Medicine and Health Sciences Commons^™

Association Of Nt-Probnp, Blood Pressure, And Cardiovascular Events: The Aric Study, Aliza Hussain, Wensheng Sun, Anita Deswal, James A De Lemos, John W Mcevoy, Ron C Hoogeveen, Kunihiro Matsushita, David Aguilar, Biykem Bozkurt, Salim S Virani, Amil M Shah, Elizabeth Selvin, Chiadi Ndumule, Christie M Ballantyne, Vijay Nambi

Faculty, Staff and Students Publications

BACKGROUND: Although intensive blood pressure reduction has cardiovascular benefits, the absolute benefit is greater in those at higher cardiovascular disease (CVD) risk.

OBJECTIVES: This study examined whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) helps identify subjects at higher risk for CVD events across systolic blood pressure (SBP), diastolic blood pressure (DBP), or pulse pressure (PP) categories.

METHODS: Participants from the ARIC (Atherosclerosis Risk In Communities) study visit 4 (1996 to 98) were grouped according to SBP, DBP, or PP categories and further stratified by NT-proBNP categories. Cox regression models were used to estimate hazard ratios for incident CVD (coronary heart disease, …

Common Questions And Misconceptions About Creatine Supplementation: What Does The Scientific Evidence Really Show?, Jose Antonio, Darren G Candow, Scott C Forbes, Bruno Gualano, Andrew R Jagim, Richard B Kreider, Eric S Rawson, Abbie E Smith-Ryan, Trisha A Vandusseldorp, Darryn S Willoughby, Tim N Ziegenfuss

Faculty, Staff and Students Publications

Supplementing with creatine is very popular amongst athletes and exercising individuals for improving muscle mass, performance and recovery. Accumulating evidence also suggests that creatine supplementation produces a variety of beneficial effects in older and patient populations. Furthermore, evidence-based research shows that creatine supplementation is relatively well tolerated, especially at recommended dosages (i.e. 3-5 g/day or 0.1 g/kg of body mass/day). Although there are over 500 peer-refereed publications involving creatine supplementation, it is somewhat surprising that questions regarding the efficacy and safety of creatine still remain. These include, but are not limited to: 1. Does creatine lead to water retention? 2. …

Impaired Eif5a Function Causes A Mendelian Disorder That Is Partially Rescued In Model Systems By Spermidine., Víctor Faundes, Martin D. Jennings, Siobhan Crilly, Sarah Legraie, Sarah E. Withers, Sara Cuvertino, Sally J. Davies, Andrew G L Douglas, Andrew E. Fry, Victoria Harrison, Jeanne Amiel, Daphné Lehalle, William G. Newman, Patricia Newkirk, Judith Ranells, Miranda Splitt, Laura A. Cross, Carol J. Saunders, Bonnie Sullivan, Jorge L. Granadillo, Christopher T. Gordon, Paul R. Kasher, Graham D. Pavitt, Siddharth Banka

Manuscripts, Articles, Book Chapters and Other Papers

The structure of proline prevents it from adopting an optimal position for rapid protein synthesis. Poly-proline-tract (PPT) associated ribosomal stalling is resolved by highly conserved eIF5A, the only protein to contain the amino acid hypusine. We show that de novo heterozygous EIF5A variants cause a disorder characterized by variable combinations of developmental delay, microcephaly, micrognathia and dysmorphism. Yeast growth assays, polysome profiling, total/hypusinated eIF5A levels and PPT-reporters studies reveal that the variants impair eIF5A function, reduce eIF5A-ribosome interactions and impair the synthesis of PPT-containing proteins. Supplementation with 1 mM spermidine partially corrects the yeast growth defects, improves the polysome profiles …

Efficacy And Safety Of The Mrna-1273 Sars-Cov-2 Vaccine, Lindsey R Baden, Hana M El Sahly, Brandon Essink, Karen Kotloff, Sharon Frey, Rick Novak, David Diemert, Stephen A Spector, Nadine Rouphael, C Buddy Creech, John Mcgettigan, Shishir Khetan, Nathan Segall, Joel Solis, Adam Brosz, Carlos Fierro, Howard Schwartz, Kathleen Neuzil, Larry Corey, Peter Gilbert, Holly Janes, Dean Follmann, Mary Marovich, John Mascola, Laura Polakowski, Julie Ledgerwood, Barney S Graham, Hamilton Bennett, Rolando Pajon, Conor Knightly, Brett Leav, Weiping Deng, Honghong Zhou, Shu Han, Melanie Ivarsson, Jacqueline Miller, Tal Zaks, Cove Study Group

Faculty, Staff and Students Publications

BACKGROUND: Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle-encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19.

