Digital Commons Network^™

Vesicular Stomatitis Virus Chimeras Expressing The Oropouche Virus Glycoproteins Elicit Protective Immune Responses In Mice, Sarah Hulsey Stubbs, Marjorie Cornejo Pontelli, Nischay Mishra, Changhong Zhou, Juliano De Paula Souza, Rosa Maria Mendes Viana, W Ian Lipkin, David M Knipe, Eurico Arruda, Sean P J Whelan

Open Access Publications

Oropouche virus (OROV) infection of humans is associated with a debilitating febrile illness that can progress to meningitis or encephalitis. First isolated from a forest worker in Trinidad and Tobago in 1955, the arbovirus OROV has since been detected throughout the Amazon basin with an estimated 500,000 human infections over 60 years. Like other members of the family

Atypical Idiopathic Intracranial Hypertension Presenting As Cyclic Vomiting Syndrome: A Case Report, Nafee T Talukder, Amanda H Clorfeine, Moira K Black, Shade B Moody

Faculty, Staff and Student Publications

BACKGROUND: Idiopathic intracranial hypertension is a disorder of increased intracranial pressure in the absence of cerebrospinal outflow obstruction, mass lesion, or other underlying cause. It is a rare phenomenon in prepubertal children and is most typically found in women of childbearing age. The classic presentation consists of headaches, nausea, vomiting, and visual changes; however, children present more atypically. We report a case of idiopathic intracranial hypertension in an otherwise healthy, 4-year-old child with atypical symptoms resembling those of cyclic vomiting syndrome.

CASE PRESENTATION: A 4-year-old Caucasian, otherwise healthy, male child presented to our emergency department with episodic intermittent early-morning vomiting …

Whole-Genome Association Analyses Of Sleep-Disordered Breathing Phenotypes In The Nhlbi Topmed Program, Brian E Cade, Jiwon Lee, Tamar Sofer, Heming Wang, Man Zhang, Han Chen, Sina A Gharib, Daniel J Gottlieb, Xiuqing Guo, Jacqueline M Lane, Jingjing Liang, Xihong Lin, Hao Mei, Sanjay R Patel, Shaun M Purcell, Richa Saxena, Neomi A Shah, Daniel S Evans, Craig L Hanis, David R Hillman, Sutapa Mukherjee, Lyle J Palmer, Katie L Stone, Gregory J Tranah, Gonçalo R Abecasis, Eric A Boerwinkle, Adolfo Correa, L Adrienne Cupples, Robert C Kaplan, Deborah A Nickerson, Kari E North, Bruce M Psaty, Jerome I Rotter, Stephen S Rich, Russell P Tracy, Ramachandran S Vasan, James G Wilson, Xiaofeng Zhu, Susan Redline

Faculty, Staff and Student Publications

BACKGROUND: Sleep-disordered breathing is a common disorder associated with significant morbidity. The genetic architecture of sleep-disordered breathing remains poorly understood. Through the NHLBI Trans-Omics for Precision Medicine (TOPMed) program, we performed the first whole-genome sequence analysis of sleep-disordered breathing.

METHODS: The study sample was comprised of 7988 individuals of diverse ancestry. Common-variant and pathway analyses included an additional 13,257 individuals. We examined five complementary traits describing different aspects of sleep-disordered breathing: the apnea-hypopnea index, average oxyhemoglobin desaturation per event, average and minimum oxyhemoglobin saturation across the sleep episode, and the percentage of sleep with oxyhemoglobin saturation < 90%. We adjusted for age, sex, BMI, study, and family structure using MMSKAT and EMMAX mixed linear model approaches. Additional bioinformatics analyses were performed with MetaXcan, GIGSEA, and ReMap.

RESULTS: We identified a …

Progression Of Sars-Cov-2 Seroprevalence In St. Louis, Missouri, Through January 2021, Brittany K Smith, Andrew B Janowski, Arim C Fremont, Lucas J Adams, Ya-Nan Dai, Christopher W Farnsworth, Ann M Gronowski, Stephen M Roper, David Wang, Daved H Fremont

Open Access Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seropositivity was assessed for 3,066 individuals visiting hospitals in St. Louis, Missouri, during July 2020, November 2020, or January 2021. Seropositivity in children increased from 5.22% in July to 21.16% in January. In the same time frame, seropositivity among adults increased from 4.52% to 19.03%, prior to initiation of mass vaccination.

