Diseases Commons^™

Mechanisms Of Trinucleotide Repeat Instability During Dna Synthesis, Kara Y. Chan

Theses and Dissertations--Toxicology and Cancer Biology

Genomic instability, in the form of gene mutations, insertions/deletions, and gene amplifications, is one of the hallmarks in many types of cancers and other inheritable genetic disorders. Trinucleotide repeat (TNR) disorders, such as Huntington’s disease (HD) and Myotonic dystrophy (DM) can be inherited and repeats may be extended through subsequent generations. However, it is not clear how the CAG repeats expand through generations in HD. Two possible repeat expansion mechanisms include: 1) polymerase mediated repeat extension; 2) persistent TNR hairpin structure formation persisting in the genome resulting in expansion after subsequent cell division. Recent in vitro studies suggested that a …

How Do Teachers Use Comics To Promote Engagement, Equity, And Diversity In Science Classrooms?, Camilla Matuk, Talia Hurwich, Amy Spiegel, Judy Diamond

World of Viruses

Equitable learning opportunities are critical to the goals of science education. However, major curriculum standards are vague on how to achieve equity goals, and educators must often develop their own resources and strategies to achieve equity goals. This study examines how educators used a comic book series designed to interest youth in virology as a way to make science more broadly appealing to their diverse students. We begin with the notion of Pedagogical Design Capacity, which describes a dynamic relationship between teachers and their tools and the ability for teachers to perceive and leverage affordances of artifacts as tools in …

The Effects Of In Utero Levothyroxine Exposure On Anterior-Posterior Craniofacial Development In A Mouse Model, Ashley Rogers Albrecht

MUSC Theses and Dissertations

Introduction: The purpose of this study was to investigate the effects of in utero levothyroxine exposure on anterior-posterior craniofacial development in a mouse model. Methods: In order to determine the effects of in utero levothyroxine exposure on anterior-posterior craniofacial development, a study group (n=19) of C57BL6 mice were exposed to high dose (~667ng per day) levothyroxine during fetal development. Mice were sacrificed day 15 post-natal. Skulls were fixed in a solution of 4% paraformaldehyde, then switched to 70% ethanol in preparation for microCT imaging. Scans were loaded into Dolphin Imaging Software and lateral cephalograms were rendered and analyzed. Results: According …

Concerns Of Female Adolescents About Menarche And First Sexual Intercourse: Mixed Methods Analysis Of Social Media Questions, Nikkie Saldivar Hodgson, Elad Yom-Tov, William F. Strong, Priscilla L. Flores, Giselle N. Ricoy

Communication Faculty Publications

Background: Adolescents use social media for information on medical and social aspects of maturation.

Objective: The aim of this study was to investigate the concerns and information needs of adolescents regarding menarche and first sexual intercourse.

Methods: Questions about menarche or first sexual intercourse were obtained from Yahoo Answers, a community-based social media question-and-answer website. A total of 1226 questions were analyzed. We focused on 123 question pairs made by users who asked questions on both topics and reported their ages at each. Quantitative and qualitative analyses were performed on these question pairs.

Results: Qualitative analysis identified uncertainty as a …

Special Collection On Electroporation-Based Therapies: A Selection Of Papers From The Second World Congress On Electroporation, Richard Heller, Rafael V. Davalos

Bioelectrics Publications

No abstract provided.

Comparative Assessment Of Methicillin Resistant Staphylococcus Aureus Diagnostic Assays For Use In Resource-Limited Settings, A. Ayebare, Lisa M. Bebell, Joel Bazira, S. Ttendo, V. Katawera, David Bangsberg, Mark J. Siedner, Multiple Additional Authors

OHSU-PSU School of Public Health Faculty Publications and Presentations

Background: The rise of methicillin-resistant Staphylococcus aureus(MRSA) is a global health concern. Paucity of data on MRSA carriage prevalence and diagnostic methods in resource-limited settings hampers efforts to define the problem and plan an appropriate response. Additionally, high variability in cost and logistical characteristics of MRSA screening methods may impede infection control efforts. We compared the performance of locally-available chromogenic agar BD CHROMagar MRSA II and two PCR-based assays (Hain GenoQuick MRSA and Cepheid Xpert SA Complete) for the detection of asymptomatic MRSA carriage in nasal swabs.

