Digital Commons Network^™

Agreement Between Sars-Cov-2 Pcr Test Results Using Nasopharyngeal And Mid-Turbinate Specimens Among Asymptomatic Working-Age Adults, Judy Wendt Hess, Faiyaz Bhojani, Derrick Cameron, Mary Freire De Carvalho, Fayaz Momin

Faculty, Staff and Student Publications

OBJECTIVE: The aim of this study was to determine whether mid-turbinate specimens reliably detect active infection in asymptomatic adults undergoing regular COVID-19 PCR testing.

METHODS: Qualitative agreement between 2481 paired nasopharyngeal and mid-turbinate PCR results was assessed. Mean cycle threshold values for each positive result were evaluated as an indicator of active infection.

RESULTS: Overall agreement between nasopharyngeal and mid-turbinate tests was 98.4%. Positive percent agreement was 37.2%, and negative percent agreement was ~100%. Test pairs with lower cycle thresholds (≤30 and ≤25) reached 67% and 100% positive percent agreement, respectively.

CONCLUSIONS: SARS-CoV-2 infections with high viral loads were detected …

Health Care Utilization And Costs Associated With Functional Status In Patients With Psoriatic Arthritis, Alexis Ogdie, Mark Hwang, Phani Veeranki, Alexandria Portelli, Steven Sison, Jason Shafrin, Sofia Pedro, Steven Hass, Peter Hur, Nina Kim, Esther Yi, Kaleb Michaud

Faculty, Staff and Student Publications

BACKGROUND: The Health Assessment Questionnaire Disability Index (HAQ-DI) has been validated and widely used in psoriatic arthritis (PsA) clinical trials for the assessment of patient functional status. Significant improvements in the HAQ-DI have been reported in response to therapeutic interventions; however, few US studies have evaluated the economic impact of functional disability in patients with PsA.

OBJECTIVE: To evaluate the association of functional status with health care resource utilization (HCRU) and total health care costs in US patients diagnosed with PsA.

METHODS: This retrospective study included adult patients with PsA enrolled in FORWARD between July 2009 and June 2019 who …

Epigenetic Grimage Acceleration And Cognitive Impairment In Bipolar Disorder, Camila N C Lima, Robert Suchting, Giselli Scaini, Valeria A Cuellar, Alexandra Del Favero-Campbell, Consuelo Walss-Bass, Jair C Soares, Joao Quevedo, Gabriel R Fries

Faculty, Staff and Student Publications

Bipolar disorder (BD) has been previously associated with clinical signs of premature aging, including accelerated epigenetic aging in blood and brain, and a steeper age-related decline in cognitive function. However, the clinical drivers and cognitive correlates of epigenetic aging in BD are still unknown. We aimed to investigate the relationship between multiple measures of epigenetic aging acceleration with clinical, functioning, and cognitive outcomes in patients with BD and controls. Blood genome-wide DNA methylation levels were measured in BD patients (n = 153) and matched healthy controls (n = 50) with the Infinium MethylationEPIC BeadChip (Illumina). Epigenetic age estimates were calculated …

National Network Of Depression Centers' Recommendations On Harmonizing Clinical Documentation Of Electroconvulsive Therapy, Peter P Zandi, Michael Morreale, Irving M Reti, Daniel F Maixner, William M Mcdonald, Paresh D Patel, Eric Achtyes, Mahendra T Bhati, Brent R Carr, Susan K Conroy, Mario Cristancho, Marc J Dubin, Andrew Francis, Kara Glazer, Wendy Ingram, Khurshid Khurshid, Shawn M Mcclintock, Omar F Pinjari, Kevin Reeves, Nelson F Rodriguez, Shirlene Sampson, Stephen J Seiner, Salih Selek, Yvette Sheline, Roy W Smetana, Takahiro Soda, Nicholas T Trapp, Jesse H Wright, Mustafa Husain, Richard D Weiner

