Translational Medical Research Commons^™

Advancing Population Health: New Models And The Role Of Research. An Overview Of The 22nd Annual Health Care Systems Research Network Conference, Robert T. Greenlee, Lois E. Lamerato, Sarah M. Greene

Journal of Patient-Centered Research and Reviews

The Health Care Systems Research Network (HCSRN; formerly HMO Research Network) held its annual conference in Atlanta, Georgia, in April 2016. A consortium of research organizations affiliated with 20 large health care delivery systems, the HCSRN met for the 22^nd consecutive year to report on scientific achievements, develop and share skills and best practices, and promote new research collaborations. The 2016 conference, with a theme of “Advancing Population Health: New Models and the Role of Research,” was co-hosted on behalf of HCSRN by Marshfield Clinic Research Foundation and Henry Ford Health System’s Public Health Sciences Department. The 350 conference …

Characterization Of Left-Ventricular Thrombus Formation Using High Frequency Ultrasound, Kelsey A. Bullens, Arvin H. Soepriatna, Pavlos P. Vlachos, Craig J. Goergen

The Summer Undergraduate Research Fellowship (SURF) Symposium

Heart failure is a leading cause of death in the United States, and cardiac thrombus, a common morbidity associated with heart failure, significantly increases a patient’s risk of embolic events. The objective of this project is to characterize left-ventricular (LV) thrombus development using high frequency ultrasound imaging in a murine model. C57BL/6J wild-type mice (n=6) were injected intraperitoneally with iron dextran five times a week for six weeks to increase oxidative stress in the heart. Granulocyte-colony stimulating factor (G-CSF) was subcutaneously injected daily during the second week to initiate stem cell migration and stimulate endothelial cell activation, thus increasing the …

Blood-Tissue Barriers And Autoantibodies In Neurodegenerative Disease Pathogenesis: An Approach To Diagnostics And Disease Mechanism, Eric Luria Goldwaser

Graduate School of Biomedical Sciences Theses and Dissertations

Brain homeostasis can be affected in a number of ways that lead to gross anatomical, cellular, and molecular disturbances giving rise to diseases like Alzheimer’s disease (AD) and related dementias. Unfortunately, the mechanistic pathoetiology of AD’s hallmark features of cerebral amyloid plaque buildup and neuronal death are still disputed. Using human brain AD sections, immunohistochemistry experiments revealed internalized surface proteins, co-localized to an expanded lysosomal compartment. Other stains for amyloid-β1-42 (Aβ42) and various immunoglobulin (Ig) species displayed them leaking out of the cerebrovasculature through a dysfunctional blood-brain barrier (BBB), binding to neurons in the vicinity, and localizing to intracellular vesicles …

Clinical Significance Of Homologous Recombination Deficiency Score Testing In Endometrial Cancer, Jean M. Hansen

Dissertations and Theses (Open Access)

Objectives: Homologous recombination deficiency (HRD) score is related to chemotherapy response in breast and ovarian cancers. The role of HRD is unknown in endometrial cancer. We examined the relationship between HRD score and survival in a cohort of endometrial cancer patients and with tumor growth using murine orthotopic models.

Methods: TCGA was queried to determine frequency and clinical significance of alterations in the HR pathway in endometrial cancer. 137 formalin-fixed paraffin-embedded endometrioid adenocarcinoma patient samples were tested for HRD score, microsatellite instability (MSI) and high mutation load (HML) using a next generation sequencing assay targeting the coding regions of 43 …

Restriction Therapy In Acute Heart Failure Is Not Shown To Be Effective, Amrit K. Basi, Colleen W. Harkreader, Nicholus H. Yee M.D., Shadia A. Yeihey M.D., Suraiya K. Azom M.D.

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Travers B, O’Loughlin C, Murphy NF, et al. Fluid restriction in the management of decompensated heart failure: no impact on time to clinical stability. J Card Fail. 2007;13(2):128-132. doi: 10.1016/j.cardfail.2006.10.012

Vedolizumab Should Be The Next Line Agent For The Treatment Of Refractory Crohn’S Disease, Mitchell Kentor

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Shelton E, Allegretti J, Stevens B et al. Efficacy of Vedolizumab as Induction Therapy in Refractory IBD Patients. Inflammatory Bowel Diseases. 2015 Dec;21(12):2879-2885. doi:10.1097/mib.0000000000000561

Statin Therapy For Elderly Patients Should Be Assessed For Each Individual, Raymond Gong

