Medicine and Health Sciences Commons^™

Evaluation Of Dna Methylation Episignatures For Diagnosis And Phenotype Correlations In 42 Mendelian Neurodevelopmental Disorders., Erfan Aref-Eshghi, Jennifer Kerkhof, Victor P Pedro, Mouna Barat-Houari, Nathalie Ruiz-Pallares, Jean-Christophe Andrau, Didier Lacombe, Julien Van-Gils, Patricia Fergelot, Christèle Dubourg, Valerie Cormier-Daire, Sophie Rondeau, François Lecoquierre, Pascale Saugier-Veber, Gaël Nicolas, Gaetan Lesca, Nicolas Chatron, Damien Sanlaville, Antonio Vitobello, Laurence Faivre, Christel Thauvin-Robinet, Frederic Laumonnier, Martine Raynaud, Mariëlle Alders, Marcel Mannens, Peter Henneman, Raoul C Hennekam, Guillaume Velasco, Claire Francastel, Damien Ulveling, Andrea Ciolfi, Simone Pizzi, Marco Tartaglia, Solveig Heide, Delphine Héron, Cyril Mignot, Boris Keren, Sandra Whalen, Alexandra Afenjar, Thierry Bienvenu, Philippe M Campeau, Justine Rousseau, Michael A Levy, Lauren Brick, Mariya Kozenko, Tugce B Balci, Victoria Mok Siu, Alan Stuart, Mike Kadour, Jennifer Masters, Kyoko Takano, Tjitske Kleefstra, Nicole De Leeuw, Michael Field, Marie Shaw, Jozef Gecz, Peter J Ainsworth, Hanxin Lin, David I Rodenhiser, Michael J Friez, Matt Tedder, Jennifer A Lee, Barbara R Dupont, Roger E Stevenson, Steven A Skinner, Charles E Schwartz, David Genevieve, Bekim Sadikovic

Paediatrics Publications

Genetic syndromes frequently present with overlapping clinical features and inconclusive or ambiguous genetic findings which can confound accurate diagnosis and clinical management. An expanding number of genetic syndromes have been shown to have unique genomic DNA methylation patterns (called "episignatures"). Peripheral blood episignatures can be used for diagnostic testing as well as for the interpretation of ambiguous genetic test results. We present here an approach to episignature mapping in 42 genetic syndromes, which has allowed the identification of 34 robust disease-specific episignatures. We examine emerging patterns of overlap, as well as similarities and hierarchical relationships across these episignatures, to highlight …

Error-Corrected Sequencing Strategies Enable Comprehensive Detection Of Leukemic Mutations Relevant For Diagnosis And Minimal Residual Disease Monitoring, Erin L Crowgey, Nitin Mahajan, Wing Hing Wong, Anilkumar Gopalakrishnapillai, Sonali P Barwe, E Anders Kolb, Todd E Druley

2020-Current year OA Pubs

BACKGROUND: Pediatric leukemias have a diverse genomic landscape associated with complex structural variants, including gene fusions, insertions and deletions, and single nucleotide variants. Routine karyotype and fluorescence in situ hybridization (FISH) techniques lack sensitivity for smaller genomic alternations. Next-generation sequencing (NGS) assays are being increasingly utilized for assessment of these various lesions. However, standard NGS lacks quantitative sensitivity for minimal residual disease (MRD) surveillance due to an inherently high error rate.

METHODS: Primary bone marrow samples from pediatric leukemia (n = 32) and adult leukemia subjects (n = 5), cell line MV4-11, and an umbilical cord sample were utilized for …

Predictors Of Bicuspid Aortic Valve-Associated Aortopathy In Childhood: A Report From The Mibava Consortium, Michael Grattan, Andrea Prince, Rawan K Rumman, Conall Morgan, Michele Petrovic, Amanda Hauck, Luciana Young, Anders Franco-Cereceda, Bart Loeys, Salah A Mohamed, Harry Dietz, Seema Mital, Chun-Po Steve Fan, Cedric Manlhiot, Gregor Andelfinger, Luc Mertens

Paediatrics Publications

BACKGROUND: Bicuspid aortic valve (BAV) is the most prevalent congenital heart defect affecting 1% to 2% of the population. It is associated with ascending aorta dilatation. Valve morphology, aortic stenosis (AS), and aortic insufficiency (AI) have been proposed as potential risk factors; however, evaluating their role is difficult, as these factors are inherently related. The aim of this study was to determine whether BAV morphology and dysfunction are independent determinants for ascending aorta dilatation in pediatric patients.

