Translational Medical Research Commons^™

Sex Differences In The Sex Differences In The Effects Of Environmental Enrichment After An Early Life Stressor, Alfredo Gutierrez, Annelyn Torres-Reverón, Phd, Raura Doreste-Méndez

Journal of Health Disparities Research and Practice

Studies have shown that environmental enrichment can compensate for the effects of an early life stressor such as maternal separation. Behavioral responses and immunohistochemical markers in rats are affected by environmental enrichment after maternal separation. In this study we seek to investigate whether sex influences the behavioral responses of environmental enrichment after maternal separation.

Prior scientific evidence suggests that there are behavioral sex differences in: 1) neural processes underlying successful or failed fear extinction (Gruene et al, 2014); (2) prenatal stress exposure and response to behavioral anxiety tests (Said et al, 2015); and (3) glutamate receptor expression in response to …

Cox2 Plays An Important Role In Maintenance Of Mammary Cancer Stem Cell Population In Human Breast Cancer Cell Lines, Mayra Garcia, Shehla Pervin, Phd, Easter Thames, Meher Parveen, Phd, Melanie Baker

Journal of Health Disparities Research and Practice

Breast cancer is a malignant growth in the adipose-rich mammary gland. Initiation and progression of breast tumors involve multiple cell types, among which mammary cancer stem cells play an important role. There are two main types of adipocytes; white adipocytes have previously been found to influence the disease while brown adipocytes, which uniquely express uncoupling protein 1 (UCP1), were recently detected in breast tumors.

We have detected Myf5, a transcription factor, which is expressed in the progenitor population of brown adipocytes, in breast cancer cell lines. We also found an association between expression of Myf5 and COX2 (or Ptgs2), which …

The Role Of Integrin-Associated Protein “Pinch” In Kidney Development, Tyrone Gamble Jr, Roy Zent, Phd, Bertha C. Elias, Phd

Journal of Health Disparities Research and Practice

PINCH (a particularly interesting new cysteine-histidine-rich protein) is a protein that binds with Integrin-linked kinase and Parvin, to form an IPP complex. This complex is formed only when integrin molecules are activated upon interaction with the basement membrane. The IPP complex then acts as a platform for other proteins to come together and regulate cell signaling to and from the extracellular matrix (ECM). This allows for various cellular activities to progress like cell adhesion, migration, proliferation, etc. There are two types of PINCH proteins, PINCH-1 and PINCH-2. Studies from our group have shown that the lack of PINCH-1 in the …

Nitric Oxide And Cyclic Gmp Signaling In Cancer Therapy, Armond Dorsey, Ferid Murad, Md, Phd, Ka Bian, Md, Phd

Journal of Health Disparities Research and Practice

The nitric oxide-3’,5’-cyclic guanosine monophosphate signaling pathway (NO-cGMP signaling pathway) is a well-known signal transduction pathway which elicits several physiological processes including: cell proliferation, vasodilation, cardiac protection, etc. In this pathway, NO binds to the ferrous heme of histidine-105 on the prosthetic heme of the β₁ subunit of soluble guanylyl cyclase, resulting in the production of cGMP. This pathway, however, is inhibited in certain cancer cells—as observed in glioma cell lines. As a result, the production of cGMP is reduced. This mechanism may facilitate uncontrolled tumor cell growth.

The cancers under research—lung carcinoma, glioma, and pancreatic carcinoma—are all highly …

Potential Cost Savings Of Not Doing Cd4 Counts In Hiv Positive People In Rhode Island With An Undetectable Viral Load, Ruth Dele-Oni, Ferdinand Schumacher, Zachary Markus, Timothy Flanigan, Md

Journal of Health Disparities Research and Practice

CD4 cells fight infections in the body. When someone contacts Human Immunodeficiency Virus (HIV), their CD4 cells are taken over by HIV which turns them into manufacturers of many copies of the virus. The Viral Load (VL) measures the amount of virus in the blood. When HIV takes over the CD4 cells, the VL increases while the number of necessary CD4 cells decreases. When patients maintain stable treatment, their CD4 counts rise, and VLs may become undetectable, indicating the virus is too little to be detected in their blood. Knowing this, is frequent CD4 counts necessary for those with undetectable …

