Medical Specialties Commons^™

The Sineb1 Element In The Long Non-Coding Rna Malat1 Is Necessary For Tdp-43 Proteostasis, Tuan M Nguyen, Elena B Kabotyanski, Lucas C Reineke, Jiaofang Shao, Feng Xiong, Joo-Hyung Lee, Julien Dubrulle, Hannah Johnson, Fabio Stossi, Phoebe S Tsoi, Kyoung-Jae Choi, Alexander G Ellis, Na Zhao, Jin Cao, Oluwatoyosi Adewunmi, Josephine C Ferreon, Allan Chris M Ferreon, Joel R Neilson, Michael A Mancini, Xi Chen, Jongchan Kim, Li Ma, Wenbo Li, Jeffrey M Rosen

Faculty, Staff and Students Publications

Transposable elements (TEs) comprise a large proportion of long non-coding RNAs (lncRNAs). Here, we employed CRISPR to delete a short interspersed nuclear element (SINE) in Malat1, a cancer-associated lncRNA, to investigate its significance in cellular physiology. We show that Malat1 with a SINE deletion forms diffuse nuclear speckles and is frequently translocated to the cytoplasm. SINE-deleted cells exhibit an activated unfolded protein response and PKR and markedly increased DNA damage and apoptosis caused by dysregulation of TDP-43 localization and formation of cytotoxic inclusions. TDP-43 binds stronger to Malat1 without the SINE and is likely 'hijacked' by cytoplasmic Malat1 to the …

Discovery Of A Bacterial Peptide As A Modulator Of Glp-1 And Metabolic Disease, Catherine Tomaro-Duchesneau, Stephanie L Levalley, Daniel Roeth, Liang Sun, Frank T Horrigan, Markus Kalkum, Joseph M Hyser, Robert A Britton

Faculty, Staff and Students Publications

Early work in rodents highlighted the gut microbiota's importance in metabolic disease, including Type II Diabetes Mellitus (T2DM) and obesity. Glucagon-like peptide-1 (GLP-1), an incretin secreted by L-cells lining the gastrointestinal epithelium, has important functions: promoting insulin secretion, insulin sensitivity, and β-cell mass, while inhibiting gastric emptying and appetite. We set out to identify microbial strains with GLP-1 stimulatory activity as potential metabolic disease therapeutics. Over 1500 human-derived strains were isolated from healthy individuals and screened for GLP-1 modulation by incubating bacterial cell-free supernatants with NCI H716 L-cells. Approximately 45 strains capable of increasing GLP-1 were discovered. All GLP-1 positive …

Pain Squad+ Smartphone App To Support Real-Time Pain Treatment For Adolescents With Cancer: Protocol For A Randomised Controlled Trial., Lindsay Jibb, Paul C Nathan, Vicky Breakey, Conrad Fernandez, Donna Johnston, Victor Lewis, Sarah Mckillop, Serina Patel, Christine Sabapathy, Caron Strahlendorf, J Charles Victor, Myla E Moretti, Cynthia Nguyen, Amos Hundert, Celia Cassiani, Graziella El-Khechen Richandi, Hayley Insull, Rachel Hamilton, Geoffrey Fang, Susan Kuczynski, Jennifer Stinson

Paediatrics Publications

INTRODUCTION: Pain negatively affects the health-related quality of life (HRQL) of adolescents with cancer. The Pain Squad+ smartphone-based application (app), has been developed to provide adolescents with real-time pain self-management support. The app uses a validated pain assessment and personalised pain treatment advice with centralised decision support via a registered nurse to enable real-time pain treatment in all settings. The algorithm informing pain treatment advice is evidence-based and expert-vetted. This trial will longitudinally evaluate the impact of Pain Squad+, with or without the addition of nurse support, on adolescent health and cost outcomes.