METHODS: A multicenter, retrospective, cross-sectional study of pediatric BAV patients followed since 2004 was performed. Imaging data were assessed for BAV morphology, severity …

Osteochondritis Dissecans In Pediatric Patients With Juvenile Idiopathic Arthritis., Bradley C Jackson, Debra L Bartley, Roberta A Berard

Paediatrics Publications

No abstract provided.

Labour Progression In Obese Women: Are Women With Increased Body Mass Index Having Unnecessary Cesarean Sections?, Caroline Shenouda, Aloka Wijesooriya, Amanda Toufeili, Michael R Miller, Debbie Penava, Barbra De Vrijer

Obstetrics & Gynaecology Publications

OBJECTIVE: This study sought to determine whether obese pregnant women undergo cesarean sections without an adequate trial of labour. This may affect future birth and pregnancy outcomes.

METHODS: A retrospective analysis was done on 526 parturients at Victoria Hospital in London, Ontario. Women were categorized according to parity and pre-pregnancy body mass index (BMI; normal weight, BMI 18.5-24.9 kg/m

RESULTS: Obese class II and III primiparous women required an additional 1.62 and 2.67 hours (P = 0.012), respectively, to reach a dilation of 10 cm compared with their normal weight counterparts; obese class II and III multiparous women required an …

Effect Of Dual-Tasking On Walking And Cognitive Demands In Adults With Alzheimer's Dementia Experienced In Using A 4-Wheeled Walker, Susan W. Hunter, Humberto Omana, Edward Madou, Walter Wittich, Keith D Hill, Andrew M Johnson, Alison Divine, Jeffrey D Holmes

Physical Therapy Publications

BACKGROUND: Learning to walk with a 4-wheeled walker increases cognitive demands in people with Alzheimer's dementia (AD). However, it is expected that experience will offset the increased cognitive demand. Current research has not yet evaluated gait in people with AD experienced in using a 4-wheeled walker under complex gait situations.

RESEARCH QUESTION: What is the effect of dual-task testing on the spatial-temporal gait parameters and cognitive performance of people with AD experienced with a 4-wheeled walker?

METHODS: Twenty-three adults with mild to moderate AD (87.4 ± 6.2 years, 48 % female) and at least 6 months of walker use experience …

Amylin As A Potential Link Between Type 2 Diabetes And Alzheimer Disease, Florin Despa, Larry B. Goldstein, Geert Jan Biessels

Pharmacology and Nutritional Sciences Faculty Publications

No abstract provided.

Polr1b And Neural Crest Cell Anomalies In Treacher Collins Syndrome Type 4, Elodie Sanchez, Tomi L Toler, Walton Nephi, Marcia Willing, Et Al.

2020-Current year OA Pubs

PURPOSE: Treacher Collins syndrome (TCS) is a rare autosomal dominant mandibulofacial dysostosis, with a prevalence of 0.2-1/10,000. Features include bilateral and symmetrical malar and mandibular hypoplasia and facial abnormalities due to abnormal neural crest cell (NCC) migration and differentiation. To date, three genes have been identified: TCOF1, POLR1C, and POLR1D. Despite a large number of patients with a molecular diagnosis, some remain without a known genetic anomaly.

METHODS: We performed exome sequencing for four individuals with TCS but who were negative for pathogenic variants in the known causative genes. The effect of the pathogenic variants was investigated in zebrafish.