Comprehensive Characterization Of 536 Patient-Derived Xenograft Models Prioritizes Candidatesfor Targeted Treatment., Hua Sun, Song Cao, R Jay Mashl, Chia-Kuei Mo, Simone Zaccaria, Michael C Wendl, Sherri R Davies, Matthew H Bailey, Tina M Primeau, Jeremy Hoog, Jacqueline L Mudd, Dennis A Dean, Rajesh Patidar, Li Chen, Matthew A Wyczalkowski, Reyka G Jayasinghe, Fernanda Martins Rodrigues, Nadezhda V Terekhanova, Yize Li, Kian-Huat Lim, Andrea Wang-Gillam, Brian A Van Tine, Cynthia X Ma, Rebecca Aft, Katherine C Fuh, Julie K Schwarz, Jose P Zevallos, Sidharth V Puram, John F Dipersio, Nci Pdxnet Consortium, Brandi Davis-Dusenbery, Matthew J Ellis, Michael T Lewis, Michael A Davies, Meenhard Herlyn, Bingliang Fang, Jack A Roth, Alana L Welm, Bryan E Welm, Funda Meric-Bernstam, Feng Chen, Ryan C Fields, Shunqiang Li, Ramaswamy Govindan, James H Doroshow, Jeffrey A Moscow, Yvonne A Evrard, Jeffrey Chuang, Benjamin J Raphael, Li Ding, Carol J Bult, Peter N Robinson

Faculty Research 2021

Development of candidate cancer treatments is a resource-intensive process, with the research community continuing to investigate options beyond static genomic characterization. Toward this goal, we have established the genomic landscapes of 536 patient-derived xenograft (PDX) models across 25 cancer types, together with mutation, copy number, fusion, transcriptomic profiles, and NCI-MATCH arms. Compared with human tumors, PDXs typically have higher purity and fit to investigate dynamic driver events and molecular properties via multiple time points from same case PDXs. Here, we report on dynamic genomic landscapes and pharmacogenomic associations, including associations between activating oncogenic events and drugs, correlations between whole-genome duplications …

Rheumatic Heart Disease In The United States: Forgotten But Not Gone: Results Of A 10 Year Multicenter Review., Sarah R De Loizaga, Lindsay Arthur, Bhawna Arya, Brian Beckman, Wubishet Belay, Cole Brokamp, Nak Hyun Choi, Sean Connolly, Soham Dasgupta, Tavenner Dibert, Marylou M Dryer, Lakshmi R Gokanapudy Hahn, Elizabeth Anne Greene, Daphney Kernizan, Omar Khalid, Jennifer Klein, Ryan Kobayashi, Subhrajit Lahiri, Raymond P Lorenzoni, Andrea Otero Luna, Jennifer Marshall, Theodore Millette, Lily Moore, Babu Muhamed, Meghna Murali, Kinjal Parikh, Amy Sanyahumbi, Divya Shakti, Elizabeth Stein, Sanket Shah, Hannah Wilkins, Mcallister Windom, Scott Wirth, Meghan Zimmerman, Andrew F Beck, Nicholas Ollberding, Craig Sable, Andrea Beaton

Pediatrics Research and Scholarship

Background Recent evaluation of rheumatic heart disease (RHD) mortality demonstrates disproportionate disease burden within the United States. However, there are few contemporary data on US children living with acute rheumatic fever (ARF) and RHD. Methods and Results Twenty-two US pediatric institutions participated in a 10-year review (2008-2018) of electronic medical records and echocardiographic databases of children 4 to 17 years diagnosed with ARF/RHD to determine demographics, diagnosis, and management. Geocoding was used to determine a census tract-based socioeconomic deprivation index. Descriptive statistics of patient characteristics and regression analysis of RHD classification, disease severity, and initial antibiotic prescription according to community …

Favorable Outcomes With Reduced Steroid Use In Juvenile Dermatomyositis, Amir B Orandi, Lampros Fotis, Jamie Lai, Hallie Morris, Andrew J White, Anthony R French, Kevin W Baszis

2020-Current year OA Pubs

BACKGROUND: High-intensity glucocorticoid regimens are commonly used to induce and maintain remission in Juvenile Dermatomyositis but are associated with several adverse side-effects. Evidence-based treatment guidelines from North American and European pediatric rheumatology research societies both advocate induction with intravenous pulse steroids followed by high dose oral steroids (2 mg/kg/day), which are then tapered. This study reports the time to disease control with reduced glucocorticoid dosing.

METHODS: We retrospectively reviewed the records at a single tertiary-care children's hospital of patients diagnosed with Juvenile Dermatomyositis between 2000 and 2014 who had a minimum of 2 years of follow-up. The primary outcome measure …

Differential Classification Of States Of Consciousness Using Envelope- And Phase-Based Functional Connectivity, Catherine Duclos, Michael S Avidan, Et Al.

