Medicine and Health Sciences Commons^™

Unification Of De Novo And Acquired Ibrutinib Resistance In Mantle Cell Lymphoma., Xiaohong Zhao, Tint Lwin, Ariosto Silva, Bijal Shah, Jiangchuan Tao, Bin Fang, Eduardo Sotomayor, +Several Additional Authors

Medicine Faculty Publications

The novel Bruton’s tyrosine kinase inhibitor ibrutinib has demonstrated high response rates in B-cell lymphomas; however, a growing number of ibrutinib-treated patients relapse with resistance and fulminant progression. Using chemical proteomics and an organotypic cell-based drug screening assay, we determine the functional role of the tumour microenvironment (TME) in ibrutinib activity and acquired ibrutinib resistance. We demonstrate that MCL cells develop ibrutinib resistance through evolutionary processes driven by dynamic feedback between MCL cells and TME, leading to kinome adaptive reprogramming, bypassing the effect of ibrutinib and reciprocal activation of PI3K-AKT-mTOR and integrin-β1 signalling. Combinatorial disruption of B-cell receptor signalling and …

Newborn Care Curriculum: Newborn Medications, Lauren Rechtman, Rebekah Conroy

E-Learning Modules

Introduction: Based on a 2014 newborn education needs assessment, 39.6% of surveyed pediatric hospitalists expressed interest in receiving more education on newborn medications, and 94% were interested in computer-based learning modules as the method of learning. Thus, this module was designed to serve as a self-study tool or as a tool for small-group teaching.

Methods: Initially designed for pediatric hospitalists, the module can be used for any learner interested in newborn care as it is meant to provide practical applications to the bedside clinician. This module was first implemented as part of the multimodule Newborn Care Curriculum within the pediatric …

Constitutive Activation Of Kappa Opioid Receptors At Ventral Tegmental Area Inhibitory Synapses Following Acute Stress., Abigail M Polter, Kelsey Barcomb, Rudy W Chen, Paige M Dingess, Nicholas M Graziane, Travis E Brown, Julie A Kauer

Pharmacology and Physiology Faculty Publications

Stressful experiences potently activate kappa opioid receptors (κORs). κORs in the ventral tegmental area regulate multiple aspects of dopaminergic and non-dopaminergic cell function. Here we show that at GABAergic synapses on rat VTA dopamine neurons, a single exposure to a brief cold-water swim stress induces prolonged activation of κORs. This is mediated by activation of the receptor during the stressor followed by a persistent, ligand-independent constitutive activation of the κOR itself. This lasting change in function is not seen at κORs at neighboring excitatory synapses, suggesting distinct time courses and mechanisms of regulation of different subsets of κORs. We also …

Positive Affect Predicts Cerebral Glucose Metabolism In Late Middle-Aged Adults., Christopher Nicholas, Siobhan M Hoscheidt, Lindsay R Clark, Annie M Racine, Sara E Berman, Rebecca L Koscik, N Maritza Dowling, Sanjay Asthana, Bradley T Christian, Mark A Sager, Sterling C Johnson

GW Biostatistics Center

Positive affect is associated with a number of health benefits; however, few studies have examined the relationship between positive affect and cerebral glucose metabolism, a key energy source for neuronal function and a possible index of brain health. We sought to determine if positive affect was associated with cerebral glucose metabolism in late middle-aged adults (n = 133). Participants completed the positive affect subscale of the Center for Epidemiological Studies Depression Scale at two time points over a two-year period and underwent 18F-fluorodeoxyglucose-positron emission tomography scanning. After controlling for age, sex, perceived health status, depressive symptoms, anti-depressant use, family …

Metastasis-Associated Protein 1 Is An Upstream Regulator Of Dnmt3a And Stimulator Of Insulin-Growth Factor Binding Protein-3 In Breast Cancer., S Deivendran, Hezlin Marzook, T R Santhoshkumar, Rakesh Kumar, M Radhakrishna Pillai

