Medicine and Health Sciences Commons^™

A Systems Biology Approach To Detect Eqtls Associated With Mirna And Mrna Co-Expression Networks In The Nucleus Accumbens Of Chronic Alcoholic Patients, Mohammed Mamdani

Theses and Dissertations

Alcohol Dependence (AD) is a chronic substance use disorder with moderate heritability (60%). Linkage and genome-wide association studies (GWAS) have implicated a number of loci; however, the molecular mechanisms underlying AD are unclear. Advances in systems biology allow genome-wide expression data to be integrated with genetic data to detect expression quantitative trait loci (eQTL), polymorphisms that regulate gene expression levels, influence phenotypes and are significantly enriched among validated genetic signals for many commonly studied traits including AD.

We integrated genome-wide mRNA and miRNA expression data with genotypic data from the nucleus accumbens (NAc), a major addiction-related brain region, of 36 …

Symptoms, Cytokines, And Quality Of Life Of Patients With Chronic Graft-Versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation, Debra Kelly

Theses and Dissertations

Introduction: Chronic graft-versus-host disease (cGVHD) is a serious complication following allo-HSCT characterized by immune dysregulation, organ dysfunction, risk for infection, and distressing symptoms. Complications may include scleroderma, hepatic dysfunction and bronchiolitis obliterans. Advances in allo-HSCT for many hematologic dyscrasias (e.g. acute and chronic leukemias, aplastic anemia, and myelodysplastic syndrome) have improved survival which has generated a renewed focus on survivorship issues. Distressing symptoms are noted as negatively impacting quality of life (QoL). The relationship between inflammation and behavioral responses may impact symptoms. Examining patterns and levels of inflammation with symptoms is relevant. Objective: The aims of this study were to …

An Analysis Of Fatty Acid Metabolism’S Role In The Development Of Acute Functional Tolerance To Ethanol In Caenorhabditis Elegans, Richard Raabe

Theses and Dissertations

An individual’s naïve level of response (LR) to ethanol is predictive of their lifetime likelihood to abuse alcohol. LR is heavily genetically influenced, suggesting that the genes responsible for LR may also be central to the development of abuse disorders. Our laboratory uses the model organism C. elegans to investigate the genetic influences on responses to acute ethanol exposure. We recently found that changes in TAG levels can alter LR. From this result we investigated the role of long-chain polyunsaturated fatty acids (LC-PUFAs) as well enzymes involved in lipid modifications of proteins. We found that LC-PUFAs are necessary for acute …

The Cytotoxic Effect Of The Bcl-2 Family Of Proteins In Breast Cancer Cells, Yamileth Chin

Theses and Dissertations

Breast cancer is the second leading cause of death amongst women ages 20 to 59. Despite advancements in cancer therapies, more research is necessary to improve the diagnoses and treatment of several types of breast cancer. Paclitaxel (Taxol) is a commonly utilized anti-cancer drug for various types of solid tumors. However, the molecular mechanism utilized by paclitaxel to induce cell death is still elusive. Previous studies in our laboratory have shown that the pro-apoptotic BCL-2 family protein, BAK (BCL-2 homologous antagonist/killer) plays an important role in paclitaxel-induced cell death. In untreated breast cancer cells, BAK is associated with the anti-apoptotic …

Characterization Of Complement Evasion Of The Periopathogen, Treponema Denticola, Daniel Patrick Miller

Theses and Dissertations

Periodontitis is a polymicrobially-induced, chronic inflammatory disease of the tissues that support and surround the tooth. While greater than 500 organisms are found in dental plaque, Treponema denticola is one of only a few species associated with disease. It has been hypothesized that oral bacteria disrupt host homeostasis through manipulation of the innate immune system. In this study, we examine the impact of binding and subsequent cleavage of factor H, a complement regulator, by T. denticola in the evasion and subversion of complement. The molecular interaction between the sole FH-binding protein, FhbB, and FH was detailed by x-ray crystallography, site-directed …

Hiv And Opiates-Mediated Neurotoxicity: Gsk3Β Is A Potential Therapeutic Target, Ruturaj Masvekar