METHODS: This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. …

Risk Factors For Stress Fractures In Female Runners: Results Of A Survey, Therese Johnston, Allison E Jakavick, Caroline A Mancuso, Kathleen C Mcgee, Lily Wei, Morgan L Wright, Jeremy Close, Md, Ayako Shimada, Benjamin E Leiby

Department of Rehabilitation Medicine Faculty Papers

Background: Few studies compare women with and without stress fractures and most focus on younger, elite runners.

Hypothesis/purpose: Compare risk factors between female runners with and without a stress fracture history.

Study design: Case control.

Methods: An online survey targeting women age ≥18 years was distributed primarily via social media. Questions included demographics, running details, cross training, nutrition, injury history, medical/menstrual history, and medications. Women with stress fracture histories answered questions about location, number, and changes made. Data were compared between groups using t-tests, chi-square tests, or Fisher's exact tests. Multivariable logistic regression models simultaneously investigated associations of multiple factors …

Risk Stratification Among Survivors Of Cardiac Arrest Considered For Coronary Angiography., Ahmed A Harhash, Teresa L May, Chiu-Hsieh Hsu, Sachin Agarwal, David B Seder, Michael R Mooney, Nainesh C. Patel Md, John Mcpherson, Paul Mcmullan, Richard Riker, Eldar Soreide, Karen G Hirsch, Pascal Stammet, Alison Dupont, Sten Rubertsson, Hans Friberg, Niklas Nielsen, Tanveer Rab, Karl B Kern

Cardiology Division

BACKGROUND: The American College of Cardiology Interventional Council published consensus-based recommendations to help identify resuscitated cardiac arrest patients with unfavorable clinical features in whom invasive procedures are unlikely to improve survival.

OBJECTIVES: This study sought to identify how many unfavorable features are required before prognosis is significantly worsened and which features are most impactful in predicting prognosis.

METHODS: Using the INTCAR (International Cardiac Arrest Registry), the impact of each proposed "unfavorable feature" on survival to hospital discharge was individually analyzed. Logistic regression was performed to assess the association of such unfavorable features with poor outcomes.

RESULTS: Seven unfavorable features (of …

Defining The Genotypic And Phenotypic Spectrum Of X-Linked Msl3-Related Disorder, Theresa Brunet, Kirsty Mcwalter, Katharina Mayerhanser, Grace M Anbouba, Amy Armstrong-Javors, Ingrid Bader, Evan Baugh, Amber Begtrup, Caleb P Bupp, Bert L Callewaert, Anna Cereda, Margot A Cousin, Juan C Del Rey Jimenez, Laurie Demmer, Nikita R Dsouza, Nicole Fleischer, Ralitza H Gavrilova, Sumedha Ghate, Elisabeth Graf, Andrew Green, Sarah R Green, Maria Iascone, Ameni Kdissa, Dirk Klee, Eric W Klee, Emily Lancaster, Kristin Lindstrom, Johannes A Mayr, Meriel Mcentagart, Naomi J L Meeks, Dana Mittag, Harrison Moore, Anne K Olsen, Damara Ortiz, Gretchen Parsons, Loren D M Pena, Richard E Person, Sumit Punj, Gonzalo Alonso Ramos-Rivera, Maria J Guillen Sacoto, G Bradley Schaefer, Rhonda E Schnur, Tiana M Scott, Daryl A Scott, Carolyn R Serbinski, Vandana Shashi, Victoria Mok Siu, Barbro Fossøy Stadheim, Jennifer A Sullivan, Jana Švantnerová, Lea Velsher, David S Wargowski, Ingrid M Wentzensen, Dagmar Wieczorek, Juliane Winkelmann, Patrick Yap, Michael Zech, Michael T Zimmermann, Thomas Meitinger, Felix Distelmaier, Matias Wagner

Paediatrics Publications

PURPOSE: We sought to delineate the genotypic and phenotypic spectrum of female and male individuals with X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome).