Results: During 2015, we enrolled 500 patients from five hospital …

Improving Access To Clean Water In Rural Ecuador: The Connection Between Willingness To Pay And Population Health, Micalea Leaska

Capstone Collection

Climate change is affecting social and environmental determinants of health through access to safe drinking water, safely managed sanitation systems, and access to health care services and the ability for individuals to break free from unsuitable circumstances. Ecological disturbances such as those caused by climate change can cause a shift in host vectors or a change in habitat that results in a greater likelihood of the pathogen coming in contact with humans. Water, sanitation, and hygiene (WASH) services and their accessibility to populations can directly impact a community’s vulnerability to diseases and limiting factors to increase economic growth. If rural …

Impact Of Contemporary Low Dose Aspirin Use And Cardiovascular Disease, Pratik Sharma, Ramona Stone

Public Health Sciences Student Work

No abstract provided.

Investigating The Role Of Neuronal Aging In Fragile X-Associated Tremor/Ataxia Syndrome, Katlin Marie Hencak

Honors Undergraduate Theses

Fragile X-associated tremor/ataxia syndrome (FXTAS) is an X-linked late-onset neurodegenerative disorder caused by a noncoding trinucleotide repeat expansion in the FMR1 gene. This gene produces fragile x mental retardation protein (FMRP), an RNA binding protein whose targets are involved in brain development and synaptic plasticity. One of the proposed mechanisms of FXTAS pathogenesis is an RNA gain-of-function in which the repeat expansion causes toxic mRNA that sequesters important proteins in the cell, interfering with their functions. Another suggested method of pathogenesis is through a mutant protein called FMRpolyG. This protein results from repeat-associated non-AUG (RAN) translation, in which the expanded …

Elucidating The Role Of Oxygen And Biotype In The Environmental Persistence Of Vibrio Cholerae, Amy M. Freiberg

Honors Undergraduate Theses

Vibrio cholerae is a natural inhabitant of aquatic environments and serves as the etiological agent for the severe diarrheal disease, cholera. Cholera epidemics follow a regular seasonal pattern, which account for tens to hundreds of thousands of deaths in a given year. V. choleraenaturally persist between epidemics through entry into a dormant state known as viable but nonculturable (VBNC). Research has shown that V. choleraein this VBNC state experience drastic morphological and metabolic changes, which serve as survival mechanisms until environmental conditions become suitable again. The natural marine ecosystem that V. cholerae inhabitis comprised of a complex …

Strategies To Increase Human Immunodeficiency Virus Testing In Rural Areas Of The United States: A Systematic Review, Avery Petrucci, Kristen Custer, Eric C. Nemec

Physician Assistant Studies Student Publications

Purpose: HIV incidence continues to increase, with a large portion of new diagnoses found in rural areas of the United States. The worsening statistics in rural areas may be attributed to stigma alone and contribute to the lack of testing available for patients. The objective of this systematic review is to identify accessible and feasible strategies to increase HIV testing within the rural communities in the United States. Methods: A systematic literature search of CINAHL Complete, MEDLINE with Full Text, and PsycINFO with restrictions of the English language and rural communities outside of the United States through August 2, 2018. …

Autologous Peripheral Nerve Grafts To The Brain For The Treatment Of Parkinson's Disease, Andrew Welleford

Theses and Dissertations--Neuroscience

Parkinson’s disease (PD) is a disorder of the nervous system that causes problems with movement (motor symptoms) as well as other problems such as mood disorders, cognitive changes, sleep disorders, constipation, pain, and other non-motor symptoms. The severity of PD symptoms worsens over time as the disease progresses, and while there are treatments for the motor and some non-motor symptoms there is no known cure for PD. Thus there is a high demand for therapies to slow the progressive neurodegeneration observed in PD. Two clinical trials at the University of Kentucky College of Medicine (NCT02369003, NCT01833364) are currently underway that …

