Medicine and Health Sciences Commons^™

Molecular Modelling A Key Method For Potential Therapeutic Drug Discovery, Omar Karkoutly, Anupam Dhasmana, Vijian Dhevan, Subhash C. Chauhan, Manish Tripathi

School of Medicine Publications

The well-defined and characterized 3D crystal structure of a protein is important to explore the topological and physiological features of the protein. The distinguished topography of a protein helps medical chemists design drugs on the basis of the pharmacophoric features of the protein. Structure-based drug discovery, specifically for pathological proteins that cause a higher risk of disease, takes advantage of this fact. Current tools for studying drug-protein interactions include physical, chromatographic, and electrophoretic methods. These techniques can be separated into either non-spectroscopic (equilibrium dialysis, ultrafiltration, ultracentrifugation, etc.) or spectroscopic (Fluorescence spectroscopy, NMR, X-ray diffraction, etc.) methods. These methods, however, can …

Differential And Shared Genetic Effects On Kidney Function Between Diabetic And Non-Diabetic Individuals, Thomas W. Winkler, Humaira Rasheed, Alexander Teumer, Mathias Gorski, Bryce X. Rowan, Kira J. Stanzick, Laurent F. Thomas, Adrienne Tin, Anselm Hoppmann, Mikko Kuokkanen

School of Medicine Publications

Reduced glomerular filtration rate (GFR) can progress to kidney failure. Risk factors include genetics and diabetes mellitus (DM), but little is known about their interaction. We conducted genome-wide association meta-analyses for estimated GFR based on serum creatinine (eGFR), separately for individuals with or without DM (nDM = 178,691, nnoDM = 1,296,113). Our genome-wide searches identified (i) seven eGFR loci with significant DM/noDM-difference, (ii) four additional novel loci with suggestive difference and (iii) 28 further novel loci (including CUBN) by allowing for potential difference. GWAS on eGFR among DM individuals identified 2 known and 27 potentially responsible loci for diabetic …

Antibody-Mediated Lilrb2-Receptor Antagonism Induces Human Myeloid-Derived Suppressor Cells To Kill Mycobacterium Tuberculosis, Vipul K. Singh, Arshad Khan, Yitian Xu, Sunny Mai, Licheng Zhang, Abhishek Mishra, Blanca I. Restrepo, Ping-Ying Pan, Shu-Hsia Chen

School of Medicine Publications

Tuberculosis is a leading cause of death in mankind due to infectious agents, and Mycobacterium tuberculosis (Mtb) infects and survives in macrophages (MФs). Although MФs are a major niche, myeloid-derived suppressor cells (MDSCs) are an alternative site for pathogen persistence. Both MФs and MDSCs express varying levels of leukocyte immunoglobulin-like receptor B (LILRB), which regulate the myeloid cell suppressive function. Herein, we demonstrate that antagonism of LILRB2 by a monoclonal antibody (mab) induced a switch of human MDSCs towards an M1-macrophage phenotype, increasing the killing of intracellular Mtb. Mab-mediated antagonism of LILRB2 alone and its combination with a pharmacological blockade …

Comprehensive Genetic Analysis Of The Human Lipidome Identifies Loci Associated With Lipid Homeostasis With Links To Coronary Artery Disease, Gemma Cadby, Corey Giles, Phillip E. Melton, Kevin Huynh, Natalie A. Mellett, Thy Duong, Anh Nguyen, Michelle Cinel, Alex Smith, John Blangero

School of Medicine Publications

We integrated lipidomics and genomics to unravel the genetic architecture of lipid metabolism and identify genetic variants associated with lipid species putatively in the mechanistic pathway for coronary artery disease (CAD). We quantified 596 lipid species in serum from 4,492 individuals from the Busselton Health Study. The discovery GWAS identified 3,361 independent lipid-loci associations, involving 667 genomic regions (479 previously unreported), with validation in two independent cohorts. A meta-analysis revealed an additional 70 independent genomic regions associated with lipid species. We identified 134 lipid endophenotypes for CAD associated with 186 genomic loci. Associations between independent lipid-loci with coronary atherosclerosis were …

Evaluating Internal Medicine Resident Cardiology Knowledge By In-Service Training Exam Performance: A Four-Year Review, Schamma Salomon, Chelsea Chang

School of Medicine Publications

The In-Service Training Examination in Internal Medicine (IM-ITE) has been offered annually to all trainees in U.S. medical residency programs since 1988. Its purpose is to provide residents and program directors with an objective assessment of each resident's performance on a written, multiple-choice examination and the performance of the residency program compared with that of its peers.

