Medicine and Health Sciences Commons^™

It’S Playoff Time – And A Reminder That Brain Health Comes First, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

The Toxoplasma Gondii Cyst Wall Protein Cst1 Is Critical For Cyst Wall Integrity And Promotes Bradyzoite Persistence, Tadakimi Tomita, David J. Bzik, Yan Fen Ma, Barbara A. Fox

Dartmouth Scholarship

Toxoplasma gondii infects up to one third of the world's population. A key to the success of T. gondii as a parasite is its ability to persist for the life of its host as bradyzoites within tissue cysts. The glycosylated cyst wall is the key structural feature that facilitates persistence and oral transmission of this parasite. Because most of the antibodies and reagents that recognize the cyst wall recognize carbohydrates, identification of the components of the cyst wall has been technically challenging. We have identified CST1 (TGME49_064660) as a 250 kDa SRS (SAG1 related sequence) domain protein with a large …

Sensitization Of Human Cancer Cells To Gemcitabine By The Chk1 Inhibitor Mk-8776: Cell Cycle Perturbation And Impact Of Administration Schedule In Vitro And In Vivo, Ryan Montano, Ruth Thompson, Injae Chung, Huagang Hou, Nadeem Khan, Alan Eastman

Dartmouth Scholarship

Chk1 inhibitors have emerged as promising anticancer therapeutic agents particularly when combined with antimetabolites such as gemcitabine, cytarabine or hydroxyurea. Here, we address the importance of appropriate drug scheduling when gemcitabine is combined with the Chk1 inhibitor MK-8776, and the mechanisms involved in the schedule dependence.

Creating A Christmas Memory For A Huntington’S Family, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Interactions Of Peptide Triazole Thiols With Env Gp120 Induce Irreversible Breakdown And Inactivation Of Hiv-1 Virions, Arangassery Bastian, Mark Contarino, Lauren D. Bailey, Rachna Aneja, Diogo Rodrigo Magalhaes Moreira, Kevin Freedman, Karyn Mcfadden, Caitlin Duffy, Ali Emileh

Dartmouth Scholarship

Background: We examined the underlying mechanism of action of the peptide triazole thiol, KR13 that has been shown previously to specifically bind gp120, block cell receptor site interactions and potently inhibit HIV-1 infectivity.

Results: KR13, the sulfhydryl blocked KR13b and its parent non-sulfhydryl peptide triazole, HNG156, induced gp120 shedding but only KR13 induced p24 capsid protein release. The resulting virion post virolysis had an altered morphology, contained no gp120, but retained gp41 that bound to neutralizing gp41 antibodies. Remarkably, HIV-1 p24 release by KR13 was inhibited by enfuvirtide, which blocks formation of the gp41 6-helix bundle during membrane fusion, while …

Characterizing The Human Vaginal Microbiome Using High-Throughput Sequencing, Jean Megan E. Macklaim

Electronic Thesis and Dissertation Repository

The human vaginal microbiome undoubtedly has a significant role in reproductive health and for protection from infectious organisms. Recent efforts to characterize the bacterial species of the vagina using molecular techniques have uncovered an unexpected diversity. Using high-throughput sequencing I sought to describe the structure and function of the vaginal microbiome under different physiological states including healthy, bacterial vaginosis (BV), post-menopausal vaginal atrophy, and acute vulvovaginal candidiasis (VVC).

Partial 16S rRNA gene sequencing revealed that healthy, asymptomatic women most often have vaginal biotas dominated by Lactobacillus iners or L. crispatus. In contrast, BV is a heterogeneous, highly diversified condition …

Exploring The Structure And Biochemistry Of Oxidation-Mediated Inhibitation Of The Peptidyl-Prolyl Isomerase Pin1, Brendan T. Innes

Electronic Thesis and Dissertation Repository

Pin1 is a phosphorylation-dependent peptidyl-prolyl isomerase that has been shown to be neuroprotective in aging-related neurodegenerative diseases such as Alzheimer's disease (AD). However, it is not active in AD brain, and a recent proteomic screen of Mild Cognitive Impairment (MCI) brain samples revealed that Pin1 is oxidized in the brains of these pre-AD patients. This suggests that this oxidation may be the cause of the loss of the neuroprotective Pin1 function in AD. The Pin1 active site contains a functionally critical cysteine residue (Cys113) with a low predicted pKa, making it highly susceptible to oxidation. We hypothesize that Pin1 is …

