Digital Commons Network^™

The Lack Of Natural Igm Increases Susceptibility And Impairs Anti-Vi Polysaccharide Igg Responses In A Mouse Model Of Typhoid, Akhil S. Alugupalli, Matthew P. Cravens, Justin A. Walker, Dania Gulandijany, Gregory S. Dickinson, Genevieve Lewis, Gudrun F. Debes, Dieter M. Schifferli, Andreas J. Bäumler, Kishore R. Alugupalli

Department of Microbiology and Immunology Faculty Papers

Circulating IgM present in the body prior to any apparent Ag exposure is referred to as natural IgM. Natural IgM provides protective immunity against a variety of pathogens. Salmonella enterica serovar Typhi (S. Typhi) is the causative agent of typhoid fever in humans. Because mice are not permissive to S. Typhi infection, we employed a murine model of typhoid using S. enterica serovar Typhimurium expressing the Vi polysaccharide (ViPS) of S. Typhi (S. Typhimurium strain RC60) to evaluate the role of natural IgM in pathogenesis. We found that natural mouse IgM binds to S. Typhi and S. Typhimurium. The severity …

Long Read Sequencing And Expression Studies Of Ahdc1 Deletions In Xia-Gibbs Syndrome Reveal A Novel Genetic Regulatory Mechanism, Varuna Chander, Medhat Mahmoud, Jianhong Hu, Zain Dardas, Christopher M Grochowski, Moez Dawood, Michael M Khayat, He Li, Shoudong Li, Shalini Jhangiani, Viktoriya Korchina, Hua Shen, George Weissenberger, Qingchang Meng, Marie-Claude Gingras, Donna M Muzny, Harsha Doddapaneni, Jennifer E Posey, James R Lupski, Aniko Sabo, David R Murdock, Fritz J Sedlazeck, Richard A Gibbs

Faculty, Staff and Students Publications

Xia-Gibbs syndrome (XGS; MIM# 615829) is a rare mendelian disorder characterized by Development Delay (DD), intellectual disability (ID), and hypotonia. Individuals with XGS typically harbor de novo protein-truncating mutations in the AT-Hook DNA binding motif containing 1 (AHDC1) gene, although some missense mutations can also cause XGS. Large de novo heterozygous deletions that encompass the AHDC1 gene have also been ascribed as diagnostic for the disorder, without substantial evidence to support their pathogenicity. We analyzed 19 individuals with large contiguous deletions involving AHDC1, along with other genes. One individual bore the smallest known contiguous AHDC1 deletion (∼350 Kb), encompassing eight …

Statin Use And Risk Of Diabetes By Subclinical Atherosclerosis Burden (From A Multi-Ethnic Study Of Atherosclerosis Report), Mahmoud Al Rifai, Moyses Szklo, Jaideep Patel, Michael J Blaha, Christie M Ballantyne, Vera Bittner, Pamela Morris, John W Mcevoy, Michael D Shapiro, Mouaz H Al-Mallah, Philip Greenland, Salim S Virani

Faculty, Staff and Students Publications

Although there is a significant reduction in atherosclerotic cardiovascular disease risk with statins, a higher risk of diabetes mellitus has been demonstrated in randomized clinical trials. The risk of incident diabetes with statins may be heterogeneous by presence of coronary artery calcium (CAC). We evaluated participants without prevalent diabetes at baseline from the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of subjects free of clinical cardiovascular disease at baseline. We used multivariable-adjusted Cox proportional hazards models to study the association between statin use and incident diabetes, adjusting for sociodemographic and cardiovascular risk factors, including time-varying statin use and …

18f-Fdg Pet/Ct Staging Of Head And Neck Cancer: Interobserver Agreement And Accuracy—Results From Multicenter Acrin 6685 Clinical Trial, Rathan M Subramaniam, Fenghai M Duan, Justin Romanoff, Jian Qin Yu, Twyla Bartel, Farrokh Dehdashti, Charles M Intenzo, Lilja Solnes, Jorean Sicks, Brendan C Stack, Val J Lowe

Department of Radiology Faculty Papers

To our knowledge, no prior multicenter clinical trial has reported interobserver agreement of 18F-FDG PET/CT scans for staging of clinical N0 neck in head and neck cancer. Methods: A total of 287 participants were recruited. For visual analysis, positive nodal uptake of 18F-FDG was defined as uptake visually greater than activity seen in the blood pool. Results: The negative predictive value of the 18F-FDG PET/CT for N0 clinical neck was 86% or above for visual assessment (95% CI, 86%-88%) for the 2 central readers and above 90% (95% CI, 90%-95%) for SUVmax for central reads and site reads dichotomized at …