METHODS: Twenty-five individuals (15 males, 10 females) with causative variants in MSL3 were ascertained through exome or genome sequencing at ten different sequencing centers.

RESULTS: We identified multiple variant types in MSL3 (ten nonsense, six frameshift, four splice site, three missense, one in-frame-deletion, one multi-exon deletion), most proven to be de novo, and clustering in the terminal eight exons suggesting that truncating variants in the first five exons might be compensated by an alternative MSL3 transcript. Three-dimensional modeling of …

Changes In Patient Reported Outcome Measures After Treatment Of Female Urethral Stricture, Alyssa Gracely, Giulia I. Lane, Pansy Uberoi, Una Lee, Ariana Smith, Priya Padmanabhan

Conference Presentation Abstracts

Introduction: There is a paucity of patient reported outcome measures (PROM) data for women with urethral strictures. Prior literature focuses on anatomic success, with almost no data describing patient centered outcomes. To fill this critical gap, we aim to evaluate change in PROM among women who underwent surgery for stricture. Methods: Data were collected as part of a multiinstitutional retrospective cohort study of women treated for urethral stricture between 2010-19. Median change between baseline and postoperative follow-up on the American Urological Association Symptom Index (AUA-SI) and Urinary Distress Inventory (UDI-6) were assessed using paired Wilcoxon signed-rank tests. Results: Of the …

Association Of Long-Term Trajectories Of Neighborhood Socioeconomic Status With Weight Change In Older Adults, Dong Zhang, Cici Bauer, Tiffany Powell-Wiley, Qian Xiao

Faculty, Staff and Student Publications

IMPORTANCE: Studying long-term changes in neighborhood socioeconomic status (SES) may help to better understand the associations between neighborhood exposure and weight outcomes and provide evidence supporting neighborhood interventions. Little previous research has been done to examine associations between neighborhood SES and weight loss, a risk factor associated with poor health outcomes in the older population.

OBJECTIVE: to determine whether improvements in neighborhood SES are associated with reduced likelihoods of excessive weight gain and excessive weight loss and whether declines are associated with increased likelihoods of these weight outcomes.

DESIGN, STUDY, AND PARTICIPANTS: This cohort study was conducted using data from …

Prediction Model For Freedom From Tlr From A Multi-Study Analysis Of Long-Term Results With The Zilver Ptx Drug-Eluting Peripheral Stent., Michael D Dake, Fabrizio Fanelli, Aaron E Lottes, Erin E O'Leary, Heidi Reichert, Xiaohui Jiang, Weiguo Fu, Osamu Iida, Kan Zen, Marc Schermerhorn, Thomas Zeller, Gary M Ansel

Heart and Vascular Articles

PURPOSE: Develop a prediction model to determine the impact of patient and lesion factors on freedom from target lesion revascularization (ffTLR) for patients who are candidates for Zilver PTX drug-eluting stent (DES) treatment for femoropopliteal lesions.

METHODS: Patient factors, lesion characteristics, and TLR results from five global studies were utilized for model development. Factors potentially associated with TLR (sex, age, diabetes, hypertension, hypercholesterolemia, renal disease, smoking status, Rutherford classification, lesion length, reference vessel diameter (RVD), popliteal involvement, total occlusion, calcification severity, prior interventions, and number of runoff vessels) were analyzed in a Cox proportional hazards model. Probability of ffTLR was …

Levonorgestrel Intrauterine Device Use For Medical Indications In Nulliparous Adolescents And Young Adults., Beth I Schwartz, Morgan Alexander, Lesley L Breech

Department of Obstetrics and Gynecology Faculty Papers

PURPOSE: Intrauterine devices (IUDs) are highly effective at preventing pregnancy. Levonorgestrel (LNG) IUDs also have beneficial effects on menstrual bleeding and abdominal and pelvic pain. Although there are increasing data on use of IUDs for contraception in adolescents and for medical indications in adults, there are extremely limited data on LNG IUD use for medical indications in adolescents. Our objective is to describe the characteristics and experiences of LNG IUD use in nulliparous adolescents and young women using IUDs for medical indications.