2020-Current year OA Pubs

The development of sophisticated computational tools to quantify changes in the brain's oscillatory dynamics across states of consciousness have included both envelope- and phase-based measures of functional connectivity (FC), but there are very few direct comparisons of these techniques using the same dataset. The goal of this study was to compare an envelope-based (i.e. Amplitude Envelope Correlation, AEC) and a phase-based (i.e. weighted Phase Lag Index, wPLI) measure of FC in their classification of states of consciousness. Nine healthy participants underwent a three-hour experimental anesthetic protocol with propofol induction and isoflurane maintenance, in which five minutes of 128-channel electroencephalography were …

Daily Energy Expenditure Through The Human Life Course, Herman Pontzer, Yosuke Yamada, Hiroyuki Sagayama, Philip N Ainslie, Lene F Andersen, Liam J Anderson, Lenore Arab, Issaad Baddou, Kweku Bedu-Addo, Ellen E Blaak, Stephane Blanc, Alberto G Bonomi, Carlijn V C Bouten, Pascal Bovet, Maciej S Buchowski, Nancy F Butte, Stefan G Camps, Graeme L Close, Jamie A Cooper, Richard Cooper, Sai Krupa Das, Lara R Dugas, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Annelies H Goris, Michael Gurven, Catherine Hambly, Asmaa El Hamdouchi, Marjije B Hoos, Sumei Hu, Noorjehan Joonas, Annemiek M Joosen, Peter Katzmarzyk, Kitty P Kempen, Misaka Kimura, William E Kraus, Robert F Kushner, Estelle V Lambert, William R Leonard, Nader Lessan, Corby Martin, Anine C Medin, Erwin P Meijer, James C Morehen, James P Morton, Marian L Neuhouser, Teresa A Nicklas, Robert M Ojiambo, Kirsi H Pietiläinen, Yannis P Pitsiladis, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Roberto A Rabinovich, Susan B Racette, David A Raichlen, Eric Ravussin, Rebecca M Reynolds, Susan B Roberts, Albertine J Schuit, Anders M Sjödin, Eric Stice, Samuel S Urlacher, Giulio Valenti, Ludo M Van Etten, Edgar A Van Mil, Jonathan C K Wells, George Wilson, Brian M Wood, Jack Yanovski, Tsukasa Yoshida, Xueying Zhang, Alexia J Murphy-Alford, Cornelia Loechl, Amy H Luke, Jennifer Rood, Dale A Schoeller, Klaas R Westerterp, William W Wong, John R Speakman

Children’s Nutrition Research Center Staff Publications

Total daily energy expenditure (“total expenditure”, MJ/d) reflects daily energy needs and is a critical variable in human health and physiology, yet it is unclear how daily expenditure changes over the life course. Here, we analyze a large, globally diverse database of total expenditure measured by the doubly labeled water method for males and females aged 8 days to 95 yr. We show that total expenditure is strongly related to fat free mass in a power-law manner and identify four distinct metabolic life stages. Fat free mass-adjusted daily expenditure accelerates rapidly in neonates (0-1yr) to ~46% above adult values at …

Longitudinal Assessment Of Cytokine Expression And Plasminogen Activation In Hantavirus Cardiopulmonary Syndrome Reveals Immune Regulatory Dysfunction In End-Stage Disease, Peter Simons, Yan Guo, Virginie Bondu, Susan L. Tigert, Michelle Harkins, Samuel Goodfellow, Cana Tompkins, Devon Chabot-Richards, Xuexian O. Yang, Laura Gonzalez Bosc, Steven Bradfute, Daniel A. Lawrence, Tione Buranda

Pathology Research and Scholarship

Pathogenic New World orthohantaviruses cause hantavirus cardiopulmonary syndrome (HCPS), a severe immunopathogenic disease in humans manifested by pulmonary edema and respiratory distress, with case fatality rates approaching 40%. High levels of inflammatory mediators are present in the lungs and systemic circulation of HCPS patients. Previous studies have provided insights into the pathophysiology of HCPS. However, the longitudinal correlations of innate and adaptive immune responses and disease outcomes remain unresolved. This study analyzed serial immune responses in 13 HCPS cases due to Sin Nombre orthohantavirus (SNV), with 11 severe cases requiring extracorporeal membrane oxygenation (ECMO) treatment and two mild cases. We …

Year 1 Of The Bundled Payments For Care Improvement-Advanced Model, Karen E Joynt Maddox, E John Orav, Jie Zheng, Arnold M Epstein

Open Access Publications

BACKGROUND: The Center for Medicare and Medicaid Innovation launched the Medicare Bundled Payments for Care Improvement-Advanced (BPCI-A) program for hospitals in October 2018. Information is needed about the effects of the program on health care utilization and Medicare payments.