Neurochemical Factors Associated With The Initial Pathophysiological Reaction To Large Vessel Occlusion Stroke, Sarah R. Martha

Theses and Dissertations--Nursing

Ischemic stroke is the leading cause of disability world-wide and affects over 800,000 people per year in the United States. The majority of these strokes are ischemic due to a blockage of blood flow to the brain. Damage to the brain occurs at the onset of stroke, neuronal cell death is irreversible and therefore, quick treatment to remove blockage is critical factor in the recovery from stroke. Mechanical thrombectomy as a treatment for ischemic stroke provides an ideal opportunity to collect blood distal and proximal to the cerebral thrombus to examine neurochemical changes occurring during stroke.

The purpose of this …

End-Of-Life Decision-Making In Patients With A Cardiac Device, Jessica Harman Thompson

Theses and Dissertations--Nursing

Heart failure (HF) is one of the top causes of mortality in the United States and globally. In order to combat the high mortality rates of this disease, medical technology, including internal cardioverter defibrillators (ICD) and left ventricular assist devices (LVAD), have become one of the most common treatments. Over the past 10 years the utilization of these cardiac devices has increased exponentially, which has created a new phenomenon of how we discuss death with patients who have one of these devices. The purpose of this dissertation is to increase understanding of the end-of-life decision making processes and current experiences …

Understanding The Contributions Of Alzheimer’S Disease & Cardiovascular Risks To Cerebral Small Vessel Disease Manifest As White Matter Hyperintensities On Magnetic Resonance Imaging (Mri), Omar M. Al-Janabi

Theses and Dissertations--Clinical and Translational Science

Introduction: Alzheimer’s Diseases (AD) & cerebral small vessel disease associated with cardiovascular risk factors (cSVD) frequently coexist, differentially affecting both imaging and clinical features associated with aging and dementia. We hypothesized that Magnetic Resonance Imaging (MRI) can be used in novel ways to identify relative contributions of AD & cardiovascular risks to cSVD and brain atrophy, generating new biomarkers & insights into mixed disease states associated with cognitive decline and dementia.

Methods: Three experiments were conducted to address the overarching hypothesis. First, we visually rated the clinical MRI of 325 participants from a community-based cross-sectional sample to elucidate the relative …

Changes In Muscle Size, Quality And Power Are Related To Physical Function In Patients With Critical Illness, Kirby Mayer

Theses and Dissertations--Rehabilitation Sciences

Patients admitted to intensive care unit (ICU) are known to develop significant impairments in physical function. Patients with critical illness suffer up to 30% reductions in muscle size within the first ten days of admission to the ICU. Muscle strength testing, Medical Research Council-sum score, is current gold-standard to diagnosis ICU-acquired weakness and predicts risk of mortality and long-term physical function. Muscle power different from muscle strength in that it accounts for velocity of movement, is potentially a better independent predictor of function that has not been studied in this population. In addition, we hypothesize that muscle size and quality …

Pyocyanin, A Virulence Factor Produced By Sepsis-Causing Pseudomonas Aeruginosa, Promotes Adipose Wasting And Cachexia, Nika Larian

Theses and Dissertations--Pharmacology and Nutritional Sciences

Sepsis is a leading cause of death among critically ill patients that results in metabolic alterations including hypercatabolism, lipoatrophy, and muscle wasting, contributing to the development of cachexia. Septic cachexia is associated with loss of body weight, fat mass, and lean mass and dysregulated immune function. There are currently no efficacious treatment strategies for septic cachexia, and nutritional interventions have limited success in preventing hypercatabolic wasting. Pyocyanin is a virulence factor produced by sepsis-causing Pseudomonas aeruginosa that has been shown to activate the aryl hydrocarbon receptor (AhR), increase inflammation, and produce reactive oxygen species. Thus, pyocyanin represents a novel mechanistic …

Effects Of Pituitary Pars Intermedia Dysfunction And Prascend® Treatment On Endocrine And Immune Function In Senior Horses, Ashton B. Miller

