Medical Specialties Commons^™

Two Structurally Defined Aβ Polymorphs Promote Different Pathological Changes In Susceptible Mice, Ruben Gomez-Gutierrez, Ujjayini Ghosh, Wai-Ming Yau, Nazaret Gamez, Katherine Do, Carlos Kramm, Hamid Shirani, Laura Vegas-Gomez, Jonathan Schulz, Ines Moreno-Gonzalez, Antonia Gutierrez, K Peter R Nilsson, Robert Tycko, Claudio Soto, Rodrigo Morales

Faculty, Staff and Student Publications

Misfolded Aβ is involved in the progression of Alzheimer's disease (AD). However, the role of its polymorphic variants or conformational strains in AD pathogenesis is not fully understood. Here, we study the seeding properties of two structurally defined synthetic misfolded Aβ strains (termed 2F and 3F) using in vitro and in vivo assays. We show that 2F and 3F strains differ in their biochemical properties, including resistance to proteolysis, binding to strain-specific dyes, and in vitro seeding. Injection of these strains into a transgenic mouse model produces different pathological features, namely different rates of aggregation, formation of different plaque types, …

Therapeutic Effects Of Fully Reduced Hmgb1 On Fibroblasts And Pre-Osteoblasts Cultured Under Diabetic Conditions, Alfonso Reyes, Bhuvana Lakkasetter Chandrashekar, Peter Elvin, Danieli Rodrigues, Javier La Fontaine, Claudia Biguetti

School of Podiatric Medicine - Student Research

Background: Recent studies have shown that fully reduced High Mobility Group Box-1 (FR-HMGB1) can improve wound healing under normoglycemic conditions, but it has not been tested for diabetic conditions. This study aimed to assess the regenerative potential of FR-HMGB1 under high glucose levels in vitro.

Methods: Migration of human fibroblasts (HF) was tested using a scratch assay in control conditions, and in the presence of FR-HMGB1 (1.0 µg/mL and 10 µg/mL), both in non-diabetic (ND) and diabetic (D) conditions (60mM of glucose added to the culture media). HF cells were tested after 18 hours of scratching and stained with …

Piezo2 In Somatosensory Neurons Controls Gastrointestinal Transit, M Rocio Servin-Vences, Ruby M Lam, Alize Koolen, Yu Wang, Dimah N Saade, Meaghan Loud, Halil Kacmaz, Suzanne Frausto, Yunxiao Zhang, Arthur Beyder, Kara L Marshall, Carsten G Bönnemann, Alexander T Chesler, Ardem Patapoutian

Duncan NRI Faculty and Staff Publications

The gastrointestinal tract is in a state of constant motion. These movements are tightly regulated by the presence of food and help digestion by mechanically breaking down and propelling gut content. Mechanical sensing in the gut is thought to be essential for regulating motility; however, the identity of the neuronal populations, the molecules involved, and the functional consequences of this sensation are unknown. Here, we show that humans lacking PIEZO2 exhibit impaired bowel sensation and motility. Piezo2 in mouse dorsal root, but not nodose ganglia is required to sense gut content, and this activity slows down food transit rates in …

Effectiveness Of An Emergency Department-Based Machine Learning Clinical Decision Support Tool To Prevent Outpatient Falls Among Older Adults: Protocol For A Quasi-Experimental Study, Daniel J Hekman, Amy L Cochran, Apoorva P Maru, Hanna J Barton, Manish N Shah, Douglas Wiegmann, Maureen A Smith, Frank Liao, Brian W Patterson

Faculty, Staff and Student Publications

Background

Emergency department (ED) providers are important collaborators in preventing falls for older adults because they are often the first health care providers to see a patient after a fall and because at-home falls are often preceded by previous ED visits. Previous work has shown that ED referrals to falls interventions can reduce the risk of an at-home fall by 38%. Screening patients at risk for a fall can be time-consuming and difficult to implement in the ED setting. Machine learning (ML) and clinical decision support (CDS) offer the potential of automating the screening process. However, it remains unclear whether …

Urachal Xanthogranuloma: A Rare But Important Case Presenting As A Urachal Mass, Kunal Jain, Esha Jain, Richard Dilena, Rola Saleeb, Umesh Jain

Faculty, Staff and Student Publications

BACKGROUND: A urachal mass is a relatively rare presentation to the urologists' practice, often requiring radical surgical excision for a definitive diagnosis. Xanthogranulomatous inflammation of the urachus is an extremely rare entity with few cases reported worldwide, and to the best of our knowledge, no cases reported in the western world.