Theses and Dissertations

HIV-1 enters the CNS soon after initial systemic infection. HIV-1 can induce a wide range of neurological deficits, collectively known as HIV-1-associated neurocognitive disorders (HAND). Mature neurons are not infected by HIV-1; instead, infected and/or activated glial cells release various viral and cellular factors that induce direct and/or indirect neuronal toxicity, leading to HAND. Injection drug abuse is a significant risk factor for HIV-infection, and opiate drug abusers show increased HIV-neuropathology, even with anti-retroviral treatments. Our previous work has largely modeled HIV-neuropathology using the individual viral proteins Tat or gp120, with murine striatal neurons as targets. To model disease processes …

Evaluating The Antibody Response Against Ospa, Ospc, And Ospe Recombinant Proteins Over Time In Borrelia Burgdorferi Positive Serum Samples, Bridget Dillon

Theses and Dissertations

Lyme disease is the most common tick-borne illness in North America. It can be hard to detect using blood tests, especially in the early stage. Due to the number of significant complications from untreated or undertreated Lyme disease, better methods need to be found to detect the disease. Some surface lipoproteins may be used to detect early disease due to their early expression. Others are maintained for the duration of the infection and can be used to detect chronic Lyme disease. Antibody responses to OspA, OspC and OspE were measured in sera from experimentally infected dogs. The response to OspA …

Characterization Of Tonb-Dependent Metal Transporters Within Neisseria Gonorrhoeae, Mary Kathryne Dickinson

Theses and Dissertations

Neisseria gonorrhoeae, the etiologic agent of gonorrhea, utilizes TonB-dependent transporters to import essential nutrients such as iron. Study of TonB-dependent transporters is extremely important due to the fact that they make excellent vaccine targets. In order to learn more about the structure, function, expression, and regulation of selected TonB-dependent transporters, three goals were established for this study. The first goal was to examine the role of two highly conserved regions of TbpB in lipidation. One of the conserved regions of TbpB, the LSAC motif, was shown to be critical for lipidation. The second goal was to determine whether MisR/MisS regulates …

Characterization Of A Putative Tonb Deficient Porphyromonas Gingivalis Mutant, Soheil Rostami

Theses and Dissertations

Porphorymonas gingivalis is one of the major bacterial pathogens responsible for the initiation and progression of periodontal disease. The bacterium requires hemin uptake for its growth and has developed sophisticated mechanisms to extract hemin from hemin containing proteins in the oral cavity. Hemin first binds to receptors on the surface of P. gingivalis and is then taken up in an energy dependent manner. TonB is an inner membrane bound protein that spans the periplasm and is believed to be involved in the passage of hemin through the double membrane of P. gingivalis. However, the TonB protein in P. gingivalis is …

Android-Based Smartphone Application Simulation And Systematic Design To Reduce Medication Administration Error In Prehospital Emergency Care., Natalie Vazquez

Theses and Dissertations

Since 1999 when the report To Err is Human: Building a Safer Health System was released, medical errors have come into focus (Kohn, 2000). In an effort to reduce medication administration errors in prehospital emergency care, an android-based smartphone application simulation was created. The app has components including QR barcode scanning, text to speech for medication cross-checking, weight-based medication dose calculations, and time stamped medication data wirelessly transferring to a database in real-time. Color standard identification was implemented, aiding to a designed systematic process for patient treatment to reduce medication errors. Direct observation was performed of emergency patient calls with …

Identifying Functional Variation In Schizophrenia Gwas Loci By Pooled Sequencing, Erik Loken

Theses and Dissertations

Schizophrenia demonstrates high heritability in part accounted for by common simple nucleotide variants (SNV), rare copy number variants (CNV) and, most recently, rare SNVs Although heritability explained by rare SNVs and CNVs is small compared to that explained by common SNVs, rare SNVs in functional sequences may identify specific disease mechanisms. However, current exome methods do not capture a large proportion of potentially functional bases where rare variation may impact disease risk: as much as two-thirds of conserved sequences lie outside the exome in non-coding regions of cross-species evolutionary constraint. We reasoned that the candidate loci from the Psychiatric Genomics …