METHODS AND ANALYSIS: This will be a …

Public Social Media Consultations For Dermatologic Conditions: An Online Survey, Elizabeth Schoenberg, Doaa Shalabi, Jordan Wang, Nazanin Saedi, Matthew Keller

Department of Dermatology and Cutaneous Biology Faculty Papers

The use of social media in medicine has been increasingly studied in recent years, especially concerning its role in patient outreach, education, diagnosis, and management. Dermatology is a unique field in that patients can post photographs of their skin ailments when seeking online medical advice and information. This study examines the role of public social media consultations for dermatologic conditions. A large portion of patients utilize social media for dermatologic consultations and many do not seek care from a dermatologist afterward. Future studies should trend this phenomenon, especially as the use of social media continues to expand.

Circulating Leptin Levels Are Associated With Adiposity In Survivors Of Childhood Brain Tumors., E Danielle Sims, William J. Jennings, Brianna Empringham, Adam Fleming, Carol Portwine, Donna L. Johnston, Shayna M. Zelcer, Shahrad Rod Rassekh, Sarah Burrow, Lehana Thabane, M Constantine Samaan

Paediatrics Publications

Survivors of Childhood Brain Tumors (SCBT) are at a higher risk of developing cardiovascular disease and type 2 diabetes compared to the general population. Adiposity is an important risk factor for the development of these outcomes, and identifying biomarkers of adiposity may help the stratification of survivors based on their cardiovascular risk or allow for early screening and interventions to improve cardiometabolic outcomes. Leptin is an adipokine that positively correlates with the adipose mass in the general population and is a predictor of adverse cardiometabolic outcomes, yet its association with adiposity in SCBT has not been studied. The aim of …

Evaluation Of Dna Methylation Episignatures For Diagnosis And Phenotype Correlations In 42 Mendelian Neurodevelopmental Disorders., Erfan Aref-Eshghi, Jennifer Kerkhof, Victor P Pedro, Mouna Barat-Houari, Nathalie Ruiz-Pallares, Jean-Christophe Andrau, Didier Lacombe, Julien Van-Gils, Patricia Fergelot, Christèle Dubourg, Valerie Cormier-Daire, Sophie Rondeau, François Lecoquierre, Pascale Saugier-Veber, Gaël Nicolas, Gaetan Lesca, Nicolas Chatron, Damien Sanlaville, Antonio Vitobello, Laurence Faivre, Christel Thauvin-Robinet, Frederic Laumonnier, Martine Raynaud, Mariëlle Alders, Marcel Mannens, Peter Henneman, Raoul C Hennekam, Guillaume Velasco, Claire Francastel, Damien Ulveling, Andrea Ciolfi, Simone Pizzi, Marco Tartaglia, Solveig Heide, Delphine Héron, Cyril Mignot, Boris Keren, Sandra Whalen, Alexandra Afenjar, Thierry Bienvenu, Philippe M Campeau, Justine Rousseau, Michael A Levy, Lauren Brick, Mariya Kozenko, Tugce B Balci, Victoria Mok Siu, Alan Stuart, Mike Kadour, Jennifer Masters, Kyoko Takano, Tjitske Kleefstra, Nicole De Leeuw, Michael Field, Marie Shaw, Jozef Gecz, Peter J Ainsworth, Hanxin Lin, David I Rodenhiser, Michael J Friez, Matt Tedder, Jennifer A Lee, Barbara R Dupont, Roger E Stevenson, Steven A Skinner, Charles E Schwartz, David Genevieve, Bekim Sadikovic

Paediatrics Publications

Genetic syndromes frequently present with overlapping clinical features and inconclusive or ambiguous genetic findings which can confound accurate diagnosis and clinical management. An expanding number of genetic syndromes have been shown to have unique genomic DNA methylation patterns (called "episignatures"). Peripheral blood episignatures can be used for diagnostic testing as well as for the interpretation of ambiguous genetic test results. We present here an approach to episignature mapping in 42 genetic syndromes, which has allowed the identification of 34 robust disease-specific episignatures. We examine emerging patterns of overlap, as well as similarities and hierarchical relationships across these episignatures, to highlight …