Biochemistry and Molecular Medicine Faculty Publications

Despite a recognized role of DNA methyltransferase 3a (DNMT3a) in human cancer, the nature of its upstream regulator(s) and relationship with the master chromatin remodeling factor MTA1, continues to be poorly understood. Here, we found an inverse relationship between the levels of MTA1 and DNMT3a in human cancer and that high levels of MTA1 in combination of low DNMT3a status correlates well with poor survival of breast cancer patients. We discovered that MTA1 represses DNMT3a expression via HDAC1/YY1 transcription factor complex. Because IGFBP3 is an established target of DNMT3a, we investigated the effect of MTA1 upon IGFBP3 expression, and found …

Mll3/Mll4 Are Required For Cbp/P300 Binding On Enhancers And Super-Enhancer Formation In Brown Adipogenesis., Binbin Lai, Ji-Eun Lee, Younghoon Jang, Lifeng Wang, Weiqun Peng, Kai Ge

Anatomy and Regenerative Biology Faculty Publications

Histone H3K4me1/2 methyltransferases MLL3/MLL4 and H3K27 acetyltransferases CBP/p300 are major enhancer epigenomic writers. To understand how these epigenomic writers orchestrate enhancer landscapes in cell differentiation, we have profiled genomic binding of MLL4, CBP, lineage-determining transcription factors (EBF2, C/EBPβ, C/EBPα, PPARγ), coactivator MED1, RNA polymerase II, as well as epigenome (H3K4me1/2/3, H3K9me2, H3K27me3, H3K36me3, H3K27ac), transcriptome and chromatin opening during adipogenesis of immortalized preadipocytes derived from mouse brown adipose tissue (BAT). We show that MLL4 and CBP drive the dynamic enhancer epigenome, which correlates with the dynamic transcriptome. MLL3/MLL4 are required for CBP/p300 binding on enhancers activated during adipogenesis. Further, MLL4 …

Pulmonary Microrna Profiles Identify Involvement Of Creb1 And Sec14l3 In Bronchial Epithelial Changes In Allergic Asthma., Sabine Bartel, Nikola Schulz, Francesca Alessandrini, Andrea C Schamberger, Philipp Pagel, Fabian J Theis, Katrin Milger, Elfriede Noessner, Stephen M Stick, Anthony Kicic, Oliver Eickelberg, Robert J Freishtat, Susanne Krauss-Etschmann

Medicine Faculty Publications

Asthma is highly prevalent, but current therapies cannot influence the chronic course of the disease. It is thus important to understand underlying early molecular events. In this study, we aimed to use microRNAs (miRNAs) - which are critical regulators of signaling cascades - to identify so far uncharacterized asthma pathogenesis pathways. Therefore, deregulation of miRNAs was assessed in whole lungs from mice with ovalbumin (OVA)-induced allergic airway inflammation (AAI). In silico predicted target genes were confirmed in reporter assays and in house-dust-mite (HDM) induced AAI and primary human bronchial epithelial cells (NHBE) cultured at the air-liquid interface. We identified and …

Subanesthetic Ketamine For Pain Management In Hospitalized Children, Adolescents, And Young Adults: A Single-Center Cohort Study, K A. Sheehy, C Lippoid, A L. Rice, R Nobrega, Julia C. Finkel, Zenaide Quezado

Anesthesiology and Critical Care Medicine Faculty Publications

¹Division of Anesthesiology, Pain, and Perioperative Medicine, The Sheikh Zayed Institute for Pediatric Surgical Innovation, Children’s Research Institute, Children’s National Health System, George Washington University School of Medicine and Health Sciences, ²Center for Neuroscience Research, Children’s Research Institute, Children’s National Health System, Washington, DC, USA *These authors contributed equally to this work Background: Subanesthetic doses of ketamine, an N-methyl-D-aspartate receptor antagonist used as an adjuvant to opioid for the treatment of pain in adults with acute and chronic pain, have been shown, in some instances, to improve pain intensity and to decrease opioid intake. However, less is …

Projected Financial Losses Experienced By Community Health Centers Under A Scenario Of Major Cuts In Key Sources Of Federal Funding: 2018-2022, Avi Dor, Eric Luo, Ali Moghtaderi, Anne Rossier Markus