CASE PRESENTATION: In this case, a 55-year-old male patient presented with bothersome lower urinary tract symptoms and computed tomography findings demonstrating a urachal mass that was worrisome for urachal carcinoma. Following surgical intervention, histopathology revealed urachal xanthogranuloma. Post-operatively, the patient recovered well, and eventually, he had symptomatic and radiologic …

Mavs Signaling Is Required For Preventing Persistent Chikungunya Heart Infection And Chronic Vascular Tissue Inflammation, Maria G Noval, Sophie N Spector, Eric Bartnicki, Franco Izzo, Navneet Narula, Stephen T Yeung, Payal Damani-Yokota, M Zahidunnabi Dewan, Valeria Mezzano, Bruno A Rodriguez-Rodriguez, Cynthia Loomis, Kamal M Khanna, Kenneth A Stapleford

Faculty, Staff and Student Publications

Chikungunya virus (CHIKV) infection has been associated with severe cardiac manifestations, yet, how CHIKV infection leads to heart disease remains unknown. Here, we leveraged both mouse models and human primary cardiac cells to define the mechanisms of CHIKV heart infection. Using an immunocompetent mouse model of CHIKV infection as well as human primary cardiac cells, we demonstrate that CHIKV directly infects and actively replicates in cardiac fibroblasts. In immunocompetent mice, CHIKV is cleared from cardiac tissue without significant damage through the induction of a local type I interferon response from both infected and non-infected cardiac cells. Using mice deficient in …

Safety And Efficacy Of Immune Checkpoint Inhibitors In Patients With Cancer And Viral Hepatitis: The Md Anderson Cancer Center Experience, Mirella Nardo, Bulent Yilmaz, Blessie Elizabeth Nelson, Harrys A Torres, Lan Sun Wang, Bruno Palma Granwehr, Juhee Song, Hanna R F Dalla Pria, Van A Trinh, Isabella C Glitza Oliva, Sapna P Patel, Nizar M Tannir, Ahmed Omar Kaseb, Mehmet Altan, Sunyoung S Lee, Ethan Miller, Hao Zhang, Bettzy A Stephen, Aung Naing

Faculty, Staff and Student Publications

Background: Despite the clinical benefit of immune checkpoint inhibitors (ICIs), patients with a viral hepatitis have been excluded from clinical trials because of safety concerns. The purpose of this study was to determine the incidence rate of adverse events (AEs) in patients with viral hepatitis who received ICIs for cancer treatment.

Materials and methods: We conducted a retrospective study in patients with cancer and concurrent hepatitis B or C, who had undergone treatment with ICI at MD Anderson Cancer Center from January 1, 2010 to December 31, 2019.

Results: Of the 1076 patients screened, we identified 33 with concurrent hepatitis. …

Spatial Distribution Of Mycobacterium Tuberculosis Mrna And Secreted Antigens In Acid-Fast Negative Human Antemortem And Resected Tissue, Job Dekker, Frank Alber, Sarah Aufmkolk, Brian J Beliveau, Benoit G Bruneau, Andrew S Belmont, Lacramioara Bintu, Alistair Boettiger, Riccardo Calandrelli, Christine M Disteche, David M Gilbert, Thomas Gregor, Anders S Hansen, Bo Huang, Danwei Huangfu, Reza Kalhor, Christina S Leslie, Wenbo Li, Yun Li, Jian Ma, William S Noble, Peter J Park, Jennifer E Phillips-Cremins, Katherine S Pollard, Susanne M Rafelski, Bing Ren, Yijun Ruan, Yaron Shav-Tal, Yin Shen, Jay Shendure, Xiaokun Shu, Caterina Strambio-De-Castillia, Anastassiia Vertii, Huaiying Zhang, Sheng Zhong

Faculty, Staff and Student Publications

The four-dimensional nucleome (4DN) consortium studies the architecture of the genome and the nucleus in space and time. We summarize progress by the consortium and highlight the development of technologies for (1) mapping genome folding and identifying roles of nuclear components and bodies, proteins, and RNA, (2) characterizing nuclear organization with time or single-cell resolution, and (3) imaging of nuclear organization. With these tools, the consortium has provided over 2,000 public datasets. Integrative computational models based on these data are starting to reveal connections between genome structure and function. We then present a forward-looking perspective and outline current aims to …