Predictors Of Bicuspid Aortic Valve-Associated Aortopathy In Childhood: A Report From The Mibava Consortium, Michael Grattan, Andrea Prince, Rawan K Rumman, Conall Morgan, Michele Petrovic, Amanda Hauck, Luciana Young, Anders Franco-Cereceda, Bart Loeys, Salah A Mohamed, Harry Dietz, Seema Mital, Chun-Po Steve Fan, Cedric Manlhiot, Gregor Andelfinger, Luc Mertens

Paediatrics Publications

BACKGROUND: Bicuspid aortic valve (BAV) is the most prevalent congenital heart defect affecting 1% to 2% of the population. It is associated with ascending aorta dilatation. Valve morphology, aortic stenosis (AS), and aortic insufficiency (AI) have been proposed as potential risk factors; however, evaluating their role is difficult, as these factors are inherently related. The aim of this study was to determine whether BAV morphology and dysfunction are independent determinants for ascending aorta dilatation in pediatric patients.

METHODS: A multicenter, retrospective, cross-sectional study of pediatric BAV patients followed since 2004 was performed. Imaging data were assessed for BAV morphology, severity …

Osteochondritis Dissecans In Pediatric Patients With Juvenile Idiopathic Arthritis., Bradley C Jackson, Debra L Bartley, Roberta A Berard

Paediatrics Publications

No abstract provided.

Labour Progression In Obese Women: Are Women With Increased Body Mass Index Having Unnecessary Cesarean Sections?, Caroline Shenouda, Aloka Wijesooriya, Amanda Toufeili, Michael R Miller, Debbie Penava, Barbra De Vrijer

Obstetrics & Gynaecology Publications

OBJECTIVE: This study sought to determine whether obese pregnant women undergo cesarean sections without an adequate trial of labour. This may affect future birth and pregnancy outcomes.

METHODS: A retrospective analysis was done on 526 parturients at Victoria Hospital in London, Ontario. Women were categorized according to parity and pre-pregnancy body mass index (BMI; normal weight, BMI 18.5-24.9 kg/m

RESULTS: Obese class II and III primiparous women required an additional 1.62 and 2.67 hours (P = 0.012), respectively, to reach a dilation of 10 cm compared with their normal weight counterparts; obese class II and III multiparous women required an …

Amylin As A Potential Link Between Type 2 Diabetes And Alzheimer Disease, Florin Despa, Larry B. Goldstein, Geert Jan Biessels

Pharmacology and Nutritional Sciences Faculty Publications

No abstract provided.

Cost-Effectiveness Analysis Of Ocriplasmin Versus Watchful Waiting For Treatment Of Symptomatic Vitreomacular Adhesion In The Us, Arshad M Khanani, Pravin U Dugel, Julia A Haller, Alan L Wagner, Benedicte Lescrauwaet, Ralph Schmidt, Craig Bennison

Wills Eye Hospital Papers

Aim: Evaluate the cost-effectiveness of ocriplasmin in symptomatic vitreomacular adhesion (VMA) with or without full-thickness macular hole ≤400 μm versus standard of care.

Methods: A state-transition model simulated a cohort through disease health states; assignment of utilities to health states reflected the distribution of visual acuity. Efficacy of ocriplasmin was derived from logistic regression models using Ocriplasmin for Treatment for Symptomatic Vitreomacular Adhesion Including Macular Hole trial data. Model inputs were extracted from Phase III trials and published literature. The analysis was conducted from a US Medicare perspective.

Results: Lifetime incremental cost-effectiveness ratio was US$4887 per quality-adjusted life year gained …

Coaction Between Physical Activity And Fruit And Vegetable Intake In Racially Diverse, Obese Adults, Natalia I Heredia, Maria E Fernandez, Alexandra E Van Den Berg, Casey P Durand, Harold W Kohl, Belinda M Reininger, Kevin O Hwang, Lorna H Mcneill

Faculty, Staff and Student Publications

PURPOSE: There is minimal understanding of the potential for coaction, defined as action on one behavior increasing the likelihood of taking action on another behavior, between physical activity (PA) and fruit and vegetable (FV) intake. The purpose of this study was to assess the bidirectional coaction between FV intake and PA, as well as self-efficacy for these behaviors, in a racially diverse sample of obese adults.

