Digital Commons Network^™

Moving Toward A Potential Treatment: Isis, Chdi Researchers Outline Upcoming Huntington's Disease Gene-Silencing Trials, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Enhancing Immunomodulation On Innate Immunity By Shape Transition Among Rna Triangle, Square And Pentagon Nanovehicles, Emil F. Khisamutdinov, Hui Li, Daniel L. Jasinski, Jiao Chen, Jian Fu, Peixuan Guo

Center for Research on Environmental Disease Faculty Publications

Modulation of immune response is important in cancer immunotherapy, vaccine adjuvant development and inflammatory or immune disease therapy. Here we report the development of new immunomodulators via control of shape transition among RNA triangle, square and pentagon. Changing one RNA strand in polygons automatically induced the stretching of the interior angle from 60° to 90° or 108°, resulting in self-assembly of elegant RNA triangles, squares and pentagons. When immunological adjuvants were incorporated, their immunomodulation effect for cytokine TNF-α and IL-6 induction was greatly enhanced in vitro and in animals up to 100-fold, while RNA polygon controls induced unnoticeable effect. The …

Nack Is An Integral Component Of The Notch Transcriptional Activation Complex And Is Critical For Development And Tumorigenesis, Kelly L Weaver, Marie-Clotilde Alves-Guerra, Ke Jin, Zhiqiang Wang, Xiaoqing Han, Prathibha Ranganathan, Xiaoxia Zhu, Thiago Dasilva, Wei Liu, Francesca Ratti, Renee M Demarest, Cristos Tzimas, Meghan Rice, Rodrigo Vasquez-Del Carpio, Nadia Dahmane, David J Robbins, Anthony J Capobianco

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The Notch signaling pathway governs many distinct cellular processes by regulating transcriptional programs. The transcriptional response initiated by Notch is highly cell context dependent, indicating that multiple factors influence Notch target gene selection and activity. However, the mechanism by which Notch drives target gene transcription is not well understood. Herein, we identify and characterize a novel Notch-interacting protein, Notch activation complex kinase (NACK), which acts as a Notch transcriptional coactivator. We show that NACK associates with the Notch transcriptional activation complex on DNA, mediates Notch transcriptional activity, and is required for Notch-mediated tumorigenesis. We demonstrate that Notch1 and NACK are …

Factors Associated With Neurodevelopment For Children With Single Ventricle Lesions., Caren S. Goldberg, Minmin Lu, Lynn A. Sleeper, William T. Mahle, J William Gaynor, Ismee A. Williams, Kathleen A. Mussatto, Richard G. Ohye, Eric M. Graham, Deborah U. Frank, Jeffrey P. Jacobs, Catherine Krawczeski, Linda Lambert, Alan Lewis, Victoria L. Pemberton, Renee Sananes, Erica Sood, Stephanie B. Wechsler, David C. Bellinger, Jane W. Newburger, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To measure neurodevelopment at 3 years of age in children with single right-ventricle anomalies and to assess its relationship to Norwood shunt type, neurodevelopment at 14 months of age, and patient and medical factors.

STUDY DESIGN: All subjects in the Single Ventricle Reconstruction Trial who were alive without cardiac transplant were eligible for inclusion. The Ages and Stages Questionnaire (ASQ, n = 203) and other measures of behavior and quality of life were completed at age 3 years. Medical history, including measures of growth, feeding, and complications, was assessed through annual review of the records and phone interviews. The …

Delayed Switch Of Antiretroviral Therapy After Virologic Failure Associated With Elevated Mortality Among Hiv-Infected Adults In Africa, Maya L. Petersen, Linh Tran, Elvin H. Geng, Steven J. Reynolds, Andrew Kambugu, Robin Wood, David Bangsberg, Constantin T. Yiannoutsos, Steven G. Deeks, Jeffrey N. Martin

OHSU-PSU School of Public Health Faculty Publications and Presentations

Objective—Routine monitoring of plasma HIV RNA among HIV-infected patients on antiretroviral therapy (ART) is unavailable in many resource-limited settings. Alternative monitoring approaches correlate poorly with virologic failure and can substantially delay switch to second-line therapy. We evaluated the impact of delayed switch on mortality among patients with virologic failure in Africa.

Design—A cohort.