METHODS: We conducted a retrospective chart review of all nulliparous patients aged 22 years and younger who underwent …

Fronto-Cerebellar Connectivity Mediating Cognitive Processing Speed, Clive H Y Wong, Jiao Liu, Tatia M C Lee, Jing Tao, Alex W K Wong, Bolton K H Chau, Lidian Chen, Chetwyn C H Chan

2020-Current year OA Pubs

Processing speed is an important construct in understanding cognition. This study was aimed to control task specificity for understanding the neural mechanisms underlying cognitive processing speed. Forty young adult subjects performed attention tasks of two modalities (auditory and visual) and two levels of task rules (compatible and incompatible). Block-design fMRI captured BOLD signals during the tasks. Thirteen regions of interest were defined with reference to publicly available activation maps for processing speed tasks. Cognitive speed was derived from task reaction times, which yielded six sets of connectivity measures. Mixed-effect LASSO regression revealed six significant paths suggestive of a cerebello-frontal network …

Decoding Visual Information From High-Density Diffuse Optical Tomography Neuroimaging Data, Kalyan Tripathy, Zachary E Markow, Andrew K Fishell, Arefeh Sherafati, Tracy M Burns-Yocum, Mariel L Schroeder, Alexandra M Svoboda, Adam T Eggebrecht, Mark A Anastasio, Bradley L Schlaggar, Joseph P Culver

2020-Current year OA Pubs

BACKGROUND: Neural decoding could be useful in many ways, from serving as a neuroscience research tool to providing a means of augmented communication for patients with neurological conditions. However, applications of decoding are currently constrained by the limitations of traditional neuroimaging modalities. Electrocorticography requires invasive neurosurgery, magnetic resonance imaging (MRI) is too cumbersome for uses like daily communication, and alternatives like functional near-infrared spectroscopy (fNIRS) offer poor image quality. High-density diffuse optical tomography (HD-DOT) is an emerging modality that uses denser optode arrays than fNIRS to combine logistical advantages of optical neuroimaging with enhanced image quality. Despite the resulting promise …

Relation Of Magnetic Resonance Imaging Based Arterial Signal Enhancement To Markers Of Peripheral Artery Disease, Olga A Gimnich, Jonathan Holbrook, Tatiana Belousova, Christina M Short, Addison A Taylor, Vijay Nambi, Joel D Morrisett, Christie M Ballantyne, Jean Bismuth, Dipan J Shah, Gerd Brunner

Faculty, Staff and Students Publications

Peripheral artery disease (PAD) is associated with impaired lower extremity function. We hypothesized that contrast-enhanced magnetic resonance imaging (CE-MRI) based arterial signal enhancement (SE) measures are associated with markers of PAD. A total of 66 participants were enrolled, 10 were excluded due to incomplete data, resulting in 56 participants for the final analyses (36 PAD, 20 matched controls). MR imaging was performed postreactive hyperemia using bilateral thigh blood-pressure cuffs. First pass-perfusion images were acquired at the mid-calf region with a high-resolution saturation recovery gradient echo pulse sequence, and arterial SE was measured for the lower extremity arteries. As expected, peak …

Association Of Baseline Characteristics With Insulin Sensitivity And Β-Cell Function In The Glycemia Reduction Approaches In Diabetes: A Comparative Effectiveness (Grade) Study Cohort, Neda Rasouli, Naji Younes, Kristina M Utzschneider, Silvio E Inzucchi, Ashok Balasubramanyam, Andrea L Cherrington, Faramarz Ismail-Beigi, Robert M Cohen, Darin E Olson, Ralph A Defronzo, William H Herman, John M Lachin, Steven E Kahn, Grade Research Group

Faculty, Staff and Students Publications

OBJECTIVE: We investigated sex and racial differences in insulin sensitivity, β-cell function, and glycated hemoglobin (HbA

RESEARCH DESIGN AND METHODS: This is a cross-sectional analysis of baseline data from 3,108 GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) participants. All had type 2 diabetes diagnosedβ-cell function were evaluated using the HOMA of insulin sensitivity and estimates from oral glucose tolerance tests, including the Matsuda Index, insulinogenic index, C-peptide index, and oral disposition index (DI).