Theses and Dissertations--Veterinary Science

Pituitary pars intermedia dysfunction (PPID) is one of the most common endocrine diseases affecting senior horses. PPID causes abnormally high concentrations of adrenocorticotropic hormone (ACTH) in the plasma and a very distinct, long, shaggy haircoat (hypertrichosis). At present, the recommended treatment for PPID is daily oral administration of pergolide mesylate. Due to the increased ACTH levels associated with PPID, it is commonly thought that these horses are immunosuppressed and at increased risk of opportunistic infections, although current research in this area is sparse. Additionally, it is not well-understood how treatment with Prascend^® (pergolide tablets) affects endocrine measures other than …

Adaptation Of The Streptococcal Collagen-Like Protein 1, Scl1, Of Group A Streptococcus To Recognize Fibronectin Type Iii Repeats, Dudley H. Mcnitt

Graduate Theses, Dissertations, and Problem Reports (ETD)

Background: Group A Streptococcus (GAS) is responsible more than 700 million infections worldwide each year. Most of these infections start with initial colonization of the throat and skin, which is augmented by surface adhesins. The streptococcal collagen-like protein 1 (Scl1) is a major adhesin expressed by GAS that contains an N-terminal sequence-variable (V) domain, protruded away from the cell surface by the collagen domain. The Scl-V domain is comprised of three pairs of anti-parallel α-helices interconnected by surface-exposed loops. For attachment, GAS adhesins require a portal of entry, such as a wound or breach in the epithelium, to enter …

Regulation Of The Long Non-Coding Rna Fam83h-As1 By Human Papillomavirus In Cervical Cancer, Jamie Ann Barr Ph.D.

Graduate Theses, Dissertations, and Problem Reports (ETD)

Non-coding RNAs (NcRNAs), such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been found to be involved in a variety of critical biological processes, and dysregulation of ncRNAs have been involved with several human diseases including cancer.

High-risk human papillomavirus (HPV) infection is one of the first events in the process of carcinogenesis in cervical and a subset of head and neck cancers. The expression of the viral oncoproteins E6 and E7 is essential in this process by inactivating the tumor suppressor proteins p53 and Rb, respectively, in addition to their interactions with other host proteins and regulation of …

Heterogeneity Of Disease-Causing Variants In The Swedish Galactosemia Population: Identification Of 16 Novel Galt Variants, Annika Ohlsson, Mary Hunt, Anna Wedell, Ulrika Von Döbeln

Articles

The aim was to determine disease-causing variants in the GALT gene which codes for the enzyme galactose-1-phosphate uridylyltransferase. Loss of activity of this enzyme causes classical galactosemia-a life threatening, treatable disorder, included in the Swedish newborn screening program since 1967. A total of 66 patients with the disease are known in Sweden and 56 index patients were investigated. An additional two patients with Duarte galactosemia were included. The disease-causing variants were identified in all patients. As reported from other countries only a few variants frequently recur in severe disease. The two variants p.(Gln188Arg) (c.563A>G) and p.(Met142Lys) (c.425T>A) are …

Effect Of Neoadjuvant Chemoradiation On Preoperative Pulmonary Physiology, Postoperative Respiratory Complications And Quality Of Life In Patients With Oesophageal Cancer, J. A. Elliott, L. O'Byrne, G. Foley, C. F. Murphy, Suzanne Doyle, S. King, E. M. Guinan, N. Ravi, V. Reynolds

Articles

Background: It remains controversial whether neoadjuvant chemoradiation (nCRT) for oesophageal cancer influences operative morbidity, in particular pulmonary, and quality of life. This study combined clinical outcome data with systematic evaluation of pulmonary physiology to determine the impact of nCRT on pulmonary physiology and clinical outcomes in locally advanced oesophageal cancer.