RESULTS: …

Correction Of Respiratory Artifacts In Mri Head Motion Estimates, Damien A. Fair, Abraham Z. Snyder, Andrew N. Van, Jonathan M. Koller, Amy E. Mirro, Jacqueline M Hampton, Babatunde Adeyemo, Timothy O. Laumann, Deanna J. Greene, Deann M. Barch, Steven E. Petersen, Nico U. F. Dosenbach, Et Al.

2020-Current year OA Pubs

Head motion represents one of the greatest technical obstacles in magnetic resonance imaging (MRI) of the human brain. Accurate detection of artifacts induced by head motion requires precise estimation of movement. However, head motion estimates may be corrupted by artifacts due to magnetic main field fluctuations generated by body motion. In the current report, we examine head motion estimation in multiband resting state functional connectivity MRI (rs-fcMRI) data from the Adolescent Brain and Cognitive Development (ABCD) Study and comparison 'single-shot' datasets. We show that respirations contaminate movement estimates in functional MRI and that respiration generates apparent head motion not associated …

2019 Hrs/Ehra/Aphrs/Lahrs Expert Consensus Statement On Catheter Ablation Of Ventricular Arrhythmias: Executive Summary, Edmond M Cronin, Phillip Cuculich, Et Al.

2020-Current year OA Pubs

Ventricular arrhythmias are an important cause of morbidity and mortality and come in a variety of forms, from single premature ventricular complexes to sustained ventricular tachycardia and fibrillation. Rapid developments have taken place over the past decade in our understanding of these arrhythmias and in our ability to diagnose and treat them. The field of catheter ablation has progressed with the development of new methods and tools, and with the publication of large clinical trials. Therefore, global cardiac electrophysiology professional societies undertook to outline recommendations and best practices for these procedures in a document that will update and replace the …

Targeted Therapy For Advanced Salivary Gland Carcinoma Based On Molecular Profiling: Results From Mypathway, A Phase Iia Multiple Basket Study, R Kurzrock, D W Bowles, H Kang, F Meric-Bernstam, J Hainsworth, D R Spigel, R Bose, H Burris, C J Sweeney, M S Beattie, S Blotner, K Schulze, V Cuchelkar, C Swanton

2020-Current year OA Pubs

BACKGROUND: Systemic therapy options for salivary cancers are limited. MyPathway (NCT02091141), a phase IIa study, evaluates targeted therapies in non-indicated tumor types with actionable molecular alterations. Here, we present the efficacy and safety results for a subgroup of MyPathway patients with advanced salivary gland cancer (SGC) matched to targeted therapies based on tumor molecular characteristics.

PATIENTS AND METHODS: MyPathway is an ongoing, multiple basket, open-label, non-randomized, multi-center study. Patients with advanced SGC received pertuzumab + trastuzumab (HER2 alteration), vismodegib (PTCH-1/SMO mutation), vemurafenib (BRAF V600 mutation), or atezolizumab [high tumor mutational burden (TMB)]. The primary endpoint is the objective response rate …

Deep Learning In Clinical Natural Language Processing: A Methodical Review, Stephen Wu, Kirk Roberts, Surabhi Datta, Jingcheng Du, Zongcheng Ji, Yuqi Si, Sarvesh Soni, Qiong Wang, Qiang Wei, Yang Xiang, Bo Zhao, Hua Xu

Faculty, Staff and Student Publications

OBJECTIVE: This article methodically reviews the literature on deep learning (DL) for natural language processing (NLP) in the clinical domain, providing quantitative analysis to answer 3 research questions concerning methods, scope, and context of current research.

MATERIALS AND METHODS: We searched MEDLINE, EMBASE, Scopus, the Association for Computing Machinery Digital Library, and the Association for Computational Linguistics Anthology for articles using DL-based approaches to NLP problems in electronic health records. After screening 1,737 articles, we collected data on 25 variables across 212 papers.