METHODS: We conducted a modified segmented regression analysis using Medicare claims and including patients with discharge dates from January 2017 through September 2019 to assess differences between BPCI-A participants and two control groups: hospitals that never joined the BPCI-A program (nonjoining hospitals) and hospitals that joined the BPCI-A program in January 2020, after the conclusion of the intervention period (late-joining hospitals). …

Cabotegravir For Hiv Prevention In Cisgender Men And Transgender Women, Raphael J Landovitz, Deborah Donnell, Meredith E Clement, Brett Hanscom, Leslie Cottle, Lara Coelho, Robinson Cabello, Suwat Chariyalertsak, Eileen F Dunne, Ian Frank, Jorge A Gallardo-Cartagena, Aditya H Gaur, Pedro Gonzales, Ha V Tran, Juan C Hinojosa, Esper G Kallas, Colleen F Kelley, Marcelo H Losso, J Valdez Madruga, Keren Middelkoop, Nittaya Phanuphak, Breno Santos, Omar Sued, Javier Valencia Huamaní, Edgar T Overton, Shobha Swaminathan, Carlos Del Rio, Roy M Gulick, Paul Richardson, Philip Sullivan, Estelle Piwowar-Manning, Mark Marzinke, Craig Hendrix, Maoji Li, Zhe Wang, Jeanne Marrazzo, Eric Daar, Aida Asmelash, Todd T Brown, Peter Anderson, Susan H Eshleman, Marcus Bryan, Cheryl Blanchette, Jonathan Lucas, Christina Psaros, Steven Safren, Jeremy Sugarman, Hyman Scott, Joseph J Eron, Sheldon D Fields, Nirupama D Sista, Kailazarid Gomez-Feliciano, Andrea Jennings, Ryan M Kofron, Timothy H Holtz, Katherine Shin, James F Rooney, Kimberly Y Smith, William Spreen, David Margolis, Alex Rinehart, Adeola Adeyeye, Myron S Cohen, Marybeth Mccauley, Beatriz Grinsztejn

Faculty, Staff and Student Publications

BACKGROUND: Safe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preventing HIV infection.

METHODS: We conducted a randomized, double-blind, double-dummy, noninferiority trial to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of …

Developing Methods To Detect And Diagnose Chronic Traumatic Encephalopathy During Life: Rationale, Design, And Methodology For The Diagnose Cte Research Project, Michael L Alosco, Daniel S Marcus, Et Al.

2020-Current year OA Pubs

BACKGROUND: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that has been neuropathologically diagnosed in brain donors exposed to repetitive head impacts, including boxers and American football, soccer, ice hockey, and rugby players. CTE cannot yet be diagnosed during life. In December 2015, the National Institute of Neurological Disorders and Stroke awarded a seven-year grant (U01NS093334) to fund the "Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy (DIAGNOSE CTE) Research Project." The objectives of this multicenter project are to: develop in vivo fluid and neuroimaging biomarkers for CTE; characterize its clinical presentation; refine …

Ceftolozane/Tazobactam Versus Meropenem In Patients With Ventilated Hospital-Acquired Bacterial Pneumonia: Subset Analysis Of The Aspect-Np Randomized, Controlled Phase 3 Trial, Jean-François Timsit, Jennifer A Huntington, Richard G Wunderink, Nobuaki Shime, Marin H Kollef, Ülo Kivistik, Martin Nováček, Álvaro Réa-Neto, Ignacio Martin-Loeches, Brian Yu, Erin H Jensen, Joan R Butterton, Dominik J Wolf, Elizabeth G Rhee, Christopher J Bruno

2020-Current year OA Pubs

BACKGROUND: Ceftolozane/tazobactam is approved for treatment of hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP) at double the dose approved for other infection sites. Among nosocomial pneumonia subtypes, ventilated HABP (vHABP) is associated with the lowest survival. In the ASPECT-NP randomized, controlled trial, participants with vHABP treated with ceftolozane/tazobactam had lower 28-day all-cause mortality (ACM) than those receiving meropenem. We conducted a series of post hoc analyses to explore the clinical significance of this finding.