This study aims to determine which measurable educational objectives contributed to improving In-training examinations in cardiology and which did not. Furthermore, we hope to highlight the strengths and weaknesses of the current knowledge to objectively evaluate and improve our cardiology rotation and education.

Influence Of The Human Lipidome On Epicardial Fat Volume In Mexican American Individuals, Ana C. Leandro, Laura F. Michael, Marcio Almeida, Mikko Kuokkanen, Kevin Huynh, Corey Giles, Thy Duong, Vincent P. Diego, Ravindranath Duggirala, Geoffrey D. Clarke, John Blangero, Joanne E. Curran

School of Medicine Publications

Introduction: Cardiovascular disease (CVD) is the leading cause of mortality worldwide and is the leading cause of death in the US. Lipid dysregulation is a well-known precursor to metabolic diseases, including CVD. There is a growing body of literature that suggests MRI-derived epicardial fat volume, or epicardial adipose tissue (EAT) volume, is linked to the development of coronary artery disease. Interestingly, epicardial fat is also actively involved in lipid and energy homeostasis, with epicardial adipose tissue having a greater capacity for release and uptake of free fatty acids. However, there is a scarcity of knowledge on the influence of plasma …

Two-Year Responses Of Renal Function To First Occupational Lead Exposure, Yu-Ling Yu, Lutgarde Thijs, Dong-Mei Wei, Jesus D. Melgarejo, Cai-Guo Yu, Wen-Yi Yang, Harry A. Roels, Zhen-Yu Zhang, Tim S. Nawrot, Jan A. Staessen

School of Medicine Publications

Introduction

Whether in advanced countries lead exposure still contributes to renal impairment is debated, because blood lead (BL) level is declining toward preindustrial levels and because longitudinal studies correlating renal function and BL changes over time are scarce.

Methods

The Study for Promotion of Health in Recycling Lead (SPHERL) evaluated the 2-year renal function responses in 251 workers (mean age, 29.7 years) transiting from environmental to occupational exposure. Main study end point was the estimated glomerular filtration rate (eGFR) derived from serum creatinine (eGFRcrt), cystatin C (eGFRcys), or both (eGFRcc). BL level was measured by inductively coupled plasma mass spectrometry …

Non-Compartmental Toxicokinetic Studies Of The Nigerian Naja Nigricollis Venom, Auwal A. Bala, Sani Malami, Yusuf Abubakar Muhammad, Binta Kurfi, Ismaila Raji, Sanusi Muhammad Salisu, Mustapha Mohammed, George Oche Ambrose, Murtala Jibril, Jacob Galan

School of Medicine Publications

Snakebite envenoming (SBE) is a neglected public health problem, especially in Asia, Latin America and Africa. There is inadequate knowledge of venom toxicokinetics especially from African snakes. To mimic a likely scenario of a snakebite envenoming, we used an enzyme-linked immunosorbent assay (ELISA) approach to study the toxicokinetic parameters in rabbits, following a single intramuscular (IM) administration of Northern Nigeria Naja nigricollis venom. We used a developed and validated non-compartmental approach in the R package PK to determine the toxicokinetic parameters of the venom and subsequently used pharmacometrics modelling to predict the movement of the toxin within biological systems. We …

Extent Of Craniofacial Fungal Osteomyelitis In A Ketoacidotic Patient May Predict Optic Nerve Involvement: A Case Report, Jennifer Adams, Khalid Sheikh, Adam Bender-Heine

School of Medicine Publications

Introduction: Mucormycosis is an opportunistic mycosis common in poorly-controlled insulin dependent diabetic patients particularly with ketoacidosis. Fungal osteomyelitis is a life-threatening condition affectation of the nose and paranasal sinuses within the orofacial region.