Methods: Consecutive patients treated between 2010 and 2016 were included. Three-dimensional conformal radiation was standard, with a lung dose–volume histogram of V20 less than 25 per cent, and total radiation between 40 and 41⋅4Gy. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and diffusion capacity …

Feasibility Of A Point-Of-Care Test Based On Quantum Dots With A Mobile Phone Reader For Detection Of Antibody Responses, Chan Lee, John Noh, Seth E. O’Neal, Armando E. Gonzalez, Hector H. Garcia, Multiple Additional Authors

OHSU-PSU School of Public Health Faculty Publications and Presentations

We developed a novel and portable fluorescent sensor that integrates a lateral flow assay with a quantum dot (Qdots) label and a mobile phone reader for detection of specific antibodies in human serum. We evaluated the utility of this assay to test for antibodies to the Taenia solium rT24H antigen. It was a retrospective study by examining 112 positive human sera from patients with neurocysticercosis (NCC) including samples from patients with single viable cyst (n = 18), two or more viable cysts (n = 71), and subarachnoid (racemose) cysts (n = 23). These samples were collected from previous study subjects …

Hematologic Safety Of Chronic Brain-Penetrating Erythropoietin Dosing In App/Ps1 Mice, Jiahong Sun, Joshua Yang, Kathrine Whitman, Charlene Zhu, David H. Cribbs, Ruben J. Boado, William M. Pardridge, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Introduction: Low blood-brain barrier (BBB) penetration and hematopoietic side effects limit the therapeutic development of erythropoietin (EPO) for Alzheimer's disease (AD). A fusion protein of EPO and a chimeric monoclonal antibody targeting the mouse transferrin receptor (cTfRMAb) has been engineered. The latter drives EPO into the brain via receptor-mediated transcytosis across the BBB and increases its peripheral clearance to reduce hematopoietic side effects of EPO. Our previous work shows the protective effects of this BBB-penetrating EPO in AD mice but hematologic effects have not been studied. Herein, we investigate the hematologic safety and therapeutic effects of chronic cTfRMAb-EPO dosing, …

Synthesis And Biological Evaluation Of 2,4-Diaminopyrimidine-5-Carbonitrile And N-(2-Amino-5-Cyanopyrimidin-4-Yl)Benzamide Derivatives As Egfr Inhibitors, Pathan Sultan Ismail, Irfan Khan, Vivek Kumar Kashyap, Ved Prakash Verma, Monika Shukla, Anupam Dhasmana, Shashi Pandey, Girdhar Pal Singh, Shahnawaz Khan, Jaybir Singh

School of Medicine Publications

A series of 2,4-diaminopyrimidine-5-carbonitrile and N-(2-amino-5-cyanopyrimidin-4-yl) benzamide derivatives (5–14) were synthesized and their chemical structures were confirmed by 1 H, 13C NMR and mass spectral data. Anticancer activity of all the synthesized compounds were evaluated for in vitro cytotoxic activity against a panel of four human cancer cell lines i.e., human breast (MCF-7,), cervical cancer (C33A), oral (KB) and prostrate (DU-145). All the examined compounds, demonstrated potent to moderate anticancer activity. Among all the synthesized compounds, 6 and 11 were exhibited more potent activity. Docking studies for 6 and 11 into EGFR active site was carried out to investigate their …

Art Adherence And Viral Suppression Are High Among Most Non-Pregnant Individuals With Early-Stage, Asymptomatic Hiv Infection: An Observational Study From Uganda And South Africa, Jessica E. Haberer, Bosco M. Bwana, Catherine Orrell, Stephen Asiimwe, Gideon Amanyire, Nicholas Musinguzi, Mark J. Siedner, Lynn T. Matthews, Alexander Tsai, Ingrid T. Katz, Kathleen Bell, Annet Kembabazi, Stephen Mugisha, Victoria Kibirige, Anna Cross, Nicola Kelly, Bethany Hedt-Gauthie, David R. Bangsberg

OHSU-PSU School of Public Health Faculty Publications and Presentations

Introduction

The success of universal antiretroviral therapy (ART) access and aspirations for an AIDS‐free generation depend on high adherence in individuals initiating ART during early‐stage HIV infection; however, adherence may be difficult in the absence of illness and associated support.

