Digital Commons Network^™

Doxorubicin-Induced Cardiotoxicity Is Mediated By Neutrophils Through Release Of Neutrophil Elastase, Anchit Bhagat, Pradeep Shrestha, Prince Jeyabal, Zhanglong Peng, Stephanie S Watowich, Eugenie S Kleinerman

Faculty, Staff and Student Publications

The mechanisms by which Doxorubicin (Dox) causes acute and late cardiotoxicity are not completely understood. One understudied area is the innate immune response, and in particular the role of neutrophils in Dox-induced cardiotoxicity. Here, using echocardiography, flow cytometry and immunofluorescence staining, we demonstrated increased infiltration of neutrophils that correlated with decreased heart function, disruption of vascular structures and increased collagen deposition in the heart after Dox treatment. Depleting neutrophils protected the heart from Dox-induced cardiotoxicity and changes in vascular structure. Furthermore, our data using neutrophil elastase (NE) knock-out mice and the NE inhibitor AZD9668 suggest that neutrophils cause this damage …

Growth In Achondroplasia Including Stature, Weight, Weight-For-Height And Head Circumference From Clarity: Achondroplasia Natural History Study-A Multi-Center Retrospective Cohort Study Of Achondroplasia In The Us, Julie E Hoover-Fong, Kerry J Schulze, Adekemi Y Alade, Michael B Bober, Ethan Gough, S Shahrukh Hashmi, Jacqueline T Hecht, Janet M Legare, Mary Ellen Little, Peggy Modaff, Richard M Pauli, David F Rodriguez-Buritica, Maria E Serna, Cory Smid, Chengxin Liu, John Mcgready

Faculty, Staff and Student Publications

BACKGROUND: Achondroplasia is the most common genetic skeletal disorder causing disproportionate short stature/dwarfism. Common additional features include spinal stenosis, midface retrusion, macrocephaly and a generalized spondylometaphyseal dysplasia which manifest as spinal cord compression, sleep disordered breathing, delayed motor skill acquisition and genu varus with musculoskeletal pain. To better understand the interactions and health outcomes of these potential complications, we embarked on a multi-center, natural history study entitled CLARITY (achondroplasia natural history study). One of the CLARITY objectives was to develop growth curves (length/height, weight, head circumference, weight-for-height) and corresponding reference tables of mean and standard deviations at 1 month increments …

Phase 3 Safety And Efficacy Of Azd1222 (Chadox1 Ncov-19) Covid-19 Vaccine, Ann R Falsey, Magdalena E Sobieszczyk, Ian Hirsch, Stephanie Sproule, Merlin L Robb, Lawrence Corey, Kathleen M Neuzil, William Hahn, Julie Hunt, Mark J Mulligan, Charlene Mcevoy, Edwin Dejesus, Michael Hassman, Susan J Little, Barbara A Pahud, Anna Durbin, Paul Pickrell, Eric S Daar, Larry Bush, Joel Solis, Quito Osuna Carr, Temitope Oyedele, Susan Buchbinder, Jessica Cowden, Sergio L Vargas, Alfredo Guerreros Benavides, Robert Call, Michael C Keefer, Beth D Kirkpatrick, John Pullman, Tina Tong, Margaret Brewinski Isaacs, David Benkeser, Holly E Janes, Martha C Nason, Justin A Green, Elizabeth J Kelly, Jill Maaske, Nancy Mueller, Kathryn Shoemaker, Therese Takas, Richard P Marshall, Menelas N Pangalos, Tonya Villafana, Antonio Gonzalez-Lopez

Faculty, Staff and Student Publications

BACKGROUND: The safety and efficacy of the AZD1222 (ChAdOx1 nCoV-19) vaccine in a large, diverse population at increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United States, Chile, and Peru has not been known.

METHODS: In this ongoing, double-blind, randomized, placebo-controlled, phase 3 clinical trial, we investigated the safety, vaccine efficacy, and immunogenicity of two doses of AZD1222 as compared with placebo in preventing the onset of symptomatic and severe coronavirus disease 2019 (Covid-19) 15 days or more after the second dose in adults, including older adults, in the United States, Chile, and Peru.