Geiger Gibson/RCHN Community Health Foundation Research Collaborative

Congress is currently considering options to significantly reduce federal funding for the Medicaid expansion and the Marketplace subsidies implemented under the Affordable Care Act (ACA). Separately, the Health Centers Fund, which currently accounts for 70% of all federal health center grant funding, is set to expire in September 2017. These potential changes in federal funding could have a dramatic impact on health centers and the communities they serve. The purpose of this brief is to simulate the potential combined impact of these major changes in federal funding that will directly affect community health centers. Secondarily, this brief also assesses the …

Decreasing Social Isolation Through An Intergenerational Social Engagement Program, Jacqueline Kendona

Doctor of Occupational Therapy Capstone Projects

Social isolation is the absence of meaningful contact with others. Older adults who perceived themselves as socially isolated are at risk of negative health outcomes. A person’s psychological wellbeing can be improved through engaging in meaningful leisure activities.

The Intergenerational Social Engagement Program, or the ISEP, was developed to connect older adults and high school students to help decrease social isolation in older adults. The ISEP incorporates concepts from the Canadian Model of Occupational Performance and is intended for implementation in senior living communities. The program is to be led by an occupational therapist. Occupational therapy practitioners have an understanding …

Gw Nursing, Spring 2017, George Washington University, School Of Nursing

GW Nursing Magazine

No abstract provided.

The Rejoice Trial: A Phase 3 Randomized, Controlled Trial Evaluating The Safety And Efficacy Of A Novel Vaginal Estradiol Soft-Gel Capsule For Symptomatic Vulvar And Vaginal Atrophy., Ginger D Constantine, James A Simon, James H Pickar, David F Archer, Harvey Kushner, Brian Bernick, Gina Gasper, Shelli Graham, Sebastian Mirkin

Obstetrics and Gynecology Faculty Publications

OBJECTIVE: To evaluate the safety and efficacy of TX-004HR vaginal estradiol soft-gel capsules for moderate-to-severe dyspareunia associated with postmenopausal vulvar and vaginal atrophy.

METHODS: In this randomized, double-blind, placebo-controlled, phase 3 study, postmenopausal women with a self-identified most bothersome symptom of dyspareunia received 4, 10, or 25 μg TX-004HR or placebo for 12 weeks. Four co-primary efficacy endpoints were change from baseline to week 12 in percentages of superficial and parabasal cells, vaginal pH, and severity of dyspareunia. Secondary endpoints included severity of vaginal dryness and vulvar and/or vaginal itching or irritation. Endometrial histology and adverse events (AEs) were included …

Use Of P53-Silenced Endothelial Progenitor Cells To Treat Ischemia In Diabetic Peripheral Vascular Disease., Nabanita Kundu, Cleyton C Domingues, Cyril Chou, Neeki Ahmadi, Sara Houston, D Joseph Jerry, Sabyasachi Sen

Medicine Faculty Publications

Background Peripheral vascular disease is a major diabetes mellitus‐related complication. In this study, we noted that expressions of proapoptotic p53 gene and its downstream cascade gene such as p21 are upregulated in hyperglycemia. Therefore, we investigated whether p53‐ and p21‐silenced endothelial progenitor cells (EPCs) were able to survive in hyperglycemic milieu, and whether transplantation of either p53 knockout (KO) or p21KO or p53‐ and p21‐silenced EPCs could improve collateral vessel formation and blood flow in diabetic vaso‐occlusive peripheral vascular disease mouse models.

Methods and Results We transplanted p53 and p21KO mouse EPCs (mEPCs) into streptozotocin–induced diabetic (type 1 diabetes mellitus …

Internal Medicine Resident Perspectives Regarding Broad-Spectrum Antibiotic Usage., Ann M Laake, Gayle Bernabe, James Peterson, Angelike P Liappis

Medicine Faculty Publications

Focus groups held with internal medicine residents discussed their perspectives regarding broad-spectrum antibiotic (BSA) usage. Residents knew of BSA-associated adverse events, but they did not associate such events with increased patient morbidity and mortality, and they were more likely to use BSA in situations with diagnostic uncertainty and sick patients.