Effects Of Glp-1 Receptor Agonists On Cardiovascular Outcomes In Patients With Type 2 Diabetes And Chronic Kidney Disease: A Systematic Review And Meta-Analysis, Michael Kelly, Jelena Lewis, Hindu Rao, Jessica Carter, Ivan Portillo, Richard Beuttler

College of Pharmacy Faculty Papers

AIM: To evaluate the cardiovascular outcomes of glucagon-like peptide-1 receptor agonists (GLP1-RA) in patients with type 2 diabetes (T2DM) and chronic kidney disease (CKD).

MATERIALS AND METHODS: We searched PubMed, Ovid MEDLINE, CINAHL, and Web of Science databases for randomized controlled trials reporting event rates for a composite cardiovascular outcome of cardiovascular death, myocardial infarction, and stroke in patients with T2DM and CKD receiving GLP1-RA or placebo. Studies were restricted to those reporting specific event rates for patients with CKD separately from the overall population. We conducted a meta-analysis using a random-effects model. This meta-analysis was registered on PROSPERO (CRD42022320157). …

Identification Of A Novel Large Multigene Deletion And A Frameshift Indel In Pde6b As The Underlying Cause Of Early-Onset Recessive Rod-Cone Degeneration, Riccardo Sangermano, Pooja Biswas, Lori S Sullivan, Emily M Place, Shyamanga Borooah, Juerg Straubhaar, Eric A Pierce, Stephen P Daiger, Kinga M Bujakowska, Radha Ayaggari

Faculty, Staff and Student Publications

A family, with two affected identical twins with early-onset recessive inherited retinal degeneration, was analyzed to determine the underlying genetic cause of pathology. Exome sequencing revealed a rare and previously reported causative variant (c.1923_1969delinsTCTGGG; p.Asn643Glyfs*29) in the

Sex-Related Differences In Violence Exposure, Neural Reactivity To Threat, And Mental Health, Heather E Dark, Nathaniel G Harnett, Danielle R Hurst, Muriah D Wheelock, Kimberly H Wood, Adam M Goodman, Sylvie Mrug, Marc N Elliott, Susan Tortolero Emery, Mark A Schuster, David C Knight

Faculty, Staff and Student Publications

The prefrontal cortex (PFC), hippocampus, and amygdala play an important role in emotional health. However, adverse life events (e.g., violence exposure) affect the function of these brain regions, which may lead to disorders such as depression and anxiety. Depression and anxiety disproportionately affect women compared to men, and this disparity may reflect sex differences in the neural processes that underlie emotion expression and regulation. The present study investigated sex differences in the relationship between violence exposure and the neural processes that underlie emotion regulation. In the present study, 200 participants completed a Pavlovian fear conditioning procedure in which cued and …

Effect Of The Environment On Home-Based Self-Sampling Kits For Anal Cancer Screening, Jenna Nitkowski, Anna Giuliano, Tim Ridolfi, Elizabeth Chiao, Maria E Fernandez, Vanessa Schick, Michael D Swartz, Jennifer S Smith, Ellen A Schneider, Bridgett Brzezinski, Alan G Nyitray

Faculty, Staff and Student Publications

BACKGROUND: Anal cancer incidence has increased in Western countries in recent decades and currently there are no consensus screening guidelines. Home-based self-sampling kits might facilitate screening for anal precancer/cancer but could require travel through postal mail where they may experience extreme temperatures or long transport times.

OBJECTIVE: To determine the effect of the environment on specimen adequacy for HPV genotyping of a mailed home-based self-sampling anal cancer screening kit.