Novel Murine Glioblastoma Models That Reflect The Immunotherapy Resistance Profile Of A Human Disease, Chao-Hsien Chen, Renee L Chin, Genevieve P Hartley, Spencer T Lea, Brian J Engel, Cheng-En Hsieh, Rishika Prasad, Jason Roszik, Takashi Shingu, Gregory A Lizee, Amy B Heimberger, Steven W Millward, Jian Hu, David S Hong, Michael A Curran

Faculty, Staff and Student Publications

BACKGROUND: The lack of murine glioblastoma models that mimic the immunobiology of human disease has impeded basic and translational immunology research. We, therefore, developed murine glioblastoma stem cell lines derived from Nestin-CreERT2QkL/L; Trp53L/L; PtenL/L (QPP) mice driven by clinically relevant genetic mutations common in human glioblastoma. This study aims to determine the immune sensitivities of these QPP lines in immunocompetent hosts and their underlying mechanisms.

METHODS: The differential responsiveness of QPP lines was assessed in the brain and flank in untreated, anti-PD-1, or anti-CTLA-4 treated mice. The impact of genomic landscape on the responsiveness of each tumor was measured through …

Her3 Targeting Augments The Efficacy Of Panobinostat In Claudin-Low Triple-Negative Breast Cancer Cells, Hui Lyu, Defu Hou, Hao Liu, Sanbao Ruan, Congcong Tan, Jiande Wu, Chindo Hicks, Bolin Liu

School of Medicine Faculty Publications

Patients with triple-negative breast cancer (TNBC) have a poor prognosis and high relapse rate due to limited therapeutic options. This study was conducted to determine the mechanisms of action of panobinostat, a pan-inhibitor of histone deacetylase (HDAC) and FDA-approved medication for multiple myeloma, in TNBC and to provide a rationale for effective drug combinations against this aggressive disease. RNA sequencing analyses of the claudin-low (CL) TNBC (MDA-MB-231) cells untreated or treated with panobinostat were performed to identify the differentially expressed genes. Adaptive alterations in gene expression were analyzed and validated in additional CL TNBC cells. Tumor xenograft models were used …

Donor-Recipient Specificity And Age-Dependency In Fecal Microbiota Therapy And Probiotic Resolution Of Gastrointestinal Symptoms, Qinglong Wu, Prapaporn Boonma, Shyam Badu, Nazli Yalcinkaya, Sik Yu So, Kevin W Garey, Kent Williams, L Eugene Arnold, Robert J Shulman, Richard Kellermayer, Tor C Savidge

Faculty, Staff and Students Publications

Fecal microbiota transplantation (FMT) has proven to be an effective treatment for recurrent Clostridioides difficile infection (rCDI) in both adult and pediatric patients. However, as microbiome development is a critical factor in children, it remains unclear whether adult fecal donors can provide age-appropriate functional restoration in pediatric patients. To address this issue, we conducted an integrated systems approach and found that concordant donor strain engraftment, along with metabolite restoration, are associated with FMT outcomes in both adult and pediatric rCDI patients. Although functional restoration after FMT is not strain-specific, specialized metabolic functions are retained in pediatric patients when adult fecal …

Monoallelic Variation In Dhx9, The Gene Encoding The Dexh-Box Helicase Dhx9, Underlies Neurodevelopment Disorders And Charcot-Marie-Tooth Disease, Daniel G Calame, Tianyu Guo, Chen Wang, Lillian Garrett, Angad Jolly, Moez Dawood, Alina Kurolap, Noa Zunz Henig, Jawid M Fatih, Isabella Herman, Haowei Du, Tadahiro Mitani, Lore Becker, Birgit Rathkolb, Raffaele Gerlini, Claudia Seisenberger, Susan Marschall, Jill V Hunter, Amanda Gerard, Alexis Heidlebaugh, Thomas Challman, Rebecca C Spillmann, Shalini N Jhangiani, Zeynep Coban-Akdemir, Seema Lalani, Lingxiao Liu, Anya Revah-Politi, Alejandro Iglesias, Edwin Guzman, Evan Baugh, Nathalie Boddaert, Sophie Rondeau, Clothide Ormieres, Giulia Barcia, Queenie K G Tan, Isabelle Thiffault, Tomi Pastinen, Kazim Sheikh, Suur Biliciler, Davide Mei, Federico Melani, Vandana Shashi, Yuval Yaron, Mary Steele, Emma Wakeling, Elsebet Østergaard, Lusine Nazaryan-Petersen, Undiagnosed Diseases Network, Francisca Millan, Teresa Santiago-Sim, Julien Thevenon, Ange-Line Bruel, Christel Thauvin-Robinet, Denny Popp, Konrad Platzer, Pawel Gawlinski, Wojciech Wiszniewski, Dana Marafi, Davut Pehlivan, Jennifer E Posey, Richard A Gibbs, Valerie Gailus-Durner, Renzo Guerrini, Helmut Fuchs, Martin Hrabě De Angelis, Sabine M Hölter, Hoi-Hung Cheung, Shen Gu, James R Lupski