Faculty, Staff and Student Publications

Electroconvulsive therapy (ECT) is a highly therapeutic and cost-effective treatment for severe and/or treatment-resistant major depression. However, because of the varied clinical practices, there is a great deal of heterogeneity in how ECT is delivered and documented. This represents both an opportunity to study how differences in implementation influence clinical outcomes and a challenge for carrying out coordinated quality improvement and research efforts across multiple ECT centers. The National Network of Depression Centers, a consortium of 26+ US academic medical centers of excellence providing care for patients with mood disorders, formed a task group with the goals of promoting best …

Revisiting Sex Differences In The Acquisition And Extinction Of Threat Conditioning In Humans, Zhenfu Wen, Jamie Fried, Edward F Pace-Schott, Sara W Lazar, Mohammed R Milad

Faculty, Staff and Student Publications

Findings pertaining to sex differences in the acquisition and extinction of threat conditioning, a paradigm widely used to study emotional homeostasis, remain inconsistent, particularly in humans. This inconsistency is likely due to multiple factors, one of which is sample size. Here, we pooled functional magnetic resonance imaging (fMRI) and skin conductance response (SCR) data from multiple studies in healthy humans to examine sex differences during threat conditioning, extinction learning, and extinction memory recall. We observed increased functional activation in males, relative to females, in multiple parietal and frontal (medial and lateral) cortical regions during acquisition of threat conditioning and extinction …

Trends In The Diversity Of Pediatric Faculty: 2000 To 2020, Emma A Omoruyi, Colin J Orr, Greg Russell, Kimberly Montez

Faculty, Staff and Student Publications

OBJECTIVE: Academic medicine diversity is important for addressing health disparities and training the next generation. A recent study highlighted the lack of diversity among pediatric trainees over time. However, trends in US pediatric faculty diversity have not been clearly illuminated. The aim of this study is to evaluate pediatric faculty diversity trends and compare racial/ethnic representation between pediatric faculty and the US population.

METHODS: Repeat cross-sectional study of the Association of American Medical Colleges Faculty Roster of pediatric faculty from 2000 to 2020. Trends in sex, race, ethnicity, and rank were compared with the Cochran-Armitage test. Data on faculty race/ethnicity …

Association Of Antenatal Steroid Exposure At 21 To 22 Weeks Of Gestation With Neonatal Survival And Survival Without Morbidities, Sanjay Chawla, Myra H Wyckoff, Matthew A Rysavy, Ravi Mangal Patel, Dhuly Chowdhury, Girija Natarajan, Abbot R Laptook, Satyan Lakshminrusimha, Edward F Bell, Seetha Shankaran, Krisa P Van Meurs, Namasivayam Ambalavanan, Rachel G Greenberg, Noelle Younge, Erika F Werner, Abhik Das, Waldemar A Carlo, Eunice Kennedy Shriver National Institute Of Child Health And Human Development Neonatal Research Network

Faculty, Staff and Student Publications

IMPORTANCE: The provision of antenatal corticosteroids to pregnant patients at gestational age (GA) 22 6/7 weeks or less remains controversial and lacks support from randomized clinical trials.

OBJECTIVE: To compare rates of survival and survival without major morbidities among infants born at GA 22 0/7 to 23 6/7 weeks after exposure to antenatal steroids at 22 6/7 weeks' gestation or less vs no exposure to antenatal steroids.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study enrolled infants born at GA 22 0/7 to 23 6/7 weeks between January 1, 2016, and December 31, 2019, at centers in the National Institute of …

A Quality Improvement Initiative To Decrease Time To Analgesia In Patients With Sickle Cell And Vaso-Occlusive Crisis: A Population With Disparities In Treatment, Tyler Arnold, R Lane Coffee, Leon Rosenberg, Seethal A Jacob, Sean Thompson, Heather Saavedra, Stephen John Cico, Brian Wagers

Faculty, Staff and Student Publications

INTRODUCTION: Vaso-occlusive crises (VOCs) are the leading cause of emergency department (ED) visits and hospitalizations in patients with sickle cell disease (SCD). Timely administration of analgesia, within 60 minutes of patient registration, is the standard of care for SCD patients with VOCs. Patients with VOCs have longer times to initial analgesia compared to similar painful conditions. The primary aim of the project is to have 75% of patients with VOCs receive initial analgesia within 60 minutes of being registered, the current recommended time frame from the National Heart, Lung, and Blood Institute (NHLBI).