DESIGN: This is a secondary analysis using data collected from the Path to Health study, a randomized controlled trial. ClinicalTrials.gov Identifier: NCT03674229.

SAMPLE: Obese adults who completed baseline and 6-month follow-up assessments.

MEASURES: For …

Fibrin Clots Maintain The Viability And Proliferative Capacity Of Human Mesenchymal Stem Cells: An In Vitro Study, Ryan J Warth, Paul G Shupe, Xueqin Gao, Mohammad Syed, Walter R Lowe, Johnny Huard, Christopher D Harner

Faculty, Staff and Student Publications

BACKGROUND: Augmentation of soft-tissue repairs with an autologous fibrin clot has been used clinically for nearly four decades; however, fibrin clots tend to produce an abundance of scar tissue, which is known to inhibit soft-tissue regeneration. Mesenchymal stem cells (MSCs) embedded in fibrin clots before repair could reduce scar tissue deposition and facilitate soft-tissue regeneration. To our knowledge, no published studies have directly evaluated the viability or bioactivity of MSCs in fresh human fibrin clots over time. The purpose of this study was to evaluate the viability and bioactivity of human MSCs inside human fibrin clots over time in nutritive …

The Impact Of Diabetic Foot Ulcers And Unilateral Offloading Footwear On Gait In People With Diabetes, Erica Ling, Brian Lepow, He Zhou, Ana Enriquez, Ashley Mullen, Bijan Najafi

Faculty, Staff and Students Publications

BACKGROUND: Unilateral offloading footwear prescribed to patients with diabetic foot ulcers elevates one limb relative to the other, which may lead to limp and abnormal gait. This study investigated whether the unilateral foot ulcer and offloading combination negatively impacts gait function beyond diabetic peripheral neuropathy.

METHODS: Eighty-six participants were recruited in 3 groups: 12 with diabetic peripheral neuropathy and unilateral foot ulcers wearing offloading footwear (offloading group, age = 55.6 ± 9.5 years, BMI = 30.9 ± 4.5 kg/m

FINDINGS: The offloading group exhibited deteriorated gait function compared to the non-diabetic group (p < 0.005, Cohen's effect size d = 0.90-2.61). They also had decreased gait speed (p < 0.001, d = 1.79) and stride length (p < 0.001, d = 1.76), as well as increased gait cycle time (p < 0.001, d = 1.67) and limp (p < 0.050, d = 0.72-1.49) compared to the neuropathy group. The offloading group showed increased gait unsteadiness compared to the neuropathy group, but the difference did not reach statistical significance in our samples.

INTERPRETATION: This study demonstrated that while diabetic …

Probable African Tick Bite Fever In The United States, Kami Lowery, Theodore Rosen

Faculty, Staff and Students Publications

African tick bite fever (ATBF) is a tick-borne rickettsial disease most often observed in North American and European tourists returning home from the southern portion of Africa. Ticks infected with Rickettsia africae transmit this parasitic bacterium to humans, who subsequently develop an influenza-like illness, one or more inoculation eschars, and in some cases, a cutaneous rash. Because ATBF often presents with non-specific symptoms that suggest other infectious diseases, establishing the diagnosis may be difficult. Confirmatory assays, including serology and nucleic acid amplification, may take weeks to return and cannot help with acute treatment decisions. We present a case of a …

Temporal Trends And Geographic Variations In Mortality Rates From Prescription Opioids: Lessons From Florida And West Virginia, Sarah A Palumbo, Charles H Hennekens, Janet D Robishaw, Robert S Levine

Faculty, Staff and Students Publications

OBJECTIVES: To explore temporal trends and geographic variations in mortality from prescription opioids from 1999 to 2016.