Dr. Who?: The Science And Culture Of Medical Wear Design, Patricia Duignan

Theses and Dissertations

The multi-million-dollar medical uniform industry has not utilized advancements in garment and textile technology that could positively impact the protection of healthcare professionals and patients. In most cases the uniforms meet basic requirements – they clothe the professional in a recognizable way. Little innovation in design, function and performance, has been applied to these garments. This is particularly evident in the case of the stereotypical white lab coat worn by many physicians, despite evidence indicating that these lab coats may carry contamination and play a role in the spread of deadly bacteria. Healthcare Associated Infections (HAIs) are among the most …

Transformation Of Human Mast Cells By Interferon-Gamma And The Potential Role Of Myeloid Derived Suppressor Cells In Mastocytosis., Sahar Lotfi-Emran

Theses and Dissertations

Mast cells respond to a variety of signals, are associated with both increased inflammation and regulation of the immune response, and are able to interact with a variety of hematopoietic and non-hematopoietic cells. The majority of the work that highlights mast cell pleiotropic abilities has been completed in murine models. Though these models have significantly advanced our understanding of what mast cells can do, they cannot inform us as to what mast cells actually do in human beings. The goal of this dissertation is to assess fully mature, primary human mast cell function beyond the well-defined type 1 hypersensitivity function …

Hydropathic Interactions And Protein Structure: Utilizing The Hint Force Field In Structure Prediction And Protein‐Protein Docking., Mostafa H. Ahmed

Theses and Dissertations

Protein structure predication is a field of computational molecular modeling with an enormous potential for improvement. Side-chain geometry prediction is a critical component of this process that is crucial for computational protein structure predication as well as crystallographers in refining experimentally determined protein crystal structures. The cornerstone of side-chain geometry prediction are side-chain rotamer libraries, usually obtained through exhaustive statistical analysis of existing protein structures. Little is known, however, about the driving forces leading to the preference or suitability of one rotamer over another. Construction of 3D hydropathic interaction maps for nearly 30,000 tyrosines extracted from the PDB reveals their …

Examining The Effect Of Race On The Relationship Between Posttraumatic Stress Disorder And Metabolic Syndrome In Women, Leia Harper

Theses and Dissertations

Posttraumatic stress disorder (PTSD) is a psychiatric condition affecting approximately 8% of the adult U.S. population with rates twice as high in women than men. Increasingly, evidence has suggested a close relationship between PTSD and increased risk of metabolic diseases. However, the literature on PTSD and metabolic disease risk factors has been limited by the lack of investigation of the potential influence of race on this relation. The current study examined the possible effect of race on the relation between PTSD and metabolic risk. Data for this study were provided from sample of that included 50 African American women and …

Novel Therapeutic Strategies For Pancreatic Cancer, Bridget A. Quinn

Theses and Dissertations

Pancreatic cancer is a devastating disease that leaves patients with a very poor prognosis and few therapeutic options. Many of the treatment options available are the same that have been used for almost 2 decades. There is a dire need for both novel treatments for this disease as well as novel strategies of treatment. This body of work will introduce and provide evidence in support of a novel combination therapy for pancreatic cancer treatment, a novel strategy of modifying currently used chemotherapeutics for pancreatic cancer therapy, and a novel transgenic preclinical mouse model of pancreatic cancer. Sabutoclax, an antagonist of …

Mda-9/Syntenin: From Glioblastoma Pathogenesis To Targeted Therapy, Timothy P. Kegelman

Theses and Dissertations

The most common malignant glioma, glioblastoma multiforme (GBM), remains an intractable tumor despite advances in therapy. Its proclivity to infiltrate surrounding brain tissue contributes greatly to its treatment failure and the grim prognosis of patients. Radiation is a staple in modern therapeutic regimens, though cells surviving radiation become more aggressive and invasive. Consequently, it is imperative to define further the cellular mechanisms that control GBM invasion and identify promising novel therapeutic targets. Melanoma differentiation associated gene-9 (MDA-9/Syntenin) is a highly conserved PDZ domain-containing scaffolding protein that promotes invasion and metastasis in human melanoma models. We show that MDA-9/Syntenin is robustly …

Differential Effects Of Fatigue On Movement Variability, N. Cortes, J. Onate, S. Morrison