RESULTS: The cohort was 56.6 ± 10 years of age (mean ± SD), 63.8% male, with BMI 34.2 ± 6.7 kg/m

CONCLUSIONS: In the …

Association Of Baseline Characteristics With Insulin Sensitivity And Β-Cell Function In The Glycemia Reduction Approaches In Diabetes: A Comparative Effectiveness (Grade) Study Cohort, Neda Rasouli, Naji Younes, Kristina M Utzschneider, Silvio E Inzucchi, Ashok Balasubramanyam, Andrea L Cherrington, Faramarz Ismail-Beigi, Robert M Cohen, Darin E Olson, Ralph A Defronzo, William H Herman, John M Lachin, Steven E Kahn

Faculty, Staff and Students Publications

OBJECTIVE: We investigated sex and racial differences in insulin sensitivity, β-cell function, and glycated hemoglobin (HbA

RESEARCH DESIGN AND METHODS: This is a cross-sectional analysis of baseline data from 3,108 GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) participants. All had type 2 diabetes diagnosedβ-cell function were evaluated using the HOMA of insulin sensitivity and estimates from oral glucose tolerance tests, including the Matsuda Index, insulinogenic index, C-peptide index, and oral disposition index (DI).

RESULTS: The cohort was 56.6 ± 10 years of age (mean ± SD), 63.8% male, with BMI 34.2 ± 6.7 kg/m

CONCLUSIONS: In the …

Robotic Bronchoscopy For Peripheral Pulmonary Lesions: A Multicenter Pilot And Feasibility Study (Benefit), Alexander C Chen, Nicholas J Pastis Jr, Amit K Mahajan, Sandeep J Khandhar, Michael J Simoff, Michael S Machuzak, Joseph Cicenia, Thomas R Gildea, Gerard A Silvestri

2020-Current year OA Pubs

BACKGROUND: The diagnosis of peripheral pulmonary lesions (PPL) continues to present clinical challenges. Despite extensive experience with guided bronchoscopy, the diagnostic yield has not improved significantly. Robotic-assisted bronchoscopic platforms have been developed potentially to improve the diagnostic yield for PPL. Presently, limited data exist that evaluate the performance of robotic systems in live human subjects.

RESEARCH QUESTION: What is the safety and feasibility of robotic-assisted bronchoscopy in patients with PPLs?

STUDY DESIGN AND METHODS: This was a prospective, multicenter pilot and feasibility study that used a robotic bronchoscopic system with a mother-daughter configuration in patients with PPL 1 to 5 …

Genome-Wide Meta-Analysis Of Muscle Weakness Identifies 15 Susceptibility Loci In Older Men And Women, Garan Jones, Katerina Trajanoska, Adam J Santanasto, Najada Stringa, Chia-Ling Kuo, Janice L Atkins, Joshua R Lewis, Thuyvy Duong, Shengjun Hong, Mary L Biggs, Jian'an Luan, Chloe Sarnowski, Kathryn L Lunetta, Toshiko Tanaka, Mary K Wojczynski, Ryan Cvejkus, Maria Nethander, Sahar Ghasemi, Jingyun Yang, M Carola Zillikens, Stefan Walter, Kamil Sicinski, Erika Kague, Cheryl L Ackert-Bicknell, Dan E Arking, B Gwen Windham, Eric Boerwinkle, Megan L Grove, Misa Graff, Dominik Spira, Ilja Demuth, Nathalie Van Der Velde, Lisette C P G M De Groot, Bruce M Psaty, Michelle C Odden, Alison E Fohner, Claudia Langenberg, Nicholas J Wareham, Stefania Bandinelli, Natasja M Van Schoor, Martijn Huisman, Qihua Tan, Joseph Zmuda, Dan Mellström, Magnus Karlsson, David A Bennett, Aron S Buchman, Philip L De Jager, Andre G Uitterlinden, Uwe Völker, Thomas Kocher, Alexander Teumer, Leocadio Rodriguéz-Mañas, Francisco J García, José A Carnicero, Pamela Herd, Lars Bertram, Claes Ohlsson, Joanne M Murabito, David Melzer, George A Kuchel, Luigi Ferrucci, David Karasik, Fernando Rivadeneira, Douglas P Kiel, Luke C Pilling

Faculty, Staff and Student Publications

Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n = 48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1 p = 4 × 10