Presentation of case: We present a 63-year-old diabetic male patient with maxillary mucormycotic osteomyelitis threatening his better seeing eye and review the clinical symptoms, relevant imaging, and management.

Discussion: We highlight a rare pattern of craniofacial fungal bone infection with maxillary and orbital involvement that ultimately spared the optic nerve. This case report offers the clinician a review of important clinical and diagnostic findings that …

Covid-19 Infection And Treatment-Resistant Cocaine-Induced Pyoderma Gangrenosum: A Case Report, Jennifer Adams, Daniel Habenicht, Yaman Gibran

School of Medicine Publications

Introduction

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis of non-infectious etiology. Cocaine-induced PG (CIPG) is a documented clinical variant.

Case presentation

We report an exceptional case of cocaine-induced PG flare unresponsive to conventional treatment in the context of positive COVID status. A 41year-old male with past medical history of recent COVID infection, pyoderma gangrenosum and chronic cocaine abuse presented with acutely worsening multifocal ulcerations covering multiple limbs approximately 30% body surface area (BSA) one day after cocaine use. After hospitalization for ten days with no improvement in cutaneous symptoms, he was transferred to a burn center for disease control …

Duration Of Ischemia Affects Outcomes Independent Of Infarct Size In Stroke, Youngran Kim, Swapnil Khose, Osama Zaidat, Ameer E. Hassan, Johanna T. Fifi, Ashish Nanda, Benjamin Atchie, Britton Woodward, Arnd Doerfler, Alejandro Tomasello

School of Medicine Publications

BACKGROUND:

Delays in endovascular reperfusion for patients with large vessel occlusion stroke are known to worsen outcomes, and the mechanism is believed to be time-dependent expansion of the ischemic infarction. In this study, we hypothesize that delays in onset to reperfusion (OTR) assert an effect on outcomes independent of effects of final infarct (FI).

METHODS:

We performed a subgroup analysis from the prospective multicenter COMPLETE (International Acute Ischemic Stroke Registry With the Penumbra System Aspiration Including the 3D Revascularization Device; Penumbra, Inc) registry for 257 patients with anterior circulation large vessel occlusion who underwent endovascular therapy with successful reperfusion (modified …

Human M1 Macrophages Express Unique Innate Immune Response Genes After Mycobacterial Infection To Defend Against Tuberculosis, Arshad Khan, Kangling Zhang, Vipul K. Singh, Abhishek Mishra, Priyanka Kachroo, Tian Bing, Jong Hak Won, Eder Ledezma-Campos, Genesis P. Aguillón-Durán, Blanca I. Restrepo

School of Medicine Publications

Mycobacterium tuberculosis (Mtb) is responsible for approximately 1.5 million deaths each year. Though 10% of patients develop tuberculosis (TB) after infection, 90% of these infections are latent. Further, mice are nearly uniformly susceptible to Mtb but their M1-polarized macrophages (M1-MΦs) can inhibit Mtb in vitro, suggesting that M1-MΦs may be able to regulate anti-TB immunity. We sought to determine whether human MΦ heterogeneity contributes to TB immunity. Here we show that IFN-γ-programmed M1-MΦs degrade Mtb through increased expression of innate immunity regulatory genes (Inregs). In contrast, IL-4-programmed M2-polarized MΦs (M2-MΦs) are permissive for Mtb proliferation and exhibit reduced …

Bromodomains In Human-Immunodeficiency Virus-Associated Neurocognitive Disorders: A Model Of Ferroptosis-Induced Neurodegeneration, Adonis Sfera, Karina G. Thomas, Christina V. Andronescu, Nyla Jafri, Dan O. Sfera, Sarvin Sasannia, Carlos Zapata-Martin Del Campo, Jose E. Campo Maldonado