Rehabilitation Sciences Faculty Publications

When individuals perform purposeful actions to fatigue, there is typically a general decline in their movement performance. This study was designed to investigate the effects exercise-induced fatigue has on lower limb kinetics and kinematics during a side-step cutting task. In particular, it was of interest to determine what changes could be seen in mean amplitude and all metrics of signal variability with fatigue. The results of the study revealed that post-fatigue there was an overall decrease in absolute force production as reflected by a decline in mean amplitude and variability (SD) of the ground reaction forces (GRF_V and GRF …

The Roles Of Krüppel-Like Factor 1 (Klf1) In The Human Fetal Erythroid Compartment., Safa Mohamad

Theses and Dissertations

Erythroid Krüppel-like factor (EKLF or KLF1) is a transcription factor with roles in embryonic and adult erythropoiesis. KLF1 knockout mouse embryos die due to severe anemia. Dominant human mutations in KLF1 can cause hereditary persistence of fetal hemoglobin. We show that KLF1 positively regulates β-globin and Bcl11A gene expression using KLF1 knockdown in in vitro-differentiated CD34+ human umbilical cord blood cells. -globin expression appears dependent on KLF1; it is increased with modest KLF1 knockdown but not in cells with low KLF1. KLF2 mRNA amounts are usually increased in KLF1 knockdown. KLF1 knockdown in CD34+ cells results in reduced colony forming …

Synthetic, Sulfated, Lignin-Based Anticoagulants, Akul Mehta

Theses and Dissertations

Chemoenzymatically synthesized low molecular weight lignin polymers have been previously found to be potent inhibitors of a number of serine proteases via allosteric mechanisms targeting heparin binding sites. Herein, we describe the creation of synthetic sulfated β-O4 lignin (SbO4L) polymer, which is more homogenous compared to previous lignins with respect to its inter-monomeric linkage. SbO4L is a selective inhibitor of thrombin and plasmin. SbO4L was found to act via a unique mechanism targeting thrombin exosite 2 in a manner similar to platelet glycoprotein Ibα (GPIbα). Advanced hemostasis and thrombosis assays demonstrated that SbO4L acts via a dual mechanism: as an …

The Effect Of Obesity On Il-1Β, Il-1ra, And Leptin Following Acute Mental Stress, Heather Caslin

Theses and Dissertations

Research regarding the development of cardiovascular disease (CVD) is important because CVD is the leading cause of death in the United States (US) and many countries abroad. Risk factors, such as obesity and psychological stress, should be studied in order to understand contributing factors for CVD and the cellular mechanisms which link risk factors with the development of disease. Specifically, the combined influence of multiple risk factors on inflammation is of interest because many individuals have more than one risk factor, which additively increases an individual’s risk for CVD. Obesity is already characterized by disordered inflammation, which suggests that the …

The Relationship Between Select Demographic Characteristics And Body Mass Index Among Native Hawaiian And Other Pacific Islander Caregiving Adults, Jane Lassetter Phd, Rn, Lauren Clark Phd, Rn, Faan, Sharla E. Morgan Fnp, Lora Beth Brown Phd, Gwen Vanservellen Phd, Rn, Faan, Katrina Duncan Fnp, Betsy S. Hopkins

Faculty Publications

Native Hawaiian or other Pacific Islanders (NHOPIs) are people with genetic origins in Hawaii, Samoa, or other Pacific Islands (Hixson, Hepler, & Kim, 2012). NHOPI prevalence of overweight or obesity is among the highest in the world. Nauru, a Pacific Island nation, is considered the most obese country in the world with an overweight and obesity prevalence of 93% (WHO, 2011). Hawaii’s overall prevalence of overweight or obesity is 52.1%, but the prevalence for Native Hawaiian residents is 69.6% (Hawaii Department of Health, 2011). Inasmuch as NHOPIs are one of the fastest growing ethnic groups in the U.S. (Hixson et …

Age-Specific Differences Between Conventional And Ambulatory Daytime Blood Pressure Values, David Conen, Stefanie Aeschbacher, Lutgarde Thijs, Yan Li, José Boggia, Kei Asayama, Tine W. Hansen, Masahiro Kikuya, Kristina Björklund-Bodegård, Takayoshi Ohkubo, Gladys Maestre