METHODS: Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research Multiple Cause of Death files were used to calculate age-adjusted rates and 95% confidence intervals (CIs) and create spatial cluster maps.

RESULTS: From 1999 to 2016, counties in West Virginia experienced the highest overall mortality rates in the United States from prescription opioids. Specifically, from 1999 to 2004, the highest rate in West Virginia of 24.87/100,000 (95% CI 17.84-33.73) was the fourth highest in the United States. From 2005 to …

Orthostatic Hypotension, Cardiovascular Outcomes, And Adverse Events: Results From Sprint, Stephen P Juraschek, Addison A Taylor, Jackson T Wright, Gregory W Evans, Edgar R Miller, Timothy B Plante, William C Cushman, Tanya R Gure, William E Haley, Imran Moinuddin, John Nord, Suzanne Oparil, Carolyn Pedley, Christianne L Roumie, Jeff Whittle, Alan Wiggers, Ciarán Finucane, Rose Anne Kenny, Lawrence J Appel, Raymond R Townsend

Faculty, Staff and Students Publications

Orthostatic hypotension (OH) is frequently observed with hypertension treatment, but its contribution to adverse outcomes is unknown. The Systolic Blood Pressure Intervention Trial (SPRINT) was a randomized trial of adults, age ≥50years at high risk for cardiovascular disease (CVD) with a seated systolic BP (SBP) of 130–180 mmHg and a standing SBP ≥110 mmHg. Participants were randomized to a SBP treatment goal of either <120 mmHg or <140 mmHg. OH was defined as a drop in SBP≥20 or diastolic BP ≥10 mmHg one minute after standing from a seated position. We used Cox models to examine the association of OH with CVD or adverse study events by randomized BP goal. During the follow-up period (median 3years), there were 1,170 (5.7%) instances of OH among those assigned a standard BP goal, and 1,057 (5.0%) among those assigned the intensive BP goal. OH was not associated with higher risk of CVD events (primary outcome: HR 1.06; 95%CI: 0.78,1.44). Moreover, OH was not associated with syncope, electrolyte abnormalities, injurious falls, or acute renal failure. OH was associated with hypotension-related hospitalizations or emergency department visits (HR 1.77; 1.11,2.82) and bradycardia (HR 1.94; 1.19,3.15), but these associations did not differ by BP treatment goal. OH was not associated with a higher risk of CVD events and BP treatment goal had no effect on OH’s association with hypotension and bradycardia. Symptomless OH during hypertension treatment should not be viewed as a reason to down-titrate therapy even in the setting of a lower BP goal.

Methyl-Sensing Nuclear Receptor Liver Receptor Homolog-1 Regulates Mitochondrial Function In Mouse Hepatocytes, Sungwoo Choi, Bingning Dong, Chih-Chun Janet Lin, Mi Jeong Heo, Kang Ho Kim, Zhen Sun, Martin Wagner, Nagireddy Putluri, Jae Myoung Suh, Meng C Wang, David D Moore

Faculty, Staff and Students Publications

Liver receptor homologue-1 (LRH-1; NR5A2) is a nuclear receptor that regulates metabolic homeostasis in the liver. Previous studies identified phosphatidylcholines as potential endogenous agonist ligands for LRH-1. In the liver, distinct subsets of phosphatidylcholine species are generated by two different pathways: choline addition to phosphatidic acid via the Kennedy pathway, or trimethylation of phosphatidylethanolamine via Phosphatidylethanolamine N-methyl Transferase (PEMT). Here we report that a PEMT - LRH-1 pathway specifically couples methyl metabolism and mitochondrial activities in hepatocytes. We show that the loss of Lrh-1 reduces mitochondrial number, basal respiration, beta-oxidation and ATP production in hepatocytes, and decreases expression of mitochondrial …

Mail-Back Envelopes For Retrieval Of Opioids After Pediatric Surgery, Adam C Adler, Ammar N Yamani, Caitlin D Sutton, Danielle M Guffey, Arvind Chandrakantan

Faculty, Staff and Students Publications

BACKGROUND: Opioid overprescription has the potential to lead to harmful medications remaining in homes and to a rise in accidental or deliberate ingestion by children and adolescents. Although methods for opioid disposal are available, many are costly or require greater than minimal effort for the patient. In this study, we used a mail-back return envelope to retrieve unused opioids after ambulatory pediatric surgery.