School of Medicine Publications

Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) comprise a group of illnesses marked by memory and behavioral dysfunction that can occur in up to 50% of HIV patients despite adequate treatment with combination antiretroviral drugs. Iron dyshomeostasis exacerbates HIV-1 infection and plays a major role in Alzheimer’s disease pathogenesis. In addition, persons living with HIV demonstrate a high prevalence of neurodegenerative disorders, indicating that HAND provides a unique opportunity to study ferroptosis in these conditions. Both HIV and combination antiretroviral drugs increase the risk of ferroptosis by augmenting ferritin autophagy at the lysosomal level. As many viruses and their proteins …

Human Macrophages Exhibit Gm-Csf Dependent Restriction Of Mycobacterium Tuberculosis Infection Via Regulating Their Self-Survival, Differentiation And Metabolism, Abhishek Mishra, Vipul K. Singh, Chinnaswamy Jagannath, Margaret Sunitha Selvaraj, Selvakumar Subbian, Blanca I. Restrepo, Marie-Claire Gauduin, Arshad Khan

School of Medicine Publications

GM-CSF is an important cytokine that regulates the proliferation of monocytes/macrophages and its various functions during health and disease. Although growing evidences support the notion that GM-CSF could play a major role in immunity against tuberculosis (TB) infection, the mechanism of GM-CSF mediated protective effect against TB remains largely unknown. Here in this study we examined the secreted levels of GM-CSF by human macrophages from different donors along with the GM-CSF dependent cellular processes that are critical for control of M. tuberculosis infection. While macrophage of different donors varied in their ability to produce GM-CSF, a significant correlation was observed …

Evidence Of Areca Nut Consumption In The United States Mainland: A Cross‑Sectional Study, Irene Tami‑Maury, Suzanne Nethan, Jessy Feng, Hongyu Miao, George Delclos, Ravi Mehrotra

School of Medicine Publications

Background

Areca nut (AN) is an addictive substance consumed in the Southeast region and is highly associated with oral premalignant lesions and oral cancer. The impact of AN use in the United States (US) is largely unknown, but the products are readily available and probably used by a significant fraction of Asian immigrants or descendants living in the US. We aimed at assessing AN use prevalence among the Asian community in Houston, Texas.

Methods

A cross-sectional questionnaire was used to interview adult individuals (≥ 18 years of age) who self-identified as Asian immigrants or descendants residing in Houston. Means, frequencies, …

Thrombectomy For Large‐Vessel Occlusion With Pretreatment Intracranial Hemorrhage, Daniel A. Tonetti, Shashvat M. Desai, Stephanie Casillo, Sohum Desai, Ameer E. Hassan, Gabriel Flores-Milan, Maxim Mokin, Mudassir Farooqui, Santiago Ortega‐Gutierrez, Ashutosh P. Jadhav

School of Medicine Publications

Background

Many patients treated with endovascular thrombectomy (EVT) in clinical practice would not have qualified for inclusion in the initial clinical trials demonstrating benefit for EVT, yet likely will benefit from reperfusion. One such subset for which data are sparse is patients with emergent large‐vessel occlusion and concomitant intracranial hemorrhage (ICH). The objective of this report is to document patients who underwent thrombectomy for large‐vessel occlusion in the presence of concomitant ICH and evaluate their clinical characteristics and outcomes.

Methods

We retrospectively reviewed prospectively collected patient records at 4 comprehensive stroke centers from 2012 to 2019. Patients were identified who …

Combined Treatment With Niclosamide And Camptothecin Enhances Anticancer Effect In U87 Mg Human Glioblastoma Cells, Laura Valdez, Benxu Cheng, Daniela Gonzalez, Reanna Rodriguez, Paola Campano, Andrew Tsin, Xiaoqian Fang