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002;360(9346):1623-30. doi:10.1016/S0140-6736(02)11600-X

It Is Reasonable To Treat Patients With Type 1 Hepatorenal Syndrome With Midodrine And Octreotide, William Kane

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Esrailian E, Pantangco ER, Kyulo NL, Hu KQ, Runyon BA. Octreotide/midodrine therapy significantly improves renal function and 30-day survival in patients with type 1 hepatorenal syndrome. Dig Dis Sci. 2007;52(3):742-748. doi: 10.1007/s10620-006-9312-0

Salvage Therapy For Non-Acetaminophen-Induced Acute Liver Failure Includes N-Acetylcysteine, David Robinson

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Lee WM, Hynan LS, Rossaro L, et al. Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure. Gastroenterology. 2009;137(3):856-864. doi: 10.1053/j.gastro.2009.06.006

From The Editors, Thomas C. Bolig, William Kane, Mitchell Kentor

Clinical Research in Practice: The Journal of Team Hippocrates

Introduction to Volume 2, Issue 2 by the new Senior Student Editors.

Racial And Ethnic Disparities In Dermatology Office Visits Among Insured Patients, 2005-2010, Valerie M. Harvey, Joan Paul, L. Ebony Boulware,

Journal of Health Disparities Research and Practice

Objective:To determine whether differences in race and ethnicity affect the usage of dermatological services.

Methods: Data from the National Ambulatory Medical Care Survey were used to study trends in ethnic/race rates of outpatient dermatology office visits among publicly and privately insured patients from 2005-2010. In multivariable models, we explored the magnitude of ethnic/race differences in dermatology visit attendance for patients with public vs. private insurance.

Results: From 2005-2010, dermatology visit utilization increased among insured Hispanics, but not among insured non-Hispanic Blacks or whites. Visits were less frequent by those with public insurance compared to private insurance. Privately and publicly …

Hispanic Representation In A Longitudinal Birth Cohort Study, Julie Postma, Lisa R. Younglove, Kerry Brooks, Tamara Odom-Maryon, Shirley Beresford, Thomas Burbacher, Phillip Butterfield, Patricia Butterfield, Nicole Cederblom, Kimberly Grant, Elaine M. Faustman

Journal of Health Disparities Research and Practice

Background: The purpose of this paper is to report: 1) strategies used to engage Hispanic women and their families in a longitudinal birth cohort study, and 2) comparisons of Hispanic and non-Hispanic groups that received those strategies. This paper augments the current literature by reporting methods and results specific to a subpopulation of Hispanic women, that of self-identified Mexican women. Comparisons between Hispanic and non-Hispanic groups that received those strategies will build the evidence base that supports effective outreach and engagement strategies.

Methods: Cultural responsiveness theory was used to structure outreach and engagement, including: 1) assembling a culturally competent team; …

Guidelines Are Not Evidence, James P. Meza Md, Phd, Nicholus H. Yee Md

Clinical Research in Practice: The Journal of Team Hippocrates

Guidelines are inherently flawed when caring for an individual patient, because they apply to populations, not individuals. A strong competency in reading and interpreting clinical research gives doctors the power to evaluate guidelines and make appropriate shared decisions with their patients.

Glucocorticoids Do Not Decrease Mortality In Severe Alcoholic Hepatitis, Thomas C. Bolig

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Thursz MR, Richardson P, Allison M, et al. Prednisolone or pentoxifylline for alcoholic hepatitis. N Engl J Med. 2015;372(17):1619-28. doi: 10.1056/NEJMoa1412278

Ikkβ Is Essential For Adipocyte Survival And Adaptive Adipose Remodeling In Obesity, Se-Hyung Park, Zun Liu, Yipeng Sui, Robert N. Helsley, Beibei Zhu, David K. Powell, Philip A. Kern, Changcheng Zhou

Clinical and Translational Science Faculty Publications

IκB kinase β (IKKβ), a central coordinator of inflammatory responses through activation of nuclear factor-κB (NF-κB), has been implicated as a critical molecular link between inflammation and metabolic disorders; however, the role of adipocyte IKKβ in obesity and related metabolic disorders remains elusive. Here we report an essential role of IKKβ in the regulation of adipose remodeling and adipocyte survival in diet-induced obesity. Targeted deletion of IKKβ in adipocytes does not affect body weight, food intake, and energy expenditure but results in an exaggerated diabetic phenotype when challenged with a high-fat diet (HFD). IKKβ-deficient mice have multiple histopathologies in visceral …