Faculty, Staff and Student Publications

DExD/H-box RNA helicases (DDX/DHX) are encoded by a large paralogous gene family; in a subset of these human helicase genes, pathogenic variation causes neurodevelopmental disorder (NDD) traits and cancer. DHX9 encodes a BRCA1-interacting nuclear helicase regulating transcription, R-loops, and homologous recombination and exhibits the highest mutational constraint of all DDX/DHX paralogs but remains unassociated with disease traits in OMIM. Using exome sequencing and family-based rare-variant analyses, we identified 20 individuals with de novo, ultra-rare, heterozygous missense or loss-of-function (LoF) DHX9 variant alleles. Phenotypes ranged from NDDs to the distal symmetric polyneuropathy axonal Charcot-Marie-Tooth disease (CMT2). Quantitative Human Phenotype Ontology (HPO) …

Proteogenomic Analysis Of Chemo-Refractory High-Grade Serous Ovarian Cancer, Shrabanti Chowdhury, Jacob J Kennedy, Richard G Ivey, Oscar D Murillo, Noshad Hosseini, Xiaoyu Song, Francesca Petralia, Anna Calinawan, Sara R Savage, Anna B Berry, Boris Reva, Umut Ozbek, Azra Krek, Weiping Ma, Felipe Da Veiga Leprevost, Jiayi Ji, Seungyeul Yoo, Chenwei Lin, Uliana J Voytovich, Yajue Huang, Sun-Hee Lee, Lindsay Bergan, Travis D Lorentzen, Mehdi Mesri, Henry Rodriguez, Andrew N Hoofnagle, Zachary T Herbert, Alexey I Nesvizhskii, Bing Zhang, Jeffrey R Whiteaker, David Fenyo, Wilson Mckerrow, Joshua Wang, Stephan C Schürer, Vasileios Stathias, X Steven Chen, Mary Helen Barcellos-Hoff, Timothy K Starr, Boris J Winterhoff, Andrew C Nelson, Samuel C Mok, Scott H Kaufmann, Charles Drescher, Marcin Cieslik, Pei Wang, Michael J Birrer, Amanda G Paulovich

Faculty, Staff and Student Publications

To improve the understanding of chemo-refractory high-grade serous ovarian cancers (HGSOCs), we characterized the proteogenomic landscape of 242 (refractory and sensitive) HGSOCs, representing one discovery and two validation cohorts across two biospecimen types (formalin-fixed paraffin-embedded and frozen). We identified a 64-protein signature that predicts with high specificity a subset of HGSOCs refractory to initial platinum-based therapy and is validated in two independent patient cohorts. We detected significant association between lack of Ch17 loss of heterozygosity (LOH) and chemo-refractoriness. Based on pathway protein expression, we identified 5 clusters of HGSOC, which validated across two independent patient cohorts and patient-derived xenograft (PDX) …

Beyond The Exome: What’S Next In Diagnostic Testing For Mendelian Conditions, Monica H Wojcik, Chloe M Reuter, Shruti Marwaha, Medhat Mahmoud, Michael H Duyzend, Hayk Barseghyan, Bo Yuan, Philip M Boone, Emily E Groopman, Emmanuèle C Délot, Deepti Jain, Alba Sanchis-Juan, Genomics Research To Elucidate The Genetics Of Rare Diseases (Gregor) Consortium, Lea M Starita, Michael Talkowski, Stephen B Montgomery, Michael J Bamshad, Jessica X Chong, Matthew T Wheeler, Seth I Berger, Anne O'Donnell-Luria, Fritz J Sedlazeck, Danny E Miller