RESULTS: DL in clinical NLP publications more than doubled each year, through 2018. Recurrent neural networks (60.8%) …

Bone Marrow Concentrate (Bmc) Therapy In Musculoskeletal Disorders: Evidence-Based Policy Position Statement Of American Society Of Interventional Pain Physicians (Asipp), Laxmaiah Manchikanti, Christopher J. Centeno, Sairam Atluri, Sheri L. Albers, Shane Shapiro, Gerard A. Malanga, Alaa Abd-Elsayed, Mairin Jerome, Joshua A. Hirsch, Alan David Kaye, Steve M. Aydin, Douglas Beall, Don Buford, Joanne Borg-Stein, Ricardo M. Buenaventura, Joseph A. Cabaret, Aaron K. Calodney, Kenneth D. Candido, Cameron Cartier, Richard Latchaw, Sudhir Diwan, Ehren Dodson, Zachary Fausel, Michael Fredericson, Christopher G. Gharibo, Mayank Gupta, Adam M. Kaye, Nebojsa Nick Knezevic, Radomir Kosanovic, Matthew Lucas, Maanasa V. Manchikanti, R. Amadeus Mason, Kenneth Mautner, Samuel Murala, Annu Navani, Vidyasagar Pampati, Sarah Pastoriza, Ramarao Pasupuleti, Cyril Philip, Mahendra R Sanapati, Theodore Sand, Rinoo V Shah, Amol Soin, Ian Stemper, Bradley W Wargo, Philippe Hernigou

School of Pharmacy Faculty Articles

BACKGROUND: The use of bone marrow concentrate (BMC) for treatment of musculoskeletal disorders has become increasingly popular over the last several years, as technology has improved along with the need for better solutions for these pathologies. The use of cellular tissue raises a number of issues regarding the US Food and Drug Administration's (FDA) regulation in classifying these treatments as a drug versus just autologous tissue transplantation. In the case of BMC in musculoskeletal and spine care, this determination will likely hinge on whether BMC is homologous to the musculoskeletal system and spine.

OBJECTIVES: The aim of this review is …

Cost-Effectiveness Analysis Of Ocriplasmin Versus Watchful Waiting For Treatment Of Symptomatic Vitreomacular Adhesion In The Us, Arshad M Khanani, Pravin U Dugel, Julia A Haller, Alan L Wagner, Benedicte Lescrauwaet, Ralph Schmidt, Craig Bennison

Wills Eye Hospital Papers

Aim: Evaluate the cost-effectiveness of ocriplasmin in symptomatic vitreomacular adhesion (VMA) with or without full-thickness macular hole ≤400 μm versus standard of care.

Methods: A state-transition model simulated a cohort through disease health states; assignment of utilities to health states reflected the distribution of visual acuity. Efficacy of ocriplasmin was derived from logistic regression models using Ocriplasmin for Treatment for Symptomatic Vitreomacular Adhesion Including Macular Hole trial data. Model inputs were extracted from Phase III trials and published literature. The analysis was conducted from a US Medicare perspective.

Results: Lifetime incremental cost-effectiveness ratio was US$4887 per quality-adjusted life year gained …

Evidence For Gene-Smoking Interactions For Hearing Loss And Deafness In Japanese American Families, Jia Y Wan, Christina Cataby, Andrew Liem, Emily Jeffrey, Trina M Norden-Krichmar, Deborah Goodman, Stephanie A Santorico, Karen L Edwards

Faculty, Staff and Student Publications

BACKGROUND: This study investigated the relationship between smoking and hearing loss and deafness (HLD) and whether the relationship is modified by genetic variation. Data for these analyses was from the subset of Japanese American families collected as part of the American Diabetes Association Genetics of Non-insulin Dependent Diabetes Mellitus study. Logistic regression with generalized estimating equations assessed the relationship between HLD and smoking. Nonparametric linkage analysis identified genetic regions harboring HLD susceptibility genes and ordered subset analysis was used to identify regions showing evidence for gene-smoking interactions. Genetic variants within these candidate regions were then each tested for interaction with …