STUDY DESIGN: The Prevent Anal Cancer (PAC) Study in Milwaukee, Wisconsin recruited men who have sex with men (MSM) and transgender persons 25 years of age and older. Participants were randomized …

Food Safety Attitudes, Behaviors, And Hygiene Measures Among Predominantly Low-Income Parents In Houston, Texas, Christina K Carstens, Joelle K Salazar, Shreela V Sharma, Wenyaw Chan, Charles Darkoh

Faculty, Staff and Student Publications

ABSTRACT: Foodborne infections in the United States affect racial-ethnic minority and low-income populations at higher rates than the general population. to identify the prevalence of food safety behaviors and demographic characteristics associated with food handling practices among a susceptible, high-risk population, a cross-sectional survey was administered to 106 parents with children enrolled at two elementary schools serving predominantly low-income families in Houston, Texas. Relationships between demographic characteristics and food safety behavioral outcomes were examined using cross-tabulations and Fisher's exact test. Most respondents were female (93.4%), Hispanic, Latino, or Mexican American (94.9%), and had no previous food handling employment experience (75.0%). …

Genetic Diversity Fuels Gene Discovery For Tobacco And Alcohol Use, Gretchen R B Saunders, Xingyan Wang, Fang Chen, Seon-Kyeong Jang, Mengzhen Liu, Chen Wang, Shuang Gao, Yu Jiang, Chachrit Khunsriraksakul, Jacqueline M Otto, Clifton Addison, Masato Akiyama, Christine M Albert, Fazil Aliev, Alvaro Alonso, Donna K Arnett, Allison E Ashley-Koch, Aneel A Ashrani, Kathleen C Barnes, R Graham Barr, Traci M Bartz, Diane M Becker, Lawrence F Bielak, Emelia J Benjamin, Joshua C Bis, Gyda Bjornsdottir, John Blangero, Eugene R Bleecker, Jason D Boardman, Eric Boerwinkle, Dorret I Boomsma, Meher Preethi Boorgula, Donald W Bowden, Jennifer A Brody, Brian E Cade, Daniel I Chasman, Sameer Chavan, Yii-Der Ida Chen, Zhengming Chen, Iona Cheng, Michael H Cho, Hélène Choquet, John W Cole, Marilyn C Cornelis, Francesco Cucca, Joanne E Curran, Mariza De Andrade, Danielle M Dick, Anna R Docherty, Ravindranath Duggirala, Charles B Eaton, Marissa A Ehringer, Tõnu Esko, Jessica D Faul, Lilian Fernandes Silva, Edoardo Fiorillo, Myriam Fornage, Barry I Freedman, Maiken E Gabrielsen, Melanie E Garrett, Sina A Gharib, Christian Gieger, Nathan Gillespie, David C Glahn, Scott D Gordon, Charles C Gu, Dongfeng Gu, Daniel F Gudbjartsson, Xiuqing Guo, Jeffrey Haessler, Michael E Hall, Toomas Haller, Kathleen Mullan Harris, Jiang He, Pamela Herd, John K Hewitt, Ian Hickie, Bertha Hidalgo, John E Hokanson, Christian Hopfer, Joukejan Hottenga, Lifang Hou, Hongyan Huang, Yi-Jen Hung, David J Hunter, Kristian Hveem, Shih-Jen Hwang, Chii-Min Hwu, William Iacono, Marguerite R Irvin, Yon Ho Jee, Eric O Johnson, Yoonjung Y Joo, Eric Jorgenson, Anne E Justice, Yoichiro Kamatani, Robert C Kaplan, Jaakko Kaprio, Sharon L R Kardia, Matthew C Keller, Tanika N Kelly, Charles Kooperberg, Tellervo Korhonen, Peter Kraft, Kenneth Krauter, Johanna Kuusisto, Markku Laakso, Jessica Lasky-Su, Wen-Jane Lee, James J Lee, Daniel Levy, Liming Li, Kevin Li, Yuqing Li, Kuang Lin, Penelope A Lind, Chunyu Liu, Donald M Lloyd-Jones, Sharon M Lutz, Jiantao Ma, Reedik Mägi, Ani Manichaikul, Nicholas G Martin, Ravi Mathur, Nana Matoba, Patrick F Mcardle, Matt Mcgue, Matthew B Mcqueen, Sarah E Medland, Andres Metspalu, Deborah A Meyers, Iona Y Millwood, Braxton D Mitchell, Karen L Mohlke, Matthew Moll, May E Montasser, Alanna C Morrison, Antonella Mulas, Jonas B Nielsen, Kari E North, Elizabeth C Oelsner, Yukinori Okada, Valeria Orrù, Nicholette D Palmer, Teemu Palviainen, Anita Pandit, S Lani Park, Ulrike Peters, Annette Peters, Patricia A Peyser, Tinca J C Polderman, Nicholas Rafaels, Susan Redline, Robert M Reed, Alex P Reiner, John P Rice, Stephen S Rich, Nicole E Richmond, Carol Roan, Jerome I Rotter, Michael N Rueschman, Valgerdur Runarsdottir, Nancy L Saccone, David A Schwartz, Aladdin H Shadyab, Jingchunzi Shi, Suyash S Shringarpure, Kamil Sicinski, Anne Heidi Skogholt, Jennifer A Smith, Nicholas L Smith, Nona Sotoodehnia, Michael C Stallings, Hreinn Stefansson, Kari Stefansson, Jerry A Stitzel, Xiao Sun, Moin Syed, Ruth Tal-Singer, Amy E Taylor, Kent D Taylor, Marilyn J Telen, Khanh K Thai, Hemant Tiwari, Constance Turman, Thorarinn Tyrfingsson, Tamara L Wall, Robin G Walters, David R Weir, Scott T Weiss, Wendy B White, John B Whitfield, Kerri L Wiggins, Gonneke Willemsen, Cristen J Willer, Bendik S Winsvold, Huichun Xu, Lisa R Yanek, Jie Yin, Kristin L Young, Kendra A Young, Bing Yu, Wei Zhao, Wei Zhou, Sebastian Zöllner, Luisa Zuccolo, 23andme Research Team, Biobank Japan Project, Chiara Batini, Andrew W Bergen, Laura J Bierut, Sean P David, Sarah A Gagliano Taliun, Dana B Hancock, Bibo Jiang, Marcus R Munafò, Thorgeir E Thorgeirsson, Dajiang J Liu, Scott Vrieze

