Translational Medical Research Commons^™

From The Editors, Anthony M. Provenzano B.A., John Dawdy B.Sc., Mhs

Clinical Research in Practice: The Journal of Team Hippocrates

Welcome to the inaugural issue of Clinical Research in Practice: The Journal of Team Hippocrates.

Female Breakfast Skippers Display A Disrupted Cortisol Rhythm And Levated Blood Pressure, Megan Witbracht, Nancy L. Keim, Shavawn Forester, Adrianne Widaman, Kevin D. Laugero

United States Department of Agriculture-Agricultural Research Service / University of Nebraska-Lincoln: Faculty Publications

Chronic stress and over-activity in the hypothalamic–pituitary–adrenal (HPA) axis may link breakfast skipping and poor cardiometabolic health. Missing the first major meal of the day in rodents prolongs elevated circulating corticosterone at a time when it's normally decreasing. To extend these findings to humans, we hypothesized that habitual breakfast skippers would display a similar pattern of circulating cortisol and alterations in meal and stress-induced cortisol reactions. Normal weight to obese women aged 18–45 years old who were strictly defined as either breakfast skippers (n = 30) or breakfast eaters (n = 35) were invited to participate in our …

Exploration Of Factors Associated With Patient Adherence In Upper Extremity Rehabilitation: A Mixed-Methods Embedded Design, Enrique V. Smith-Forbes

Theses and Dissertations--Rehabilitation Sciences

Adherence is considered a prerequisite for the success of exercise programs for musculoskeletal disorders. The negative effects of non-adherence to exercise recommendations impact the cost of care, and also treatment effectiveness, treatment duration, the therapeutic relationship, waiting times, the efficiency of personnel and use of equipment. Adherence to therapeutic exercise intervention is a multifaceted problem.

The World Health Organization (WHO) established the multidimensional adherence model (MAM). The MAM describes five interactive dimensions (socioeconomic, healthcare team and system, condition-related, therapy-related, and patient-related factors) that have an effect on patient adherence.

The first purpose of this dissertation was to explore the MAM …

The Metabolomic Effects Of Metformin On Colon Cancer, Jennifer W. Harris

Theses and Dissertations--Clinical and Translational Science

Metformin is an oral biguanide that is prescribed to over 120 million people worldwide for the treatment of conditions including type II diabetes mellitus, polycystic ovarian syndrome, and gestational diabetes. This hypoglycemic agent is rapidly emerging as a potential cost-effective anti-oncogenic agent. Over the past decade multiple epidemiologic studies have consistently associated metformin with decreased cancer incidence and cancer-related mortality. More recently numerous preclinical and clinical studies have demonstrated anti-cancer effects of metformin, leading to the proposal of numerous clinical trials to better understand this drug and its mechanism of action.

Previously experts believed metformin primarily targeted AMP-activated protein kinase …

Combination Of Music And Aromatherapy To Improve The Efficiency Of Motor Functions And Speech In Patients Paralyzed From Stroke., Mounica Bevara

Undergraduate Research Posters

With the rapid development of medical technology, millions of dollars are being spent on discovering innovative methods of treating fatal diseases such as stroke that may also result in temporary paralysis. Physiotherapy treatments aimed at restoring brain function in patients paralyzed following a stroke is subjective to the patient and does not guarantee complete rehabilitation. While many practitioners have attempted to employ complementary and alternative methods of treatment such as massage therapy, acupuncture therapy, siddha, and marma therapy, none of them proved to be equally as effective as physiotherapy. However, prior studies support the notion that aromatherapy used in combination …

Targeting Autophagy In Multiple Myeloma, Yun Dai

Theses and Dissertations

Apoptosis (Type I) and autophagy (Type II) represent two major forms of programmed cell death. Numerous anticancer agents employed in standard chemotherapy or novel targeted therapy induce both apoptosis and autophagy. Of note, a cytoprotective autophagic response often counteracts apoptosis triggered by such agents, potentially contributing to drug-resistance. Mechanistically, autophagy and apoptosis share molecular regulatory mechanisms primarily governed by the Bcl-2 family proteins. However, since autophagy acts as the double-edge sword in cancer, whether autophagy should be inhibited or activated in cancer treatment remains the subject of debate. Here we report a) a novel autophagy-targeted strategy that targeting the adaptor …