Examining Measurement Reactivity In Daily Diary Data On Substance Use: Results From A Randomized Experiment, Anne Buu, Songshan Yang, Runze Li, Marc A Zimmerman, Rebecca M Cunningham, Maureen A Walton

Faculty, Staff and Student Publications

The debate about whether measurement reactivity exists in daily diary research on substance use is still unsettled due to the issues of study design and statistical methodology. This study proposes a time-varying effect model (TVEM) that characterizes the trajectory of substance use behaviors with nonparametric functions determined by the data rather than imposes presumed parametric functions. It also allows researchers to investigate the effect of measurement reactivity on not only the likelihood of using substances but also the amount of substance use. The TVEM was applied to analyze diary data on alcohol and marijuana use collected from an experiment, which …

Coaction Between Physical Activity And Fruit And Vegetable Intake In Racially Diverse, Obese Adults, Natalia I Heredia, Maria E Fernandez, Alexandra E Van Den Berg, Casey P Durand, Harold W Kohl, Belinda M Reininger, Kevin O Hwang, Lorna H Mcneill

Faculty, Staff and Student Publications

PURPOSE: There is minimal understanding of the potential for coaction, defined as action on one behavior increasing the likelihood of taking action on another behavior, between physical activity (PA) and fruit and vegetable (FV) intake. The purpose of this study was to assess the bidirectional coaction between FV intake and PA, as well as self-efficacy for these behaviors, in a racially diverse sample of obese adults.

DESIGN: This is a secondary analysis using data collected from the Path to Health study, a randomized controlled trial. ClinicalTrials.gov Identifier: NCT03674229.

SAMPLE: Obese adults who completed baseline and 6-month follow-up assessments.

MEASURES: For …

Fibrin Clots Maintain The Viability And Proliferative Capacity Of Human Mesenchymal Stem Cells: An In Vitro Study, Ryan J Warth, Paul G Shupe, Xueqin Gao, Mohammad Syed, Walter R Lowe, Johnny Huard, Christopher D Harner

Faculty, Staff and Student Publications

BACKGROUND: Augmentation of soft-tissue repairs with an autologous fibrin clot has been used clinically for nearly four decades; however, fibrin clots tend to produce an abundance of scar tissue, which is known to inhibit soft-tissue regeneration. Mesenchymal stem cells (MSCs) embedded in fibrin clots before repair could reduce scar tissue deposition and facilitate soft-tissue regeneration. To our knowledge, no published studies have directly evaluated the viability or bioactivity of MSCs in fresh human fibrin clots over time. The purpose of this study was to evaluate the viability and bioactivity of human MSCs inside human fibrin clots over time in nutritive …

Staged Laser Interstitial Thermal Therapy (Litt) Treatments To Left Insular Low-Grade Glioma, Daniel M. Hafez, Caroline Liekweg, Eric C. Leuthardt

2020-Current year OA Pubs

BACKGROUND AND IMPORTANCE: Low-grade insular gliomas remain challenging tumors for aggressive resection because of the numerous functional and vascular structures surrounding them. Because of the potential morbidities associated with open surgical resection, less invasive techniques may confer a more optimal balance between cytoreduction and surgical complications. For this reason, we evaluated the use of laser interstitial thermal therapy (LITT) for resection of a dominant hemisphere oligodendroglioma World Health Organization (WHO) grade II in a 68-yr-old patient by use of multiple staged surgeries for its resection.

CLINICAL PRESENTATION: Patient KK was a 68-yr-old female who was found to have a large, …

Temporal Trends And Geographic Variations In Mortality Rates From Prescription Opioids: Lessons From Florida And West Virginia, Sarah A Palumbo, Charles H Hennekens, Janet D Robishaw, Robert S Levine

Faculty, Staff and Students Publications

OBJECTIVES: To explore temporal trends and geographic variations in mortality from prescription opioids from 1999 to 2016.

METHODS: Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research Multiple Cause of Death files were used to calculate age-adjusted rates and 95% confidence intervals (CIs) and create spatial cluster maps.

