Diseases Commons^™

Differential Virus Host-Ranges Of The Fuselloviridae Of Hyperthermophilic Archaea: Implications For Evolution In Extreme Environments, Ruben Michael Ceballos, Caleb D. Marceau, Joshua O. Marceau, Steven Morris, Adam J. Clore, Kenneth M. Stedman

Biological Sciences Faculty Publications and Presentations

An emerging model for investigating virus-host interactions in hyperthermophilic Archaea is the Fusellovirus-Sulfolobus system. The host, Sulfolobus, is a hyperthermophilic acidophile endemic to sulfuric hot springs worldwide. The Fuselloviruses, also known as Sulfolobus Spindle-shaped Viruses (SSVs), are “lemon” or “spindle”-shaped double-stranded DNA viruses, which are also found worldwide. Although a few studies have addressed the host-range for the type virus, Sulfolobus Spindle-shaped Virus 1 (SSV1), using common Sulfolobus strains, a comprehensive host-range study for SSV-Sulfolobus systems has not been performed. Herein, we examine six bona fide SSV strains (SSV1, SSV2, SSV3, SSVL1, SSVK1, SSVRH) and their respective infection characteristics on …

Playing In The Fourth Quarter Of Life As Huntington's Disease Looms, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Serial Analysis Of The Gut And Respiratory Microbiome In Cystic Fibrosis In Infancy: Interaction Between Intestinal And Respiratory Tracts And Impact Of Nutritional Exposures, J. C. Madan, D. C. Koestler, B. A. Stanton, L. Davidson, L. A. Moulton, M. L. Housman, J. H. Moore, M. F. Guill, H. G. Morrison, M. L. Sogin, T. H. Hampton, M. R. Karagas, P. E. Palumbo, J. A. Foster, P. L. Hibberd, G. A. O’Toole

Dartmouth Scholarship

Pulmonary damage caused by chronic colonization of the cystic fibrosis (CF) lung by microbial communities is the proximal cause of respiratory failure. While there has been an effort to document the microbiome of the CF lung in pediatric and adult patients, little is known regarding the developing microflora in infants. We examined the respiratory and intestinal microbiota development in infants with CF from birth to 21 months. Distinct genera dominated in the gut compared to those in the respiratory tract, yet some bacteria overlapped, demonstrating a core microbiota dominated by Veillonella and Streptococcus. Bacterial diversity increased significantly over time, …

Coronary Artery Remodeling In A Model Of Left Ventricular Pressure Overload Is Influenced By Platelets And Inflammatory Cells, Fanmuyi Yang, Anping Dong, Paul Mueller, Jessica Caicedo, Alyssa Moore Sutton, Juliana Odetunde, Cordelia J. Barrick, Yuri M. Klyachkin, Ahmed Abdel-Latif, Susan S. Smyth

Internal Medicine Faculty Publications

Left ventricular hypertrophy (LVH) is usually accompanied by intensive interstitial and perivascular fibrosis, which may contribute to arrhythmogenic sudden cardiac death. The mechanisms underlying the development of cardiac fibrosis are incompletely understood. To investigate the role of perivascular inflammation in coronary artery remodeling and cardiac fibrosis during hypertrophic ventricular remodeling, we used a well-established mouse model of LVH (transverse aortic constriction [TAC]). Three days after pressure overload, macrophages and T lymphocytes accumulated around and along left coronary arteries in association with luminal platelet deposition. Consistent with these histological findings, cardiac expression of IL-10 was upregulated and in the systemic circulation, …

Murine Gammaherpesvirus 68 Lana Acts On Terminal Repeat Dna To Mediate Episome Persistence, Aline C. Habison, Chantal Beauchemin, J. Pedro Simas, Edward J. Usherwood