METHODS: ASPECT-NP was a multinational, phase 3, noninferiority trial comparing ceftolozane/tazobactam with meropenem for treating vHABP and VABP; study design, efficacy, and safety results have been reported previously. The …

Adipose Tissue Hyaluronan Production Improves Systemic Glucose Homeostasis And Primes Adipocytes For Cl 316,243-Stimulated Lipolysis, Yi Zhu, Na Li, Mingyang Huang, Mason Bartels, Sophie Dogné, Shangang Zhao, Xi Chen, Clair Crewe, Leon Straub, Lavanya Vishvanath, Zhuzhen Zhang, Mengle Shao, Yongjie Yang, Christy M Gliniak, Ruth Gordillo, Gordon I Smith, William L Holland, Rana K Gupta, Bingning Dong, Nathalie Caron, Yong Xu, Yucel Akgul, Samuel Klein, Philipp E Scherer

Faculty, Staff and Students Publications

Plasma hyaluronan (HA) increases systemically in type 2 diabetes (T2D) and the HA synthesis inhibitor, 4-Methylumbelliferone, has been proposed to treat the disease. However, HA is also implicated in normal physiology. Therefore, we generated a Hyaluronan Synthase 2 transgenic mouse line, driven by a tet-response element promoter to understand the role of HA in systemic metabolism. To our surprise, adipocyte-specific overproduction of HA leads to smaller adipocytes and protects mice from high-fat-high-sucrose-diet-induced obesity and glucose intolerance. Adipocytes also have more free glycerol that can be released upon beta3 adrenergic stimulation. Improvements in glucose tolerance were not linked to increased plasma …

Simple Energy Balance Or Microbiome For Childhood Obesity Prevention?, Tom Baranowski, Kathleen J Motil

Children’s Nutrition Research Center Staff Publications

Obesity prevention interventions generally have either not worked or had effects inadequate to mitigate the problem. They have been predicated on the simple energy balance model, which has been severely questioned by biological scientists. Numerous other etiological mechanisms have been proposed, including the intestinal microbiome, which has been related to childhood obesity in numerous ways. Public health research is needed in regard to diet and the microbiome, which hopefully will lead to effective child obesity prevention.

A Noncoding Rna Modulator Potentiates Phenylalanine Metabolism In Mice, Yajuan Li, Zhi Tan, Yaohua Zhang, Zhao Zhang, Qingsong Hu, Ke Liang, Yao Jun, Youqiong Ye, Yi-Chuan Li, Chunlai Li, Lan Liao, Jianming Xu, Zhen Xing, Yinghong Pan, Sujash S Chatterjee, Tina K Nguyen, Heidi Hsiao, Sergey D Egranov, Nagireddy Putluri, Cristian Coarfa, David H Hawke, Preethi H Gunaratne, Kuang-Lei Tsai, Leng Han, Mien-Chie Hung, George A Calin, Fares Namour, Jean-Louis Guéant, Ania C Muntau, Nenad Blau, V Reid Sutton, Manuel Schiff, François Feillet, Shuxing Zhang, Chunru Lin, Liuqing Yang

Faculty, Staff and Students Publications

The functional role of long noncoding RNAs (lncRNAs) in inherited metabolic disorders, including phenylketonuria (PKU), is unknown. We demonstrated that the mouse lncRNA Pair and human HULC associate with phenylalanine hydroxylase (PAH). Pair-knockout mice exhibited excessive blood phenylalanine, musty odor, hypopigmentation, growth retardation, and progressive neurological symptoms including seizures, which faithfully models human PKU. HULC depletion led to reduced PAH enzymatic activities in human induced pluripotent stem cell (hiPSC)-differentiated hepatocytes. Mechanistically, HULC modulated the enzymatic activities of PAH by facilitating PAH-substrate and PAH-cofactor interactions. To develop a therapeutic strategy for restoring liver lncRNAs, we designed GalNAc-tagged lncRNA mimics that …

Census Tract Patterns And Contextual Social Determinants Of Health Associated With Covid-19 In A Hispanic Population From South Texas: A Spatiotemporal Perspective, Cici Bauer, Kehe Zhang, Miryoung Lee, Susan Fisher-Hoch, Esmeralda Guajardo, Joseph Mccormick, Isela De La Cerda, Maria E Fernandez, Belinda Reininger

Faculty, Staff and Student Publications

BACKGROUND: Previous studies have shown that various social determinants of health (SDOH) may have contributed to the disparities in COVID-19 incidence and mortality among minorities and underserved populations at the county or zip code level.