RESULTS: …

Intra-Tumoral Nerve-Tracing In A Novel Syngeneic Model Of High-Grade Serous Ovarian Carcinoma, Jeffrey L Barr, Allison Kruse, Anthony C Restaino, Natalia Tulina, Sarah Stuckelberger, Samuel J Vermeer, Caitlin S Williamson, Daniel W Vermeer, Marianna Madeo, Jillian Stamp, Maria Bell, Mark Morgan, Ju-Yoon Yoon, Marilyn A Mitchell, Anna Budina, Dalia K Omran, Lauren E Schwartz, Ronny Drapkin, Paola D Vermeer

Faculty, Staff and Student Publications

Dense tumor innervation is associated with enhanced cancer progression and poor prognosis. We observed innervation in breast, prostate, pancreatic, lung, liver, ovarian, and colon cancers. Defining innervation in high-grade serous ovarian carcinoma (HGSOC) was a focus since sensory innervation was observed whereas the normal tissue contains predominantly sympathetic input. The origin, specific nerve type, and the mechanisms promoting innervation and driving nerve-cancer cell communications in ovarian cancer remain largely unknown. The technique of neuro-tracing enhances the study of tumor innervation by offering a means for identification and mapping of nerve sources that may directly and indirectly affect the tumor microenvironment. …

Radioembolization With Chemotherapy For Colorectal Liver Metastases: A Randomized, Open-Label, International, Multicenter, Phase Iii Trial, Mary F Mulcahy, Armeen Mahvash, Marc Pracht, Amir H Montazeri, Steve Bandula, Robert C G Martin, Ken Herrmann, Ewan Brown, Darryl Zuckerman, Gregory Wilson, Tae-You Kim, Andrew Weaver, Paul Ross, William P Harris, Janet Graham, Jamie Mills, Alfonso Yubero Esteban, Matthew S Johnson, Constantinos T Sofocleous, Siddharth A Padia, Robert J Lewandowski, Etienne Garin, Philip Sinclair, Riad Salem

Faculty, Staff and Student Publications

PURPOSE: To study the impact of transarterial Yttrium-90 radioembolization (TARE) in combination with second-line systemic chemotherapy for colorectal liver metastases (CLM).

METHODS: In this international, multicenter, open-label phase III trial, patients with CLM who progressed on oxaliplatin- or irinotecan-based first-line therapy were randomly assigned 1:1 to receive second-line chemotherapy with or without TARE. The two primary end points were progression-free survival (PFS) and hepatic PFS (hPFS), assessed by blinded independent central review. Random assignment was performed using a web- or voice-based system stratified by unilobar or bilobar disease, oxaliplatin- or irinotecan-based first-line chemotherapy, and

RESULTS: Four hundred twenty-eight patients from …

Practical Considerations Of Dissolved Oxygen Levels For Platelet Function Under Hypoxia, Branden Kusanto, Andrew Gordon, Leigh Naylor-Adamson, Lloyd Atkinson, Charlie Coupland, Zoe Booth, Yusra Ahmed, Isabel M Pires, Graeme J Stasiuk, Roger Sturmey, Simon D J Calaminus, Mònica Arman

Faculty, Staff and Student Publications

Investigating human platelet function in low-oxygen environments is important in multiple settings, including hypobaric hypoxia (e.g., high altitude), sea level hypoxia-related disease, and thrombus stability. These studies often involve drawing blood from which platelets are isolated and analysed at atmospheric conditions or re-exposed to low oxygen levels in hypoxia chambers before testing. However, it remains unknown how the in vitro handling of the samples itself changes their dissolved oxygen concentration, which might affect platelet function and experimental results. Here, we prepared healthy donor platelet-rich plasma and washed platelet (WP) suspensions and exposed them to 2% oxygen. We found that the …