There Is Relief For Constipated Patients Taking Opioids., Ahmad Mohammadieh, James Choi, Md, Chelsea Gonzalez, Do, Diyanah Elyaman, Md

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Tack J, Lappalainen J, Diva U, Tummala R, Sostek M. Efficacy and safety of naloxegol in patients with opioid-induced constipation and laxative-inadequate response. United European Gastroenterol J. 2015 Oct;3(5):471-80. doi: 10.1177/2050640615604543

Carotid Ultrasound Is Not Helpful In Simple Syncope, Nicholus Yee M.D., Shilin Patel M.D., Raymond Gong

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Scott JW, Schwartz AL, Gates JD, Gerhard-Herman M, Havens JM. Choosing wisely for syncope: low-value carotid ultrasound use. J Am Heart Assoc. 2014 Aug 13;3(4). pii: e001063. doi: 10.1161/JAHA.114.001063

Using Mathematical Modeling To Unmask The Concealed Nature Of Long Qt-3 Syndrome, Steven Poelzing, Amara Greer-Short, Seth H. Weinberg

Biology and Medicine Through Mathematics Conference

No abstract provided.

Viruses, Vaccines And The Public, Judy Diamond, Julia Mcquillan, Amy Spiegel, Patricia Wonch Hill, Rebecca Smith, John T. West, Charles Wood

World of Viruses

Current research in virology is changing public conceptions about vaccines and infectious disease. The University of Nebraska State Museum collaborated with research virologists, science writers, artists and learning researchers to create public outreach materials about viruses and infectious disease. The project, funded by the National Institute of Health’s SEPA program, developed comics, a book with Carl Zimmer, and other materials and programs. The project launched three kinds of learning research: 1) a survey of Nebraska adults on their opinions about vaccines and infectious disease; 2) a study comparing the mental models of viruses, vaccines and infection from virologists, teachers, and …

Acrolein Is A Critical Mediator Of Alcohol-Induced Liver And Intestinal Injury In Alcoholic Liver Disease., Wei-Yang (Jeremy) Chen

Electronic Theses and Dissertations

Alcohol consumption can cause alcoholic liver disease (ALD), which remains a major cause of morbidity and mortality in the United States. Chronic alcohol consumption causes a pro-oxidant environment in the liver and increases hepatic lipid peroxidation. Acrolein is the most reactive and toxic aldehyde generated through lipid peroxidation. Acrolein forms protein adducts and triggers endoplasmic reticulum (ER) stress and hepatocyte apoptosis, which are recognized etiologic factors in ALD. Several studies have established the critical role of the gut-liver axis in ALD pathogenesis, wherein alcohol-induced gut barrier dysfunction contributes to liver injury. This study investigates, in vitro and in vivo, the …

Poly (Adp) Ribose Polymerase Inhibitors For The Treatment Of Malignant Peripheral Nerve Sheath Tumor, Christine M. Kivlin

Dissertations and Theses (Open Access)

Malignant peripheral nerve sheath tumor (MPNST) is a rare subtype of soft tissue sarcoma. Surgical excision has remained the standard of care for this highly aggressive malignancy for over a decade. Conventional chemotherapy and radiotherapy have shown limited efficacy in MPNST; therefore, it is imperative that targeted treatment be identified to improve the outcome for MPNST patients. Poly (ADP) ribose polymerase (PARP) inhibitors were first reported over a decade ago to have substantial anti-tumorigenic effects in malignancies with defective DNA repair, specifically those with BRCA1/2 (breast cancer, early onset 1/2) mutations. Further evaluation of these inhibitors has shown multiple mechanisms …

Advocating For Our Patients Using Clinical Research, Brandon Baker

Clinical Research in Practice: The Journal of Team Hippocrates

This reflection is about experiences trying to relate medical research evidence to actual patient care. This piece talks about shared decision-making about screening mammography.