School of Medicine Publications

Glioblastoma multiforme (GBM) is one of the deadliest cancers of the brain. Its ability to infiltrate healthy brain tissues renders it difficult to remove surgically. Furthermore, it exhibits high rates of radio- and chemoresistance, making the survival rates of patients with GBM poor. Therefore, novel effective therapies for GBM remain urgently in demand. Niclosamide is an anti-helminthic drug and recently it has been receiving attention due to its reported anticancer effects in cancer models, including GBM. Furthermore, camptothecin (CPT) is a naturally-occurring alkaloid and has been previously reported to be a potential chemotherapeutic agent by targeting the nuclear topoisomerase I. …

The Value Of Rare Genetic Variation In The Prediction Of Common Obesity In European Ancestry Populations, Zhe Wang, Shing Wan Choi, Nathalie Chami, Eric Boerwinkle, Myriam Fornage, Susan Redline, Joshua C. Bis, Jennifer A. Brody, Bruce M. Psaty, John Blangero

School of Medicine Publications

Polygenic risk scores (PRSs) aggregate the effects of genetic variants across the genome and are used to predict risk of complex diseases, such as obesity. Current PRSs only include common variants (minor allele frequency (MAF) ≥1%), whereas the contribution of rare variants in PRSs to predict disease remains unknown. Here, we examine whether augmenting the standard common variant PRS (PRScommon) with a rare variant PRS (PRSrare) improves prediction of obesity. We used genome-wide genotyped and imputed data on 451,145 European-ancestry participants of the UK Biobank, as well as whole exome sequencing (WES) data on 184,385 participants. We performed single variant …

The Effects Of Leadership Curricula With And Without Implicit Bias Training On Graduate Medical Education: A Multicenter Randomized Trial, Matt Hansen, Tabria Harrod, Nathan Bahr, Amanda Schoonover, Karen Adams, Josh Kornegay, Amy Stenson, Vivienne Ng, Jennifer Plitt, Tony Ogburn

School of Medicine Publications

Purpose: To determine whether a brief leadership curriculum including high-fidelity simulation can improve leadership skills among resident physicians.

Method: This was a double-blind, randomized controlled trial among obstetrics-gynecology and emergency medicine (EM) residents across 5 academic medical centers from different geographic areas of the United States, 2015-2017. Participants were assigned to 1 of 3 study arms: the Leadership Education Advanced During Simulation (LEADS) curriculum, a shortened Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS) curriculum, or as active controls (no leadership curriculum). Active controls were recruited from a separate site and not randomized to limit any unintentional …

An Opportunity For Primary Prevention Research In Psychotic Disorders, Elliot S. Gershon, S. Hong Lee, Xuan Zhou, John A. Sweeney, Carol Tamminga, Godfrey A. Pearlson, Brett A. Clementz, Matcheri S. Keshavan, Ney Alliey-Rodriguez, Matthew Hudgens-Haney

School of Medicine Publications

An opportunity has opened for research into primary prevention of psychotic disorders, based on progress in endophenotypes, genetics, and genomics. Primary prevention requires reliable prediction of susceptibility before any symptoms are present. We studied a battery of measures where published data supports abnormalities of these measurements prior to appearance of initial psychosis symptoms. These neurobiological and behavioral measurements included cognition, eye movement tracking, Event Related Potentials, and polygenic risk scores. They generated an acceptably precise separation of healthy controls from outpatients with a psychotic disorder.

Methods

The Bipolar and Schizophrenia Network on Intermediate Phenotypes (B-SNIP) measured this battery …

Endoscopic Management Of Polyps Arising From Diverticula, Mohammed Shakhatreh, Grigoriy L. Rapoport, Asif Zamir

School of Medicine Publications

Colon polyps arising from diverticula are rare with only a few cases reported to date.1 Most colon diverticula are considered “false diverticula” and are composed mainly of mucosa and submucosa that protrude through the muscularis externa layer and are covered by the serosa. Because of this, endoscopic resection of such polyps carries a high risk of perforation and management has traditionally been with surgical intervention, which increases the risk of complications. In this series, we present 2 cases of successful excision of an adenomatous polyp located within the lumen of a diverticulum using endoscopic mucosal resection (EMR).