Temperature Changes During Implant Osteotomy Preparations In Human Cadaver Tibiae Comparing Mis® Straight Drills With Densah® Burs, Andrew C Griggs, Crystal M Fausett, Richard J Simonson, Kimberly N Williams, Tiffany M Bisbey, Elizabeth H Lazzara, Joseph R Keebler, Deborah Diazgranados, Vimal K Mishra, Eric J Thomas, Eduardo Salas

Faculty, Staff and Student Publications

INTRODUCTION: Telerounding is slated to become an important avenue for future healthcare practice. As utilization of telerounding is increasing, a review of the literature is necessary to distill themes and identify critical considerations for the implementation of telerounding. We provide evidence of the utility of telerounding and considerations to support its implementation in future healthcare practice based on a scoping review.

METHOD: We collected articles from nine scientific databases from the earliest dated available articles to August 2020. We identified whether each article centered on telerounding policies, regulations, or practice. We also organized information from each article and sorted themes …

Tavr In Older Adults: Moving Toward A Comprehensive Geriatric Assessment And Away From Chronological Age: Jacc Family Series, Joy M Schmitz, Scott D Lane, Michael F Weaver, Ponnada A Narayana, Khader M Hasan, Delisa D Russell, Robert Suchting, Charles E Green

Faculty, Staff and Student Publications

Cocaine use continues to be a significant public health problem with limited treatment options and no approved pharmacotherapies. Cognitive-behavioral therapy (CBT) remains the mainstay treatment for preventing relapse, however, people with chronic cocaine use display cognitive impairments that are associated with poor response to CBT. Emerging evidence in animal and human studies suggests that the peroxisome proliferator-activated receptor-gamma (PPAR- γ) agonist, pioglitazone, improves white matter integrity that is essential for cognitive function. This project will determine whether adjunctive use of pioglitazone enhances the effect of CBT in preventing relapse during the early phase of recovery from cocaine use disorder. This …

Profile Of Autism Spectrum Disorder In Tuberous Sclerosis Complex: Results From A Longitudinal, Prospective, Multisite Study, Jamie K Capal, Marian E Williams, Deborah A Pearson, Robin Kissinger, Paul S Horn, Donna Murray, Kristn Currans, Bridget Kent, Martina Bebin, Hope Northrup, Joyce Y Wu, Mustafa Sahin, Darcy A Krueger, Tacern Study Group

Faculty, Staff and Student Publications

OBJECTIVE: Tuberous sclerosis complex (TSC) is highly associated with autism spectrum disorder (ASD). Objectives of the study were to characterize autistic features in young children with TSC.

METHODS: Participants included 138 children followed from ages 3 to 36 months with TSC from the Tuberous Sclerosis Complex Autism Center of Excellence Research Network (TACERN), a multicenter, prospective observational study aimed at understanding the underlying mechanisms of ASD in TSC. Developmental and autism-specific assessments were administered, and a clinical diagnosis of ASD was determined for all participants at 36 months. Further analyses were performed on 117 participants with valid autism assessments based …

Defining The Epidemiology Of Safety Risks In Neonatal Intensive Care Unit Patients Requiring Surgery, Daniel J France, Jason Slagle, Emma Schremp, Sarah Moroz, L Dupree Hatch, Peter Grubb, Timothy J Vogus, Matthew S Shotwell, Amanda Lorinc, Christoph U Lehmann, Jamie Robinson, Marlee Crankshaw, Maria Sullivan, Timothy A Newman, Tamara Wallace, Matthew B Weinger, Martin L Blakely

Faculty, Staff and Student Publications

OBJECTIVE: The aim of the study was to determine the incidence, type, severity, preventability, and contributing factors of nonroutine events (NREs)-events perceived by care providers or skilled observers as a deviations from optimal care based on the clinical situation-in the perioperative (i.e., preoperative, operative, and postoperative) care of surgical neonates in the neonatal intensive care unit and operating room.