Methods

From March 2015 to October 2017, we prospectively observed three groups initiating ART in routine care in Uganda and South Africa: men and non‐pregnant women with early‐stage HIV infection (CD4 > 350 cells/μL), pregnant women with early‐stage HIV infection and men and non‐pregnant women with late‐stage HIV infection (CD4 < 200 cells/μL). Socio‐behavioural questionnaires were administered and viral loads were performed at 0, 6 and 12 months. Adherence was monitored electronically.

Results

Adherence data were available for 869 participants: 322 (37%) early/non‐pregnant, …

Case–Control Research Study Of Auto-Brewery Syndrome, Barbara Jean Cordell, Anup Kanodia, Gregory K. Miller

Faculty Publications

Background: Auto-brewery syndrome (ABS), also known as Gut Fermentation Syndrome and Endogenous Ethanol Fermentation, is afflicting people worldwide, but little is known about ABS patients’ demographics, health history, lifestyle factors, and diet.

Method: We conducted a broad-based case–control survey study on 52 patients known to have a diagnosis of ABS and their household members. The research compares the symptomatic group (N ¼ 28) to the asymptomatic group (N ¼ 18) regarding lifestyle and health, diet, and medical history.

Results: With a response rate of 88% and using rank-sum tests, the data demonstrate that patients with ABS have …

Multistate Survey Of American Dog Ticks (Dermacentor Variabilis) For Rickettsia Species, Joy A. Hecht, Michelle E.J. Allerdice, Elizabeth A. Dykstra, Laura Mastel, Rebecca J. Eisen, Tammi L. Johnson, Holly D. Gaff, Andrea S. Varela-Stokes, Jerome Goddard, Benedict B. Pagac, Christopher D. Paddock, Sandor E. Karpathy

Biological Sciences Faculty Publications

Dermacentor variabilis, a common human-biting tick found throughout the eastern half and along the west coast of the United States, is a vector of multiple bacterial pathogens. Historically, D. variabilis has been considered a primary vector of Rickettsia rickettsii, the causative agent of Rocky Mountain spotted fever. A total of 883 adult D. variabilis, collected between 2012 and 2017 from various locations in 12 states across the United States, were screened for rickettsial DNA. Tick extracts were evaluated using three real-time PCR assays; an R. rickettsii-specific assay, a Rickettsia bellii-specific assay, and a Rickettsia genus-specific …

Host Factors Against Plant Viruses, Hernan García-Ruiz

Department of Plant Pathology: Faculty Publications

Plant virus genome replication and movement is dependent on host resources and factors. However, plants respond to virus infection through several mechanisms, such as autophagy, ubiquitination, mRNA decay and gene silencing, that target viral components. Viral factors work in synchrony with pro-viral host factors during the infection cycle and are targeted by antiviral responses. Accordingly, establishment of virus infection is genetically determined by the availability of the pro-viral factors necessary for genome replication and movement, and by the balance between plant defence and viral suppression of defence responses. Sequential requirement of pro-viral factors and the antagonistic activity of antiviral factors …

Effects Of The Dual Orexin Receptor Antagonist Dora-22 On Sleep In 5xfad Mice, Marilyn J. Duncan, Hannah Farlow, Chairtra Tirumalaraju, Do-Hyun Yun, Chanung Wang, James A. Howard, Madison N. Sanden, Bruce F. O'Hara, Kristen J. Mcquerry, Adam D. Bachstetter

Neuroscience Faculty Publications

Introduction: Sleep disruption is a characteristic of Alzheimer's disease (AD) that may exacerbate disease progression. This study tested whether a dual orexin receptor antagonist (DORA) would enhance sleep and attenuate neuropathology, neuroinflammation, and cognitive deficits in an AD-relevant mouse model, 5XFAD.

Methods: Wild-type (C57Bl6/SJL) and 5XFAD mice received chronic treatment with vehicle or DORA-22. Piezoelectric recordings monitored sleep and spatial memory was assessed via spontaneous Y-maze alternations. Aβ plaques, Aβ levels, and neuroinflammatory markers were measured by immunohistochemistry, enzyme-linked immunosorbent assay, and real-time polymerase chain reaction, respectively.

Results: In 5XFAD mice, DORA-22 significantly increased light-phase sleep without reducing Aβ levels, …