Methods—We examined patients with confirmed virologic failure on first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens from four cohorts with serial HIV RNA monitoring in Uganda and South Africa. Marginal structural models aimed to estimate the effect of delayed switch on mortality in a hypothetical trial in which …

Persistent Hiv-Related Stigma In Rural Uganda During A Period Of Increasing Hiv Incidence Despite Treatment Expansion, Brian T. Chan, Sheri D. Weiser, Yap Boum Ii, Mark J. Siedner, Rain Mocello, Jessica E. Haberer, Peter Hunt, Jeffrey N. Martin, Kenneth H. Mayer, David Bangsberg, Alexander C. Tsai

OHSU-PSU School of Public Health Faculty Publications and Presentations

Objective—Program implementers have argued that the increasing availability of anti-retroviral therapy (ART) will reduce the stigma of HIV. We analyzed data from Uganda to assess how HIV-related stigma has changed during a period of ART expansion.

Design—Serial cross-sectional surveys.

Methods—We analyzed data from the Uganda AIDS Rural Treatment Outcomes (UARTO) study during 2007-2012 to estimate trends in internalized stigma among people living with HIV (PLHIV) at the time of treatment initiation. We analyzed data from the Uganda Demographic and Health Surveys (DHS) from 2006 and 2011 to estimate trends in stigmatizing attitudes and anticipated stigma in the general population. We …

Inflammation And C-Reactive Protein In Atrial Fibrillation: Cause Or Effect?, Roberto Galea, Maria Teresa Cardillo, Annalisa Caroli, Maria Giulia Marini, Chiara Sonnino, Maria L Narducci, Luigi M Biasucci

The Texas Heart Institute Journal

Atrial fibrillation is associated with substantial morbidity and mortality rates. The incompletely understood pathogenesis of this cardiac dysrhythmia makes it difficult to improve approaches to primary and secondary prevention. Evidence has accumulated in regard to a relationship between inflammation and atrial fibrillation. Investigators have correlated the dysrhythmia with myocarditis, pericardiotomy, and C-reactive protein levels, suggesting that inflammation causes atrial fibrillation or participates in its onset and continuation. Conversely, other investigators suggest that atrial fibrillation induces an inflammatory response. In this review, we summarize and critically discuss the nature and clinical role of inflammation and C-reactive protein in atrial fibrillation.

High Medication Adherence During Periconception Periods Among Hiv-1–Uninfected Women Participating In A Clinical Trial Of Antiretroviral Pre-Exposure Prophylaxis, Lynn T. Matthews, Renee Heffron, Nelly R. Mugo, Craig R. Cohen, Craig W. Hendrix, Connie Celum, David Bangsberg, Jared M. Baten

OHSU-PSU School of Public Health Faculty Publications and Presentations

Introduction: Pre-exposure prophylaxis (PrEP) may be an important safer conception strategy for HIV-1–uninfected women with HIV-1–infected partners. Understanding medication adherence in this population may inform whether PrEP is a feasible safer conception strategy.

Methods: We evaluated predictors of pregnancy and adherence to study medication among HIV-1–uninfected women enrolled in a randomized placebo-controlled trial of PrEP among African HIV-1– serodiscordant couples. Participants were counseled on HIV-1 risk reduction, contraception, and adherence and tested for pregnancy at monthly study visits. Pill counts of dispensed drug were performed and, at a subset of visits, plasma was collected to measure active drug concentration.

Results: …

A Rhetorical Analysis Of The Rethinking Aids Website, Jennifer Dettmann

Journal of Undergraduate Research at Minnesota State University, Mankato

A group of scientists known as the Group for Scientific Reappraisal of the HIV-AIDS hypothesis created a web site title, Rethinking AIDS. The group behind the web site argues that AIDS is not a sexually transmitted disease. They even question the existence of the virus entity. My analysis is driven by the critical question: Does the web site construct a reality that affectively alters our perception of HIV-AIDS? In order to answer this question, Goodnight and Poulakos 1981 article, Conspiracy rhetoric: from pragmatism to fantasy to public discourse (Western Journal of Speech), will be utilized.