METHODS: A prospective observational study of noncardiac surgical neonates, who received preoperative and postoperative neonatal intensive care unit care, was conducted at an urban academic children's hospital between November 1, 2016, and March 31, 2018. One hundred twenty-nine surgical cases in …

Limitations Of Available Blood Products For Massive Transfusion During Mass Casualty Events At Us Level 1 Trauma Centers, James Williams, Michael Gustafson, Yu Bai, Samuel Prater, Charles E Wade, Oscar D Guillamondegui, Mansoor Khan, Megan Brenner, Paula Ferrada, Derek Roberts, Tal Horer, David Kauvar, Andrew Kirkpatrick, Carlos Ordonez, Bruno Perreira, Artai Priouzram, Juan Duchesne, Bryan A Cotton

Faculty, Staff and Student Publications

INTRODUCTION: Exsanguination remains a leading cause of preventable death in traumatically injured patients. To better treat hemorrhagic shock, hospitals have adopted massive transfusion protocols (MTPs) which accelerate the delivery of blood products to patients. There has been an increase in mass casualty events (MCE) worldwide over the past two decades. These events can overwhelm a responding hospital's supply of blood products. Using a computerized model, this study investigated the ability of US trauma centers (TCs) to meet the blood product requirements of MCEs.

METHODS: Cross-sectional survey data of on-hand blood products were collected from 16 US level-1 TCs. A discrete …

Mission-Based Filters In The Electronic Residency Application Service: Saving Time And Promoting Diversity, Jennifer L Swails, Sasha Adams, Mark Hormann, Emma Omoruyi, Omowunmi Aibana

Faculty, Staff and Student Publications

BACKGROUND: Holistic review promotes diversity, but widespread implementation remains limited.

OBJECTIVE: We aimed to develop a practical approach to incorporate holistic review principles in screening applicants in the Electronic Residency Application Service (ERAS) and to assess the impact on diversity.

METHODS: Three residency programs (internal medicine [IM], pediatrics, and surgery) at McGovern Medical School developed filters to identify applicants with experiences/attributes aligned with the institutional mission. These filters were retroactively applied to each program's 2019-2020 applicant pool using built-in ERAS capabilities to group applicants by user-defined features. We compared the demographics of applicants reviewed during the cycle with those identified …

Long-Term Impacts Faced By Patients And Families After Harmful Healthcare Events, Madelene J Ottosen, Emily W Sedlock, Aitebureme O Aigbe, Sigall K Bell, Thomas H Gallagher, Eric J Thomas

Faculty, Staff and Student Publications

BACKGROUND: Patients and families report experiencing a multitude of harms from medical errors resulting in physical, emotional, and financial hardships. Little is known about the duration and nature of these harms and the type of support needed to promote patient and family healing after such events. We sought to describe the long-term impacts (LTIs) reported by patients and family members who experienced harmful medical events 5 or more years ago.

METHODS: We performed a content analysis on 32 interviews originally conducted with 72 patients or family members about their views of the factors contributing to their self-reported harmful event. Interviews …

Nrf1 Association With Auts2-Polycomb Mediates Specific Gene Activation In The Brain, Sanxiong Liu, Kimberly A Aldinger, Chi Vicky Cheng, Takae Kiyama, Mitali Dave, Hanna K Mcnamara, Wukui Zhao, James M Stafford, Nicolas Descostes, Pedro Lee, Stefano G Caraffi, Ivan Ivanovski, Edoardo Errichiello, Christiane Zweier, Orsetta Zuffardi, Michael Schneider, Antigone S Papavasiliou, M Scott Perry, Jennifer Humberson, Megan T Cho, Astrid Weber, Andrew Swale, Tudor C Badea, Chai-An Mao, Livia Garavelli, William B Dobyns, Danny Reinberg

Faculty, Staff and Student Publications

The heterogeneous family of complexes comprising Polycomb repressive complex 1 (PRC1) is instrumental for establishing facultative heterochromatin that is repressive to transcription. However, two PRC1 species, ncPRC1.3 and ncPRC1.5, are known to comprise novel components, AUTS2, P300, and CK2, that convert this repressive function to that of transcription activation. Here, we report that individuals harboring mutations in the HX repeat domain of AUTS2 exhibit defects in AUTS2 and P300 interaction as well as a developmental disorder reflective of Rubinstein-Taybi syndrome, which is mainly associated with a heterozygous pathogenic variant in CREBBP/EP300. Moreover, the absence of AUTS2 or mutation in its …