School of Medicine Publications

Mean daytime ambulatory blood pressure (BP) values are considered to be lower than conventional BP values, but data on this relation among younger individuals < 50 years are scarce. Conventional and 24-hour ambulatory BP were measured in 9550 individuals not taking antihypertensive treatment from 13 population-based cohorts. We compared individual differences between daytime ambulatory and conventional BP according to 10-year age categories. Age-specific prevalences of white coat and masked hypertension were calculated. Among individuals aged 18 to 30, 30 to 40, and 40 to 50 years, mean daytime BP was significantly higher than the corresponding conventional BP (6.0, 5.2, and 4.7 mm Hg for systolic; 2.5, 2.7, and 1.7 mm Hg for diastolic BP; all P< 0.0001). In individuals aged 60 to 70 and ≥70 years, conventional BP was significantly higher than daytime ambulatory BP (5.0 and 13.0 mm Hg for systolic; 2.0 and 4.2 mm Hg for diastolic BP; all P< 0.0001).The prevalence of white coat hypertension exponentially increased from 2.2% to 19.5% from those aged 18 to 30 years to those aged ≥70 years, with little variation between men and women (8.0% versus 6.1%; P=0.0003). Masked hypertension was more prevalent among men (21.1% versus 11.4%; P< 0.0001). The age-specific prevalences of masked hypertension were 18.2%, 27.3%, 27.8%, 20.1%, 13.6%, and 10.2% among men and 9.0%, 9.9%, 12.2%, 11.9%, 14.7%, and 12.1% among women. In conclusion, this large collaborative analysis showed that the relation between daytime ambulatory and conventional BP strongly varies by age. These findings may have implications for diagnosing hypertension and its subtypes in clinical practice.

Public Health Emergencies: What Counts?, Lawrence O. Gostin

Georgetown Law Faculty Publications and Other Works

Vaccines and drugs to prevent and treat Ebola Virus Disease that have never been tested in humans, and in scarce supply raise profound ethical challenges. What if good evidence emerged demonstrating safety and efficacy of drugs? What would be an ethical method of allocating scarce beneficial resources? The apparent preference given to foreign aid workers over West Africans provoked a firestorm. In addition to discussing the ethical allocation of scarce drugs, this article also asks a more fundamental question: Why did it take nearly 40 years after the first Ebola outbreak in 1976 to launch clinical trials?

Mesure, Contrôle Et Caractérisation Des Nanoparticules : Procédure Appliquée À L’Usinage Et Au Frottement Mécanique, Victor Songmene, Riad Khettabi, Martin Viens, Jules Kouam, Stéphane Hallé, François Morency, Jacques Masounave, Abdelhakim Djebara

Rapports de recherche scientifique

Click here for the English version of this report

Alors que les nanotechnologies émergentes ouvrent des voies prometteuses dans plusieurs secteurs d’activité, des études suggèrent que les nanoparticules (NP) qu’elles génèrent pourraient avoir des effets négatifs, notamment sur la santé et sur l’environnement. Celles-ci peuvent être générées lors de la fabrication, de la manutention et de l’assemblage de pièces métalliques ordinaires et de celles à base de nanomatériaux. D’autres activités quotidiennes, telles que le freinage des automobiles, peuvent aussi produire des NP. Il est donc urgent de trouver des moyens de contrôler ces risques. Cependant, les techniques et méthodes usuelles …

Supporting A Return To Work After An Absence For A Mental Health Problem: Design, Implementation, And Evaluation Of An Integrated Practices Program, Louise St-Arnaud, Catherine Briand, Marc Corbière, Marie-José Durand, Renée Bourbonnais, Micheline Saint-Jean, Mariève Pelletier, Stéphanie Delisle, Evelyn Kedl

Rapports de recherche scientifique

Cliquez ici pour la version française de ce rapport

Les problèmes de santé mentale au travail représentent actuellement l’une des plus importantes causes d’absence au travail, et ce phénomène a connu une croissance marquée au cours des deux dernières décennies. Les travaux entrepris dans le domaine de la réadaptation professionnelle et de la santé mentale au travail ont permis de mettre en évidence l’importance d’une démarche de collaboration entre les acteurs concernés par le processus de retour au travail. Toutefois, si quelques études ont porté précisément sur la réintégration professionnelle de travailleurs déjà insérés en emploi et qui se sont …