Dartmouth Scholarship

Murine gammaherpesvirus 68 (MHV68) ORF73 (mLANA) has sequence homology to Kaposi’s sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen (LANA). LANA acts on the KSHV terminal repeat (TR) elements to mediate KSHV episome maintenance. Disruption of mLANA expression severely reduces the ability of MHV68 to establish latent infection in mice, consistent with the possibility that mLANA mediates episome persistence. Here we assess the roles of mLANA and MHV68 TR (mTR) elements in episome persistence. mTR-associated DNA persisted as an episome in latently MHV68-infected tumor cells, demonstrating that the mTR elements can serve as a cis-acting element for MHV68 episome maintenance. In some …

Microbiological Components In Mainstream And Sidestream Cigarette Smoke, Lennart Larsson, Christina Pehrson, Tenzin Dechen, Mardi Crane-Godreau

Dartmouth Scholarship

Research has shown that tobacco smoke contains substances of microbiological origin such as ergosterol (a fungal membrane lipid) and lipopolysaccharide (LPS) (in the outer membrane of Gram-negative bacteria). The aim of the present study was to compare the amounts of ergosterol and LPS in the tobacco and mainstream (MS) and sidestream (SS) smoke of some popular US cigarettes. We measured LPS 3-hydroxy fatty acids and fungal biomass biomarker ergosterol in the tobacco and smoke from cigarettes of 11 popular brands purchased in the US. University of Kentucky reference cigarettes were also included for comparison.

Green Tea Extract Protects Against Fibrogenesis Associated With Nonalcoholic Fatty Liver Disease In Diet-Induced Obese Rats, Allyson M. Bower

Master's Theses

No abstract provided.

Does Anti-Malarial Drug Knowledge Predict Anti-Malarial Dispensing Practice In Drug Outlets? A Survey Of Medicine Retailers In Western Kenya., Andria Rusk, Nathan Smith, Diana Menya, Andrew Obala, Chrispinus Simiyu, Barasa Khwa-Otsyula, Wendy O'Meara

Collected Faculty Scholarship

Background

Malaria is a major cause of morbidity and mortality in Kenya, where it is the fifth leading cause of death in both children and adults. Effectively managing malaria is dependent upon appropriate treatment. In Kenya, between 17 to 83 percent of febrile individuals first seek treatment for febrile illness over the counter from medicine retailers. Understanding medicine retailer knowledge and behaviour in treating suspected malaria and dispensing anti-malarials is crucial.

Methods

To investigate medicine retailer knowledge about anti-malarials and their dispensing practices, a survey was conducted of all retail drug outlets that sell anti-malarial medications and serve residents of …

California Stem Cell Agency Approves $19 Million Clinical Trial Project As Huntington's Disease Families 'Change The Course Of Science', Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Quantification And In Vitro Analysis Of Nanolipoproteins (Nlps) Containing Adjuvants, Purna Venkataraman, Craig Blanchette, Nicholas O. Fischer

STAR Program Research Presentations

Nanolipoprotein particles (NLPs) self-assemble into nanoscale structures that can be used as vaccines or drug delivery agents. Due to the nature of the NLPs, a variety of immune stimulating compounds or adjuvants can be readily incorporated into NLPs: a characteristic difficult to engineer into most other nanoscale platforms. In light of this, a method for quantifying the amount adjuvant actually incorporated into NLPs is a question of high importance. Through the use of reverse phase High-Performance Liquid Chromatography (HPLC) and an Evaporative Light Scattering Detector (ELSD), standard curves can be constructed by analyzing mixtures of NLP components of known concentration, …

Improving Outcomes Of Acute Coronary Syndrome Patients Through Disease Specific Care Certification, Terri Ginn Lemon

Doctoral Projects

Cardiovascular disease remains the number one killer of Americans, accounting for over 800,000 deaths in 2008. Improving a hospital’s performance by obtaining and maintaining The Joint Commission Disease-Specific Care Certification is one method of impacting acute coronary syndrome patient outcomes. The purpose of this capstone project was to provide consultation services to ready the cardiology division of a large community hospital in south Mississippi for the process of obtaining Joint Commission Disease-Specific Care Certification in the area of acute coronary syndrome. The activities of the consultation included facilitating an examination of the current organization of ACS patient care; reviewing core …

Exogenous Alpha-Synuclein Induces Cell Death Related Proteins In C6 Oligodendrocyte-Like Cells Corresponding To Protein Expression Observed In Multiple System Atrophy, Derrick Samuel Hilton