‘Alive And Well’ Captures Struggle Against Untreatable Brain Disorder, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

A Pilot Study To Investigate Concerns In Patients Undergoing Neck Dissection Surgery, Daniel Sundar Raj Arulananda Doss

Electronic Thesis and Dissertation Repository

Abstract:

This study investigates concerns in patients undergoing neck dissection surgery. Forty patients were recruited at Pre-surgery, Discharge and 1-month Post-surgery. The Patient Concerns Inventory - Level of Importance questionnaire (PCI-LOI), Shoulder Pain and Disability Index (SPADI), Neck Dissection Impairment Index (NDII) and the University of Washington - Quality of Life questionnaire (UWQOL) were used.

The study identified "Anxiety" at Pre-surgery and "Appearance" at Discharge and 1-month Post-surgery as the important patient concerns. Patients’ concerns were found to change over time. Support for cross-sectional convergent validity of the PCI-LOI was evidenced by significant correlations between the PCI-LOI and the UWQOL …

Primordium Of An Artificial Bruch's Membrane Made Of Nanofibers For Engineering Of Retinal Pigment Epithelium Cell Monolayers, Patrick Warnke, Mohammad Alamein, Stuart Skabo, Sebastien Stephens, Robert Bourke, Peter Heiner, Qin Liu

Qin Liu

Transplanted Retinal Pigment Epithelium(RPE) cells hold promise for treatment of Age-related Macular Degeneration(AMD) and Stargardt Disease(SD), but it is conceivable that the degenerated host Bruch's membrane(BM) as a natural substrate for RPE might not optimally support transplanted cell survival with correct cellular organization. We fabricated novel ultrathin 3-dimensional(3D) nanofibrous membranes from Collagen type I and poly(lactic-co-glycolic acid) (PLGA) by an advanced clinical-grade needle-free-electrospinning process. The nanofibrillar 3D networks highly mimicked the fibrillar architecture of the native inner collagenous layer of human BM. Human RPE cells grown on our nanofibrous membranes bore striking resemblance to native human RPE. They exhibited a …

Prenatal Programming Of Hepatic Glucose And Cholesterol Regulation In Male Rat Offspring By Chronic Intermittent Hypoxia, Waseem Iqbal

Electronic Thesis and Dissertation Repository

Obstructive sleep apnea (OSA) is a chronic disorder involving repetitive interruptions in breathing during sleep. Sufferers of OSA are exposed to chronic intermittent hypoxia (CIH), characterized by cyclical reductions in oxygen availability. A number of studies have established a link between OSA and various cardiovascular and metabolic comorbidities in adulthood, including hypertension, obesity, and type II diabetes. While the consequences of OSA in adults have been well described, the cross-generational impact of this condition and potential effects on fetal development are not known. Epidemiological and animal studies have demonstrated that physiological insults during pregnancy lead to diminished growth of offspring …

Diabetes Alters Contraction-Induced Mitogen Activated Protein Kinase Activation In The Rat Soleus And Plantaris, Anjaiah Katta, Deborah L. Preston, Sunil K. Kakarla, Shinichi Asano, Sarath Meduru, Sriram P. Mupparaju, Ellie Yokochi, Kevin M. Rice, Devashish H. Desai, Eric R. Blough

Deborah L Preston

The prescription of anaerobic exercise has recently been advocated for the management of diabetes; however exercise-induced signaling in diabetic muscle remains largely unexplored. Evidence from exercise studies in nondiabetics suggests that the extracellular-signal-regulated kinases (Erk1/2), p38, and c-JUN NH2-terminal kinase (Jnk) mitogen-activated protein kinases (MAPKs) are important regulators of muscle adaptation. Here, we compare the basal and the in situ contraction-induced phosphorylation of Erk1/2- p38- and Jnk-MAPK and their downstream targets (p90rsk and MAPKAP-K2) in the plantaris and soleus muscles of normal and obese (fa/fa) Zucker rats. Compared to lean animals, the time course and magnitude of Erk1/2, p90rsk and …

Diabetes Alters Vascular Mechanotransduction: Pressure-Induced Regulation Of Mitogen Activated Protein Kinases In The Rat Inferior Vena Cava, Kevin M. Rice, Devashish H. Desai, Sunil K. Kakarla, Anjaiah Katta, Deborah L. Preston, Paulette Wehner, Eric R. Blough