Faculty, Staff and Student Publications

Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury1-4. These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries5. Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power …

Leveraging Pleiotropy To Discover And Interpret Gwas Results For Sleep-Associated Traits, Sung Chun, Sebastian Akle, Athanasios Teodosiadis, Brian E Cade, Heming Wang, Tamar Sofer, Daniel S Evans, Katie L Stone, Sina A Gharib, Sutapa Mukherjee, Lyle J Palmer, David Hillman, Jerome I Rotter, Craig L Hanis, John A Stamatoyannopoulos, Susan Redline, Chris Cotsapas, Shamil R Sunyaev

Faculty, Staff and Student Publications

Genetic association studies of many heritable traits resulting from physiological testing often have modest sample sizes due to the cost and burden of the required phenotyping. This reduces statistical power and limits discovery of multiple genetic associations. We present a strategy to leverage pleiotropy between traits to both discover new loci and to provide mechanistic hypotheses of the underlying pathophysiology. Specifically, we combine a colocalization test with a locus-level test of pleiotropy. In simulations, we show that this approach is highly selective for identifying true pleiotropy driven by the same causative variant, thereby improves the chance to replicate the associations …

Association Of Hematologic Response And Assay Sensitivity On The Prognostic Impact Of Measurable Residual Disease In Acute Myeloid Leukemia: A Systematic Review And Meta-Analysis, Nicholas J Short, Chenqi Fu, Donald A Berry, Roland B Walter, Sylvie D Freeman, Christopher S Hourigan, Xuelin Huang, Graciela Nogueras Gonzalez, Hyunsoo Hwang, Xinyue Qi, Hagop Kantarjian, Shouhao Zhou, Farhad Ravandi

Faculty, Staff and Student Publications

Measurable residual disease (MRD) is associated with relapse and survival in acute myeloid leukemia (AML). We aimed to quantify the impact of MRD on outcomes across clinical contexts, including its association with hematologic response and MRD assay sensitivity. We performed systematic literature review and meta-analysis of 48 studies that reported the association between MRD and overall survival (OS) or disease-free survival (DFS) in AML and provided information on the MRD threshold used and the hematologic response of the study population. Among studies limited to patients in complete remission (CR), the estimated 5-year OS for the MRD-negative and MRD-positive groups was …

Hpv-Associated Anal Cancer Knowledge, Attitudes, And Health Communication Behaviors Among Non-Clinical Providers At Hiv/Aids Service Organizations In Southern United States Region, Olufunto A Olusanya, Aditi Tomar, Jonathan Thomas, Praisy Johnson, Lisa T Wigfall