Absent B Cells, Agammaglobulinemia, And Hypertrophic Cardiomyopathy In Folliculin-Interacting Protein 1 Deficiency, Francesco Saettini, Cecilia Poli, Jaime Vengoechea, Sonia Bonanomi, Julio C Orellana, Grazia Fazio, Fred H Rodriguez, Loreani P Noguera, Claire Booth, Valentina Jarur-Chamy, Marissa Shams, Maria Iascone, Maja Vukic, Serena Gasperini, Manuel Quadri, Amairelys Barroeta Seijas, Elizabeth Rivers, Mario Mauri, Raffaele Badolato, Gianni Cazzaniga, Cristina Bugarin, Giuseppe Gaipa, Wilma G M Kroes, Daniele Moratto, Monique M Van Oostaijen-Ten Dam, Frank Baas, Silvère Van Der Maarel, Rocco Piazza, Zeynep H Coban-Akdemir, James R Lupski, Bo Yuan, Ivan K Chinn, Lucia Daxinger, Andrea Biondi

Faculty, Staff and Student Publications

Agammaglobulinemia is the most profound primary antibody deficiency that can occur due to an early termination of B-cell development. We here investigated 3 novel patients, including the first known adult, from unrelated families with agammaglobulinemia, recurrent infections, and hypertrophic cardiomyopathy (HCM). Two of them also presented with intermittent or severe chronic neutropenia. We identified homozygous or compound-heterozygous variants in the gene for folliculin interacting protein 1 (FNIP1), leading to loss of the FNIP1 protein. B-cell metabolism, including mitochondrial numbers and activity and phosphatidylinositol 3-kinase/AKT pathway, was impaired. These defects recapitulated the Fnip1-/- animal model. Moreover, we identified either uniparental disomy …

Post-Partum Skin-To-Skin Care And Infant Safety: Results Of A State-Wide Hospital Survey, Eileen Tyrala, Md, Michael H. Goodstein, Md, Erich Batra, Md, Barbara Kelly, Md, Judy Bannon, Mba, Ted Bell, Ms

Department of Medicine Faculty Papers

Objectives: Survey current experience with Skin to Skin care (SSC) in Pennsylvania Maternity Centers.

Study Design: The nursing director of each Maternity Center in PA (n = 95) was sent an on-line confidential survey querying SSC practices. Responses were compared by delivery size, location, and nature of affiliation. Statistics analyzed by chi-square and student t-test.

Results: Of these 64/95 MCs (67%) responded. All allowed SSC after vaginal deliveries, 55% after C-section, 73% mother’s room. Monitoring included delivery room nurse (94%) with support from other providers (61%), family members (37%), and electronic monitoring (5%). If SSC occurred in mother’s …

Spliceosome-Targeted Therapies Trigger An Antiviral Immune Response In Triple-Negative Breast Cancer, Elizabeth A Bowling, Jarey H Wang, Fade Gong, William Wu, Nicholas J Neill, Ik Sun Kim, Siddhartha Tyagi, Mayra Orellana, Sarah J Kurley, Rocio Dominguez-Vidaña, Hsiang-Ching Chung, Tiffany Y-T Hsu, Julien Dubrulle, Alexander B Saltzman, Heyuan Li, Jitendra K Meena, Gino M Canlas, Srinivas Chamakuri, Swarnima Singh, Lukas M Simon, Calla M Olson, Lacey E Dobrolecki, Michael T Lewis, Bing Zhang, Ido Golding, Jeffrey M Rosen, Damian W Young, Anna Malovannaya, Fabio Stossi, George Miles, Matthew J Ellis, Lihua Yu, Silvia Buonamici, Charles Y Lin, Kristen L Karlin, Xiang H-F Zhang, Thomas F Westbrook

Faculty, Staff and Students Publications

Many oncogenic insults deregulate RNA splicing, often leading to hypersensitivity of tumors to spliceosome-targeted therapies (STTs). However, the mechanisms by which STTs selectively kill cancers remain largely unknown. Herein, we discover that mis-spliced RNA itself is a molecular trigger for tumor killing through viral mimicry. In MYC-driven triple-negative breast cancer, STTs cause widespread cytoplasmic accumulation of mis-spliced mRNAs, many of which form double-stranded structures. Double-stranded RNA (dsRNA)-binding proteins recognize these endogenous dsRNAs, triggering antiviral signaling and extrinsic apoptosis. In immune-competent models of breast cancer, STTs cause tumor cell-intrinsic antiviral signaling, downstream adaptive immune signaling, and tumor cell death. Furthermore, RNA …