METHODS: A multi-disciplinary team used quality improvement …

Machine Learning-Based Prediction Of Masked Hypertension Among Children With Chronic Kidney Disease, Sunjae Bae, Joshua A Samuels, Joseph T Flynn, Mark M Mitsnefes, Susan L Furth, Bradley A Warady, Derek K Ng, Ckid Study

Faculty, Staff and Student Publications

BACKGROUND: Ambulatory blood pressure monitoring (ABPM) is routinely performed in children with chronic kidney disease to identify masked hypertension, a risk factor for accelerated chronic kidney disease progression. However, ABPM is burdensome, and developing an accurate prediction of masked hypertension may allow using ABPM selectively rather than routinely.

METHODS: To create a prediction model for masked hypertension using clinic blood pressure (BP) and other clinical characteristics, we analyzed 809 ABPM studies with nonhypertensive clinic BP among the participants of the Chronic Kidney Disease in Children study.

RESULTS: Masked hypertension was identified in 170 (21.0%) observations. We created prediction models for …

Cannabis Use And Sinonasal Symptoms In Us Adults, Francis Reyes Orozco, Matthew Lin, Kevin Hur

Faculty, Staff and Student Publications

IMPORTANCE: Cannabis is the most commonly used illicit substance in the US and worldwide. Understanding the association between cannabis use and sinonasal symptoms may help clinicians and patients better understand the symptomatology associated with cannabis use.

OBJECTIVE: To assess the association between frequency of cannabis use and presence of sinonasal symptoms in a nationally representative sample of US adults.

DESIGN, SETTING, AND PARTICIPANTS: This population-based, retrospective cross-sectional study included adults aged 20 to 69 years who had completed data on sinonasal symptoms and substance use for the 2013 to 2014 National Health and Nutrition Examination Survey. The data were analyzed …

Comparing Entrustment Decision-Making Outcomes Of The Core Entrustable Professional Activities Pilot, 2019-2020, David R Brown, Jeremy J Moeller, Douglas Grbic, Dorothy A Andriole, William B Cutrer, Vivian T Obeso, Mark D Hormann, Jonathan M Amiel

Faculty, Staff and Student Publications

IMPORTANCE: Gaps in readiness for indirect supervision have been identified for essential responsibilities encountered early in residency, presenting risks to patient safety. Core Entrustable Professional Activities (EPAs) for entering residency have been proposed as a framework to address these gaps and strengthen the transition from medical school to residency.

OBJECTIVE: To assess progress in developing an entrustment process in the Core EPAs framework.

DESIGN, SETTING, AND PARTICIPANTS: In this quality improvement study in the Core EPAs for Entering Residency Pilot, trained faculty made theoretical entrustment determinations and recorded the number of workplace-based assessments (WBAs) available for each determination in 2019 …

Remission And Relapse Of Dyslipidemia After Vertical Sleeve Gastrectomy Vs Roux-En-Y Gastric Bypass In A Racially And Ethnically Diverse Population, Karen J Coleman, Anirban Basu, Lee J Barton, Heidi Fischer, David E Arterburn, Douglas Barthold, Anita Courcoulas, Cecelia L Crawford, Benjamin B Kim, Peter N Fedorka, Edward C Mun, Sameer B Murali, Kristi Reynolds, Robert E Zane, Sami Alskaf

Faculty, Staff and Student Publications

IMPORTANCE: The comparative effectiveness of the most common operations in the long-term management of dyslipidemia is not clear.

OBJECTIVE: To compare 4-year outcomes associated with vertical sleeve gastrectomy (VSG) vs Roux-en-Y gastric bypass (RYGB) for remission and relapse of dyslipidemia.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective comparative effectiveness study was conducted from January 1, 2009, to December 31, 2016, with follow-up until December 31, 2018. Participants included patients with dyslipidemia at the time of surgery who underwent VSG (4142 patients) or RYGB (2853 patients). Patients were part of a large integrated health care system in Southern California. Analysis was conducted …

Distinguishing Intrathyroid Parathyroid Adenoma From Colloid Nodules And Papillary Thyroid Carcinomas Using Multiphasic Multidetector Computed Tomography, J Matthew Debnam, T Linda Chi, Michael Kwon, Jia Sun, Dawid Schellingerhout, Brandon T Golant, Salmaan Ahmed, Nancy D Perrier, Thinh Vu

Faculty, Staff and Student Publications

OBJECTIVE: The aim of the study is to determine whether multiphase multidetector computed tomography (4D-MDCT) can differentiate between intrathyroid parathyroid adenomas (ITPAs), colloid nodules, and papillary thyroid carcinoma (PTC).