METHODS: This feasibility study was performed to assess the rate of opioid return by using a mail-back envelope for children ages 0 to 18 prescribed opioids after outpatient surgery. Participants were provided a return envelope as well …

Characterization Of Urinary Concentrations Of Heavy Metals Among Socioeconomically Disadvantaged Black Pregnant Women, Inkyu Han, Kristina W Whitworth, Xueying Zhang, Masoud Afshar, Pamela D Berens, Elaine Symanski

Faculty, Staff and Student Publications

The objective of this study was to characterize exposures to metals using biological samples collected on socioeconomically disadvantaged black pregnant women. We obtained 131 anonymous urine samples provided by black pregnant women visiting a Medicaid-serving prenatal clinic in Houston, TX, from March 27, 2017 to April 11, 2017. We analyzed urine samples for 15 metals including cadmium (Cd), arsenic (As), lead (Pb), and nickel (Ni) and for creatinine and cotinine. We found that median concentrations of zinc (Zn), selenium (Se), and aluminum (Al) among black pregnant women in this study were 1.5 to 3 times higher than levels reported among …

Simulation-Based Mastery Learning Compared To Standard Education For Discussing Diagnostic Uncertainty With Patients In The Emergency Department: A Randomized Controlled Trial., Danielle M. Mccarthy, Rhea E. Powell, Kenzie A. Cameron, David H. Salzman, Dimitrios Papanagnou, Amanda Doty, Benjamin E. Leiby, Katherine Piserchia, Matthew R. Klein, Xiao C. Zhang, William C. Mcgaghie, Kristin L. Rising

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: Diagnostic uncertainty occurs frequently in emergency medical care, with more than one-third of patients leaving the emergency department (ED) without a clear diagnosis. Despite this frequency, ED providers are not adequately trained on how to discuss diagnostic uncertainty with these patients, who often leave the ED confused and concerned. To address this training need, we developed the Uncertainty Communication Education Module (UCEM) to teach physicians how to discuss diagnostic uncertainty. The purpose of the study is to evaluate the effectiveness of the UCEM in improving physician communications.

METHODS: The trial is a multicenter, two-arm randomized controlled trial designed to …

Development Of An Abbreviated Symptom Score For The Neonatal Abstinence Syndrome., I. Chervoneva, S. C. Adeniyi-Jones, F. Blanco, W. K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

OBJECTIVE: We sought a shortened MOTHER neonatal abstinence syndrome (NAS) and Finnegan score that would retain comparable performance characteristics of the full instrument.

STUDY DESIGN: Retrospective cohort.

RESULTS: In total, 124,170 MOTHER NAS scores between August 2007 and May 2016 from 775 infants (≥36 weeks) were examined. Classification and regression tree model identified the most important subsets of the scored variables. A 9-element shortened scale yielded >90% sensitivity and specificity to predict clinical endpoints based on the full 19-element MOTHER NAS score. Conversion of the data sets to the Finnegan score, and applying the same procedure resulted in a nine-element …

Comparison Of Microneutralization And Histo-Blood Group Antigen-Blocking Assays For Functional Norovirus Antibody Detection, Robert L Atmar, Khalil Ettayebi, B Vijayalakshmi Ayyar, Frederick H Neill, Ralph P Braun, Sasirekha Ramani, Mary K Estes

Faculty, Staff and Students Publications

BACKGROUND: The development of an in vitro cultivation system for human noroviruses allows the measurement of neutralizing antibody levels.