Nutrigenetic Reprogramming Of Oxidative Stress, Joseph Ryu, Huzeifa Gulamhusein, Jin Kyun Oh, Joseph H. Chang, Jocelyn Chen, Stephen H. Tsang

School of Medicine Publications

Retinal disorders such as retinitis pigmentosa, age-related retinal degeneration, oxygen-induced retinopathy, and ischemia-reperfusion injury cause debilitating and irreversible vision loss. While the exact mechanisms underlying these conditions remain unclear, there has been a growing body of evidence demonstrating the pathological contributions of oxidative stress across different cell types within the eye. Nuclear factor erythroid-2-related factor (Nrf2), a transcriptional activator of antioxidative genes, and its regulator Kelch-like ECH-associated protein 1 (Keap1) have emerged as promising therapeutic targets. The purpose of this review is to understand the protective role of the Nrf2-Keap1 pathway in different retinal tissues and shed light on the …

Sars-Cov-2 Is Associated With Changes In Brain Structure In Uk Biobank, Gwenaëlle Douaud, Soojin Lee, Fidel Alfaro-Almagro, Christoph Arthofer, Chaoyue Wang, Paul Mccarthy, Frederik Lange, Jesper L. R. Andersson, Ludovica Griffanti, Anderson M. Winkler

School of Medicine Publications

There is strong evidence of brain-related abnormalities in COVID-191,2,3,4,5,6,7,8,9,10,11,12,13. However, it remains unknown whether the impact of SARS-CoV-2 infection can be detected in milder cases, and whether this can reveal possible mechanisms contributing to brain pathology. Here we investigated brain changes in 785 participants of UK Biobank (aged 51–81 years) who were imaged twice using magnetic resonance imaging, including 401 cases who tested positive for infection with SARS-CoV-2 between their two scans—with 141 days …

Computational Modeling Of Threat Learning Reveals Links With Anxiety And Neuroanatomy In Humans, Rany Abend, Diana Burk, Sonia G. Ruiz, Andrea L. Gold, Julia L. Napoli, Jennifer C. Britton, Kalina J. Michalska, Tomer Shechner, Anderson M. Winkler, Ellen Leibenluft

School of Medicine Publications

Influential theories implicate variations in the mechanisms supporting threat learning in the severity of anxiety symptoms. We use computational models of associative learning in conjunction with structural imaging to explicate links among the mechanisms underlying threat learning, their neuroanatomical substrates, and anxiety severity in humans. We recorded skin-conductance data during a threat-learning task from individuals with and without anxiety disorders (N=251; 8-50 years; 116 females). Reinforcement-learning model variants quantified processes hypothesized to relate to anxiety: threat conditioning, threat generalization, safety learning, and threat extinction. We identified the best-fitting models for these processes and tested associations among latent learning parameters, whole-brain …

Disease Severity And Response To Induction Therapy In Hispanic Patients With Antineutrophilic Cytoplasmic Autoantibody-Associated Vasculitis-Related Diffuse Alveolar Hemorrhage, Christine Loftis, Emilia C. Dulgheru, Rosa White

School of Medicine Publications

Objectives We examined the response to induction therapy of Hispanic patients with antibody-associated vasculitis (AAV)-related diffuse alveolar hemorrhage (DAH). This study aimed to determine the severity of disease at presentation and the response to induction therapy in our patient population.

Methods We retrospectively reviewed the clinical data of Hispanic patients hospitalized with antineutrophil cytoplasmic antibody (ANCA) vasculitis between October 1, 2010, and December 31, 2021. We identified 98 Hispanic patients hospitalized with AAV and 19 admitted with AAV-related DAH. The Birmingham Vasculitis Activity Score (BVAS) was obtained from all patients on presentation.