Apathy Is Not Associated With A Panel Of Biomarkers In Older Adults With Hiv Disease, Steven Paul Woods, Jennifer L Thompson, Michelle A Babicz, Lokesh Shahani, Gabriela Delevati Colpo, Natalia P Rocha, Erin E Morgan, Antonio L Teixeira

Faculty, Staff and Student Publications

OBJECTIVE: Apathy is prevalent in HIV disease and can significantly impact personal well-being; however, little is known about its neurobiological substrates in persons with HIV (PWH) disease.

METHODS: This cross-sectional, correlational study examined the association between apathy and several plasma biomarkers (tumor necrosis factor alpha, kynurenine, tryptophan, quinolinic acid, brain-derived neurotrophic factor, glial fibrillary acidic protein, neurofilament light chain, and phosphorylated tau at position threonine 181) in 109 PWH and 30 seronegative participants ages 50 and older. Apathy was measured with a composite score derived from subscales of the Frontal Systems Behavior Scale and the Profile of Mood States.

RESULTS: …

Identification Of An Atp/P2x7/Mast Cell Pathway Mediating Ozone-Induced Bronchial Hyperresponsiveness, Xiaomei Kong, William C Bennett, Corey M Jania, Kelly D Chason, Zachary German, Jennifer Adouli, Samuel D Budney, Brandon T Oby, Catharina Van Heusden, Eduardo R Lazarowski, Ilona Jaspers, Scott H Randell, Barry A Hedgespeth, Glenn Cruse, Xiaoyang Hua, Stephen A Schworer, Gregory J Smith, Samir Np Kelada, Stephen L Tilley

Faculty, Staff and Student Publications

Ozone is a highly reactive environmental pollutant with well-recognized adverse effects on lung health. Bronchial hyperresponsiveness (BHR) is one consequence of ozone exposure, particularly for individuals with underlying lung disease. Our data demonstrated that ozone induced substantial ATP release from human airway epithelia in vitro and into the airways of mice in vivo and that ATP served as a potent inducer of mast cell degranulation and BHR, acting through P2X7 receptors on mast cells. Both mast cell-deficient and P2X7 receptor-deficient (P2X7-/-) mice demonstrated markedly attenuated BHR to ozone. Reconstitution of mast cell-deficient mice with WT mast cells and P2X7-/- mast …

Citalopram For Treatment Of Cocaine Use Disorder: A Bayesian Drop-The-Loser Randomized Clinical Trial, Robert Suchting, Charles E Green, Constanza De Dios, Jessica Vincent, F Gerard Moeller, Scott D Lane, Joy M Schmitz

Faculty, Staff and Student Publications

BACKGROUND: Medication development research for cocaine use disorder (CUD) has been a longstanding goal in addiction research, but has not resulted in an FDA-approved treatment. Rising cocaine use rates underscore the need for efficient adaptive designs. This study compared differences between two doses of the selective serotonin reuptake inhibitor (SSRI) citalopram (versus placebo) on duration of cocaine abstinence and applied adaptive decision rules to select the 'best efficacy' dose.

METHODS: A double-blind, placebo-controlled, randomized Bayesian drop-the-loser (DTL) trial with three arms compared placebo to citalopram 20 mg and 40 mg. Adults (N = 107) with CUD attended thrice-weekly clinic visits …

Revisiting The Controversy: The Role Of Fungi In Chronic Rhinosinusitis, Matthew A Tyler, Kent Lam, Michael J Marino, William C Yao, Isaac Schmale, Martin J Citardi, Amber U Luong

Faculty, Staff and Student Publications

In the last two decades, the development of culture-independent genomic techniques has facilitated an increased appreciation of the microbiota-immunity interactions and their role in a multitude of chronic inflammatory diseases such as chronic rhinosinusitis (CRS), asthma, inflammatory bowel disease and dermatitis. While the pathologic role of bacteria in chronic inflammatory diseases is generally accepted, the understanding of the role of fungi remains controversial.

