubs

INTRODUCTION: Electroconvulsive therapy (ECT) is an effective intervention for patients with major depressive disorder (MDD). Despite longstanding use, the underlying mechanisms of ECT are unknown, and there are no objective prognostic biomarkers that are routinely used for ECT response. Two electroencephalographic (EEG) markers, sleep slow waves and sleep spindles, could address these needs. Both sleep microstructure EEG markers are associated with synaptic plasticity, implicated in memory consolidation, and have reduced expression in depressed individuals. We hypothesize that ECT alleviates depression through enhanced expression of sleep slow waves and sleep spindles, thereby facilitating synaptic reconfiguration in pathologic neural circuits.

METHODS: Correlating …

Expression Variation Of Ogg1 And Hprt Gene And Dna Damage In Arsenic Exposed Industrial Workers, Zertashia Akram, Ishrat Mahjabeen, Muhammad Umair, Muhammad Fahim, Mahmood Akhter Kayani, Lulu Fatima, Malik Waqar Ahmad, Sarwat Jahan, Tayyaba Afsar, Ali Almajwal, Nawaf W. Alruwaili, Iftikhar Ali Khawar, Suhail Razak

2020-Current year OA Pubs

Arsenic exposure alters redox balance, induces DNA damage, and deregulates many genes. OGG1 gene involved in base repair mechanism, for excision of 8-oxoguanine (8-oxoG) from DNA formed as a result of accumulation of ROS in cell. HPRT gene encode transferase enzymes involved in purine recycling mechanism. The main focus of the study was to evaluate the expression variation in HPRT, OGG1 gene expression, and DNA damage of industrial workers. Blood samples of 300 occupational workers were collected from welding, brick kiln, furniture, pesticide, and paint industry (n = 60/industry) to evaluate the expression variation in HPRT, OGG1 gene expression, and …

Neors: A Neonatal Resting State Fmri Data Preprocessing Pipeline, Vicente Enguix, Jeanette Kenley, David Luck, Julien Cohen-Adad, Gregory Anton Lodygensky

2020-Current year OA Pubs

Resting state functional MRI (rsfMRI) has been shown to be a promising tool to study intrinsic brain functional connectivity and assess its integrity in cerebral development. In neonates, where functional MRI is limited to very few paradigms, rsfMRI was shown to be a relevant tool to explore regional interactions of brain networks. However, to identify the resting state networks, data needs to be carefully processed to reduce artifacts compromising the interpretation of results. Because of the non-collaborative nature of the neonates, the differences in brain size and the reversed contrast compared to adults due to myelination, neonates can't be processed …

Apoe Mediated Neuroinflammation And Neurodegeneration In Alzheimer's Disease, Samira Parhizkar, David M Holtzman

2020-Current year OA Pubs

Neuroinflammation is a central mechanism involved in neurodegeneration as observed in Alzheimer's disease (AD), the most prevalent form of neurodegenerative disease. Apolipoprotein E4 (APOE4), the strongest genetic risk factor for AD, directly influences disease onset and progression by interacting with the major pathological hallmarks of AD including amyloid-β plaques, neurofibrillary tau tangles, as well as neuroinflammation. Microglia and astrocytes, the two major immune cells in the brain, exist in an immune-vigilant state providing immunological defense as well as housekeeping functions that promote neuronal well-being. It is becoming increasingly evident that under disease conditions, these immune cells become progressively dysfunctional in …

Il-1 Reprogramming Of Adult Neural Stem Cells Limits Neurocognitive Recovery After Viral Encephalitis By Maintaining A Proinflammatory State, Allison L Soung, Veronica A Davé, Charise Garber, Eric D Tycksen, Lauren L Vollmer, Robyn S Klein

2020-Current year OA Pubs

Innate immune responses to emerging RNA viruses are increasingly recognized as having significant contributions to neurologic sequelae, especially memory disorders. Using a recovery model of West Nile virus (WNV) encephalitis, we show that, while macrophages deliver the antiviral and anti-neurogenic cytokine IL-1β during acute infection; viral recovery is associated with continued astrocyte inflammasome-mediated production of inflammatory levels of IL-1β, which is maintained by hippocampal astrogenesis via IL-1R1 signaling in neural stem cells (NSC). Accordingly, aberrant astrogenesis is prevented in the absence of IL-1 signaling in NSC, indicating that only newly generated astrocytes exert neurotoxic effects, preventing synapse repair and promoting …