Dissertations

Multiple System Atrophy (MSA) consists of three disorders; Autonomic Dysfunction, Cerebellar Ataxia, and Parkinsonism. In MSA, the protein Alpha-Synuclein (SNCA) appears in the central nervous system as misfolded protein aggregates primarily in oligodendrocytes. This dissertation reports the results from studies examining the effect of exogenous SNCA has on a cell model: C6 oligodendrocyte-like cells. Treated cells were evaluated using western blot and DNA microarray. In addition the expression of proteins was evaluated using immunocytochemistry in MSA patient tissue.

C6 cells were shown to take up SNCA when added to the media. SNCA also underwent a truncation when taken up by …

Evaluation Of Smoking Cessation Services In Ireland: Design And Pilot Of A Smoking Cessation Treatment Database, Sheila Keogan

Masters

A reduction in tobacco use is one of the stated aims of the National Health Promotion Strategy
(2000-2005) (Department of Health and Children, 2000a) as well being the core activity of
membership for all health promoting hospitals (HPH).
AIMS OF THE STUDY

1. To develop a database of smoking cessation services in Ireland.

2. Do a census of the smoking cessation services in Ireland and evaluate the range and
availability of them.
3. Develop a database for use in smoking cessation treatment services which would schedule
consultations with patients and gather all relevant demographics, treatments and their outcomes,
(cessation treatment …

Frequency Of Poor Quality Of Life And Predictors Of Health Related Quality Of Life In Cirrhosis At A Tertiary Care Hospital Pakistan, Om Parkash, Romaina Iqbal, Fatima Jafri, Iqbal Azam, Wasim Jafri

Section of Gastroenterology

Background

Cirrhosis produces variety of symptoms which eventually lead to a negative impact on Health Related Quality of Life (HRQOL). The general aim of this study was to evaluate the magnitude of poor HRQOL and to assess factors related with HRQOL in patients with CLD in Pakistan.

Findings

This was a cross sectional study conducted in gastroenterology outpatient clinics of Aga Khan University Hospital, Karachi on adult patients with cirrhosis. In this study chronic liver disease questionnaire (CLDQ) was used to assess HRQOL of these patients and CLDQ score was used as an outcome measure to determine factors related with …

Multidrug Resistant Pulmonary Tuberculosis Treatment Regimens And Patient Outcomes: An Individual Patient Data Meta-Analysis Of 9,153 Patients, Shama D. Ahuja, David Ashkin, Monika Avendano, Rita Banerjee, Melissa Bauer, Jamie N. Bayona

Dartmouth Scholarship

Dick Menzies and colleagues report findings from a collaborative, individual patient-level meta-analysis of treatment outcomes among patients with multidrug-resistant tuberculosis.

Background: Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB.

Inhibition Of Breast Cancer Angiogenesis And Metastasis Ay Targeting Hypoxia-Inducible Factor-1Α, Chikezie O. Madu

Theses and Dissertations (ETD)

The current clinical chemotherapy agents are not ideal for breast cancer as they are not curative, but only provide a modest extension of survival with sometimes a severely adverse effect on the patient’s quality of life. There is, therefore, an urgent need to search for new and more effective anti-breast cancer drugs. However, the existing screening system is inefficient and time-consuming despite the extremely large amount of small molecule compounds in database currently available, and thereby hindering the effort for selecting new and effective anti-cancer drugs.

The majority of locally advanced solid tumors contain regions of reduced oxygen availability. Hypoxia …

Discovery Of Dihydroartemisinin And Dasatinib Drug Combination To Cure Pooroutcome Bcr-Abl+ Acute Lymphoblastic Leukemia, Harpreet Singh

Theses and Dissertations (ETD)

Oncogenic signaling by the Philadelphia chromosome-encoded BCR-ABL fusion kinase initiates and drives both Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) and chronic myelogenous leukemia (CML). Food and Drug Administration (FDA)- approved BCR-ABL-specific kinase inhibitors (BCR-ABL–KIs) imatinib, dasatinib and nilotinib induce prolonged remissions in CML but poor leukemia-reduction and relapse-control in Ph+ ALL. The relative primary BCR-ABL–KI-resistance in Ph+ ALL patients carrying predominantly BCR-ABLWT disease cannot be attributed to drug-resistant BCR-ABL mutations (BCR-ABLMUTANTS), and remains poorly understood.