Faculty, Staff and Student Publications

Co-infection with HIV/HPV and bio-behavioral risk factors (e.g., immunodeficiency, un-protected sex) increase likelihood for developing anal and other HPV-associated cancers among people living with HIV/AIDS (PLWHA). We explored knowledge, attitudes, and health communication regarding HPV-associated anal cancers among HIV/AIDS service organization (ASO) employees/volunteers delivering non-clinical services to PLWHA. Participants (n=59) were recruited from six ASOs located in the South United States Census region and completed a 118-item self-administered survey. For current analyses, outcome measures were knowledge, attitudes, and health communication regarding anal cancer. Descriptive statistics assessed outcome measures which were subsequently dichotomized into binary variables (i.e., high/favorable or low/unfavorable). Fisher's …

Hypofractionated, 3-Week, Preoperative Radiotherapy For Patients With Soft Tissue Sarcomas (Hyport-Sts): A Single-Centre, Open-Label, Single-Arm, Phase 2 Trial, B Ashleigh Guadagnolo, Roland L Bassett, Devarati Mitra, Ahsan Farooqi, Caroline Hempel, Courtney Dorber, Tiara Willis, Wei-Lien Wang, Ravin Ratan, Neeta Somaiah, Robert S Benjamin, Keila E Torres, Kelly K Hunt, Christopher P Scally, Emily Z Keung, Robert L Satcher, Justin E Bird, Patrick P Lin, Bryan S Moon, Valerae O Lewis, Christina L Roland, Andrew J Bishop

Faculty, Staff and Student Publications

BACKGROUND: The standard preoperative radiotherapy regimen of 50 Gy delivered in 25 fractions for 5 weeks for soft tissue sarcomas results in excellent local control, with major wound complications occurring in approximately 35% of patients. We aimed to investigate the safety of a moderately hypofractionated, shorter regimen of radiotherapy, which could be more convenient for patients.

METHODS: This single-centre, open-label, single-arm, phase 2 trial (HYPORT-STS) was done at a single tertiary cancer care centre (MD Anderson Cancer Center, Houston, TX, USA). We administered preoperative radiotherapy to a dose of 42·75 Gy in 15 fractions of 2·85 Gy/day for 3 weeks …

A Cross-National Comparison Of The Linkages Between Family Structure Histories And Early Adolescent Substance Use, Haley Stritzel, Michael Green, Robert Crosnoe

Faculty, Staff and Student Publications

Family structure can influence adolescent health with cascading implications into adulthood. Life course theory emphasizes how this phenomenon is dynamic across time, contextualized in policy systems, and grounded in processes of selection and socialization. This study used data from the U.S. (National Longitudinal Survey of Youth 1979 Child and Young Adults, n = 6,236) and U.K. (Millennium Cohort Study, n = 11,095) to examine associations between a single mother family structure between ages 0-14 and early adolescent substance use at age 14 across time and place, using inverse probability of treatment weighting to explore how results varied by selection into …

Further Evidence That Arih1 Rare Variants Predispose To Thoracic Aortic Disease, Maura L Boerio, Nicole M Engelhardt, Sanmati Cuddapah, Jessica I Gold, Isabella C Marin, Amélie Pinard, Dongchuan Guo, Siddharth K Prakash, Dianna M Milewicz

Faculty, Staff and Student Publications

No abstract provided.

Bcl11b And Atoh8 Coordinate Cellular Plasticity For Reprogramming And Transformation, Mo-Fan Huang, Rachel Shoemaker, Dung-Fang Lee

Faculty, Staff and Student Publications

By dissecting and comparing the transcriptional trajectories and epigenomic traits of reprogramming and transforming cells at the single-cell resolution, Huyghe et al discovered Bcl11b and Atoh8, two key transcription factors controlling cell plasticity during pluripotent reprogramming and oncogenic transformation.

Defective Synaptic Plasticity In A Model Of Coffin-Lowry Syndrome Is Rescued By Simultaneously Targeting Pka And Mapk Pathways, Rong-Yu Liu, Yili Zhang, Paul Smolen, Leonard J Cleary, John H Byrne

Faculty, Staff and Student Publications

Empirical and computational methods were combined to examine whether individual or dual-drug treatments can restore the deficit in long-term synaptic facilitation (LTF) of the Aplysia sensorimotor synapse observed in a cellular model of Coffin–Lowry syndrome (CLS). The model was produced by pharmacological inhibition of p90 ribosomal S6 kinase (RSK) activity. In this model, coapplication of an activator of the mitogen-activated protein kinase (MAPK) isoform ERK and an activator of protein kinase A (PKA) resulted in enhanced phosphorylation of RSK and enhanced LTF to a greater extent than either drug alone and also greater than their additive effects, which is termed …