Immunotherapy Of Cancer: Reprogramming Tumor/Immune Cellular Crosstalk To Improve Anti-Tumor Efficacy, Kyle K. Payne

Theses and Dissertations

Immunotherapy of cancer has been shown to be promising in prolonging patient survival. However, complete elimination of cancer and life-long relapse-free survival remain to be major challenge for anti-cancer therapeutics. We have previously reported that ex vivo reprogramming of tumor-sensitized immune cells by bryostatin 1/ionomycin (B/I) and the gamma-chain (γ-c) cytokines IL-2, IL-7, and IL-15 resulted in the generation of memory T cells as well as CD25+ NKT cells and CD25+ NK cells. Adoptive cellular therapy (ACT) utilizing these reprogrammed immune cells protected FVBN202 mice from tumor challenge, and overcame the suppressive functions of myeloid-derived suppressor cells (MDSCs). We then …

Meta-Analysis Of Gene Expression Studies, Umaporn Siangphoe

Theses and Dissertations

Combining effect sizes from individual studies using random-effects models are commonly applied in high-dimensional gene expression data. However, unknown study heterogeneity can arise from inconsistency of sample qualities and experimental conditions. High heterogeneity of effect sizes can reduce statistical power of the models. We proposed two new methods for random effects estimation and measurements for model variation and strength of the study heterogeneity. We then developed a statistical technique to test for significance of random effects and identify heterogeneous genes. We also proposed another meta-analytic approach that incorporates informative weights in the random effects meta-analysis models. We compared the proposed …

The Effects Of Temperature And Seasons On Subcutaneous White Adipose Tissue In Humans: Evidence For Thermogenic Gene Induction, Philip A. Kern, Brian S. Finlin, Beibei Zhu, Neda Rasouli, Robert E. Mcgehee Jr., Philip M. Westgate, Esther E. Dupont-Versteegden

Clinical and Translational Science Faculty Publications

Context: Although brown adipose tissue (BAT) activity is increased by a cold environment, little is known of the response of human white adipose tissue (WAT) to the cold.

Design: We examined both abdominal and thigh subcutaneous (SC) WAT from 71 subjects who were biopsied in the summer or winter, and adipose expression was assessed after an acute cold stimulus applied to the thigh of physically active young subjects.

Results: In winter, UCP1 and PGC1 α mRNA were increased 4 to 10-fold (p<0.05) and 1.5 to 2-fold, respectively, along with beige adipose markers, and UCP1 protein was 3-fold higher in the winter. The seasonal increase in abdominal SC WAT UCP1 mRNA was considerably diminished in subjects with a BMI > 30 kg/m², suggesting that dysfunctional WAT in obesity inhibits adipose thermogenesis. After applying an acute …

Sustained Adrenergic Signaling Promotes Cervical Cancer Progression, Nouara C. Sadaoui

Dissertations and Theses (Open Access)

Background: Chronic stress and sustained adrenergic signaling are known to promote tumor progression. The underlying mechanisms behind this process are not well understood. We examined the effects of sustained adrenergic signaling on cervical cancer progression through increased expression of HPV oncogenes, E6 and E7.