Histological Evaluation Of The Cryo-Destruction Of The Zona Glomerulosa (Outermost Layer) Of The Adrenal Cortex, Huda Ahmed, Jonida Pone

Journal of Undergraduate Research at Minnesota State University, Mankato

The outer portion, or cortex, of the adrenal gland produces three hormones, two of which are highly critical to normal function of the body. The cortex itself is divided into three layers, each responsible for a certain hormone synthesis. The outermost layer (zona glomerulosa) produces aldosterone, a hormone involved in the regulation of body sodium, blood volume, and blood pressure. The middle layer produces co rticosterone, a hormone that is active in a variety of biological functions, and necessary for life. Due to its effects on blood volume, aldosterone has been implicated in the development of hypertension, or high blood …

Disrupted Human–Pathogen Co-Evolution: A Model For Disease, Nuri Kodaman, Rafal S. Sobota, Robertino Mera, Barbara G. Schneider, Scott M. Williams

Dartmouth Scholarship

A major goal in infectious disease research is to identify the human and pathogenic genetic variants that explain differences in microbial pathogenesis. However, neither pathogenic strain nor human genetic variation in isolation has proven adequate to explain the heterogeneity of disease pathology. We suggest that disrupted co-evolution between a pathogen and its human host can explain variation in disease outcomes, and that genome-by-genome interactions should therefore be incorporated into genetic models of disease caused by infectious agents. Genetic epidemiological studies that fail to take both the pathogen and host into account can lead to false and misleading conclusions about disease …

News Flash: Isis And Roche Hope To Start Huntington's Gene-Silencing Trials In First Half Of 2015, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Sma-Causing Missense Mutations In Survival Motor Neuron (Smn) Display A Wide Range Of Phenotypes When Modeled In Drosophila, Kavita Praveen, Ying Wen, Kelsey M. Gray, John J. Noto, Akash R. Patlolla, Gregory D. Van Duyne, A. Gregory Matera

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Mutations in the human survival motor neuron 1 (SMN) gene are the primary cause of spinal muscular atrophy (SMA), a devastating neuromuscular disorder. SMN protein has a well-characterized role in the biogenesis of small nuclear ribonucleoproteins (snRNPs), core components of the spliceosome. Additional tissue-specific and global functions have been ascribed to SMN; however, their relevance to SMA pathology is poorly understood and controversial. Using Drosophila as a model system, we created an allelic series of twelve Smn missense mutations, originally identified in human SMA patients. We show that animals expressing these SMA-causing mutations display a broad range of …

Infection With Mers-Cov Causes Lethal Pneumonia In The Common Marmoset, Darryl Falzarano, Emmie De Wit, Friederike Feldmann, Angela L. Rasmussen, Atsushi Okumura, Xinxia Peng, Matthew J. Thomas, Neeltje Van Doremalen, Elaine Haddock, Lee Nagy, Rachel Lacasse, Tingting Liu, Jiang Zhu, Jason S. Mclellan, Dana P. Scott, Michael G. Katze, Heinz Feldmann, Vincent J. Munster

Dartmouth Scholarship

The availability of a robust disease model is essential for the development of countermeasures for Middle East respiratory syndrome coronavirus (MERS-CoV). While a rhesus macaque model of MERS-CoV has been established, the lack of uniform, severe disease in this model complicates the analysis of countermeasure studies. Modeling of the interaction between the MERS-CoV spike glycoprotein and its receptor dipeptidyl peptidase 4 predicted comparable interaction energies in common marmosets and humans. The suitability of the marmoset as a MERS-CoV model was tested by inoculation via combined intratracheal, intranasal, oral and ocular routes. Most of the marmosets developed a progressive severe pneumonia …

Bidding Farewell To Coq10: A Long-Studied Supplement Proves Ineffective In The Fight Against Huntington's Disease, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Effect Of Sweeteners On The Renin-Angiotensin System In Rats, Jacob Ball

Journal of Undergraduate Research at Minnesota State University, Mankato

Normal abundant dietary sugars such as fructose and sucrose can contribute to hypertension and other health issues. To avoid these health complications, many individuals use artificial sweeteners. An equivalent intake of some artificial sweeteners also can lead to hypertension. However, Stevia, a sweetener that is isolated from a Paraguayan plant, was shown in relevant literature to decrease blood pressure in both rat specimens and humans. The general purpose of this research project was to study the effect of Stevia, saccharin, and sucrose on the expression of two key components of the renin-angiotensin- aldosterone system (RAAS): prorenin receptor (PRR) and angiotensin …

An Uncommon Presentation For Cardiac Melanoma, Burcu Gul, Michael N. Young, David A. Slosky, Mark A. Lawson, Jeffrey N. Rottman

Journal of Patient-Centered Research and Reviews

A 66-year-old man with locally advanced malignant melanoma, which was surgically resected, presented with a 3-week history of dizziness, recurrent near-syncopal episodes and generalized weakness. He was found to have sustained polymorphic ventricular tachycardia in the setting of cardiac melanoma. We draw attention to an unusual presentation of malignant melanoma with cardiac metastasis and discuss both its etiology and treatment options.