Deborah L Preston

Background Diabetes mellitus is an important risk factor for increased vein graft failure after bypass surgery. However, the cellular and molecular mechanism(s) underlying vessel attrition in this population remain largely unexplored. Recent reports have suggested that the pathological remodeling of vein grafts may be mediated by mechanically-induced activation of the mitogen activated protein kinase (MAPK) signaling pathways and the MAPK-related induction of caspase-3 activity. On the basis of these findings, we hypothesized that diabetes may be associated with alterations in how veins "sense" and "respond" to altered mechanical loading. Methods Inferior venae cavae (IVC) from the non-diabetic lean (LNZ) and …

In Vivo Bioluminescence Imaging To Evaluate Systemic And Topical Antibiotics Against Community-Acquired Methicillin-Resistant Staphylococcus Aureus-Infected Skin Wounds In Mice, Yi Guo, Romela Irene Ramos, John S. Cho, Niles P. Donegan, Ambrose L. Cheung, Lloyd S. Miller

Dartmouth Scholarship

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) frequently causes skin and soft tissue infections, including impetigo, cellulitis, folliculitis, and infected wounds and ulcers. Uncomplicated CA-MRSA skin infections are typically managed in an outpatient setting with oral and topical antibiotics and/or incision and drainage, whereas complicated skin infections often require hospitalization, intravenous antibiotics, and sometimes surgery. The aim of this study was to devel

Mediterranean Diet Is An Effective Method For Treating Type 2 Diabetes In Adults, Amy Bois

Health Sciences Undergraduate Publications

Type 2 diabetes has been a health issue for many years, and as more people throughout the world become obese or overweight this issue becomes more serious. Type 2 diabetes is called insulin resistance which means the body does not use insulin properly. At first the pancreas will make extra insulin, but over time the pancreas is not able to keep up and cannot make enough insulin to keep blood glucose at normal levels. Type 2 diabetes is most common in adults who are obese or overweight, and this health problem can be life-threatening. There is no cure for type …

Screening For Tuberculosis In Pregnancy: Do We Need More Than A Symptom Screen? Experience From Western Kenya, R J. Kosgei, D Szkwarko, S Callens, P Gichangi, Marleen Temmerman, A-B Kihara, J J. Sitienei, E J. Cheserem, P M. Ndavi, A J. Reid, E J. Carter

Obstetrics and Gynaecology, East Africa

Objectives: 1) To explore the utility of tuberculosis (TB) symptom screening for symptoms of ⩾2 weeks’ duration in a routine setting, and 2) to compare differences in TB diagnosis between human immunodeficiency virus (HIV) infected and non-HIV-infected pregnant women in western Kenya.

Design: Comparative cross-sectional study among pregnant women with known HIV status screened for TB from 2010 to 2012, in Eldoret, western Kenya.

Results: Of 2983 participants, respectively 34 (1%), 1488 (50.5%) and 1461 (49.5%) had unknown, positive and negative HIV status. The median age was respectively 30 years (interquartile range [IQR] 26–35) and 26 years (IQR 24–31) in …

Tetraspanin Cd9: Contributions To Cancer Cell And Vascular Cell Phenotypes From The Sixth Man, Michael James Herr Ii

Theses and Dissertations (ETD)

Cancer and vascular disease are the two most predominant causes of mortality in the United States. Potential regulatory mechanisms for these two diseases have consumed research interests. Tetraspanins are cell surface proteins that organize the cell membrane. Cellular membrane organization is a prerequisite for cellular signaling to occur. Deregulation of cellular signaling often precedes the formation of cancer or vascular disease phenotypes. This insinuates the necessity to understand how tetraspanins contribute to membrane organization and subsequent downstream signaling. This work examines tetraspanin CD9 contributions in a model of cancer cell invasion and vascular cell contraction. The findings presented here demonstrate …

Development And Characterization Of A Recombinant Vesicular Stomatitis Virus (Rvsv) For The Treatment Of Glioblastoma, Erika A. Dillard

Theses and Dissertations (ETD)

Background: Over the past 30 years, little has changed in the treatment modalities and prognosis of patients suffering from Glioblastoma multiforme (GBM), the most common and by far the most devastating adult primary malignant brain tumor. Conventional therapies provide only a marginal increase in survival of GBM patients, post-diagnosis. Therefore, more novel means of treating GBM are needed to increase long-term survival and quality of life for those affected. Replication competent oncolytic viruses (OVs) have recently emerged as a possible option for treatment of high-grade gliomas. Particularly, recombinant vesicular stomatitis virus (rVSV), an enveloped, negative strand RNA virus, has shown …