Seat Belt Assemblies For Counterbalanced Lift Tructs: Preliminary Study Of Normative And Usability Criteria, Denis Rancourt, Sylvie Beaugrand, Christian Larue, Geneviève Masson

Rapports de recherche scientifique

Cliquez ici pour la version française de ce rapport

Depuis l’entrée en vigueur d’un nouvel article du Règlement québécois sur la santé et la sécurité du travail (RSST), les chariots élévateurs en porte-à-faux à grande levée, à poste de conduite au centre non élevable et à conducteur assis doivent être munis d’un dispositif de retenue empêchant le cariste d’être écrasé par la structure du chariot lors d’un renversement. La ceinture de sécurité pelvienne est un des moyens les plus couramment utilisés actuellement pour satisfaire cette exigence. À partir de la consultation des écrits, de l’examen sommaire de quelques ceintures vendues …

Safety Of Workers Behind Heavy Vehicles: Assessment Of Three Types Of Reverse Alarm, Véronique Vaillancourt, Hugues Nélisse, Chantal Laroche, Christian Giguère, Jérôme Boutin, Pascal Laferrière

Rapports de recherche scientifique

Cliquez ici pour la version française de ce rapport

Une nouvelle technologie d’alarmes de recul de véhicule lourd a fait récemment son apparition sur le marché. Cette technologie, basée sur l’utilisation d’un signal large-bande (bruit de type « pschitt- pschitt ») serait, selon le manufacturier, plus sécuritaire pour les travailleurs tout en causant moins de nuisance environnementale que l’alarme tonale conventionnelle (bruit de type « beep-beep »). Il demeurait toutefois difficile de se prononcer sur la supériorité de cette technologie puisqu’il existe très peu d’études scientifiques indépendantes et rigoureuses portant sur celle-ci.

Cette étude visait à comparer la nouvelle technologie …

Evaluation Of The Implementation And Impact Of The Prévicap Program, Michèle Rivard, Jean-Louis Denis, André-Pierre Contandriopoulos, Michel Rossignol, Henriette Bilodeau, Geneviève Ste-Marie, Valérie Lederer

Rapports de recherche scientifique

Cliquez ici pour la version française de ce rapport

En 2001, l'IRSST a demandé à l'équipe de recherche du Dr Rivard d'évaluer le programme PRÉVICAP (PRÉVention des situations de handICAP au travail) mis en place dans quatre centres de réadaptation du Québec et impliquant onze directions régionales de la CSST. Ce projet pilote lancé en 2000 était le fruit d'une entente entre la CSST, l'IRSST et le Réseau en réadaptation au travail du Québec (RRTQ). Il a permis la prise en charge PRÉVICAP de 571 travailleurs ayant subi une lésion professionnelle entre 2001 et 2004.

Le programme PRÉVICAP est fondé …

Genetic Mechanisms Underlying The Pathogenicity Of Cold-Stressed Salmonella Enterica Serovar Typhimurium In Cultured Intestinal Epithelial Cells, J. Shah, P. T. Desai, B. C. Weimer

Nutrition, Dietetics, and Food Sciences Faculty Publications

Salmonella encounters various stresses in the environment and in the host during infection. The effects of cold (5 C, 48 h), peroxide (5 mM H2O2, 5 h) and acid stress (pH 4.0, 90 min) were tested on pathogenicity of Salmonella. Prior exposure of Salmonella to cold stress significantly (P < 0.05) increased adhesion and invasion of cultured intestinal epithelial (Caco-2) cells. This increased Salmonella-host cell association was also correlated with significant induction of several virulence-associated genes, implying an increased potential of cold-stressed Salmonella to cause an infection. In Caco-2 cells infected with cold-stressed Salmonella, genes involved in the electron transfer chain were significantly induced, but no simultaneous significant increase in expression of antioxidant genes that neutralize the effect of superoxide radicals or reactive oxygen species was observed. Increased production of caspase 9 and caspase 3/7 was confirmed during host cell infection with cold-stressed Salmonella. Further, a prophage gene, STM2699, induced in cold-stressed Salmonella and a spectrin gene, SPTAN1, induced in Salmonella-infected intestinal epithelial cells were found to have a significant contribution in increased adhesion and invasion of cold-stressed Salmonella in epithelial cells.