Implications Of The Pegasus-Timi 54 Trial For Us Clinical Practice, S M. Bradley, G P. Hess, P Stewart, E J. Armstrong, Steven A. Farmer, J H. Wasfy, J A. Valle, A Sandhu, T M. Maddox

Medicine Faculty Publications

Objectives This study aims to determine the proportion of real-world patients with myocardial infarction (MI) who would have been eligible for the PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54) trial, to characterise their current use of P2Y₁₂ inhibitors and to explore the estimated costs and ischaemic event consequences of increasing P2Y₁₂ inhibitor use among these patients.

Methods In the US national ACTION Registry–GWTG (Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With The Guidelines), we identified 273 328 patients …

Return To University After A Stroke: An Autoethnography, Rachel Sieber

Doctor of Occupational Therapy Capstone Projects

Background and Aims: Return to university presents a unique transition for the person with stroke who may demonstrate with impairments and may have difficulties while engaging in this change. This study will explore elements that comprise the needs and factors of the stroke survivor and supports or accommodations that may improve success of the student returning to university.

Methods: An autoethnography was used with narrative journals and poems dated June 2003 to October 2005, interviews with friends, family and professors and a literature review. Data analysis included an open-coding procedure to find themes from the journal entries, interviews and narrative …

Medicine + Health Magazine, Spring 2017, George Washington University, School Of Medicine And Health Sciences, Office Of Communications And Marketing

Medicine + Health Magazine

No abstract provided.

A Comparative Study On The Impact Evaluation Of World Vision’S Water, Sanitation And Hygiene Program In Malawi, Mozambique, And Zambia: Analyses Using Lives Saved Tool, Chulwoo Park, Armen Martirosyan, Erin A. Jones, Ashley Labat, Yvonne Tam, Emmanuel Opong

GW Research Days 2016 - 2020

Background

According to the World Health Organization, diarrheal disease is the second top killer of children under five years of age (U5), claiming around 760,000 young children’s lives every year, and 88% of diarrheal disease is attributed to unsafe water supply, inadequate sanitation and hygiene. The humanitarian aid organization, World Vision, launched community-based water, sanitation and hygiene (WASH) project in 76 Area Development Programs (ADPs) for 506,019 target U5 population across Southern Africa Region (SAR): Malawi, Mozambique and Zambia in 2010.

Objective

This study estimated the retrospective health impact of the project between 2010 and 2014 to measure how effectively …

Promotion Of New Diabetes Products In The District Of Columbia, Joy Eckert, Dilpan Sundaramoorthy, Alycia Hogenmiller

GW Research Days 2016 - 2020

Background: Growth in pharmaceutical expenditures for diabetes outpaced growth in diabetes prevalence. Prescribers accepting gifts and meals from pharmaceutical companies have been linked with higher prescription rates and costs[1]. Pharmaceutical marketing to these prescribers and patients often promotes newer, more expensive drugs, such as the GLP-1 analogues and SGL-2 inhibitors. These two drug classes are more expensive but no more effective than metformin,[2] the recommended first-line treatment for diabetes, and the oldest and cheapest available treatment. We investigated how cost of diabetes treatment was affected by marketing practices in the District of Columbia.

Methods: The AccessRx program …

What May Be Associated With Young Adult E-Cigarette Use? Examination Of Key Correlates, Diane J. Martinez, Monique M. Turner, Kathleen Roche, Kimberly Horn

GW Research Days 2016 - 2020

Given increasing rates of e-cigarette use among young adults, research is needed on the attitudes and beliefs that drive use among this age group. Tobacco control approaches used to prevent cigarette smoking may not work as effectively for preventing e-cigarette use. To address this research gap, the present study applied the Integrated Behavior Model (IBM) encompassing the affect heuristic theory to examine the individual-level determinants (i.e., attitude, perceived norm, personal agency, intention, and e-cigarette risk perception) of young adults' e-cigarette use. The 2013-2014 Population Assessment of Tobacco and Health (PATH) Study Wave 1 baseline adult dataset consisted of 9,112 young …