Humans' Bonding With Their Companion Dogs: Cardiovascular Benefits During And After Stress, Rebecca A. Campo, Bert N. Uchino

The Journal of Sociology & Social Welfare

This study examined whether having one's companion dog present during and after stress posed similar cardiovascular benefits as having a close friend present, even when the relationship quality for both the companion dog and friend was highly positive. Positive aspects of relationship quality for participants' dog and friend were not associated with one another, suggesting that these relationships exist independently. Additionally, compared to participants with a close friend present, those with their dog present had lower heart rate and diastolic blood pressure (p's < .05) while undergoing the stressors, and tended to have lower heart rate and systolic blood pressure (p's < .09) when recovering from stressors. This study indicates that even when relationship quality is similarly high for companion dogs and friends, dogs may be associated with greater reductions in owners' cardiovascular reactivity to stress, particularly if there is a potential for evaluation apprehension in the human friendships. These findings support the value of the human- companion animal relationship in promoting human welfare.

Scanned Ion Beam Therapy For Thoracic Tumors, John Gordon Eley

Dissertations & Theses (Open Access)

Although frequently cured of Hodgkin lymphoma, adolescents and young adults can develop radiation induced second cancers. These patients could potentially benefit from scanned ion radiotherapy yet likely would require motion mitigation strategies. In theory, four-dimensional (4D) optimization of ion beam fields for individual motion states of respiration can enable superior sparing of healthy tissue near moving targets, compared to other motion mitigation strategies. Furthermore, carbon-ion therapy can sometimes provide greater relative biological effectiveness (RBE) for cell sterilization in a target but nearly equivalent RBE in tissue upstream of the target, compared to proton therapy. Thus, we expected that for some …

The Staphylococcus Pseudintermedius Adhesin Spsd Contains A Central Fibronectin-Binding Domain, Andrea S. Bordt

Dissertations & Theses (Open Access)

Staphylococcus pseudintermedius is a Gram-positive bacterium significant because of its ability to cause costly and difficult to treat veterinary infections worldwide. It exhibits several similarities to Staphylococcus aureus, however, very little is known about its surface adhesins. Surface adhesins in S. aureus are significant contributors to pathogenesis. S. pseudintermedius encodes the surface protein SpsD, which contains characteristics of the microbial surface components recognizing adhesive matrix molecules family and confers attachment of the heterologous host Lactococcus lactis to fibronectin. This work has identified a centrally-located fibronectin binding domain in SpsD which binds the 30 kDa N-terminal domain of fibronectin with …

Sympathetic Nerve Modulation Of Joint Pathology In Adjuvant-Induced Arthritis, Carlo Anthony Wood

Loma Linda University Electronic Theses, Dissertations & Projects

Background: There is increasing data suggesting a net increase in sympathetic tone plays an important role in rheumatoid arthritis. Several studies have reported altered distribution and density of autonomic nerves in patients with rheumatoid arthritis and animal models for the disease. This provides anatomical evidence that supports a neurally-mediated drive in inflammation and joint destruction. Methods: Adult rats were injected with complete Freund’s adjuvant. At 12 days post immunization, animals were randomly placed into a drug treatment group (SH1293, which interacts with - and ß2-ARs), an adjuvant arthritic group, or a control group. These animals were sacrificed at 14, 21, …

The Partial Characterization Of The 142r Protein Of Tanapox Virus, Krystal N. Seibert

Dissertations

Due to the complex nature of cancer, a variety of strategies are being employed to treat patients. Among these are oncolytic viruses that conditionally replicate in tumor cells with specific cellular landscapes. Several viruses including Herpesviruses, Adenoviruses, and Poxviruses, predominantly vaccinia virus (VV), have been explored for their oncolytic potential. Most of these viruses can productively infect a variety of cell types and it is one goal to create conditionally lethal viruses that can only replicate in tumor cells. Due to the prevalence of p53 inactivating mutations in cancers viruses that are restricted to p53 null cells are desirable and …

Identification Of Biomarkers Associated With Ascites Incidence In Broilers, Kaylee Rowland