Defining The Role For Zbp-89 In Atm-Mediated Dna Damage Response To Irradiation In The Intestine, Christine Carethers, Juanita L. Merchant, Md, Phd

Journal of Health Disparities Research and Practice

ZBP-89 (ZNF148, Zfp148) is a zinc-finger transcription factor that inhibits cellular proliferation when overexpressed in cell lines. ZBP-89 forms a protein-protein interaction with p53 and Ataxia-telangiectasia mutated (ATM). However, it is unclear how the interaction modulates the function of these two proteins in vivo.

Double strand DNA breakage induced by -irradiation induces ATM phosphoinositol kinase activity, which initiates a cascade of events culminating in cell cycle arrest, DNA repair or apoptosis. Elevated levels of ZBP-89 induce growth arrest and apoptosis in gastrointestinal cell lines. Therefore, we hypothesize that ZBP-89 facilitates cell growth arrest and activation of the DNA repair pathway …

Induction Of Dusp9 In Xenografts From Human Breast Cancer Cell Lines Increases Mammary Cancer Stem Cells, Albert Barrios, Meher Parveen, Phd, Easter Thames, Melanie Baker, Shelha Pervin, Phd

Journal of Health Disparities Research and Practice

Breast cancer remains a complex disease that kills 40,000 women every year. Initiation and progression of breast cancer is influenced by heterogeneous groups of cells, including mammary cancer stem cells (MCSCs). Progression of this dreadful disease is driven by many signaling pathways among which MAPK pathway is highly prominent. Since targeting prominent kinases in MAPK pathway has been unsuccessful to control breast cancer, it is important to examine the phosphatases that regulate the activity of these kinases.

Using xenograft model from breast cancer cell lines, our lab has found that during the initial stages of xenograft development (week 1-4, 100-200mg …

Preparing Underrepresented High School Students To Increase Diversity In The Research And Health Professions, Dolores E. Caffey-Fleming, Ms, Mph, Christopher Reid, Md, Phd

Journal of Health Disparities Research and Practice

This article introduces the work that was done through the Coordinating Center at Charles R. Drew University of Medicine and Science.

The Step Up Program, Lawrence Agodoa, Md

Journal of Health Disparities Research and Practice

The Short-Term Research Experience Program for Underrepresented Persons (STEP-UP) was established as part of the NIDDK Strategic Plan on Minority Health Disparities. This article provides an overview and introduction of this program. All of the articles that are included in this special issue reflect the work of our coordinating centers, the mentors and their staff, as well as the students.

Anticoagulation Following Gastrointestinal Bleeding: Assessing Harms And Benefits, Jacob Jeffers

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Sengupta N, Feuerstein JD, Patwardhan VR, et al. The risks of thromboembolism vs. recurrent gastrointestinal bleeding after interruption of systemic anticoagulation in hospitalized in patients with gastrointestinal bleeding: a prospective study. Am. J. Gastroenterol. 2014;110:328-335. doi: 10.1038/ajg.2014.398

Sharing Experiences And Expertise: The Health Care Systems Research Network Workshop On Patient Engagement In Research, Sarah Madrid, Leah Tuzzio, Cheryl D. Stults, Leslie A. Wright, Gina Napolitano, Ellis Dillon, Heather Tabano, Sarah M. Greene

Journal of Patient-Centered Research and Reviews

The Health Care Systems Research Network’s (HCSRN) Patient Engagement in Research Scientific Interest Group (PER SIG) held a half-day workshop for researchers attending HCSRN’s 22nd annual conference, April 16, 2016, in Atlanta, Georgia. The workshop blended didactic and interactive content to facilitate co-learning. Both researchers and patient partners developed the content, including three broad topics: engagement of patient partners in developing research studies, nurturing partnerships, and assessing the impact of patient engagement in research. Each module presented approaches relevant to the specific topic, including lessons from the literature and in-the-field experience. Patient partners reflected on their experience related to each …

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 …