Anatomical Knowledge Retention In Changing Curricula, Alexa Lean, Juliet Lee, Ellen Goldman, Gisela Butera, Kirsten Brown, Rosalyn Jurjus

GW Research Days 2016 - 2020

Traditionally anatomy is one of the first subjects taught in medical school. Practicing physicians have commented on medical students’ poor anatomical knowledge in surgically oriented clerkships. Literature also shows that correlating clinical and anatomical sciences throughout early medical education may improve anatomical knowledge retention. With major medical school curricular changes happening across the nation, more quantitative data confirming this correlation is needed.

The medical curriculum at the George Washington University School of Medicine recently underwent reorganization, transforming an earlier discipline-based curriculum to that of an integrated system-based one. In order to determine whether reorganization has an effect on anatomical knowledge …

Emergency Department Approach To Electrical Toothbrush Associated Hand Injury, A Unique Case Of Non-Oropharyngeal Injury., Hannah Robinson, Neal Sikka, Chimere Little, Ali Pourmand

GW Research Days 2016 - 2020

Puncture wounds are common injuries treated in the emergency department (ED). Prior studies have shown that toothbrushes are common reservoirs for oral flora, especially in regions near the head of the toothbrush near the bristles. ED providers must be aware of the danger associated with bacterial contamination of the associated wound and should be familiar with different pathogens and options for treatment. We present a unique case of a 30-year-old male with non-intraoral injury who presented to the ED after puncturing his left palm with the metal post of an electric toothbrush.

A Review Of Pain Control In Pediatric Cardiac Bypass Surgery, Pranathi Ari, Andrew T. Waberski, Nina Deutsch

GW Research Days 2016 - 2020

Background: Children undergoing cardiac surgery with cardiopulmonary bypass receive high dose opioids for analgesia and to reduce the neurohormonal stress response. While opioids have excellent pharmacodynamics profiles adverse effects include: respiratory depression, bradycardia, nausea, vomiting, and tolerance. Additionally, opioids with short half-lives like fentanyl require several boluses to be administered during surgery causing fluctuating levels analgesia. Several strategies to advance pain control incorporate regional and neuraxial anesthetic techniques, however anticoagulation preclude its routine use. Alternatively using opioids with longer half-lives for analgesia may improve pain control and reduce adverse effects.

Objective: The objective of this study is to quantify postoperative …

Medical Resource Utilization Of Outpatient Care For Children With Neurofibromatosis Type 1, Rabia Idrees, Michael Fisher, Rachel Hachen, Brian Callaghan, Robert A. Avery

GW Research Days 2016 - 2020

Background:

Neurofibromatosis Type 1 (NF1) is an autosomal dominant syndrome with manifestations affecting the central nervous system, musculoskeletal system, peripheral nervous system, and cognitive/behavioral functions. Many of these manifestations persist throughout life and require medical/surgical interventions.

The resource utilization and economic burden of caring for children with NF1 is unknown. Prior research has inherent selection bias and does not accurately reflect the incidence/resource utilization of morbidities. In order to identify which disease manifestations are in the most need of improved clinical algorithms and novel therapeutics, the frequency/type of resources utilized (i.e., diagnostic imaging and specialty visits) must be determined.

The …

Stakeholders' Perceptions Of A Hospital Based Emergency Medicine Education & Training Program: A System Change, Kate Douglass, Jay Pandya, Michael Brennan, Kyle Yoder, Janice Blanchard, Natasha Powell, Zohray Talib

GW Research Days 2016 - 2020

Background: Emergency Medicine (EM) is a new and developing specialty around the world. In India, one model for capacity building has been the development of partnerships between US academic institutions and private healthcare institutions for implementing post-graduate education and training in EM. Initiated in 2007, programs have grown both in number and scope and have continued to attract new students and partner institutions. This study was undertaken to better understand the impact of EM training programs on hospital systems.