Faculty, Staff and Student Publications

Despite advances in clinical genetic testing, including the introduction of exome sequencing (ES), more than 50% of individuals with a suspected Mendelian condition lack a precise molecular diagnosis. Clinical evaluation is increasingly undertaken by specialists outside of clinical genetics, often occurring in a tiered fashion and typically ending after ES. The current diagnostic rate reflects multiple factors, including technical limitations, incomplete understanding of variant pathogenicity, missing genotype-phenotype associations, complex gene-environment interactions, and reporting differences between clinical labs. Maintaining a clear understanding of the rapidly evolving landscape of diagnostic tests beyond ES, and their limitations, presents a challenge for non-genetics professionals. …

Leveraging Telehealth Supportive Oncology Services To Combat Covid-19 Isolation In Breast Cancer Patients: A Cancer Center’S Perspective, Jake R. Erickson, Maranda K. Pahlkotter, Paul D. Thielking, Jane M. Porretta, Regina Rosenthal, Cindy B. Matsen, Kirstyn E. Brownson

Patient Experience Journal

During the COVID-19 pandemic, breast cancer patient in-person visits were converted to telehealth visits. Given our concerns about increased isolation amongst breast cancer patients during the pandemic, and the deleterious effects of such isolation on patient outcomes, we investigated utilization rates of psycho-social services amongst newly diagnosed breast cancer patients at our institution. We explored visit platforms (telehealth versus in-person) and time points prior to and encompassing the early pandemic. Despite decreased new breast cancer visits, there was a greater than 2-fold increase in supportive oncology service encounters in breast cancer patients during COVID-19 suggesting increased need for psycho-oncology resources. …

The Initial Psychometric Evaluation Of A New Emergency Department Patient-Reported Experience Measure (Ed Prem), Claudia Bull, Julia Crilly, Sharon Latimer, Emma Hall, Brigid M. Gillespie

Patient Experience Journal

Patient-reported experience measures (PREMs) are critical to evaluating the person-centeredness, safety, and quality of healthcare services internationally. The aim of this study was to describe the initial psychometric evaluation of a new Emergency Department (ED) PREM. Adult patients presenting to the ED of a tertiary hospital in southeast Queensland, Australia during January 2022 were recruited in-person. Participants selected their preferred ED PREM mode of administration from online, telephone, or postal, and had 14 days from recruitment to complete the survey. Item reduction, structural validity, discriminant validity, and internal consistency reliability were assessed. A sample of 349 (68.4%) was achieved. Item …

Ot's Role In Facilitating Successful Role Transition For Informal Caregivers Of People Living With Dementia, Kiyatta Freeman, Monica Watford, Evyline Chioma

Summer 2023 Virtual OTD Capstone Symposium

The aim of this capstone project was to identify education and training needs for family caregivers of individuals living with dementia and create an educational workshop based on these identified needs. This workshop is a dementia training course focused on education on the dementia diagnosis and effective care strategies to promote occupational participation and safety for the care recipient and the caregiver. The aim is to improve care competency, reduce stress, and facilitate role transition.

The Importance Of Addressing Sleep As An Occupation Within Assisted Living Communities, Brittany Kiattitananan, Kendra Orcutt, Lisa Griggs-Stapleton

Summer 2023 Virtual OTD Capstone Symposium

Around 40-70% of older adults have difficulty sleeping (Sheth & Thomas, 2019). This poster presents an occupation-based sleep intervention program developed for residents of an assisted living community and serves to inform OT practitioners on addressing sleep in their own practice.

Persistence To Anti-Cgrp Monoclonal Antibodies And Onabotulinumtoxina Among Patients With Migraine: A Retrospective Cohort Study, Larry Charleston, Brian Talon, Christine Sullivan, Carlton Anderson, Steven Kymes, Stephane A. Regnier, Seema Soni-Brahmbhatt, Stephanie J. Nahas

Department of Jefferson Headache Center Papers and Presentations

BACKGROUND: To date, real-world evidence on persistence to anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAbs) or onabotulinumtoxinA have excluded eptinezumab. This retrospective cohort study was performed to compare treatment persistency among patients with migraine on anti-CGRP mAbs (erenumab, fremanezumab, galcanezumab, or eptinezumab) or onabotulinumtoxinA.