RESULTS: From 1999 to 2016, counties in West Virginia experienced the highest overall mortality rates in the United States from prescription opioids. Specifically, from 1999 to 2004, the highest rate in West Virginia of 24.87/100,000 (95% CI 17.84-33.73) was the fourth highest in the United States. From 2005 to …

Probable African Tick Bite Fever In The United States, Kami Lowery, Theodore Rosen

Faculty, Staff and Students Publications

African tick bite fever (ATBF) is a tick-borne rickettsial disease most often observed in North American and European tourists returning home from the southern portion of Africa. Ticks infected with Rickettsia africae transmit this parasitic bacterium to humans, who subsequently develop an influenza-like illness, one or more inoculation eschars, and in some cases, a cutaneous rash. Because ATBF often presents with non-specific symptoms that suggest other infectious diseases, establishing the diagnosis may be difficult. Confirmatory assays, including serology and nucleic acid amplification, may take weeks to return and cannot help with acute treatment decisions. We present a case of a …

Mail-Back Envelopes For Retrieval Of Opioids After Pediatric Surgery, Adam C Adler, Ammar N Yamani, Caitlin D Sutton, Danielle M Guffey, Arvind Chandrakantan

Faculty, Staff and Students Publications

BACKGROUND: Opioid overprescription has the potential to lead to harmful medications remaining in homes and to a rise in accidental or deliberate ingestion by children and adolescents. Although methods for opioid disposal are available, many are costly or require greater than minimal effort for the patient. In this study, we used a mail-back return envelope to retrieve unused opioids after ambulatory pediatric surgery.

METHODS: This feasibility study was performed to assess the rate of opioid return by using a mail-back envelope for children ages 0 to 18 prescribed opioids after outpatient surgery. Participants were provided a return envelope as well …

The Impact Of Diabetic Foot Ulcers And Unilateral Offloading Footwear On Gait In People With Diabetes, Erica Ling, Brian Lepow, He Zhou, Ana Enriquez, Ashley Mullen, Bijan Najafi

Faculty, Staff and Students Publications

BACKGROUND: Unilateral offloading footwear prescribed to patients with diabetic foot ulcers elevates one limb relative to the other, which may lead to limp and abnormal gait. This study investigated whether the unilateral foot ulcer and offloading combination negatively impacts gait function beyond diabetic peripheral neuropathy.

METHODS: Eighty-six participants were recruited in 3 groups: 12 with diabetic peripheral neuropathy and unilateral foot ulcers wearing offloading footwear (offloading group, age = 55.6 ± 9.5 years, BMI = 30.9 ± 4.5 kg/m

FINDINGS: The offloading group exhibited deteriorated gait function compared to the non-diabetic group (p < 0.005, Cohen's effect size d = 0.90-2.61). They also had decreased gait speed (p < 0.001, d = 1.79) and stride length (p < 0.001, d = 1.76), as well as increased gait cycle time (p < 0.001, d = 1.67) and limp (p < 0.050, d = 0.72-1.49) compared to the neuropathy group. The offloading group showed increased gait unsteadiness compared to the neuropathy group, but the difference did not reach statistical significance in our samples.

INTERPRETATION: This study demonstrated that while diabetic …

Methyl-Sensing Nuclear Receptor Liver Receptor Homolog-1 Regulates Mitochondrial Function In Mouse Hepatocytes, Sungwoo Choi, Bingning Dong, Chih-Chun Janet Lin, Mi Jeong Heo, Kang Ho Kim, Zhen Sun, Martin Wagner, Nagireddy Putluri, Jae Myoung Suh, Meng C Wang, David D Moore