OBJECTIVE: This analysis was carried out at a granular spatial resolution of census tracts to explore the spatial patterns and contextual SDOH associated with COVID-19 incidence from a Hispanic population mostly consisting of a Mexican American population living in Cameron County, Texas on the border of the United States and Mexico. We performed age-stratified analysis to identify different contributing SDOH and quantify their effects by …

Family-Based Obesity Prevention Interventions Among Hispanic Children And Families: A Scoping Review, Erica G Soltero, Armando Peña, Veronica Gonzalez, Edith Hernandez, Guisela Mackey, Chishinga Callender, Jayna M Dave, Debbe Thompson

Children’s Nutrition Research Center Staff Publications

This scoping review examined intervention and sample characteristics of family-based obesity prevention interventions among Hispanic youth. This review also examined the degree to which existing interventions were culturally-adapted, acknowledged social determinants of health (SDoH), and collaborated with community stakeholders. A comprehensive search across Medline Ovid, Embase, Scopus, PsycInfo, and Pubmed was used to identify 13 studies primarily based in the U.S. (92.3%). Data was extracted by two independent reviewers. Most used a randomized control trial design (69.2%), a behavior change theory (84.6%), and reported moderate to high (≥70%) retention (69.2%). Studies targeted improvements in physical activity (69.2%) and fruit and …

"Friendly Reminder: Hi! It Is That Time Again ☺": Understanding Pmtct Care Text Message Design Preferences Amongst Pre- And Post-Partum Women And Their Male Partners., Natabhona M. Mabachi, Melinda Brown, Catherine Wexler, Kathy Goggin, May Maloba, Dama Olungae, Brad Gautney, Sarah Finocchario-Kessler

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Prevention of mother-to-child HIV transmission (PMTCT) services in Kenya can be strengthened through the delivery of relevant and culturally appropriate SMS messages.

METHODS: This study reports on the results of focus groups conducted with pre and postnatal women living with HIV (5 groups, n = 40) and their male partners (3 groups, n = 33) to elicit feedback and develop messages to support HIV+ women's adherence to ART medication, ANC appointments and a facility-based birth. The principles of message design informed message development.

RESULTS: Respondents wanted ART adherence messages that were low in verbal immediacy (ambiguous), came from an …

Beneficial Effects Of The 30-Minute Door-To-Needle Time Standard For Alteplase Administration, Suja S Rajan, Marquita Decker-Palmer, Jessica Wise, Thanh Dao, Cindy Salem, Sean I Savitz

Faculty and Staff Publications

Objective: The American Heart Association recently raised the bar on the timely treatment of acute ischemic stroke (AIS) with intravenous alteplase. Our study looks at the effectiveness of this new standard, by examining the effect of varying door-to-needle times of alteplase initiation on the clinical, quality of care, and efficiency of care outcomes.

Methods: This retrospective case-control study examined 752 AIS patients treated with intravenous alteplase in a large academic health system during 2015-2018, and compared their outcomes after treatment within 30, 45, and 60 min of arrival. The outcomes compared were: (1) clinical - discharge and 90-day modified Rankin …

Musculoskeletal Injuries In Us Air Force Security Forces, January 2009 To December 2018, Julia N Sundstrom, Bryant J Webber, George L Delclos, John R Herbold, David Gimeno Ruiz De Porras

Faculty, Staff and Student Publications

OBJECTIVE: to determine the incidence, types, and risk factors of musculoskeletal injuries in a military security forces population.

METHODS: Demographic and diagnostic data were retrieved on enlisted US Air Force security forces personnel who served on active duty between January 2009 and December 2018. Incidence rates and ratios were calculated using Poisson regression.

RESULTS: During 251,787 person-years of exposure, 62,489 personnel served on active duty. Of these, 40,771 (65.2%) were diagnosed with at least one musculoskeletal injury. The majority (60.1%) of the 164,078 unique musculoskeletal injuries were inflammation and pain secondary to overuse. After adjusting for other factors, women had …

Hypertrophic Cardiomyopathy Associated E22k Mutation In Myosin Regulatory Light Chain Decreases Calcium-Activated Tension And Stiffness And Reduces Myofilament Ca2+ Sensitivity, Jiajia Zhang, Li Wang, Katarzyna Kazmierczak, Hang Yun, Danuta Szczesna-Cordary, Masataka Kawai

Faculty, Staff and Student Publications

We investigated the mechanisms associated with E22K mutation in myosin regulatory light chain (RLC), found to cause hypertrophic cardiomyopathy (HCM) in humans and mice. Specifically, we characterized the mechanical profiles of papillary muscle fibers from transgenic mice expressing human ventricular RLC wild-type (Tg-WT) or E22K mutation (Tg-E22K). Because the two mouse models expressed different amounts of transgene, the B6SJL mouse line (NTg) was used as an additional control. Mechanical experiments were carried out on Ca

SUB-DISCIPLINE: Bioenergetics.