Chronic rhinosinusitis, specifically the phenotype linked to nasal polyps, represents a spectrum of chronic inflammatory diseases typically characterized by a Type 2 immune response. Studies on the microbiota within sinus cavities from healthy and diseased patients have …

Mitophagy In Depression: Pathophysiology And Treatment Targets, Ashutosh Tripathi, Giselli Scaini, Tatiana Barichello, João Quevedo, Anilkumar Pillai

Faculty, Staff and Student Publications

Mitochondria, the 'powerhouse' of eukaryotic cells, play a key role in cellular homeostasis. However, defective mitochondria increase mitochondrial ROS (mtROS) production and cell-free mitochondrial DNA (mtDNA) release, leading to increased inflammation. Mitophagy is a vital pathway, which selectively removes defective mitochondria through the process of autophagy. Thus, an impairment in the mitophagy pathway might trigger the gradual accumulation of defective mitochondria. Accumulating evidence suggest that inflammation and mitochondrial dysfunction are linked to the pathogenesis of depression. In this article, we have reviewed the role of impaired mitophagy as a contributing factor in depression pathophysiology. Further, we have discussed the potential …

Hop2 Interacts With The Transcription Factor Cebpα And Suppresses Adipocyte Differentiation, Tonghui Lin, Yang Zhang, Tingting Zhang, Rita A Steckler, Xiangli Yang

Faculty, Staff and Student Publications

CCAAT enhancer binding protein (CEBP) transcription factors (TFs) are known to promote adipocyte differentiation; however, suppressors of CEBP TFs have not been reported thus far. Here, we find that homologous chromosome pairing protein 2 (Hop2) functions as an inhibitor for the TF CEBPα. We found that Hop2 mRNA is highly and specifically expressed in adipose tissue, and that ectopic Hop2 expression suppresses reporter activity induced by CEBP as revealed by DNA transfection. Recombinant and ectopically expressed Hop2 was shown to interact with CEBPα in pull-down and coimmunoprecipitation assays, and interaction between endogenous Hop2 and CEBPα was observed in the nuclei …

A Comparison Of Methods Of Discontinuing Nasal Cpap In Premature Infants <30 Weeks Gestation: A Feasibility Study, Brittany Duyka, Claire Beaullieu, Amir M Khan

Faculty, Staff and Student Publications

OBJECTIVE: The objective of this study was to determine whether abrupt discontinuation vs gradual wean of nasal CPAP (NCPAP) in infantstherapy.

STUDY DESIGN: We performed a single-center, randomized control trial of premature infants born(n = 66), comparing discontinuation of NCPAP from 6 cmH

RESULTS: Duration of NCPAP or mechanical ventilation was longer in the slow wean arm compared to the fast wean arm (17 vs 12 days, p = 0.03). There were no differences observed in secondary outcomes.

CONCLUSION: In weaning NCPAP, abrupt discontinuation may be associated with a shorter duration of positive pressure respiratory support compared to a gradual …

Positron Emission Tomography In The Covid-19 Pandemic Era, Chentao Jin, Xiaoyun Luo, Shufang Qian, Kai Zhang, Yuanxue Gao, Rui Zhou, Peili Cen, Zhoujiao Xu, Hong Zhang, Mei Tian

Faculty, Staff and Student Publications

Coronavirus disease 2019 (COVID-19) has become a major public health problem worldwide since its outbreak in 2019. Currently, the spread of COVID-19 is far from over, and various complications have roused increasing awareness of the public, calling for novel techniques to aid at diagnosis and treatment. Based on the principle of molecular imaging, positron emission tomography (PET) is expected to offer pathophysiological alternations of COVID-19 in the molecular/cellular perspectives and facilitate the clinical management of patients. A number of PET-related cases and research have been reported on COVID-19 over the past one year. This article reviews the current studies of …