Methods: A mixed-methods evaluation was undertaken at 5 program sites across India in the summer of 2016. Two researchers conducted onsite …

Removing Barriers To Care For The Underserved: Provider And Patient Perception Of Direct To Consumer Telemedicine, Robert M. Grell, Rachel Hatcliffe, Sean M. Gillen, Craig Sable, Vanessa Grant, Matthew Ledda, Mary Fuska, Shireen Atabaki

GW Research Days 2016 - 2020

Purpose of Study: Lack of access to pediatric subspecialty care is a major barrier to pediatric health for underserved populations in the Washington DC, Virginia and Maryland area. Lack of access to transportation, long office wait times, and missed school and work are barriers that prevent access to subspecialty care. Direct to consumer (DTC) telemedicine provides this service to our underserved population by bringing care into their own home through use of computers, tablets, and smart phones.

Methods Used: Structured interviews of parents and providers were performed prior to implementation of a subspecialty DTC telemedicine program for underserved children in …

Fungus Amungus -- A Common Disease State That Is Commonly Missed: A Survey Based Study, Ramsin Yadgar, Adam Friedman, Neal Bhatia

GW Research Days 2016 - 2020

Background: Dermatophyte infections involving the skin, hair, or nails affect an estimated 25% of the world's population, and accounted for 51 million outpatient visits over a ten-year period (1995-2004) in the United States alone. Dermatomycosis is routinely managed by dermatologists, though given the diversity of clinical presentations, is sometimes misdiagnosed, which can result in inappropriate therapy, worsening of symptoms, and even result in additional skin and soft tissue infections.

Methods: An interactive survey of board-certified dermatologists was conducted at the 2016 Orlando Dermatology Aesthetic & Clinical Conference, during a seminar on superficial mycotic infections. The structure of the survey entailed …

Secondary Prevention At The Aswan Heart Centre, Amira Athanasios

GW Research Days 2016 - 2020

Cardiovascular disease remains the leading cause of death globally, taking the lives of almost 18 million patients around the world each year. The overwhelming majority of cardiovascular deaths take place in low- to mid-income counties, suggesting that most cardiovascular deaths are preventable. In this study, current literature on secondary prevention of coronary artery disease was analyzed. Specific emphasis was given to preventative measures and successes in low income countries. Based on a literature review, a patient questionnaire to better understand patient adherence to preventative measures was created. This questionnaire focuses on patients receiving dual antiplatelet therapy post acute myocardial infarct …

Mutations In Braf Are Associated With Higher Levels Of Immune Infiltrates In Microsatellite-Stable Colon Cancer, Jake Rubin, Eduard Porta Parto

GW Research Days 2016 - 2020

While BRAF is among the most well-established oncogenes in human cancers, more recently it has garnered attention for its role in suppressing antitumor immunity, especially in melanoma. Because tumor-infiltrating lymphocyte (TIL) density is strongly prognostic in colorectal cancer (CRC)⁷, we decided to investigate the connection between TIL density and the BRAF-activating V600E mutation in CRC.

We used ESTIMATE to quantify immune infiltrate in samples from the TCGA colon adenocarcinoma (COAD) dataset (n = 216). This is an algorithm that uses the gene-expression signature of 141 immune-related genes to infer the presence of immune cells in the tumor infiltrate. …

Healthcare Provider And Patient Knowledge, Attitudes And Practices (Kap) Regarding Zika Virus, Quinton Katler, Prachi Godiwala, Charles Macri, Beth Pineles, Aileen Chang, Homa Ahmadzia

GW Research Days 2016 - 2020

Introduction:

Zika virus emergence in the western hemisphere has prompted the critical need for tailored risk counseling. Our team created a KAP survey in order to assess provider and patient awareness of Zika virus symptoms, transmission, treatment, and current and future concerns in order to inform local risk counseling efforts.

Methods:

The cross-sectional survey was issued in Medical Faculty Associates (MFA) clinics and via online link to healthcare providers and community members. The REDCap Data Collection tool was used to capture responses with subsequent SAS data analysis.

Results:

A total of 172 responses were collected. Most respondents (97%) were aware …