METHODS: We studied 22 ITPAs, 22 colloid nodules, and 11 PTCs in 55 patients. Hounsfield unit (HU) values of the nodules were measured on 4D-MDCT in the precontrast, arterial, venous, and delayed phases. Raw HU values, phase with peak enhancement, and washout percentages between the phases were evaluated.

RESULTS: Regardless of size, all ITPAs (22/22) showed peak enhancement in the arterial phase, which was significantly greater than both colloid nodules (15/22) …

Practice Patterns And Adherence To Society Guidelines For Suspected Choledocholithiasis: A Comparison Of Academic And Community Settings From A Large Us Healthcare System, Shahrooz Rashtak, Hemant Goyal, Aswathi Chandran, Bhavtosh Dedania, Prithvi Patil, Vaibhav Wadhwa, Sushovan Guha, Tomas Davee, Srinivas Ramireddy, Nirav Thosani

Faculty, Staff and Student Publications

BACKGROUND: The American Society of Gastrointestinal Endoscopy (ASGE) has proposed practice guidelines for evaluating patients with suspected choledocholithiasis. This study aims to assess and compare practice patterns for following ASGE guidelines for choledocholithiasis in a large academic vs. community hospital setting.

METHODS: A total of one thousand ER indicated for choledocholithiasis were randomly selected. Patients' demographics, total bilirubin, imaging studies including magnetic resonance cholangiopancreatography (MRCP), intraoperative cholangiogram (IOC), endoscopic ultrasound (EUS), and ERCP results were retrospectively collected. Patients with prior sphincterotomy were excluded. We examined the following practice deviations from the current ASGE guidelines; (1) ERCP was potentially delayed in …

Indocyanine Green Angiography As The Principal Design And Perfusion Assessment Tool For The Supraclavicular Artery Island Flap In Head And Neck Reconstruction, Jo-Lawrence M Bigcas, Carolyn A Debiase, Tang Ho

Faculty, Staff and Student Publications

A consecutive case series of supraclavicular artery island flaps was designed using indocyanine green angiography (IcG-A) in head and neck reconstruction to demonstrate its utilization in supraclavicular artery island flap (SCAIF) head and neck reconstruction. IcG-A was used consecutively between April 2014 and July 2015 to evaluate its use in flap design, inset, and intraoperative decision-making in five patients undergoing head and neck reconstruction. Six SCAIFs were harvested in five patients where IcG-A was used as the primary tool for flap design by visually mapping the supraclavicular artery under fluorescence. Each flap was harvested around the mapped course of the …

Ugrc 2021 Recommendations On Gme Transition: Pros And Cons, Opportunities And Limitations, John R Gimpel, Jennifer L Swails, Jessica L Bienstock, Grant L Lin, Michelle A Roett, Juhee K Patel, Daniel W Giang

Faculty, Staff and Student Publications

The Coalition for Physician Accountability's Undergraduate Medical Education-Graduate Medical Education (UME-GME) Review Committee (UGRC): Recommendations for Comprehensive Improvement of the UME-GME Transition final report includes a total of 34 recommendations and outlines opportunities to transform the current processes of learner transition from a US-based MD- or DO-granting medical school or international medical education pathway into residency training in the United States. This review provides a reflection on the recommendations from the authors, all members of the UGRC, describing the pros and cons and the opportunities and limitations, in the hopes that they might inspire readers to dig deeper into the …

Informed Consent For Placebo-Controlled Trials: Do Ethics And Science Conflict?, Hope A Feldman, James A Feldman, Charles C Miller, Garrett Walsh, Jon E Tyson