Implications Of Oligomeric Amyloid-Beta (Oaβ42) Signaling Through Α7Β2-Nicotinic Acetylcholine Receptors (Nachrs) On Basal Forebrain Cholinergic Neuronal Intrinsic Excitability And Cognitive Decline, Andrew A George, Jaime M Vieira, Cameron Xavier-Jackson, Michael T Gee, John R Cirrito, Heather A Bimonte-Nelson, Marina R Picciotto, Ronald J Lukas, Paul Whiteaker

2020-Current year OA Pubs

Neuronal and network-level hyperexcitability is commonly associated with increased levels of amyloid-β (Aβ) and contribute to cognitive deficits associated with Alzheimer's disease (AD). However, the mechanistic complexity underlying the selective loss of basal forebrain cholinergic neurons (BFCNs), a well-recognized characteristic of AD, remains poorly understood. In this study, we tested the hypothesis that the oligomeric form of amyloid-β (oAβ

An Economic And Disease Transmission Model Of Human Papillomavirus And Oropharyngeal Cancer In Texas, Chengxue Zhong, Li Xu, Ho-Lan Peng, Samantha Tam, Li Xu, Kristina R Dahlstrom, Chi-Fang Wu, Shuangshuang Fu, Wenyaw Chan, Erich M Sturgis, Lois M Ramondetta, Libin Rong, David R Lairson, Hongyu Miao

Faculty, Staff and Student Publications

In 2017, 46,157 and 3,127 new oropharyngeal cancer (OPC) cases were reported in the U.S. and Texas, respectively. About 70% of OPC were attributed to human papillomavirus (HPV). However, only 51% of U.S. and 43.5% of Texas adolescents have completed the HPV vaccine series. Therefore, modeling the demographic dynamics and transmission of HPV and OPC progression is needed for accurate estimation of the economic and epidemiological impacts of HPV vaccine in a geographic area. An age-structured population dynamic model was developed for the U.S. state of Texas. With Texas-specific model parameters calibrated, this model described the dynamics of HPV-associated OPC …

Houston Hurricane Harvey Health (Houston-3h) Study: Assessment Of Allergic Symptoms And Stress After Hurricane Harvey Flooding, Abiodun O Oluyomi, Kristen Panthagani, Jesus Sotelo, Xiangjun Gu, Georgina Armstrong, Dan Na Luo, Kristi L Hoffman, Diana Rohlman, Lane Tidwell, Winifred J Hamilton, Elaine Symanski, Kimberly Anderson, Joseph F Petrosino, Cheryl Lyn Walker, Melissa Bondy

Faculty, Staff and Students Publications

BACKGROUND: In August 2017, Hurricane Harvey caused unprecedented flooding across the greater Houston area. Given the potential for widespread flood-related exposures, including mold and sewage, and the emotional and mental toll caused by the flooding, we sought to evaluate the short- and long-term impact of flood-related exposures on the health of Houstonians. Our objectives were to assess the association of flood-related exposures with allergic symptoms and stress among Houston-area residents at two time points: within approximately 30 days (T1) and 12 months (T2) after Hurricane Harvey's landfall.

METHODS: The Houston Hurricane Harvey Health (Houston-3H) Study enrolled a total of 347 …

Emergency Department Use Following Incentives To Provide After-Hours Primary Care: A Retrospective Cohort Study., Michael Hong, Amardeep Thind, Gregory S Zaric, Sisira Sarma

Epidemiology and Biostatistics Publications

BACKGROUND: Access to primary care outside of regular working hours is limited in many countries. This study investigates the relation between the after-hours premium, an incentive for primary care physicians to provide services after hours, and less-urgent visits to the emergency department in Ontario, Canada.

METHODS: We analyzed a retrospective cohort of a random sample of Ontario residents from April 2002 to March 2006, and a subcohort of patients followed from April 2005 to March 2016. We linked patient and primary care physician data with emergency department visit data. We used fixed-effects regression models to analyze the association between the …

The Health-Related Quality Of Life, Work Productivity, Healthcare Resource Utilization, And Economic Burden Associated With Levels Of Suicidal Ideation Among Patients Self-Reporting Moderately Severe Or Severe Major Depressive Disorder In A National Survey., Carmela Benson, David Singer, Colleen M Carpinella, May Shawi, Larry Alphs

College of Population Health Faculty Papers

Background: Suicidal ideation (SI) is a cardinal aspect of major depressive disorder (MDD); however, patient-reported outcomes data from large-scale surveys are limited concerning SI in the context of MDD. This study aims to understand the association between varying levels of SI and health-related quality of life (HRQoL), work productivity, healthcare resource utilization (HRU), and associated costs in patients with moderately severe/severe MDD.