We established a cell-based platform to evaluate the modulation of anti-Ph+ ALL activity of drugs by both tumor-extrinsic cytokines normally present in the leukemia …

Utilization Of A Metabolic Syndrome Index In Evaluating The Life In Balance Lifestyle Intervention For Prevention Of Type 2 Diabetes Among Urban American Indians And Alaska Natives, Hongbin Jin

UNLV Theses, Dissertations, Professional Papers, and Capstones

Background: A myriad of diabetes prevention programs modeled on the Diabetes Prevention Program (DPP) are carried out worldwide to fight against the current diabetes pandemic. The percentage of weight reduction is a widely used indicator to evaluate diabetes prevention programs. However, weight change alone may not fully reflect the efficacy of lifestyle intervention. A metabolic syndrome index is a promising novel scale for evaluation of diabetes prevention programs because it is a systematic, comprehensive, and stable indicator that reflects the metabolic risk reduction for diabetes and its complications at multiple levels and dimensions.

Methods: A total of 22 overweight and …

The Ventricular Volume Variability Study Of The Pediatric Heart Network: Study Design And Impact Of Beat Averaging And Variable Type On The Reproducibility Of Echocardiographic Measurements In Children With Chronic Dilated Cardiomyopathy., Steven D. Colan, Girish S. Shirali, Renee Margossian, Dianne Gallagher, Karen Altmann, Charles Canter, Shan Chen, Fraser Golding, Elizabeth Radojewski, Michael Camitta, Michael Carboni, Jack Rychik, Mario Stylianou, Lloyd Y. Tani, Elif Seda Selamet Tierney, Yanli Wang, Lynn A. Sleeper, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Clinical trials often rely on echocardiographic measures of left ventricular size and function as surrogate end points. However, the quantitative impact of factors that affect the reproducibility of these measures is unknown. To address this issue, the National Heart, Lung, and Blood Institute-funded Pediatric Heart Network designed a longitudinal observational study of children with known or suspected dilated cardiomyopathy aged 0 to 22 years from eight pediatric clinical centers.

METHODS: Clinical data were collected together with 150 echocardiographic indices of left ventricular size and function. Separate observers performed duplicate echocardiographic imaging. Multiple observers performed measurements from three cardiac cycles …

Refining The Global Spatial Limits Of Dengue Virus Transmission By Evidence-Based Consensus, Oliver J. Brady, Peter W. Gething, Samir Bhatt, Jane P. Messina, John S. Brownstein, Anne G. Hoen

Dartmouth Scholarship

Background: Dengue is a growing problem both in its geographical spread and in its intensity, and yet current global distribution remains highly uncertain. Challenges in diagnosis and diagnostic methods as well as highly variable national health systems mean no single data source can reliably estimate the distribution of this disease. As such, there is a lack of agreement on national dengue status among international health organisations. Here we bring together all available information on dengue occurrence using a novel approach to produce an evidence consensus map of the disease range that highlights nations with an uncertain dengue status.

Methods/Principle Findings: …

“That Pregnancy Can Bring Noise Into The Family”: Exploring Intimate Partner Sexual Violence During Pregnancy In The Context Of Hiv In Zimbabwe, Simukai Shamu, Naeemah Abrahams, Marleen Temmerman, Tamara Shefer, Christina Zarowsky

Obstetrics and Gynaecology, East Africa

Background: Globally, studies report a high prevalence of intimate partner sexual violence (IPSV) and an association with HIV infection. Despite the criminalisation of IPSV and deliberate sexual HIV infection in Zimbabwe, IPSV remains common. This study explored women’s and health workers’ perspectives and experiences of sexuality and sexual violence in pregnancy, including in relation to HIV testing.