Cardio-Oncology: Success Breeds New Challenges, Opportunities, Charles A. Bomzer, Bijoy K. Khandheria

Journal of Patient-Centered Research and Reviews

N/A

Clinical Outcomes Of Unprotected Left Main Coronary Artery Stenting In Nonsurgical Patients: A Single-Center Experience, John-Paul Pham, Abdelazim Hashim, Naoyo Mori, Mohamed Taha, Mohamed Djelmami-Hani, Joaquin Solis, Suhail Allaqaband, Tanvir Bajwa, Anjan Gupta

Journal of Patient-Centered Research and Reviews

Purpose: Coronary artery bypass graft is the standard treatment for unprotected left main disease; however, some patients are poor surgical candidates due to comorbidities. We assessed the safety and clinical outcome of elective, unprotected left main coronary artery stenting in nonsurgical patients.

Methods: Between October 2004 and June 2006, 50 consecutive patients underwent elective, unprotected left main coronary artery stenting at our institution. Patients were followed for a median of 16 and 96 months and clinical outcomes monitored.

Results: Median logistic euroSCORE was 28.6 (interquartile range: 14.6-43.4). Median baseline left ventricular ejection fraction (LVEF) was 50%. Procedural success rate was …

Computational Model Of A Left Ventricle: Showing The Effects Of Inertia On Cardiac Dyssynchrony, Andrew Mcnally, Matthew Korpela, Erin Lamke, Matthew Hudson

Journal of Undergraduate Research at Minnesota State University, Mankato

In an effort to research heart failure, a leading cause of death in the industrialized world, this research team has developed a segmented lumped parameter model of the left ventricle. The computations model developed focuses on dyssynchrony, a heart condition where some regions of the heart vary significantly in properties like internal muscle resistance, mass, or elastance. Inertial effects are often assumed as negligible by cardiovascular models. One primary function of this model is to investigate inertial effects as they relate to mechanical cardiac dyssynchrony. An added dimension of this analysis is to observe the thermodynamics of the cardiac cycle …

Making The Threat Of Huntington’S Disease ‘Small Stuff', Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Effects Of Pde4 Pathway Inhibition In Rat Experimental Stroke, Fan Yang, Rachita K. Sumbria, Dong Xue, Chuanhui Yu, Dan He, Shuo Liu, Annlia Paganini-Hill, Mark J. Fisher

Pharmacy Faculty Articles and Research

PURPOSE: The first genomewide association study indicated that variations in the phosphodiesterase 4D (PDE4D) gene confer risk for ischemic stroke. However, inconsistencies among the studies designed to replicate the findings indicated the need for further investigation to elucidate the role of the PDE4 pathway in stroke pathogenesis. Hence, we studied the effect of global inhibition of the PDE4 pathway in two rat experimental stroke models, using the PDE4 inhibitor rolipram. Further, the specific role of the PDE4D isoform in ischemic stroke pathogenesis was studied using PDE4D knockout rats in experimental stroke. METHODS: Rats were subjected to either the …

Three Dimensional Quantification Of Angiotensin Ii-Induced Murine Abdominal Aortic Aneurysms Using High Frequency Ultrasound, Amelia R. Adelsperger, Alexa A. Yrineo, Hilary D. Schroeder, Ashley Nicole Blaize, Katherine E. Wilson, Evan H. Phillips, Frederick W. Damen, Craig J. Goergen

The Summer Undergraduate Research Fellowship (SURF) Symposium

Abdominal aortic aneurysms (AAAs), a localized dilation of the vessel wall of 50% or more above normal, claims approximately 14,000 U.S. lives yearly due to aortic rupture. This commonly asymptomatic disease can only be treated by endovascular stent grafts or invasive surgery, usually after the AAA diameter reaches 5 cm. Because these treatment methods carry serious risk, stem cell therapy is being explored in order to provide a low risk option for managing smaller AAAs. To determine if stem cell therapy, once administered, could stabilize or reduce AAA growth, baseline 3D ultrasound measurements in a control group were first needed. …

Diabetes Care Management In The Cancer Center: Challenging Current Models Of Care To Optimize Outcomes For A Complex Population, Cara Habeck Rn, Cde, Joyce Najarian Msn, Rn, Cde, Gregory R. Harper Md, Phd, Gretchen Perilli Md, Janelle M. Sharma Dnp, Crnp, Melissa Kratz Rn, Msn, Aocn, Patricia Shearburn Rn, Msn, Aocn, Cathy A. Coyne Phd, Mph, Hope Kincaid Mph, Cph, Roya Hamadani Mph

Patient Care Services / Nursing

No abstract provided.