METHODS: Serum neutralizing antibody levels were determined using a GII.4/Sydney/2012-like virus in human intestinal enteroids in samples collected before and 4 weeks after administration of an investigational norovirus vaccine and were compared with those measured in histo-blood group antigen (HBGA)-blocking assays.

RESULTS: Neutralizing antibody seroresponses were observed in 71% of 24 vaccinated adults, and antibody levels were highly correlated (r = 0.82, P < .001) with those measured by HBGA blocking.

CONCLUSIONS: HBGA-blocking antibodies are a surrogate for neutralization in human noroviruses.

Treatment De-Escalation For Hpv-Associated Oropharyngeal Squamous Cell Carcinoma With Radiotherapy Vs. Trans-Oral Surgery (Orator2): Study Protocol For A Randomized Phase Ii Trial., Anthony C Nichols, Pencilla Lang, Eitan Prisman, Eric Berthelet, Eric Tran, Sarah Hamilton, Jonn Wu, Kevin Fung, John R De Almeida, Andrew Bayley, David P Goldstein, Antoine Eskander, Zain Husain, Houda Bahig, Apostolos Christopoulous, Michael Hier, Khalil Sultanem, Keith Richardson, Alex Mlynarek, Suren Krishnan, Hien Le, John Yoo, S Danielle Macneil, Adrian Mendez, Eric Winquist, Nancy Read, Varagur Venkatesan, Sara Kuruvilla, Andrew Warner, Sylvia Mitchell, Martin Corsten, Murali Rajaraman, Stephanie Johnson-Obaseki, Libni Eapen, Michael Odell, Shamir Chandarana, Robyn Banerjee, Joseph Dort, T Wayne Matthews, Robert Hart, Paul Kerr, Samuel Dowthwaite, Michael Gupta, Han Zhang, Jim Wright, Christina Parker, Bret Wehrli, Keith Kwan, Julie Theurer, David A Palma

Paediatrics Publications

BACKGROUND: Patients with human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPC) have substantially better treatment response and overall survival (OS) than patients with HPV-negative disease. Treatment options for HPV+ OPC can involve either a primary radiotherapy (RT) approach (± concomitant chemotherapy) or a primary surgical approach (± adjuvant radiation) with transoral surgery (TOS). These two treatment paradigms have different spectrums of toxicity. The goals of this study are to assess the OS of two de-escalation approaches (primary radiotherapy and primary TOS) compared to historical control, and to compare survival, toxicity and quality of life (QOL) profiles between the two approaches. …

A Ten-Year Retrospective Evaluation Of Acute Flaccid Myelitis At 5 Pediatric Centers In The United States, 2005-2014., Margaret M. Cortese, Anita K. Kambhampati, Jennifer E. Schuster, Zaid Alhinai, Gary R. Nelson, Gloria J. Guzman Perez-Carrillo, Arastoo Vossough, Michael A. Smit, Robert C. Mckinstry, Timothy Zinkus, Kevin R. Moore, Jeffrey M. Rogg, Meghan S. Candee, James J. Sejvar, Sarah E. Hopkins

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Acute flaccid myelitis (AFM) is a severe illness similar to paralytic poliomyelitis. It is unclear how frequently AFM occurred in U.S. children after poliovirus elimination. In 2014, an AFM cluster was identified in Colorado, prompting passive US surveillance that yielded 120 AFM cases of unconfirmed etiology. Subsequently, increased reports were received in 2016 and 2018. To help inform investigations on causality of the recent AFM outbreaks, our objective was to determine how frequently AFM had occurred before 2014, and if 2014 cases had different characteristics.