METHODS: This retrospective study used IQVIA PharmMetrics data. Adult patients with migraine treated with an anti-CGRP mAb or onabotulinumtoxinA who had 12 months of continuous insurance enrollment before starting treatment were included. A "most recent treatment episode" analysis was used in which the most recent episode was defined as the latest treatment period with the same …

The Effects Of Covid-19 On Cognition In The Pediatric Population, Mia Ramirez, Hope Mccarroll, Lisa Griggs-Stapleton

Summer 2023 Virtual OTD Capstone Symposium

Coronavirus disease or COVID-19, is an infectious disease caused by the SARS-CoV-2 virus. COVID-19 can affect adults and children by causing long-term symptoms such as difficulty concentrating, anxiety, depression, long-term breathing problems, and even heart complications. Children represent about 19% of all reported COVID-19 cases since the pandemic first began. Children also can have trouble concentrating, which can impact their ability to attend school and do their daily activities that require concentration, such as dressing, showering, and social participation. Cognitive deficits due to COVID-19 can impact the pediatric population as they may have decreased occupational performance in desired occupations, such …

Program Development In Pediatric Prosthetic Training For Occupational Therapists, Paulina Alas, Monica Watford, Grace Evasco

Summer 2023 Virtual OTD Capstone Symposium

This project delves into the necessity for professional tools designed to assist occupational therapists (OTs) in readying themselves for the treatment of pediatric patients requiring upper limb prosthetics. The endeavor encompasses an examination of various diagnoses that warrant prosthetic intervention, an exploration of diverse prosthetic variants, and a comprehensive manual detailing pre-prosthetic and prosthetic functional training.

The Importance Of Occupational Therapy During The Transition From The Nicu To Home For Parents’ Confidence In Co-Occupations, Randa Sloan, Mary Jan Greer, Faith Saunders

Summer 2023 Virtual OTD Capstone Symposium

Parents often transition home from the NICU with decreased confidence in their abilities to care for their infant after having extensive specialized care (Craig et al., 2015). Boykova (2016) explained that parents experienced low self-confidence and fear of making mistakes in their infants’ care upon arriving home. The problem is the lack of support and education about resources for parents during the transition from the NICU to home. Parents lack knowledge about the vital role OT plays in improving confidence in co-occupations which will play a role in improved parental mental health. Furthermore, parents and caregivers lack knowledge on how …

Implementation Of Tai Chi Among Individuals With Dementia In Long-Term Memory Care, Patricia I. Cordova, Lisa Griggs-Stapleton, Kim Broussard

Summer 2023 Virtual OTD Capstone Symposium

This project focused on a dementia population within long-term care, where increased disablement occurs. A Tai Chi program was implemented into the daily routine of individuals in a long-term memory care facility to improve dynamic sitting balance for the performance of daily occupations.