DATABASE: The data that support the findings of this study are available from the corresponding authors upon reasonable request.

ANIMAL PROTOCOL: BK20150353 (Soochow …

Association Of Low Center Performance Evaluations And Pediatric Heart Transplant Center Behavior In The United States, Shahnawaz Amdani, Gerard Boyle, Joseph Rossano, Janet Scheel, Marc Richmond, Susana Arrigain, Jesse D Schold

2020-Current year OA Pubs

BACKGROUND: To date, no study has evaluated the effects of low center performance evaluations (CPE) on pediatric heart transplant center behavior. We sought to assess the impact of low CPE flags on pediatric heart transplant center listing and transplant volumes and center recipient and donor characteristics.

METHODS: We included centers performing at least 10 pediatric (age <18 years) transplants during the Scientific Registry of Transplant Recipients reporting period January 2009-June 2011 and evaluated consecutive biannual program specific reports until the last reporting period January 2016-June 2018. We evaluated changes in center behavior at following time points: a year before flagging, a year and two years after the flag; and at last reporting period.

RESULTS: During our study period, 24 pediatric centers were non-flagged and 6 were flagged. Compared to non-flagged centers, there was a decline in candidate listings in flagged centers at the last reporting period (mean increase of 5.5 ± 12.4 listings vs"?> mean decrease of …

Il-7 Expands Lymphocyte Populations And Enhances Immune Responses To Sipuleucel-T In Patients With Metastatic Castration-Resistant Prostate Cancer (Mcrpc), Russell K Pachynski, Chihiro Morishima, Et Al

2020-Current year OA Pubs

BACKGROUND: Sipuleucel-T (sip-T) is a Food and Drug Administration (FDA)-approved autologous cellular immunotherapy for metastatic castration-resistant prostate cancer (mCRPC). We hypothesized that combining sip-T with interleukin (IL)-7, a homeostatic cytokine that enhances both B and T cell development and proliferation, would augment and prolong antigen-specific immune responses against both PA2024 (the immunogen for sip-T) and prostatic acid phosphatase (PAP).

METHODS: Fifty-four patients with mCRPC treated with sip-T were subsequently enrolled and randomized 1:1 into observation (n=26) or IL-7 (n=28) arms of a phase II clinical trial (NCT01881867). Recombinant human (rh) IL-7 (CYT107) was given weekly×4. Immune responses were evaluated using …

Perceptions And Challenges Experienced By African Physicians When Prescribing Methotrexate For Rheumatic Disease: An Exploratory Study, Carol A Hitchon, Girsh M Mody, Candace H Feldman, Yan Lau, Steven Shi, Michele Meltzer, Rosie Scuccimarri, Michael E Weinblatt, Ines Colmegna

Department of Medicine Faculty Papers

OBJECTIVE: Guidelines for methotrexate (MTX) use in rheumatic disease may not be feasible for physicians practicing in the least developed countries. We aimed to understand the experiences of MTX prescribers relating to MTX use for rheumatic disease in African countries to inform the development of culturally and geographically appropriate recommendations.

METHODS: African physicians who self-identified as MTX prescribers from countries classified as having a low versus a medium or high Human Development Index (L-HDI versus MH-HDI) participated in semistructured interviews between August 2016 and September 2017. Interviews were transcribed verbatim, coded thematically, and stratified by HDI.

RESULTS: Physicians (23 rheumatologists; …

Thromboelastography-Based Profiling Of Coagulation Status In Patients Undergoing Bariatric Surgery: Analysis Of 422 Patients, John C Cowling, Xu Zhang, Kulvinder S Bajwa, Ekatarina G Elliott, Melissa M Felinski, Julie Holihan, Michelle Scerbo, Brad E Snyder, Michael D Trahan, Todd D Wilson, Sharon L Courtney, Connie L Klein, Angielyn R Rivera, Erik B Wilson, Shinil K Shah, Davide Cattano

Faculty, Staff and Student Publications

Introduction/purpose: Some clinical indicators suggest hypercoagulability/hyperaggregability in patients with morbid obesity. Thromboelastography (TEG®) has been used to profile coagulation status in surgical patients. We aimed to assess coagulation profiles in patients with morbid obesity undergoing bariatric surgery by correlating demographic and patient characteristics to pre-operative TEG® values.

Materials and methods: Pre-operative TEG® values from 422 patients undergoing bariatric surgery were evaluated. TEG® results were analyzed by gender, use of medications known to alter the coagulation profile, and body mass index (BMI).

