Translational Medical Research Commons^™

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 …

Magnitude Of And Prognostic Factors Associated With 1-Year Mortality After Hospital Discharge For Acute Decompensated Heart Failure Based On Ejection Fraction Findings, Andrew H. Coles, Mayra Tisminetzky, Jorge L. Yarzebski, Darleen M. Lessard, Joel M. Gore, Chad E. Darling, Robert J. Goldberg

Jorge L. Yarzebski

BACKGROUND: Limited data exist about the magnitude of and the factors associated with prognosis within 1 year for patients discharged from the hospital after acute decompensated heart failure. Data are particularly limited from the more generalizable perspective of a population-based investigation and should be further stratified according to currently recommended ejection fraction (EF) findings.

METHODS AND RESULTS: The hospital medical records of residents of the Worcester, Massachusetts, metropolitan area who were discharged after acute decompensated heart failure from all 11 medical centers in central Massachusetts during 1995, 2000, 2002, 2004, and 2006 were reviewed. The average age of the 4025 …

Attitudes Toward Substance Abuse Clients: An Empirical Study Of Clinical Psychology Trainees, Chandra Mundon, Melissa Anderson, Lisa Najavits

Melissa L. Anderson

Despite the high prevalence of substance use disorder (SUD) and its frequent comorbidity with mental illness, individuals with SUD are less likely to receive effective SUD treatment from mental health practitioners than SUD counselors. Limited competence and interest in treating this clinical population are likely influenced by a lack of formal training in SUD treatment. Using a factorial survey-vignette design that included three clinical vignettes and a supplementary survey instrument, we investigated whether clinical psychology doctoral students differ in their level of negative emotional reactions toward clients with SUD versus major depressive disorder (MDD); whether they differ in their attributions …

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.

From The Editors, John Dawdy, J. Timothy Caldwell

Clinical Research in Practice: The Journal of Team Hippocrates

Editorial introduction to the third issue of Clinical Research in Practice: The Journal of Team Hippocrates.

The Role Of Ng2 Proteoglycan In Glioma., Sridevi Yadavilli, Eugene I Hwang, Roger J. Packer, Javad Nazarian

Neurology Faculty Publications

Neuron glia antigen-2 ((NG2), also known as chondroitin sulphate proteoglycan 4, or melanoma-associated chondroitin sulfate proteoglycan) is a type-1 membrane protein expressed by many central nervous system (CNS) cells during development and differentiation and plays a critical role in proliferation and angiogenesis. 'NG2' often references either the protein itself or the highly proliferative and undifferentiated glial cells expressing high levels of NG2 protein. NG2 glia represent the fourth major type of neuroglia in the mammalian nervous system and are classified as oligodendrocyte progenitor cells by virtue of their committed oligodendrocyte generation in developing and adult brain. Here, we discuss NG2 …

Role Of Proteolipid Protein In Hsv-1 Entry In Oligodendrocytic Cells, Raquel Bello-Morales, Antonio Jesús Crespillo, Beatriz Praena, Enrique Tabarés, Yolanda Revilla, Elena García, Alberto Fraile-Ramos, Wia Baron, Claude Krummenacher, José Antonio López-Guerrero

Faculty Scholarship for the College of Science & Mathematics

Herpes simplex virus type 1 (HSV-1) has the ability to enter many different hosts and cell types by several strategies. This highly prevalent alphaherpesvirus can enter target cells using different receptors and different pathways: fusion at a neutral pH, low-pH-dependent and low-pH-independent endocytosis. Several cell receptors for viral entry have been described, but several observations suggest that more receptors for HSV-1 might exist. In this work, we propose a novel role for the proteolipid protein (PLP) in HSV-1 entry into the human oligodendrocytic cell line HOG. Cells transfected with PLP-EGFP showed an increase in susceptibility to HSV-1. Furthermore, the infection …

Understanding And Targeting The C-Terminal Binding Protein (Ctbp) Substrate-Binding Domain For Cancer Therapeutic Development, Benjamin L. Morris