Induction Egfr Tyrosine Kinase Inhibitors Prior To Definitive Chemoradiotherapy In Unresectable Stage Iii Egfr-Mutated Non-Small Cell Lung Cancer, Jacqueline V Aredo, Heather A Wakelee, Angela Bik-Yu Hui, Sukhmani K Padda, Nitin D Joshi, H Henry Guo, Aadel Chaudhuri, Maximilian Diehn, Billy W Loo Jr, Joel W Neal

2020-Current year OA Pubs

INTRODUCTION: Increasing evidence suggests that consolidation durvalumab confers limited benefits for patients with stage III EGFR-mutated NSCLC. Induction or maintenance EGFR tyrosine kinase inhibitors (TKIs) added to concurrent chemoradiotherapy (CRT) may optimize definitive treatment, but there are limited data supporting an induction TKI strategy.

METHODS: We evaluated the efficacy and safety of induction EGFR TKIs administered before concurrent CRT in a retrospective series of patients with unresectable locally advanced EGFR-mutated NSCLC. Circulating tumor DNA (ctDNA) analysis was performed on a patient subset using CAPP-seq and correlated with outcomes.

RESULTS: Of six patients, three received erlotinib and three osimertinib as induction …

Inferring The Dynamical Effects Of Stroke Lesions Through Whole-Brain Modeling, Sebastian Idesis, Chiara Favaretto, Nicholas V Metcalf, Joseph C Griffis, Gordon L Shulman, Maurizio Corbetta, Gustavo Deco

2020-Current year OA Pubs

Understanding the effect of focal lesions (stroke) on brain structure-function traditionally relies on behavioral analyses and correlation with neuroimaging data. Here we use structural disconnection maps from individual lesions to derive a causal mechanistic generative whole-brain model able to explain both functional connectivity alterations and behavioral deficits induced by stroke. As compared to other models that use only the local lesion information, the similarity to the empirical fMRI connectivity increases when the widespread structural disconnection information is considered. The presented model classifies behavioral impairment severity with higher accuracy than other types of information (e.g.: functional connectivity). We assessed topological measures …

Identification And Management Of Aggressive Meningiomas, Bhuvic Patel, Rupen Desai, Sangami Pugazenthi, Omar H Butt, Jiayi Huang, Albert H Kim

2020-Current year OA Pubs

Meningiomas are common primary central nervous system tumors derived from the meninges, with management most frequently entailing serial monitoring or a combination of surgery and/or radiation therapy. Although often considered benign lesions, meningiomas can not only be surgically inaccessible but also exhibit aggressive growth and recurrence. In such cases, adjuvant radiation and systemic therapy may be required for tumor control. In this review, we briefly describe the current WHO grading scale for meningioma and provide demonstrative cases of treatment-resistant meningiomas. We also summarize frequently observed molecular abnormalities and their correlation with intracranial location and recurrence rate. We then describe how …

Rhamnose Is Superior To Mannitol As A Monosaccharide In The Dual Sugar Absorption Test: A Prospective Randomized Study In Children With Treatment-Naïve Celiac Disease, Lori R Holtz, Julie Hoffmann, Laura Linneman, Mai He, Thomas C Smyrk, Ta-Chiang Liu, Nurmohammad Shaikh, Cynthia Rodriguez, Roy B Dyer, Ravinder J Singh, William A Faubion

2020-Current year OA Pubs

BACKGROUND AND AIM: We sought to correlate two different measures of gut permeability [lactulose:mannitol (L:M) and lactulose:rhamnose (L:R)] to the severity of duodenal histopathology in children with and without elevated antibodies to tissue transglutaminase (tTG). A secondary objective was to correlate gut permeability with celiac disease (CD) serology and indices of inflammation and bacterial product translocation.

METHODS: We prospectively randomized children undergoing endoscopy with abnormal (

RESULTS: Of the 54 cases with positive celiac serology, 31 and 69% had modified Marsh 0/1 scores or ≥3a, respectively. Circulating tTG IgA correlated with the modified Marsh score (

CONCLUSIONS: L:R, but not …

Functional And Phylogenetic Characterization Of Bacteria In Bovine Rumen Using Fractionation Of Ruminal Fluid, Ruth Hernández, Maryam Chaib De Mares, Hugo Jimenez, Alejandro Reyes, Alejandro Caro-Quintero