Faculty, Staff and Students Publications

Liver receptor homologue-1 (LRH-1; NR5A2) is a nuclear receptor that regulates metabolic homeostasis in the liver. Previous studies identified phosphatidylcholines as potential endogenous agonist ligands for LRH-1. In the liver, distinct subsets of phosphatidylcholine species are generated by two different pathways: choline addition to phosphatidic acid via the Kennedy pathway, or trimethylation of phosphatidylethanolamine via Phosphatidylethanolamine N-methyl Transferase (PEMT). Here we report that a PEMT - LRH-1 pathway specifically couples methyl metabolism and mitochondrial activities in hepatocytes. We show that the loss of Lrh-1 reduces mitochondrial number, basal respiration, beta-oxidation and ATP production in hepatocytes, and decreases expression of mitochondrial …

Orthostatic Hypotension, Cardiovascular Outcomes, And Adverse Events: Results From Sprint, Stephen P Juraschek, Addison A Taylor, Jackson T Wright, Gregory W Evans, Edgar R Miller, Timothy B Plante, William C Cushman, Tanya R Gure, William E Haley, Imran Moinuddin, John Nord, Suzanne Oparil, Carolyn Pedley, Christianne L Roumie, Jeff Whittle, Alan Wiggers, Ciarán Finucane, Rose Anne Kenny, Lawrence J Appel, Raymond R Townsend

Faculty, Staff and Students Publications

Orthostatic hypotension (OH) is frequently observed with hypertension treatment, but its contribution to adverse outcomes is unknown. The Systolic Blood Pressure Intervention Trial (SPRINT) was a randomized trial of adults, age ≥50years at high risk for cardiovascular disease (CVD) with a seated systolic BP (SBP) of 130–180 mmHg and a standing SBP ≥110 mmHg. Participants were randomized to a SBP treatment goal of either <120 mmHg or <140 mmHg. OH was defined as a drop in SBP≥20 or diastolic BP ≥10 mmHg one minute after standing from a seated position. We used Cox models to examine the association of OH with CVD or adverse study events by randomized BP goal. During the follow-up period (median 3years), there were 1,170 (5.7%) instances of OH among those assigned a standard BP goal, and 1,057 (5.0%) among those assigned the intensive BP goal. OH was not associated with higher risk of CVD events (primary outcome: HR 1.06; 95%CI: 0.78,1.44). Moreover, OH was not associated with syncope, electrolyte abnormalities, injurious falls, or acute renal failure. OH was associated with hypotension-related hospitalizations or emergency department visits (HR 1.77; 1.11,2.82) and bradycardia (HR 1.94; 1.19,3.15), but these associations did not differ by BP treatment goal. OH was not associated with a higher risk of CVD events and BP treatment goal had no effect on OH’s association with hypotension and bradycardia. Symptomless OH during hypertension treatment should not be viewed as a reason to down-titrate therapy even in the setting of a lower BP goal.

Characterization Of Urinary Concentrations Of Heavy Metals Among Socioeconomically Disadvantaged Black Pregnant Women, Inkyu Han, Kristina W Whitworth, Xueying Zhang, Masoud Afshar, Pamela D Berens, Elaine Symanski

Faculty, Staff and Student Publications

The objective of this study was to characterize exposures to metals using biological samples collected on socioeconomically disadvantaged black pregnant women. We obtained 131 anonymous urine samples provided by black pregnant women visiting a Medicaid-serving prenatal clinic in Houston, TX, from March 27, 2017 to April 11, 2017. We analyzed urine samples for 15 metals including cadmium (Cd), arsenic (As), lead (Pb), and nickel (Ni) and for creatinine and cotinine. We found that median concentrations of zinc (Zn), selenium (Se), and aluminum (Al) among black pregnant women in this study were 1.5 to 3 times higher than levels reported among …

Simulation-Based Mastery Learning Compared To Standard Education For Discussing Diagnostic Uncertainty With Patients In The Emergency Department: A Randomized Controlled Trial., Danielle M. Mccarthy, Rhea E. Powell, Kenzie A. Cameron, David H. Salzman, Dimitrios Papanagnou, Amanda Doty, Benjamin E. Leiby, Katherine Piserchia, Matthew R. Klein, Xiao C. Zhang, William C. Mcgaghie, Kristin L. Rising

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: Diagnostic uncertainty occurs frequently in emergency medical care, with more than one-third of patients leaving the emergency department (ED) without a clear diagnosis. Despite this frequency, ED providers are not adequately trained on how to discuss diagnostic uncertainty with these patients, who often leave the ED confused and concerned. To address this training need, we developed the Uncertainty Communication Education Module (UCEM) to teach physicians how to discuss diagnostic uncertainty. The purpose of the study is to evaluate the effectiveness of the UCEM in improving physician communications.