Genetic Insights Into Resting Heart Rate And Its Role In Cardiovascular Disease, Yordi J Van De Vegte, Ruben N Eppinga, M Yldau Van Der Ende, Yanick P Hagemeijer, Yuvaraj Mahendran, Elias Salfati, Albert V Smith, Vanessa Y Tan, Dan E Arking, Ioanna Ntalla, Emil V Appel, Claudia Schurmann, Jennifer A Brody, Rico Rueedi, Ozren Polasek, Gardar Sveinbjornsson, Cecile Lecoeur, Claes Ladenvall, Jing Hua Zhao, Aaron Isaacs, Lihua Wang, Jian'an Luan, Shih-Jen Hwang, Nina Mononen, Kirsi Auro, Anne U Jackson, Lawrence F Bielak, Linyao Zeng, Nabi Shah, Maria Nethander, Archie Campbell, Tuomo Rankinen, Sonali Pechlivanis, Lu Qi, Wei Zhao, Federica Rizzi, Toshiko Tanaka, Antonietta Robino, Massimiliano Cocca, Leslie Lange, Martina Müller-Nurasyid, Carolina Roselli, Weihua Zhang, Marcus E Kleber, Xiuqing Guo, Henry J Lin, Francesca Pavani, Tessel E Galesloot, Raymond Noordam, Yuri Milaneschi, Katharina E Schraut, Marcel Den Hoed, Frauke Degenhardt, Stella Trompet, Marten E Van Den Berg, Giorgio Pistis, Yih-Chung Tham, Stefan Weiss, Xueling S Sim, Hengtong L Li, Peter J Van Der Most, Ilja M Nolte, Leo-Pekka Lyytikäinen, M Abdullah Said, Daniel R Witte, Carlos Iribarren, Lenore Launer, Susan M Ring, Paul S De Vries, Peter Sever, Allan Linneberg, Erwin P Bottinger, Sandosh Padmanabhan, Bruce M Psaty, Nona Sotoodehnia, Ivana Kolcic, Dcct/Edic Research Group, David O Arnar, Daniel F Gudbjartsson, Hilma Holm, Beverley Balkau, Claudia T Silva, Christopher H Newton-Cheh, Kjell Nikus, Perttu Salo, Karen L Mohlke, Patricia A Peyser, Heribert Schunkert, Mattias Lorentzon, Jari Lahti, Dabeeru C Rao, Marilyn C Cornelis, Jessica D Faul, Jennifer A Smith, Katarzyna Stolarz-Skrzypek, Stefania Bandinelli, Maria Pina Concas, Gianfranco Sinagra, Thomas Meitinger, Melanie Waldenberger, Moritz F Sinner, Konstantin Strauch, Graciela E Delgado, Kent D Taylor, Jie Yao, Luisa Foco, Olle Melander, Jacqueline De Graaf, Renée De Mutsert, Eco J C De Geus, Åsa Johansson, Peter K Joshi, Lars Lind, Andre Franke, Peter W Macfarlane, Kirill V Tarasov, Nicholas Tan, Stephan B Felix, E-Shyong Tai, Debra Q Quek, Harold Snieder, Johan Ormel, Martin Ingelsson, Cecilia Lindgren, Andrew P Morris, Olli T Raitakari, Torben Hansen, Themistocles Assimes, Vilmundur Gudnason, Nicholas J Timpson, Alanna C Morrison, Patricia B Munroe, David P Strachan, Niels Grarup, Ruth J F Loos, Susan R Heckbert, Peter Vollenweider, Caroline Hayward, Kari Stefansson, Philippe Froguel, Leif Groop, Nicholas J Wareham, Cornelia M Van Duijn, Mary F Feitosa, Christopher J O'Donnell, Mika Kähönen, Markus Perola, Michael Boehnke, Sharon L R Kardia, Jeanette Erdmann, Colin N A Palmer, Claes Ohlsson, David J Porteous, Johan G Eriksson, Claude Bouchard, Susanne Moebus, Peter Kraft, David R Weir, Daniele Cusi, Luigi Ferrucci, Sheila Ulivi, Giorgia Girotto, Adolfo Correa, Stefan Kääb, Annette Peters, John C Chambers, Jaspal S Kooner, Winfried März, Jerome I Rotter, Andrew A Hicks, J Gustav Smith, Lambertus A L M Kiemeney, Dennis O Mook-Kanamori, Brenda W J H Penninx, Ulf Gyllensten, James F Wilson, Stephen Burgess, Johan Sundström, Wolfgang Lieb, J Wouter Jukema, Mark Eijgelsheim, Edward L M Lakatta, Ching-Yu Cheng, Marcus Dörr, Tien-Yin Wong, Charumathi Sabanayagam, Albertine J Oldehinkel, Harriette Riese, Terho Lehtimäki, Niek Verweij, Pim Van Der Harst

Faculty, Staff and Student Publications

Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample …

Alternative Splicing Of Ceacam1 By Hypoxia-Inducible Factor-1Α Enhances Tolerance To Hepatic Ischemia In Mice And Humans, Kenneth J Dery, Hidenobu Kojima, Shoichi Kageyama, Kentaro Kadono, Hirofumi Hirao, Brian Cheng, Yuan Zhai, Douglas G Farmer, Fady M Kaldas, Xiaoyi Yuan, Holger K Eltzschig, Jerzy W Kupiec-Weglinski

Faculty, Staff and Student Publications

Although alternative splicing (AS) drives transcriptional responses and cellular adaptation to environmental stresses, its contributions in organ transplantation have not been appreciated. We have shown that carcinoembryonic antigen-related cell adhesion molecule (Ceacam1; CD66a), a transmembrane biliary glycoprotein expressed in epithelial, endothelial, and immune cells, determines donor liver transplant quality. Here, we studied how AS of Ceacam1 affects ischemia-reperfusion injury (IRI) in mouse and human livers. We found that the short cytoplasmic isoform Ceacam1-S increased during early acute and late resolution phases of warm IRI injury in mice. Transfection of Ceacam1-deficient mouse hepatocytes with adenoviral Ceacam1-S mitigated hypoxia-induced loss of …