Methods: This qualitative study was part of a larger study of the dynamics of intimate partner violence and HIV in pregnancy in Zimbabwe. Key informant interviews were conducted with health workers and focus group discussions were held with 64 pregnant or nursing mothers …

Synergistic Effects Of Nanosecond Pulsed Electric Fields Combined With Low Concentration Of Gemcitabine On Human Oral Squamous Cell Carcinoma In Vitro, Jing Wang, Jinsong Guo, Shan Wu, Hongqing Feng, Shujun Sun, Jie Pan, Jue Zhang, Stephen J. Beebe

Bioelectrics Publications

Treatment of cancer often involves uses of multiple therapeutic strategies with different mechanisms of action. In this study we investigated combinations of nanosecond pulsed electric fields (nsPEF) with low concentrations of gemcitabine on human oral cancer cells. Cells (Cal-27) were treated with pulse parameters (20 pulses, 100 ns in duration, intensities of 10, 30 and 60 kV/cm) and then cultured in medium with 0.01 mu g/ml gemcitabine. Proliferation, apoptosis/necrosis, invasion and morphology of those cells were examined using MTT, flow cytometry, clonogenics, transwell migration and TEM assay. Results show that combination treatments of gemcitabine and nsPEFs exhibited significant synergistic activities …

Yeast Surface Display Of Cd154, Iaryna Masniuk

Graduate Theses and Dissertations

The CD154 (CD40L) is a member of tumor necrosis factor (TNF) family that plays a crucial role in regulation of both cell-mediated and humoral immunity by activating antigen presenting cells (APCs). Previously, studies in the laboratory demonstrated that yeast surface display system allows the expression of biologically functional antigen, such as subunit HA, against influenza virus. Yeast surface display system seems to be an excellent system to be utilized to develop anti-influenza virus vaccine. Thus, it is of interest to study the adjuvant function of CD154 on the subunit HA vaccine against influenza virus. In this project, the CD154 encoding …

Carrs Surveillance Study: Design And Methods To Assess Burdens From Multiple Perspectives, Manisha Nair, Mohammed K. Ali, Vamadevan S. Ajay, Roopa Shivashankar, Viswanathan Mohan, Rajendra Pradeepa, Mohan Deepa, Hassan Mehmood Khan, Muhammad Masood Kadir, Zafar Fatmi, Srinath Srinath Reddy, Nikhil Tandon, Km Venkat Narayan, Dorairaj Prabhakaran

Community Health Sciences

Background: Cardio-metabolic diseases (CMDs) are a growing public health problem, but data on incidence, trends, and costs in developing countries is scarce. Comprehensive and standardised surveillance for non-communicable diseases was recommended at the United Nations High-level meeting in 2011.
Aims: To develop a model surveillance system for CMDs and risk factors that could be adopted for continued assessment of burdens from multiple perspectives in South-Asian countries.
Design: Hybrid model with two cross-sectional serial surveys three years apart to monitor trend, with a three-year prospective follow-up of the first cohort.Sites: Three urban settings (Chennai and New Delhi in India; Karachi in …

Missed Opportunities For Diagnosis And Treatment Of Diabetes, Hypertension, And Hypercholesterolemia In A Mexican American Population, Cameron County Hispanic Cohort, 2003-2008, Susan P. Fisher-Hoch, Kristina Vatcheva, Susan T. Laing, Monir Hossain, M Hossein Rahbar, Craig Hanis, H Shelton Brown, Anne R. Rentfro, Belinda M. Reininger, Joseph B. Mccormick

School of Mathematical & Statistical Sciences Faculty Publications

Introduction

Diabetes, hypertension, and hypercholesterolemia are common chronic diseases among Hispanics, a group projected to comprise 30% of the US population by 2050. Mexican Americans are the largest ethnically distinct subgroup among Hispanics. We assessed the prevalence of and risk factors for undiagnosed and untreated diabetes, hypertension, and hypercholesterolemia among Mexican Americans in Cameron County, Texas.