METHODS: The trial is a multicenter, two-arm randomized controlled trial designed to …

Development Of An Abbreviated Symptom Score For The Neonatal Abstinence Syndrome., I. Chervoneva, S. C. Adeniyi-Jones, F. Blanco, W. K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

OBJECTIVE: We sought a shortened MOTHER neonatal abstinence syndrome (NAS) and Finnegan score that would retain comparable performance characteristics of the full instrument.

STUDY DESIGN: Retrospective cohort.

RESULTS: In total, 124,170 MOTHER NAS scores between August 2007 and May 2016 from 775 infants (≥36 weeks) were examined. Classification and regression tree model identified the most important subsets of the scored variables. A 9-element shortened scale yielded >90% sensitivity and specificity to predict clinical endpoints based on the full 19-element MOTHER NAS score. Conversion of the data sets to the Finnegan score, and applying the same procedure resulted in a nine-element …

Immune Checkpoint Modulation Enhances Hiv-1 Antibody Induction., Todd Bradley, Masayuki Kuraoka, Chen-Hao Yeh, Ming Tian, Huan Chen, Derek W Cain, Xuejun Chen, Cheng Cheng, Ali H Ellebedy, Robert Parks, Maggie Barr, Laura L. Sutherland, Richard M. Scearce, Cindy M. Bowman, Hilary Bouton-Verville, Sampa Santra, Kevin Wiehe, Mark G. Lewis, Ane Ogbe, Persephone Borrow, David Montefiori, Mattia Bonsignori, M Anthony Moody, Laurent Verkoczy, Kevin O. Saunders, Rafi Ahmed, John R. Mascola, Garnett Kelsoe, Frederick W. Alt, Barton F. Haynes

Manuscripts, Articles, Book Chapters and Other Papers

Eliciting protective titers of HIV-1 broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development, but current vaccine strategies have yet to induce bnAbs in humans. Many bnAbs isolated from HIV-1-infected individuals are encoded by immunoglobulin gene rearrangments with infrequent naive B cell precursors and with unusual genetic features that may be subject to host regulatory control. Here, we administer antibodies targeting immune cell regulatory receptors CTLA-4, PD-1 or OX40 along with HIV envelope (Env) vaccines to rhesus macaques and bnAb immunoglobulin knock-in (KI) mice expressing diverse precursors of CD4 binding site HIV-1 bnAbs. CTLA-4 blockade augments HIV-1 Env …

Comparison Of Microneutralization And Histo-Blood Group Antigen-Blocking Assays For Functional Norovirus Antibody Detection, Robert L Atmar, Khalil Ettayebi, B Vijayalakshmi Ayyar, Frederick H Neill, Ralph P Braun, Sasirekha Ramani, Mary K Estes

Faculty, Staff and Students Publications

BACKGROUND: The development of an in vitro cultivation system for human noroviruses allows the measurement of neutralizing antibody levels.

METHODS: Serum neutralizing antibody levels were determined using a GII.4/Sydney/2012-like virus in human intestinal enteroids in samples collected before and 4 weeks after administration of an investigational norovirus vaccine and were compared with those measured in histo-blood group antigen (HBGA)-blocking assays.

RESULTS: Neutralizing antibody seroresponses were observed in 71% of 24 vaccinated adults, and antibody levels were highly correlated (r = 0.82, P < .001) with those measured by HBGA blocking.

CONCLUSIONS: HBGA-blocking antibodies are a surrogate for neutralization in human noroviruses.