Methods: This was a retrospective, cross-sectional analysis of 2013 national survey data. Patients who self-reported moderately severe or severe MDD and completed the Short Form Survey Version 2 (SF-36v2), Work Productivity Loss and Activity Impairment questionnaire (WPAI), and …

Comparison Of N- And C-Terminally Endogenously Gfp-Tagged Wee-1.3 Strains In, Lourds M Fernando, Kyrionna Golliday, Ruby Boateng, Anna K Allen

Faculty Research 2021

We have generated a WEE-1.3 strain in C. elegans where we have endogenously tagged the C-terminus with GFP. In this publication we demonstrate that this new strain exhibits the same expression localization pattern as the WEE-1.3 antibody and N-terminally endogenously GFP-tagged WEE-1.3 strain that have been previously published. We also show for the first time that endogenously tagging WEE-1.3 at either termini does not affect the reproductive function of the worms.

Relationship Between Clinicopathologic Factors And Fdg Avidity In Radioiodine-Negative Recurrent Or Metastatic Differentiated Thyroid Carcinoma, Le Ngoc Ha, Amir Iravani, Nguyen Thi Nhung, Ngo Thi Minh Hanh, Febby Hutomo, Mai Hong Son

2020-Current year OA Pubs

BACKGROUND: In this study, we investigated the relationship between clinicopathologic factors, BRAF

METHODS: From 2015 to 2018 all patients with suspected recurrent or metastatic radioiodine-negative DTC patients who underwent FDG positron emission tomography/computed tomography (PET/CT) were retrospectively reviewed. Suspected lesions on FDG PET/CT were biopsied and underwent BRAF

RESULTS: Sixty-three consecutive patients, 55 (87.3%) female, with median age of 48 (range 17-81) were included. The majority of patients had BRAF

CONCLUSION: The majority of recurrent or metastatic RAI-negative DTC have BRAF

Disparities In Cardiovascular Disease Outcomes Among Pregnant And Post-Partum Women, Mohamed M Gad, Islam Y Elgendy, Ahmed N Mahmoud, Anas M Saad, Toshiaki Isogai, Isadora Sande Mathias, Rabel Misbah Rameez, Johnny Chahine, Hani Jneid, Samir R Kapadia

Faculty, Staff and Students Publications

Background

The incidence of cardiovascular disease among pregnant women is rising in the United States. Data on racial disparities for the major cardiovascular events during pregnancy are limited.

Methods and Results

Pregnant and post‐partum women hospitalized from January 2007 to December 2017 were identified from the Nationwide Inpatient Sample. The outcomes of interest included: in‐hospital mortality, myocardial infarction, stroke, pulmonary embolism, and peripartum cardiomyopathy. Multivariate regression analysis was used to assess the independent association between race and in‐hospital outcomes. Among 46 700 637 pregnancy‐related hospitalizations, 21 663 575 (46.4%) were White, 6 302 089 (13.5%) were Black, and 8 914 …

Molecular Characterization Of Cryptosporidium Spp. From Humans In Ethiopia, Ambachew W. Hailu, Abraham Degarege, Haileeyesus Adamu, Damien Costa, Venceslas Villier, Abdelmounaim Mouhajir, Loic Favennec, Romy Razakandrainibe, Beyene Petros

Journal Articles: Epidemiology

Data on the distribution and genotype of Cryptosporidium species is limited in Ethiopia. This study examined the presence and genetic diversity of Cryptosporidium species circulating in Ethiopian human population. Stool samples collected from patients who visited rural (n = 94) and urban (n = 93) health centers in Wurgissa and Hawassa district, respectively, were examined for the presence of Cryptosporidium spp. using microscopy, nested PCR and real-time PCR. To detect infection with PCR, analysis of 18S ribosomal RNA was performed. Subtyping was performed by sequencing a fragment of GP60 gene. The overall prevalence of infection was 46% (n = 86) …