METHODS: We conducted a retrospective study covering 2005-2014 at 5 pediatric centers in 3 …

A Broad-Spectrum Antiviral Molecule, Ql47, Selectively Inhibits Eukaryotic Translation, Mélissanne De Wispelaere, Margot Carocci, Dominique J Burri, William J Neidermyer, Calla M Olson, Imme Roggenbach, Yanke Liang, Jinhua Wang, Sean P J Whelan, Nathanael S Gray, Priscilla L Yang

Faculty, Staff and Students Publications

Small-molecule inhibitors of translation are critical tools to study the molecular mechanisms of protein synthesis. In this study, we sought to characterize how QL47, a host-targeted, small-molecule antiviral agent, inhibits steady-state viral protein expression. We demonstrate that this small molecule broadly inhibits both viral and host protein synthesis and targets a translation step specific to eukaryotic cells. We show that QL47 inhibits protein neosynthesis initiated by both canonical cap-driven and noncanonical initiation strategies, most likely by targeting an early step in translation elongation. Our findings thus establish QL47 as a new small-molecule inhibitor that can be utilized to probe the …

Association Of Time-Varying Blood Pressure With Chronic Kidney Disease Progression In Children., Ben Christopher Reynolds, Jennifer Lynn Roem, Derek Kai Sing Ng, Mina Matsuda-Abedini, Joseph Thomas Flynn, Susan Lynn Furth, Bradley A. Warady, Rulan Savita Parekh

Manuscripts, Articles, Book Chapters and Other Papers

Importance: Optimal blood pressure (BP) management in children with chronic kidney disease (CKD) slows progression to end-stage renal disease. Studies often base progression risk on a single baseline BP measurement, which may underestimate risk.

Objective: To determine whether time-varying BP measurements are associated with a higher risk of progression of CKD than baseline BP measurements.

Design, Setting, and Participants: The ongoing longitudinal, prospective cohort study Chronic Kidney Disease in Children (CKID) recruited children from January 19, 2005, through March 19, 2014, from pediatric nephrology centers across North America, with data collected at annual study visits. Participants included children aged 1 …

The Role Of Noninvasive Tests For Differentiating Nash From Nafl And Diagnosing Advanced Fibrosis Among Patients With Nafld, Maya Balakrishnan, Rohit Loomba

Faculty, Staff and Students Publications

Assessing for the presence of non-alcoholic steatohepatitis (NASH) and the presence of advanced fibrosis is vital among patients with non-alcoholic fatty liver disease (NAFLD) as each is predictive of disease outcomes. A liver biopsy is the gold standard method for doing so but is impossible to perform among all patients with NAFLD. Reliable methods for noninvasively detecting for the presence of NASH and advanced fibrosis are thus a pressing need. The search for noninvasive tests has been more successful for advanced fibrosis than for NASH. Clinical prediction models and elastography have acceptable accuracy for ruling out advanced fibrosis; when used …

Patients' Perspectives Of Tuberculosis Treatment Challenges And Barriers To Treatment Adherence In Ukraine: A Qualitative Study, Omowunmi Aibana, Emily Dauria, Tetiana Kiriazova, Olena Makarenko, Mariya Bachmaha, Natasha Rybak, Timothy Palen Flanigan, Vasyl Petrenko, Anne E Becker, Megan B Murray

Faculty, Staff and Student Publications

OBJECTIVES: To understand the challenges faced by patients with tuberculosis (TB) and factors that influence TB treatment adherence in Ukraine.

DESIGN: Qualitative study.

SETTING: TB treatment facilities in Kyiv Oblast, Ukraine.

PARTICIPANTS: Sixty adults who had undergone treatment for drug-sensitive TB between June 2012 and August 2015.

METHODS: We conducted semistructured, in-depth, individual interviews among a purposively selected clinical sample of patients previously treated for drug-sensitive TB. Interview content encompassed WHO's framework for barriers to adherence to long-term therapies and included questions about patient preferences and motivators concerning treatment adherence. We examined treatment experience across strata defined by previously identified …

Insights Image For "Evidence Of Increased Hypoxia Signalling In Fetal Liver From Maternal Nutrient Restriction In Mice"., Bethany N Radford, Victor K M Han

Paediatrics Publications

No abstract provided.