An Investigation Of The Relationship Between Plantar Weight Distribution And The Condition Of Osteoarthritic Knees During Quiet Standing, Brian Joseph Sutterer

Graduate Theses - Biology & Biomedical Engineering

Osteoarthritis (OA) is a damaging disease that commonly affects the knee and can impact function of the lower limb. This study examined how plantar weight distribution is related to the changes in knee alignment and various types of joint damage in patients with OA. A force mat was used to measure plantar weight distribution on 37 patients with knee OA, and the internal condition of the knee was evaluated during surgery. Analysis showed a relationship between medial plantar weight distribution and an increase in knee alignment angle (0.20, p < 0.001). For the damage models, an indirect relationship was found between medial weight distribution and ACL damage (-0.14, p=0.029). No relationship was found for the other types of OA damage. It is reasonable to believe they do exist, however. This study found a connection between weight distribution and alignment, and previous research has shown one between alignment and OA.

Heart Rate Variability Measured Early In Patients With Evolving Acute Coronary Syndrome And 1-Year Outcomes Of Rehospitalization And Mortality, Patricia R.E. Harris, Phyllis K. Stein, Gordon L. Fung, Barbara J. Drew

Collected Faculty Scholarship

Objective: This study sought to examine the prognostic value of heart rate variability (HRV) measurement initiated immediately after emergency department presentation for patients with acute coronary syndrome (ACS).

Background: Altered HRV has been associated with adverse outcomes in heart disease, but the value of HRV measured during the earliest phases of ACS related to risk of 1-year rehospitalization and death has not been established.

Methods: Twenty-four-hour Holter recordings of 279 patients with ACS were initiated within 45 minutes of emergency department arrival; recordings with �18 hours of sinus rhythm were selected for HRV analysis (number [N] �193). Time domain, frequency …

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 …

Characterization Of Hcmv-Encoded Chemokine Receptor Us28 Transduced Msu1.1 Human Fibroblast Cells, Danielle R. Vanbeckum

All NMU Master's Theses

Human Cytomegalovirus (HCMV) encodes the G-protein coupled receptor US28. Using a mouse model system, US28 was previously found to be oncomodulatory, increasing proliferation, inducing anchorage independent growth and loss of contact inhibition. Similarly, in the human glioblastoma cell line U373, US28 activated VEGF expression. To determine if US28 is oncomodulatory in normal human cells, we engineered the human fibroblast cell line MSU1.1 to express US28 via lentivirus infection. MSU1.1 cells were transduced with pHAGE-US28-ZsGreen. Fluorescent confocal microscopy was utilized to detect the ZsGreen tag and confirmed the successful transduction of MSU1.1 cells with the US28 vector or empty pHAGE vector. …

New Beginnings: A Discussion Guide Adaptation For Living With Diabetes Among An Urban American Indian Community, Eudora Lynette Claw

UNLV Theses, Dissertations, Professional Papers, and Capstones

Diabetes is a chronic disease where the body has the inability to control the sugar levels in the blood to convert into to usable energy needed to fuel the body's cells. Some common diabetic complications include heart disease, stroke, amputations, and possibly blindness. It can be successfully managed with routine care of monitoring of sugar levels, eating a healthy diet, and daily exercise. The occurrence of type 2 diabetes is rising rapidly worldwide, but is a burden for AI/ANs (American Indian/Alaska Natives) at a substantially disproportionate rate. The purpose of this pilot study was to participate in a one-day curriculum …

Evaluation Of The Effectiveness Of A Newly Implemented, Proactive Approach To Legionellosis Investigations Conducted By The Southern Nevada Health District, Devin Charlotte Raman

UNLV Theses, Dissertations, Professional Papers, and Capstones

This project is an evaluation of a new, more proactive approach to legionellosis investigations conducted by the Southern Nevada Health District. The new protocol was conceived, written and adopted in April of 2012 with the goal of preventing outbreaks of Legionnaires' disease that can have a significant impact on public health and the resort industry of Las Vegas. The objectives of this project were to determine if the remediation methods were successful at eliminating the target organism from water systems and maintaining a negative status throughout the monitoring period, to conduct a cost/benefit analysis, and to compare this protocol with …