Theses and Dissertations

Cancer involves the dysregulated proliferation and growth of cells throughout the body. C-terminal binding proteins (CtBP) 1 and 2 are transcriptional co-regulators upregulated in several cancers, including breast, colorectal, and ovarian tumors. CtBPs drive oncogenic properties, including migration, invasion, proliferation, and survival, in part through repression of tumor suppressor genes. CtBPs encode an intrinsic dehydrogenase activity, utilizing intracellular NADH concentrations and the substrate 4-methylthio-2-oxobutyric acid (MTOB), to regulate the recruitment of transcriptional regulatory complexes. High levels of MTOB inhibit CtBP dehydrogenase function and induce cytotoxicity among cancer cells in a CtBP-dependent manner. While encouraging, a good therapeutic would utilize >100-fold …

Overcoming Treatment Resistance In Heterogeneous Tumors, Nikhil Hebbar

Theses and Dissertations--Toxicology and Cancer Biology

Most primary tumors are heterogeneous and are often composed of therapy-sensitive and emerging therapy-resistant cancer cells. Rather unexpectedly, treatment of therapy-sensitive tumor cells in heterogeneous tumor microenvironments resulted in apoptosis of the therapy-resistant cancer cells. We identified a novel Par-4 amino-terminal fragment (PAF, which includes amino acids 1-131 of Par-4) that is produced and released by therapy-sensitive cancer cells following therapy-induced caspase-dependent cleavage of the tumor suppressor Par-4. PAF caused paracrine apoptosis in therapy-resistant cancer cells. Unlike Par-4-inducible apoptosis, which is dependent on the cell surface GRP78 receptor, PAF produced cancer-selective apoptosis independent of cell surface GRP78 function. Par-4 contains …

Surface-Initiated Polymerizations For The Rapid Sorting Of Rare Cancer Cells, Jacob L. Lilly

Theses and Dissertations--Chemical and Materials Engineering

Cancer metastasis directly accounts for an estimated 90% of all cancer related deaths and is correlated with the presence of malignant cells in systemic circulation. This observed relationship has prompted efforts to develop a fluid biopsy, with the goal of detecting these rare cells in patient peripheral blood as surrogate markers for metastatic disease as a partial replacement or supplement to tissue biopsies. Numerous platforms have been designed, yet these have generally failed to support a reliable fluid biopsy due to poor performance parameters such as low throughput, low purity of enriched antigen positive cells, and insufficiently low detection thresholds …

Privatization Of Biomedical Research: A Short Term Answer With Long Term Consequences, Frederick Azalekor

Nebraska College Preparatory Academy: Senior Capstone Projects

Biomedical research owned by the government is now available to be owned by private institutions. This results in stagnant innovations because researchers have trouble with all the restrictions that are placed by private institutions. Privatization of biomedical research has short term positive effects but its negative effects are overarching and disastrous. One way to combat this, is for licenses to be deployed slowly with future consequences in mind.

• Privatization has short term benefits but long term disadvantages are disastrous. • To reduce damaging effect, privatization must be deployed slowly and carefully. • Patents or proprietary ownership must be given …

Introducing Novel Combinatorial Targeted Therapies In Multiple Types Of Cancer, Mehrad Tavallai

Theses and Dissertations

The cancers of liver, colon and breast are amongst the top five most prevalent and most fatal worldwide. As the Raf/MEK/ERK pathway is frequently deregulated in hepatocellular carcinoma (HCC), sorafenib, a Raf kinase inhibitor, became the first systemic therapy approved for the treatment of patients with HCC. However, sorafenib only produced modest effects with low response rates in the clinic. Similarly, regorafenib, which was approved for the treatment of metastatic colorectal cancer (CRC), has had a poor response rate in the clinic. Since phosphodiesterase type 5 has been reported to be overexpressed in HCC and CRC, we hypothesized that sildenafil, …

Radioprotective Cerium Oxide Nanoparticles: Molecular Imaging Investigations Of Conps’ Pharmacokinetics, Efficacy, And Mechanisms Of Action, Philip R. Mcdonagh Iii

Theses and Dissertations

Cerium oxide nanoparticles (CONPs) are being investigated for several anti-oxidant applications in medicine. One of their most promising applications is as a radioprotective drug, an area of research in need due to the severe side effects from radiation therapy. In this work, the potential of CONPs as a radioprotective drug is examined using four criteria: favorable biodistribution/pharmacokinetics, low toxicity, ability to protect normal tissue from radiation damage, and lack of protection of tumor. The mechanisms of action of CONPs are also studied. Biodistribution was determined in radiolabeled CONPs with surface coatings including citrate, dextran T10-amine (DT10-NH₂), dextran T10-polyethylene …