Results: Patients have a mean of 45.03 ± 11.8 years, female (76.3%), and with a mean BMI of 42 …

Metabolomics Profiling Of Patients With A-Β+ Ketosis-Prone Diabetes During Diabetic Ketoacidosis, Farook Jahoor, Jean W Hsu, Paras B Mehta, Kelly R Keene, Ruchi Gaba, Surya Narayan Mulukutla, Eunice Caducoy, W Frank Peacock, Sanjeet G Patel, Rasmus Bennet, Ake Lernmark, Ashok Balasubramanyam

Faculty, Staff and Students Publications

When stable and near-normoglycemic, patients with “A−β+” ketosis-prone diabetes (KPD) manifest accelerated leucine catabolism and blunted ketone oxidation, which may underlie their proclivity to develop diabetic ketoacidosis (DKA). To understand metabolic derangements in A−β+ KPD patients during DKA, we compared serum metabolomics profiles of adults during acute hyperglycemic crises, without (n = 21) or with (n = 74) DKA, and healthy control subjects (n = 17). Based on 65 kDa GAD islet autoantibody status, C-peptide, and clinical features, 53 DKA patients were categorized as having KPD and 21 type 1 diabetes (T1D); 21 nonketotic patients were categorized as …

Sugar-Sweetened Beverage Consumption May Modify Associations Between Genetic Variants In The Chrebp (Carbohydrate Responsive Element Binding Protein) Locus And Hdl-C (High-Density Lipoprotein Cholesterol) And Triglyceride Concentrations, Danielle E Haslam, Gina M Peloso, Melanie Guirette, Fumiaki Imamura, Traci M Bartz, Achilleas N Pitsillides, Carol A Wang, Ruifang Li-Gao, Jason M Westra, Niina Pitkänen, Kristin L Young, Mariaelisa Graff, Alexis C Wood, Kim V E Braun, Jian'an Luan, Mika Kähönen, Jessica C Kiefte-De Jong, Mohsen Ghanbari, Nathan Tintle, Rozenn N Lemaitre, Dennis O Mook-Kanamori, Kari North, Mika Helminen, Yasmin Mossavar-Rahmani, Linda Snetselaar, Lisa W Martin, Jorma S Viikari, Wendy H Oddy, Craig E Pennell, Frits R Rosendall, M Arfan Ikram, Andre G Uitterlinden, Bruce M Psaty, Dariush Mozaffarian, Jerome I Rotter, Kent D Taylor, Terho Lehtimäki, Olli T Raitakari, Kara A Livingston, Trudy Voortman, Nita G Forouhi, Nick J Wareham, Renée De Mutsert, Steven S Rich, Joann E Manson, Samia Mora, Paul M Ridker, Jordi Merino, James B Meigs, Hassan S Dashti, Daniel I Chasman, Alice H Lichtenstein, Caren E Smith, Josée Dupuis, Mark A Herman, Nicola M Mckeown

Faculty, Staff and Students Publications

BACKGROUND: ChREBP (carbohydrate responsive element binding protein) is a transcription factor that responds to sugar consumption. Sugar-sweetened beverage (SSB) consumption and genetic variants in the

METHODS: Data from 11 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (N=63 599) and the UK Biobank (N=59 220) were used to quantify associations of SSB consumption, genetic variants, and their interaction on HDL-C and triglyceride concentrations using linear regression models. A total of 1606 single nucleotide polymorphisms within or near

RESULTS: In a meta-analysis, rs71556729 was significantly associated with higher HDL-C concentrations only among the highest SSB consumers …

Comparative Effectiveness Of Sodium-Glucose Cotransporter 2 Inhibitors Vs Sulfonylureas In Patients With Type 2 Diabetes, Yan Xie, Benjamin Bowe, Andrew K Gibson, Janet B Mcgill, Geetha Maddukuri, Ziyad Al-Aly

2020-Current year OA Pubs

IMPORTANCE: In the treatment of type 2 diabetes, evidence of the comparative effectiveness of sodium-glucose cotransporter 2 (SGLT2) inhibitors vs sulfonylureas-the second most widely used antihyperglycemic class after metformin-is lacking.

OBJECTIVE: To evaluate the comparative effectiveness of SGLT2 inhibitors and sulfonylureas associated with the risk of all-cause mortality among patients with type 2 diabetes using metformin.

DESIGN, SETTING, AND PARTICIPANTS: A cohort study used data from the US Department of Veterans Affairs compared the use of SGLT2 inhibitors vs sulfonylureas in individuals receiving metformin for treatment of type 2 diabetes. A total of 23 870 individuals with new use of …