Racism And Cancer Screening Among Low-Income, African American Women: A Multilevel, Longitudinal Analysis Of 2-1-1 Texas Callers, Lynn N Ibekwe, Maria Eugenia Fernández-Esquer, Sandi L Pruitt, Nalini Ranjit, Maria E Fernández

Faculty, Staff and Student Publications

Although racism is increasingly being studied as an important contributor to racial health disparities, its relation to cancer-related outcomes among African Americans remains unclear. The purpose of this study was to help clarify the relation between two indicators of racism-perceived racial discrimination and racial residential segregation-and cancer screening. We conducted a multilevel, longitudinal study among a medically underserved population of African Americans in Texas. We assessed discrimination using the Experiences of Discrimination Scale and segregation using the Location Quotient for Racial Residential Segregation. The outcome examined was "any cancer screening completion" (Pap test, mammography, and/or colorectal cancer screening) at follow-up …

Glycogen Storage Disease Type Ia: Current Management Options, Burden And Unmet Needs, Terry G J Derks, David F Rodriguez-Buritica, Ayesha Ahmad, Foekje De Boer, María L Couce, Sarah C Grünert, Philippe Labrune, Nerea López Maldonado, Carolina Fischinger Moura De Souza, Rebecca Riba-Wolman, Alessandro Rossi, Heather Saavedra, Rupal Naik Gupta, Vassili Valayannopoulos, John Mitchell

Faculty, Staff and Student Publications

Glycogen storage disease type Ia (GSDIa) is caused by defective glucose-6-phosphatase, a key enzyme in carbohydrate metabolism. Affected individuals cannot release glucose during fasting and accumulate excess glycogen and fat in the liver and kidney, putting them at risk of severe hypoglycaemia and secondary metabolic perturbations. Good glycaemic/metabolic control through strict dietary treatment and regular doses of uncooked cornstarch (UCCS) is essential for preventing hypoglycaemia and long-term complications. Dietary treatment has improved the prognosis for patients with GSDIa; however, the disease itself, its management and monitoring have significant physical, psychological and psychosocial burden on individuals and parents/caregivers. Hypoglycaemia risk persists …

Allografts For Skin Closure During In Utero Spina Bifida Repair In A Sheep Model, Lovepreet K Mann, Jong Hak Won, Rajan Patel, Eric P Bergh, Jeannine Garnett, Meenakshi B Bhattacharjee, Ponnada A Narayana, Ranu Jain, Stephen A Fletcher, Dejian Lai, Ramesha Papanna

Faculty, Staff and Student Publications

OBJECTIVES: Use of off-label tissue graft materials, such as acellular dermal matrix (ADM), for in utero repair of severe spina bifida (SB), where primary skin layer closure is not possible, is associated with poor neurological outcomes. The cryopreserved human umbilical cord (HUC) patch has regenerative, anti-inflammatory, and anti-scarring properties, and provides watertight SB repair. We tested the hypothesis that the HUC is a superior skin patch to ADM for reducing inflammation at the repair site and preserving spinal cord function.

METHODS: In timed-pregnant ewes with twins, on gestational day (GD) 75, spina bifida was created without a myelotomy (functional model). …

A Selective Antibiotic For Lyme Disease, Nadja Leimer, Xiaoqian Wu, Yu Imai, Madeleine Morrissette, Norman Pitt, Quentin Favre-Godal, Akira Iinishi, Samta Jain, Mariaelena Caboni, Inga V Leus, Vincent Bonifay, Samantha Niles, Rachel Bargabos, Meghan Ghiglieri, Rachel Corsetti, Megan Krumpoch, Gabriel Fox, Sangkeun Son, Dorota Klepacki, Yury S Polikanov, Cecily A Freliech, Julie E Mccarthy, Diane G Edmondson, Steven J Norris, Anthony D'Onofrio, Linden T Hu, Helen I Zgurskaya, Kim Lewis