Delayed-Interval Delivery In Multiple Gestation Pregnancies: Neonatal Mortality, Morbidity, And Development, Nicolas J Bouey, Shampa Saha, Deanne E Wilson-Costello, Matthew A Rysavy, Michele Walsh, Myra H Wyckoff, Anna Maria Hibbs

Faculty, Staff and Student Publications

OBJECTIVE: Delayed-interval delivery (DID) is the delivery of the first fetus in a multiple gestation pregnancy without prompt delivery of the remaining fetus(es). We aimed to assess infant outcomes of DID.

STUDY DESIGN: We performed a retrospective cohort study of infants born 22-28 weeks' gestation or weighing 401-1500 g. DID was defined as a passage of >24 h between the birth of firstborn and retained infants. Rates of mortality, morbidity, and developmental outcomes were compared within DID multiples, to other multiples not born by DID, and all infants in the Generic Database and follow-up datasets (excluding DID-born).

RESULTS: DID-born multiples …

Reproducing Statistics Performed In Published Randomized Controlled Trials, Naila H Dhanani, Oscar A Olavarria, Cynthia S Bell, Julie L Holihan, Mike K Liang

Faculty, Staff and Student Publications

INTRODUCTION: Randomized controlled trials (RCT) represent evidence at the lowest potential risk for bias. Clinicians in all specialties depend upon RCTs to guide patient care. Issues such as statistical discordance, or reporting statistical results that cannot be reproduced, should be uncommon. Our aim was to confirm the statistical reproducibility of published RCTs.

METHODS: PubMed was searched using "randomized controlled trial." Studies were selected using a random number generator. Studies were included if the primary outcome could be reproduced using the data and statistical test reported in the manuscript. The reproduced p-value from our analysis and the published p-value were compared. …

Etiology And Pathophysiology Of Hypoparathyroidism: A Narrative Review, Janice L Pasieka, Kelly Wentworth, Caitlin T Yeo, Serge Cremers, David Dempster, Seiji Fukumoto, Ravinder Goswami, Pascal Houillier, Michael A Levine, Jesse D Pasternak, Nancy D Perrier, Antonio Sitges-Serra, Dolores M Shoback

Faculty, Staff and Student Publications

The approach utilized a systematic review of the medical literature executed with specifically designed criteria that focused on the etiologies and pathogenesis of hypoparathyroidism. Enhanced attention by endocrine surgeons to new knowledge about parathyroid gland viability are reviewed along with the role of intraoperative parathyroid hormone (ioPTH) monitoring during and after neck surgery. Nonsurgical etiologies account for a significant proportion of cases of hypoparathyroidism (~25%), and among them, genetic etiologies are key. Given the pervasive nature of PTH deficiency across multiple organ systems, a detailed review of the skeletal, renal, neuromuscular, and ocular complications is provided. The burden of illness …

Non-Traumatic Open Globe Injuries: Presenting Characteristics And Visual Outcomes, Andrew W Gross, James Z Fan, Margaret L Pfeiffer, Alice Z Chuang, Karina Richani, Eric L Crowell

Faculty, Staff and Student Publications

Purpose: To describe clinical characteristics and visual outcomes of non-traumatic open globe injuries.

Setting: A level 1 trauma centre in a large urban medical centre.

Design: Retrospective study.

Methods: Charts of non-traumatic open globe patients admitted to MHH-TMC from 1/2010 to 3/2015 were reviewed for demographics, cause, clinical characteristics, visual acuity (VA) and enucleation.

Results: Thirty eyes were included: 15 (50%) were males with a mean age of 47 (±28) years. All presented with zone 1 injury. Twenty-five (83%) had a perforated corneal ulcer. Presenting VA was count fingers (n = 3, 10%) to NLP (n = 6, 20%). Twenty-four …

Evaluation Of Murine Host Sex As A Biological Variable In Transplanted Human Intestinal Organoid Development, Eoin P Mcneill, Vikas S Gupta, David J Sequeira, Noah F Shroyer, Allison L Speer

Faculty, Staff and Student Publications

Background: Human intestinal organoids (HIOs), when transplanted into immunocompromised mice (tHIOs), demonstrate significant growth and maturation. While both male and female mice are reported to be viable hosts for these experiments, a direct comparison of sex-related differences in tHIO structure and development has not been performed.