Materials and Methods: ADRβ expression levels were examined in patient-derived cervical cancer samples. We used an orthotopic model of cervical cancer to investigate the effects of restraint stress on tumor growth and metastasis. We evaluated the in vivo effects of a β-blocker, propranolol, and HPV E6/E7 siRNA. In vitro, ADRβ positive cervical cancer cells were …

Targeting Cox-2 And Rank In Aggressive Breast Cancers: Inflammatory Breast Cancer And Triple-Negative Breast Cancer, Monica Elizabeth Reyes

Dissertations and Theses (Open Access)

Inflammatory breast cancer (IBC) and triple-negative breast cancer (TNBC) are two highly aggressive breast cancer subtypes associated with a poor outcome. Despite sensitivity to current treatment, these breast cancers subtypes have a high recurrence rate and proclivity to metastasize early. The aggressiveness of IBC and TNBC have been linked to CSCs and epithelial to mesenchymal transition (EMT), which are critical features of breast cancer progression and metastasis. The clinical challenge faced in the treatment of IBC and TNBC is finding a treatment strategy to target the cancer stem-like (CSC) population to block metastasis. Cyclooxygenase-2 (COX-2) and receptor activator of nuclear …

Targeting Cox-2 And Rank In Aggressive Breast Cancers: Inflammatory Breast Cancer And Triple-Negative Breast Cancer, Monica E. Reyes

Dissertations and Theses (Open Access)

Inflammatory breast cancer (IBC) and triple-negative breast cancer (TNBC) are two highly aggressive breast cancer subtypes associated with a poor outcome. Despite sensitivity to current treatment, these breast cancers subtypes have a high recurrence rate and proclivity to metastasize early. The aggressiveness of IBC and TNBC have been linked to CSCs and epithelial to mesenchymal transition (EMT), which are critical features of breast cancer progression and metastasis. The clinical challenge faced in the treatment of IBC and TNBC is finding a treatment strategy to target the cancer stem-like (CSC) population to block metastasis. Cyclooxygenase-2 (COX-2) and receptor activator of nuclear …

Can Mhealth Improve Risk Assessment In Underserved Populations? Acceptability Of A Breast Health Questionnaire App In Ethnically Diverse, Older, Low-Income Women., Carolina Bravo, Cristina O’Donoghue, Celia P. Kaplan, Judith Luce, Elissa Ozanne

Journal of Health Disparities Research and Practice

Background: Use of mobile health (mHealth) tools has expanded rapidly but little research has been done on its acceptability by low-income, diverse, older patient populations.

Objective: To assess the attitudes of a diverse group of underserved women on the acceptability and usability of mHealth tools in a clinical setting using a breast health questionnaire application (app) at a public hospital mammography clinic.

Methods: Semi-structured interviews were conducted in a breast-imaging center of an urban safety net institution from July-August 2012. Interviews included pre- and post-questions. Women completed the Athena breast health questionnaire app on an iPad and were asked about …

Neglected Or Non-Compliant? Assessing The Difficulties Of Tuberculosis Patients In Salvador-Ba, Brazil, Erin Slatery

Independent Study Project (ISP) Collection

Objective: The aim of this study is to analyze how Instituto Brasileiro para Investigação da Tuberculose (IBIT), a philanthropic tuberculosis clinic in Salvador, Brazil, maintains treatment abandonment rates much lower than those of surrounding public clinics. This study also aims to evaluate how professionals conceptualize and address the difficulties faced by patients.

Methods: Interviews were conducted with 8 IBIT professionals and 16 patients in treatment for tuberculosis in the aforementioned institution via semi-structured and structured questionnaires, respectively. Participant observation guided the analysis of relationships between patients and professionals.

Results: Patients found varying aspects of treatment difficult depending on personal circumstances, …

Racial And Ethnic Disparities In Time To Cure Of Incontinence Present At Nursing Home Admission, Donna Z. Bliss, Olga Gurvich, Kay Savik, Lynn Eberly, Susan Harms, Jean F. Wyman

Journal of Health Disparities Research and Practice

Abstract

As many as half of older people that are admitted to nursing homes (NHs) are incontinent of urine and/or feces. Not much is known about the rate of cure of incontinence present at NH admission, but available reports suggest the rate is low. There have been racial and ethnic disparities in incontinence treatment, but the role of disparities in the cure of incontinence is understudied. Using the Peters-Belson method and multilevel predictors, our findings showed that there were disparities in the time to cure of incontinence for Hispanic NH admissions. A significantly smaller proportion of older Hispanic admissions were …