Methods

We analyzed cross-sectional baseline data collected from 2003 to 2008 in the Cameron County Hispanic Cohort, a randomly selected, community-recruited cohort of 2,000 Mexican American adults aged 18 or older, to assess prevalence of diabetes, hypertension, and hypercholesterolemia; to assess the extent to …

Early Stage Drug Treatment That Normalizes Proinflammatory Cytokine Production Attenuates Synaptic Dysfunction In A Mouse Model That Exhibits Age-Dependent Progression Of Alzheimer's Disease-Related Pathology, Adam D. Bachstetter, Christopher M. Norris, Pradoldej Sompol, Donna M. Wilcock, Danielle Goulding, Janna H. Neltner, Daret St. Clair, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

Overproduction of proinflammatory cytokines in the CNS has been implicated as a key contributor to pathophysiology progression in Alzheimer's disease (AD), and extensive studies with animal models have shown that selective suppression of excessive glial proinflammatory cytokines can improve neurologic outcomes. The prior art, therefore, raises the logical postulation that intervention with drugs targeting dysregulated glial proinflammatory cytokine production might be effective disease-modifying therapeutics if used in the appropriate biological time window. To test the hypothesis that early stage intervention with such drugs might be therapeutically beneficial, we examined the impact of intervention with MW01-2-151SRM (MW-151), an experimental therapeutic that …

Discrimination Of Colon Cancer Stem Cells Using Noncanonical Amino Acid, Xinrui Duan, Honglin Li, Hexin Chen, Qian Wang

Faculty Publications

Cancer stem cells (CSCs) may be responsible for tumor recurrence. Metabolic labelling of newly synthesized proteins with non-canonical amino acids allows us to discriminate CSCs in mixed populations due to the quiescent nature of these cells.

Purification And Characterization Of Mycobacterium Tuberculosis Esx-1 Secreted Protein Esat-6, Sebastian Montalvo, Gouzhong Jiang, Jianjun Sun

COURI Symposium Abstracts, Summer 2012

Mycobacterium tuberculosis ESX-1 secreted protein ESAT-6 has been shown to contribute to the pathogenesis and virulence of M. tuberculosis. Despite many studies, little is known about how this protein interacts with the host’s membrane and evades the host’s defense mechanism. In this project, we successfully purified and characterized of ESAT-6 wild type (E6-WT) and ESAT-6 mutant with either a single (E6-S) or double (E6-D) amino acid mutation that are supposed to diminish the membrane-interacting activity of ESAT-6. The methods used in our project include: cloning in plasmid vectors, cloning in PCR products with T-Vectors, chemical transformation of E. coli, affinity …

Surveillance Of Mosquitoes For Arthropod-Borne Viruses In El Paso, Tx., Stephanie Coronado, Douglas Watts

COURI Symposium Abstracts, Summer 2012

West Nile encephalitis is the only arthropod-borne virus that causes annual cases of human illness in El Paso, Texas. Cases more commonly affect the young and elderly and the illness may range from a mild febrile disease to fatal encephalitis. The primary vector(s) of West Nile virus are Culex species mosquitoes, including Culex tarsalis and Culex quinquefaciatus. Further, surveillance is needed to determine the relative importance of these and possibly other mosquito species. More recently, cases of dengue fever and fatal hemorrhagic fever have been occurring in communities along the USA-Mexico border. Dengue has been endemic in Mexico since the …

From Engagement To Action: Assessing Community Readiness For Disparities Mobilization, Linda S. Sprague Martinez, Elmer Freeman, Flavia C. Perea

Journal of Health Disparities Research and Practice

In an effort to engage communities across the state of Massachusetts in tackling health disparities, Critical MASS (CM), in partnership with local researchers piloted a readiness assessment to identify community assets, perceptions of disparities, and interest in partnership. The research process was used to facilitate the development of partnerships between outside organizers, researchers, and community stakeholders. Partnership outcomes included a disparities conference aimed at bringing attention to concerns in the community, and a grant submission aimed at addressing community identified disparities. Despite the successes the partnership faced challenges. Logistics and limited resources hindered partner efforts to sustain the relationship. This …