Graduate Theses and Dissertations

Poultry is key in genetic research due to breeding feasibility, relatively short generation interval, and distinct phenotypes. It is estimated that 8% of broiler deaths annually can be attributed to ascites, an economically important disease that has been challenging the industry for the past 2 decades. Genetically selected ascites resistant (RES) and susceptible (SUS) chicken lines have been established and maintained by the University of Arkansas, Fayetteville. Intensive research efforts have been made to reveal physiological and biochemical characteristics for the incidence of ascites. Since the whole genome of the major ancestral chicken, the Red Jungle Fowl, has been sequenced, …

Phenotypic, Physiological And Growth Interactions Among Salmonella Serovars, Juliany Rivera Calo

Graduate Theses and Dissertations

This thesis consists of four research parts: a literature review that covers Salmonella spp., one of the more prominent foodborne pathogens that represents a major risk to humans (chapter 1). Understanding the growth of Salmonella serovars and strains is an important basis for more in depth research. In this case we studied a) the aerobic and anaerobic growth responses of multiple strains from six different serovars, b) how the spent media from different serovars, more importantly S. Heidelberg, affect the growth of S. Typhimurium, and c) determined whether or not two different serovars undergo competitive interactions when they were …

Effect Of Electrostatic Spraying Of Food-Grade Organic And Inorganic Acids, And Grape Seed Extract On Salmonella Typhimurium And Escherichia Coli O157:H7 On Spinach And Iceberg Lettuce, Vijayalakshmi Ganesh

Graduate Theses and Dissertations

The safety of fresh produce is often challenged by the sporadic incidences of outbreaks owing to Salmonella Typhimurium (S.T.) and Escherichia coli O157:H7 (E.c.). Washing and current disinfection strategies do not completely decontaminate leafy greens such as spinach and iceberg lettuce. Therefore, more effective treatments are essential to ensure the microbial safety of the produce at the selling point. Here, a multiple hurdle approach was applied: (1) Natural antimicrobials - organic acids (malic, lactic and tartaric acids; MA, LA, TA, respectively) and plant extract (grape seed extract, GSE) and (2) Application method - Electrostatic spraying, was …

Electrostatic Spray Application Of Food-Grade Organic Acids And Plant Extracts To Decrease Escherichia Coli O157:H7 And Salmonella Typhimurium On Select Produce, Leighanna Maeree Massey

Graduate Theses and Dissertations

Both consumers and suppliers have been negatively affected by an increase in foodborne pathogens contaminating fruits. Consequently, there is a need for the development of more efficient antimicrobials and application techniques to decrease contamination. Natural preservatives such as organic acids and plant extracts have demonstrated promising results in decontaminating produce. In addition, the effectiveness of such preservatives may be enhanced by the use of an electrostatic sprayer. The objective of this research was to determine the combinations and concentrations of organic acids and plant extract that were able to reduce Salmonella Typhimurium (ST) and Escherichia coli O157:H7 (EC) inoculated fruits …

A Novel Mechanism Of Enhanced Susceptibility To Bacterial Pneumonia In Influenza-Infected Hosts, Hazem Elsayed Ghoneim

Theses and Dissertations (ETD)

Viruses such as influenza suppress host immune function by a variety of methods. This may result in a significant morbidity through several pathways, including facilitation of secondary bacterial pneumonia from pathogens such as Streptococcus pneumoniae. Lungresident alveolar macrophages (AMs) act as the first line of innate cellular immunity against respiratory bacterial pathogens, including pneumococcus. Therefore, they represent an attractive target for study Before investigating the impact of influenza infection on resident AMs, we first characterized different subsets of lung-resident macrophages in naïve mice using a novel in vivo labeling approach in conjunction with multicolor flow cytometric analysis and confocal microscopic …

Erg11-Mediated Azole Resistance In Candida Albicans, Stephanie Ann Flowers

Theses and Dissertations (ETD)

Although many medically important Candida species are commensal to the gut or colonizers of the skin, these organisms have the propensity to cause disease in the event of a waning immune system. Clinical manifestations of infections with Candida species can range from superficial mucosal infections to deep organ involvement usually resulting from haematogenous spread of infection. Despite significant progress made in the management of patients with fungal infections, the emergence of antifungal resistant clinical isolates creates significant problem in regards to antifungal prophylaxis and empirical treatment strategies. Antifungal resistance is associated with high mortality rates and hefty medical costs. The …

Arkansas Animal Science Department Report 2013, David L. Kreider, Paul Beck

Arkansas Agricultural Experiment Station Research Series

No abstract provided.