Faculty, Staff and Student Publications

The use of a placebo has been considered the best method for controlling bias in a prospective randomized clinical trial and provides the most rigorous test of treatment efficacy for evaluating a medical therapy. Placebos commonly produce clinically important effects particularly in studies where the primary outcomes are subjective. Yet the potential beneficial or harmful effects of placebos are often not addressed in designing a clinical trial, calculating the sample size, seeking consent, or interpreting clinical trial results. In this manuscript, we use an actual study to indicate three approaches that might be considered in seeking informed consent for placebo-controlled …

Duration Of Ischemia Affects Outcomes Independent Of Infarct Size In Stroke, Youngran Kim, Swapnil Khose, Osama O Zaidat, Ameer E Hassan, Johanna T Fifi, Ashish Nanda, Benjamin Atchie, Britton Woodward, Arnd Doerfler, Alejandro Tomasello, Albert J Yoo, Sunil A Sheth

Faculty, Staff and Student Publications

Background: Delays in endovascular reperfusion for patients with large vessel occlusion stroke are known to worsen outcomes, and the mechanism is believed to be time-dependent expansion of the ischemic infarction. In this study, we hypothesize that delays in onset to reperfusion (OTR) assert an effect on outcomes independent of effects of final infarct (FI).

Methods: We performed a subgroup analysis from the prospective multicenter COMPLETE (International Acute Ischemic Stroke Registry With the Penumbra System Aspiration Including the 3D Revascularization Device; Penumbra, Inc) registry for 257 patients with anterior circulation large vessel occlusion who underwent endovascular therapy with successful reperfusion (modified …

Reproductive Health Perspectives Of Young Women With Perinatally And Behaviourally Acquired Hiv: A Qualitative Study, Lizelle Comfort, Dana Watnick, Melissa Peskin, Julie Gutierrez, Jacob Abadi, Jessica Atrio

Faculty, Staff and Student Publications

INTRODUCTION: The aim of this study was to describe the sexual and reproductive goals of female adolescents with human immunodeficiency virus (HIV) in an urban cohort and decipher if they vary depending on the mode of HIV acquisition.

METHODS: We conducted in-depth qualitative interviews with 25 Black and/or Hispanic/Latinx female adolescents living with HIV (14 perinatally, 11 behaviourally acquired) aged 17-25 years who have access to care and antiretroviral therapy at an urban public hospitals (NYC, NY). Interviews were transcribed, coded and analysed using thematic analysis.

RESULTS: Interviews demonstrated that access to antiretroviral therapy and HIV disclosure to a sexual …

Biophysical And Biochemical Characterization Of The Receptor Binding Domain Of Sars-Cov-2 Variants, Ritika Khatri, Hilal Ahmad Parray, Gazala Siddiqui, Adarsh Kumar Chiranjivi, Sneha Raj, Rachel Kaul, Vikas Maithil, Sweety Samal, Shubbir Ahmed

Faculty, Staff and Student Publications

The newly emerging SARS-CoV-2 variants are potential threat and posing new challenges for medical intervention due to high transmissibility and escaping neutralizing antibody (NAb) responses. Many of these variants have mutations in the receptor binding domain (RBD) of SARS-CoV-2 spike protein that interacts with the host cell receptor. Rapid mutation in the RBD through natural selection to improve affinity for host receptor and antibody pressure from vaccinated or infected individual will greatly impact the presently adopted strategies for developing interventions. Understanding the nature of mutations and how they impact the biophysical, biochemical and immunological properties of the RBD will help …

Outcomes Of The Second Aqueous Shunt Implant Versus Transscleral Cyclophotocoagulation Treatment Study: A Randomized Comparative Trial, Robert M Feldman, Alice Z Chuang, Steve L Mansberger, Angelo P Tanna, Lauren S Blieden, Nicholas P Bell, Ronald L Gross, Louis R Pasquale, David S Greenfield, Jeffrey M Liebmann, Robert N Weinreb

Faculty, Staff and Student Publications

PRCIS: Short-term overall success rates were high with either SGDD or CPC. However, SGDD was associated with more clinic visits and an increased risk of additional glaucoma surgery. Both treatments were reasonable options for eyes with inadequately controlled IOP after a single GDD.