Results Based on the 2012 Revised International Chapel …

Surgical Management Of Vascular Tumors And Malformations Of The Head And Neck In Adults, Rachel A. Giese, Cristina Valero, Jatin P. Shah

School of Medicine Publications

Vascular tumors and malformations present a diagnostic and therapeutic challenge to many physicians. Because these lesions are rare, few surgeons have enough experience with them other than those practicing in tertiary vascular anomaly treatment centers. Some patients may have been misdiagnosed or mistreated during childhood and present in adult age with either recurrence or with an untreated lesion. Ideally, a multidisciplinary treatment team should be involved to discuss management with the patient including specialists in surgery, interventional radiology, pathology, hematology, genetics, and dermatology. As our understanding of the pathogenesis of these lesions grows, novel therapies are being employed which may …

Complex Chromosomal Rearrangement Involving 15q11-Q13 Interstitial Triplication And Duplication: A New Case Report Of Dysmorphic And Neuropsychiatric Features, Lekha Chilakamarri, Estrella Lizbeth Mellin-Sanchez

School of Medicine Publications

Our patient is the first to encompass the full spectrum of reported features related to tetrasomy of the Prader–Willi Angelman Critical Region. She has a complex chromosomal rearrangement including an interstitial triplication reported in twelve cases till date and a rare interstitial duplication reported in only four cases till date.

Acute Lower Extremity Posterior Compartment Syndrome: A Rare Complication Of Apixaban Use, Jennifer Adams, Jose H. Ramos, Shyama Appareddy M.D., Hoang Anh Thi Nguyen, Gustavo Garcia

School of Medicine Publications

Apixaban is an oral anticoagulant that directly inhibits Factor Xa and is indicated for the prophylaxis and treatment of deep venous thrombosis and stroke prevention in non-valvular atrial fibrillation. Acute lower extremity Posterior Compartment Syndrome is a rare complication of Apixaban use. We present a 78-year-old male with significant medical morbidities taking Apixaban for Atrial Fibrillation presenting with post-traumatic extensive hemorrhagic bullae on the left proximal pretibial region secondary to anticoagulation. We recommend that clinicians develop awareness of the potential for serious bleeding complications of anticoagulants and devise strategies to identify the need for early recognition and prompt management.

Burden Of Type 2 Diabetes And Associated Cardiometabolic Traits And Their Heritability Estimates In Endogamous Ethnic Groups Of India: Findings From The Indigenius Consortium, Vettriselvi Venkatesan, Rector Arya, Juan Carlos Lopez Alvarenga, Krishna K. Sharma, Roy G. Resendez, Juliet A. Ezeilo, Marcio Almeida, Srinivas Mummidi, John Blangero, Ravindranath Duggirala

School of Medicine Publications

To assess the burden of type 2 diabetes (T2D) and its genetic profile in endogamous populations of India given the paucity of data, we aimed to determine the prevalence of T2D and estimate its heritability using family-based cohorts from three distinct Endogamous Ethnic Groups (EEGs) representing Northern (Rajasthan [Agarwals: AG]) and Southern (Tamil Nadu [Chettiars: CH] and Andhra Pradesh [Reddys: RE]) states of India. For comparison, family-based data collected previously from another North Indian Punjabi Sikh (SI) EEG was used. In addition, we examined various T2D-related cardiometabolic traits and determined their heritabilities. These studies were conducted as part of the …

Urinary Proteomic Profile Of Arterial Stiffness Is Associated With Mortality And Cardiovascular Outcomes, Dongmei Wei, Jesus D. Melgarejo, Lutgarde Thijs, Xander Temmerman, Thomas Vanassche, Lucas Van Aelst, Stefan Janssens, Jan A. Staessen, Peter Verhamme, Zhen-Yu Zhang

School of Medicine Publications

Background

The underlying mechanisms of arterial stiffness remain not fully understood. This study aimed to identify a urinary proteomic profile to illuminate its pathogenesis and to determine the prognostic value of the profile for adverse outcomes.

Methods and Results

We measured aortic stiffness using pulse wave velocity (PWV) and analyzed urinary proteome using capillary electrophoresis coupled with mass spectrometry in 669 randomly recruited Flemish patients (mean age, 50.2 years; 51.1% women). We developed a PWV‐derived urinary proteomic score (PWV‐UP) by modeling PWV with proteomics data at baseline through orthogonal projections to latent structures. PWV‐UP that consisted of 2336 peptides explained …