Splenic Biopsies Are Underutilized Due To Overestimation Of Bleeding Risks, Nicholas Destefano

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Civardi G, Vallisa D, Berte R, et al. Ultrasound-guided fine needle biopsy of the spleen: high clinical efficacy and low risk in a multicenter Italian study. Am J Hematol. 2001 Jun;67(2):93-9. doi:10.1002/ajh.1085

Dental Health Practices In Us College Students: The American College Health Association-National College Health Assessment Findings, Lori Dewald Edd, Atc, Mches, F-Aahe

Journal of Health Disparities Research and Practice

Objective: The purpose of this study is to investigate the dental health seeking practices of US college students. Participants: The total number of college students who participated in the ACHA-NCHA survey from 2000-2013 was 1,201,531. Methods: The data requested were the demographic questions and the dental health question from both the ACHA-NCHA I and II. The data were analyzed using SPSS version 20. Results: The percentage of students who reported having a dental exam and cleaning in the last year averaged 76.6% in this study period of time. However, dental health care declined annually following their freshman year. More females …

Targeting Iκb Kinase Β In Adipocyte Lineage Cells For Treatment Of Obesity And Metabolic Dysfunctions, Robert N. Helsley, Yipeng Sui, Se-Hyung Park, Zun Liu, Richard G. Lee, Beibei Zhu, Philip A. Kern, Changcheng Zhou

Clinical and Translational Science Faculty Publications

IκB kinase β (IKKβ), a central coordinator of inflammation through activation of nuclear factor-κB, has been identified as a potential therapeutic target for the treatment of obesity-associated metabolic dysfunctions. In this study, we evaluated an antisense oligonucleotide (ASO) inhibitor of IKKβ and found that IKKβ ASO ameliorated diet-induced metabolic dysfunctions in mice. Interestingly, IKKβ ASO also inhibited adipocyte differentiation and reduced adiposity in high-fat (HF)-fed mice, indicating an important role of IKKβ signaling in the regulation of adipocyte differentiation. Indeed, CRISPR/Cas9-mediated genomic deletion of IKKβ in 3T3-L1 preadipocytes blocked these cells differentiating into adipocytes. To further elucidate the role of …

The Fertility Problem Inventory And Infertility-Related Stress: A Case Study, Staci L. Born, Jennifer J. Preston

The Qualitative Report

More than seven million people of childbearing age in the United States experience infertility. Oftentimes, for women, the experience of infertility is stressful. The Fertility Problem Inventory (FPI) has been used to quantitatively measure women’s experience of infertility-related stress. However, the construct of infertility-related stress is poorly described in existing literature. The purpose of this case study was to understand how women experience the FPI as a measure of infertility-related stress. To address this issue, women who were undergoing infertility treatment completed the FPI and participated in unstructured interviews. Archival documents were also retrieved to corroborate findings and satisfy saturation. …

Molecular Analyses Of Circadian Gene Variants Reveal Sex-Dependent Links Between Depression And Clocks, S-Q Shi, M. J. White, H. M. Borsetti, Julie S. Pendergast, A. Hida, C. M. Ciarleglio, P. A. De Verteuil, A. G. Cadar, C. Cala, D. G. Mcmahon, R. C. Shelton, S. M. Williams, C. H. Johnson

Biology Faculty Publications

An extensive literature links circadian irregularities and/or sleep abnormalities to mood disorders. Despite the strong genetic component underlying many mood disorders, however, previous genetic associations between circadian clock gene variants and major depressive disorder (MDD) have been weak. We applied a combined molecular/functional and genetic association approach to circadian gene polymorphisms in sex-stratified populations of control subjects and case subjects suffering from MDD. This approach identified significant sex-dependent associations of common variants of the circadian clock genes hClock, hPer3 and hNpas2 with major depression and demonstrated functional effects of these polymorphisms on the expression or activity of the hCLOCK …

Abnormal Uterine Bleeding Guidelines And Clinical Practice Are Based On Poor Quality Evidence, Mirek Mychajlowycz

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Munro MG, Mainor N, Basu R, Brisinger M, Barreda L. Oral medroxyprogesterone acetate and combination oral contraceptives for acute uterine bleeding: A randomized controlled trial. Obstet Gynecol. 2006 Oct;108(4):924-929. doi:10.1097/01.AOG.0000238343.62063.22

Induced Hypothermia Post Cardiac Resuscitation Works In Hospitalized Patients But Not During Transport To Hospital, A Logical Inconsistency Of Evidence, Joshua Frederick

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Kim F, Nichol G, Maynard C, et al. Effect of prehospital induction of mild hypothermia on survival and neurological status among adults with cardiac arrest. JAMA 2013;311(1):45-52. doi:10.1001/jama.2013.282173

Defining Quality In Medical Practice, Nicholas E. Boggs

Clinical Research in Practice: The Journal of Team Hippocrates

We need physicians who are willing to participate in creating the standard of care, and to hold insurance companies accountable for real evidence-based quality markers. Only then will patients receive adequate care and we as educators in medicine be able to adequately teach the next generation of physicians.