PURPOSE: The purpose of this study is to compare the implantation of a second glaucoma drainage device (SGDD) and transscleral cyclophotocoagulation (CPC) in eyes with inadequately controlled intraocular pressure (IOP), despite the presence of a preexisting glaucoma drainage device.

METHODS: Patients with inadequately controlled IOP, despite the medical therapy and a preexisting glaucoma drainage device, were enrolled …

Frosted Branch Angiitis After Smallpox Vaccination, Kristen Collister, Sam S Dahr

Faculty, Staff and Student Publications

PURPOSE: To describe a patient presenting with frosted branch angiitis soon after small-pox vaccination.

OBSERVATIONS: Frosted branch angiitis (FBA) is an acute onset retinal vasculitis featuring prominent perivascular sheathing in otherwise healthy individuals. FBA has been associated with noninfectious and infectious etiologies. This report describes a twenty-year-old African American female who developed bilateral frosted branch angiitis one week after small-pox vaccination. At presentation, the patient had bilateral, para-central visual field defects and subjective visual disturbances. On dilated exam, the patient demonstrated diffuse vasculitis bilaterally. The patient's field defects and clinical exam responded dramatically to oral prednisone therapy.

CONCLUSIONS AND IMPORTANCE: …

Metaphyseal Dysplasia, Spahr Type; A Case Report Of Variable Expressivity In Non-Consanguineous Filipino Siblings, Kailash Panchapakesan, Brennan Roper, Kate Mowrey, Paul Hillman, Shiraz Younas

Faculty, Staff and Student Publications

Introduction:

Metaphyseal dysplasia describes a heterogenous group of skeletal dysplasias with varying inheritance patterns, which preferentially demonstrate dysplastic changes within the metaphyseal region of long bones. The clinical consequences of these dysplastic changes are highly variable, but most uniformly include decreased stature, increased upper-to-lower segment proportions, genu varus, and knee pain. Metaphyseal dysplasia, Spahr type (MDST) [MIM: 250400] is a rare primary bone dysplasia that was first clinically described in 1961 in four of five siblings with moderate short stature, metaphyseal dysplasia, mild genu vara, and no biochemical signs of rickets. For many decades, MDST was a clinical diagnosis, but …

Altered Bladder-Related Brain Network In Multiple Sclerosis Women With Voiding Dysfunction, Zhaoyue Shi, Christof Karmonik, Amelia Soltes, Khue Tran, John A Lincoln, Timothy Boone, Rose Khavari

Faculty, Staff and Student Publications

Objectives:

A number of neuro-urology imaging studies have mainly focused on investigating the brain activations during micturition in healthy and neuropathic patients. It is, however, also necessary to study brain functional connectivity (FC) within bladder-related regions in order to understand the brain organization during the execution of bladder function. This study aims to identify the altered brain network associated with bladder function in multiple sclerosis (MS) women with voiding dysfunction through comparisons with healthy subjects via concurrent urodynamics (UDS)/fMRI.

Materials and Methods:

Ten healthy adult women and nine adult ambulatory women with clinically stable MS for ≥ 6 months and …

Predominantly Persistent Intraretinal Fluid In The Comparison Of Age-Related Macular Degeneration Treatments Trials, Jason Q Core, Maxwell Pistilli, Peiying Hua, Ebenezer Daniel, Juan E Grunwald, Cynthia A Toth, Glenn J Jaffe, Daniel F Martin, Maureen G Maguire, Gui-Shuang Ying, Comparison Of Age-Related Macular Degeneration Treatments Trials (Catt) Research Group

Faculty, Staff and Student Publications

PURPOSE: To describe predominantly persistent intraretinal fluid (PP-IRF) and its association with visual acuity (VA) and retinal anatomic findings at long-term follow-up in eyes treated with pro re nata (PRN) ranibizumab or bevacizumab for neovascular age-related macular degeneration.

DESIGN: Cohort within a randomized clinical trial.

PARTICIPANTS: Participants in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT) assigned to PRN treatment.