Faculty, Staff and Student Publications

Lyme disease is on the rise. Caused by a spirochete Borreliella burgdorferi, it affects an estimated 500,000 people in the United States alone. The antibiotics currently used to treat Lyme disease are broad spectrum, damage the microbiome, and select for resistance in non-target bacteria. We therefore sought to identify a compound acting selectively against B. burgdorferi. A screen of soil micro-organisms revealed a compound highly selective against spirochetes, including B. burgdorferi. Unexpectedly, this compound was determined to be hygromycin A, a known antimicrobial produced by Streptomyces hygroscopicus. Hygromycin A targets the ribosomes and is taken up by B. burgdorferi, explaining …

Using Increased Trust In Medical Researchers To Increase Minority Recruitment: The Recruit Cluster Randomized Clinical Trial, Barbara C Tilley, Arch G Mainous, Rossybelle P Amorrortu, M Diane Mckee, Daniel W Smith, Ruosha Li, Stacia M Desantis, Sally W Vernon, Gary Koch, Marvella E Ford, Vanessa Diaz, Jennifer Alvidrez

Faculty, Staff and Student Publications

While extensive literature exists on barriers and strategies to increase minority participation in clinical trials, progress is limited. Few strategies were evaluated in randomized trials. We studied the impact of RECRUIT, a trust-based, cluster randomized minority recruitment trial layered on top of four traditional NIH-funded parent trials (BMT CTN, CABANA, PACES, STEADY-PD III; fifty specialty sites). RECRUIT was conducted from July 2013 through April 2017. Intervention sites implemented trust-based approaches customized to individual sites, promoting relationships between physician-investigators and minority-serving physicians and their minority patients. Control sites implemented only parent trials' recruitment procedures. Adjusting for within-site clustering, we detected no …

A Novel Imputation Approach For Sharing Protected Public Health Data, Elizabeth A Erdman, Leonard D Young, Dana L Bernson, Cici Bauer, Kenneth Chui, Thomas J Stopka

Faculty, Staff and Student Publications

Objectives. To develop an imputation method to produce estimates for suppressed values within a shared government administrative data set to facilitate accurate data sharing and statistical and spatial analyses.

Methods. We developed an imputation approach that incorporated known features of suppressed Massachusetts surveillance data from 2011 to 2017 to predict missing values more precisely. Our methods for 35 de-identified opioid prescription data sets combined modified previous or next substitution followed by mean imputation and a count adjustment to estimate suppressed values before sharing. We modeled 4 methods and compared the results to baseline mean imputation.

Results. We assessed performance by …

Barriers To Human Papillomavirus Vaccine Uptake Among Racial/Ethnic Minorities: A Systematic Review, Trisha L Amboree, Charles Darkoh

Faculty, Staff and Student Publications

BACKGROUND: Human papillomavirus (HPV) is associated with poor health outcomes, including cervical cancer. Racial/ethnic minority populations experience poor health outcomes associated with HPV at higher rates. A vaccine is available to protect against HPV infections and prevent HPV-related sequelae; however, vaccination rates have remained low in the United States (U.S.) population. Thus, there is an urgent need to increase the HPV vaccination rate. Moreover, little is known about barriers to HPV vaccination in racial/ethnic minority groups. This paper highlights the most recent findings on barriers experienced by these groups.

METHODS: The PubMed database was searched on July 30, 2020, for …

Flowcharts Improve Periodontal Diagnosis By Dental And Dental Hygiene Students, Karo Parsegian, Srinivas Ayilavarapu, Tulsi Patel, Harold A Henson, Nikola Angelov

Faculty, Staff and Student Publications

BACKGROUND: In 2017, the American Academy of Periodontology and the European Federation of Periodontology updated the classification of periodontal and peri-implant diseases and conditions. The goal of the present crossover study was to develop straightforward, illustrative flowcharts and determine their impact on the accuracy and speed of diagnosing periodontal conditions by predoctoral dental students (DS) and dental hygiene students (DHS).

METHODS: Two flowcharts (a decision-tree flowchart and one based on the periodontal disease/condition entity) were developed using updated diagnostic determinants proposed by the 2017 classification. A total of 26 second-, third-, and fourth-year DS (DS2, DS3, and DS4, respectively) and …