Aims: We sought to identify host sex-related differences in tHIO engraftment, morphology, and epithelial and mesenchymal development.

Methods: HIOs were generated in vitro and transplanted beneath the kidney capsule of NSG male and female mice. tHIOs were harvested at 8-9 weeks. Anthropometric measurements were captured. tHIOs were divided in half and histology or RT-qPCR …

Using Single Molecule Molecular Inversion Probes As A Cost-Effective, High-Throughput Sequencing Approach To Target All Genes And Loci Associated With Macular Diseases, Rebekkah J Hitti-Malin, Claire-Marie Dhaenens, Daan M Panneman, Zelia Corradi, Mubeen Khan, Anneke I Den Hollander, G Jane Farrar, Christian Gilissen, Alexander Hoischen, Maartje Van De Vorst, Femke Bults, Erica G M Boonen, Patrick Saunders, Susanne Roosing, Frans P M Cremers

Faculty, Staff and Student Publications

Macular degenerations (MDs) are a subgroup of retinal disorders characterized by central vision loss. Knowledge is still lacking on the extent of genetic and nongenetic factors influencing inherited MD (iMD) and age-related MD (AMD) expression. Single molecule Molecular Inversion Probes (smMIPs) have proven effective in sequencing the ABCA4 gene in patients with Stargardt disease to identify associated coding and noncoding variation, however many MD patients still remain genetically unexplained. We hypothesized that the missing heritability of MDs may be revealed by smMIPs-based sequencing of all MD-associated genes and risk factors. Using 17,394 smMIPs, we sequenced the coding regions of 105 …

A Cluster-Randomized Controlled Trial Of Automated Internet Weight-Loss Programs In Primary Care: Role Of Automated Provider Feedback, Deborah F Tate, Jennifer L Kraschnewski, Caitlin Martinez, Molly Diamond, Susan Veldheer, Kevin O Hwang, Erik B Lehman, Chengwu Yang, Christopher N Sciamanna

Faculty, Staff and Student Publications

OBJECTIVE: Despite the high prevalence of obesity and associated health risks in the United States adult population, few primary care providers (PCPs) have time and training to provide weight-management counseling to their patients. This study aims to compare the effect of referral to a comprehensive automated digital weight-loss program, with or without provider email feedback, with usual care on weight loss in patients with overweight or obesity.

METHODS: A total of 550 adults (mean [SD], 51.4 [11.2] years, BMI = 35.1 [5.5] kg/m

RESULTS: Weight changes (mean [SE]) at 12 months were -0.92 (0.46), -3.68 (0.46), and -3.58 (0.48) kg …

Association Of Patient Belief About Success Of Antibiotics For Appendicitis And Outcomes: A Secondary Analysis Of The Coda Randomized Clinical Trial, Writing Group For The Coda Collaborative, Irene Y Zhang, Emily C Voldal, Giana H Davidson, Joshua M Liao, Callie M Thompson, Wesley H Self, Lillian S Kao, Jill Cherry-Bukowiec, Krishnan Raghavendran, Amy H Kaji, Daniel A Deugarte, Eva Gonzalez, Katherine A Mandell, Kristen Ohe, Nicole Siparsky, Thea P Price, David C Evans, Jesse Victory, William Chiang, Alan Jones, Matthew E Kutcher, Hailie Ciomperlik, Mike K Liang, Heather L Evans, Brett A Faine, Miriam Neufeld, Sabrina E Sanchez, Anusha Krishnadasan, Bryan A Comstock, Patrick J Heagerty, Sarah O Lawrence, Sarah E Monsell, Erin E C Fannon, Larry G Kessler, David A Talan, David R Flum

Faculty, Staff and Student Publications

IMPORTANCE: A patient's belief in the likely success of a treatment may influence outcomes, but this has been understudied in surgical trials.

OBJECTIVE: To examine the association between patients' baseline beliefs about the likelihood of treatment success with outcomes of antibiotics for appendicitis in the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial.