2020-Current year OA Pubs

Cattle productivity depends on our ability to fully understand and manipulate the fermentation process of plant material that occurs in the bovine rumen, which ultimately leads to the improvement of animal health and increased productivity with a reduction in environmental impact. An essential step in this direction is the phylogenetic and functional characterization of the microbial species composing the ruminal microbiota. To address this challenge, we separated a ruminal fluid sample by size and density using a sucrose density gradient. We used the full sample and the smallest fraction (5%), allowing the enrichment of bacteria, to assemble metagenome-assembled genomes (MAGs). …

Driving Performance In Older Adults: Current Measures, Findings, And Implications For Roadway Safety, Robert Toups, Theresa J Chirles, Johnathon P Ehsani, Jeffrey P Michael, John P K Bernstein, Matthew Calamia, Thomas D Parsons, David B Carr, Jeffrey N Keller

2020-Current year OA Pubs

BACKGROUND AND OBJECTIVES: Over 10,000 people a day turn 65 in the United States. For many older adults, driving represents an essential component of independence and is one of the most important factors in overall mobility. Recent survey studies in older adults suggest that up to 60% of older adult drivers with mild cognitive impairment, and up to 30% with dementia, continue to drive. The purpose of this review is to provide a comprehensive and detailed resource on the topics of cognition and driving for clinicians, researchers, and policymakers working on efforts related to older adult drivers.

RESEARCH DESIGN AND …

Follistatin Protein Enhances Satellite Cell Counts In Reinnervated Muscle, Mark A. Feger, Jonathan Isaacs, Satya Mallu, Dorne Yager, Mary Shall, Gaurangkumar Patel, Omar Protzuk, Akhil S Bokkisam

2020-Current year OA Pubs

No abstract provided.

Proportional Constrained Longitudinal Data Analysis Models For Clinical Trials In Sporadic Alzheimer's Disease, Guoqiao Wang, Lei Liu, Yan Li, Andrew J Aschenbrenner, Randall J Bateman, Paul Delmar, Lon S Schneider, Richard E Kennedy, Gary R Cutter, Chengjie Xiong

2020-Current year OA Pubs

INTRODUCTION: Clinical trials for sporadic Alzheimer's disease generally use mixed models for repeated measures (MMRM) or, to a lesser degree, constrained longitudinal data analysis models (cLDA) as the analysis model with time since baseline as a categorical variable. Inferences using MMRM/cLDA focus on the between-group contrast at the pre-determined, end-of-study assessments, thus are less efficient (eg, less power).

METHODS: The proportional cLDA (PcLDA) and proportional MMRM (pMMRM) with time as a categorical variable are proposed to use all the post-baseline data without the linearity assumption on disease progression.

RESULTS: Compared with the traditional cLDA/MMRM models, PcLDA or pMMRM lead to …

Skeletal Muscle Contractile Function In Heart Failure With Reduced Ejection Fraction - A Focus On Nitric Oxide, Lauren K Park, Andrew R Coggan, Linda R Peterson

2020-Current year OA Pubs

Despite advances over the past few decades, heart failure with reduced ejection fraction (HFrEF) remains not only a mortal but a disabling disease. Indeed, the New York Heart Association classification of HFrEF severity is based on how much exercise a patient can perform. Moreover, exercise capacity-both aerobic exercise performance and muscle power-are intimately linked with survival in patients with HFrEF. This review will highlight the pathologic changes in skeletal muscle in HFrEF that are related to impaired exercise performance. Next, it will discuss the key role that impaired nitric oxide (NO) bioavailability plays in HFrEF skeletal muscle pathology. Lastly, it …

Diabetic Retinopathy As A Predictor Of Cardiovascular Morbidity And Mortality In Subjects With Type 2 Diabetes, Joan Barrot, Jordi Real, Bogdan Vlacho, Pedro Romero-Aroca, Rafael Simó, Didac Mauricio, Manel Mata-Cases, Esmeralda Castelblanco, Xavier Mundet-Tuduri, Josep Franch-Nadal

2020-Current year OA Pubs

This study aimed to evaluate the predictive value of diabetic retinopathy (DR) and its stages with the incidence of major cardiovascular events and all-cause mortality in type 2 diabetes mellitus (T2DM) persons in our large primary healthcare database from Catalonia (Spain). A retrospective cohort study with pseudo-anonymized routinely collected health data from SIDIAP was conducted from 2008 to 2016. We calculated incidence rates of major cardiovascular events [coronary heart disease (CHD), stroke, or both-macrovascular events] and all-cause mortality for subjects with and without DR and for different stages of DR. The proportional hazards regression analysis was done to assess the …