Role Of The Ang-Tie2 Pathway In The Invasive Recurrence Of Gbm Following Anti-Vegf Therapy, Nahir Cortes Santiago

Dissertations and Theses (Open Access)

Strong pre-clinical and clinical data supporting the effectiveness of bevacizumab, a humanized monoclonal anti-VEGF antibody, for the treatment of gliomas led to its accelerated approval for the treatment of patients with recurrent glioma. However, despite strong anti-tumor effects, upon treatment with bevacizumab, patients will invariably recur with a tumor characterized by enhanced invasiveness and resistance to therapy. This study aims to elucidate the mechanisms leading to this enhanced malignancy with the hope of uncovering new potential therapeutic targets for combined treatment. Using tissue sections from U87-derived glioma bearing mice treated with or without aflibercept (another anti-VEGF antibody) we have gathered …

Targeting The Redox System To Overcome Mechanisms Of Drug Resistance In Chronic Lymphocytic Leukemia, Marcia A. Ogasawara

Dissertations and Theses (Open Access)

Chronic Lymphocytic Leukemia (CLL) is the most common form of leukemia diagnosed in Western countries and is characterized by clonal expansion of B cells. The clinical course of CLL is diverse and nearly 50% of patients present with chromosomal abnormalities. Deletion of the short arm on chromosome 17 (del17p) occurs in 5-7% of cases and presents with the shortest median survival time and often respond poorly to therapy. The tumor suppressor gene, TP53 is located on this region and it is well established that the p53 protein regulates multiple functions including: mitochondria biogenesis, response to DNA damage and redox balance. …

Targeting The Mdm2-P53 Axis For The Treatment Of Dedifferentiated Liposarcoma, Katelynn Bill

Dissertations and Theses (Open Access)

Dedifferentiated liposarcoma (DDLPS) is an aggressive malignancy characterized by a high rate of recurrence and dismal patient outcome. Minimal improvement in patient survival has been made in the last several decades, highlighting the crucial need for improved therapeutic strategies. A better understanding of the molecular deregulations underlying DDLPS would facilitate the discovery of improved therapeutic approaches. MDM2 is a well characterized oncoprotein and the most known negative regulator of p53. MDM2 amplification is considered the “hallmark” of DDLPS. Additionally, these tumors are known to harbor wild-type p53. We sought to take advantage of this knowledge and evaluate the role of …

Promoting Teamwork In Translational Medical Teams: Insights And Recommendations From Science And Practice, Lauren E. Benishek, Ashley M. Hughes, Megan E. Gregory, Shirley C. Sonesh, Eduardo Salas, Elizabeth H. Lazzara

Publications

Translational medical teams are transdisciplinary, highly collaborative, and operate within dynamic environments to solve time-sensitive and complex problems. These teams are tasked with turning observations in the laboratory and clinic into effective interventions that improve the health of individuals and the public. The nature of the problems they seek to solve requires coordination among clinicians, scientists, and experts from various scientific disciplines. Characteristically, translational medical teams have complex compositions, structure, and pluralistic goals, which pose significant challenges and barriers to enacting effective teamwork, compromising team performance. Given these challenges, it is imperative to glean insights from teams research and the …

Shape And Position Of The Node And Notochord Along The Bilateral Plane Of Symmetry Are Regulated By Cell-Extracellular Matrix Interactions., Maria Pulina, Dong Liang, Sophie Astrof

Center for Translational Medicine Faculty Papers

The node and notochord (and their equivalents in other species) are essential signaling centers, positioned along the plane of bilateral symmetry in developing vertebrate embryos. However, genes and mechanisms regulating morphogenesis of these structures and their placement along the embryonic midline are not well understood. In this work, we provide the first evidence that the position of the node and the notochord along the bilateral plane of symmetry are under genetic control and are regulated by integrin α5β1 and fibronectin in mice. We found that the shape of the node is often inverted in integrin α5-null and fibronectin-null mutants, and …