DESIGN, SETTING, AND PARTICIPANTS: This was a secondary analysis of the CODA randomized clinical trial. Participants from 25 US medical centers were enrolled between May 3, 2016, and February 5, 2020. Included in the analysis were participants with appendicitis who were randomly assigned to receive …

Continued Treatment With Nintedanib In Patients With Systemic Sclerosis-Associated Interstitial Lung Disease: Data From Senscis-On, Yannick Allanore, Madelon C Vonk, Oliver Distler, Arata Azuma, Maureen D Mayes, Martina Gahlemann, Alexandra James, Veronika Kohlbrenner, Margarida Alves, Dinesh Khanna, Kristin B Highland, Senscis-On Trial Investigators

Faculty, Staff and Student Publications

Objectives: In the SENSCIS trial in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD), nintedanib reduced the rate of decline in forced vital capacity (FVC) versus placebo, with adverse events that were manageable for most patients. An open-label extension trial, SENSCIS-ON, is assessing safety and FVC decline during longer term nintedanib treatment.

Methods: Patients who completed the SENSCIS trial or a drug-drug interaction (DDI) study of nintedanib and oral contraceptive on treatment were eligible to enter SENSCIS-ON. Adverse events and changes in FVC over 52 weeks of SENSCIS-ON were assessed in patients who received nintedanib in SENSCIS and continued nintedanib …

An Optimized Cell-Based Assay To Assess Influenza Virus Replication By Measuring Neuraminidase Activity And Its Applications For Virological Surveillance, Mira C Patel, Daniel Flanigan, Chenchen Feng, Anton Chesnokov, Ha T Nguyen, Anwar Abd Elal, John Steel, Rebecca J Kondor, David E Wentworth, Larisa V Gubareva, Vasiliy P Mishin

Faculty, Staff and Student Publications

Year-round virological characterization of circulating epidemic influenza viruses is conducted worldwide to detect the emergence of viruses that may escape pre-existing immunity or acquire resistance to antivirals. High throughput phenotypic assays are needed to complement the sequence-based analysis of circulating viruses and improve pandemic preparedness. The recent entry of a polymerase inhibitor, baloxavir, into the global market further highlighted this need. Here, we optimized a cell-based assay that considerably streamlines antiviral and antigenic testing by replacing lengthy immunostaining and imaging procedures used in current assay with measuring the enzymatic activity of nascent neuraminidase (NA) molecules expressed on the surface of …

A Pilot Survey: Retention In Pain Medicine Among Fellowship Trained Anesthesiologists, Sarang S Koushik, Kelly Leap, Kenneth Seier, Kay See Tan, Naum Shaparin, Alan D Kaye, Omar Viswanath, Grant H Chen

Faculty, Staff and Student Publications

BACKGROUND: We aim to explore the factors related to job satisfaction among pain physicians and identify the reasons why individuals minimize or stop practicing outpatient pain medicine.

OBJECTIVES/STUDY DESIGN: This is a survey-based study with the primary goal to identify factors determining job satisfaction and dissatisfaction among pain medicine fellowship graduates who continue to practice and those who are no longer practicing interventional pain. A secondary goal is to elucidate reasons for anesthesiologists trained in pain medicine to leave pain medicine, despite an additional year of training, and to work as general anesthesiologists.

METHODS: In this study, all 114 pain …

Right Ventricular Energetic Biomarkers From 4d Flow Cmr Are Associated With Exertional Capacity In Pulmonary Arterial Hypertension, Xiaodan Zhao, Shuang Leng, Ru-San Tan, Ping Chai, Tee Joo Yeo, Jennifer Ann Bryant, Lynette L S Teo, Marielle V Fortier, Wen Ruan, Ting Ting Low, Ching Ching Ong, Shuo Zhang, Rob J Van Der Geest, John C Allen, Marina Hughes, Pankaj Garg, Teng Hong Tan, James W Yip, Ju Le Tan, Liang Zhong

Faculty, Staff and Student Publications

BACKGROUND: Cardiovascular magnetic resonance (CMR) offers comprehensive right ventricular (RV) evaluation in pulmonary arterial hypertension (PAH). Emerging four-dimensional (4D) flow CMR allows visualization and quantification of intracardiac flow components and calculation of phasic blood kinetic energy (KE) parameters but it is unknown whether these parameters are associated with cardiopulmonary exercise test (CPET)-assessed exercise capacity, which is a surrogate measure of survival in PAH. We compared 4D flow CMR parameters in PAH with healthy controls, and investigated the association of these parameters with RV remodelling, RV functional and CPET outcomes.

METHODS: PAH patients and healthy controls from two centers were prospectively …