Penumbra Aspiration Thrombectomy Of The Superior Mesenteric Artery For Mesenteric Ischemia, Brandon A. Creisher, Prashanth Palvannan, Dawn Salvatore, Paul J. Dimuzio, Babak Abai, Michael Nooromid

Department of Surgery Faculty Papers

Acute mesenteric ischemia from thromboembolic occlusion is a life-threatening emergency associated with a high mortality rate. Prompt diagnosis and intervention are vital to preserve viable bowel and prevent mortality. In the past decade, a shift has occurred toward minimally invasive alternatives such as endovascular therapies. We present a case of acute mesenteric ischemia from superior mesenteric artery thrombosis treated promptly with the Penumbra suction thrombectomy device (Penumbra Inc).

Skp2-Mediated Mlkl Degradation Confers Cisplatin-Resistant In Non-Small Cell Lung Cancer Cells, Huiling Zhou, Li Zhou, Qing Guan, Xuyang Hou, Cong Wang, Lijun Liu, Jian Wang, Xinfang Yu, Wei Li, Haidan Liu

Faculty, Staff and Students Publications

Non-small cell lung cancer (NSCLC) is the most prevalent type of cancer and the leading cause of cancer-related death. Chemotherapeutic resistance is a major obstacle in treating NSCLC patients. Here, we discovered that the E3 ligase Skp2 is overexpressed, accompanied by the downregulation of necroptosis-related regulator MLKL in human NSCLC tissues and cell lines. Knockdown of Skp2 inhibited viability, anchorage-independent growth, and in vivo tumor development of NSCLC cells. We also found that the Skp2 protein is negatively correlated with MLKL in NSCLC tissues. Moreover, Skp2 is increased and accompanied by an upregulation of MLKL ubiquitination and degradation in cisplatin-resistant …

An Sms Text Message-Based Type 2 Diabetes Prevention Program For Hispanic Adolescents With Obesity: Qualitative Co-Design Process, Erica Soltero, Callie Lopez, Sandra Mihail, Ayleen Hernandez, Salma M Musaad, Teresia M O'Connor, Debbe Thompson

Faculty, Staff and Students Publications

BACKGROUND: SMS text message-based interventions are a promising approach for reaching and engaging high-risk youths, such as Hispanic adolescents with obesity, in health promotion and disease prevention opportunities. This is particularly relevant, given that SMS text messaging is widely accessible and available and that adolescents are frequent texters. Including youths in the development of SMS text message content can lead to more acceptable and relevant messaging; however, few studies include this group as cocollaborators.

OBJECTIVE: This study aimed to use a co-design process to inform the development of SMS text messages that promote healthy physical activity (PA) and sleep behaviors …

The Efficacy Of Analgesic Subdissociative Dose Ketamine In Trauma Casualties Treated By U.S. Military Special Operations Medical Professionals In A Prehospital Environment, Darin Schwartz

Theses & Dissertations

Research Focus. This study’s main objective was to determine the efficacy of sub-dissociative ketamine to reduce the pain of trauma casualties treated by U.S. military medical professionals in a prehospital environment evidenced by the 0–10 numeric rating scale (NRS) for pain. Research Methods. This quantitative study was accomplished using a pragmatic approach integrating social cognitive theory complemented by mixing methods using qualitative phenomenological influence through narrative inquiry. This exploratory retrospective, cross-sectional study, utilizing a quasi-experimental pretest-posttest design, used deidentified sample data (N = 47) for secondary analysis from U.S. Special Operations medical providers and were included in a casualty …

Use Of Electronic Health Record Reminders To Improve Primary Care Providers’ Colorectal Cancer Screening Recommendations., Terra Renee Schrembs

Doctor of Nursing Practice Papers

Background: Colorectal cancer (CRC) is the third most common worldwide cause of cancer morbidity and mortality. CRC mortality is preventable through regular screening. Electronic health record (EHR) reminders for providers can increase providers’ CRC screening recommendations and lead to earlier CRC diagnosis. According to the National Cancer Institute’s Screening and Risk Factors Report for Kentucky by County 2008-2010, 62.7% of adults in a rural Kentucky county aged 50-75 had completed a home based FOBT in the past two years or have ever had a colorectal endoscopy.

Purpose: The purpose of this DNP project was to implement and evaluate an …