METHODS: The presence of intraretinal fluid (IRF) on OCT scans was assessed at baseline and monthly follow-up visits by Duke OCT Reading Center. Predominantly persistent intraretinal fluid through week 12, year 1, and year 2 was defined as the …

Hepatic Circadian And Differentiation Factors Control Liver Susceptibility For Fatty Liver Disease And Tumorigenesis, Baharan Fekry, Aleix Ribas-Latre, Rachel Van Drunen, Rafael Bravo Santos, Samay Shivshankar, Yulin Dai, Zhongming Zhao, Seung-Hee Yoo, Zheng Chen, Kai Sun, Frances M Sladek, Mamoun Younes, Kristin Eckel-Mahan

Faculty, Staff and Student Publications

Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths, and the most common primary liver malignancy to present in the clinic. With the exception of liver transplant, treatment options for advanced HCC are limited, but improved tumor stratification could open the door to new treatment options. Previously, we demonstrated that the circadian regulator Aryl Hydrocarbon-Like Receptor Like 1 (ARNTL, or Bmal1) and the liver-enriched nuclear factor 4 alpha (HNF4α) are robustly co-expressed in healthy liver but incompatible in the context of HCC. Faulty circadian expression of HNF4α- either by isoform switching, or loss of expression- results in an increased …

Dockopathies: A Systematic Review Of The Clinical Pathologies Associated With Human Dock Pathogenic Variants, Adrienne Samani, Katherine G English, Michael A Lopez, Camille L Birch, Donna M Brown, Gurpreet Kaur, Elizabeth A Worthey, Matthew S Alexander

Faculty, Staff and Student Publications

The Dedicator of Cytokinesis (DOCK) family (DOCK1-11) of genes are essential mediators of cellular migration, growth, and fusion in a variety of cell types and tissues. Recent advances in whole-genome sequencing of patients with undiagnosed genetic disorders have identified several rare pathogenic variants in DOCK genes. We conducted a systematic review and performed a patient database and literature search of reported DOCK pathogenic variants that have been identified in association with clinical pathologies such as global developmental delay, immune cell dysfunction, muscle hypotonia, and muscle ataxia among other categories. We then categorized these pathogenic DOCK variants and their associated clinical …

Mir-486 Is Essential For Muscle Function And Suppresses A Dystrophic Transcriptome, Adrienne Samani, Rylie M Hightower, Andrea L Reid, Katherine G English, Michael A Lopez, J Scott Doyle, Michael J Conklin, David A Schneider, Marcas M Bamman, Jeffrey J Widrick, David K Crossman, Min Xie, David Jee, Eric C Lai, Matthew S Alexander

Faculty, Staff and Student Publications

miR-486 is a muscle-enriched microRNA, or “myomiR,” that has reduced expression correlated with Duchenne muscular dystrophy (DMD). To determine the function of miR-486 in normal and dystrophin-deficient muscles and elucidate miR-486 target transcripts in skeletal muscle, we characterized mir-486 knockout mice (mir-486 KO). mir-486 KO mice developed disrupted myofiber architecture, decreased myofiber size, decreased locomotor activity, increased cardiac fibrosis, and metabolic defects were exacerbated in mir-486 KO:mdx5cv (DKO) mice. To identify direct in vivo miR-486 muscle target transcripts, we integrated RNA sequencing and chimeric miRNA eCLIP sequencing to identify key transcripts and pathways that contribute towards mir-486 …

Informed Consent For Placebo-Controlled Trials: Do Ethics And Science Conflict?, Hope A Feldman, James A Feldman, Charles C Miller, Garrett Walsh, Jon E Tyson

Faculty, Staff and Student Publications

The use of a placebo has been considered the best method for controlling bias in a prospective randomized clinical trial and provides the most rigorous test of treatment efficacy for evaluating a medical therapy. Placebos commonly produce clinically important effects particularly in studies where the primary outcomes are subjective. Yet the potential beneficial or harmful effects of placebos are often not addressed in designing a clinical trial, calculating the sample size, seeking consent, or interpreting clinical trial results. In this manuscript, we use an actual study to indicate three approaches that might be considered in seeking informed consent for placebo-controlled …

The Effect Of Body Mass Index On Therapeutic Response To Bacterial Vaginosis In Pregnancy, Kevin P Lee, Misha V Koshelev, D3code Team, Omar Pacha

Faculty, Staff and Student Publications

No abstract provided.